Neonatal Surgery

Contemporary Strategies
from Fetal Life to the
First Year of Age
Mario Lima
Olivier Reinberg 
Editors

123
Neonatal Surgery
Mario Lima  •  Olivier Reinberg
Editors

Neonatal Surgery
Contemporary Strategies from Fetal
Life to the First Year of Age
Editors
Mario Lima Olivier Reinberg
Pediatric Surgery, S.Orsola Hospital Pediatric Surgeon FMH EBPS
University of Bologna Lausanne-Pully, Switzerland
Bologna, Italy

ISBN 978-3-319-93532-4    ISBN 978-3-319-93534-8 (eBook)

https://doi.org/10.1007/978-3-319-93534-8

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Contents

1 Introduction to Neonatal Surgery��������������������������������������������������   1

Olivier Reinberg

Part I General

2 Anesthesiological Considerations: Stabilization

of the Neonate, Fluid Administration, Electrolyte
Balance, Vascular Access, ECMO, Bronchoscopy,
and Pain in Neonates ����������������������������������������������������������������������   7
Fabio Caramelli, Maria Teresa Cecini, Monica Fae,
Elisa Iannella, and Maria Cristina Mondardini
3 Imaging in Neonates������������������������������������������������������������������������  25
Filomena Carfagnini, Laura Greco, Donatella Vivacqua,
Gianluca Rasetto, Antonio Poerio, and Michelangelo Baldazzi
4 Neonatal Surgical Education in Minimally Invasive
Surgery Based on Simulation����������������������������������������������������������  51
Maximiliano Maricic and María Marcela Bailez

Part II Head and Neck

5 Congenital Choanal Atresia������������������������������������������������������������  67

Pedro Saraiva Teiga, Kishore Sandu, and Lluís Nisa
6 Facial Cleft and Pierre Robin Sequence����������������������������������������  73
Anthony S. de Buys Roessingh, Oumama El Ezzi,
Georges Herzog, and Martin Broome
7 Macroglossia ������������������������������������������������������������������������������������ 101
Pedro Saraiva Teiga, Kishore Sandu, and Lluís Nisa
8 Midline and Lateral Cysts and Sinuses of the Neck �������������������� 111
Francesco Fascetti-Leon and Piergiorgio Gamba

Part III Chest

9 Congenital Thoracic Deformities���������������������������������������������������� 117

Giovanna Riccipetitoni, Sara Costanzo, and Francesca Destro

v
vi Contents

10 Mediastinal Masses�������������������������������������������������������������������������� 139

Mario Lima and Michela Maffi
11 Pneumothorax and Chylothorax���������������������������������������������������� 151
Sebastiano Cacciaguerra, Pieralba Catalano, Enrica Antonelli,
and Salvatore Arena
12 Congenital Pulmonary Airway Malformations: From the
Prenatal Diagnosis to the Postoperative Follow-Up���������������������� 167
Arnaud Bonnard
13 Congenital Diaphragmatic Hernia ������������������������������������������������ 177
Mario Lima, Michela Maffi, Giovanni Parente,
and Chiara Cordola
14 Esophageal Atresia and Tracheoesophageal Fistula �������������������� 187
David C. van der Zee, Maud Y. van Herwaarden,
Stefaan H. Tytgat, Michela Maffi, and Mario Lima

Part IV Gastrointestinal

15 Gastroesophageal Reflux in the First Year of Life������������������������ 209

Juan A. Tovar
16 Hypertrophic Pyloric Stenosis and Other Pyloric
Affections������������������������������������������������������������������������������������������ 225
Mirko Bertozzi, Elisa Magrini, and Antonino Appignani
17 Gastric Volvulus ������������������������������������������������������������������������������ 239
Ascanio Martino, Francesca Mariscoli, and Fabiano Nino
18 Bowel Atresia and Stenosis�������������������������������������������������������������� 243
François Varlet, Sophie Vermersch, and Aurélien Scalabre
19 Meconium Ileus�������������������������������������������������������������������������������� 265
Philip Corbett and Amulya Saxena
20 Gastrointestinal Tract Duplications ���������������������������������������������� 279
Carmelo Romeo, Patrizia Perrone, and Pietro Antonuccio
21 Mesenteric and Omental Cysts ������������������������������������������������������ 293
Mario Lima and Neil Di Salvo
22 Surgical Necrotizing Enterocolitis: Early
Surgery - The Key to Live Bowel and Quality Life���������������������� 299
Adrian Bianchi
23 Hirschsprung’s Disease�������������������������������������������������������������������� 311
Maria Grazia Faticato and Girolamo Mattioli
24 Anorectal Malformations���������������������������������������������������������������� 323
Kristiina Kyrklund and Risto Rintala
25 Congenital Pouch Colon������������������������������������������������������������������ 339
Devendra K. Gupta, Shilpa Sharma, and Kashish Khanna
Contents vii

26 Inguinal Hernia and Hydrocele������������������������������������������������������ 351

Ciro Esposito, Maria Escolino, Alessandro Settimi,
and Giuseppe Cortese
27 Intestinal Malrotation and Volvulus���������������������������������������������� 369
Luisa Ferrero, François Becmeur, and Olivier Reinberg

Part V Liver and Biliary Tract

28 Biliary Atresia: New Developments������������������������������������������������ 387

Filippo Parolini and Mark Davenport
29 Congenital Hepatic Cysts���������������������������������������������������������������� 401
Morven Allan and Mark Davenport
30 Choledochal Cyst and Congenital Biliary Dilatation ������������������ 409
Alessandro Settimi, Alessandra Farina, Francesco Turrà,
Maria Escolino, Mariapina Cerulo, and Ciro Esposito

Part VI Anterior Abdominal Wall Defects

31 Gastroschisis and Omphalocele������������������������������������������������������ 417

Mikko P. Pakarinen, Antti Koivusalo, and Janne Suominen
32 Omphalomesenteric Duct and Urachal Remnants ���������������������� 429
Daniele Alberti and Giovanni Boroni
33 The Bladder Exstrophy-Epispadias Complex (BEEC)���������������� 441
Geoffroy de Sallmard, Omar Alhadeedi, Delphine Demède,
and Pierre Mouriquand
34 Prune-Belly Syndrome�������������������������������������������������������������������� 459
Mario Messina, Francesco Molinaro, and Rossella Angotti

Part VII Tumors

35 Neuroblastoma in Neonates������������������������������������������������������������ 471

Matteo Carella, Riccardo Masetti, Claudio Antonellini,
Beatrice Randi, Andrea Pession, and Mario Lima
36 Hepatic Tumours������������������������������������������������������������������������������ 479
Matteo Carella, Riccardo Masetti, Claudio Antonellini,
Beatrice Randi, and Andrea Pession
37 Wilms Tumor in Neonates �������������������������������������������������������������� 485
Matteo Carella, Riccardo Masetti, Claudio Antonellini,
Beatrice Randi, and Andrea Pession
38 Neonatal Ovarian Cysts������������������������������������������������������������������ 491
Gloria Pelizzo
39 Teratoma: Sacrococcygeal and Cervical���������������������������������������� 499
Olivier Reinberg
viii Contents

Part VIII Genitourinary
40 Congenital Ureteropelvic Junction Obstruction �������������������������� 515
Michela Maffi and Mario Lima
41 Multicystic Dysplastic Kidney�������������������������������������������������������� 527
Michela Maffi and Mario Lima
42 Vesicoureteral Reflux���������������������������������������������������������������������� 533
Michela Cing Yu Wong and Girolamo Mattioli
43 Ureterocele���������������������������������������������������������������������������������������� 555
Pierluigi Lelli Chiesa, Dacia Di Renzo, and Giuseppe Lauriti
44 Posterior Urethral Valves: Fetal and Neonatal Aspects���������������� 579
Lisieux Eyer de Jesus and João Luiz Pippi-Salle
45 Hydrometrocolpos���������������������������������������������������������������������������� 591
Devendra K. Gupta, Shilpa Sharma, and Kashish Khanna
46 Different Sexual Development (DSD)�������������������������������������������� 601
Maria Marcela Bailez
47 Congenital Anomalies of the External Male Genitalia ���������������� 607
Francesco Di Lorenzo, Neil Di Salvo, and Mario Lima

Part IX Nervous System

48 Surgical Treatment of Central Nervous System

Malformations���������������������������������������������������������������������������������� 615
Mirko Scagnet, Federico Mussa, Flavio Giordano, Regina
Mura, Elena Arcovio, Massimiliano Sanzo, Pier Arturo
Donati, Barbara Spacca, Manuela Grandoni, Giuseppe
Oliveri, and Lorenzo Genitori
49 Central Nervous System Congenital Tumors�������������������������������� 653
Barbara Spacca, Iacopo Sardi, Annamaria Buccoliero,
Regina Mura, Milena Guidi, Chiara Caporalini,
Flavio Giordano, Leonardo Bussolin, Massimiliano Sanzo,
and Lorenzo Genitori

Part X Miscellaneous

50 Vascular Anomalies in Children ���������������������������������������������������� 687

Oumama El Ezzi and Anthony de Buys Roessingh
Index���������������������������������������������������������������������������������������������������������� 703
Contributors

Daniele  Alberti Clinica Chirurgica Pediatrica, Università degli studi di

Brescia, ASST Spedali Civili di Brescia, Brescia, Italy
Omar Alhadeedi  Service de Chirurgie Uro-génitale de l’Enfant, Hospices
Civils de Lyon, Université Claude Bernard, Lyon1, Hôpital Mère-Enfant,
Bron, France
Morven Allan  Department of Paediatric Surgery, Kings College Hospital,
London, UK
Enrica Antonelli  Department of Paediatric Surgery, University of Messina,
Messina, Italy
Claudio  Antonellini Department of Pediatric Surgery, Sant’Orsola-­
Malpighi University Hospital, Bologna, Italy
Pietro  Antonuccio Department of Human Pathology in Adult and
Developmental Age “Gaetano Barresi”, Unit of Paediatric Surgery, University
of Messina, Messina, Italy
Antonino Appignani  S.C. di Clinica Chirurgica Pediatrica, S. Maria della
Misericordia Hospital, University of Perugia, Perugia, Italy
Elena  Arcovio Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Salvatore Arena  Department of Paediatric Surgery, University of Messina,
Messina, Italy
María Marcela  Bailez Department of Pediatric Surgery, Garrahan’s
Children’s Hospital—Surgical Simulation Center, CeSim, University of
Buenos Aires, Buenos Aires, Argentina
Michelangelo  Baldazzi Department of Pediatric Radiology, S.  Orsola-­
Malpighi Hospital, Bologna, Italy
François Becmeur  Department of Pediatric Surgery, University Hospitals,
Strasbourg, France
Mirko  Bertozzi S.C. di Clinica Chirurgica Pediatrica, S.  Maria della
Misericordia Hospital, University of Perugia, Perugia, Italy
Adrian Bianchi  Royal Manchester Children’s Hospital, Manchester, UK

ix
x Contributors

Arnaud Bonnard  Department of General Pediatric Surgery, Robert Debre

Children University Hospital, APHP, Paris, France
Giovanni  Boroni Clinica Chirurgica Pediatrica, ASST Spedali Civili di
Brescia, Brescia, Italy
Martin Broome  Multidisciplinary Cleft Team, University Hospital Center
of the Canton of Vaud (CHUV), Lausanne, Switzerland
Annamaria  Buccoliero Pathology, “Anna Meyer” Children’s Hospital,
Florence, Italy
Leonardo  Bussolin Neuroanesthesiology, “Anna Meyer” Children’s
Hospital, Florence, Italy
Sebastiano  Cacciaguerra  Department of Paediatric Surgery,
A.R.N.A.S. Garibaldi, Catania, Italy
Chiara Caporalini  Pathology, “Anna Meyer” Children’s Hospital, Florence,
Italy
Fabio  Caramelli  Department of Anaesthesia and Pediatric Intensive Care
Unit, S.Orsola University Hospital, Bologna, Italy
Matteo  Carella  Department of Pediatric Hematology Oncology,
Sant’Orsola-Malpighi University Hospital, Bologna, Italy
Filomena  Carfagnini Department of Pediatric Radiology, S.  Orsola-­
Malpighi Hospital, Bologna, Italy
Pieralba Catalano  Department of Paediatric Surgery, A.R.N.A.S. Garibaldi,
Catania, Italy
Maria  Teresa  Cecini Department of Anaesthesia and Pediatric Intensive
Care Unit, S.Orsola University Hospital, Bologna, Italy
Mariapina  Cerulo Pediatric Surgery Unit, Department of Translational
Medical Sciences, Federico II University, Naples, Italy
Chiara  Cordola Department of Pediatric Surgery, S.Orsola Hospital,
Bologna University, Bologna, Italy
Philip  Corbett Department of Pediatric Surgery, Chelsea Children’s
Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, Imperial
College London, London, UK
Giuseppe Cortese  Department of Anesthesiology, Pediatric Anesthesiology
Unit, Federico II University, Naples, Italy
Sara  Costanzo Pediatric Surgery Department, Ospedale dei Bambini
V. Buzzi, Milano, Italy
Dacia Di Renzo  Department of Pediatric Surgery, “Spirito Santo” Hospital,
Pescara, and “G. d’Annunzio” University, Chieti-Pescara, Italy
Mark Davenport  Department of Paediatric Surgery, Kings College Hospital,
London, UK
Contributors xi

Anthony  S.  de Buys  Roessingh  Department of Pediatric Surgery, Centre

Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland
Multidisciplinary Cleft Team, University Hospital Center of the Canton of
Vaud (CHUV), Lausanne, Switzerland
Lisieux Eyer de Jesus  Pediatric Surgery and Urology Department, Antonio
Pedro University Hospital, Rio de Janeiro, Brazil
Servidores do Estado Federal Hospital, Rio de Janeiro, Brazil
Delphine Demède  Service de Chirurgie Uro-génitale de l’Enfant, Hospices
Civils de Lyon, Université Claude Bernard, Lyon1, Hôpital Mère-Enfant,
Bron, France
Geoffroy  de Sallmard Service de Chirurgie Uro-génitale de l’Enfant,
Hospices Civils de Lyon, Université Claude Bernard, Lyon1, Hôpital Mère-­
Enfant, Bron, France
Francesca  Destro Pediatric Surgery Department, Ospedale dei Bambini
V. Buzzi, Milano, Italy
Francesco Di Lorenzo  Department of Pediatric Surgery, S.Orsola Hospital,
Bologna University, Bologna, Italy
Neil Di Salvo  Department of Pediatric Surgery, S.Orsola Hospital, Bologna
University, Bologna, Italy
Pier  Arturo  Donati Department of Neurosurgery, Ospedale Pediatrico
Meyer, Firenze, Italy
Maria  Escolino Pediatric Surgery Unit, Department of Translational
Medical Sciences, Federico II University, Naples, Italy
Ciro Esposito  Pediatric Surgery Unit, Department of Translational Medical
Sciences, Federico II University, Naples, Italy
Oumama  El Ezzi Department of Pediatric Surgery, Centre Hospitalier
Universitaire Vaudois (CHUV), Lausanne, Switzerland
Multidisciplinary Cleft Team, University Hospital Center of the Canton of
Vaud (CHUV), Lausanne, Switzerland
Monica Fae  Department of Anaesthesia and Pediatric Intensive Care Unit,
S.Orsola University Hospital, Bologna, Italy
Alessandra  Farina Pediatric Surgery Unit, Department of Translational
Medical Sciences, Federico II University, Naples, Italy
Francesco  Fascetti-Leon  Pediatric Surgery, Department of Women’s and
Children’s Health, University of Padova, Padova, Italy
Maria Grazia Faticato  Paediatric Surgery Unit, Istituto Giannina Gaslini,
DINOGMI University of Genoa, Genoa, Italy
Luisa  Ferrero Department of Pediatric Surgery, Regina Margherita
Children’s Hospital, Turin, Italy
xii Contributors

Francesco Molinaro  Division of Pediatric Surgery, Department of Medical,

Surgical and Neurological Sciences, University of Siena, Siena, Italy
Piergiorgio  Gamba Pediatric Surgery, Department of Women’s and
Children’s Health, University of Padova, Padova, Italy
Lorenzo Genitori  Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Neurosurgery, “Anna Meyer” Children’s Hospital, Florence, Italy
Flavio Giordano  Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Neurosurgery, “Anna Meyer” Children’s Hospital, Florence, Italy
Giovanni  Parente Department of Pediatric Surgery, S.Orsola Hospital,
Bologna University, Bologna, Italy
Giuseppe  Lauriti Department of Pediatric Surgery, “Spirito Santo”
Hospital, Pescara, and “G. d’Annunzio” University, Chieti-Pescara, Italy
Manuela  Grandoni Department of Neurosurgery, Ospedale Pediatrico
Meyer, Firenze, Italy
Laura  Greco Department of Pediatric Radiology, S.  Orsola-Malpighi
Hospital, Bologna, Italy
Milena  Guidi Neuro-Oncology, “Anna Meyer” Children’s Hospital,
Florence, Italy
Devendra K. Gupta  Department of Pediatric Surgery, All India Institute of
Medical Sciences, New Delhi, India
Georges Herzog  Multidisciplinary Cleft Team, University Hospital Center
of the Canton of Vaud (CHUV), Lausanne, Switzerland
Elisa Iannella  Department of Anaesthesia and Pediatric Intensive Care Unit,
S.Orsola University Hospital, Bologna, Italy
Kashish  Khanna Department of Pediatric Surgery, All India Institute of
Medical Sciences, New Delhi, India
Antti  Koivusalo Section of Pediatric Surgery, Children’s Hospital,
University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Kristiina Kyrklund  Department of Pediatric Surgery, Children’s Hospital,
Helsinki University Central Hospital, Helsinki, Finland
Mario Lima  Department of Pediatric Surgery, S.Orsola Hospital, Bologna
University, Bologna, Italy
Michela Maffi  Department of Pediatric Surgery, S.Orsola Hospital, Bologna
University, Bologna, Italy
Maximiliano Maricic  Pedro de Elizalde Children’s Hospital, Buenos Aires,
Argentina
Contributors xiii

Garrahan Children’s Hospital—Surgical Simulation Center, CeSim, Buenos

Aires, Argentina
Elisa  Magrini S.C. di Clinica Chirurgica Pediatrica, S.  Maria della
Misericordia Hospital, University of Perugia, Perugia, Italy
Mario  Messina Division of Pediatric Surgery, Department of Medical,
Surgical and Neurological Sciences, University of Siena, Siena, Italy
Francesca  Mariscoli Pediatric Surgery Unit, Salesi Children’s Hospital,
Ancona, Italy
Ascanio  Martino Pediatric Surgery Unit, Salesi Children’s Hospital,
Ancona, Italy
Riccardo  Masetti Department of Pediatric Hematology Oncology,
Sant’Orsola-Malpighi University Hospital, Bologna, Italy
Girolamo  Mattioli Paediatric Surgery Unit, Istituto Giannina Gaslini,
DINOGMI University of Genoa, Genoa, Italy
Maria  Cristina  Mondardini Department of Anaesthesia and Pediatric
Intensive Care Unit, S.Orsola University Hospital, Bologna, Italy
Pierre  Mouriquand Service de Chirurgie Uro-génitale de l’Enfant,
Hospices Civils de Lyon, Université Claude Bernard, Lyon1, Hôpital Mère-­
Enfant, Bron, France
Regina  Mura Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Neurosurgery, “Anna Meyer” Children’s Hospital, Florence, Italy
Federico Mussa  Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Fabiano Nino  Pediatric Surgery Unit, Salesi Children’s Hospital, Ancona,
Italy
Lluís  Nisa Department of Otorhinolaryngology, Head and Neck Surgery,
Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland
Giuseppe Oliveri  Department of Neurosurgery, Policlinico Le Scotte, Siena,
Italy
Mikko  P.  Pakarinen Section of Pediatric Surgery and Pediatric Liver
and Gut Research Group, Children’s Hospital, University of Helsinki and
Helsinki University Hospital, Helsinki, Finland
Filippo Parolini  Department of Paediatric Surgery, Kings College Hospital,
London, UK
Gloria  Pelizzo Pediatric Surgery Unit, Children’s Hospital, ARNAS
Civico-Di Cristina-Benfratelli, Palermo, Italy
xiv Contributors

Patrizia  Perrone Department of Human Pathology in Adult and

Developmental Age “Gaetano Barresi”, Unit of Paediatric Surgery, University
of Messina, Messina, Italy
Andrea  Pession  Department of Pediatric Hematology Oncology,
Sant’Orsola-Malpighi University Hospital, Bologna, Italy
Pierluigi  Lelli Chiesa Department of Pediatric Surgery, “Spirito Santo”
Hospital, Pescara, and “G. d’Annunzio” University, Chieti-Pescara, Italy
João  Luiz  Pippi-Salle Division Chief of Urology Sidra Medical and
Research Center, Doha, Qatar
Antonio  Poerio Department of Pediatric Radiology, S.  Orsola-Malpighi
Hospital, Bologna, Italy
Beatrice  Randi Department of Pediatric Surgery, Sant’Orsola-Malpighi
University Hospital, Bologna, Italy
Gianluca Rasetto  Department of Pediatric Radiology, S. Orsola-Malpighi
Hospital, Bologna, Italy
Olivier Reinberg  Department of Pediatric Surgery, Lausanne, Switzerland
Giovanna  Riccipetitoni Pediatric Surgery Department, Ospedale dei
Bambini V. Buzzi, Milano, Italy
Risto  Rintala Department of Pediatric Surgery, Children’s Hospital,
Helsinki University Central Hospital, Helsinki, Finland
Carmelo  Romeo Department of Human Pathology in Adult and
Developmental Age “Gaetano Barresi”, Unit of Paediatric Surgery, University
of Messina, Messina, Italy
Rossella  Angotti Division of Pediatric Surgery, Department of Medical,
Surgical and Neurological Sciences, University of Siena, Siena, Italy
Kishore  Sandu Department of Otorhinolaryngology, Head and Neck
Surgery, Lausanne University Hospital, CHUV, Lausanne, Switzerland
Massimiliano  Sanzo Department of Neurosurgery, Ospedale Pediatrico
Meyer, Firenze, Italy
Neurosurgery, “Anna Meyer” Children’s Hospital, Florence, Italy
Iacopo  Sardi Neuro-Oncology, “Anna Meyer” Children’s Hospital,
Florence, Italy
Amulya  Saxena Department of Pediatric Surgery, Chelsea Children’s
Hospital, Chelsea and Westminster Hospital NHS Foundation Trust, Imperial
College London, London, UK
Mirko  Scagnet  Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Aurelién  Scalabre Department of Pediatric Surgery, University Hospital
Centre, Saint-Etienne Cedex 2, France
Contributors xv

Alessandro  Settimi Pediatric Surgery Unit, Department of Translational

Medical Sciences, Federico II University, Naples, Italy
Shilpa  Sharma Department of Pediatric Surgery, All India Institute of
Medical Sciences, New Delhi, India
Barbara Spacca  Department of Neurosurgery, Ospedale Pediatrico Meyer,
Firenze, Italy
Neurosurgery, “Anna Meyer” Children’s Hospital, Florence, Italy
Janne  Suominen Section of Pediatric Surgery, Children’s Hospital,
University of Helsinki and Helsinki University Hospital, Helsinki, Finland
Pedro Saraiva Teiga  Department of Otorhinolaryngology, Head and Neck
Surgery, Lausanne University Hospital, CHUV, Lausanne, Switzerland
Juan A. Tovar  Department of Pediatric Surgery, Hospital Universitario La
Paz, Madrid, Spain
Department of Pediatrics, Universidad Autonoma de Madrid, Madrid, Spain
Francesco  Turrà Pediatric Surgery Unit, Department of Translational
Medical Sciences, Federico II University, Naples, Italy
Stefaan  H.  Tytgat Department of Pediatric Surgery, University Medical
Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
David C. van der Zee  Department of Pediatric Surgery, University Medical
Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The Netherlands
Maud  Y.  van Herwaarden Department of Pediatric Surgery, University
Medical Center Utrecht, Wilhelmina Children’s Hospital, Utrecht, The
Netherlands
Francois  Varlet Department of Pediatric Surgery, University Hospital
Centre, Saint-Etienne Cedex 2, France
Sophie  Vermersch Department of Pediatric Surgery, University Hospital
Centre, Saint-Etienne Cedex 2, France
Donatella Vivacqua  Department of Pediatric Radiology, S. Orsola-Malpighi
Hospital, Bologna, Italy
Michela Cing Yu Wong  Paediatric Surgery Unit, Istituto Giannina Gaslini,
DINOGMI University of Genoa, Genoa, Italy
 Introduction to Neonatal Surgery
1
Olivier Reinberg

In 1989, the British National Confidential We live now in the era of evidence-based med-
Enquiry into Perioperative Deaths (NCEPOD) icine (EBM), and best evidences are generated
ruled “that pediatricians and general surgeons from prospective trials. Unfortunately, when
must recognize that small babies differ from compared with adult general surgeons who may
other patients not only in size and stated that they operate hundreds of similar cases, pediatric sur-
pose quite separate problems of pathology and geons perform a great variety of different proce-
management” [1]. dures but few of each. Consequently, the
As pediatric surgeons, we are convinced that indications for surgery and the type of procedure
children are not just small adults. This is all the performed in neonates are rarely supported by
more true for neonates. Neonates have some randomized controlled trials, the majority being
unique problems that require very special knowl- supported by retrospective studies and surgeon’s
edge, special surgical managements, and facili- preferences. Hall and Pierro have tried to sum-
ties specifically designed for them. Pediatric marize what was the EBM randomized controlled
surgeons must understand their special needs and trial (RCT) (level I evidence) of some of the most
that of their relatives. They must learn team common neonatal procedures (esophageal atre-
working with other specialists. They have to cre- sia, congenital diaphragmatic hernia (CDH),
ate the conditions to follow their patients from bowel atresia, anorectal malformations, anterior
birth into adulthood as the treatments do not end abdominal wall defects, congenital lung lesions,
with the healing of the problem but once the child Hirschsprung’s disease, inguinal hernia, necro-
has become an adult. tizing enterocolitis, pyloric stenosis). Their
With the rapid advances in fetal diagnosis, review highlights the fact that a quality evidence
babies are no longer referred at the time of birth, base supporting many of these interventions is
but when prenatal diagnosis is made even if ter- lacking. Only a few randomized controlled trials
mination of pregnancy is planned because of an have been done in neonatal diseases such as con-
expected poor prognosis. Direct contacts between genital diaphragmatic hernia, necrotizing entero-
the prenatal team, the neonatologists, and the colitis, pyloric stenosis, and inguinal hernia. All
pediatric surgeons are also highly recommended of these trials have been based on collaboration
to ensure continuity in the messages delivered to between pediatric surgical units convinced by the
the parents. importance of networks to promote multicenter
prospective studies [2].

O. Reinberg (*)
Department of Pediatric Surgery, Lausanne, Switzerland

© Springer Nature Switzerland AG 2019 1

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_1
2 O. Reinberg

In 1999, Hardin and Stylianos undertake to ried out by surgeons and anesthetists whose pedi-
study the current state of the pediatric surgery lit- atric workload is of adequate volume to maintain
erature and its value in determining best clinical a high level of surgical competence and to allow
practice. As of March 1, 1998, they found 9373 the training of the residents. Congenital birth
references provided through Medline. After defects complicate 3–6% of pregnancies leading
review, only 34 studies (0.3%) were classified as to live birth. As for example of the structural birth
prospective, randomized, controlled studies [3]. defects associated with significant mortality/
Twelve years later, Ostlie and St Peter have done morbidity, CDH is among one of the most com-
a similar study in 2010, collecting all randomized mon anomalies, occurring in about one per 2000–
controlled trials from January 1999 through 3000 live births. Consequently, the opportunity
December 2009 published in the English litera- of training—and to keep his expertise—on a
ture excluding transplant, oncology, and the other CDH is low. Added to these facts, the combina-
non-general subspecialties, to conclude that ran- tion of a shortened training period and the “new
domized controlled trials represent less than deal” on junior doctors about the number of hours
0.05% of all publications involving pediatric sur- has serious implications for training.
gery in the 26 journals with at least one trial (<1 This means that neonatal malformations need
trial for every 200 articles) [4]. It is concerning to be concentrated in some centers to allow suf-
that they document a similar lack in the twenty-­ ficient case load. There are arguments for and
first century, despite the increased educational against such large regional specialist pediatric
and public expectations placed on EBS. centers. The benefits of centralization include
In a recent lecture, Juan Tovar advocated to concentration of expertise, more appropriate con-
which extent pediatric surgery needs to base its sultants on call, development of support services,
therapeutic attitudes and operations on a solid and training. The disadvantages include children
research background [5]. This is particularly and their families far from their homes and the
difficult on the field of clinical research because loss of expertise at a local level. The benefits of
of the low prevalence of many of the conditions centralization far outweigh the adverse effects of
involved and also because of the fact that having to take children to a regional pediatric
patients are minors that are not entitled to give intensive care center [6]. Unfortunately, in many
informed consent by themselves for random- places, politicians favor the multiplication of
ized studies. As regards laboratory research, small regional centers to satisfy their voters who
this specialty is scarcely interesting for basic are poorly informed of the cold hard facts.
scientists. This situation can only be improved Nowadays, it is unacceptable to train on real
by prospective randomized studies performed patients. The new technologies, namely, minimal
in network collaboration with other hospitals/ invasive surgery and simulators, have been of
countries and by basic research conducted by great help using simulation technology to reduce
pediatric surgeons and/or in association with risks to both students and patients by allowing
other scientists [5]. training, practice, and testing in a safe environ-
Among the three particularly relevant recom- ment prior to real-world exposure. This is sup-
mendations that NCEPOD made in the report on ported by interest in quality of care, restrictions
perioperative pediatric deaths [1], the first one on the use of animal models, limited number of
was: “surgeons and anesthetists should not under- cases, medicolegal pressures, and cost-effective
take occasional pediatric practice”. This was also performance. Many models are available. The
a statement of the European Union of Medical usefulness of mechanical simulators with faithful
Specialists (EUMS) in 1995: “Surgeons taking models have been proven efficient: hypertrophic
care of children should have adequate training in pyloric stenosis (Plymale, 2010), closure of pat-
a pediatric surgical unit. They should also con- ent peritoneo-vaginal tract (Breaud, 2014),
tinue to have regular exposure to this type of pyeloplasty (Breaud, 2014), esophageal atresia
patients.” Neonatal surgery should only be car- (Maricic and Bailez, 2012; Barsness, 2014), and
1  Introduction to Neonatal Surgery 3

CDH (Barsness, 2013). They have shift to realis- collaboration. This will be the challenge of the
tic interactive models. Computerized modern new generation of pediatric surgeons to promote
technology with electronically assisted devices collaboration between pediatric surgical units
and virtual reality environment has provided new and to create networks as to publish multicenter
tools to the mechanical simulators. prospective studies with adequate sample sizes.
We have now the tools to evaluate cognitive/ In spite of these daunting challenges, they
clinical skills, technical skills, and social/interactive remain some courageous volunteers as you prob-
skills as we have seen how important this could be ably are, you reader of this book. We need neona-
in neonatal surgery. Surgical simulators (mechani- tal surgeons, motivated, well trained, wishing to
cal, computerized, virtual) and models (animals and transmit their skills and their knowledge to the
interactive) are the appropriate tools to learn, to future one.
train, to assess surgical skills, and to keep his exper-
tise, in spite of the small number of cases.
Becoming a pediatric surgeon requires com-
References
pletion of one of the longest training programs 1. NCEPOD (National Confidential Enquiry into
among the medical systems and probably the Perioperative Deaths). Health Serv Manage.
widest as they have to learn a great variety of pro- 1990;86(5):203.
cedures but few of each. While specialization 2. Hall NJ, Eaton S, Pierro A.  The evidence base for
­neonatal surgery. Early Hum Dev. 2009;85:713–8.
among adult surgeons usually focuses on a par- 3. Hardin WD, Stylianos S, Lally KP.  Evidence-­
ticular organ or region of the body, pediatric sur- based practice in pediatric surgery. J Pediatr Surg.
gery deals with a defined age group. Pediatric 1999;34(5):908–13.
surgeons are trained to operate anywhere on the 4. Ostlie DJ, St Peter SD.  The current state of
evidence-­based pediatric surgery. J Pediatr Surg.
body, and thus they appear to be probably the last 2015;45:1940–6.
general surgeons. They must ask their authorities 5. Tovar JA. Research in pediatric surgery. E-Mem Acad
to provide them modern tools to avoid training on Natl Chir. 2016;15(3):67–70. http://www.academie-
real babies. Undoubtedly, this is expensive, but as chirurgie.fr/ememoires/005_2016_15_3_067x070.
pdf.
said by Bok Derek at Harvard Law School, “If 6. Arul GS, Spicer RD.  In where should paediatric
you think education is expensive, try ignorance!” surgery be performed? Arch Dis Child. 1998;79(1):
They have to learn teamwork and multicenter 65–70; discussion 70–2.
 Part I
General
 Anesthesiological Considerations:
Stabilization of the Neonate, Fluid 2
Administration, Electrolyte
Balance, Vascular Access, ECMO,
Bronchoscopy, and Pain
in Neonates

Fabio Caramelli, Maria Teresa Cecini, Monica Fae,

Elisa Iannella, and Maria Cristina Mondardini

2.1 Introduction and animal studies [1, 2], as well as some epide-
miological and cohort studies in humans [3–6],
Despite progress in anesthesiology, neonatal provide evidence of neurotoxic (apoptotic) effects
anesthesia today still represents one of the most of anesthetics during the synaptogenesis, which
challenging areas in this field for the anatomical, can induce long-term neurocognitive deficits.
physiopathological, and pharmacological fea- On December 14, 2016, the Food and Drug
tures of newborn babies and requires not only Administration (FDA) issued a warning state-
highly specialist knowledge but also manual and ment for the USA regarding the use of anesthesia
technical skills, owing to the size and fragility of or sedation in children less than 3  years of age
these patients. [7]. Nevertheless, the hypothesis of anesthetic
The mortality rate linked to anesthesiological neurotoxicity has not been confirmed in humans,
problems has fallen dramatically in neonates and at least for a single and short-term anesthesia [8,
infants from 1/10,000 in the 1960s to 1/100,000 9]; therefore, the FDA warning is not shared by
(1/1,000,000 in healthy patients) today, but it is several Anesthesia European Societies [10].
considerably higher than the equivalent rate in At the same time, the focus is actually concen-
adults. trating also on the need to ensure the newborn a
This proves the particular vulnerability of this safe conduct of general anesthesia and good peri-
patient group, mainly due to difficulties in airway operative clinical practice. The Safetots initiative
management, the presence of congenital lesion or (http://www.safetots.org/) highlights that there is
syndromes, coexisting pathologies, and, poten- a casual relationship between poor anesthetic
tially, prematurity. conduct and risk of neuromorbidity.
Furthermore, the developing brain seems to be In fact, several perioperative events may cause
susceptible to the damaging effects of the anes- cerebral morbidity. The concept of 10-N has been
thetic drugs. Extensive literature from laboratory proposed by the Safetots initiative to prevent neu-
rological injury. The 10-N principles provide a
F. Caramelli (*) · M. T. Cecini · M. Fae simple matrix of clinical goals: No fear,
E. Iannella · M. C. Mondardini Normovolemia, Normotension, Normal heart
Department of Anaesthesia and Pediatric Intensive rate, Normoxemia, Normocapnia, Normonatremia,
Care Unit, S.Orsola University Hospital, Normoglycemia, Normothermia, and No
Bologna, Italy
e-mail: [email protected] ­postoperative discomfort [11]. It is recommended

© Springer Nature Switzerland AG 2019 7

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_2
8 F. Caramelli et al.

that the 10-N be applied to maintain physiological emergencies—detailed medical history, exhaus-
homeostasis. tive physical exam, and management of
The development of pharmacological knowl- ABCDE—such as maintaining correct body tem-
edge, the availability of new smaller medical devices, perature, fighting respiratory insufficiency, opti-
the doubts related to the aforementioned safety of mizing blood volume, and cardiac output.
anesthetic agents, and, above all, the increased Monitoring, respiratory and cardiac support,
spread of ultrasound in the field of anesthesia have fluid and electrolyte replacement, and optimal
led to a progressive increase in the use of locore- analgesia are the cornerstones of this process, and
gional anesthesia techniques even in babies. this strategy should be carried on also in the oper-
These safe and effective techniques can be ating theater to avoid any clinical deterioration.
easily used in selected cases, even without seda- In fact, as already mentioned, maintenance of
tive drugs, employing non-pharmacological tech- physiological homeostasis is key for the safe con-
niques of distraction, as demonstrated by duct of anesthesia. Experience is recommended to
preliminary report of the ongoing GAS trial [8]. avoid or minimize complications and adverse events,
In the following pages, only certain aspects of especially in neonates, which are prone to hypoten-
the anatomy and physiology of the newborn and sion, desaturation, and effects of anesthetics.
their changing features over time will be touched During the perioperative period, it is impor-
on briefly within each individual topic, apart from tant to avoid not only hypotension, hypocapnia,
those of fluid balance and body composition. and hypoxemia but also hyperoxemia and hypo-
natremia, especially in neonates. All these events
can cause subclinical neuronal damage: hypoten-
2.2 Surgical Emergencies sion and hypocapnia can lead to cerebral hypo-
and Stabilization perfusion; hypoxemia is tolerated only for a short
time because neonates have higher oxygen
With the advances in care of the newborn over demand and lower oxygen reserves [13].
the last 20 years, most of the surgical pathologies Congenital diaphragmatic hernia (CDH) is
that were emergencies in the past no longer prototype of this changed paradigm.
require immediate surgery. Approximately 1 in 3000 babies is born with a
This change in the approach toward the surgi- congenital diaphragmatic hernia [14].
cal neonate was also born from the evidence that The disorder is characterized by herniation of
adequate stabilization time before the operation the abdominal viscera into the thoracic cavity and
is able to improve outcomes, leading the patient pulmonary hypoplasia. This one, with associated
to the surgery in the best possible conditions. pulmonary hypertension and ventricular dysfunc-
The stabilization of the patient is even more tion/hypoplasia, is key factor which contributes
important if he has to be transferred, given that to the morbidity and mortality associated with
the transport is challenging for the physiologic CDH (30–40%).
reserve of the critically ill newborn. The current strategy to postpone surgery until the
In fact there is greater risk for babies requiring cardiorespiratory function is stabilized reflects the
neonatal intensive care who are transferred ex idea that surgery cannot correct these factors [15].
utero than those transferred in utero [12]. Firstly, after delivery, the infant should be
Stabilization is optimization of clinical condi- intubated immediately without bag and mask
tions and physiologic functions on the basis of ventilation, and a nasogastric tube should be
the underlying pathology and its pathophysiol- positioned to avoid bowel distension that can
ogy, targeting the therapy also on coexisting dis- limit the expansion of the lung [15].
eases (e.g., CHDs), as failure to do so may mean Routine use of surfactant is not recommended
futile every other efforts. [16], and conventional ventilation seems to offer
The fundamental concepts of the stabilization better results in comparison with high-frequency
are always the same in medical and surgical oscillatory ventilation (HFOV) regarding time on
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 9

mechanical ventilation, need of extracorporeal 2.3 Fluid Administration

membrane oxygenation (ECMO), inhaled nitric and Electrolyte
oxide (iNO), sildenafil, inotropes, and numbers Balance in Neonate
of failed treatment, as shown by the recent VICI in the Perioperative Period
(Conventional mechanical ventilation versus
high-frequency oscillatory ventilation for con- Fluid and electrolyte therapy is an essential com-
genital diaphragmatic hernia: a randomized clini- ponent of the care of the neonatal surgical patient,
cal trial (the VICI-trial)) [17]. and an accurate understanding of the changing
These results probably suggest that minimiz- requirements of growing is fundamental in appre-
ing lung injury is much more important than the ciating the many important pharmacokinetic
used strategy to reach it. changes that occur from birth to childhood.
However, ventilation is not the only way to There are developmental considerations that
improve blood oxygenation. Inotropes and pulmo- anesthesiologists should consider.
nary vasodilators are also needed to maintain better Total body water (TBW) content changes
systemic/pulmonary blood pressure (BP) and to remarkably from before birth until 1 year of age.
counteract right-to-left shunting across the ductus. At 24 weeks’ gestational age, a baby’s TBW con-
Extensive use of echocardiography can not only tent is close to 85% of total body weight (BW),
give several prognostic factors [18, 19] but also which is due to a large extracellular fluid (ECF)
helps in clinical management, allowing for moni- volume of 40–50% of BW (in comparison with
toring of pulmonary hypertension, diastolic func- 20% in adults) [32]. This percentage decreases to
tion of the right ventricle, dysfunction/hypoplasia 75% of total BW for a term newborn but small
of the left ventricle, and response to the therapy. for gestational age (SGA); preterm infants have
iNO, the most frequently used pulmonary an even higher TBW content than appropriate for
vasodilators [20], failed to improve survival or gestational age babies (AGA) [33].
reduce the need for ECMO, but, in some cases, After birth, the excess of TBW is mobilized
an increase in PaO2 was observed [21]. and excreted, and the newborn may lose up to
Pulmonary hypertension may also be treated 10–15% of its weight (in preterm babies) in the
by several other agents (Milrinone, sildenafil, first week of life. Then, the intracellular fluid
PGI2, inhaled iloprost, bosentan) even if there is (ICF) compartment progressively increases at the
limited evidence of positive effects on primary expense of the ECF compartment. This means
outcomes [22–26]. that extracellular water content falls in parallel
However, the hemodynamics, the cardiac with TBW content, from 45% at term to 20–25%
insufficiency, and the pulmonary hypertension at 1 year of age. The ECF is further divided into
should be managed simultaneously, as previously plasma volume (intravascular fluid, equal to
described, in order to progressively obtain the 4–5% of BW and proportionally similar at all
better oxygenation and perfusion with the lesser ages) and the interstitial fluid.
ventilatory insult during the stabilization phase. There is a similarity in extracellular and intra-
From this point of view, prostaglandin-E cellular electrolyte composition in children and
(PGE)1 can also be used to improve the hemody- adults, but, due to the higher ECF volume in
namics, employing the ductus as a ventricular infants, there is more sodium and chloride per
vent in case of severe pH and right ventricular kilogram and less potassium in infants than in
dysfunction [27, 28]. adults.
There are no standard criteria to define physi- Furthermore, newborns carry a lower liver
ologic stabilization, but also our group has pro- mass (glycogen stores) and muscle mass (protein
posed the trend and the value of five different stores) and, therefore, are less able to maintain
respiratory and blood-gas-derived indices to the normoglycemia during fasting through glyco-
guide the timing of surgery [29]. The reliability genolysis and gluconeogenesis.
of these indices may probably be increased by the The postnatal shift in body fluid is principally
use of echocardiography [30, 31]. mediated through the regulation of water and
10 F. Caramelli et al.

sodium excretion by the kidneys (due to the increase management. Although the pathophysiological
in atrial natriuretic peptide (ANP) secretion and bases are well-investigated, some aspects still
tubular insensitivity to aldosterone) [34, 35]. remain controversial, mainly in newborn infants.
A term newborn’s glomerular filtration rate is The goal of infusion therapy is to maintain or
about 25% of that of an adult, and this impairs the reestablish the neonate’s normal physiological
ability to excrete a water load. Renal function is state in blood volume, tissue perfusion, metabolic
not completely developed, and, in particular, function, electrolyte, and acid-base balance [43].
sodium clearance is limited. Therefore, the neo- The optimal regimen of fluid management is
nate’s kidneys have limited capacity to excrete still a matter of debate, and great concerns remain
both concentrated and diluted urine so are unable about the type of fluids, the ideal composition of
to concentrate urine despite dehydration [36, 37]. solutions, and the amount of fluids that should be
Neonates also have large blood volume, high administered [44].
metabolism, and high fluid turnover rates relative In any event, the neonatal anesthesiologist
to their body weight. These changes have impor- must bear in mind that the preoperative fasting
tant implications for drug therapy, fluid manage- times for patients should be as short as possible
ment, electrolyte needs, and glucose requirements to prevent newborn dehydration, ketoacidosis,
in the perioperative period. and discomfort [45].
In particular, neonates undergoing major sur- In line with the European Consensus Statement
gery are at greater risk of developing dehydra- Guidelines, recent literature recommends the use
tion, hyponatremia, and alteration in blood of low glucose (1–2.5%) isotonic balance solu-
glucose level [38]. tions during neonatal surgery. These types of flu-
Hyponatremia is the most frequent electrolyte ids have been shown to maintain acceptable
disorder in the postoperative period [39]. Recent glucose levels and prevent electrolyte imbalances
studies have shown that hyponatremia is due to in the perioperative period [46].
the administration of hypotonic solutions and the Due to the renal function immaturity, the
presence of multiple non-osmotic stimuli for majority of synthetic colloids should not be used.
antidiuretic hormone (ADH) release [40]. Severe The colloid molecules are large and cannot be fil-
hyponatremia leads to cerebral edema, the main tered by the kidneys; therefore, they remain in
clinical signs being a decreasing level of con- plasmatic volume for an unpredictable time.
sciousness, disorientation, and, in the most severe Albumin 5% has been considered the gold
cases, seizure, permanent handicap, or death standard for the maintenance of colloid osmotic
[41]. Therefore, avoiding infusion of hypotonic pressure in neonates and continues to be the most
fluids, during surgery and in the early postopera- frequently used fluid in volume replacement
tive period, should prevent hyponatremia [42]. therapy.
Fluid requirement can increase due to high The “right amount” of fluid administration
liquid loss during the perioperative stage, caused still remains uncertain; however, a fluid infusion
by prolonged fasting, vomit, diarrhea, fever, and rate of approximately 10 mL/kg/h is required in
major tissue exposure occurring during abdomi- neonates [47].
nal and thoracic surgery. Therefore, fluid admin- The most useful parameters that assess the effi-
istration for the neonatal surgical patients must cacy of the intraoperative infusion therapy are
be aimed at supplying basal metabolism require- mean arterial blood pressure, heart rate, capillary
ments (maintenance fluids), compensating preop- refill time, core-peripheral temperature gradients,
erative fasting and fluid losses (deficit fluids) and base deficits, and blood glucose levels.
replacing losses during surgery (replacement Measurement of central venous pressure and diure-
fluids). sis do not predict the real fluid responsiveness.
Conceptually, this distinction between main- In case of major surgery, regular (hourly)
tenance requirements, deficits, and replacement blood gas analyses should be performed to assess
loss is helpful to plan any intraoperative fluid the acid-base status (base excess, lactate) and
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 11

blood glucose level. It is recommended to use a Therefore, clinical evaluation maintains a piv-
syringe pump or infusion pump in order to avoid otal role in the management of anesthesia.
accidental overload fluid infusions during neona- In this setting, inhalation agents usually
tal intraoperative fluid therapy. remain the preferred choice of neonatal anesthe-
In the postoperative period, neonates on intra- siologists for their versatility, predictability, and
venous fluid therapy need to be evaluated regu- singular pharmacokinetics, independent of the
larly with daily weight measurements, fluid different organ functions.
balance assessment, plasma electrolytes, and glu-
cose concentrations.
2.5 Vascular Access in Neonates

2.4 Pharmacology Adequate vascular access is often challenging in

neonates [56] but is fundamental in modern
The pharmacokinetics and the pharmacodynamics emergency and intensive care and plays a deci-
in neonates are often difficult to predict; there are sive role in stabilization of the patient.
considerable interindividual differences and vari- Nowadays, the use of ultrasound (US) has
ability related to gestational age, postnatal age, greatly increased the percentage of success in
coexisting diseases, and different genetic poly- gaining vascular access [57], but, given the size
morphisms. Indeed, pharmacological data is often of neonatal structures, equipment with a small
lacking and extrapolated from adults by allometric linear probe at high frequency (>10  MHz) is
equations with corrective factors for the matura- needed. Furthermore, it should include Doppler,
tion of metabolic functions [48] (Box 2.1). which allows screening for occlusion and throm-
Not only is distribution volume increased in bosis, and zoom functions.
neonates but also metabolic/elimination ability is The vessel can be visualized in the short-axis
reduced at birth; this depends on postconcep- view (SAX), where the probe is placed transver-
tional age and changes quite rapidly over time sally to the direction of the vessel, which is seen
[49, 50]. in cross section, and in the longitudinal view or
Pharmacodynamics of anesthetics is also long-axis view (LAX), where the probe follows
affected by rapid changes in neuronal connec- the direction of the vessel, which is seen in its
tions, functional interrelationships, regional length.
blood flow, and number of γ-aminobutyric acid According to the chosen visualization
type A (GABAA) receptors in the developing approach, the progression of the needle will be
human brain [51]. placed in the US beam, so called in-plane (IP) or
Often the use of drugs is off-label in neonates; will cross it perpendicularly, so called out-of-­
only a minority (<5%) of the medications used in plane (OOP).
hospitalized neonates had been approved by the Obviously, in the first case, the movement and
FDA, and no anesthetics had updated labeling for position of the needle can be seen clearly, but it is
premature babies above 29 weeks of GA [52, 53]. not simple to keep the needle in the US beam.
Neonates have narrower margins of error in
drug delivery and dilution as well as a higher
incidence of drug substitution and drug dosage 2.5.1 Peripheral and Central Venous
errors in comparison with adults, increasing the Catheterization
clinical risk of drugs with a low therapeutic
index, like anesthetics [54]. Several different approaches are possible, and the
Furthermore, adult monitoring systems of choice among these different options is made on
anesthesia levels are not validated for use in neo- gestational age, size, site availability, underlying
nates, making the measurement of the pharmaco- pathology, and, above all, duration of and indica-
dynamics anesthetic targets impossible [55]. tion for vascular access.
12 F. Caramelli et al.

They can be classified on the basis of site of In addition to needle cannulas, long cannulas
access and tip position (umbilical, peripheral, (mini-midline) and long peripheral catheters
central peripherally inserted, and central) and of (midline) may be used, and, in these cases with
expected length of use (short term, long term, and peripheral access, it is possible to advance and
permanent). position the catheter up to a great vessel, which
allows for it to be kept in place for a longer period
2.5.1.1 Umbilical Catheters (UC) of time and to be used for endovenous solutions
The umbilical vein is the recommended emer- with higher osmolarity.
gency access for neonatal resuscitation, and cath- Peripheral access can also be gained by using
eters can easily be positioned in the first few days a surgical venous cutdown (the saphenous vein is
of life, sometimes up to the end of first week. It is the usual primary choice). This method, fre-
to consider as any other central line but must be quently used in the past, today has a limited role
removed after 5–7 days [58]. only in emergency situations when other periph-
Indications for positioning of UC are low GA eral, central, and intraosseous attempts fail.
(<29 weeks) or higher GA (>29 weeks) but need-
ing mechanical ventilation (MV), total parenteral Intraosseous Catheters
nutrition (TPN), hemodynamic support, or intra- Intraosseous catheters still have a major role in
venous infusion in cases of difficult peripheral life-threatening emergency situations when other
access [59]. access methods fail and when time is of the
The choice of size according to ultrasound mea- utmost importance.
surement of the diameter of the inferior vena cava In neonates, the preferred choice is the proxi-
and ecographic evaluation of tip position are mal tibia, but other sites are the distal tibia and
strongly recommended. A high position is optimal, distal femur [60].
where the catheter is advanced through the ductus The pediatric resuscitation guidelines from
venosus into the IVC. If a radiological check is car- the American College of Surgeons Advanced
ried out, the optimal response is the T6–T9 space, Trauma Life Support (ATLS) manual recom-
above the diaphragm. The tip of a UC in the heart mend that intraosseous access should be estab-
may result in perforation, pericardial effusion with lished in the newborn in case of circulatory
cardiac tamponade, potentially fatal arrhythmias, collapse if umbilical venous access cannot be
endocavitary thrombosis, or pleural effusion. rapidly achieved [61].
A UC placed in the portal system can lead to
necrotizing enterocolitis, colonic perforation, 2.5.1.3 Peripherally Inserted Central
necrosis and hepatic hematomas, hepatic cysts Catheters (PICC)
perforating vessels of the portal system, and por- In the same way, as described above for midline
tal hypertension. Future perspective is to follow catheters, the tip can be placed in a central posi-
the catheter under echographic vision along its tion (at the junction of the superior vena cava
progression up to the optimal point. UC migra- with the right atrium).
tions have been demonstrated in 50% of patients Usually, a suitable vein is selected under US
in the first 24–48 h. guidance, and the skin is carefully cleaned and
draped. The vein is cannulated using a removable
2.5.1.2 Peripheral Venous needle, a peelable cannula, or semi-Seldinger
Catheters (PC) technique. The catheter is then inserted into the
They are generally inserted at the level of superficial vein and slowly advanced up to the desired
veins of the upper limbs, lower limbs or, in certain length. Correct catheter tip location must be veri-
cases, at the level of the scalp. They are indicated in fied either radiologically or ultrasonographically
preterm births >31 weeks. GA or at term which or using intracavitary electrocardiography.
should receive non-hyperosmolar fluid therapy for a PICCs combine the advantages of peripheral
short period of time (maximum 6 days). catheters (less infection risk, fewer complications
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 13

during implant) with the advantages of central Complications of Central Access

catheters (long-term use, high osmolarity of flu- Perforation, infection, and thrombosis are the
ids infused). three major late complications of central venous
Its main disadvantages are hazardous venous access. The early complications are malposition,
progression after initial cannulation and small-­ arterial puncture, hematoma or hemorrhage, and
caliber catheters that may preclude blood sam- pneumothorax or hemothorax in the cases of IJV
pling, transfusion, and rapid fluid rates. or SV.
Thrombosis and catheter occlusion (10% risk) A strict protocol of catheterization technique
are the most frequent mechanical complications and management is needed to avoid infection. The
with PICCs, but even cases of rupture and embo- use of maximal sterile barriers is recommended.
lization have been described. Aseptic technique is mandatory as echographic
However, a Cochrane review suggested that guidance. Tunneling reduces the incidence of
PICC use improves nutrition in newborns with- infection [65].
out any evidence of increased adverse events, Two percent chlorhexidine is now recom-
including systemic infection [62]. mended, especially in preterm infants, for disin-
fection. Over the last 10 years, several studies
2.5.1.4 Central-Inserted Central have shown its superiority to iodopovidone
Catheter (CICC) (harmful due to reabsorption of iodine), and it
Central access (internal jugular, IJV; subclavian, can be used even for continuous antisepsis at the
SV; or femoral vein, FM) can be gained percuta- exit point [66].
neously through direct puncture with a landmark Any strategy stabilizing the catheter at the onset
approach, but a US- guided technique has fewer reduces risk of infection and thrombosis. For this
risks of complications. reason, the use of “sutureless” devices for catheter
After the vein puncture, the catheter is placed stabilization and semipermeable transparent dress-
into the vein using the Seldinger technique and ings is highly recommended, as well as the appli-
an atraumatic guide wire with a J-tip. cation of iso-acrylic glue at the exit point.
Unfortunately, in the smaller patient, the radius There is no great consensus on efficacy and
of curvature of the J-tip is close to, or larger than, safety of heparin for prevention of catheter-­
the vein. This can produce difficulties when associated thrombosis and occlusion. In fact, pro-
introducing the guide wire [63, 64]. phylactic continuous heparin infusion does not seem
The central way is chosen when the periph- to reduce the risk of thrombosis, but it may obstacu-
eral approach is not achievable, and the patient late catheter occlusion and prolong its life [67].
needs medium- or long-term infusion of TPN, However, on the basis of a Cochrane review
drugs or inotropes, and hemodynamic monitor- [68] and RCT [69], the Antithrombotic Therapy
ing (CVP). and Prevention of Thrombosis in Infants and
Whatever the site of insertion, verifying the Children Guidelines from the American College
catheter tip position with X-rays is mandatory. of Chest Physicians (ACCP) published in 2012
For catheters placed in the superior vena cava [70] recommend a UFH continuous infusion at
(SVC), the tip should be [1] outside the pericar- 0.5 units/kg/h over no prophylaxis (Grade 1A) or
dial sac to avoid perforation and tamponade and intermittent local thrombolysis (Grade 2C) to
[2] parallel to the vessel wall to avoid perforation. maintain catheter patency.
For catheters in the inferior vena cava (IVC), the
tip should be below the level of the renal veins so
as not to obstaculate drainage. 2.5.2 Arterial Catheterization
In case of CVP monitoring, the tip should be
placed in the upper part of the right atrium, but Despite noninvasive monitoring techniques,
this increases the risk of dysrhythmias, thrombo- indwelling arterial catheters are often required
sis, and perforation. in the management of critically ill neonates or
14 F. Caramelli et al.

neonates undergoing major surgery for continu- • Feeding difficulties with failure to thrive
ous hemodynamic monitoring and blood • Repeated failed extubation attempts
sampling. • Associated congenital anomalies especially
The umbilical, the radial, and femoral artery cardiac defects
are the most frequently used. The humeral artery • Signs of dysmorphism
should be considered with caution (terminal • Recurrent aspiration pneumonia
artery, proximity of median nerve), even if one • Persistent atelectasis or lobar hyperinflation
study shows the same complication rate as the on chest X-ray
radial artery [71]. The temporal artery should no
longer be used for the risk of cerebral emboliza- Bronchoscopy is essential to determine the
tion when flushing the line. In neonates, the pos- extent and severity of the airway problem and to
terior tibial artery and the dorsalis pedis artery plan treatment strategy [72].
can easily be cannulated. This can be done using flexible bronchoscopes
The major complications of arterial cannula- at the bedside or rigid bronchoscopes in the oper-
tion are nerve injury and ischemia. Ischemia may ating room.
be related to [1] vasospasm, usually temporary
[2], thrombosis, much more dangerous, but often
blood flow resumes several weeks after removal 2.6.1 Flexible Bronchoscopy (FB)
and therapy [3], embolism.
The ACCP guidelines, previously men- For the neonate with small airways, lung disease,
tioned, also recommend the prophylactic infu- and very little respiratory reserve, a bedside study
sion of unfractionated heparin to prolong with a flexible scope is possible, but a rigid bron-
catheter patency and avoid thrombosis. The choscopy with general anesthesia is likely to be
usual dose suggested is 0.5 U/mL/h at 1 mL/h, needed in the operating room.
except for arterial UCs (0.25–1  U/mL,
25–200 U/kg/day) [70]. 2.6.1.1 Indications
FB enables us to obtain anatomical and dynamic
information of the airways and to perform cyto-
2.6 Neonatal Bronchoscopy logical and microbiological studies. Its indica-
tions arise with the need to respond to symptoms
Airway problems in the neonatal population are or radiological anomalies that cannot be explained
often life-threatening and raise challenging issues by noninvasive methods or to obtain samples
in diagnosis and management. from the lower airways [73].
The airway problems may result from con-
genital or acquired lesions and can be broadly –– Persistent Stridor
classified into those causing obstruction or those Its main cause is the laryngomalacia tending to
due to an abnormal “communication” in the disappear within the first year and therefore
airway. does not usually require endoscopic revision; in
A high index of suspicion helps ensure an case of atypical presentation in association with
early diagnosis. Consider the possibility of an syndromes or malformations, a complete
airway problem and check whether the following exploration is recommended as there may be
symptoms/signs are present: anatomical, congenital, or acquired anomalies.
–– Persistent/Recurring Atelectasis
• Recurrent stridor or wheeze The most frequent findings are mucus plug-
• Chronic cough ging, foreign bodies, extrinsic compression in
• Recurrent cyanotic episodes cases of congenital cardiopathy, and inflam-
• Life-threatening events matory granulation tissue.
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 15

–– Therapeutic Procedures The majority of indications for RB are thera-

FB can be useful for resolving atelectasis due to peutic: endoscopic treatment of localized airway
the retention of secretions or mucus plugging. obstruction, extraction of foreign bodies, and
The percentage of radiological re-­expansion is therapeutic instrumentation of the airway.
variable, generally not higher than 50%. RB can be of use in the perioperative manage-
–– Difficult and Selective Indications ment of tracheoesophageal fistulas, both isolated
Bronchoscopy can act as a guideline for intu- and recurrent, as it allows for its identification
bation in cases of craniofacial anomalies and and canalization, facilitating the surgical
polymalformative syndromes or in selective approach [74].
bronchial intubation. Pediatric RB is a procedure not regularly per-
formed in most centers; therefore, learning this
2.6.1.2 Contraindications technique usually requires specific training, gen-
The indication for FB should be individualized, erally in a reference center [75].
evaluating the risk/benefit for each patient.
Some absolute contraindications impede per- 2.6.2.1 Obstruction of the Central
forming bronchoscopy: severe refractory hypox- Airways
emia, hemodynamic instability, uncorrected The larynx, trachea, and main bronchi are the
hemorrhagic diathesis, or the lack of authoriza- bane of various surgical pathologies causing ste-
tion for the procedure by the parent. nosis of the lumen, from tumor to inflammatory
There are some relative contraindications deter- lesions. RB is the endoscopic best procedure
mined by the team’s experience or the hospital’s when open surgery cannot be contemplated to
level of critical care: very premature newborns, treat these processes either with the application
congenital cyanotic cardiopathies with an increase of laser, implantation of endoprosthesis, or other
in bronchial collateral circulation, severe pulmo- therapies.
nary hypertension, or coagulation alterations. In critical stenosis of the common airway with
a reduction to 20% of the predicted lumen and
2.6.1.3 Complications the patient’s life at risk due to asphyxia, RB can
Neonatal FB is in general a safe procedure. be a lifesaving procedure as it allows for the
Possible complications depend on the patient’s immediate restitution of the airway. It can dilate,
risk factors, the type of procedure carried out, opening the airway or progressively dilating the
inadequate sedation/anesthesia, choice of instru- inflammatory stenosis.
ments of an improper size, and the inexperience This not only avoids the need for tracheotomy
of the bronchoscopist. if the obstruction is laryngeal, but it is also the
only option when the obstruction is located under
2.6.2 Rigid Bronchoscopy (RB) the cervical trachea.

FB has slowly acquired a predominant role in 2.6.2.2 Extraction of Foreign Body

pediatric bronchoscopy, and, although it has sub- Rigid bronchoscopy is the best procedure for the
stituted RB in most centers, rigid bronchoscopy safe and quick extraction of foreign bodies in
is still widely used. The basic reason is the high children. Although there are publications endors-
incidence of foreign bodies in children. ing the good performance of FB [76], it is usually
On the other hand, despite there being new a complicated procedure in small children. In
ultrafine scopes for exploring newborns and these patients, RB is preferred as it offers the
infants, RB is still useful as a diagnostic or thera- advantages of general anesthesia, assisted venti-
peutic tool when there is compromised ventila- lation, larger instruments, and a greater variety of
tion, when extensive biopsies are necessary or accessories.
when atelectasis should be resolved with the The ideal procedure would start with FB,
elimination of mucus plugging. yielding greater reach in the exploration and the
16 F. Caramelli et al.

identification of the foreign body, then extraction the data from its registry showed an approximate
with RB, and finally a revision with FB in order 80% survival rate in 12,175 patients, treated with
to rule out a residual foreign body. In some cases ECMO from 1988 to 1998, with neonatal respira-
in which the clinical and/or radiological informa- tory failure with a predicted mortality rate of
tion is conclusive, the procedure may be directly approximately 80% [84].
initiated with RB. In spite of these results and the improvement
in the technology of ECLS systems (centrifugal
2.6.2.3 Complications pump with levitation technology, heparin-bonded
The complications of RB are due to the instru- circuits, miniaturization of cannula and pumps,
mentation with the bronchoscope itself, the medi- dual-lumen catheters, etc.), nowadays, the use of
cation used, the ventilation technique, the neonatal ECMO is reducing, as shown by the
underlying pathology, the experience of the ELSO registry and by many randomized studies;
endoscopist, and the type of intervention. this is probably because the introduction of
inhaled NO, HFOV, and surfactant into clinical
practice has progressively reduced the need for
2.7  xtracorporeal Life Support
E its use [85].
(ECLS or ECMO) Eighty percent of cases have a primary respi-
ratory diagnosis, the others have a primary car-
Extracorporeal life support (ECLS), also called diac diagnosis; 4% of ECMO runs are cases of
ECMO, is a modified form of heart and lung bypass extracorporeal cardiopulmonary resuscitation
used on a temporary basis and as an alternative to (eCPR) [85].
conventional methods of life support. This com- This implies that the usual ECMO patient is
pensates, when aggressive therapy and mechanical now much more complex, unstable, with lower
ventilation (MV) fail to maintain acceptable oxy- GA or weight and requiring a longer period of
genation and perfusion, for the deficit of cardiocir- support than in the past.
culatory and/or pulmonary functions until the body Therefore, in comparison with the previous
recovers and extracorporeal support is no longer era, complications and mortality rates are a little
needed. Therefore, ECLS is a rescue therapy for higher.
patients with a predicted mortality of 80–100%. Respiratory ECMO in newborn babies con-
Indications for the use of neonatal ECMO are cerns two conditions—primary diagnoses associ-
severe respiratory failure and/or major circula- ated with primary pulmonary hypertension of the
tory insufficiency, refractory to maximal medical newborn (PPHN) (idiopathic PPHN, meconium
management (INO, HFOV, and surfactant aspiration syndrome, neonatal acute respiratory
included) but a potentially reversible etiology. distress syndrome, group B streptococcal sepsis,
With the introduction of membrane oxygen- and asphyxia) and congenital diaphragmatic her-
ators in clinical practice, ECLS for prolonged nia (CDH)—but the outcome can be very differ-
periods of time became feasible, and so, in 1975, ent depending on the etiology (better in case of
Bartlett and colleagues reported the first success- meconium aspiration syndrome, worse in CDH)
ful use of ECMO to treat severe respiratory dis- and the GA at time of cannulation.
tress in a newborn baby [77, 78]. CDH remains an indication to ECMO, but
After initial promising results, many prospec- systematic reviews do not demonstrate a substan-
tive randomized trials and one uncontrolled trial tial benefit [86–88]. This is probably related to
demonstrated a better survival rate with ECMO the difficulty of predicting the reversibility of the
than conventional therapy in the neonatal age. PPHM and the related lung hypoplasia, because
The same result was not confirmed by a similar the ECMO efficacy depends on it. ECMO is a
RCT in adults [79–83]. support, not a therapy.
The Extracorporeal Life Support Organization Observed-to-expected lung-to-head ratios
(ELSO) was founded in 1989, and, after 10 years, (O/E LHR) and MRI total lung volume (TLV)
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 17

can predict the need of ECMO and mortality [89, maximal medical therapy or persistent episodes of
90] but have not yet been strongly correlated with decompensation, severe hypoxic respiratory fail-
morbidity or PPHN [91]. ure with acute decompensation (PaO2 < 40) unre-
However, not only the overall survival rate sponsive to intervention, severe pulmonary
should be considered but also the survival rate strat- hypertension with evidence of right ventricular
ified according to the differences in referral pattern, dysfunction and/or left ventricular dysfunction,
as suggested by Zalla and coworkers in 2015 [92]. and pressor-resistant hypotension [98].
At present, there is no single test or index Contraindications are related to the specific
available to predict this reversibility nor strong benefit risk/ratio. According to the ELSO guide-
RCTs to assist in all issues of ECMO manage- lines, these can be divided into absolute and rela-
ment in CDH, although many authors and institu- tive, as shown in Table 2.1.
tions have proposed similar referral criteria to The extracorporeal circuit is usually applied in
ECMO in this setting [93–95]. two different modes: (1) veno-venous bypass,
Even if these criteria may help the decision where the blood is withdrawn from a central vein,
regarding ECMO runs, survival benefit of ECMO pumped into the system, oxygenated, and
in CDH could not be established with the referral ­reinjected always in a central vein at the same
criteria used at that time, as suggested also by one level or in another place, and (2) venoarterial
large review in the UK [86]. bypass, where the blood is returned to the body
However, the absence of an initial response to through a cannula placed not in a central vein but
resuscitation with preductal saturation >85% and through the right common carotid artery into the
a PCO2 <65 mmHg are strongly associated with aortic arch.
worse prognosis and constitute relative exclusion The first method allows only respiratory sup-
criteria for ECMO in some centers [96]. port, leading to an improvement of hemodynam-
The ideal length of time on ECMO in patients ics only by an increase in tissue oxygenation.
with CDH is difficult to establish; it may be iden- The second also provides circulatory assis-
tified within 3–4  weeks, but a higher time on tance, increasing cardiac output through the flow
ECMO can be needed even with satisfactory pul- of the pump (but with an increase in the LV after-
monary outcome [97]. load that can sometimes worsen an underlying
Selection criteria for ECMO in neonates [98] are heart failure).
gestational age of 34 weeks or more, birth weight of Additionally, in postcardiotomy shock, direct
2000  g or higher, no significant coagulopathy or cannulation of the right (±left) atrium and aorta is
uncontrolled bleeding, no major intracranial hemor- preferred, like in adults [99], but, in this case, a
rhage (grade 1 intracranial hemorrhage), mechani- sternotomy is necessary with the associated
cal ventilation for 10–14  days or less, reversible higher risk of infection.
lung injury, no lethal malformations, no major
untreatable cardiac malformation, and failure of
Table 2.1  Absolute and relative ECMO controindications
maximal medical therapy.
The decision to respiratory ECMO runs is Absolute Relative
Lethal chromosomal Irreversible organ
guided by the ratio between the degree of ventila-
disorder (includes trisomy damage (unless
tory injury and the effects of ventilator support; 13, 18 but not 21) or other considered for organ
therefore, usual referral criteria are peak inspira- lethal anomaly transplant)
tory pressure  >35  cm H2O, the alveolar-arterial Irreversible brain damage <2 kg
(A-a) gradient >600–624 mmHg for 4–12 h, and, Uncontrolled bleeding <34 weeks post-­
menstrual age (increased
above all, the oxygenation index (OI) >40 in 3 of
incidence of increased
5 post ductal gas determinations obtained intracranial hemorrhage)
30–60 min apart. Grade III or greater Mechanical ventilation
ECMO may be indicated also in failure to wean intraventricular greater than 10–14 days
from 100% oxygen despite prolonged (>48  h) hemorrhage
18 F. Caramelli et al.

Even if one method has specific advantages/ ECMO strategy remains a procedure with
disadvantages over the other, the choice of can- very high risk of complications, so that its use is
nulation technique is more often dictated firstly justified only by the highest risk of mortality
by vessel size and anatomy, as well as the pres- without this extracorporeal support.
ence of hemodynamic instability. The major complications are related to the dif-
VA (Vascular Access) cannulation ensures car- ficulty of managing the delicate balance between
diocirculatory support, as previously described, thrombosis and hemorrhage (due to the foreign
but supplies less oxygenated blood to the myocar- surfaces of the system and the underlying condi-
dium and is burdened by more risks of systemic tions) and to the high risk of infection, also linked
embolization with more intracranial bleeds and to the immunosuppressive effect of the ECLS.
seizure; VV cannulation helps to decrease pulmo- However, after more than 40  years since its
nary artery pressure, pumping oxygenated blood first successful use and despite improvements in
directly into the pulmonary artery, but needs the medical and surgical management of severe
higher pump flow, neonate weight  >2.5  kg, and respiratory/cardiac insufficiency of the newborn,
strict control of positioning to avoid recirculation. neonatal ECMO continues to be the only evidence-­
Some studies, which were not randomized and based ECLS strategy and maintains its own role in
controlled, reported better outcomes for VV the management of very critically ill patients.
ECMO (except in the cardiac patient), but prob-
ably this data reflects a selection bias for the
aforementioned reasons [100, 101]. 2.8 Pain in the Newborn
In fact, despite the potential benefits of VV
mode, the most frequently used approach remains The important metabolic and hormonal response
VA ECLS with surgical cannulation and ligation of newborns undergoing invasive procedures,
of the internal jugular vein and the carotid artery performed without antalgic coverage, was the
(72% according to the ELSO registry). main element that led research to the demonstra-
This probably testifies to the greater hemody- tion of the capacity to perceive and manifest pain
namic instability of today’s respiratory ECMO in neonates [103].
patient. However, the use of new dual-lumen can- These studies emphasized that at every age (fetus,
nula is becoming more popular because it enables premature, in-term newborn, infant, baby), there is a
a veno-venous bypass with only one cannulation, definite perception and response to pain; the indi-
usually through the IJV. vidual is born with an anatomically structured and
Before ECMO starts, the patient must be anti- functionally active nociceptive system [104].
coagulated, and, at the beginning, the usual rapid The state of immaturity makes the newborn
correction of oxygenation and carbon dioxide far more vulnerable to pain stimulus. In fact, the
level makes strict control of hyperoxia, hypocap- conduction pathways of the inhibitory system are
nia, and their dangerous effects mandatory. not yet completely myelinated, and the discrimi-
During the stabilization phase, ventilation nating capacity between sensory stimulus and
must be reduced and positive inspiratory pressure harmful stimulus is low.
(PIP) lowered. Fluid overload is common and As the newborn develops, the ability to differ-
must be treated aggressively, eventually using entiate stimuli will mature as will the capacity to
continuous renal replacement therapy (CRRT) on process information through cognitive ability,
the circuit [102]. adaptation, memory, and affective and emotional
Given the high risk of neurological complica- influences.
tion, careful neuro-monitoring should be rou- At birth, the central nervous system (CNS) is not
tinely performed by cranial ultrasound, and completely developed; the synaptogenesis starts
cerebral oxygenation should be continuously from the 24th week of gestational age, with the
evaluated by NIRS (near-infrared spectrometry). development of the synaptic connection network.
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 19

The “brain growth spurt period” in humans pain in the newborn who has to undergo invasive
commences in the last trimester of pregnancy and procedures.
continues at least until the second year of life. Taking care of pain means, first of all,
During this period, alongside the differentia- ­evaluating it.
tion, maturation, and neuronal migration, a The assessment of acute pain at the neonatal
genetically determined cellular suicide process is age makes use of algometric instruments, some
observed. Redundant neurons and those that have validated also for premature birth as the Premature
failed to connect to targets are eliminated by Infant Pain Profile (PIPP) scale. It is a simple-to-­
apoptosis. Only neurons that receive adequate use observational scale that analyzes the varia-
trophic factors are able to survive. tion of physiological parameters (SatO2, heart
Neurotransmitters are the trophic factors rate) together with the observation of the most
involved in neuronal survival: the glutamate, typical pain behavior in the newborn—crying
excitatory neurotransmitter, and the GABA, and facial expressions.
inhibitory neurotransmitter. Management of acute neonatal pain must rely
Synaptogenesis is an activity-dependent pro- on pharmacological strategies, complemented by
cess, and an excessive depression of neuronal activ- specific non-pharmacological techniques such as
ity may constitute a signal that induces apoptosis. sensory saturation that includes three types of
Sedative anesthetic drugs reduce neuronal stimulation—oral, tactile, and auditory [107].
activity through an NMDA (N-Methyl-D- In neonates, pharmacokinetics and pharmaco-
aspartate receptor) receptor antagonist or dynamics of analgesics, as well as other drugs,
GABA-A receptor agonist mechanism. differ from that of adults due to different degrees
In theory, the exposure of developing neurons of functional organ maturity. Metabolism is
to these agents could alter homeostasis, transform- slowed by enzymatic immaturity, and renal
ing apoptosis from a biological phenomenon into a excretion is reduced, potentially resulting in
pathological phenomenon, with short- and long- accumulation of drugs and active metabolites.
term sequelae on neurocognitive development. Genetic polymorphism also influences pharma-
This phenomenon has been demonstrated in cokinetics inducing different enzymatic patterns
the brains of guinea pigs and nonhuman primates, with different enzymatic activity.
in preclinical studies, but it has not been con- For that reason, there are both slow and ultra-
firmed in humans, at least for single exposure to fast metabolizers of some specific drugs. This
anesthetics [8, 9]. results in a great interindividual variability of
There is a lack of data on repeated or pro- drug response: for some, the ineffectiveness and,
longed administration, as sometimes needed in for others, a greater risk of toxicity.
critically sick newborns in intensive care, and This phenomenon has been demonstrated for
there is no evidence of safety in the use of analge- codeine and is suspected for tramadol, hydroco-
sics [105, 106]. done, and oxycodone [108].
However, it has been shown that the newborn In the case of morphine, the active metabolite,
that has experienced early, recurring, and pro- morphine-6-glucuronide (M6G), is primarily
longed pain has a high risk of developing sequelae responsible for the analgesic effect, but the enzymes
in neurocognitive development and altered pain of glucuronidation are immature at the neonatal age,
response. The longer the exposure to stimulation, and the amount of M6G produced is uncertain.
the less the newborn will be able to modulate and Genetic differences also influence the pharma-
modify the reinforcement of frequently activated codynamics determining morphological varia-
neuronal circuits and will have a greater risk of tions of the binding receptors.
developing pain memory. Extreme variability of effect supports a cau-
This supports the importance of paying close tious approach, using small doses titrated on clin-
attention to the treatment and the prevention of ical response.
20 F. Caramelli et al.

Research into drugs without kinetics depen- effects, enhance synergies, and achieve maxi-
dent on hepatic and renal function led to remifen- mum effectiveness.
tanil, a drug metabolized by tissue esterases,
already present and functioning at birth. However,
the rapid offset of remifentanil opens the problem 2.9 Summary
of treatment discontinuation and suspension.
Furthermore, the hemodynamic response and the Even with the improvement in knowledge and
risk of thoracic rigidity are two major adverse availability of new dedicated medical devices,
effects. the particular vulnerability of newborns still
Regional neuraxial anesthesia and peripheral makes neonatal anesthesia and intensive care
nerve blocks represent a valid strategy in intra- challenging.
and postoperative pain management, especially There are still many unanswered questions
nowadays, given the improvement of equipment and topics for discussion. Evidence-based data is
specifically designed for neonatals, the use of lacking, and many decisions are made even today
eco-guided techniques, and new safer local on the basis of pathophysiological deductions
anesthetics. and good clinical “common sense.”
Regional anesthesia, however, is a challeng- Further studies and research should be carried
ing technique and, especially in the newborn out in order to obtain better evidence-based data,
baby, requires expertise and experience. Careful as is available for adults, and to improve to a
analysis of the risk/benefit balance and a metic- greater extent the outcomes in neonatal anesthe-
ulous technique are always recommended [109, sia and perioperative intensive care.
110].
Non-opioid analgesics usually have an opioid-­
sparing effect but can substitute them in case of Box 2.1 Allometric equation and corrective
slight pain. NSAIDs are not indicated in neonates factors of Hill model
due to the risk of adverse effects on renal perfu-
y = a ´ BodyMassPWR
sion, thrombophilic profile, platelet dysfunction,
and damage of gastric mucosa. y is the variable of interest (e.g. Clearance)
Paracetamol represents the most non-opioid a is the allometric coefficient
analgesic used at the neonatal age. PWR is the allometric exponent
The risk of hepatic overdose and accumula- Allometry alone is insufficient to pre-
tion of the metabolite N-acetyl-p-benzoquinone dict the clearance of drugs in neonates and
imine (NAPQI) are very low due to the functional infants from adult estimates. The Hill
immaturity of the CYP2E1 enzyme and the model describes maturation introducing
resulting low concentration of the toxic metabo- the maturation factors (MF)
lite. For the most recent intravenous formulation,
Allegaert in 2011 [111] studied pharmacokinetic MF = ( PMA )
Hill
( Hill
/ TM 50 + PMA Hill )
variables of paracetamol, such as clearance, vol-
ume of distribution, and half-life and found TM50 = maturation half-time
10 mg/kg every 6 h to be an optimal dose for neo- The Hill coefficient relates to the slope of
nates of >32 weeks GA. this maturation profile
A previous study had suggested even higher
P = Pstd ´ Fsize ´ MF ´ OF
doses of 15  mg/kg every 6  h for the full-term
newborn, advising a reduction in the case of P = Pharmacokinetic parameter
hyperbilirubinemia [112]. Pstd = value in a standard size healthy adult
In light of the above, the optimal therapy of Fsize = (W/70)PWR
acute pain in newborns must provide a multi- OF = organ function
modal regimen in order to minimize adverse
2  Anesthesiological Considerations: Stabilization of the Neonate, Fluid Administration, Electrolyte… 21

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 Imaging in Neonates
3
Filomena Carfagnini, Laura Greco,
Donatella Vivacqua, Gianluca Rasetto,
Antonio Poerio, and Michelangelo Baldazzi

The study of neonatal surgical diseases, both tho- In the following paragraphs, we will discuss
racic and abdominal, involves the use of different individually the surgical thoracic, gastrointesti-
diagnostic techniques, sometimes complemen- nal, and urogenital disease as observed in neonatal
tary, each with specific characteristics. age, emphasizing for each district the indication
The most neonatal pathologies currently have of the different imaging techniques and the rela-
prenatal diagnosis, generally ultrasonography, tionship between them, in order to define optimal
when deemed necessary confirmed by studies of diagnostic and reproducible algorithms.
fetal magnetic resonance.
Postnatally, the first-level examinations are
ultrasonography and conventional radiology, 3.1 Neonatal Chest Imaging
both plain radiographs and contrast studies, the
latter for the gastroenteric and urinary tract. The study of neonatal chest takes advantage of
MRI is part of the second-level diagnostic different diagnostic techniques, each one with its
techniques, which has among its great perks the own features, suitable to answer specific clinical
lack of ionizing radiation, multiplanar and mul- questions.
tiparametric capabilities, and the high contrast As for other systems and apparatuses, diag-
resolution; its limitation is instead the relative nosis of neonatal surgical pathologies is often
length of the sequences with consequent need to prenatal, thanks to fetal ultrasonography and
perform the sedation/anesthesia investigation. fetal magnetic resonance imaging (fetal MRI),
Although it is a very reliable diagnostic test, especially in very complex conditions (such as
thanks to the high spatial resolution, the CT congenital diaphragmatic hernia and high air-
has limited indications in neonatal age, due to way obstruction) that require a planned deliv-
the high radiation dose, used only in a very few ery in a third-level center and specific obstetric
selected thoracic diseases. techniques (e.g., EXIT). In particular, in case of
congenital diaphragmatic hernia, fetal MRI gives
information about localization (left or right), her-
F. Carfagnini (*) · L. Greco · D. Vivacqua · G. Rasetto
A. Poerio · M. Baldazzi
niated organs, lung volumes and degree of matu-
Department of Pediatric Radiology, ration, mediastinal shift, polyhydramnios, and
S. Orsola-­Malpighi Hospital, Bologna, Italy associated pathologies [1].
e-mail: [email protected]; All the major diagnostic studies are useful for
[email protected]; [email protected];
[email protected];
the diagnosis of neonatal thoracic pathologies,
[email protected]; starting from chest X-ray and ultrasonography;
[email protected] second-level examination is magnetic resonance

© Springer Nature Switzerland AG 2019 25

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_3
26 F. Carfagnini et al.

imaging (MRI), while computed tomography a

(CT) is reserved to large lung/mediastinal expan-
sive lesions, pre-surgical planning of congenital
pulmonary dysplasias, and severe respiratory dis-
tress from unrecognized cause.

3.1.1 Radiography

After birth, the first-level examination for the

newborn remains the chest radiograph (be it digi-
tal or analogue). This exam is relatively cheap,
easy to execute, and widespread; the informa-
tion it gives are rapidly available, and, in expert b
hands, the radiation dose is very low.
The radiograph is routinely executed in a
single, anteroposterior view with patient laying
in supine position. Additional views, such as
translateral and lateral decubitus with horizontal
beam, can be useful for diagnosis. The collima-
tion of the X-ray beam should be as narrow as
possible to avoid exposure of other organs and
systems.
Chest X-ray allows to easily differentiate med-
ical from surgical causes of respiratory distress
in newborns; in many cases, it confirms prenatal
Fig. 3.1  Anteroposterior chest radiograph of a newborn
suspects of several pathologies. With chest radio- showing bilateral pneumothorax and pneumomediasti-
graph it is possible to evaluate lung expansion and num (a) and left lateral decubitus confirming right pneu-
radiolucency, heart size and mediastinal silhou- mothorax (b)
ette, and position of catheters, endotracheal tubes,
and thoracic drainages. A hyperlucency of a hemi-
thorax and a shift of the mediastinal silhouette
allow the diagnosis of pneumothorax (Fig. 3.1); if
the hyperlucency is limited to a localized area of
parenchyma, cystic dysplasia (Fig. 3.2), congeni-
tal lobar overinflation, or bronchial atresia is the
most likely diagnosis, which must be confirmed
with second-level examinations.
On the other hand, a pulmonary opacifica-
tion can be caused by a pleural effusion or an
expansive mass, bronchogenic cysts, pulmonary
sequestration, or cystic dysplasia in a very early
stage, when cysts are still filled with fluid.
Furthermore, chest X-ray can show a wid-
ening of the mediastinal silhouette in the rare
expansive pathology of this district, such as Fig. 3.2  Chest radiograph of a newborn showing multi-
lymphangiomas, thymic neoplastic diseases, ple air-filled cysts in the inferior part of the right lobe
3  Imaging in Neonates 27

and paravertebral neoplasias (neuroblastoma, the usual homogeneous fluid content becomes
ganglioneuroblastoma, and ganglioneuroma). corpusculated, with contextual levels.
A peculiar appearance is represented by con-
genital diaphragmatic hernias, both poste-
rior (Bochdalek) and anterior (Morgagni) 3.1.3 Magnetic Resonance
and by the rarest cases of eventration of the Imaging (MRI)
diaphragm.
For many years magnetic resonance imag-
ing (MRI) has been considered an experimen-
3.1.2 Ultrasonography (US) tal study technique for pulmonary parenchyma
examination. This assumption was based on the
Ultrasonography (US) of the chest is performed poor quality of images, due to movement artifacts
with high-resolution multifrequency transduc- resulting from breathing and heartbeat.
ers, convex or linear [2]. It does not use ionizing Nevertheless, over the years, the develop-
radiations and does not require sedation, charac- ment of faster sequences (e.g., turbo spin-echo
teristics that make it a very useful tool in neona- T2-weighted) with movement artifact reduction
tal imaging. Adding to this, low mineralization of techniques (multi-vane) and the use of triggers
the bones allows other approaches than in adults. have extended the indications for MRI in the
It is operator dependent and this remains its main study of the chest.
limit. MRI does not use ionizing radiations; thus it
US is especially useful in pleural effusion plays an important role in the postnatal confir-
identification and quantification and can be a mation of congenital pulmonary malformations,
guiding tool for thoracentesis. US is the most both air malformative diseases such as congeni-
reliable technique to evaluate pleural effusions, tal pulmonary airway malformations (CPAM)
allowing to discriminate between homogeneous, and vascular ones, such as pulmonary seques-
anechoic fluid effusion and complicated ones, tration. For example, CPAM is characterized
when features such as echogenic debris, mobile by round, hyperintense areas in T2-weighted
fibrin strands, septations, or a honeycombing sequences; pulmonary sequestration is seen as
appearance are present [3]. an area of the lung with different signal inten-
Its use is nowadays extended to parenchymal sity, higher than the surrounding healthy paren-
and mediastinal examination: it allows to evalu- chyma, and with associated intralesional flow
ate diaphragmatic profiles, to analyze which void images. It is also possible to identify the
abdominal organs are herniated into the thorax afferent arterial vessel, usually originating from
in case of diaphragmatic hernia, and to identify supra- or infradiaphragmatic aorta, thanks to
solid pulmonary lesions, mediastinal masses, and “black-blood” angiographic sequences, without
congenital pulmonary malformations (e.g., pul- the need of intravenous contrast medium injec-
monary sequestration). Thanks to color Doppler tion (Fig. 3.3).
techniques, US evaluates blood vessels without It is possible to perform this examination
endovascular contrast medium. either in sedation or during natural sleep, without
Finally, it is of paramount importance in the need of anesthesia, making it feasible already
those pathologies which can involve also the in the first days of neonatal life, delaying the
neck, such as lymphangiomas and anomalies of execution of CT for the surgical planning to the
branchial apparatuses: on the base of the differ- following months, just before the surgery.
ent echogenicity, it can diagnose bleedings that One of the most important fields of application
can cause sudden growth in size of the lesions, of the chest MRI is the examination of mediasti-
with subsequent airway compression or disloca- nal masses (e.g., thymic cystic teratomas, medi-
tion. These complications are suspected when astinal lymphangiomas, pleuropericardic cysts,
28 F. Carfagnini et al.

pulmonary dysplasias, both for those which

need a precocious surgical operation and for
the “programmable” ones, which anyway need
a pre-­ surgical planning. The former include
those malformations which cause a mediastinal
shift, such as congenital lobar overinflation and
large congenital pulmonary airway malforma-
tions [5, 6].
Congenital lobar overinflation (also known
as congenital lobar emphysema) is character-
ized by an expanded hemithorax, a hyperinflated
low-­attenuation lobe with pulmonary vascular
pruning, variable degrees of atelectasis of ipsi-
lateral adjacent lobes, and mediastinal shift into
the opposite hemithorax. Measurements of lung
attenuation value of the affected lobe are not
needed for diagnosis, because visual assessment
Fig. 3.3  Postnatal MRI of a 3-day-old newborn, showing usually suffices to identify hyperinflation. In the
a pulmonary sequestration, in the lower left lobe: the immediate postnatal period, the attenuation value
afferent arterial vessel and venous drainage are identified
by intralesional flow void images
may be increased, closer to that of soft tissue due
to impaired clearance of retained lung fluid; as
fluid is resorbed, the attenuation value of the lobe
esophageal cystic duplications), especially of the decreases.
posterior mediastinum (e.g., neuroblastoma). The appearance of congenital pulmonary air-
way malformations (CPAM) on CT depends on
the relative presence of cystic and solid com-
3.1.4 Computed Tomography (CT) ponents and whether there is superimposed
infection. CPAM is seen as multiple thin- or
Computed tomography (CT) is the gold stan- thick-walled, air- or fluid-filled cysts of variable
dard technique for the study of the chest [4]; in size, expanding the affected lobe or lobes and
the newborn, due to the high radiation dose, this displacing the mediastinum to the opposite hemi-
diagnostic procedure has a very limited use and is thorax. Type III, which is very rare, appears as
dedicated to a few clinical indications. a solid mass. A higher attenuation equal to soft
It is possible to acquire large volumes in a tissue or thick walls may be seen when the cyst
short time, and ever-thinner slices allow multi- contents are infected or hemorrhagic. Air-fluid
planar reconstructions from raw data. Thus, CT levels can be seen occasionally, but they do not
is able to study the airways and create 3D recon- necessarily indicate infection.
structions for virtual endoscopy, to identify blood Large CPAM may mimic cystic pleuropulmo-
vessels (especially when there is a suspect of vas- nary blastoma (Fig. 3.4): the latter appears at CT
cular anomalies such as vascular rings and a pul- examination as a solid, cystic, or mixed attenu-
monary artery sling) and, most of all, to evaluate ation mass in the lung periphery often adjacent
pulmonary parenchyma and its pathologies (e.g., to the pleura in the lower zones; associated find-
cystic parenchymal malformations, broncho- ings include pleural effusion and contralateral
genic cysts, pulmonary sequestration, lobar over- mediastinal shift. The solid components of the
inflation, or bronchial atresia) [5]. mass lesion are seen to enhance with intravenous
As already indicated above, CT (with intra- contrast administration. Cross-sectional imaging
venous contrast medium injection) is a second- should include the mediastinum as hilar metasta-
level investigation for the study of congenital ses can occur.
3  Imaging in Neonates 29

a b

Fig. 3.4  Pleuropulmonary blastoma. Chest radiograph (a) and CT coronal reconstruction (b) show multiple cysts
occupying the left hemithorax, crossing the midline, and displacing the mediastinum to the right

In the other cases, when there are no urgency from the distal thoracic aorta, and venous drain-
conditions, CT execution is postponed to the age via the pulmonary veins into the left atrium.
third–sixth month of life of the infant. This is the In extralobar sequestration, CT shows a homoge-
case of bronchial atresia, pulmonary sequestra- neous, well-delimited, round, ovoid, or triangular
tion, noncomplicated congenital pulmonary air- mass, sometimes with internal cystic areas; arte-
way malformations, and hybrid lesions [5–7]. rial supply is always systemic (upper abdominal
In bronchial atresia, air enters the affected or lower thoracic aorta), while venous drainage
segment via collateral channels, producing over- is usually to the inferior vena cava or the azygos
inflation and air trapping, while mucus secretions system and occasionally the coronary artery or
generated in the affected bronchus accumulate portal veins. The cysts of CPAM communicate
originating mucus impaction (mucocele): CT is with the airways, and their vascular supply comes
diagnostic because it shows the segmental over- from pulmonary circulation; however, there are
inflation and mucous impaction with great pre- many examples of CPAM fed by systemic blood
cision. In some cases, a cystic lesion containing vessels, and in these cases it is extremely dif-
gas and fluid corresponding to a severely dilated ficult to differentiate CPAM from pulmonary
bronchus just distal to segmental bronchial atre- sequestration, as they correspond to overlapping
sia can also be seen. malformations (hybrid lesions) (Fig.  3.5): from
Pulmonary sequestration can be intralobar the radiological viewpoint, the differentiation
or extralobar [8, 9]. CT findings of intralobar between CPAM with systemic supply and pul-
sequestration include a homogeneous or inho- monary sequestration is impossible.
mogeneous solid mass, with or without definable Finally, CT is used to study mediastinal and
cystic changes; it can also appear as an aggre- thoracic masses, specifically in poorly explorable
gate of multiple small cystic lesions with air or areas (e.g., pulmonary apex, near the diaphragm,
fluid content, a well-defined cystic mass, or a adjacent the chest wall or central airways), and to
large cavitary lesion with air-fluid level; adjacent evaluate soft tissues, vessels, and airway infiltra-
emphysematous changes are common. Contrast tion; in these cases, nevertheless, it is preferable
medium intravenous injection is necessary to to use MRI, which is analogously diagnostic but
show systemic arterial supply, most commonly not radiative.
30 F. Carfagnini et al.

a tomography, whose use is almost exceptional,

does not find significant indications [12, 13].
It must be remembered that many gastro-
intestinal tract abnormalities have a prenatal
diagnosis, and this often changes and influences
postnatal diagnostic strategies.

3.2.1 Radiography

b The air present in the digestive system is a natu-

ral contrast agent, which is positively used in
conventional radiographs performed during
neonatal age [10–14].
After birth, the normal progression of the air
along the whole alimentary canal occurs within a
few hours; the air is visible in the stomach within
a few minutes, and then it progresses in about
3  h toward the loops of the small intestine and
finally becomes visible in the sigmoid rectum
after about 6–8 h.
Neonatal obstructions occur when the air
progression is interrupted, generally due to the
presence of an atresic trait but also in cases of
meconium ileus or peritonitis, Hirschsprung dis-
ease, and functional immaturity of the colon; all
these conditions can be effectively diagnosed
Fig. 3.5  Axial (a) and coronal MIP reconstruction (b)
CT show a cystic lesion and a systemic arterial supply in with exclusive use of conventional radiology
a hybrid lesion (Fig. 3.6); even in doubtful cases, plain abdomi-
nal radiographs can be useful to indicate subse-
quent diagnostic procedures.
The obstructions may be incomplete, for
3.2 Gastrointestinal Neonatal example, due to the presence of stenotic traits,
Imaging webs, duplications, intestinal malrotation, perito-
neal bands, and aganglionosis; these pathological
The most important diagnostic techniques for the conditions may occur later, and other diagnostic
digestive system in neonatal age are still today procedures are generally necessary for diagnosis.
plain abdominal radiographs and conventional The abdominal radiograph in the neonatal age
contrast studies [10, 11]. is exclusively performed with supine anteroposte-
In recent years, ultrasound has been added to rior view; only in some cases the translateral view
these techniques with an increasingly important with horizontal beam is added, which allows the
role, so much so as to be considered an extension recognition of air-fluid levels and facilitates the
of clinical evaluation, both in terms of urgency visualization of pneumoperitoneum; in the latter
and in elective studies. condition, an additional view in left lateral decu-
Magnetic resonance is reserved for selected bitus with horizontal beam can be performed.
cases, especially in the evaluation of com- All cases of pneumoperitoneum, however
plex malformation patterns or in the presence determined, have an exclusive radiographic diag-
of expansive diseases, while the computerized nosis as well as the high-obstructive conditions,
3  Imaging in Neonates 31

a is suspected due to the presence of polyhydram-

nios, lower intraluminal liquid in fetal gut, and
inability to detect the fetal stomach.
On anteroposterior and lateral chest radio-
graph, the radiological findings are a blind pouch
of the proximal esophagus, distended with air.
Radiographic evaluation always should
include the abdomen to assess the presence or
the absence of gastrointestinal air due to the
existence or not of the fistula, allowing the tra-
cheoesophageal atresia classification [15]. A
complete absence of air in the stomach and bowel
is observed in the I and II types, while the air is
commonly present in III and IV types.
The necrotizing enterocolitis (NEC) is one
of the most common acquired, life-threatening
gastrointestinal diseases in the newborn, espe-
cially in premature infants of extremely low birth
weight [11, 14–16]. In NEC bowel dilatation is a
nonspecific, early sand commonest finding, best
appreciated on the plain abdominal radiograph,
b and may be the only sign present in many patients
with either mild or severe forms of the disease.
The dilatation is usually due to an ileus and may
be generalized or focal, depending on the extent
of bowel involvement. Furthermore, the degree
of dilatation usually correlates well with the
clinical severity of the disease, and the distribu-
tion of the dilated loops in serial examinations is
related to clinical progression. An ominous sign
Fig. 3.6  Plain abdominal radiographs. Supine anteropos- is the change from generalized dilatation to an
terior view (a) and translateral view (b) show the presence asymmetric distribution where dilatation is con-
of many dilated intestinal loops with air-fluid levels in low fined to a more localized area of the abdomen. It
intestinal obstruction is even more worrisome if the asymmetric pat-
tern persists and the dilated loops maintain the
between those duodenal atresia with the sign of same appearance as fixed loops on follow-up
the double bubble and the less frequent pyloric plain abdominal radiographs. This suggests the
atresia with the sign of the single bubble and development of full-thickness necrosis and may
jejunal atresia, with a few loops dilated upstream precede clinical deterioration including signs of
obstruction and complete meteoric silence peritonitis. For these reasons, the degree and pat-
downstream. tern of bowel dilatation are the most important
Usually all these conditions do not require signs for early diagnosis and for follow-up.
further radiologic evaluation after radiography: Intramural gas is also an early sign that may
complementary procedures are not usually help- precede clinical signs. Although intramural gas
ful and contrast studies are contraindicated. may be present in other neonatal conditions, it is
The esophageal atresia has a diagnostic role most commonly seen in NEC and thus has been
in the plain abdominal radiograph combined with considered a virtually pathognomonic sign of
the chest radiograph; at prenatal US this disease NEC. However, intramural gas is not present in
32 F. Carfagnini et al.

all cases of NEC; it is more commonly present the periphery of both hepatic lobes, and the
in the distal small bowel and large bowel and is extent depends on the amount of portal venous
therefore most commonly seen in the right lower gas present.
quadrant. Plain abdominal radiograph has a role in ano-
The amount of intramural gas present does not rectal malformations studies, when you need to
always relate to the clinical severity of NEC in perform plain abdominal radiograph in translateral
any particular patient, and disappearance of intra- prone view for the evaluation of the rectal cul-de-
mural gas does not always correlate with clinical sac and its distance from the perineum [11–13].
improvement. On plain abdominal radiographs, Furthermore this study allows to detect sacrococ-
intramural gas may be diffused or localized and cygeal anomalies often found in caudal regression
appears as linear or rounded radiolucencies; the syndrome or other skeletal abnormalities in dif-
rounded lucencies represent intramural gas in the ferent syndromes (VACTERL association).
submucosa, and when extensive they may have
a bubbly appearance; the linear lucencies, often
curvilinear, represent intramural gas in the sub- 3.2.2 Contrast Studies
serosa (Fig. 3.7).
In NEC, portal venous gas is an extension of The contrast studies are still useful for the assess-
intramural gas that enters the veins of the bowel ment of some congenital gastrointestinal diseases;
wall and passes into the portal venous system; for neonatal conditions they are basically upper
it’s not always associated with a fatal outcome. gastrointestinal (UGI) series, small bowel follow-
However, like intramural gas, portal venous through (SBFT), water-soluble contrast enema,
gas may appear and disappear rapidly. Its dis- and, less frequently, the barium enema [10–15].
appearance is not always associated with clini- Loopograms have an important role in chil-
cal improvement. On a supine plain abdominal dren who have a stoma.
radiograph, portal venous gas appears as branch- The aim of the modern pediatric radiologist is
ing, linear, radiolucent vessels that may extend to work in close collaboration with the surgeon to
from the region of the main portal vein toward perform contrast studies only in selected patients,
using correct technique, at the lowest dose pos-
sible to meet specific diagnostic questions.
The continuous fluoroscopy technique with
the last image capture technique or the pulsed
fluoroscopy with capture of the acquired series
is now commonly used. High-dose standard
full exposures are reserved for cases of dif-
ficult diagnosis or when a more definite ana-
tomical detail is essential (e.g., thin fistulas
tracheoesophageal).
Barium formulations are not preferentially
used. In neonates, especially in premature babies,
and in circumstances where aspiration is a risk
or a perforation is suspected, a low-osmolality
water-soluble non-ionic contrast media is prefer-
entially used.
The high-osmolality water-soluble iodinated
contrast media should never be used in the UGI
for the aspiration risk and the consequent possible
Fig. 3.7  Plain abdominal radiographs. Massive submu-
cosal and subserosal pneumatosis of the left colonic wall serious complication, as acute pulmonary edema.
in NEC It is instead preferred for the enema in neonates
3  Imaging in Neonates 33

with suspected meconium ileus or meconium raphy, which demonstrates a few dilated bowel
plug syndrome for its therapeutic effect. loops, which are more than would be seen in
With regard to the proximal digestive tracts, duodenal atresia and fewer than in ileal atresia
the main neonatal surgical conditions in which or other causes of low bowel obstruction. There
contrast studies are currently applied as tracheo- is no gas in the lower portion of the abdomen.
esophageal fistulas and partially high obstruc- The patient usually requires no further radiologic
tive conditions, such as duodenal webs, annular investigation, although barium enema examina-
pancreas, duodenal and jejunal stenosis, and con- tions are still performed in attempts to exclude
genital bands in the intestinal malrotation; the second and third areas of atresia lower in the
contrast studies are instead obsolete in midgut bowel. In isolated proximal atresia of the jeju-
volvulus, whose diagnosis is today determined num, the colon is normal in size because the
by sonography. remaining small bowel distal to the atresia pro-
In neonates with tracheoesophageal fistula, duces sufficient intestinal secretions to produce a
the tube esophagram (as part of an UGI series) normal-caliber colon.
is the gold standard examination for H-type tra- Neonatal low intestinal obstruction is defined
cheoesophageal fistula, mostly in those neonates as an obstruction that occurs in the distal ileum
known to have aspiration or being ventilated at or colon; the clinical signs include vomiting,
the time of the study. abdominal distention, and failure to pass meco-
It is worth noting that even a high-quality tube nium. Ileal and colonic atresia, meconium ileus
esophagram does not always demonstrate an occult or peritonitis, Hirschsprung disease, and func-
fistula, and in occasional cases bronchoscopy may tional immaturity of the colon can determine the
also have to be performed. Similarly bronchos- obstruction. Anorectal malformations are also
copy may miss a fistula revealed by a contrast an important cause of low intestinal obstruc-
study. The tests are therefore complementary. tion but are almost always evident at physical
In neonates and infants with suspected gastro- examination.
esophageal reflux disease (GERD), the 24 h pH The diagnosis of low obstruction is usually
probe is now the mainstay for making or confirm- apparent at abdominal radiography because of the
ing the diagnosis of reflux in children; however, presence of many dilated intestinal loops, but the
the UGI is still used in many centers to confirm differentiation between ileal and colonic obstruc-
that the underlying GI anatomy is normal. tion is difficult if not impossible. This distinction
Although in precipitous decline, the SBFT can readily be made with a barium enema study,
may still be performed in preparation for elec- which helps determine the presence of functional
tive gut resection and for surgical planning when microcolon (Fig.  3.8), indicates the position of
information regarding small bowel transit is the cecum with regard to possible malrotation,
required and in suspected subacute obstruction or and shows the level of the obstruction in colonic
obstruction. atresia. In ileal atresia the colon has a normal
The first part of the study is for an upper GI location but a minute caliber.
series; the serial images are then acquired at The colonic atresia is often indistinguishable
appropriate intervals to answer the specific clini- from obstruction of the distal ileum, especially
cal question. when the atresia is located in the ascending colon.
Contrast studies of the lower GI tract have not Barium enema examination usually reveals a dis-
changed substantially over recent years, and the tal microcolon with obstruction to the retrograde
water-soluble contrast enema and, more rarely, flow of barium at the site of the atresia.
the barium enema remain the mainstay of imag- Meconium ileus is the result of intraluminal
ing. The enema studies are indicated in the bowel obstruction of the colon and lower small bowel
obstruction, especially lower obstruction. due to impaction of meconium and represents the
The generic diagnosis of high intestinal earliest clinical manifestation of cystic fibrosis.
obstruction is usually straightforward at radiog- Contrast enema shows a functional microcolon,
34 F. Carfagnini et al.

abdominal radiography and US.  The calcifica-

tions of meconium peritonitis may extend into
the scrotum through a patent vaginal process to
produce a calcified mass in the scrotum.
Hirschsprung disease is a form of low intes-
tinal obstruction caused by the absence of nor-
mal myenteric ganglion cells in a segment of the
colon [11–13]. The aganglionosis extends proxi-
mally from the anal canal, and the rectosigmoid
area is involved in most cases. Ultrashort seg-
ment disease (aganglionosis limited to the region
of the internal sphincter) is very rare, as well as
aganglionosis of the entire alimentary tract. In
newborn with Hirschsprung disease, the peri-
staltic waves do not pass through the aganglionic
segment, leading to functional obstruction within
a few days after birth.
Radiography performed in children with
Hirschsprung disease yields findings similar to
those in other forms of low small bowel obstruc-
Fig. 3.8  Barium enema study shows a severe functional
microcolon in newborn with ileal atresia
tion: variable gaseous distention of the colon and
small bowel, often with air-fluid levels. The colon
is usually difficult to identify accurately, and gas
involving the entire large bowel and impacted is usually absent in the rectum. Barium enema
meconium pellets particularly in the right colon studies demonstrate patency of the colon, which
or in the distal ileum caused by retained meco- is short but usually normal in caliber. A transition
nium. Meconium ileus is among the few pediatric zone between the narrow and dilated portions of
conditions in which the enema is performed with the colon in the shape of an inverted cone is the
high-osmolality water-soluble iodinated contrast most characteristic radiologic finding (Fig. 3.9).
due to therapeutic effects. Advantage is taken of A common cause of neonatal obstruction is
the high osmotic pressure of the contrast medium: the functional immaturity of the colon, particu-
the surrounding tissue is forced to release con- larly in premature neonates and in those whose
siderable amounts of fluid, which then flows into mothers were treated during labor with mag-
the gut and dissolves the inspissated meconium. nesium preparations and sedatives and in those
Therefore, the enema is both diagnostic and with diabetic mothers. It comprises several enti-
therapeutic and can be followed by expulsion of ties, most notably small left colon syndrome and
meconium during or after the procedure. meconium plug syndrome. Affected patients
Meconium peritonitis, chemical peritonitis have abdominal distention, difficulty in initiating
resulting from intrauterine bowel perforation, evacuation, and sometimes vomiting; typically
is often associated with underlying disorders as the bowel distention is less severe than with an
small bowel atresia, meconium ileus, volvulus, organic obstruction. The condition is both diag-
and intussusception, although some cases are nosed and treated with a contrast enema; typi-
idiopathic [17]. The extruded bowel contents cally, there is clinical improvement following the
provoke an intense peritoneal inflammatory reac- enema, and over the course of hours to days, the
tion, leading to the formation of dense fibrotic radiographic and clinical signs of obstruction
tissue. This tissue often calcifies, resulting in the subside. In meconium plug syndrome, contrast
characteristic intraperitoneal calcifications iden- enema is performed with high-osmolality water-­
tified prior to birth with US and after birth with soluble contrast.
3  Imaging in Neonates 35

a b

Fig. 3.9  Plain abdominal radiographs (a) and barium enema (b) in Hirschsprung disease: note in (b) the transition zone
(white arrows) between the narrow and dilated portions of the colon

3.2.3 Ultrasonography (US) might be necessary and should be included in the

specific disease conditions, such as the supra-
Sonography is an excellent imaging modality for sternal and mediastinal US approach to visualize
the evaluation of the gastrointestinal tract in neo- the upper esophagus in tracheoesophageal atre-
natal patients, so as to be now considered exten- sia or the perineal US approach to evaluate the
sion of the clinical evaluation, both in emergency anal canal or the distal rectal pouch location and
conditions for elective studies [18, 19]. its distance to the skin surface in anorectal or in
The well-known advantages of sonography are cloacal malformations.
its lack of ionizing radiation and the easy avail-
ability, while major drawbacks include its opera- 3.2.3.1 Upper GI Tract
tor dependency and reproducibility. Moreover it In neonates esophageal atresia is usually diag-
is an excellent bedside high-yield imaging tool nosed with frontal and lateral radiograms,
in intensive care units, and it can also be used but sonography can give additional precious
to guide therapeutic maneuvers like in enema for information to the surgeon. Besides the role of
meconium ileus. abdominal and cardiac sonography to search for
In the last decades, advances in US technology, associated abnormalities, mediastinal sonog-
particularly improvement in high-resolution linear raphy allows the characterization of the length,
probes, have greatly improved the quality of GI morphology, and structure of the wall of the blind
sonographic imaging with a consequent positive upper esophageal pouch which can be improved
impact on its diagnostic yield. Likewise, progress by the administration of small amount of saline
in Doppler techniques allows better depiction and fluid through the esophageal tube; rarely even a
quantification of even slow flow of small vessels tracheoesophageal fistula may be recognized by
within the normal and pathological GI structures. sonography.
In addition to the conventional transabdominal With a superior abdominal US approach, the
approach, other less common types of approaches cardia and the adjacent distal esophagus are often
36 F. Carfagnini et al.

easily depicted, although visualization of the position, normally passing between the abdomi-
entire distal esophageal length behind the heart is nal aorta and the superior mesenteric artery; the
difficult and restricted. normal position of duodenojejunal junction can
In neonates and infants with suspected gastro- also be identified, on the left side of the aorta.
esophageal reflux disease (GERD), sonography
is a widely available, noninvasive, and sensitive 3.2.3.2 Small and Large Bowel
method that can provide both useful anatomi- The ultrasound can be used to recognize the intes-
cal and functional information, although its role tinal malrotations [21, 22]. In the past years, bar-
is still controversial and debated. The complex ium enema and radiographic study of the upper
issue of GER and GERD is related to many fac- gastrointestinal tract were used to evaluate duo-
tors, including the difficult distinction between denum morphology, duodenal-jejunum junction
physiological and pathological GER and the position, and cecum position, and it is still con-
impasse to establish a cause-effect relationship sidered the criterion standard [21–23]. Actually,
between GER and symptoms or complications in addition to these invasive examinations that
related to GERD. use X-rays, sonography with color Doppler is
US is generally considered the modality of used to identify intestinal anomalies of rotation
choice to confirm or exclude the diagnosis of and fixation. The best known sonography finding
hypertrophic pyloric stenosis as both the lumen is an abnormal relationship between the superior
and the surrounding musculature are directly ­mesenteric artery (SMA) and the superior mes-
visualized [20]. The diagnosis of HPS is based enteric vein (SMV), although a normal position
on sonographic morphological and dynamic find- does not exclude the presence of abnormal mid-
ings: the most significant criteria are a thickened gut rotation. In addition the normal position of the
pyloric muscle (greater than 3  mm), a pyloric third duodenal portion is believed to be a more
length greater than 18 mm, and the lack of lumi- reliable mark to exclude the intestinal malrotation
nal opening of the pyloric channel (Fig. 3.10). in respect to the position of the mesenteric vessel.
The gastric duplication cysts are usually eas- Midgut volvulus is the most frequent cause of
ily recognized when they have the classic sono- acute abdomen in newborns, and it is a common
graphic appearance of localized fluid formations consequence of intestinal malrotation. It’s a life-­
with a thick layered wall. The gastric emptying threatening emergency; early diagnosis is impor-
may be used to highlight the close relationship of tant in this disease, to avoid the risk of intestinal
the cyst with the gastric wall. infarct and necrosis. If not promptly diagnosed
After ultrasound evaluation of esophageal-­ and treated, it leads to death or a lifelong depen-
gastric junction, stomach and pylorus, the next dence on total parenteral nutrition in survivors
step is to follow the duodenum to check the D3 with short bowel syndrome.

a b

Fig. 3.10  US study (a, b) shows a thickened pyloric muscle without luminal opening in hypertrophic pyloric stenosis
3  Imaging in Neonates 37

a b

Fig. 3.11  US study (a) and color Doppler (b) show the whirlpool sign, with the superior mesenteric vein and mesen-
tery wrapped around the superior mesenteric artery in a clockwise direction

Therefore learning to recognize the US to assume the probable location of the obstruc-
findings of midgut volvulus is imperative: the tion thus indicating the need to perform a con-
volvulus is responsible for the whirlpool-like trast enema in case of lower bowel obstruction.
appearance on cross-sectional images, created The colon is of normal caliber (9–14 mm) in very
when the superior mesenteric vein (SMV) and proximal small bowel atresia, while the micro-
the mesentery wrap around the superior mes- colon (3–5  mm) is easily recognized in distal
enteric artery (SMA) in a clockwise direction. small bowel atresia and in meconium ileus. The
Visualization is enhanced by the vascular signal last severe microcolon is present, but the small
at color Doppler flow sonography (Fig. 3.11). bowel is less dilated and less peristaltic. The most
For the neonate with the classic appearance of important finding is the characteristic appearance
a whirlpool sign, additional imaging investiga- of the dilated bowel loops, which contain abnor-
tion is often unnecessary, and the surgeon should mal meconium: the thick meconium sticks on the
be alerted to plan for emergency surgery. The bowel walls resulting in a pseudo-thickening. The
advantages of sonography for this age group are distal bowel loops, in the right lower q­ uadrant,
apparent, since it can be performed at the bed- are small (3–4 mm), with target-like appearance
side in intensive care units and lacks the adverse due to the impacted meconial pellets.
effects of ionizing radiation. Hydrocolon is present in meconium plug syn-
The diagnosis of neonatal bowel obstruc- drome and small left colon syndrome.
tion or the confirmation of the prenatal diagno- Besides small bowel obstruction, hepatic,
sis of these conditions is based on clinical and splenic, scrotal, and peritoneal calcifications are
radiologic signs on abdominal plain radiograph, observed in the meconium peritonitis with sin-
occurring with delay of 12–24  h; in very distal gle or multiple meconium pseudocysts and free
obstruction, it may appear even later. intraperitoneal fluid [17].
Sonography can contribute with important Occasionally sonography study highlights the
additional information [10–14]; first of all it can cause of obstruction, either intrinsic (e.g., duode-
document the obstruction, showing severe disten- nal web) or extrinsic (e.g., GI duplication cyst or
sion of the proximal bowel loops (diameter from annular pancreas) [24].
16 to 40 mm) with thin walls and increased peri- In the anorectal malformations, the distance
stalsis, filled with fluid and punctuated with ech- between the rectal cul-de-sac and the perineum
odense particles of gas. The distal bowel is small can be reliably measured with perineal sonogra-
in size (3–4  mm) with echodense or target-like phy [25]. Furthermore, sonography can be per-
meconial content. formed in patients whit associated genitourinary
Furthermore sonography allows assessment tract and dysraphic abnormalities; therefore all
of the colon size and its content, a main marker patients with congenital anorectal malformations
38 F. Carfagnini et al.

should have a genito-renal tract and spinal US

examination as a screening test in the early new-
born period.
Sonography is still not routinely used for
diagnosis and follow-up of NEC, but it can pro-
vide information that is not provided by plain
abdominal radiography and that may affect the
management of NEC [16, 26]. Like radiography,
sonography can depict intramural gas, portal
venous gas, and free intraperitoneal gas; how-
ever, the main advantage of abdominal sonogra- Fig. 3.12  Color Doppler sonography shows two loops
phy over plain abdominal radiography, including with a thickened wall and ring pattern with increased
perfusion
color Doppler sonography, is that it can show
intraabdominal fluid, bowel wall thickness, and
bowel wall perfusion [27]. Thinning of bowel wall and lack of perfu-
The ability to depict abdominal fluid is the sion are instead highly suggestive of nonviable
first major advantage of sonography study over bowel and may be seen before visualization of
plain abdominal radiography, whether this is pneumoperitoneum at plain abdominal radiogra-
intraluminal or extraluminal and whether it is phy. As the mortality is higher after perforation,
free in the peritoneal cavity or a more localized earlier detection of severely ischemic or necrotic
fluid collection. loops, before perforation occurs, could improve
The second major advantage of abdominal US the morbidity and mortality in NEC.
in NEC is its ability to visualize the bowel wall
directly and to assess bowel wall thickness, echo- 3.2.3.3 Other Diseases
genicity, and peristalsis. Sonography is the imaging modality of choice
With both bowel wall thickening and thinning, to initially evaluate neonates with persis-
the normal echogenicity of the wall (so-called tent jaundice. In biliary atresia, one of the
gut signature) is lost, and it may be difficult to most common findings is an absent or small
resolve the bowel wall from echogenic intralu- (<1.5  cm) or empty gallbladder, after fasting
minal content in severely affected loops. Bowel for several hours. Absence of the gallbladder is
wall thickening is accompanied by an increased present in approximately two thirds of neonates
echogenicity of the full wall thickness; however, with biliary atresia. The triangular cord sign
it is a non-specific sign, as it is also seen in other (defined as a triangular or tube-shaped echo-
causes of diffuse edema in the absence of inflam- genic focus at the porta hepatis that follows
mation or ischemia. the portal veins and measures more than 4 mm
The third major advantage of abdominal US in thickness) is another characteristic finding.
including color Doppler is the ability to directly However, it may be difficult to distinguish this
assess arterial perfusion of the bowel wall, to sign from diffuse periportal echogenicity due
infer the viability of individual loops. to inflammation or cirrhosis. Other signs that
Three categories of flow were recognized at have been described in the diagnosis of biliary
color Doppler: normal, increased, and absent. atresia include an absent common bile duct,
The hyperemia is the result of vasodilatation of a hypertrophic hepatic artery (reported diam-
mural and mesenteric vessel secondary to intes- eter 2.2 ± 0.59 mm), and an increased hepatic
tinal inflammation, with specific flow pattern subcapsular flow on color Doppler sonography
(“zebra” pattern, “Y” pattern, and “ring” pattern) (CDS).
(Fig. 3.12). Choledochal cysts are very rare congenital
Flow is absent when no color Doppler signals saccular or fusiform dilatations of the biliary
were identified in the bowel wall. tree, usually classified according to Todani in
3  Imaging in Neonates 39

five types. Type I choledochal cysts are the most

common, occurring in up to 80–90% of cases.
Choledochal cysts usually present with choles-
tatic jaundice, but abdominal pain and fever may
also be present. As choledochal cysts are often
associated with an abnormal junction of the com-
mon bile duct and pancreatic duct, an ascending
cholangitis and/or pancreatitis belongs to the
most frequent complications, caused by reflux of
pancreatic secretions in the bile ducts.
Other complications include liver cirrho-
sis, portal hypertension, and spontaneous cyst
rupture.
Imaging plays an essential role in defining
the extent of disease and guiding the surgical
approach, as complete excision of the cysts is
usually the treatment of choice. On US, the local-
ization and degree of bile duct dilatation can be
easily identified. Due to bile stasis in the dilated
bile ducts, sludge or bile stones may be identi-
fied. As type 5 choledochal cysts (Caroli disease)
are associated with autosomal recessive polycys-
tic kidney disease, the kidneys should be exam-
ined as well.
Sonography may finally disclose other patho- Fig. 3.13  Coronal MRI: T2-weighted image shows a
large fluid mesenteric cist in the right abdomen
logic conditions such as hernias, duplication
and mesenteric cysts, and tumor and tumor-like
conditions. Although it is a rare occurrence, the onset
of oncological pathologies, such as hepatoblas-
toma, ganglioneuromas, and neuroblastomas, is
3.2.4 M
 agnetic Resonance Imaging ­possible in the neonatal period; in these cases the
(MRI) MRI, in addition to being useful in preoperative
planning, is used for staging.
The main peculiarity of MRI is to provide mul- Very important is the use of MRI in the con-
tiplanar images with high resolution of tissue genital malformations of the biliary tree, from the
contrast, without the use of ionizing radiation; atresia to the choledochal cysts, thanks in partic-
the duration of the investigation is still likely to ular to the cholangiographic sequences (MRCP)
require sedation. that allow the evaluation of the biliary tree, with-
In neonatal age, magnetic resonance imaging out using contrast medium (Fig. 3.14).
was the second-level investigation for the study In biliary atresia hepatobiliary scintigraphy
of benign expansive lesions, already diagnosed (HBS) and magnetic resonance cholangiopan-
by ultrasonography and sometimes known since creatography (MRCP) may play a role, the lat-
the prenatal age. The most frequent lesions are ter only utilized as a problem-solving technique
mesenteric cysts, intestinal duplication cysts, provided that the biliary tree is dilated. In chole-
and lymphangiomas, which the magnetic reso- dochal cysts, MRI (including MRCP) is currently
nance can confirm, providing precious and more the most accurate preoperative imaging modality
detailed pre-surgical anatomical information [24] to demonstrate the extent of disease and the rela-
(Fig. 3.13). tionship of the cysts to the surrounding tissues.
40 F. Carfagnini et al.

a b

Fig. 3.14  Coronal MRI T2-weighted image (a) and MRCP (b) in a rare case of common bile duct diverticulum

Finally, the MRI is very helpful in the study a perfect assessment of thoracic and abdominal
of anorectal abnormalities, particularly in the vascular anatomy is required.
preoperative evaluation of the newborn or infant
prior to definitive pull-through repair surgery and
in postoperative course pediatric patients with 3.3 Urogenital Neonatal
continuing problems [28]. Examination during Imaging
sedation may give them to more accurate estima-
tion of the true level of the elevator sling with Like in other body parts, urogenital system
multiplanar direct visualization of the distal rec- examination starts with a prenatal ultrasonogra-
tum and related musculature (levator ani muscle, phy, which usually is the first to underline renal,
puborectalis muscle, external sphincter). urinary tract, and genital malformations that alto-
When the radiographic or sonographic exami- gether amount to more than a third of congenital
nation is abnormal, then MRI can be used to anomalies in newborns.
accurately depict the likely associated intraspinal Usually second-level prenatal ultrasound
pathology such as tethered cord, caudal regres- exam, in association with color Doppler imaging,
sion syndrome, hydromyelia, or a lipoma of the is able to evaluate the malformation’s type and
terminal filum. Associated lesions such as sacro- seriousness.
coccygeal hypoplasia, lumbar spine, or renal However, in some complex cases or with
anomalies can also be evaluated. poly-­
malformative syndromes, or when oligo-­
anhydramnios is present, fetal MRI might be needed
to reach a more correct analysis and improve the
3.2.5 Computed Tomography (CT) postnatal clinical-therapeutic management.
Among the surgical diseases, the MRI finds
CT is a highly radiant investigation and there- use in multicystic kidneys, posterior urethral
fore a level II diagnostic technique, which does valves (hydro-ureteronephrosis evaluation and
not have significant applications in neonatal age. the frequently associated renal dysplasia), renal
The only very rare exceptions are those in which masses, neurological bladder and its associated
3  Imaging in Neonates 41

pathology (myelomeningocele), megabladder-­ flow speed and direction. Color Doppler studies
microcolon (prune belly syndrome with abdomi- can also give information and directly visualize
nal wall study), cloacal exstrophy, urogenital urethral jet.
sinus diseases and expansive diseases, and most Doppler sonography gives detailed informa-
common ovarian masses. tion on flow profiles; in newborns it is character-
ized by a physiological low flow speed, a higher
resistivity index, and peak diastolic seed a little
3.3.1 Ultrasonography (US) lower.
Doppler study is also very useful in perfusion
After birth, ultrasound imaging is often the only alteration indirect sign evaluation, as is verified
exam needed to a definitive diagnosis and the in renal vein neonatal thrombosis (that involves
key to indicate subsequent diagnostic algorithms, a higher resistivity index of the affected kidney),
significantly reducing the need for other exams renal arteries stenosis, or flow variations in kid-
[29–34]. ney failure.
It is a real-time, operator-dependent exam that Power Doppler studies show the blood flow
requires highly experienced examiner, trained in volume instead of its speed, particularly useful in
pediatric radiology. peripheral renal vascularization evaluation.
It requires high-resolution, multifrequency Its use allows focal perfusion defect (renal
(3–18 MHz) probes, with which can be meticu- infarction, segmental pyelonephritis) diagnosis
lously examined both the urinary and the genital or cortical perfusion diffuse reduction.
system. Ultrasonography recognizes several con-
genital diseases, first of all anomalies of number
3.3.1.1 Urinary System (renal agenesis), position (simple ectopia), and
Regarding the urinary tract, it’s essential that fusion (horseshoe kidney, crossed fused ectopia,
the operator is experienced with the appearance and renal duplications); those malformations
variations of the growing kidney. In the prenatal have anyway no surgical interest.
age, kidneys keep their typical fetal lobulation, On the other hand, antenatally diagnosed hydro-
showing notches or wave profile. Renal cortex nephrosis represents one of the more frequent
during this time is relatively hyperechoic com- indications to neonatal US; congenital hydrone-
pared to the liver, especially in premature new- phrosis can be secondary to mechanical or func-
borns, with increase of normal corticomedullary tional causes (Fig. 3.15). Obstruction’s mechanical
differentiation. Medullary pyramids are relatively causes include ureteropelvic junction obstruction
hypoechoic compared to cortex, while the renal (UPJO), ureterovesical junction obstruction (UVJ),
sinus is not represented due to absence or paucity simple ureterocele, and posterior urethral valves.
of fat. Pyelocaliceal cavities and ureters are visi- Functional causes include the prune belly syn-
ble only when dilated and appeared anechoic. The drome and the vesicoureteral reflux.
bladder needs to be evaluated in size and mor- In newborns with prenatal diagnosis of severe
phology, its wall thickness must be measured, and bilateral hydronephrosis, ultrasound imaging is
every endoluminal growth needs to be examined. required on the first day of life, especially in case
In addition to typical uses, there are newer of hydro-ureteronephrosis and/or suspected blad-
ones that have great relevance in urinary system der anomalies or urethral valves.
study; the use of high-frequency linear probes Instead, in case of moderate bilateral hydro-
with transperineal approach to assess male’s ure- nephrosis or unilateral hydronephrosis (with or
thra, female’s vagina, and surrounding structures without ureteral dilatation) prenatal diagnosis,
should be remembered. ultrasound examination can be delayed until
Very important are also color Doppler studies the first week of life, due to the urinary system
that allow a fast and comprehensive overview of immaturity and the risk to underestimate patho-
vascular anatomy, as well as an assessment of the logical findings presence and seriousness.
42 F. Carfagnini et al.

a b

Fig. 3.15  Sonography at birth. Important hydro-ureteronephrosis (a, b, c): the thickening of mucus lining is strongly
suggestive of vesiccoureteral reflux

US alone isn’t able to discriminate between Among the renal cystic diseases can be of sur-
obstructive uropathy and reflux diseases, so gical interest the multicystic dysplastic kidney,
definitive diagnosis requires subsequent imaging a non-hereditary developmental anomaly that is
investigations. believed to be the consequence of early in utero
Only in some cases can ultrasound imaging urinary tract obstruction.
strongly direct toward an obstructive condition, Expansive diseases diagnosis is also echo-
as is seen in cases of serious pelvic balloon-like graphic; in neonates, those diseases, although
dilatation, without corresponding ureter size rare, involve more often the kidney (mesoblastic
alteration: those cases are strongly suggestive of nephroma, nephroblastomatosis).
UPJO.  On the other hand, presence of hydro-­
ureteronephrosis with thickening of mucous 3.3.1.2 Genital System
lining is strongly suggestive of vesicoureteral The internal female genitalia are prominent at
reflux. birth due to maternal and placental hormonal
3  Imaging in Neonates 43

stimulation. After 2–3 months, the uterus is small findings on prenatal or postnatal US, but they
and malformations are easily missed. Therefore, may present postnatally as pelvic or abdominal-­
in suspected malformations of the female pelvic mass. Normally these cysts resolve within
­genitalia, the investigations should be performed a few weeks after birth and cause no complica-
shortly after birth. tions. Complications from larger ovarian cysts
Congenital anomalies of the female genital include bleeding into the cyst, ovarian torsion,
tract result from developmental anomalies of the and occasionally ovarian strangulation in an
Müllerian duct with or without combined abnor- inguinal hernia.
malities of the urogenital sinus or cloaca. The US appearances of a simple, uncompli-
There is a developmental relationship between cated cyst are the anechoic content, a thin wall,
the genital and the urinary tracts; hence anom- without intralesional septa; another finding is the
alies in both systems are often coexisting. daughter cyst sign.
Comprehensive US examination of the inter- Hemorrhagic cysts and cysts associated with
nal genitalia should be performed in all female adnexal torsion appear as complex masses con-
neonates with multicystic dysplastic kidney taining multiple septations, low-level echoes,
(MCDK), unilateral renal dysplasia, or single clotted blood, and/or fluid-debris level; other
kidney due to the high risk for associated geni- findings of torsion include thick, echogenic
tal malformation, as well as in individuals with walls, and a twisted vascular pedicle.
suspected or obvious genital or cloacal malfor- Occasionally a specific diagnosis of ovarian
mations or congenital adrenal hyperplasia. Both teratoma can be made when highly echogenic
curved array transducers of adequate size and foci with shadowing are demonstrated within a
high-resolution linear transducers must be applied complex adnexal mass.
using both abdominal and perineal approach. In Indirect sliding inguinal hernias containing
neonates the filling of the vagina, and sometimes the ovary and fallopian tube are not uncommon
also the rectum (called sonogenitography), will in neonates, with an increased risk of vascular
facilitate accurate depiction of anatomy, particu- compromise. Ultrasound is an accurate method
larly in more complex malformations. to determine the content of inguinal hernias and
The size, morphology, and position of the will help determine further management.
vagina, cervix, and uterus, including signs of uter- In male newborns, US plays an important
ine duplications and cervical or vaginal obstruc- role in extravaginal torsion (Fig. 3.16). It usually
tion, should be described, both during filling and occurs at a level of spermatic cord in utero, and
before and after voiding. If there are signs of all of the scrotal contents on the affected side are
obstruction, the distance from the site of obstruc- strangulated. Affected neonates present with a
tion to the perineal orifice should be assessed. swollen red scrotum with a firm enlarged testis.
Malformations of the female genitourinary While it is most commonly unilateral, bilateral
system may be isolated or part of a syndrome extravaginal perinatal torsion does occur. The
with other associated anomalies, particularly testis is usually necrotic at birth so that surgical
spinal or skeletal malformations. In complex salvage is unlikely. In contrast, when extravaginal
malformations such as intersex conditions, uro- torsion occurs after birth or produces only partial
genital sinus, or cloacal malformations, the child ischemia, the testis may be viable and hence sal-
should always be referred to a dedicated pediatric vageable with surgery.
center for further workup and treatment. US findings of extravaginal torsion vary
In healthy female neonates, the small, depending on the duration of torsion. Findings
anechoic follicular cysts up to 10  mm in diam- in more recent torsion include an enlarged het-
eter in the ovaries are a normal finding, and they erogeneous testis with hypoechoic and hyper-
generally do not have a pathological significance. echoic areas. More chronic torsion demonstrates
In the neonatal period, even large ovarian a minimally enlarged or normal size hypoechoic
cysts may be seen, and they may be incidental testis with peripheral echogenicity corresponding
44 F. Carfagnini et al.

a b

Fig. 3.16  Scrotal sonography in newborn: color Doppler evaluation (a) shows an enlarged heterogeneous testis with
hypoechoic and hyperechoic areas, without vascular signal; (b) normal finding of the contralateral testis

to calcifications in the tunica albuginea. Scrotal hypoechoic than the contralateral normally
skin thickening and hydroceles with debris and/ located testis.
or septations are common associated findings. Furthermore US can aid in establishing a
Doppler signals are often absent in the testis and diagnosis of an inguinal hernia, more frequent
in the spermatic cord, although some flow may be in premature, by demonstrating peristalsing fluid
seen with power Doppler imaging. The contralat- or air-filled loops of bowel in the scrotum and a
eral testis may demonstrate compensatory hyper- normal testis and epididymis. Identification of
trophy, a finding seen in other cases of congenital peristalsis favors viable bowel, while absence of
monorchism. peristalsis and blood flow in the herniated bowel
US is also used in neonates and infants with suggests ischemic changes. When omentum also
hydrocele, associated with a patent vaginalis pro- extends into the inguinal canal, the hernia will
cess, which allows peritoneal fluid to enter the appear as a complex echogenic mass.
scrotal sac. Hydroceles can present as loculated
or encysted around the spermatic cord if the vagi-
nalis process closes above the testis and below 3.3.2 Contrast Studies
internal inguinal ring.
Scrotal extratesticular calcifications may be The contrast studies are voiding cystourethrogra-
observed at ultrasonography in meconium perito- phy (VCUG) and voiding urosonography (VUS)
nitis, usually between the layers of the tunica vagi- [35–39].
nalis, as hyperechoic foci with acoustic shadowing. Voiding cystourethrography (VCUG) is
US can be requested in cryptorchidism, at still today the first-choice exam for vesicoure-
birth most frequently found in premature male teral reflux diagnosis and male urethra diseases
infants. Testicular migration can arrest any- (Fig. 3.17). The exam requires positioning a blad-
where along the course of descent from the ret- der catheter without balloon and then highly con-
roperitoneum into the scrotum; in most cases the centrated, radiopaque contrast medium bladder
undescended testes are located in the inguinal injection, until complete bladder filling. The field
canal, or just proximal to the internal inguinal of view must include all the urinary system, from
ring, while rarely are located in the abdomen. the kidneys to the urethra, to evaluate male urethra,
Hypo-­atrophy of the undescended testis is com- which is a fundamental lateral projection acquired
mon, and at US the testis is smaller and more during the urination and after the catheter removal.
3  Imaging in Neonates 45

It’s important to remember that it is a radiant For the same reasons of radioprotection,
technique, moreover without the possibility to is the use of voiding urosonography (VUS) is
shield the gonads: for this reason VCUG must be more and more widespread, possibly thanks
executed exclusively with a pulsed fluoroscopic to the introduction of second-generation echo-
technique, ideally with the lowest pulse setting, graphic contrast agents injected in the bladder
with a notable dose reduction. after catheterization, similarly to what already
said for VCUG. Those produce a high enhance-
ment and a strong harmonic response, but
most of all they have a higher resistance to the
ultrasound beam mechanical impact, allowing
a longer study time, needed to possible reflux
detection (Fig. 3.18).

3.3.3 Magnetic Resonance

Imaging (MRI)

In newborn, MRI has very peculiar indications,

usually required as second-level exam to evalu-
ate complex urinary and genital system malfor-
mation conditions (bladder exstrophy, cloaca,
urogenital sinus anomalies, genital congenital
anomalies) or more often as a functional study
in obstructive uropathy [40–48]. For the latter
today, it can be considered the only diagnostic
technique that detailed anatomical and functional
information of the urinary system, without using
ionizing radiation.
It must be considered, anyway, that the MRI is
a second-level exam, usually executed on infants
Fig. 3.17  VCUG demonstrates severe bilateral reflux
only in a limited number of selected cases, due
and normal urethra in a male neonate

a b

Fig. 3.18  Voiding urosonography (VUS): pre-contrastographic US study (a) and post-contrastographic US study (b)
with optimal VUR visualization
46 F. Carfagnini et al.

to its needing sedation/anesthesia and the use of resolution images obtained are excellent for 3D
intravenous contrast medium. VR reconstructions with the optimal visualiza-
The knowledge of the relationship between tion of the renal cortex, the medulla, the pelvi-
the administration of paramagnetic contrast agent calyceal system, and the ureter course into the
and nephrogenic systemic fibrosis requires great bladder.
caution in its use in pediatric age, particularly in The post-processing phase can be measured
neonatal and infant age, and full compliance with in various parameters of renal function and par-
all precautionary measures. ticularly the renal transit time, the calyceal tran-
Functional uro-MRI requires an initial sit time, the time-intensity curves, the differential
patient’s preparation phase (hydratation and renal function, and the glomerular filtration rate
furosemide injection), followed by pre- and post-­ (GFR). These are very important parameters,
contrast sequence acquisition. Pre-contrast imag- similar to those used in scintigraphic studies.
ing is the most important phase for the anatomic Finally the MRI is used in newborn and infants
evaluation of the urinary tract. It is performed for a better evaluation of the masses, frequently
with TSE T2-w and 3D T2-w sequences; the kidney’s masses, diagnosed with ultrasonogra-
latter are used to generate MIP and VR images, phy (Fig. 3.19).
which allow the best visualization of the pelvi-
calyceal system and ureters.
The resulting images are very useful for the 3.3.4 Other Diagnostic Techniques
evaluation of obstructed collecting system,
duplex systems and complex anatomical variants, Plain film and intravenous urography virtually
and bladder abnormalities, including ureteroceles disappeared from pediatric radiology, because
and ectopic ureteral insertion. Same sequences anatomical and functional information can be
are also fundamental in poorly functioning sys- acquired with the same or higher level of detail
tem or in functionally excluded kidneys, which with ultrasound or MRI and nuclear medicine
obviously have little or no displayed in contrasto- studies.
graphic phase, similarly to what occurs with scin- CT has instead as major drawback the high
tigraphic studies. radiation dose and, according to the ALARA
The following post-contrastographic phase, principle, should be used in children only in the
vascular and excretory, allows to dynamically rare cases in which the same diagnostic infor-
study the urinary system. Typically after the mation cannot be obtained with other, less or no
contrast administration, continuous dynamic
­ radiating, imaging techniques.
images are acquired, until the complete That is the reason why CT does not find sig-
enhancement of the excretory system. The high- nificant indications in neonates and infants.
3  Imaging in Neonates 47

b c

Fig. 3.19  US (a) and MRI (b, c) show large right kidney masses (nephroblastoma). Note in (b) the contralateral mul-
ticystic kidney

3. Wernecke K.  Ultrasound study of the pleura. Eur

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 Neonatal Surgical Education
in Minimally Invasive Surgery 4
Based on Simulation

Maximiliano Maricic and María Marcela Bailez

4.1 Introduction Even though there is not an evidence-based

research result of this ultimate goal in this topic,
Neonatal minimally invasive surgery (NMIS) with the aim of improving the learning curve for
requires a high level of training in both neonatal NMIS, the senior author decided to include simu-
and MIS disciplines. It requires a progressive lation in a regular basis in the curricula of our
goal-oriented curricula content specific to each pediatric surgical residents and created an MIS
surgical neonatal pathology. Evaluation of the education fellowship, starting in 2013.
theoretical and practical contents at each stage of We use a spiral education method, where we
training is mandatory. Surgical skills training has increase the complexity of the procedures in a
been classically done in the operating room under progressive way, but we reinforce the basic con-
the supervision of the senior surgeon and in ani- cepts of MIS in all the stages of the training and
mal models, when available. The difficult learn- incorporate suture skills from the beginning.
ing curve combined with the few cases per year
for each surgeon is a critical factor against the
spread of these procedures that are feasible and 4.2  MIS Curricula Including
N
effective in experts’ hands. Simulation in Pediatric
Simulation is used as a complementary learn- Surgery Training Programs
ing tool in minimally invasive surgery (MIS). It
allows training in a safe, standardized, and con- Neonatal/infant MIS procedures should be
trolled environment, without compromising the addressed as very advanced ones at the time of
safety of the patient. The goal of simulation is to planning the content of a curricula. The concept
transfer the acquired skills to the operating room, of progressive training should not be underesti-
improving patients’ outcome. mated and rigorous basic and intermediate levels
of MIS training courses including simulation
should be done before a NMIS course. We under-
stand this may change in relation to every region
M. Maricic (*) needs or program, for example a previous general
Pedro de Elizalde Children’s Hospital, surgery residency as a requirement to enter a
Buenos Aires, Argentina
pediatric surgery program or not.
Garrahan Children’s Hospital—Surgical Simulation An efficient training program is one in which
Center, CeSim, Buenos Aires, Argentina
skills are trained in a programmed, progressive,
M. M. Bailez specific way. An adequate evaluation system of
Garrahan Children’s Hospital—Surgical Simulation
Center, CeSim, Buenos Aires, Argentina the results and progress of the student with

© Springer Nature Switzerland AG 2019 51

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_4
52 M. Maricic and M. M. Bailez

debriefing at each stage is mandatory. A suitable

program allows performing tasks with progres-
sive complexity and precision.
The first approach to endosurgery should
include every professional aspect of MIS like
knowledge of equipment and instruments, elec-
trosurgery, ergonomy, and the art of MIS
suturing.
With this in mind we developed different lev-
els of simulation courses and not only include
them in the curricula of different residency pro-
grams but also offered them to pediatric surgeons
in need of MIS training for different reasons.
We designed three levels of in situ courses
with progressive complexity and created our own
low-cost inanimate and hybrid basic, intermedi-
ate, and specific neonatal models, some of them
already published and validated.

4.3 Course Contents

Each course has a cognitive and a simulation-

based skill content. The cognitive aspect is shared
virtually and discussion is promoted before start-
ing with the skills simulation stations. Depending
on the stage of the training we are in, we use dif-
ferent types of endotrainers, such as adult-sized
devices with an 8-L working area (Fig. 4.1),
advanced devices of 500–800 mL like Pediatric
Toronto model [1] (Fig. 4.2), and neonatal mod- Fig. 4.1  Initial box trainers 8 L
els that are specifically developed and validated
with working areas between 100 and 40 mL [2] The participants change stations every hour
(Fig. 4.3). with 32 h distributed in 3 days. A personalized
supervision avoiding the development of inad-
equate maneuvers and teaching the profes-
4.3.1 L
 evel 1: Basic or Essential sional ways and tricks to shorten the learning
Skills Course curve is undertaken and data is obtained for
debriefing to guaranty that the objectives are
It includes principles of ergonomy, electrosur- reached.
gery, equipment and instruments, art of intracor- A personalized supervision avoids inadequate
poreal and extracorporeal suturing, port maneuvers, provides the opportunity of sharing
placement, strategy for common procedures, and tips and tricks in order to have a shorter learning
team working. curve, and ensures reaching the pre-established
The goals include the use of both hands for objectives. We usually use virtual trainer devices
exposing and dissection, correct use of energy, in this stage of training (Fig. 4.4) and plan work-
lens and tissue handling, needle grabbing, and shops to acquire the practical concepts of the
Roeder extracorporeal and square intracorporeal cognitive content about electrosurgery, instru-
knot techniques. ments, and equipment.
4  Neonatal Surgical Education in Minimally Invasive Surgery Based on Simulation 53

Fig. 4.3  Neonatal advanced trainer. Own development.

Working space 100–500 mL

Fig. 4.2  Advanced box trainers. Own development and

Toronto model (below) Working area: 500–800 mL

4.3.2 MIS Suture and Knots

We consider the art of endosuture and vessels dis-

section with either sealing or ligature as the fun-
damental skills to assess before starting with the
specific models. Multiple knots have been
described. We decided to standardize some of
them for an educational purpose. Fig. 4.4  Virtual devices
54 M. Maricic and M. M. Bailez

Extracorporeal knots: These allow solving a

great number of situations, are very versatile, and
require adequate coordination, precision, and
care of the tissues. We teach how to avoid the use
of specific instruments like knot pusher and slide
it with a Maryland dissector or the needle holder.
They may be used for example in a diaphrag-
matic plication or rectourinary fistula during a
rectal pullthrough.
Square knot or surgeon knot is the main intra-
corporeal knot that we use for training and its
practice develops coordination and precision
skills.
Intracorporeal slide knot: This knot has the
benefits of intracorporeal and extracorporeal
suturing. It is designed for tissues under traction Fig. 4.5  Suture assessment
that needs to be put together gradually (for exam-
ple esophageal atresia (EA)). Most of the expert
MIS neonatal surgeons use this knot. We include mal models into the curriculum to perform guided
it in level 2 and 3 courses. procedures (cholecystectomy, salpingectomy,
Initially we teach each of these knots sepa- Nissen, nephrectomy, and diaphragmatic sutur-
rately, but the final objective is to provide the stu- ing). We use 10 kg piglets under anesthesia fol-
dent a number of tools that allow choosing the lowing the rules of the bioethics committee in
best knot for each moment and tissue. relation to the use of experimental animals.
During the last 2 years we have replaced experi-
mental animals by blocks of live tissue from farm
4.3.3 Level 2: Advanced Course animals acquired in butcher shops, making hybrid
models (Fig. 4.6). This reduces costs and clears
We start doing an assessment of suturing (square the ethical problems involved in working with
knot technique) in a tubular silicon structure live animals.
(Fig. 4.5) and dissection and vessel sealing in live
tissue (pig or cow kidney or lung into a trainer)
using a vessel filling technique. 4.3.4 L
 evel 3: Neonatal Advanced
Cognitive content includes innovation, Course
advanced technology, thoracoscopy, and other
intracorporeal suturing techniques like running It is a pure neonatal/infant MIS training course
sutures and intracorporeal sliding knots. and includes not only skills, but also team
We use plastic mannequins opened in the behavior simulation and appropriate care, of
abdominal area to introduce a block of animal the fragile ergonomic instruments essential to
viscera to simulate a Nissen procedure, colonic acquire speed and effective actions in a safe
biopsies or resections and cholecystectomy. environment. During the course instructors
These models are also used to simulate safe tro- will support participants to care instruments
car insertion technique in level 1 courses and ergonomics, and to acquire speedy, effec-
(Fig. 4.6). tive, and safe actions and movements taking
Only after a basic and advanced period of care of the simulation models as if they were
training we recommend the introduction of ani- real patients.
4  Neonatal Surgical Education in Minimally Invasive Surgery Based on Simulation 55

Fig. 4.6  Hybrid model 1

56 M. Maricic and M. M. Bailez

It is mandatory to achieve level 1 and 2 to coordination and the understanding of the value
achieve level 3. Sophisticated courses with many of being in charge of a 30-degree mini endocam-
stations and technology using either inanimate or era. Ergonomic short 3 mm instruments are used.
live models are not worth planning with partici- The instructor provides tricks and technical tips,
pants that should have practiced or even attended as well as a discussion of the clinical aspects of
a suturing course before being exposed to these the disease. Debriefing and evaluation of the
models. They are not cost-effective and may results are carried out through exams and perfor-
cause frustration in the learning process. mance evaluation forms.
Small volume trainers simulating an infant or
neonate abdomen or thorax are used only after an
assessment of basic suturing in regular trainers is 4.4  MIS Instructors, Models,
N
done. Exercises include transference, cutting pre- and Knots
cision, extracorporeal and intracorporeal suture
with fine needles and threads, for example the 4.4.1 Instructors
Toronto model [1] with a working area of about
800  mL.  This is a webcam trainer to practice The fundamental bases for effective training are
transference, precise cutting, and suturing using an adequate program, trained instructors, and
extracorporeal and intracorporeal suturing tech- specific models for each stage of training.
niques inspired in the FLS. In our training curriculum one of the
The first neonatal MIS model used in our strengths is the training of instructors, who are
institution was the one developed by Karen pediatric surgeons who operate NMIS.  All of
Diefenbach when she was a pediatric surgical fel- them must complete the curriculum and peda-
low in Yale (Fig. 4.5). This model is now part of gogical training. At the same time, they will be
an educational project shared with IPEG. the ones who train other instructors in the
We have found a shortage of training models future.
available for level 3 courses. Therefore we have As mentioned above, the role of the instructor
developed our own models of neonatal training is very clear:
with a small working area between 40 and It accompanies the educational process in all
400 mL and inspired in the expertise in NMIS. its stages, reinforcing the concepts of patient
Inspired by his daughters’ toys, our first MIS care, ergonomics, specific techniques, and team-
trainee-fellow modified the plastic handbags of work, and making continuous feedback to
their dolls and with the help of the scrub nurses students.
they developed simple neonatal trainers to prac-
tice handling and suturing in small spaces.
Until now we have developed trainers for spe- 4.4.2 Models
cific surgical procedures in newborns and infants:
esophageal atresia with tracheoesophageal fistula The high fidelity of the models is recommended
(TEF/EA), duodenal atresia (DA), congenital to improve expertise. However they are expen-
diaphragmatic hernia repair (CDH), lobectomies, sive. Most of our models are cheap. They were all
hepaticojejunostomy after choledochal cyst inspired by our experience in neonatal MIS and
resection (Figs. 4.7–4.11). we have validated the first specific model we
They challenge the tasks of working with deli- developed [2].
cate tissues, suture in extremely small spaces The combination of ex vivo animal tissue and
(e.g., less than 50 mL) in an environment of high the use of 3D printed thoracic cages like in our
anatomical similarity, resembling specific pathol- last model (CDH) have been incorporated to
ogies of the newborn. improve fidelity (Fig. 4.9).
Two participants are assigned to work together The use of live tissue enables the practice of
per model. This strengthens the skills of team energy devices and increases tactile sensation.
4  Neonatal Surgical Education in Minimally Invasive Surgery Based on Simulation 57

Fig. 4.7  Esophageal atresia with tracheoesophageal fistula (TEF/EA) model

58 M. Maricic and M. M. Bailez

Fig. 4.8  Duodenal atresia model

4  Neonatal Surgical Education in Minimally Invasive Surgery Based on Simulation 59

Fig. 4.9  Congenital diaphragmatic hernia repair (CDH) model

4.4.2.1 Esophageal Atresia • End-to-end esophageal anastomosis (muscle

with Tracheoesophageal Fistula and mucosa are represented)
(TEF/EA) [2] (Fig. 4.7) • Placement of transanastomotic probe
The model consists of a doll representing a 3500 • Debriefing and endoscopic evaluation of the
and 2000 g newborn and a spare part that resembles anastomosis
the right hemithorax and mediastinum with the tra-
chea, ribs, upper and lower esophagus with a TEF,
pneumogastric nerve, azygos vein, and mediastinal 4.4.2.2 Duodenal Atresia (DA) [3]
pleura. The simulated lung can be inflated either (Fig. 4.8)
with a resuscitation bag or connected to a ventilator The model consists of a dummy that represents a
to simulate lung movements during surgery. 4500 g baby in which a simulated type III duode-
This is a low-cost model completely inani- nal atresia, made with silicon and latex, is placed
mate and made of latex silicone and plastic. All in anatomical position. The steps that are trained
the steps of the repair of esophageal atresia are in this model are:
reproduced in this model:
• Working port placement
• Working port placement • Dissection of the proximal duodenal pouch
• Dissection and ligature of the azygos vein • Dissection of the distal duodenal pouch
• Dissection and ligature of the TEF • End-to-lateral anastomosis
• Dissection and section of the upper esopha- • Debriefing and endoscopic evaluation of the
geal pouch anastomosis
60 M. Maricic and M. M. Bailez

Fig. 4.10  Lobectomy model

4  Neonatal Surgical Education in Minimally Invasive Surgery Based on Simulation 61

Fig. 4.11  Hepaticojejunostomy model

This model can be hybridized using live tissue baby. A spare part includes the last three ribs and
from farm animals that can be previously modi- a base added that simulates the upper abdomen.
fied to resemble the anomaly. Heart, lung, and mediastinal structures are
located resembling their anatomical position.
4.4.2.3 Congenital Diaphragmatic The diaphragm with the chosen defect is placed
Hernia Repair (CDH) [4] (Fig. 4.9) on the spare part. Abdominal ex  vivo viscera is
This is an inanimate model for training thoraco- placed at the base and passed through the defect
scopic repair of left congenital diaphragmatic to the thoracic cavity. Both parts are assembled
hernia. Right defects can also be simulated. It is and covered by a layer of silicone. All kinds of
easily portable and a low-cost model made of diaphragmatic defects can be simulated (different
synthetic materials such as polylactide (PLA), positions and sizes), with or without sac. Patch
silicon, fabric, and latex. placement can also be trained. This model can
The base of the model is a 3D printed left also be hybridized and the diaphragm can be sim-
hemithorax, extracted from a CT scan of a 4 kg ulated with tissue.
62 M. Maricic and M. M. Bailez

4.4.2.4 Lobectomies (Fig. 4.10) Gladiator concept: This type of knot is a mod-
This model is completely inanimate and allows ification of the square knot that allows using the
training of different types of lobectomies. same hand to perform the knot.
Vascular and bronchial structures are anatomi- Intracorporeal sliding knot: This knot is
cally located according to the type of lobectomy. extremely useful and a key tool to solve a great
As the materials are synthetic, they do not allow amount of pathologies, including neonatal.
the use of energy; therefore we promote training Initially, and for academic reasons, we teach
in dissection, suture, or stapler. Depending on the each of these knots separately, but the final objec-
side we use a right or left 3D printed hemithorax tive is to provide the student with a number of
extracted from a 6 kg baby CT scan. This model tools that allow choosing the best knot for each
can also be hybridized by including live tissue tissue and can combine them depending on the
from farm animals as described by Kathy moment of the surgery.
Barsness [6] with the disadvantage that the anat-
omy is very difficult to emulate.
4.5 Conclusion
4.4.2.5 Hepaticojejunostomy
(Choledochal Cyst) (Fig. 4.11) Training in neonatal endosurgery (NMIS) is a
Similar to the duodenal atresia model, this is essen- challenge. Simulation tools must be included in
tially a suturing model for a tiny end-to-side anasto- the curricula to compensate the small number
mosis resembling a hepaticojejunostomy after a of patients required to improve the learning
cyst resection where the Y-roux is already made. curve.
The learner is meant to locate the loop through the We acknowledge tools available from differ-
mesocolon and perform the anastomosis either with ent groups around the world emphasizing those
running or interrupted sutures. We start with silicon developed by work groups that are dedicated to
or rubber tubes and then with live tissue. Endoscopic training in MIS [5–8]. We continued developing
evaluation of the anastomosis is mandatory. our own neonatal specific training models,
which allow us not only to improve skills but
also to advance in new techniques or tricks.
4.4.3 Knots Data about clinical outcome is needed. As we
have emphasized in this chapter the initial stages
Multiple endoscopic knots have been described of skill training should include the use of large-
in literature. We decided to standardize some of volume endotrainers (as FLS-SAGES) and vir-
them for an educational purpose. We believe that tual trainers that develops bimanual dexterity
it is necessary for the surgeon to master different and hand-eye coordination as well as tactile sen-
types of knots; this will allow a better resolution sitivity or feedback of the instruments and prac-
of the technical problems during the surgery in tice of endosuture. Advanced MIS suturing is
terms of suture. required before introducing any learner to a
Extracorporeal sliding knots: These allow neonatal model.
solving a great number of situations, are very ver- Regarding the quality of the tools, we started
satile, and require adequate coordination, preci- with low-cost models to acquire basic skills and
sion, and care of the tissues. after assessment of performance we progress to
Square knot or surgeon knot: It is the initial models with 3D printed structures and live tissue.
and main intracorporeal knot that we use for According to our training program, no student
training and that serves to center the bases of moves to practice in animal models until they
coordination and precision, and also allows us to have acquired advanced bimanual and suturing
exercise a lot of tricks that allow the knot to be skills in inanimate models.
adequate and with effective movements. Again During the last 2 years we have replaced ani-
we move from large to small endotrainers. mal models by hybrid ex vivo trainers. A team of
4  Neonatal Surgical Education in Minimally Invasive Surgery Based on Simulation 63

motivated mentors helped to fulfill the specific Published online Dec 2016. https://doi.org/10.1089/
vor.2016.0381.
goals required in the curricula. Scrub nurses 4. Maricic MA, Bailez MM.  Inanimate model to train
involved in this team have been an unexpected for the thoracoscopic repair of all varieties of left
source of success not only in relation to arranging congenital diaphragmatic hernia (CDH). Epublication
stations but also in the manufacture of the models WebSurg.com. 2018;18(7). http://websurg.com/doi/
vd01en5252.
and the education of their peers. 5. Heinrich M, Tillo N, Kirlum H-J, et al. Comparison
of different training models for laparoscopic sur-
gery in neonates and small infants. Surg Endosc.
References 2006;20:641.
6. Barsness KA, Rooney DM, Davis LM. Collaboration
in simulation: the development and initial validation
1. Azzie G, et al. Development and validation of a pedi-
of a novel thoracoscopic neonatal simulator. J Pediatr
atric laparoscopic surgery simulator. J Pediatr Surg.
Surg. 2013;48(6):1232–8.
2011;46:897–903.
7. Barsness KA, Rooney DM, Davis LM, Chin AC.
2. Maricic MA, Bailez MM, Rodriguez SP.  Validation
Validation of measures from a thoracoscopic esopha-
of an inanimate low cost model for training minimal
geal atresia/tracheoesophageal fistula repair simulator.
invasive surgery (MIS) of esophageal atresia with
J Pediatr Surg. 2014;49(1):29–32; discussion 32–3.
tracheoesophageal fistula (AE/TEF) repair. J Pediatr
8. Fahy AS, Fok K-H, Gavrilovic B, Farcas M, Carrillo
Surg. 2016;51:1429–35.
B, Gerstle JT, Azzie G.  Refinement in the analysis
3. Bailez MM, Maricic M, Aguilar JJ, Flores P, Losada
of motion within low-cost laparoscopic simulators
P, Debbag R, Schiavo P. Low-cost simulation model
of differing size: implications on assessing technical
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bined with telementoring technology: initial assess-
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ment. J Laparoendosc Adv Surg Tech B, Videosc.
 Part II
Head and Neck
 Congenital Choanal Atresia
5
Pedro Saraiva Teiga, Kishore Sandu, and Lluís Nisa

5.1 Introduction pharyngeal membrane; (3) abnormal mesodermal

adhesions in the nasal choanae; and (4) misdi-
Congenital choanal atresia (CA) is a condition rection and migration of neural crest elements
characterized by a non-permeable posterior nasal [4, 5]. While the exact embryological mecha-
aperture, also known as choana (from Greek fun- nisms remain to be fully elucidated, the fact that
nel). For incomplete forms, the term choanal ste- patients with neural crest pathologies such as
nosis should be used. For the sake of simplicity, CHARGE syndrome or Treacher Collins syn-
only CA is used in the present text. The bony drome (TCS) often present CA supports the neu-
frame of the choana is formed by the sphenoid ral crest embryological theory. Both of these
body cranially, the horizontal portion of the pala- syndromes feature hypoplasia of the facial
tal bone caudally, the vomer medially, and the bones, cleft palate, and middle and external ear
medial pterygoid lamina laterally. defects, most of which can be explained by aber-
CA is unilateral in 60–70% of the cases and rant migration of neural crest elements. The
preferentially affects the right side, usually with derivatives of the neural crest include among
an accompanying ipsilateral septum deviation. others bone and cartilage [6]. From an embryo-
Unlike previously thought, most CAs have a logic perspective, facial structures develop
mixed bony-membranous composition, with within the first 12  weeks of development. The
approximately only one third being purely bony neural crest cells migrate between the 3rd and
CAs. The estimated incidence of CA is estimated 4th weeks of development and play an essential
to be around 1:5000–1:7000 live births and hav- role in the formation of the face. With time, the
ing the female-male ratio of 2:1 [1–3]. nasobuccal membrane will separate the primitive
Classically four embryological models of CA mouth (stomodeum) and the nasal cavity. The
have been described: (1) persistence of the naso- nasobuccal membrane usually divides in order to
buccal membrane; (2) persistence of the bucco- create the posterior opening of the nasal cavity
(i.e., the primitive choana). Subsequently, cra-
niofacial development leads to a posterior dis-
P. S. Teiga · K. Sandu (*)
Department of Otorhinolaryngology, Head and Neck placement of the choana. It is thought that
Surgery, Lausanne University Hospital, CHUV, aberrant migration of the neural crest cells may
Lausanne, Switzerland indeed be the cause of a wide spectrum of mal-
e-mail: [email protected] formations. The heterogeneity of clinical mani-
L. Nisa festations of patients with neural crest disorders
Department of Otorhinolaryngology, Head and Neck remains unclear from an embryological, molecu-
Surgery, Inselspital, Bern University Hospital,
University of Bern, Bern, Switzerland lar, and genetic perspective [7, 8].

© Springer Nature Switzerland AG 2019 67

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_5
68 P. S. Teiga et al.

Diagnosis of CA relies on nasal endoscopy 5.2.2.1 CHARGE Syndrome

and CT scan. The acronym CHARGE stands for coloboma,
CA is associated with other congenital mal- heart defect, atresia choanae, retarded growth and
formations in approximately 50% of cases [3, 9]. development, genital hypoplasia, and ear anoma-
lies. Also known as Hall-Hittner syndrome,
CHARGE syndrome can occur both as an autoso-
5.2 Diagnostic Approach mal dominant and a spontaneous congenital dis-
ease, with an estimated incidence of 1  in
5.2.1 Clinical Presentation 12,000–15,000 live births. Around two thirds of
patients feature mutations of the CHD7 gene,
The manifestations of CA depend on the unilat- which encodes a chromatin remodeling protein.
eral vs. bilateral presentation. Bilateral CA can Neonates with CHARGE syndrome often present
dramatically present with asphyxia neonatorum, cyanosis at birth due to CA and a cyanotic heart
or milder respiratory distress with intermittent defect. The only therapeutic possibilities are surgi-
cyanosis, usually relieved by crying. This is due cal repair of affected organs. Patients with
to the fact that newborns are obligate nasal CHARGE syndrome have a high rate of mortality
breathers during the first 4–6 weeks of life, given during the first year of life, and the overall progno-
the superior and vertical position of the epiglottis sis depends on synchronous presence of CA, heart
and the thorough contact of the tongue with the defects, and tracheoesophageal fistula [10, 11].
palate. Respiratory distress can in some cases
present in the context of feeding, and feeding dif- 5.2.2.2 Treacher Collins Syndrome
ficulties may lead to choking during feeding or (TCS)
dis-coordinate breathing and swallowing. In chil- TCS or Franceschetti-Klein syndrome is an auto-
dren intubated orally immediately after birth, somal dominant disorder with an estimated inci-
bilateral CA can be first discovered within the dence of 1 in 10,000–50,000 live births, primarily
frame of a failed extubation. due to TCOF1 mutations. TCS features hypopla-
In contrast, unilateral CA is most often sia of the facial bones, uni- or bilateral CA, exter-
asymptomatic at birth, as it does not usually nal ear abnormalities, coloboma, and in some
present with respiratory signs. Unilateral CA cases middle ear malformations resulting in con-
indeed needs a high suspicion index in patients ductive hearing loss. Patients with TCS have a
with persistent unilateral nasal obstruction, uni- normal intelligence [6].
lateral rhinorrhea, or chronic/recurrent sinusitis.
Diagnosis of unilateral CA is in some cases late
in life. 5.2.3 Diagnostic Methods

The diagnosis of CA is primarily clinical. A high

5.2.2 Associated Comorbidities suspicion index in neonates with respiratory dis-
tress should prompt systematic endoscopic evalu-
CA is commonly associated with other congeni- ation of the airway. CA can be diagnosed by
tal malformations, whether or not within a syn- means of flexible or rigid transnasal endoscopy
dromic context. More particularly, approximately or by passing a 120° telescope transorally. CT
one third of patients with CA present laryngoma- scan is an important adjuvant diagnostic method
lacia, tracheomalacia, and/or subglottic stenosis. in order to precisely locate the stenosis and its
CA is encountered in the frame of a polymalfor- extent and to rule out differential diagnosis of
mative syndrome in around 20% of patients. It is nasal obstruction in the newborn. CT scan is best
therefore essential approaching children with CA performed after appropriate nasal decongestion
in a multidisciplinary manner. and aspiration of s­ tagnated secretions, and this is
5  Congenital Choanal Atresia 69

even helpful for operation planning and periop- mucosal trauma) and prolonged intubation.
erative guidance [2, 12]. Tracheotomy should only be considered if early
Important differential diagnoses of congenital surgical management fails or in children with
CA include pyriform aperture stenosis, encepha- underlying comorbidities, especially those with
locele, and neoplasms such as dermoid cysts, CHARGE syndrome [14]. Unilateral CA is better
chordomas, and rhabdomyosarcomas, among managed later in life (>3 years) when the surgery
other entities [12, 13]. is comparatively easy in the larger nasal
passage.
There are a number of surgical procedures to
5.3 Management definitively manage CA, including transnasal
closed and open techniques and transoral tech-
The first step in the management approach of niques. The choice of technique depends on
newborns with CA is airway management. CA patient factors and surgeon’s considerations.
(especially bilateral) can present with airway dis- The earliest surgical method was transnasal
tress at birth. In such a context, some newborns puncture followed by dilation. Puncture is suit-
will be immediately intubated orally. This able for predominantly membranous forms of
approach is however suboptimal, since definitive CA and can be guided with an endoscope.
management of CA requires its surgical correc- Postoperative stenting following puncture is
tion at the earliest. Since CA requires a high sus- often performed, though restenosis rates are rela-
picion index and some studies suggest that early tively high. Fiber-delivered CO2/KTP or diode
surgery is rarely successful, intubation of new- laser can be an option in membranous stenosis.
borns with CA could lead to prolonged intuba- Puncture is obviously not suitable for purely or
tion. If identified early, an alternative to intubation predominantly bony forms of CA [15] (Fig. 5.1).
is the so-called McGovern nipple, which consists A transpalatal approach is equally possible
of an adapted nipple with a large opening fixed in and carries a high success rate (almost 90%).
the newborn’s mouth. Newborns can be feed by However, the associated morbidity, including
means of a feeding tube passed through the dental cross bite, oro-nasal fistula, and velopha-
McGovern nipple. Therefore, the optimal timing ryngeal insufficiency, has resulted in a reduction
of surgery should ideally avoid both excessively of proponents of transpalatal approaches.
early surgery (before 7–10  days of age because Moreover, this approach is not suitable for young
surgical manipulation in very narrow nasal pas- children with small oral morphology and grow-
sages is difficult and cause increased iatrogenic ing facial bones [12, 15].

a b c

Fig. 5.1 (a) Complete unilateral choanal atresia; (b) treatment using CO2 fiber and 0° telescope; (c) rhinoscopy of the
patient 6 months later
70 P. S. Teiga et al.

Endoscopic repair progressively has become syndrome). In spite of the limited number of
the standard method of treatment. Following patients included, the authors identified
nasal decongestion, a 2.9  mm rigid endoscope weight  >2.3  kg at initial surgery, stent size
can guide the instruments to the choana. Otology >3.5 mm and duration longer than 12 weeks for
set instruments used for ear surgeries work best primary surgery, as well as no associated facial
in narrow access interventions as in anomalies as favorable outcome predictors. Other
CA.  Simultaneous passing of the telescope and predictive factors may include presence of gas-
micro-ear cold instruments requires adequate troesophageal reflux, age younger than 7–10 days
degree of expertise. A lateral mucosal flap is at the time of initial surgery, and lack of postop-
raised in order to expose and remove the bony erative follow-up [20].
plate of the atresia. In case of bilateral CA, a part The use of stents, the duration of stenting, and
of the posterior vomer is equally removed using the kind of stents remain controversial issues.
either a microdrill or a backbiting forceps, in Soft silicon tubes (endotracheal tubes) can be
order to create a common single posterior cho- used in each nostril and must be fixed to the ante-
anal opening or a neochoana [14–17] (Fig. 5.2). rior septal cartilage to avoid dislodgement.
Success rates following surgery, range During the period of stent in place, the child does
between 67% and 88% [18]. Only a limited num- have a rough period and requires adequate nurs-
ber of rather inconsistent prognostic factors fol- ing care. Typically, stents are left in place for
lowing repair of CA have been identified. A 2–3 weeks. Several studies have shown no differ-
retrospective study [19] interestingly addressed ence in terms of restenosis rates whether postop-
the prognosis of 46 children with CA following erative stenting is performed or not [18, 21, 22].
repair. Of these children, 28 had bilateral and 18 Similar controversies apply to application of
unilateral CA and were associated in 40% of the mitomycin C. So far, no study has been properly
cases with other anomalies (primarily CHARGE conducted to demonstrate its benefit [3].

R L

b c d

Fig. 5.2  Four days-old-premature girl, 2 Kg. (a) Anterior rhinoscopy with 0° endoscope; (b) Transoral retrograde view
of the choanae using 120° endoscope; (c) Axial CT scan showing bilateral bony atresia; (d) After posterior septectomy
showing a common neochoane
5  Congenital Choanal Atresia 71

In spite of controversy, there is a general agree- posterior rhinopharynx, cranio-­vertebral junction,

ment that postoperative care with saline irriga- and septum and nasal turbinates must be avoided
tions, close clinical follow-up, and crust removal during such a dilation. Progressive sizes of metal
are key to achieve optimal results [20]. These pro- urethral bougies are passed nasally under endo-
cedures are best done in operating rooms, under scopic guidance using a 120° telescope passed
general anesthesia, and with appropriate endos- transorally. We find the choanal dilation done in
copy material. Following the surgical correction this manner very effective and safe. In our unpub-
of choanae, majority of patients will require sev- lished data—following primary corrective sur-
eral additional dilation procedures. The authors gery—all patients required 2–10 dilation
use regular angioplasty balloons or cold urology procedures to achieve an age-­ appropriate and
dilators for such dilations. Injury to the skull base, symptom-free choanal size (Figs. 5.3 and 5.4).

a b

Fig. 5.3 (a) Unilateral choanal stenosis; (b) dilatation with urethral bougies and visualization using 120° telescope
passed transorally

References
1. Deutsch E, Kaufman M, Eilon A.  Transnasal endo-
scopic management of choanal atresia. Int J Pediatr
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2. Brown OE, Burns DK, Smith TH, Rutledge
JC.  Bilateral posterior choanal atresia: a morpho-
logic and histologic study, and computed tomo-
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1987;13:125–42.
3. Kwong KM.  Current updates on choanal atresia.
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4. Hengerer AS, Strome M.  Choanal atresia: a new
embryologic theory and its influence on surgical man-
agement. Laryngoscope. 1982;92:913–21.
5. Hengerer AS, Brickman TM, Jeyakumar A. Choanal
Fig. 5.4  Urethral bougies atresia: embryologic analysis and evolution of
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Park AH, Brockenbrough J, Stankiewicz
neural crest cells in the etiology and pathogenesis of J.  Endoscopic versus traditional approaches to cho-
Treacher Collins syndrome and the potential for pre- anal atresia. Otolaryngol Clin N Am. 2000;33:77–90.
vention. Am J Med Genet A. 2010;152A:2984–94. 17. Uri N, Greenberg E.  Endoscopic repair of cho-

8. Koletzko B, Majewski F.  Congenital anomalies in anal atresia: practical operative technique. Am J
patients with choanal atresia: CHARGE-association. Otolaryngol. 2001;22:321–3.
Eur J Pediatr. 1984;142:271–5. 18. Durmaz A, Tosun F, Yldrm N, Sahan M, Kvrakdal
9. Sanlaville D, Verloes A.  CHARGE syndrome: an C, Gerek M.  Transnasal endoscopic repair of cho-
update. Eur J Hum Genet. 2007;15:389–99. anal atresia: results of 13 cases and meta-analysis. J
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J Rare Dis. 2006;1:34. 19. Friedman NR, Mitchell RB, Bailey CM, Albert DM,
11. Bergman JE, Janssen N, Hoefsloot LH, Jongmans Leighton SE.  Management and outcome of choanal
MC, Hofstra RM, van Ravenswaaij-Arts CM. CHD7 atresia correction. Int J Pediatr Otorhinolaryngol.
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594–5. 2013;270:113–6.
 Facial Cleft and Pierre Robin
Sequence 6
Anthony S. de Buys Roessingh, Oumama El Ezzi,
Georges Herzog, and Martin Broome

6.1 Embryology, Epidemiology, ethnic groups. The causes of facial cleft are far
and Genetics from being understood and may be multiple.
But the majority of clefts seem to be caused by
The primary palate is the region of the upper lip genetic and environmental factors [6]. There are
and the alveolar process, the part of the gum isolated clefts, clefts as part of a syndrome,
region of the upper jaw which holds the teeth. The clefts associated with a link to a specific illness,
primary palate is formed first, already around the and clefts linked to chromosomal anomalies
seventh week of intrauterine life [2, 6]. A malfor- such as trisomy. For non-syndromic unilateral
mation can lead to partial cleft lip, complete cleft and bilateral cleft lip and palate (respectively,
lip, and alveolar cleft. The secondary palate is the UCLP and BCLP), different kinds of causes are
true palate, consisting of an anterior bony part and implicated, such as smoking, alcohol, and anti-
a soft posterior part. Many varieties of clefts can seizure drugs such as phenytoin and valproic
occur, depending on the region involved, for acid [8, 9]. In other cases, a cleft can be caused
instance, bifid uvula, cleft of the soft palate, cleft by teratogenic agents such as rubella virus, tha-
palate (CP), and Pierre Robin sequence (PRS) lidomide, cortisone, and antiepileptic drugs
(Sect. 6.4). Clefts due to primary and secondary which perturb the development of the embryo
palate malformation can be unilateral or bilateral. [9]. Research on animals has demonstrated the
A subcutaneous cleft palate is a special case teratogenic effect of substances such as cortico-
which involves both the muscular soft palate and steroids. Dietary deficiencies resulting in lack or
the hard palate and may be associated with bifid excess of vitamin A have been associated with
uvula. The muscles of the soft palate do not func- clefting in animals, especially clefting of the
tion normally, and the patient may have problems palate. Folic acid appears to play an important
with speech, swallowing, and even the middle ear role in preventing various types of malforma-
[7] (Figs. 6.1, 6.2, 6.3, and 6.4). tion, including clefts [10].
Facial cleft is present in 1 of 750 births, and UCLP is the most common and represents
its prevalence seems to vary between different 37–50% of all cases of clefts [11]. CP is present
in 25–40% of cases and cleft lip in 20% of cases.
A. S. de Buys Roessingh (*) · O. El Ezzi Clefts are twice as frequent in Asia as in Europe
G. Herzog · M. Broome and half as frequent among the black population.
Multidisciplinary Cleft Team, University Hospital CP is twice as frequent in girls and UCLP twice
Center of the Canton of Vaud (CHUV), as frequent in boys. Their incidence seems to be
Lausanne, Switzerland
e-mail: [email protected] higher in poor social conditions [12].

© Springer Nature Switzerland AG 2019 73

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_6
74 A. S. de Buys Roessingh et al.

Fig. 6.1  A labial or labio-maxillary cleft Fig. 6.3  A bilateral labio-maxillary-palatal cleft

Fig. 6.2  A unilateral labio-maxillary-palatal cleft

UCLP has a 22% risk of associated malforma-

tions and CP 33%. In monozygote twins, the risk
of having a cleft is 25–45%. In dizygote twins,
the risk of having a cleft is 5%. The risk of having Fig. 6.4  A palatal cleft with bifid uvulae
a child with a cleft without genetic family history
is 3–5%. Among cases of UCLP, 70% are iso-
lated, 5–8% show chromosomal abnormalities chromosome, hypertelorism, hypospadias), the
(especially the bilateral cases, BCLP), and 22% cleft lip-ectodermal dysplasia (EEC, ectrodac-
are accompanied by other abnormalities [13]. tyly, ectodermal dysplasia, cleft lip), the OFD1
The risk of having a child with a cleft in autoso- (cleft palate, hamartoma, malformation of the
mic dominant cases is 50% and 25% in autoso- tongue, malformation of the face and of the
mic recessive cases [14]. extremities), and the branchio-oculo-facial (BOF
For the syndromic cleft lip and/or palate, the with a cleft lip) with different mutations such as
more frequent syndromes are the Stickler (auto- PVRL1, MSX1 (4p16), FGFR1, TBX22 (cleft
somic dominant, palatal cleft), the Franceschetti and ankyloglossia), and IRF6 (Van der Woude,
(autosomic dominant), the Opitz (related to the X 80% fistula lower lip). Chromosomal disorders
6  Facial Cleft and Pierre Robin Sequence 75

leading to a cleft also include the Down ­syndrome, is to exclude the most frequent genetic disorders
the trisomies 13 and 18, the deletion 4p (with associated with a cleft.
hypertelorism, short philtrum, scalp defect, ear After confirmation of the diagnosis, a first dis-
pit), and the deletion 22q11.22 named also velo- cussion must take place between the surgeon and/
cardiofacial syndrome (orofacial cleft, DiGeorge or the team and the parents, in order to prepare
syndrome) with cleft palate, short palpebral fis- the latter. At that time, the various causes of the
sures, small ears, alar hypoplasia, and conotrun- cleft, the schedule of the surgical repair, and the
cal cardiac defect (Sect. 6.4). A single-­gene follow-up, especially concerning speech disorder
disorder is present in the CHARGE association and orthodontic problems, must be discussed. If
(ocular coloboma, choanal atresia, micropenis, deemed necessary, monthly discussions with the
cardiac defect), EEC syndrome, Fryns syndrome parents can be arranged. A dialogue can be set up
(diaphragmatic hernia, coarse face, digital hypo- between a representative of the team and the par-
plasia), Opitz syndrome, popliteal pterygium ents. Confidence can be built, thanks to this dia-
syndrome (lip pits, popliteal web, genital anoma- logue and the team’s availability. It is the
lies), and the Van der Woude syndrome. beginning of a long road for the family and the
team. Information on parent support groups can
also be offered [16].
6.2 Antenatal Diagnosis At the time of birth, one should ensure that the
midwives have been informed of the prenatal
Antenatal diagnosis helps to prepare the parents. diagnosis and that a positive atmosphere reigns in
Ultrasonography is quite reliable, but images are the delivery room. As the parents have usually
not photos, and even 3-D images have to be care- been previously informed of the expected malfor-
fully interpreted, as palatal clefts are not so easy mation, the delivery can take place in a calm
to find. Nevertheless, due to its high prevalence, atmosphere. Any separation of the mother and
it is important to exclude the possibility of a cleft the child must be avoided.
by means of a prenatal investigation. A diagnosis
of facial cleft may be established as early as the
12th week of gestation, but it is usually done at 6.3 Feeding the Baby
20 weeks. In numerous cases, an antenatal diag-
nosis of cleft lip and palate enables many future The baby’s feeding difficulties depend on the type
parents to better prepare themselves to confront and the severity of the malformation. They also
and accept the facial malformation of the baby depend on the weight of the baby and his resources
they are expecting [15]. The severity of the mal- and on whether he has the energy to suck.
formation should not be minimized, and its rec- At birth, a baby with a cleft lip may be fed nor-
ognition allows the team to establish a contact mally by breast or bottle. But for babies with a CP,
with the future parents in order to offer them breast-feeding is anatomically impossible because
information and early support. Valuable psycho- the lack of palatal muscle entails a lack of the
logical aid can be provided before birth, if neces- strength for suction [17]. Even if the baby is strong
sary and required. and heavy at birth, it may be exhausted after a few
Micro-/retrognathia can also be diagnosed by days, unable to suck and consequently losing
prenatal ultrasonography. This early diagnosis weight. This is particularly true for babies born
allows the physicians to consider the possibility with a PRS, because of respiratory difficulties [18].
of PRS (Sect. 6.4). Parents should be prepared to If feeding problems persist, a palatal plate or
face possible respiratory and/or feeding feeding plate may help. A palatal plate requires
problems. the making of an impression by the orthodontist,
Amniocentesis, followed by cytogenetic anal- usually at the hospital as soon as possible after
ysis, is recommended for bilateral clefts or when birth, so that its shape will perfectly match that of
associated malformations are suspected. The aim the palate. The baby adapts to it within a few
76 A. S. de Buys Roessingh et al.

(glossoptosis). These patients also had a CP and

micro-/retrognathia. The recognition of these
three features constitutes the primary diagnostic
criteria of PRS.  Mandibular hypoplasia (micro-
gnathia) seems to be a trigger for a cascade of
events leading to tongue displacement, cleft pal-
ate, and respiratory distress, hence the term
“sequence” (Fig. 6.6). The etiology of this type of
PRS is supposed to be the presence of oligohy-
dramnios or of an amniotic band which leads to
compression of the chin and creates retrognathia
[21]. The term “syndrome” refers to a number of
abnormalities that often vary in degree and pat-
tern of expression [22]. PRS occurs in 1 of 8500
births [21].
Glossoptosis is generally responsible for pha-
Fig. 6.5  Palatal plaque with absorbable glue along the ryngeal obstruction [23]. Due to this anatomical
borders anomaly, these children are at high risk of severe
respiratory insufficiency and prolonged hypoxia
hours or days. The plate is made of acrylic resin, [24]. The physiopathology of airway obstruction
with a rigid outer part and a softer and more flex- is explained on the one hand by brainstem imma-
ible inner layer that is in contact with the mucosa turity [23] and on the other hand by anatomical
(Fig.  6.5). A feeding plate may have several anomalies that provoke breathing difficulties: in
advantages, even if not all proved: it facilitates particular, posterior retraction of a normal-sized
bottle feeding but not breast-feeding, maintains tongue with interposition of the velum, neuro-
the tongue in a normal position, allows the full muscular impairment of the genioglossus muscle
growth potential of the maxilla by preventing the and other parapharyngeal muscles, prolapse of
tongue from getting into the cleft, protects the the medial walls of the pharynx, and medial
sutures that closed the palatal cleft after surgery, movement of the lateral pharyngeal wall [24].
and gives confidence to the parents [19]. During growth, the airway obstruction will
Patients with feeding difficulties were defined decrease as the mandibula grows, and the coordi-
by their inability to gain weight, prolonged feed- nation of the parapharyngeal muscles improves
ing time (lasting more than 45 min), and need for in conjunction with voluntary tongue control.
nutritional support with a feeding catheter. After a few months, mandibular catch-up growth
Criteria for feeding difficulties were classified in improves the prognosis for these children.
two categories: grade I, when bottle feeding with Two types of PRS are generally observed:
prosthesis and open nipple is possible (<45 min), “deformational PRS” and “malformational PRS.”
and grade II, with partial bottle feeding with Deformational PRS represents 40% of cases and
prosthesis associated with nasogastric tube [20]. is characterized by an isolated form of the three
anatomic abnormalities without any other signifi-
cant findings. Malformational PRS represents
6.4  ierre Robin Sequence
P 60% of cases and is associated with the presence
and Syndrome of other abnormalities such as various syndromes,
chromosomal anomalies, teratogenic products, or
In 1923, the French stomatologist Pierre Robin neuromuscular disease [23]. This type of PRS
described a group of patients who suffered from has a less favorable prognosis. There is a third
obstruction of the oropharynx due to the tongue type of PRS, associated with connective tissue
being situated in the back of the oropharynx dysplasia [24].
6  Facial Cleft and Pierre Robin Sequence 77

Fig. 6.6  Pierre Robin syndrome (PRS)

Pharyngeal obstruction must be anticipated at stridor, and position-dependent airway obstruc-

birth in order to avoid a catastrophic delivery, as the tion. Children with respiratory complications are
tongue may block the upper airways in the oro- assessed for oxygen saturation. Oxygen satura-
pharynx and so interfere with breathing. The sever- tion is monitored continuously by pulse oxime-
ity of airway obstruction varies considerably in try. Normal venous blood gas values are pH 7.4,
PRS children. The main key of success of airway PaCO2 40  mmHg, PaO2 100  mmHg, and HCO3
management is an accurate monitoring and treat- 24 mmol/L. Polysomnography can be organized
ment by a multidisciplinary team. The goal of the if the monitoring gives bad results. A full endos-
initial treatment is to minimize any airway obstruc- copy evaluation of the upper aerodigestive sys-
tion in order to prevent hypoxia and promote nor- tem can be carried out to exclude other potentially
mal neurological development [22, 25, 26]. treatable causes of airway obstruction [25]. But
Treatment of respiratory obstruction can be the risk of anesthesia for a child with respiratory
conservative or surgical. The different ways that difficulties must be taken into account. Close
we describe to treat these children reflect local follow-up is mandatory to prevent neurological
practices and experiences. When upper airway sequelae after prolonged or chronic hypoxia [27].
obstruction is mild, children can be handled con- Gastroesophageal reflux (GER) is common in
servatively, by being placed in prone position. babies, but even more common in children with
This positioning of the baby can be effective, as it neurodevelopmental problems. A PH probe may
prevents the tongue from falling into the hypo- be placed during polysomnography to objectivize
pharynx. It can help PRS babies with mild to the GER before starting medication.
moderate respiratory obstruction, but it is cer- Other conservative techniques are a continu-
tainly not sufficient in severe cases [27]. ous positive airway pressure (CPAP) and the use
An accurate assessment of the problem rests of a pharyngeal tube (PT) or of a laryngeal mask
on a combination of clinical observation, moni- airway (LMA) [27, 28]. CPAP is generally used
toring, and control of blood gases. Clinical crite- first, followed by PT if it proves not sufficient. PT
ria for respiratory distress are agitation, dyspnea, is a safe treatment, even over a long period, inso-
tachypnea, intercostal recession, tracheal tug, far as the tube has been correctly placed (Fig. 6.7).
78 A. S. de Buys Roessingh et al.

Tracheal intubation can be very difficult and

complicated, with a possible consequence of
pneumothorax, subcutaneous emphysema, or
death. Endotracheal intubation should be avoided
as it is very difficult to extubate these patients.
Nevertheless, this treatment can save a newborn
with severe respiratory distress.
Surgical methods include glossopexy [30],
tongue-lip adhesion (TLA) [31], tracheotomy, or
mandibular traction [32]. Surgical interventions
such as glossopexy, TLA, or tracheotomy have
been recommended for patients when airway
obstruction could not be relieved by conservative
management. Glossopexy could only relieve the
airway obstruction caused by the posterior dis-
placement of the tongue, but had little effect in
patients with airway obstruction caused by other
mechanisms. Glossopexy [30] is particularly non-
physiological and creates feeding difficulties. It
combines the difficulty to suture the button in the
right place, the risk of pulling the tongue too far,
the risk of wound infection and injuries to the
Wharton duct and of deformation of the lip and
chin and scarring of the chin and the mouth, and the
Fig. 6.7  Pharyngeal tube (PT) for a PRS risk of dental deterioration. Mandibular traction
[32] with an outrigger bar allows the child to move
The nasopharyngeal tube is inserted under lateral his head laterally. Pain and tension are caused by
X-ray control to ensure that it is cut at the correct hypertension of the neck. This method forces the
length. It is then taped to the face. The diameter child to remain in bed, and feeding is not simple.
of the tube is chosen so as to avoid nostril steno- Ensuing disorders of facial growth are not known.
sis. This treatment normally requires hospitaliza- Difficulty in feeding is a direct consequence
tion at first, but can be continued at home of airway obstruction and immaturity of degluti-
depending on the parents and on the child’s sta- tion. But even if respiratory problems are
tus. A relatively long-term use of a nasopharyn- resolved, feeding problems can endure, as the
geal airway may be appropriate, while the child palate is open and suction difficult. These prob-
matures, i.e., gains weight in order to improve lems are generally not permanent and disappear
muscle tone and neurologic maturation. LMA is with catch-up growth. Several therapeutic options
a method of ventilation support for respiratory are possible, such as prone positioning or naso-
obstruction. It can be used for long-term manage- gastric tube feeding [20]. Palatal plaque can help
ment of prolonged airway obstruction [29]. LMA these children to feed. But normal feeding with a
has the advantage of being easily inserted, with- palatal plaque can only be attempted after the
out a laryngoscope. It is less aggressive than resolution of the respiratory problems. Caouette
endotracheal intubation. It avoids vocal cord and Laberge [20] classified three categories of
edema and subglottic stenosis due to prolonged PRS patient, according to their specific respira-
intubation. It allows the patient to swallow and to tory and feeding problems: adequate respiration
strengthen the genioglossus and parapharyngeal in prone position and bottle feeding (category 1),
muscles. It does carry the risk of laryngospasm adequate respiration in prone position but feeding
and coughing. difficulties requiring gavage (category 2), and
6  Facial Cleft and Pierre Robin Sequence 79

respiratory distress with endotracheal intubation 6.5.2 Age of Surgery

and gavage (category 3). The mortality rate is,
respectively, 1.8%, 10%, and 41%. Caouette-­ The ideal age for simple cleft repair is still a sub-
Laberge found mortality rates of 22.8% in chil- ject of debate. Thanks to the progress in pediatric
dren with PRS syndrome and 5.9% in children anesthesia, surgery can be performed at a very
with PRS sequence (b). early age. Anesthesia is best performed after the
Children born with a velocardiofacial syn- age of 3 months, when breathing reflexes are nor-
drome (VCFS, DiGeorge, Shprintzen) have a mal and tissues more developed and sturdier. For
22q/11.22 microdeletion, i.e., a deletion of band both anesthetic and surgical reasons, this period
11 of the long arm of chromosome 22, a genetic seems to be the right and safe time for surgery.
disorder with a prevalence of 1/1800–1/5000, Surgery is performed under general anesthesia,
80% being sporadic. It is used to be known as the and a tracheal tube is normally used. Intubation
CATCH 22 association: cardiac malformation, helps to prevent liquid from seeping into the tra-
abnormal face, thymus anomaly, cleft palate, and chea. The tube is inserted orally in the direction
hypocalcemia [33]. These children have a 70% of the feet (ray tube) and securely taped to the
risk of cleft palate along with congenital cardiac lower lip. This position allows the use of mouth
malformation, facial anomalies, dental anoma- gags in palatal surgery and makes it possible for
lies, ocular malformation, and psychomotor and the surgeon to check the symmetry of the lip
learning disabilities, with velar insufficiency repair.
related to the cleft, scoliosis, and polydactyly. It The sequence of operations on children born
is very important to diagnose this syndrome early with a total cleft may vary largely, depending on
in order to offer the patient and the family ade- the local school of surgery and historical teach-
quate medical and psychological support. The ing. It may be complete surgical repair in one go
prognosis for development is quite good if the at 4 months of age or lip repair first at 5–6 months
child is helped in the first years of life already. and palate repair at 1 year of age. The Malek pro-
cedure [2] is soft palate repair at 3 months and
anterior hard palate and lip closure at 5 months
6.5 Primary Surgery and, in cases of BCLP, soft palate repair at 3
months and anterior hard palate and lip closure
6.5.1 Historical Elements on one side at 5 months and on the other side at 7
months. In children born with CP, closure is per-
The first cleft lip operation is thought to have been formed at 4–6 months. For UCLP and BCLP, a
performed in the year 390  AD.  Jehan Yperman vomer flap may be used to reconstruct the nasal
(1295–1351) was the first to describe cleft lip layer of the velum. All procedures have been
repair. The term “bec-de-lièvre” (harelip) was described, and they can all be performed, as long
used in France by Ambroise Paré, the famous sur- as the surgeon keeps a good record of events.
geon of four Kings (François I, Henry II, François
II and Charles IX).  The eighteenth century saw
the elaboration of new techniques concerning the 6.5.3 Preparation for the Surgery
soft palate, suture of the split velum, and primary
closure of the soft palate before cheiloplasty The child is installed at one end of the table. The
(Dessault, 1798). In the nineteenth century, sur- head rests on an adjustable support with a hyper-
gery of the palate was developed by several sur- extension position. A pad placed under the shoul-
geons: Collis (1868) was the first to describe a ders keeps the neck extended. The surgeon stands
double lip plasty. In the 1930s of the twentieth at the end of the table, with the assistant on the
century, improvements in anesthesiology allowed right side of the table and the anesthesiologist on
the development of new techniques, of which the left side. The infant’s eyes are taped shut with
Victor Veau was one of the pioneers [34]. sterile strips with a drop of Vaseline. Surgery
80 A. S. de Buys Roessingh et al.

starts with the drawing of the lip repair. Then the 1985, Millard presented another version of flaps
tissues are usually infiltrated with bupivacaine based on a lateral triangular flap for a unilateral
hydrochloride-adrenaline in order to facilitate the cleft in order to preserve the Cupid’s bow and the
mucoperiosteal undermining for a lip repair and symmetry [4].
to reduce bleeding thanks to the temporary hemo- One of the surgeons’ concerns must be the
static effect of the vasoconstrictor. The surgical symmetry of the height of the lip on the cleft side
equipment includes the specific instruments and the normal lip, and surgical procedures based
required for palate surgery, in particular the on the principal of Z-plasty are normally used
adjustable Veau mouth gag, the Trélat’s blunt (Fig. 6.8). The exact symmetry between the two
hook for the dissection and fracturing of the ham- sides must be calculated with mathematical pre-
ulus, the angulated Adson forceps, and the Veau cision. The skin without muscle must be elimi-
elevators. For palatal surgery, we use absorber nated. The muscle for both sides has to be sutured
sutures 4-0 and 5-0 and, for labial surgery, together knowing that the orientation of the mus-
absorber monofilament sutures and bipolar coag- cle fibers depends on the outlines of the incision,
ulation [2, 34]. since the cutaneous-muscular flaps are used with
a certain degree of rotation. The incision must
take into account the final direction of the muscle
6.5.4 Principles fibers which will be reinserted [37, 38].
In bilateral clefts, the Cupid’s bow is virtually
The principal aim of modern surgery is to correct nonexistent and must be created. Lip closure can
the obvious shortening of the lip. Since the 1950s, be performed in one or two stages. If performed
the flap technique is the most widely used method in one single stage, with incisions on both sides,
of repair. Earlier, in 1848, Mirault worked on a the extensive denuding of tissue might impair the
flap in the area of the Vermilion; then Jalaguier vascular supply to the bone structure and the soft
(1910) and Veau [34], his pupils, worked on tissue. It might create insufficient blood supply to
reducing excessive scarring. In 1945, Le Mesurier the lower and medial portion of the lip, leading to
[35] of Toronto described a quadrilateral flap pro- necrosis. Lip closure should therefore be per-
cedure which represents a modified version of the formed in two stages, at an interval of about 2
technique originally described by Hagedorn. In months [37, 38]. An abnormally short columella
1952, Tennison [36] introduced a triangular flap is one of the hallmarks of these malformations.
method in order to preserve the Cupid’s bow; in Since it is difficult to include the correction of the

Fig. 6.8 Z-plasty
following the Malek
procedure
6  Facial Cleft and Pierre Robin Sequence 81

short columella in either phase of a two-stage of the outer border on the vertical line from the
cheiloplasty, it seems advisable to postpone this outer alar base. In the Malek technique, this pro-
until later. The labial vestibule is virtually nonex- cedure is based on the principle of a Z-plasty
istent and must be constructed from scratch by (Fig.  6.9) Additional length is gained between
extending the outer mucosal tissue during the two points thanks to the dissection of two trian-
two-stage plasty [39]. gular flaps that share a common side. The apices
of the triangles are situated at each end of the
joined triangular flaps. After the incision, inver-
6.5.5 Labioplasty sion of the flaps results in inversion of the diago-
nals on the parallelogram initially traced. The
Plotting the reference points represents an essen- long diagonal replaces the short and vice versa,
tial step in the operation. Measurements are taken so that the desired additional length is obtained
in order to help the surgeon calculate the precise [37, 38].
dimensions of the plasty needed to obtain satis- In the Le Mesurier [35] technique, the term
factory lip height. Errors made in the initial prep- “quadrangular flap plasty” given to this proce-
aration can seriously impair the final result. The dure has confused the issue. Actually, the inferior
height of the normal lip must be calculated. This flap described by Le Mesurier is also a triangular
calculation is relatively simple for unilateral flap characterized by a 90° angle at its apex.
clefts but more difficult for bilateral clefts. The However this procedure is no longer used because
precise position of the Cupid’s bow must be it did not preserve the Cupid’s bow.
determined if a triangular flap plasty is pro- In the Millard [4] procedure, there is also a
grammed, so that the top edge of the lip and the Z-plasty. A small triangular flap with superior
lateral superior points of the Cupid’s bow are base is traced on the inner border by a curved
aligned with the middle reference point set by the incision, and a large triangular flap with a supe-
nostrils and that the distance from the nose to the rior apex involves virtually the entire outer
lip is satisfactory. In cases of bilateral clefts, this border.
normal reference does not exist. The height of the In the Tennison [36] procedure, the dissection
lip must be therefore invented during the first of a triangular flap from the outer border is des-
operation and determined during the second tined to be fitted into an incision on the inner bor-
operation by using a caliper to measure the height der. The major problem of this technique is the

a b

Fig. 6.9  Example of a labio-maxillary cleft before (a) and after (b) the surgery
82 A. S. de Buys Roessingh et al.

adequate measurement of the dimensions of the 6.5.6 Palatal Repair: Veloplasty

triangle and the inner incision so that the desired and Staphylorraphy
gain in lip height on the cleft side corresponds to
the height of the normal side. In this procedure, Surgery on the palatal cleft must be done before
there is no calculation involved and the procedure 18 months of age to facilitate language acquisi-
is purely intuitive. tion. The most widely used technique over many
In the inferior triangle flap technique with years was introduced by Veau and is called the
incisions in both borders according to the Malek Wardill palatoplasty [34]. Two thick mucoperios-
procedure [40], the essential angles are A and B, teum flaps are used in their entirety to close the
and the shape is an isosceles triangle. The math- cleft in the hard palate. This surgery is based on
ematical precision of this method, based on an the elevation of the fibro-mucosae and produces
equilateral triangle flap, allows some variation, major iatrogenic consequences, especially in the
such as the inverted triangle plasty or the double case of complete labio-palatal clefts. Scars induce
Z-plasty, which may be used when the degree of retrognathia and endognathia due to the devascu-
hypoplasia is high. For the inverted Z-plasty, larization of the bone structure through detach-
inclusion in the inner incision permits a good ment of the mucoperiosteum and creation of
reinsertion of the alar wing. The triangular flap fibrotic scar tissue. This is even more obvious
adds tissue to the upper portion of the lip, which when surgery is performed in the first months of
is often rather thin on the inner border at this life [34, 41]. Palatal cleft may be very short, very
level. For the double Z-plasty, when hypoplasia is long U-shaped, or V-shaped or present as a bifid
severe, the measurements give an equilateral tri- uvula with open bone covered by mucosa, known
angle of considerable size. as submucosa cleft (Figs. 6.10, 6.11, and 6.12).

Fig. 6.10  Submucosal cleft palate with bifid uvula

6  Facial Cleft and Pierre Robin Sequence 83

Fig. 6.11  Large palatal cleft in U-shape

6.5.7 Veloplasty When direct suturing is not possible, it becomes

necessary to create a nasal layer using vomerine
For veloplasty, incisions are made along each mar- mucosa, a procedure practiced by Veau and later
gin of the cleft as far as the half uvulae in order to by Petit. A longitudinal incision is made in the
create two flaps (Fig. 6.13). The hamulus is then lower edge of the vomerine mucosa and nasal
broken with a Trélat elevator in order to relax the mucosa, on either side, from front to back, and is
tendon of the tensor velo-palatine. One then pro- then sutured. The naso-vomerine suture continues
ceeds to the undermining, with the tissues being until the tension appears to diminish, and then, at
pushed back and carefully divided until the detach- this point, direct suturing of the nasal mucosa can
ment of the soft palate is completed. Homeostasis be performed [41, 42].
is drawn normally if necessary. The mucosa that
lines the nasal sides of the palatal shelves is easy to
detach by displacing the velum toward the inside. 6.5.8 Staphylorraphy
This procedure creates two layers, one in the oral
cavity and one in the buccal cavity. The surgeon Staphylorraphy is a perfectly reliable conven-
then sutures the first layer of the nasal mucosa tional technique which allows the closure of the
with 5-0 or 4-0 absorber filament. Sutures begin at whole palate. This technique must be postponed
the very front and the knots are tied inside the until maxillary growth is well developed. It does
nose. Each stitch must include a bit of periosteum create scars and retraction with retrognathia. In
to guarantee a firm hold. Mattress stitches are con- this technique, a longitudinal incision divides the
tinued as far as the anterior extremity of the flaps. border and continues forward up to the apex of
84 A. S. de Buys Roessingh et al.

Fig. 6.12  Palatal cleft in V-shape

Fig. 6.13  Schematic description of the veloplasty

6  Facial Cleft and Pierre Robin Sequence 85

the cleft, which often extends into the bony vault. step, after fracture of the hamulus with the Trélat
A curved incision starts behind the maxillary hook. Sutures begin with the nasal layers and
tuberosity, continues along the inside of the alve- proceed from front to back. Again, vomerine and
olar arch, and stops at the premaxillae (Fig. 6.14). lateral nasal mucosa should be sutured together
Undermining of the mucoperiosteum is the next first, taking in a larger bit of muscle than of nasal
mucosa (Fig. 6.15). Separate stitches are used for
palatal repair after reaching the uvulae [40, 41].
The Furlow technique [43] offers a different
version of the Z-plasty and makes it possible to
lengthen the soft palate. This surgery is based on
the retrodisplacement of the velar muscles, pri-
marily the levator veli palatini. It rests on the
intravelar dissection of the muscle fibers, which
are then directly sutured end to end so as to recon-
struct a muscle sling. It implies an extensive dis-
section of the muscles which strikes us as a source
of fibrosis. It lengthens the soft palate without
using the mucoperiosteum, a factor favorable to
satisfactory growth, and it allows a better muscu-
lar suture which does not impair velar contraction.
The technique is based on a large Z-plasty, and the
design of the mucosa incisions is traced in the oral
and nasal layers. Because of this lengthening, the
Fig. 6.14  Palate after surgery with small amount of scar technique is recommended in the treatment of
tissue in the middle. The cleft was closed with a minimal
mucoperiosteum undermining and no lateral palatal scar- velar inadequacy over and above the other tech-
ring tissue niques of pharyngoplasty.

Fig. 6.15  Schematic description of the staphylorraphy

86 A. S. de Buys Roessingh et al.

6.6  ar, Nose, and Throat

E The surgical insertion of a tympanostomy/
Problems ventilation tube (grommet) allows the fluid to
drain and thus provides aeration and equalization
Normal hearing during the early phase of infancy of pressure in the middle ear cavity. The use of
is critical in order to develop understanding and grommets is largely debated because their indica-
use of speech and help cognitive development. tion and the right time to insert them are not
Intelligible speech must be acquired as early as clearly defined. Tympanometry has been the most
possible for good social integration [44]. common and widely accepted tool for assessing
Due in part to velopharyngeal dysfunction and the presence of fluid in the middle ear. It seems to
problems such as secretory otitis media (OMS), have a high degree of sensitivity and a good spec-
children born with a UCLP/BCLP or a CP have ificity for detecting OMS [50, 51]. Taking into
significantly more speech and hearing problems account the different ages of the children may
than children born without a cleft [7]. The high therefore be crucial for the detection of OMS and
prevalence of OMS and its associated hearing consequently for deciding whether or not to
loss may affect the development of speech and insert a grommet. The meticulous examination of
language and lead to lower verbal activity [45, the middle ear is crucial. The insertions should be
46]. The hearing loss caused by OMS can be per- performed by means of a small incision with a
sistent or recurrent and variable in degree and microsurgical knife and under direct vision with
affect one or both ears. The diagnosis of OMS a microscope. A beneficial effect of the preven-
may be difficult, as otitis media with effusion is a tive use of grommets to improve hearing has not
condition which presents fluid in the middle ear yet been verified.
without signs and symptoms of infection. Grommets may be inserted at the time of the
Many studies have shown that Eustachian palatoplasty, under one single anesthesia. However,
tube function may remain impaired even after complications of their insertion are numerous, for
surgery in cleft children [47]. OMS is related to instance, atelectasis, perforation, tympanic mem-
the functional obstruction of the Eustachian tube brane scarring (tympanosclerosis), and cholestea-
as a result of anatomical and physiological varia- toma. Kay et  al. revealed that the incidence of
tions of the tensor and levator palatine muscle. tympanic membrane perforation was higher after
The tensor veli palatini and the levator veli pala- repeated tube insertions, after grommet insertion
tini are inserted laterally in children with a pala- at a young age, and with the use of a long-stay tube
tal cleft. This insertion provokes a dysfunction of [52]. Goudy et al. found a 25% incidence of con-
the opening of the Eustachian tube that compro- ductive hearing loss and a 5.9% incidence of cho-
mises the normal ventilation of the middle ear lesteatoma following the insertion of grommets in
cavity. Without normal ventilation, the cavity is cleft palate patients [45]. For Shapiro et  al., the
filled with a secretion of mucus and the tympanic incidence of tympanic perforation in children with
membrane is retracted. The presence of secretion cleft palate related to the insertion of grommet is
in the middle ear or of tympanic membrane about 64% [53]. But according to Shaw, children
retraction/perforation causes difficulties in with cleft palate and grommets had a better lan-
sound transmission. This impaired anatomical guage acquisition and prognosis than children
and physiological integrity may therefore hinder with cleft palate and no grommets [54, 55].
the acquisition and development of verbal lan-
guage. In order to develop speech in the early
months and years, the preservation of an aerated 6.6.1 Tympanometry
mastoid seems to be crucial [48]. Grant et  al. and Audiometry
showed that 97% of children with a cleft palate
had OMS [49]. The incidence of OMS seems to A hearing assessment is performed at variable
remain very high, up to 90%, even after cleft ages and repeated over the following years in
repair [47]. response to individual needs. In his evaluation of
6  Facial Cleft and Pierre Robin Sequence 87

the results of tympanometry and audiometry, the Table 6.1 The Borel-Maisonny classification for the
phonation
ENT has to take into account the cognitive and
linguistic capability of the children and also the Type 0 No phonation
possibility that they may be tired at the time of Type 1 Excellent phonation, no nasal air emission
Type 1/2 Good phonation, intermittent nasal air
the examination. The hearing loss is reported if it emission, good intelligibility
is conductive, but sensorineural or mixed hearing Type 2 Phonation with continuous nasal emission
loss is excluded. Depending on the age of the Type 2b Phonation with continuous nasal emission
child, a speech evaluation can also be performed but good intelligibility and no social
on the same day. discomfort
Type 2M Phonation with continuous nasal emission,
bad intelligibility
Type 2/3 Phonation with continuous nasal emission
6.7 Speech with compensatory articulation, bad
intelligibility
Speech is a cornerstone of social integration and Type 3 Continuous compensatory articulation, no
peer acceptance [44]. Intelligible speech must be intelligibility
acquired as early as possible for good social inte-
gration. Speech of children born with UCLP and obstruction. Hypernasality, hyponasality, audible
CP is characterized primarily by abnormal nasal nasal emission, voice quality, misarticulations
resonance. Nasal resonance due to velopharyngeal associated with VPI, and intelligibility should be
insufficiency (VPI) diminishes the volume and assessed. Nasal emission on separate phonemes
intelligibility of speech. VPI results from an incom- may be measured with a nasometer. Fluoroscopic
plete closure of the soft palate and the posterior velopharyngeal evaluations can be also done.
pharyngeal wall. Its etiology can be anatomical Video nasopharyngeal endoscopy is a technique
(cleft palate), neurologic, or iatrogenic (after ade- which allows direct observation of velopharyn-
noidectomy) [56]. The evaluation of a VPI begins geal movement during speech [59], but it requires
with a thorough speech and language assessment the cooperation of the child, which is not easy to
and can be complemented by instrumental investi- achieve, and its interpretation is subjective or
gations. Articulation errors, including compensa- operator-dependent. Cinefluoroscopy gives a
tory misarticulation, worsen the situation. dynamic visualization of the velopharynx but
Perceptual speech evaluation is subjective by involves high radiation exposure. The ideal
nature. If instrumental means of VPI evaluation method must be reliable, reproducible, practical,
have the advantage of being more objective than noninvasive, and capable of grading the severity
perceptual evaluation, no single instrument has of VPI. No single technique provides reproduc-
yet proved a reliable alternative to perceptual ible results, and most teams, including ours, eval-
evaluation in clinical practice [57]. There is no uate the children using a combination of
agreement in the literature on the methodology to perceptual evaluation and nasometry. Children
be used to obtain a reliable rating. In French-­ with type 1/2 Borel-Maisonny score or worse
speaking countries, the reference for the evalua- should be referred to a speech therapist near their
tion of VPI or nasal air emission is usually the home and seen by the university hospital’s spe-
Borel-Maisonny [58] score (Table  6.1). cialist once a year to evaluate progress.
Perceptual speech evaluation by qualified speech Articulation errors are divided into categories
pathologists experienced in cleft pathology is the based on their anatomical origin: labial, alveolar,
mainstay of speech evaluation in our institution. palatine, velar, nasal, pharyngeal, and glottal.
The children should be interviewed in a quiet Backing, stops, and fricative sounds are recorded
playroom in the presence of a parent. Standard for each anatomical region as compensatory
upper airway assessments should be documented, articulations. Other articulation problems, such
including the presence or absence of snoring, as simplification, replacement, or deletion of
mouth breathing, apnea, and nasal airway consonants, are also recorded (Table 6.2).
88 A. S. de Buys Roessingh et al.

Table 6.2  Compensatory phenomenon related or not to velopharyngeal insufficiency (VPI)

Simple misarticulation, Compensatory Added
not related to VPI Heavy misarticulation Voice trouble movements sounds
Sigmatisms Articulations Hyponasality Facial (syncinesia) Snoring
compensation
Posteriorizations Glottic sounds Hypernasality Mouth
breathing
Deletion of consonants Raucity Raucity Clicks
Confusions Fricative sounds
Confusions oral nasal
Backing

Speech therapy aims at strengthening the teeth and eventually permanent teeth may be
velopharyngeal muscle complex and can begin at affected in terms of shape, size, number, and
1  year of age (“guidance”) [60]. Using age-­ position. It is mostly the lateral incisors, the teeth
appropriate games and increased parental aware- in the direct neighborhood of the cleft, that are
ness of their active role in speech acquisition, involved. The teeth may have enamel hypoplasia,
breath control and correct positioning of the meaning malformation of the crown with calcifi-
tongue and lips can be obtained early. Speech cation or demineralization; they may be in a
therapy sessions can only do so much, and regu- wrong position with various degrees of malrota-
lar daily exercises at home must complete the tion or inclination [63]. Supernumerary teeth
treatment. Continued speech therapy is manda- may also be present, in a wrong position some-
tory in order to improve the mobility and strength times. The scars resulting from the primary sur-
of the velopharyngeal muscle complex. gery may also affect the growth of the upper jaw
After surgical palate repair, a significant num- and the alveolar process, as well as the position
ber of patients born with a cleft palate have per- of the teeth [64].
sisting velopharyngeal dysfunction, as lateral Indications for orthodontic treatment are func-
pharyngeal wall mobility also plays an important tional and esthetic. In general, orthodontic
role in VPI, and limited adduction of the lateral ­treatment is recommended only when the perma-
pharyngeal muscles may result in a persisting VPI nent teeth are present. It is useless to correct the
in spite of good velar mobility. If speech therapy position of teeth which are to be replaced. The
is unsuccessful, velopharyngeal dysfunction can deciduous dentition lasts up to about 7 years of
be treated prosthetically or surgically [61]. The age. During this period, parents are advised to
two major surgical procedures are cranial-­based control the exercise of the necessary dental
pharyngeal flap and sphincter pharyngoplasty hygiene. As for all children, dental care for pre-
[62]. The criteria for recommending pharyngeal vention of caries is mandatory, and as soon as the
flap surgery are based on perceptual analysis: baby teeth appear, they must be brushed with a
hypernasality, weak pressure consonants, weak soft brush in order to accustom the child to regu-
pharyngeal musculature, and nasal emission. lar dental hygiene. Malposition of the teeth is not
usually treated, because of the transitory nature
of this stage. Mixed dentition lasts between 7 and
6.8 Orthodontics and Alveolar 12 years of age. The orthodontic treatment is cor-
Bone Graft related with the planning of the alveolar bone
graft when a maxillary cleft exists with, most of
The presence of a facial cleft disturbs the har- the time, missing teeth (canine, incisor, molar) or
mony of the alveolar process by its negative hypoplastic or improperly placed teeth [65, 66].
influence of the formation of the teeth, their erup- To summarize, the first phase of active treat-
tion, and their final position. Both deciduous ment concerns the normalization of the shape of
6  Facial Cleft and Pierre Robin Sequence 89

the dental arch using an asymmetrical expanding combined orthodontic and surgical approaches,
plate before consolidation by means of a bone three phases can be described: (1) preparation of
graft [65, 67]. Normally, and except in rare cases, the upper and lower dental arches with braces for
the incisors, even when malpositioned, are not several months, (2) surgical correction, and (3)
aligned before the graft. The aim of the bone orthodontic treatment for fine alignment during a
graft is to close a cleft in the alveolar process. few months (Fig. 6.16).
The permanent teeth, especially the canines, Fixed orthodontic braces are the only quick-­
emerge when the bone of the maxilla is complete. release treatment of the complex adjustments
A bone graft allows the alveolar process to necessary to correct the often misplaced teeth.
develop almost normally and so provides the nec- Even with highly effective fixed braces, the qual-
essary environment for the development and sta- ity of the outcome also depends on the collabora-
bilization of the adjacent teeth, which need to be tion of the patients and the parents. This
set in adequate bone [68]. The planification of the collaboration begins with dental hygiene. The
alveolar graft (GOA) must be well thought out, presence of braces encourages a large number of
even if its exact timing cannot always be pre- bacteria (bacterial plaque) responsible for caries
cisely determined and varies largely between and periodontal disease.
children. It is generally accepted that the bone In general, it is important to limit interven-
graft should be done before the age of 9 or 10, but tions to a minimum in order to avoid straining the
some teams perform this graft precociously, at patient’s potential for cooperation. Their timing
about 5 years of age. The spongious bone for the must be discussed within a multidisciplinary
graft must be taken from inside the normal bone, team. There are periods in the growth and devel-
usually from the iliac crest, or from the mandibu- opment of the bone during which orthodontic
lar bone. This graft will create a bridge in the treatment is recommended. The duration of the
gum ridge between the left and right edges of the conservative treatment has to be determined not
cleft and allow the permanent teeth to come in. only in view of its final result but also in relation
Only autologous bone has the capacity to create a with the child’s behavior and his capacity to put
bridge. It is important to do a bone graft before up with it. A long-lasting and possibly poorly
the eruption of the definitive canines, as without effective conservative treatment must be avoided,
bone the permanent canines cannot erupt. not only for the sake of the child and his family
The second phase starts with the complete but also because of its cost.
healing of the bone graft (autograft). The aim is
to align the upper incisors and canines, mainly
for cosmetic reasons. The aligned teeth are stabi- 6.9 Maxillofacial Surgery
lized by a retainer made of fine steel wire bonded
to the lingual side of the teeth with composite During the growth process, the intermaxillary
resin [62, 69]. This treatment allows a good heal- relations remain good as long as the articular
ing of the bone and the integration of the graft. congruence, esthetically and functionally,
The permanent canines/incisors will be able to responds to conservative treatment. But in
erupt naturally and in a nearly normal bony envi- 10–20% of cases, a maxillary growth deficiency
ronment. Orthodontic alignment will then be is obvious, confirmed by an analysis of cephalo-
possible, and the chances that the canine and lat- metric measurements (Fig.  6.17). These mea-
eral teeth will remain stable are considerably surements must be made regularly, because bone
improved. growth of individual parts may happen at differ-
The third phase starts around the age of 12. It ent speeds and a good articular congruence with
concerns the relationship between the upper and a good esthetic profile may deteriorate quite
lower jaws and the malposition of the teeth. In quickly during puberty. Maxillary and mandibu-
this case a purely orthodontic approach is insuf- lar bones must grow in harmony, esthetically and
ficient and maxillofacial surgery is necessary. For functionally [63]. If they do not, conservative
90 A. S. de Buys Roessingh et al.

a b

c d

e f

Fig. 6.16  Evolution of the position of the teeth during the follow-up: (a, b) at the beginning of the treatment, (c, d) at
the end of the treatment, (e, f) before and after the alveolar graft. Note the presence of an oronasal fistula before the graft

treatment is not sufficient and surgical treatment increases during adolescence. According to a
proves necessary, in the form of maxillary few authors, these growth disturbances are
advancement (LeFort I), associated or not with intrinsic to the cleft itself, as they were observed
mandibular retraction (sagittal). This surgical in children whose clefts had never been surgi-
treatment must be correlated with the orthodontic cally repaired [70, 71]. However, these studies
treatment and performed at the end of the growth have been questioned, and many authors hold
period, between the ages of 16 and 18. that maxillary growth deficiency is mainly iatro-
Impairment of maxillary growth resulting in genic in nature and a consequence of the primary
retrusion of the maxilla is a frequent finding in surgical repair of the palate [72]. Liao and Mars
children born with cleft lip and palate. These [73] compared the follow-up of children born
children often have midfacial growth deficiency, with UCLP and operated only for their lip with
with a reduced upper lip support, leading to a children born with UCLP and operated for both
characteristic concave profile. This generally lip and palate; they concluded that primary
6  Facial Cleft and Pierre Robin Sequence 91

Fig. 6.17  Lateral cephalogram of a patient with a maxillary retrusion and severe impact on profile (left) and lateral
cephalogram of a patient with a similar maxillary retrusion, but a diminished impact on profile (right)

surgery on the palate was the main cause of max- whose clefts were closed following the Malek
illary retrusion. procedure and children whose clefts were closed
Consequently, special care must be taken dur- following a conventional technique.
ing the primary surgery to avoid the elevation of An objective determination of the need for
the mucoperiosteum. As a result, there will be orthognathic surgery may be based on the data
only a small area of denuded palatal bone, lateral available from the analysis of the lateral cephalo-
to the incisions on the palate, which will heal grams: the anteroposterior relationship of the
spontaneously by secondary intention. If the sur- maxillary basal arch to the anterior cranial base
gery during the first months is too aggressive, uses the SNA, SNB, and ANB angles (S = sella,
with a high elevation of the mucoperiosteum, N  =  nasion, A  =  subspinal, B  =  supramental);
large areas of palatal bone are left to heal by sec- anteroposterior jaw dysplasia may be measured
ondary intention, and the amount of scar tissue according to the Wits appraisal (perpendiculars
on the palate is thus greatly increased, leading to from points A and B onto the occlusal plane), and
retractions and difficulties in bone growth. the distance from the upper lip to the e-plane
Orthognathic surgery to correct facial dishar- (line drawn from the tip of the nose to the chin) is
mony is part of the normal follow-up of children the most used criteria. Children with poor facial
born with UCLP. When planning corrective sur- esthetics despite a more favorable lateral cepha-
gery, many factors, such as facial profile, inter- logram may also be considered for an orthogna-
maxillary discrepancies, and dentoalveolar thic correction, even if this criterion is mostly
relationship, are taken into account. Unfortunately, subjective and a matter for a family discussion.
as there is no standardized protocol, the choice of Orthognathic surgery to correct these dentofa-
procedure often remains subjective, and this can cial deformities may therefore be indicated [77].
explain why it is difficult to compare the results A maxillary advancement with a LeFort I osteot-
obtained in different centers [74, 75]. Ross et al. omy is the most common orthognathic proce-
in 1987 [76] compared lateral cephalograms of dure. Due to a possible transversal collapse of the
UCLP children whose palate surgery had fol- maxillary arches on each side of the cleft, caused
lowed different techniques, operated for their pal- by the scarring tissue, this advancement cannot
ate by different techniques, and showed very always be achieved in one piece. In these cases,
similar results and measurements for children the maxilla needs to be segmented in two or three
92 A. S. de Buys Roessingh et al.

pieces. The frequency of indications in the litera- petent people is therefore mandatory to give con-
ture for a LeFort I osteotomy in unilateral cleft fidence to the parents and to reassure them. The
lip and palate (UCLP) varies from 22% to 48.3% knowledge that a team is dealing with the malfor-
[75]. These differences may arise from different mation and is competent is essential [5, 78].
management protocols and depend also on the The announcement of the diagnosis is
patient’s access to adequate presurgical orth- extremely delicate, and people present during the
odontic care. The criteria used to determine the diagnosis must show tact and respect, especially
need for orthognathic surgery are also subjective in the matter of the words used. Prenatal discus-
to some extent and therefore may vary between sions will provide advice for the remaining
surgical teams. course of the pregnancy and also give the parents
information on where the mother should give
birth. By example, for a suspicion of Pierre Robin
6.10 Psychological Impact sequence, it is quite important that the birth take
place in a specific hospital, with a pediatric anes-
A birth in itself modifies the family harmony, and thetist and pediatric reanimation. Respiratory and
the arrival of a child causes psychological and feeding problems must be discussed in order to
physiological upheavals that specialists define as prepare the parents to the fact that in the case of a
periods of crisis in maturation. For most people, total cleft or palatal cleft, breast-feeding, for
planning a child implies a large measure of instance, will be impossible. The esthetic follow-
dreaming, high expectations, and the fulfillment ­up, the difficulties in language development, and
of a part of oneself. The fact that the parents the nature and schedule of the surgery to be
“meet” their child before birth during ultrasound expected must be discussed [15]. Individual
examination intensifies these expectations and resources and specificities play an important role.
dreams in the sense that the new baby can sud- It is impossible to predict the future of the child
denly be pictured and is the basis of a real repre- and his relationship to his parents.
sentation. The literature shows that the majority In most cases, the traumatism of the diagnosis
of parents wish to be informed of an expected can be expressed in parental terms through
defect of the baby as early as possible, in order to intense images or some kind of protective shield.
learn to face the reality of the problem. After the If these phenomena last for too long a time, they
diagnosis, they are overcome with worry and may resemble post-traumatic stress with charac-
anxiety and need time to accept it. In the course teristic symptoms of avoidance, feeling of intru-
of the follow-up and the exchanges with the med- sion, and neurovegetative reactions. As time goes
ical team, they will absorb the shock of the diag- on, we observe a progressive acceptance of their
nosis and prepare to welcome their baby. Progress role as parents and often a reaction of overprotec-
in surgery nowadays allows parents to hope for tive behavior.
high esthetic and functional results. The child, or adolescent, will be confronted
Psychological problems start before birth. with difficult episodes at different times of his
Parents either find it impossible to imagine their life, for instance, and to name only a few, the start
child’s face or have a lot of images and fantasms of school, the relation with peers, puberty, and
in their mind. Each parent thinks, be it for one the relation with girl- or boyfriends. The inter-
instant only, of interrupting the pregnancy, and vention of a third person at a special moment
this thought brings with it a strong sensation of may be necessary.
culpability. The question of whether there could The revelation that their unborn child has a
possibly be another malformation in their child, defect, for instance, a cleft, is undoubtedly a
especially concerning the brain, is quite often shock for the parents. It is a painful event which
present. The parents must go beyond the diagno- can often give rise to psychological problems.
sis and their fear in order to accept the baby. They Certain parents develop a feeling of culpability,
question the why and how. The presence of com- of loss of control, and of inadequacy as genitors,
6  Facial Cleft and Pierre Robin Sequence 93

which could well have an incidence on the nation are very bad if surgery is performed after
psycho-­affective development of the child [5, 15, this age [79–81]. Nevertheless, surgery induces
16]. This is why a psychological support to the scars with retrognathia, and the palate may be
parents from the very moment the prenatal diag- short, weak, or stiff. VPI results from an incom-
nostic is established can be useful. The social plete closure of the soft palate and the posterior
skills of the child himself, the adolescent, may pharyngeal wall. Nasal resonance due to VPI
also be affected, with resulting manifestations of diminishes the volume and intelligibility of
anxiety, poor self-esteem, or depression. speech.
The psychological consultation offered by The possible types of surgery are (a) injection
specialists in the course of each pluridisciplinary of autologous fat in the retropharyngeal space in
consultation helps to spot risky situations and to order to diminish the retro palatal space [82]; (b)
set up a program of support adapted to each indi- reconstruction of the anatomy by a simple velo-
vidual child. plasty, possibly associated with a Z-plasty [83];
(c) lengthening of the palate by means of a pha-
ryngeal flap (Fig. 6.18) based superiorly, inferi-
6.11 Secondary Surgery orly, or laterally [84–87]; (d) pharyngoplasty
with or without push-back of the palate [86, 88];
The first installment of secondary surgery, and, finally, (e) a lengthening of the palate by
between 5 and 10  years of age, is considered a means of a jugal flap (Buccinateur) [89, 90].
complementary surgery to the primary surgery. It The surgical procedures described for the
includes, first of all, a pharyngeal flap or a true treatment of VPI all aim at lengthening the soft
pharyngoplasty and closure of a bucco-nasal fis- palate. The aim is to correct velopharyngeal dys-
tula. Early rhinoplasty is also possible if the function and create a central subtotal velopharyn-
deformation of the columella or of the nasal wing geal obstruction, leaving two narrow lateral
is especially unesthetic. passages for nasal airflow. The cranial-based pha-
Subsequent surgery, after 10  years of age, ryngeal flap surgery was performed first by
includes dental repair, the purview of orthodon- Schönborn [91] and then Sanvenero-Rosselli
tists (Sect. 6.8), and alveolar grafts, the purview [92]. A broad, cranially based pharyngeal flap is
of maxillofacial surgeons (Sect. 6.8), with or incised and elevated from the prevertebral fascia
without maxillary advancement. Correction of to be sutured to the nasal side of the incised
the lip with a labioplasty is always possible for velum (Fig.  6.18). The donor site is closed
esthetic purposes, especially in the case of BCLP, directly. The soft palate is dissected and two
where the muscle of the central part of the lip is mucosal flaps are prepared. The two mucosal
missing. Rhinoplasty with lengthening of the flaps are incised on the dorsal velar side. The
columella, especially for bilateral cases, correc- pharyngeal flap, including its muscle layer, is
tion of the asymmetry of the nasal wing for uni- sutured to the nasal mucosa of the velum. In the
lateral cases, and lip surgery are performed, if midline, the two buccal flaps are joined and
possible, after the final growth of the maxillary. sutured in their entire thickness to the surface of
the flaps. This technique was modified by Fischer-­
Brandies and Nejedlo [93] because in its original
6.11.1 Pharyngoplasty version, the pedicle created between the dorsal
and Pharyngeal Flap pharyngeal wall and the soft palate was too nar-
row, due to healing by granulation, scar contrac-
Secondary surgery for the palate is proposed tion, and narrow bed. The modified technique
when continued therapy no longer improves the entails the creation of two mucosal flaps on the
child’s speech. Surgery on the palatal cleft must dorsal velar side to cover the pharyngeal flap and
be done before 18 months of age to facilitate lan- increase its width to produce a voluminous and
guage acquisition [79]. Results in terms of pho- broad flap. This modification leads to a better
94 A. S. de Buys Roessingh et al.

Fig. 6.18  Cranial-based pharyngeal flaps following the ryngeal flap is incised and elevated from the preverte-
technique described by Schönborn in 1865 [91] and bral fascia to be sutured to the nasal side of the incised
Sanvenero-Rosselli [92]. A broad, cranially based pha- velum

velopharyngeal occlusion of the muscles and pharyngeal flap will best assist closure of the
results in improved speech. However, there have velopharyngeal port during speech. Barot et  al.
been reports of airway obstruction and obstruc- [94] reported that 15% of patients who under-
tion sleep apnea associated with pharyngeal flap went pharyngeal flap surgery for velopharyngeal
surgery [7]. A polygraphy or a polysomnography dysfunction over a 9-year period required revi-
must be done before and after the surgery. sion. Witt et al. [89] described the same results in
Because of the variation in the degree of children who had received a velopharyngeal flap
shrinkage of the flap and scar contraction, the or sphincter pharyngoplasty. Post-surgery exami-
final size of the lateral velopharyngeal apertures nations are necessary to check for nasal obstruc-
cannot always be accurately predicted. The fail- tion that persists after 1 month and for sleep
ure of this technique is obvious when hypernasal- apnea.
ity persists. It can be the result of surgical error Surgical success is defined in terms of the
and/or inadequate lateral pharyngeal wall motion elimination of perceptible hypernasality or oral
[85]. Surgical errors include a too narrow flap, a resonance and of instrumental evidence of com-
poor short flap, or scar contraction [83]. They can plete velopharyngeal closure by nasoendoscopy.
also result in a velopharyngeal flap which is too Velopharyngeal assessment is generally per-
broad, causing hyponasal speech and sleep apnea. formed 4 months after surgery. Surgical failure is
Preoperative assessment of the velopharyngeal defined in terms of persistent hypernasality and/
mechanism is essential in choosing which type of or nasal turbulence observed during a perceptual
6  Facial Cleft and Pierre Robin Sequence 95

speech evaluation and of incomplete velopharyn- the fistula is based on the elevation of the muco-
geal closure evidenced by nasometry at least 6 periosteum of the entire palate. Simple closure of
months after surgery. the hole is just not possible. Closure of the fistula
must be postponed as long as possible in order to
minimize adverse consequences on the growth of
6.11.2 Oronasal Fistula the maxilla.

Fistulas of the palate remain the major complica-

tion in the early primary palate technique. These 6.11.3 Labioplasty
fistulas do not appear to be linked exclusively to
a defective surgical technique. A weakness in the Secondary surgery for the lip in UCLP children is
sutures may obviously be a contributing factor. normally done when the Cupid’s bow is not per-
Single-layered closures of the nasal mucosa on fect or when the height of the repaired lip is too
the bony vault make fistulas more likely. A sec- short. In the first case, surgery is simple, with a
ond layer of closure on the oral side significantly local correction and alignment of the white skin.
reduces the incidence of fistulas but does not In the second case, where the distance from the
eliminate them all together. One of the major nose to the lip is not satisfactory, the height of the
causes is the positive and negative pressure which “normal lip” must again be calculated and com-
the child can produce in the oral cavity after it has pared with the opposite side. The height of the lip
been completely closed. The best preventive is determined by using a caliper to measure the
measure is a suture technique based on double-­ height of the outer border on the vertical line
layered closure. However, when the customary from the outer alar base. In most cases, the
technique is followed, there is always a zone in repaired lip is short, and a Z-plasty must be done
the retroalveolar region that is covered by only by opening the skin from the lip to the nostril.
one oral layer. A number of therapeutic theories The precise position of the Cupid’s bow must
have been elaborated to help prevent these fistu- again be determined and the triangular flap plasty
las. One simple solution might lie in the use of adapted so that the top edge of the lip and the
prosthetic obturation. The obturator could be left lateral superior points of the Cupid’s bow will be
in place for a short period to allow satisfactory aligned with the middle reference point set by the
healing. nostrils.
When a fistula does exist, there is never spon- In cases of bilateral clefts, normal references
taneous closure. The consequences are, first, the do not exist and the vermilion could be too short:
leakage of fluids or soft food such as milk or Z-plasties must be done on both sides by opening
water through the nose. It is known as the “signe the lip up to the nostrils [37, 38]. Additional
du chocolat,” when chocolate food falls from the length is gained between two points thanks to the
nostril. The passage of food through the nostril dissection of two triangular flaps that share a
can also result from a too short or scarred soft common side. The apices of the triangles are situ-
plate. The second consequence is a speech disor- ated at each end of the joined triangular flaps.
der, called rhinolalia, meaning air coming After the incision, inversion of the flaps results in
through the nose during speech. The speech ther- inversion of the diagonals on the parallelogram
apist must distinguish between VPI and air com- initially traced. The long diagonal replaces the
ing from the mouth through the fistula. Indication short and vice versa, so that the desired additional
for closure of a fistula depends on the severity of length is obtained. In most cases, the muscles are
its consequences, but the child must be followed separated on both sides of the central part of the
by the speech therapist to be sure that compensa- lip. In these cases, the lip must be opened and the
tory phenomena are not present, due to the leak- muscles sutured together, removing if possible
age of air (Table 6.2). A technique of closure of the scar tissue in the middle of the lip.
96 A. S. de Buys Roessingh et al.

6.11.4 Rhinoplasty same surgery. A thermoformable splint may also

be used for several days or weeks. This surgery is
Early rhinoplasty is performed by different sur- not easy and takes time. It represents the final
geons during the primary surgical repair, the step after years and years of follow-up, knowing
labioplasty. Results in terms of growth and of that primary surgery certainly determines the
esthetic success are still being evaluated. A ther- growth of the face and of the bone and therefore
moformable splint may be used for several weeks the success of the rhinoplasty.
after the surgery. Intermediate rhinoplasty is
done between 5 and 10 years of age. It is reserved
for severe deformations accompanied by psycho- 6.12 Support Group
logical and social manifestations. This type of and Multidisciplinary Team
surgical intervention is therefore discussed dur-
ing our multidisciplinary meetings. Both objec- The multidisciplinary cleft team is composed of a
tive and subjective indications must be pediatric surgeon, a plastic surgeon, a pediatric
considered. The operation consists in reposition- ENT specialist, a craniofacial surgeon, an ortho-
ing the alar cartilage through an incision inside dontist, a speech therapist, and a psychologist. A
the nostril [95]. A thermoformable splint may geneticist and a gynecologist are also present to
also be used for several days or weeks. Late rhi- offer their collaboration to the discussion. The
noplasty is planned at the end of the growth. It is child and its parents must be seen as required by
wise to do the surgery after the orthodontic treat- the child’s and the parents’ needs.
ment is completed. The operation involves a There is a risk of the parents being destabi-
small incision below the nose and necessitates a lized or losing their landmarks when facing what
cartilage graft taken from the ear. The deviation may at times appear to be contradictory informa-
of the nasal septum is also corrected during the tions, notably in the matter of various treatment

Table 6.3  Basic general follow-up of children with a cleft

When? What? Who?
Antenatal Information Pediatric surgeon
Psychological help Psychologue
Genetic counseling
Birth Information Pediatric surgeon
Alimentary problems Nurse
Orthodontist (plaque)
3 months Primary surgery Pediatric surgeon
5–10 months Primary surgery Pediatric surgeon
18 months−3 years Check-up Pediatric surgeon
Parental guidance ENT, pediatrician
Orthophonist
3 years Bilan Team
3–9 years Follow-up Team
Guidance (speech) Pediatric surgeon
Secondary surgery: fistula, pharyngoplasty
Early secondary surgery (nose)
9 years Orthodontist Team
6–10 years Bone graft Maxillofacial surgeon
Orthodontist
12–18 years Follow-up Team
Secondary surgery: LeFort, rhinoplasty, labioplasty Pediatric surgeon
ENT
18–20 years Genetic counseling Team
6  Facial Cleft and Pierre Robin Sequence 97

methods and timing of the operations. The cleft J Oral Sci. 2017;9(2):104–9. https://doi.org/10.1038/
ijos.2016.56.
team must be a strong source of help, always 13. Ludwig KU, Ahmed ST, Böhmer AC, et  al. Meta-­
ready to answer the parents’ requests for infor- analysis reveals genome-wide significance at
mation (Table  6.3). Association of parents may 15q13 for nonsyndromic clefting of both the lip
be also very helpful. and the palate, and functional analyses implicate
GREM1 as a plausible causative gene. PLoS Genet.
2016;11:e1005914.
Acknowledgments The authors are grateful to Annette 14. Hagberg C, Larson O, Milerad J.  Incidence of cleft
Wagnière for reviewing the English text. lip and palate and risks of additional malformations.
Cleft Palate Craniofac J. 1998;35(1):40–5.
15. Rey-Bellet C, Hohlfeld J. Prenatal diagnosis of facial
clefts: evaluation of a specialised counselling. Swiss
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 Macroglossia
7
Pedro Saraiva Teiga, Kishore Sandu, and Lluís Nisa

7.1 Introduction ital macroglossia is rare but possible [3].

Macroglossia may be absolutely asymptomatic
Macroglossia is defined as an abnormally or present with mild symptoms like drooling and
enlarged tongue (from the Greek “makros + articulation impairment, while severe macroglos-
glossa”). Macroglossia was documented as early sia may lead to swallowing difficulties, upper air-
as 1550  BCE in the ancient Egyptian Papyrus way obstruction, and obstructive sleep apnea.
Ebers. Chief among congenital causes of macroglos-
From a clinical perspective, macroglossia is sia are Down syndrome, Beckwith-Wiedemann
characterized by an extension of the tongue syndrome, primary amyloidosis, and congenital
beyond the teeth or the alveolar ridge at rest, hypothyroidism. Acquired causes may include
although other definitions and criteria exist [1]. trauma, tumors, and inflammatory or infectious
In this sense, two main classifications for macro- conditions.
glossia are clinically useful. The Myer classifica- Given the fact that macroglossia is most often
tion [1] distinguishes between local and general an associated finding in several conditions, the
macroglossia based on the extent of lingual exact prevalence of macroglossia is difficult to
involvement. The Vogel classification [2] in con- determine.
trast defines true macroglossia as an enlarged The treatment of macroglossia depends both
tongue with underlying histological alterations. on its severity and clinical presentation.
Relative macroglossia designates an abnormally Management possibilities include symptomatic
enlarged tongue in proportion to other structures relief of drooling, speech therapy, or surgical
surrounding the oral cavity (Fig. 7.1). reduction of the tongue for the most severe cases.
Macroglossia is most often encountered
within the frame of an underlying condition,
whether congenital or acquired. Isolated congen- 7.2 Diagnostic Approach

The goal of the diagnostic approach in children

P. S. Teiga · K. Sandu (*)
Department of Otorhinolaryngology, Head and Neck with macroglossia must address three essential
Surgery, Lausanne University Hospital, CHUV, issues:
Lausanne, Switzerland
e-mail: [email protected] 1. Establishing the diagnosis and more specifi-
L. Nisa cally distinguishing true vs. relative
Department of Otorhinolaryngology, Head and Neck macroglossia
Surgery, Inselspital, Bern University Hospital,
University of Bern, Bern, Switzerland

© Springer Nature Switzerland AG 2019 101

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_7
102 P. S. Teiga et al.

2 . Assessing for presence of comorbidities with drooling or impaired articulation.

3. Assessing the anatomical and functional
Macroglossia can also affect the oral and pha-
impact of macroglossia ryngeal swallowing phases and result in feeding
problems and in small children possible bron-
Presenting symptoms and their intensity choaspiration. Finally, severe forms of macro-
depends on macroglossia severity and clinical glossia can also lead to upper airway obstruction,
context (Table 7.1). As mentioned above, macro- especially in supine position. During sleep this
glossia can be strictly asymptomatic or present can be responsible for snoring and obstructive

a b b1 b2

Fig. 7.1 (a) Generalized macroglossia in Beckwith-­ artoma. Pictures with kind permission from Dr. Anthony
Wiedemann syndrome. (b) Localized macroglossia. (b1) De Buys Roessingh
Foregut duplication cyst of the tongue. (b2) Tongue ham-

Table 7.1  Clinical features 1. Airway obstruction

    Obstructive sleep apnea
    Bronchoaspiration
2. Dysphagia
    Speech articulation disorders
    Glossitis
    Scalloping (fissuring of the
tongue)
    Lingual tip necrosis
    Pain
    Drooling
3. Temporomandibular joint pain
4. Dental deformities Class III malocclusion
Open bite
Crossbite
Buccal tipping of posterior teeth
5. Facial deformities Increased width of maxillary/mandibular
arches
Mandibular prognathism
Accentuated or reverse curve of Spee (in
maxillary or mandibulary arch
respectively)
Facial asymmetry in asymmetric tongue
6. Psychological
7 Macroglossia 103

sleep apnea syndrome (OSAS). Constant expo- of swallowing (FEES) in children with suspected
sure of the oral mucosae due to the fact that the swallowing disorders [7].
mouth remains constantly open may lead to Complementary studies should be guided by
angular cheilitis, ulceration, or glossitis. Cases clinical context and may include chromosomal
of acute exacerbations of previously existing studies, urine mucopolysaccharides, or evaluation
macroglossia leading to local complications of thyroid gland function. Imaging studies are
such as necrosis, often following trauma, have most commonly reserved for vascular or lym-
been reported [4]. phatic malformations, tumors, or other causes of
If not properly addressed in due time, macro- focal macroglossia, in order to obtain preoperative
glossia can result in dentoskeletal deformities assessment of lesional extent/vascular supply [8].
such as open bite, prognathism, malocclusion, Regarding genetic causes of macroglossia, it
crossbite, buccal tipping of posterior teeth, and is recommended that newborns and young infants
other alterations of the mandibular or maxillary undergo evaluation by means of abdominal ultra-
arches. In the long term, temporomandibular sonography and genetic studies for Beckwith-­
joint dysfunction tends to occur. Wiedemann syndrome (see Sect. 7.2.2.2). A
study on the genetic causes of macroglossia
reported that macroglossia was the main reason
7.2.1 Diagnostic Methods for genetic workup in almost two-thirds of the
patients (median age of 5 months) [3].
The diagnosis of macroglossia in children is first
and foremost made on the basis of clinical history
and physical examination. A comprehensive his- 7.2.2 Associated Comorbidities
tory regarding pregnancy, birth, and family dis-
eases should be obtained. Prenatal diagnosis of It is essential to realize that macroglossia most
congenital macroglossia is sometimes evident on often results from an underlying cause, whether
ultrasound examination, showing a tongue pro- or not in the frame of a wider condition. It is
trusion beyond the lips [5]. therefore essential to approach children with
It is essential to keep in mind that newborns macroglossia in the context of a multidisciplinary
tend to have a relatively large tongue. However, team including otolaryngologists, pediatricians,
congenital macroglossia is often apparent at geneticists, and maxillofacial surgeons, among
birth, especially if airway or swallowing symp- others. Generalized macroglossia in children is
toms are present. This is, for instance, the case in primarily seen in the frame of congenital dis-
children with relative macroglossia such as those eases, primarily Down and Beckwith-Wiedemann
with Pierre Robin sequence [6]. It is nevertheless syndromes, and mucopolysaccharidoses. Rarer
important to keep in mind that macroglossia in causes include congenital hypothyroidism and
children can slowly develop, even over a period systemic amyloidosis (the latter being exception-
of months to years. It is therefore essential to fol- ally rare in children). An ectopic lingual thyroid
low up children with macroglossia to ensure can equally cause congenital localized macro-
proper intervention if and when needed. glossia. Other causes of macroglossia include
Since macroglossia can lead to dentoskeletal lymphovascular malformations, which most
deformities, evaluation by an oral or craniofacial often present within the first year of life and
surgeon should be considered for all cases of slowly progress.
macroglossia, whether absolute or relative. Here are briefly discussed some of the most
Clinical examination should carefully evalu- common causes of macroglossia.
ate tongue size and mobility, as well as transnasal
flexible pharyngo-laryngoscopy to assess the 7.2.2.1 Down Syndrome
base of the tongue and upper airway. This can be Down syndrome is a well-known condition and
combined with functional endoscopic evaluation the most common genetic cause of development
104 P. S. Teiga et al.

impairment, resulting from chromosome 21 tri- neous MPS have been described. MPS are diag-
somy. Its estimated incidence is of approximately nosed on the basis of clinical examination and by
1:650 live births [9]. Macroglossia is considered measuring urine mucopolysaccharides [20]. MPS
to be a standard feature in children with Down commonly feature orofacial alterations, espe-
syndrome. Nevertheless, these patients com- cially a delay in tooth eruption and macroglossia,
monly feature midface as well as mandibular as well as hypertrophy of the tonsils and ade-
hypoplasia, therefore resulting in a smaller oral noids. Children with MPS often feature severe
cavity. Several studies suggest that children with obstructive apnea.
Down syndrome have smaller tongues than age-­
matched controls, along with smaller bony con- 7.2.2.4 Systemic Amyloidosis
fines of the oral cavity. As a result, the relative Amyloidosis is a group of systemic disorders
tongue size is larger in children with Down syn- characterized by deposition of insoluble amyloid
drome than in healthy children [10, 11]. fibers within the extracellular matrix of tissues.
The most common form of amyloidosis is light-­
7.2.2.2 Beckwith-Wiedemann chain (AL) amyloidosis, resulting from deposi-
Syndrome (BWS) tion of monoclonal immunoglobulin light chains.
BWS consists of an organ overgrowth syndrome Amyloid deposits can be systemic or localized to
resulting from methylation of key regulatory specific organs. The most commonly involved
genes on chromosome 11p15. Its incidence is of sites within the head and neck region are the lar-
approximately 1:10,000–1:15,000 live births ynx and the tongue, usually within a context of
[12–14]. In the head and neck region, BWS fea- systemic disease [21, 22]. Macroglossia within
tures macroglossia in over 95% of the cases and the context of AL amyloidosis occurs in approxi-
earlobe creases. Macroglossia in children with mately 40% of cases and can equally occur in
BWS tends to be marked and impairs chewing other types of amyloidosis [23–25].
and swallowing. In severest cases, it may even
compromise breathing [15, 16]. 7.2.2.5 Congenital Hypothyroidism
Moreover, it has been shown that parents of (CH)
children with BWS are commonly concerned CH is characterized by deficient thyroid hormone
about the negative social impact caused by a production at birth, most commonly secondary to
large protruding tongue, drooling, and impaired problems with the gland development (dysgene-
intelligibility. Other than the cosmetic appear- sis or agenesia) or by impaired hormone biosyn-
ance, macroglossia tends to be associated with thesis. CH can be transient or permanent. In the
learning difficulties in the general society. BWS latter, normal thyroid function occurs usually
children tend to have an age-appropriate intellect within the first months of life. CH can be diag-
[17, 18]. nosed within a syndromic context, especially in
It is important to keep in mind that macroglos- children with Down syndrome [26]. CH has mul-
sia in children with BWS tends to improve with tiple underlying causes. For instance, in a small
age, and it is therefore important to carefully fraction of cases, mutations in the TTF-2 lead to
evaluate the surgical indications on an individual thyroid dysgenesis. CH incidence ranges between
basis [18]. Children with BWS have the risk of 1:3000 and 1:4000 cases/living births and is most
severe postoperative hypoglycemia [19]. often diagnosed within the frame of newborn
screening [27]. Clinically, CH has a wide spec-
7.2.2.3 Mucopolysaccharidosis (MPS) trum of presentations and may affect multiple
Mucopolysaccharidoses are a group of metabolic organs. However, the most common clinical
diseases due to a functional defect of lysosomal manifestations are macroglossia, umbilical her-
enzymes histologically characterized by accumu- nia, and skin alterations [28, 29].
lation of mucopolysaccharides in the soft tissues. Macroglossia in the context of CH can be present
So far, nine main types of clinically heteroge- already at birth or more often develop as the child
7 Macroglossia 105

grows up. Moreover, children with CH often present a full physical examination in order to deter-
an impaired primary dentition, vertical facial growth, mine the underlying cause. Having ruled out
decrease of length, and skull base angle. obvious causes such as Down syndrome or if
the diagnosis of BWS is probably specific,
7.2.2.6 Lymphatic Malformation molecular testing should be performed (if it is
Lymphatic malformations affect the head and clinically driven). In case of seemingly iso-
neck region in approximately 75% of the cases. lated macroglossia, an abdominal ultrasound
Lymphatic malformations may be present at birth could provide arguments for the diagnosis of
or manifest later in life, usually within the first BWS. In case of pathological findings, molec-
2  years of life, due to infection or trauma [30]. ular testing should be used to confirm the
Lymphatic malformations are classified as mac- diagnosis.
rocystic (cysts of >2 cm) or microcystic (<2 cm). From a functional perspective, the role of the
Lymphatic malformations are a relatively com- otolaryngologist as well as of the oral surgeon is
mon cause of focal macroglossia [31]. essential. As mentioned above, FEES and diag-
nostic workup to rule out OSAS can be per-
formed. The functional impact will then be
7.2.3 Diagnostic Workflow classified as mild (no real functional impact),
moderate, or severe. This should provide impor-
Children who present general macroglossia, tant information when it comes to the decision-­
without an obvious diagnosis, should undergo making process (Fig. 7.2).

General
macroglossia

Etiology workup Functional workup

Clinical
examination

Isolated Probable BWS Syndromic General ENT FEES OSAS workup

Functional
Abd. US Workup BWS Spec. molecular
impact
testing
Pathological Pos. Neg. Microarray

Pos.
Workup BWS BWS Mild Moderate Severe
N (drooling, (disordered (airway
eg
. dental swallowing, symptoms,
Other alterations) aspiration) craniofacial
overgrowth deformity, FTT)
syndromes

Surgical
Conservative
Partial
Speech/
glossectomy
swallowing
Craniofacial
therapy
approach
Dental appliances
Tracheotomy

Fig. 7.2  Workflow for diagnostic and therapeutic approach to macroglossia

106 P. S. Teiga et al.

Cases of focal macroglossia are most often clusion, and cosmetic considerations should also
assessed by histological examination and/or be taken into consideration [3, 36, 37]. Indeed, a
imaging. nationwide survey of surgery for tongue r­ eduction
It must be stressed that interdisciplinary col- in children in the USA showed that while chil-
laboration for the diagnosis and management of dren with airway or feeding difficulties tend to
children with macroglossia is essential. undergo surgical approaches within the first year
of life, indications are increasingly dominated by
occlusal and craniofacial issues within the sec-
7.3 Management ond year of life [36].
As mentioned above, prior to undertaking any
7.3.1 Nonsurgical Management surgical procedure, it should be kept in mind that
in mild cases of macroglossia, normal mandibu-
The indications for medical therapy are restricted lar and midfacial growth may improve the clini-
to treatable underlying causes of macroglossia cal situation, thus avoiding surgery. In cases of
such as hypothyroidism or amyloidosis [32]. airway compromise, tracheotomy may some-
Several conservative approaches to lymphatic times be needed (Fig. 7.2).
malformations have been proposed, including Any surgical approach to the tongue aims at
radiotherapy, sclerotherapy, cryotherapy, and achieving a tongue size as close to normal as
sirolimus or steroid injection [33]. Minimally possible, namely, a tongue which remains behind
invasive approaches such as electrocautery, the lower dental arch at rest but which can wet
embolization, and ligation are equally possible the lips on protrusion [38–40]. Particular atten-
[33, 34]. tion should be paid to tongue mobility, mastica-
Acute tongue swelling (for instance, after tion, and swallowing (i.e., oral and pharyngeal
trauma on an underlying lymphatic malforma- phase of swallowing). Other important features
tion), despite the lack of strong evidence, can be are obviously enunciation, taste, and cosmetic
treated conservatively with a raised head, eventu- considerations.
ally adding steroids and/or antibiotics [35]. In this sense knowledge of the surgical anat-
Speech and swallowing therapy can be the omy of the tongue is essential. The tongue consists
first approach to children with macroglossia and of eight muscles, four intrinsic and four extrinsic.
impaired speech/swallowing. However, in cases When removing muscle mass, it is essential pre-
of muscular hypertrophy or hyperplasia, there is serving both the intrinsic and extrinsic functions of
no proven effective conservative management. the tongue. The neurovascular tongue supplies,
namely, the lingual artery and nerve as well as the
hypoglossal nerve (CN XII), access the tongue
7.3.2 Surgical Management posteriorly and laterally and advance anteriorly
without crossing the midline [41].
Indications for the surgical management in chil- Forms of focal or localized macroglossia,
dren with macroglossia are a matter of ongoing such as in lymphatic malformations, can be
controversy. It is generally accepted that in managed by partial resections depending on
­
patients with disordered feeding, breathing and lesion’s location. Resection techniques (Figs. 7.3
speech are the main candidates for surgery. and 7.4) include anterior wedge, central ellipse,
Moreover, improving teeth malalignment, maloc- lateral glossectomy, or submucosal resections
7 Macroglossia 107

a b c

Pichler Harris, Blair, Picher-Edgerton

d e and Hendrick
f

Morgan Austerman Dingman and Grab

and machtens

Fig. 7.3  Types of tongue reduction techniques. (a) Pichler; (b) Harris, Blair, and Hendrick; (c) Pichler-Edgerton; (d)
Morgan; (e) Austerman and Machtens; and (f) Dingman and Grab

(i.e., mucosa sparing). Some authors advocate for ume and forward growth of the jaws early in life.
the use of the CO2 laser for such lesions [42]. Consequently, every child with Down syndrome
As discussed above, the relative macroglossia and symptomatic “macroglossia” should be eval-
seen in children with Down syndrome results uated by oral surgeons. Oral appliances may be
from the shorter skull base and underdeveloped interesting adjuvants for OSAS in older and com-
palate. As such, management approaches should pliant patients but have obviously a very limited
be focused on orthodontic increase of oral vol- role in young infants [43].
108 P. S. Teiga et al.

a b c

d e f

Fig. 7.4  Surgical treatment of macroglossia in an infant with Beckwith-Wiedemann syndrome using the keyhole tech-
nique. (a, b) Macroglossia; (c) Tongue incision marked; (d, e) Reduction of tongue substance; (f) Closure of tongue
incison. Pictures with kind permission from Dr. Anthony De Buys Roessingh

8. Arrive L, Monnier-Cholley L, Mouhadi SE. Imaging

References appearance of lymphatic malformations. AJR Am J
Roentgenol. 2017;208:W29.
1. Myer CM 3rd, Hotaling AJ, Reilly JS. The diagnosis 9. Bunt CW, Bunt SK. Role of the family physician in
and treatment of macroglossia in children. Ear Nose the care of children with Down syndrome. Am Fam
Throat J. 1986;65:444–8. Physician. 2014;90:851–8.
2. Vogel JE, Mulliken JB, Kaban LB.  Macroglossia: a 10. Uong EC, McDonough JM, Tayag-Kier CE, Zhao H,
review of the condition and a new classification. Plast Haselgrove J, Mahboubi S, et al. Magnetic resonance
Reconstr Surg. 1986;78:715–23. imaging of the upper airway in children with Down syn-
3. Prada CE, Zarate YA, Hopkin RJ.  Genetic causes drome. Am J Respir Crit Care Med. 2001;163:731–6.
of macroglossia: diagnostic approach. Pediatrics. 11. Guimaraes CV, Donnelly LF, Shott SR, Amin RS,
2012;129:e431–7. Kalra M. Relative rather than absolute macroglossia
4. Lahiri A, Kok K, Sharp I, Nishikawa H. Acute exacer- in patients with Down syndrome: implications for
bation of macroglossia leading to necrosis of the ante- treatment of obstructive sleep apnea. Pediatr Radiol.
rior third of the tongue. J Plast Reconstr Aesthet Surg. 2008;38:1062–7.
2006;59:871–3. 12. Weksberg R, Nishikawa J, Caluseriu O, Fei YL,

5. Williams DH, Gauthier DW, Maizels M.  Prenatal Shuman C, Wei C, et  al. Tumor development in the
diagnosis of Beckwith-Wiedemann syndrome. Prenat Beckwith-Wiedemann syndrome is associated with a
Diagn. 2005;25:879–84. variety of constitutional molecular 11p15 alterations
6. Sidman JD, Sampson D, Templeton B.  Distraction including imprinting defects of KCNQ1OT1. Hum
osteogenesis of the mandible for airway obstruction Mol Genet. 2001;10:2989–3000.
in children. Laryngoscope. 2001;111:1137–46. 13. Shuman C, Beckwith JB, Weksberg R.  Beckwith-­

7. Leder SB, Karas DE.  Fiberoptic endoscopic evalu- Wiedemann syndrome. In: Adam MP, Ardinger HH,
ation of swallowing in the pediatric population. Pagon RA, et al., editors. GeneReviews((R)). Seattle,
Laryngoscope. 2000;110:1132–6. WA: University of Washington; 1993.
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14. Weksberg R, Shuman C, Beckwith JB.  Beckwith-­

severity and early clinical features. Arch Dis Child.
Wiedemann syndrome. Eur J Hum Genet. 1992;67:87–90.
2010;18:8–14. 29.
Alm J, Hagenfeldt L, Larsson A, Lundberg
15. McManamny DS, Barnett JS. Macroglossia as a pre- K.  Incidence of congenital hypothyroidism: retro-
sentation of the Beckwith-Wiedemann syndrome. spective study of neonatal laboratory screening versus
Plast Reconstr Surg. 1985;75:170–6. clinical symptoms as indicators leading to diagnosis.
16. Elliott M, Bayly R, Cole T, Temple IK, Maher
Br Med J. 1984;289:1171–5.
ER. Clinical features and natural history of Beckwith-­ 30. Bloom DC, Perkins JA, Manning SC.  Management
Wiedemann syndrome: presentation of 74 new cases. of lymphatic malformations. Curr Opin Otolaryngol
Clin Genet. 1994;46:168–74. Head Neck Surg. 2004;12:500–4.
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feeding, and drooling outcomes in children mas of the head and neck. Ann Otol Rhinol Laryngol.
with Beckwith Wiedemann syndrome following 2000;109:411–21.
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2012;49:e25–34. ism: a rare dental diagnosis. J Oral Maxillofac Pathol.
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clinical and molecular diagnosis, screening and man- alternatives in the treatment of life-threatening vaso-
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Wiedemann HR. [Familial malformation com- of children with various complicated vascular anoma-
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Simmonds JC, Patel AK, Mader NS, Scott
21. Kerner MM, Wang MB, Angier G, Calcaterra TC, AR.  National trends in tongue reduction surgery for
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1999;28:129–31. macroglossia. Case Rep Dent. 2013;2013:489194.
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Khoury MJ. Population study of congenital hypothy- form reduction of macroglossia. Br J Plast Surg.
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J.  Congenital hypothyroidism detected by neona- 43. Gail Demako B. Oral appliance treatment in a patient
tal screening: relationship between biochemical with down syndrome. J Dental Sleep Med. 2014;1:2.
 Midline and Lateral Cysts
and Sinuses of the Neck 8
Francesco Fascetti-Leon and Piergiorgio Gamba

8.1 Midline Cervical Swellings series. Its clinical presentation is rare in neonatal
age. Half of the thyroglossal cysts are diagnosed
Thyroglossal cyst (TC) is the remnant of the thy- and treated within 20 years of age.
roglossal duct. The duct goes from the foramen The cyst normally presents as an incidentally
cecum in the dorsal aspect of the tongue to the noticed asymptomatic soft mass. A small num-
pyramidal lobe to the thyroid gland. The first ber will present as an abscess or intermittently
description dates back to 1723 when Vater named draining sinus because of spontaneous rupture
it lingual duct [1–4]. due to infection. Surgical incision and drainage
Embryology of the thyroid gland sees the can be the temporizing maneuver in these
development of a diverticulum moving caudally situations.
after the tongue formation between the fourth The physical examination demonstrates a
and seventh week of gestation. The primitive thy- midline swelling, elastic at the palpation and
roid comes from the fourth and fifth branchial following the hyoid bone during swallow
pouch. The descent along the neck occurs at the movements.
same time with the formation of hyoid bone from Ultrasound of the neck can help the diagno-
the second branchial arch. The duct loops inferi- sis and is mandatory to confirm a normally
orly and posteriorly around the bone before con- formed thyroid gland. The most common dif-
tinuing its descent anterior to the thyrohyoid ferential diagnoses are dermoid cyst, lymph
membrane. A remnant of the tract may persist as node, isthmic thyroid adenomas, thyroid carci-
a pyramidal lobe in 50% of people. noma, ectopic thyroid gland, and lipomas
The thyroglossal tract does not regress com- (Table 8.1).
pletely in 7% of the adult population.
A cystic lesion may form at any point along
this residual tract. Table 8.1  Main diagnosis of cervical swellings
The thyroglossal cyst is the most common Lateral Midline
cause of midline cervical swelling in childhood Lymph node Lymph node
accounting for about 70–75% in most reported Neurogenic tumors Dermoid cyst
Vascular tumors Ectopic salivary glands
Parotid and salivary gland Thyroglossal cyst
F. Fascetti-Leon · P. Gamba (*) enlargement
Pediatric Surgery, Department of Women’s and Branchial cyst Ectopic thyroid
Children’s Health, University of Padova, Soft tissue sarcomas Ectopic thymus
Padova, Italy
Teratomas
e-mail: [email protected]; piergiorgio.
[email protected] Lymphangiomas

© Springer Nature Switzerland AG 2019 111

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_8
112 F. Fascetti-Leon and P. Gamba

Fig. 8.2  Thyroglossal cyst in neonatal presentation as a

Fig. 8.1  Thyroglossal cyst in common location and mar- cyst at the level of foramen cecum. Endoscopic view of
gin of resection (interrupted lines) in Sistrunk modified the cyst and laser probe applied for marsupialization.
operation Picture kindly given by Dr. Manuelli, ENT Department,
Azienda Ospedaliera Università, Padova, Italy

Rarely CT scan or MRI is needed to confirm

the diagnosis. Fine needle ago-biopsy can be 8.2  ateral Cysts and Sinus
L
used to differentiate TC from dermoid or lymph of the Neck
nodes [3, 4].
Risk of infections and tumor degeneration are Branchial remnants (cysts and sinuses) represent
main indications for surgical excision [5, 6]. The 24% of congenital neck lesions.
modified Sistrunk technique is the most used From fourth to eighth gestational week, the
approach (Fig. 8.1). It involves the removal of the mesoderm of the cranial part of the embryos forms
cyst, the central segment of the hyoid bone, and branchial arches. The arches are ectoderm-­ lined
the tract of muscle tissue ending at the foramen externally and endoderm-lined internally. The exter-
cecum. Palpating the base of the tongue from the nal layer forms cleft, while the internal pouches.
mouth can help the surgeon to determine the end Arches and clefts are four (the fourth is double).
of dissection [7]. First and second arches grow considerably, while
The presentation in the neonatal period is third and fourth deep into the embryo wall (Fig. 8.3).
extremely rare. Most of the reported TCs diag- If cleft and pouches fail obliterating, fistulas
nosed at this age are localized in the upper end of or cyst communicating with skin and mucosa can
the tract. One to eight of the TCs are “lingual” occur (Table 8.2). The majority of the lateral fis-
(Fig. 8.2). tulas and cysts of the neck are originating from
In these cases the clinical presentation in new- the second branchial arch (90%).
borns differs from that observed in children or This distribution differs in Asian population,
adults, as lingual TCs usually cause respiratory where incidence of third and fourth arch fistulas
distress due to upper airway obstruction. These has been reported in more than 50% of cases.
infants present with stridor. Direct laryngoscopy in Lesions are left-sided in more than 90% of
the operating room demonstrates a bulging mass at patients; bilateral lesions account for 1%.
the base of the tongue. CT of the neck is useful for The opening of the fistula at the level of the
the etiological work-up. Endoscopic treatment by skin can indicate its origin and internal ending
aspirating the cyst content can acutely resolve the (Fig. 8.4).
symptoms. Endoscopic marsupialization in this Fistulas of the third and fourth branchial arch
case can be the definitive treatment [8–10]. are often difficult to distinguish on the base of
Differential diagnosis with other cervical surgical findings in regard to relationship with
swellings is reported in Table 8.1. ­laryngeal nerve. They should be treated as a sin-
8  Midline and Lateral Cysts and Sinuses of the Neck 113

A
A
B

B
C

D
E C

Fig. 8.4  Skin opening helps predicting the origin of the

Fig. 8.3 Embryo and branchial structures. (A)
tract. Common sites of branchial fistulas opening. (A) first
Mandibular process; (B) first branchial clefts; (C) second
branchial fistula; (B) second branchial fistula; (C) third to
branchial clefts; (D) third branchial cleft; (E) fourth bran-
fourth branchial fistula
chial cleft

Table 8.2  Structure originating from the arches and Fistulectomy is the most used treatment in
possible fistula openings particular for the first branchial arch remnant.
First arch Jaws, cheek, lateral Fistula opening For the second to the fourth arch fistulas, the
portion of upper lip, into the ear canal
endoscopic treatment has gained popularity in
helix, tragus, middle and middle ear
ear, eustachian tube, particular for third and fourth. Endoscopic assis-
mastoid cells, ear tance may be helpful by injecting methylene
canal, tympanic blue via rigid scope into the pharyngeal fistula
membrane
opening.
Second arch Antitragus, anthelix, Fistula opening
small wing of the into the tonsillar Large masses often require cervical open
hyoid bone, pharynx fossa access for excision. For fistulas of the pyriform
Third and Wings of the hyoid Fistula opening sinus, endoscopic CO2 laser cauterization has
fourth arche bone, thymus and into the pyriform been proposed with acceptable relapse rate. The
the inferior sinus (third at
endoscopic treatment can be repeated in those
parathyroid (third), the cranial end,
superior parathyroid fourth at the cases. Endoscopic assessment is advisable in all
(fourth) apex-caudal end) cases of relapse after excision of fistula tract from
the lateral cervical skin.
Transitory facial paralysis occurs after exci-
gle entity as a “pyriform sinus fistulas.” Pyriform sion of first arch fistulas in 6% of cases. Transient
sinus fistulas can have a neonatal or childhood recurrent laryngeal nerve injury has been reported
presentation. In the first group, the patient may with the same rate in cases of third and fourth
manifest respiratory distress due to large cervical arch remnant [11–14].
mass compressing or deviating the larynx and
trachea, while the second group tends to present
with cervical infections.
CT scan or MRI are used to clarify the diagno-
References
sis in the majority of cases. Contrasting the fis- 1. Smith CD. Cysts and sinuses of the neck. In: O’Neill
tula prior to scan is rarely helpful due to the JA, et al., editors. Pediatric surgery. 5th ed. St Louis,
edema that closes the lumen. MO: Mosby; 1998. p. 757–71.
114 F. Fascetti-Leon and P. Gamba

2. Spitz L.  Thyroglossal cyst and fistula. In: Spitz L, 9. Kuint J, Horowitz Z, Kugel C. Laryngeal obstruction
et  al., editors. Operative pediatric surgery. 6th ed. caused by thyroglossal duct cyst presenting at birth.
London: Hodder Arnold; 2006. p. 53–8. Am J Perinatol. 1997;176:1193–6.
3. Hollwarth ME.  Thyroglossal duct cyst. In: Puri P, 10. Byard RW, Bourne AJ, Silver MM.  The associa-

et al., editors. Pediatric surgery, Springer atlas series. tion of lingual thyroglossal duct remnants with sud-
Berlin: Springer; 2006. p. 3–6. den death in infancy. Int J Pediatr Otorhinolaryngol.
4. Geller KA, Cohen D, Koempel JA. Thyroglossal duct 1990;20:107–12.
cyst and sinuses: a 20-year Los Angeles experience 11.
Leboulanger N, Ruellan K, Nevoux J,
and lessons learned. Int J Pediatr Otorhinolaryngol. Pezzettigotta S, Denoyelle F, Roger G, Garabedian
2014;78:264–7. E-N.  Neonatal vs delayed-onset fourth branchial
5. Vassilatou E, Proikas K, Margari N, Papadimitriou pouch anomalies. Arch Otolaryngol Head Neck
N, Hadjidakis D, Dimitriadis G. An adolescent with Surg. 2010;136:885.
a rare midline neck tumor. J Pediatr Hematol Oncol. 12. Li W, Xu H, Zhao L, Li X.  Branchial anomalies in
2014;36:407–9. children: a report of 105 surgical cases. Int J Pediatr
6. Proia G, Bianciardi Valassina MF, Palmieri G, Zama Otorhinolaryngol. 2018;104:14–8.
M.  Papillary carcinoma on a thyroglossal duct cyst: 13. James A, Stewart C, Warrick P, Tzifa C, Forte

diagnostic problems and therapeutic dilemma. A case V. Branchial sinus of the piriform fossa: reappraisal of
report. Acta Otorhinolaryngol Ital. 2014;34(3):215–7. third and fourth branchial anomalies. Laryngoscope.
7. Sistrunk WE.  Technique of removal of cysts and 2007;117:1920–4.
sinuses of the thyroglossal duct. Surg Gynecol Obstet. 14. Garrel R, Jouzdani E, Gardiner Q, Makeieff M,

1928;46:109–12. Mondain M, Hagen P, Crampette L, Guerrier
8. Diaz MC, Stormorken A, Christopher NC.  A thyro- B.  Fourth branchial pouch sinus: from diagno-
glossal duct cyst causing apnea and cyanosis in a neo- sis to treatment. Otolaryngol Head Neck Surg.
nate. Pediatr Emerg Care. 2005;21:35–7. 2006;134:157–63.
Part III
Chest
 Congenital Thoracic Deformities
9
Giovanna Riccipetitoni, Sara Costanzo,
and Francesca Destro

9.1 Introduction mately during the 6th month of gestation. It

and Classification occurs in isolated centers starting in the manu-
brium, subsequently in the middle body during
Congenital deformities of the chest wall or chest the 7th month, and finally in the lower body dur-
wall malformations (CWMs) comprise a com- ing the first postnatal year. The xiphoid process
plex spectrum of anomalies which range from will undergo ossification between the 5th and
those that do not impact on the health and quality 18th years of life, and the multiple ossification
of life of the patient to those which are life- centers do not coalesce until after puberty.
threatening [1–3]. Thoracic deformities may also be acquired,
CWM occurs when there is anomalous skele- established postnatally as secondary to other con-
tal development and/or formation of the thoracic ditions that disrupt the thoracic wall. Acquired
cavity. The formation of the thoracic cavity chest wall deformities typically follow prior
occurs after the intraembryonic cavity has formed chest surgery (e.g., costal fusions caused by tho-
(around the 4th week of gestation). At the begin- racotomies carried out in any period of child-
ning of the 5th week of gestation, the lung buds hood, sternal diastasis secondary to an infection
rapidly grow caudally and laterally at the pericar- of a sternotomy wound) or a posterolateral dia-
dioperitoneal canals inducing development of the phragmatic hernia repair (Bochdalek) or spine
thoracic wall and pleuropericardial membranes. deformities (i.e., kyphoscoliosis, hemivertebrae,
The sternum also develops during the 6th week of wedge vertebrae, defects of vertebral segmenta-
gestation. The complex development of the ster- tion). Secondary CWM may also follow fetal
num can be simplified into three stages: forma- procedures carried out for congenital pulmonary
tion, chondrification, and ossification [4]. malformations, such as thoracentesis or thoraco-­
Formation begins with the condensed mesen- amniotic shunt [5].
chyme where paired parallel mesenchymal bands Chest wall can be markedly deformed, by
migrate from the lateral plates and fuse in the various degrees of anteroposterior flattening, in
midline by the 10th week of gestation. patients affected by bronchopulmonary dyspla-
Chondrification begins immediately once the sia (BPD), a common complication of preterm
sternal plates fuse. Ossification begins approxi- birth (Fig. 9.1). The reason of this phenomenon
is not completely explained, although the combi-
nation of many factors, such as the long-standing
G. Riccipetitoni (*) · S. Costanzo · F. Destro lung function abnormalities, the presence of
Pediatric Surgery Department, Ospedale dei Bambini
V. Buzzi, Milano, Italy
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 117

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_9
118 G. Riccipetitoni et al.

Table 9.1 Acastello classification of chest wall

malformations
Type I Cartilaginous Pectus excavatum
anomalies Pectus carinatum
Type II Costal anomalies Simple
Complex
Syndromic (always
complex)
Type III Chondrocostal Poland syndrome
anomalies Thoracopagus
conjoined twins
Type IV Sternal anomalies Sternal cleft
Type V Clavicle-scapular Clavicular
anomalies Scapular
Combined
Fig. 9.1  Unilateral costal deformity in an ex-preterm
child with bronchopulmonary dysplasia
the presence of hypoplasia or aplasia of one fore-
demineralized and sometimes fractured ribs, and arm or one hand in Poland’s syndrome or the
chronic sternal retraction, which is common in visualization of an ectopic heart in sternal anom-
­respiratory distress of any cause in infants, may alies [10–12].
contribute to chest flattening [6, 7]. A detailed evaluation is required for each CWM
A straightforward and complete classification patient that comes to the medical attention [13]. It
of CWM was proposed by Eduardo Acastello in should start with an interrogation about personal
2006, distinguishing CWM into five types, and family history, since familial cases can be
according to the origin of the anomaly [8, 9] detected in up to 30% of patients. Great relevance
(Table 9.1): has to be paid to the presence of associated malfor-
mations, which can affect vital organs (e.g., heart
1. Cartilaginous and lungs) and might allow to diagnose a syn-
2. Costal dromic form (Marfan, prune belly, etc.). The
3. Chondrocostal moment of detection, its evolution, and possible
4. Sternal related symptoms must be always documented.
5. Clavicle-scapular The physical examination of the patient has to
be accurate. Inspection in the different positions
It is difficult to accurately determine the over- (standing, in front and lateral view, in dorsal
all incidence of CWM.  This is due to multiple decubitus) will provide the most relevant data, in
factors, among which their broad spectrum and order to classify the type of deformity, its sym-
the poor record of some mild deformities which metry or asymmetry, the degree of alteration
do not even come to the medical attention. (mild, moderate, or severe), functional compro-
However, the specific incidence of the majority mise, secondary deformities (kyphosis, scolio-
of them is clearly established in the published lit- sis), and postural defects (scoliotic attitude).
erature and will be detailed in the subsequent The determination of thoracic measurements
analysis of each malformation. Type I deformi- has a fundamental value in standardizing medical
ties are the most frequent, comprising more than observations. The thoracic measurements to be
90% of the entire spectrum. evaluated are:
CWMs are rarely diagnosed prenatally. Three-­
dimensional ultrasound offers a way to visualize 1 . Thoracic circumference: measured during
fetal skeletal dysplasias such as Jeune syndrome. expiration on a line that crosses the nipples on
Other CWM can be indirectly suspected on the the anterior aspect of the thorax and just below
basis of other anomalies detected, for example, the scapular angles in the posterior region.
9  Congenital Thoracic Deformities 119

2. Intermamillary distance: it measures the dis- 9.2 Pectus Excavatum

tance between the two nipples and the dis-
tance from the half-sternal line to each nipple Pectus excavatum (PE), also termed funnel chest,
separately and serves to assess the symmetry is characterized by the presence of a variably
or asymmetry of the chest. deep sternal depression associated with a malfor-
3. Thoracic index: it is the ratio between the mation of the lowest chondrosternal joints. PE is
anteroposterior and the lateral diameters of the most frequent thoracic malformation, with an
the thorax (measured at the level of the nip- incidence of 1/100–1/1000 live births, and
ples) multiplied by 100. accounts for around the 90% of all CWMs. It
occurs more frequently in males than females by
Imaging studies are necessary to complete the a 5:1 to a 3:1 ratio. About 95% of cases occur in
diagnostic work-up [14]. Chest radiograph in Caucasian patients, whereas Asian, African
double view (front and profile) can provide basic American, and Hispanic patients represent only
information about the type and the degree of the minority of PE cases. PE is most often con-
alteration and changes produced; it can identify, genital and noted in the first year of life (86%)
for example, the form of dysmorphic ribs or alter- (Figs. 9.2 and 9.3), while in the remaining cases,
ations in the shape of the thoracic cage; it is also it appears later during development; in this last
useful for long-term postoperative follow-up. group of patients, there is a frequent association
Second-level imaging techniques, such as com- with malformations of the muscular connective
puted tomography with or without three-dimen- tissue, such as Marfan and Ehlers-Danlos syn-
sional reconstruction or magnetic resonance drome. Cases of spontaneous resolution during
imaging, are usually indicated to better define the growth are very uncommon, and the more typical
anatomy of the malformation. course is worsening of the depression, either
The level of cardiopulmonary impact of each gradual or more dramatic during phases of rapid
malformation is variable and depends on the vertical growth and puberty.
particular characteristics of each pathology.
Every patient with a CWM should undergo car-
diac evaluation, comprising at least electrocar- 9.2.1 Etiopathogenesis
diographic exam and cardiac ultrasound; the
specialist will determine the following steps, The etiology of PE is not clear, and many hypoth-
after evaluating the presence of congenital heart eses have been proposed. The overgrowth of cos-
diseases and their possible functional tal cartilages could be the pathogenetic
repercussion. mechanism leading to the development of
A pulmonology evaluation has to be always PE. Another mechanism proposed is an abnormal
requested, although a proper respiratory func- tethering of the sternum to the diaphragm poste-
tional assessment is usually not feasible before riorly. This theory is supported by a 33% inci-
3 years of age. dence of acquired PE in patients after repair of
The orthopedic evaluation completes the posterolateral congenital diaphragmatic hernias
assessment of CWM children, given the high (Bochdalek). Collagen type II disorders have
incidence of other skeletal anomalies, such as been demonstrated in the costal cartilages in PE,
congenital scoliosis and vertebral deformities, in as well as overexpression or downregulations of
this group of patients. some genes playing a role in the metabolism of
With regard to treatment, not all CW malfor- cartilage and connective tissues, as collagen
mations require surgical correction. Each pathol- genes, matrix metalloproteinases, tumor necrosis
ogy presents its particular indications to factor-alpha, and filamin [16, 17]. Although there
treatment, and it is fundamental to identify the is no confirmed chromosomal abnormality, there
right timing for it, to achieve the best esthetic and is a genetic predisposition supported by a familial
functional results [15]. recurrence in up to 40% of the cases [18]; more
120 G. Riccipetitoni et al.

Fig. 9.2  Neonate with

pectus excavatum
[Courtesy by Dr. Michele
Torre, G. Gaslini
Children’s Hospital,
Genoa, Italy]

CT and MRI scans often demonstrate a leftward

displacement of the heart and a compression of
the right ventricle or atrium, deformed by the
rotation and posterior displacement of the ster-
num, with different degrees of dysfunction on the
echocardiogram. Mitral valve prolapse and mitral
valve regurgitation are frequent, due to the defor-
mation of the mitral valve annulus [20].
Pulmonary function tests (PFT) can be
altered, more on stress conditions than on rest
[21]. The most common pattern of PE is a restric-
tive one, but also obstructive or mixed patterns
are not uncommon. A possible explanation for
ease of fatigability in PE patients can be a less
Fig. 9.3  Infant with pectus excavatum [Courtesy by Dr. efficient mechanism of breathing [22, 23]. Using
Michele Torre, G.  Gaslini Children’s Hospital, Genoa, motion analysis technology, PE patients were
Italy] determined to have significantly impaired chest
wall motion at the area of the pectus defect and
rarely we can observe the presence of other increased abdominal contributions to respiratory
CWM (such as PC) in a PE family. Four different activity [24]. Other studies support the theory
possible patterns of inheritance have been sug- that exercise capacity is limited as a result of
gested: autosomal dominant, autosomal reces- reduced filling of the right heart by the compres-
sive, X-linked recessive, and complex. sive effects of PE.
PE can be observed in some neonates with
congenital diaphragmatic hernia or children with
9.2.2 Pathophysiology respiratory obstruction (bronchomalacia, hyper-
trophic tonsils). These particular cases of PE are
In cases of severe malformations, there can be the only ones that can improve during infancy.
physiological repercussions. Many studies have PE is otherwise usually mild at birth and pro-
tried to elucidate the implications of PE on the gresses over the years, especially during preado-
respiratory and cardiac function [19]. Thoracic lescent and adolescent age.
9  Congenital Thoracic Deformities 121

9.2.3 Clinical Evaluation –– Photographic documentation with different

angles (frontal, left and right lateral, left and
A complete history has to be collected, including right oblique) is very helpful for the follow-up
questions regarding onset and progression of of these patients.
chest wall deformity and investigating the possi-
ble presence of symptoms, associated conditions, A thorough chest and cardiac physical exam
and familial cases. Most young children with PE completes the first part of the evaluation of these
are asymptomatic, but, as they become more children [27].
active, particularly in their pre- and early teenage
years, exercise intolerance and lack of endurance
can appear. 9.2.4 Tests and Imaging
The morphology of the PE should be described
in detail [25, 26]. The deformity may be described CT or MRI of the chest, PFT, and cardiac evalua-
as symmetric or asymmetric; asymmetry is often tion including electrocardiogram and echocar-
associated with sternal rotation that has to be diogram are a routine part of the evaluation for a
underlined too. patient with PE [28].
PE can be morphologically classified as There are several numeric indexes, usually
follows: calculated on CT and MRI, that have been devel-
oped over time to help quantify the severity of PE
–– Grand Canyon: It is a severe form of PE, with [29–31]. The most relevant are:
a deep long canal in the sternum, which is usu-
ally extremely rotated. This type is often • Haller index (HI): described in 1987 by
asymmetric. J. Haller et al., [32] it is calculated dividing the
–– Punch or cup shape: Localized deformity, usu- transverse maximum diameter of the rib cage
ally on the inferior part of the sternum. It is by the anteroposterior diameter at the deepest
more often symmetric. It has been observed point of the deformity. The cutoff point for PE
that the punch type is the most common vari- patients is >3.25.
ant of PE (67%), more commonly symmetri- • Sternal depression index (SDI): it is the ratio
cal (80%), to the right of the midline (80%), between the maximal internal sagittal diame-
and involving the lower sternum (99%). ter of the left side of the chest and the minimal
–– Saucer shape: It is a diffuse depression involv- distance between the anterior surface of the
ing the complete anterior chest, where the tho- vertebral column and the posterior border of
rax is usually quite flat. It can be symmetric or the deepest portion of the sternum. An SDI of
asymmetric. <2.4 is associated with mild sternal deformity,
–– Transversal PE: The depression is transversal moderate sterna deformity is associated with
and below the sternum. an SDI of 2.4–2.9, and an SDI of >2.9 is con-
–– Eccentric PE: The sternal depression is eccen- clusive of severe sternal deformity.
tric to the midline. It is the highest degree of • Asymmetry index (AI): it is the ratio between
asymmetric PE. the anteroposterior diameter of the right and
–– PE with flaring chest: The lower ribs are flar- the left part of the rib cage, multiplied by 100.
ing at each side of the depressed sternum. Chest wall is considered asymmetric if AI is
–– PE-PC: It is a combined malformation with a <−0.05 or >0.05.
sunken chest and unilateral or bilateral pro- • Others: correction index (CI), eccentricity
trusion of the cartilages beside the sternum index (EI), and others.
edge.
–– Superior PE: Very rare PE, localized in the PE causes displacement of the heart into the
upper part of the sternum; lower sternum is left hemithorax. In order to measure the extent of
normal. cardiac compression, specific indexes, calculated
122 G. Riccipetitoni et al.

on CT or MRI, have been calculated, such as the predominance (4:1). Most cases of PC are spo-
cardiac compression index (CCI) and the cardiac radic; however, familial incidence has been
asymmetry index (CAI). reported in about 26% of cases; in some families,
it is possible to observe both PC and PE cases.

9.2.5 Management
9.3.1 Etiopathogenesis
The optimal age for repair is 10–14  years old
because at this time the rib cage is more mallea- The etiology is unknown, although the origin of
ble, thus allowing for rapid recovery, better PC is considered to be similar to that of PE,
results, and a lower recurrence rate as the bar related to abnormalities of connective tissue
remains in place during musculoskeletal matura- development, giving its frequent association with
tion [33, 34]. Fixing PE in the first years of life is other skeletal abnormalities such as scoliosis
probably unnecessary, and it could carry the risk (12%), and some genetic predisposition.
of relapse or postoperative severe complications PC can be either an isolated condition or part
as acquired Jeune syndrome [35]. of a syndrome (i.e., Poland syndrome) or connec-
tive tissue disorder.

9.3 Pectus Carinatum

9.3.2 Classification
Pectus carinatum (PC) is a protrusion of the ster-
num and chondrocostal joints (Fig. 9.4). It is the PC can be classified into the following types:
second most common CWM, and its incidence is
estimated to be five times less frequent than PE in –– Type 1, inferior or chondrogladiolar: It is the
North America, although in other countries, it is most frequent type; the protrusion is located in
much more common, for example, in Argentina, the inferior sternum, with maximum prominence
where it has been reported to comprise 55% of at the sterno-xiphoidal junction, which can be
chest wall deformities. There is a strong male very noticeable (“pyramidal” or “keel chest”); it

Fig. 9.4  Asymmetric pectus carinatum in frontal and lateral view

9  Congenital Thoracic Deformities 123

is usually symmetric. This type of PC can be PE. Only the variant “pouter pigeon breast” can
associated with lateral depressions of the ribs. be associated with congenital heart disease in
–– Type 2, superior or chondromanubrial: The pro- 18% of cases.
trusion is localized above the intermammary Imaging studies include posteroanterior and lat-
line. A variant of this form is called Currarino-­ eral chest radiographs, although CT scan remains
Silverman syndrome or pouter pigeon breast, the gold standard radiologic evaluation for
characterized by a high symmetric carinatum PC. Some radiological indexes, measurable on CT
chest deformity with a short thick sternum with scan, have been proposed, but in clinical practice,
a depression in the lower third [36]. Its aspect is they are less used than those calculated for PE.
of a superior PC with an inferior PE, and the
sternum is typically S-shaped on a lateral view.
9.3.4 Management
A rarer form called lateral PC has also been
described: always asymmetric by definition, it PC is usually not treated during the first years of
consists in the protrusion of some costal carti- life. Its management, either conservative through
lages, besides the chondrosternal joints, on one an orthotic brace system [37, 38] or surgical
side, with often concomitant rotation of the ster- with different techniques [39], is deferred until at
num (30–60–90°) toward the opposite side. least preschool age or early teenage years,
respectively.

9.3.3 Clinical Presentation

and Imaging 9.4 Costal Anomalies

In contrast to PE, PC usually appears later in life. Costal anomalies represent the 3.2% of thoracic
Only about one-sixth of the patients show a wall malformations. They are divided into simple
carinate deformity within the first year of life, and complex.
while in almost half of them, PC is diagnosed Simple malformations involve one or two ribs,
noted during prepuberty or puberty. The defor- up to three nonconsecutive ones, with isolated
mity, which may be mild at birth, often worsens malformations. The effects on the thoracic cage
rapidly during the growth spurt. are limited.
Most PC patients are asymptomatic, although Complex malformations compromise large
those affected by a severe anomaly may complain sections of thorax affecting the respiratory
of some degree of thoracic pain. Cardiac and pul- dynamic.
monary functions are usually less affected than in Ulterior division is shown in Table 9.2.

Table 9.2  Classification and frequency of costal anomalies

Costal anomalies Simple Unique (45.3%) Agenesis
Hypoplasia
Supernumerary
Bifid
Fusion
Dysmorphic
Double (2.6%)
Combined (10.7%)
Complex Strange (5.5%)
Fusions (29.4%)
Syndromic (6.5%) Jeune
Jarcho-Levin
Cerebrocostomandibular
Others
124 G. Riccipetitoni et al.

9.4.1 Simple Costal Anomalies –– Bifid cost: Bifurcation of the distal end of a rib. It
is uncommon and usually isolated. In most cases
–– Agenesis and costal hypoplasia: They are rare it is a radiological finding. Sometimes there is a
isolated malformations or, more frequently, tumor of the costal wall ad pain in the deformed
part of a syndrome (Poland, trisomy 13, cere- area caused by cartilaginous deformity. Thorax
brocostomandibular). Patients are asymptom- X-ray permits the diagnosis. Surgery is reserved
atic, and the management is conservative with for symptomatic patients (pain) or for esthetic
radiological and clinical evaluation during reasons, and it consists of excision of the bifid
growth. cost together with the altered cartilage.
–– Supernumerary cost: It identifies the presence –– Costal fusion: It is characterized by the union
of more than 24 ribs. The extra rib usually cor- of two ribs and it is usually an incidental find-
responds to the cervical vertebra, and it is ing. Thorax X-ray shows the ribs involved and
rudimentary, unilateral, or bilateral. It is the level of the fusion. When necessary the
uncommon and can be part of a syndrome. evaluation is completed with CT (Fig. 9.5). In
Most patients (70%) are asymptomatic. In the evaluation of patients, it is important to
symptomatic cases, signs and symptoms do detect the presence of malformations, the
not depend on cost size and can be related to ­vertebral fractures, and the degree of scoliosis.
vascular or nervous involvement (pain for The need for surgery is established on the base
arterial spasms and paresthesias). The physi- of the curvature progression.
cal examination shows a tumor in the supra- –– Dysmorphic cost:  Alteration of the costal
clavicular gap. The thorax X-ray confirms the morphology with widening of the anterior end
diagnosis. Asymptomatic patients do not of the costal arch, a spur, or an irregularity of
require treatments. Surgery is performed in the entire costal length. Patients present with a
case of symptoms and consists of resection of small tumor on the anterior or lateral thoracic
the extra rib. wall with localized pain (Fig. 9.5).

a b

Fig. 9.5  Example of costal anomalies: patient with a dysmorphic cost (a) and 3D CT reconstruction of costal fusions
(b) [Courtesy by Dr. Michele Torre, G. Gaslini Children’s Hospital, Genoa, Italy]
9  Congenital Thoracic Deformities 125

9.4.2 Double Costal Anomalies permits to identify location and features of

the malformation. It is important to evaluate
Double malformations include two unique mal- the spine praecox. Surgery is indicated in
formations homolateral or contralateral. In case case of severe scoliosis or other
of agenesis of two ribs, there is a paradoxical deformities.
mechanism during breathing with symptoms
onset. Clinical evaluation together with thorax
X-ray during growth spur is important during 9.4.4 Syndromic Costal Anomalies
follow-up. Surgery consists of rib spit and place-
ment of autologous costal graft/prosthetic mesh In this group the costal anomaly is part of a spe-
and muscular flap. cific syndrome.

9.4.4.1 Jeune Syndrome

9.4.3 Complex Costal Anomalies It is also known as asphyxiating thoracic dystro-
phy, a congenital malformation (autosomal reces-
–– Strange malformations:  Malformations that sive inheritance) with small thorax, short limbs,
do not follow a specific pattern are defined and pelvic dysplasia. Fortunately many children
strange. They are extremely rare and each do not develop respiratory asphyxia and survive
patient corresponds to a unique case. We can the neonatal period.
have costal hypoplasia, fusion, or intercostal The incidence is 1/100.000–130.000 without
space widening with lung hernia. The right sexual preponderance.
side is affected more than the left one. Patients present with narrow bell-shaped tho-
Hydrocephalus and myelomeningocele are rax and prominent abdomen (Fig.  9.6); ribs are
identified in 55% of cases. Clinical manifesta- short, and costochondral junctions do not pass
tions depend on the extent of the deformity. the anterior axillary lines. Costal cartilages have
Children with severe deformity change their a rosary shape and clavicles are fix and horizon-
anatomical thoracic configuration with risk of tals. This reduces the respiratory movements and
constrictive thoracic disease. The involvement leads to an abdominal/diaphragmatic respiration.
of cardiopulmonary function is always possi- Hypoventilation causes hypoxia and respiratory
ble. Neonates may have respiratory distress distress. The severity is variable and sometimes it
requiring mechanical ventilation. After this causes neonatal demise.
period, symptoms arise during breast-feeding,
and they are related to the presence of pulmo-
nary sequelae (dysplasia). A small number of
patients are asymptomatic, but the thorax is
always abnormal. Thorax X-ray identifies the
degree of parietal alteration. The spine should
be investigated, as well. When required, sur-
gery consists of costal block removal.
–– Costal fusion:  Costal fusion is a congenital
malformation characterized by the union of
three or more ribs in any spinal segment. It
may cause varying degrees of deformity on
the chest wall or spine. It is rare and associ-
ated to vertebral anomalies in 90% of cases.
The thoracic deformity may be evident soon
Fig. 9.6  Neonate with Jeune syndrome [Courtesy by Dr.
after birth. Restrictive respiratory symptoms Michele Torre, G.  Gaslini Children’s Hospital, Genoa,
are typical of older patients. Thorax X-ray Italy]
126 G. Riccipetitoni et al.

Renal and hepatic alterations are common: The aim is to enlarge the thoracic cavity with
progressive nephropathy from the second year median sternotomy and to keep the two sternal
of age due to glomerular sclerosis or tubular segments open with different rigid material. The
cystic dysplasia and hepatic fibrosis or cirrhosis sternotomy is performed in the neonatal period
for ductal anomalies. Pancreatic cysts are rare. and the defect is closed with a prosthetic patch.
The pelvis is small and radiological abnormali- Once patients are stable (infancy), the patch is
ties tend to decrease during growth. In neonates replaced by homologous grafts. Grafts include
there is a praecox ossification of femoral head methyl methacrylate and bone grafts. Titanium
and other bones resulting in growth retardation. patches have been used for staged procedures.
Congenital heart disease, retinal degeneration, Vertical expandable titanium rib (VEPTR)
and dolichocephaly are less frequent improves chest wall movements: they are attached
associations. to the ribs and to transverse spinal processes and
Two forms are identified based on the clinical progressively lengthened. The procedure may
picture. lead to scoliosis and patients require long-term
follow-up (Fig. 9.7).
Type I, Major Form (70%) Despite the immediate relief from symptoms,
The major form includes patients with small, surgery doesn’t seem to affect long-term results
rigid, and narrow thorax and abdominal respira- and mortality. The only improvement is prenatal
tion. In these cases, respiratory symptoms have ultrasound diagnosis that allows for consultation
early onset (severe neonatal distress), and patients and leads to an increment of pregnancy
require mechanical ventilation soon after birth. termination.
Mortality is high in the first year of age. Together
with ventilator support, patients need surgery to Type II, Minor Form (30%)
enlarge the thorax increasing the lung capacity. In these patients costal malformations are inter-
The correction should be praecox to avoid long mediate and symptoms are limited or absent.
mechanical support and improve survival. Radiological abnormalities tend to reduce over
Primary and stage repairs have been described time. Physical examination is sufficient to sus-
starting from the first months of life. Among the pect the syndrome. Thorax X-ray shows the small
surgical options, there is the median sternotomy and narrow thoracic cage with bell-shaped con-
with bone graft or prosthetic patch interposition. figuration. Ribs and clavicles are horizontals. The

Fig. 9.7  Jeune syndrome: intra- and postoperative pictures [Courtesy by Dr. Michele Torre, G.  Gaslini Children’s
Hospital, Genoa, Italy]
9  Congenital Thoracic Deformities 127

latter are shaped as bicycle handlebars and are ment. There are only costal vestiges. The typical
high. These alterations are well detected on CT costal anomaly is the aplastic segment at the pos-
scans with 3D reconstruction. Pelvis X-rays show terior costal arch with fibrosis, muscular ele-
small pelvis and irregular acetabular roof (tri- ments, and calcifications. The extension of the
dent). Iliac wings are small and squared. costal defect is variable as it is variable to the
Some authors associate the measure of the number of affected ribs. The thorax is short and
thoracic perimeter with prognosis: a perimeter flat, and the deformity worsens the glossoptosis
<28 cm correlates with bad prognosis. The mea- and the tracheal cartilage hypoplasia. The effect
sure of the thoracic cage might be responsible for is a severe respiratory distress. Forty percent of
pulmonary hypoplasia detected in some patients. patients die within the first months of life.
The clinical spectrum runs from mild to severe Between the survivors, 50% have moderate men-
forms where the rigidity of the chest does not tal retardation. Described associations are verte-
allow proper expansion. bral malformations, scoliosis, feet deformities,
Type 2 form does not always require treat- and hip dislocation.
ments being patients asymptomatic or mildly
affected. 9.4.4.4 Others
Rare type II congenital thoracic deformities
9.4.4.2 Jarcho-Levin Syndrome include deformities that have been described but
It is called costovertebral dysplasia or hemiverte- do not fit in any standard classification. They
bral syndrome, and it is characterized by a short have different features and require personalized
thorax with vertebral and costal abnormalities. treatment and management.
The inheritance is autosomal recessive with mild
male preponderance.
The hemivertebra typically involves all or 9.5 Poland Syndrome
almost all the spine with fusion or absent verte-
bral bodies. Vertebral anomalies deform the tho- Named after Sir Alfred Poland who described it
racic cage and lead the posterior costal arches to in 1841 [40], Poland syndrome (PS) is a rare con-
be fused at the costovertebral junction. Shape and genital anomaly, occurring in 1:20,000–30,000
number of ribs are abnormal. The effect is a short live births. Its main diagnostic criterion is the
and crab-shaped thorax. hypoplasia or agenesis of the pectoralis major
Neonates have respiratory distress that prog- muscle, although its phenotype can be extremely
ress into respiratory failure, and most of them die variable and frequently combined with other ipsi-
within the first year of age. The association with lateral abnormalities of the chest wall, breast, and
congenital heart disease and urological abnor- upper limb. PS is almost always unilateral, right-
malities (hydronephrosis, ureteral and urethral sided in two-thirds of cases; very rare bilateral
stenosis) is frequent. Rarely there are gastrointes- cases have been described [41]. There is a male
tinal malformations. Thorax X-ray shows the preponderance with a 2:1 male to female ratio. It
crab shape due to the short dorsolumbar column. is mainly sporadic, with around 4% of familial
There hasn’t been any attempt of surgical correc- cases described [42].
tion to date.

9.4.4.3 Cerebrocostomandibular 9.5.1 Etiopathogenesis

Syndrome
This syndrome is also called the one with seg- The etiology of PS is unknown. The most accred-
mented rib. It is rare and characterized by micro- ited hypothesis regards a possible interruption of
cephaly, micrognathia, and costal anomalies. The the vascular supply in subclavian and vertebral
type of inheritance has not been defined yet, but arteries during embryonic life, determined by
it is responsible for the altered cartilage develop- both genetic and environmental factors, leading
128 G. Riccipetitoni et al.

to different malformations of the corresponding –– Anomalies of other chest wall muscles:

districts [43]. The occurrence of familial cases Pectoralis minor results to be affected in more
has raised the hypothesis of a possible genetic than 90% of cases in some series; less frequently
etiology with different inheritance patterns, an involvement of serratus anterior, latissimus
although a specific gene has not been identified dorsi, trapezius muscle, rhomboid muscle, and
yet [44]. rectus abdominis can also be detected.
–– Chest wall anomalies: Rib dysmorphisms,
hypoplasia, and agenesis and anomalies like a
9.5.2 Clinical Presentation PE or PC or both can occur; in case of rib
and Assessment agenesis, particularly if multiple (most fre-
quently the third and the fourth ribs), lung her-
PS phenotype is extremely variable. Partial or niation and paradoxical respiratory movements
total deficit of the pectoralis major muscle is can be present.
present in 100% of patients, and the thoracic –– Breast hypoplasia or aplasia: Breast involve-
defect is usually evident at birth (Fig. 9.8a) [10]. ment regards the majority of PS patients, par-
Other clinical features are [45]: ticularly significant in females, and ranges

a b

c d e

Fig. 9.8  Poland syndrome: chest wall asymmetry in a patient with right form (a); CT picture of a right PS (b); postop-
erative pictures of the same patient at long-term follow-up (c, d); brachydactyly in PS (e)
9  Congenital Thoracic Deformities 129

from varying degrees of breast hypoplasia to thoracoabdominal ectopia cordis, and cleft or
complete absence of the breast (amastia) and bifid sternum. The heart is displaced in ectopia
nipple (athelia), usually with hypoplasia of cordis [51].
the subcutaneous tissue of the region
(Fig. 9.8b).
–– Upper limb anomalies [46, 47]: Shortness of 9.6.1 Thoracic Ectopia Cordis
the fingers (brachydactyly) (Fig.  9.8e), joined
fingers (syndactyly), and a combination of both Thoracic ectopia cordis presents with naked
(brachysyndactyly) are frequently seen hand heart (entirely bare heart outside the thorax)
anomalies, although others can be present, and no overlying somatic structures (pericar-
affecting more than half of PS patients. dium, skin, etc.). The heart has an anterior
–– Other skeletal deformities: Scoliosis and other superior apex. Intrinsic cardiac anomalies are
spine deformities, Sprengel deformity (con- frequent. Upper abdominal wall defects
genital elevated small scapula), etc. (omphalocele, diastasis recti, eventration of the
–– Cardiac/renal anomalies: They are uncommon abdominal viscera) might be associated, as
and usually mild. Dextroposition, always well. The sternum may be partially or com-
reported in cases of left PS with rib anomalies, pletely split with the heart protruding through
seems to be caused by mechanical factors dur- the defect. This condition differs from ectopia
ing embryonic life in patients with multiple cordis in which the heart is in an orthotopic
left rib agenesis [48]. intrathoracic position, has a normal anatomy,
–– Other syndromic conditions, such as Moebius and is covered by normal skin.
and Klippel-Feil syndromes, have been The lack of midline somatic tissues and the
reported in association with PS [49]. presence of a small intrathoracic cavity make the
repair difficult with risk of heart failure. The cor-
The extreme variability of the phenotype rection (primary or stage repair) should be per-
imposes a multidisciplinary approach to all chil- formed early in the first days of life. Different
dren with PS.  Diagnostic work-up includes the surgical approaches have been reported including
evaluation of all the organs and systems that can the use of skin flaps, prosthetic meshes, rib grafts,
be affected and should be completed as early as and pectoral muscle flaps. Diaphragmatic mobili-
possible. Conversely, surgical correction is zation and pericardial division from the anterior
almost never necessary in the first years of life; attachments of the chest wall might help in the
nevertheless, since it may require multiple proce- closure. In all successful cases, the creation of a
dures and stages over the years [50] (Fig. 9.8c, d) partial anterior cavity surrounding the heart
(hand surgery, restoration of the structural integ- avoids heart failure. The presence of intrinsic car-
rity of the rib cage, improvement in the appear- diac lesions and associated abdominal defects
ance of the chest, breast implants, etc.), a correct severely affects the prognosis, more than the sur-
information and presentation of all the surgical gical technique chosen for the correction.
possibilities should be early offered to the Postoperative complications include infection
families. and extrusion of the graft.

9.6 Sternal Anomalies 9.6.2 Cervical Ectopia Cordis

Sternal defects are rare and include relatively Cervical ectopia cordis is distinguished from the
benign anomalies, such as the partial sternal thoracic ectopia cordis on the base of the superior
cleft, and major defects resulting in ectopia cor- heart displacement. The heart protrudes at
dis. Four main defects can be identified: cervi- the  base of the neck, and it is often fused with
cal ectopia cordis, thoracic ectopia cordis, the  mouth, and there are many craniofacial
130 G. Riccipetitoni et al.

a­ nomalies or other fetal deformities. The progno-

sis is bad and surgical repair is very difficult.

9.6.3 Thoracoabdominal Ectopia

Cordis

Thoracoabdominal ectopia cordis presents with

heart covered by thin and pigmented skin. It is
associated with sternal cleft. There is no severe
anterior heart rotation seen in thoracic ectopia
cordis, but the heart is displaced within the thorax
with diaphragmatic and pericardial defect below
it or within the abdomen. Described associations
are somatic defects, diaphragmatic anomalies,
intrinsic cardiac malformations, and abdominal
wall defects (omphalocele, diastasis recti). This
ectopia cordis is often part of the Cantrell pental-
ogy (a cleft lower sternum, a half-moon anterior
diaphragmatic defect due to failure of develop-
ment of the septum transversum, absence of the
parietal pericardium, adjacent or completely sep- Fig. 9.9  Newborn with sternal cleft
arate omphalocele, ventral hernia or diastasis
recti, and in most patients a major form of con- Table 9.3  Sternal cleft types and frequency
genital heart disease, most commonly tetralogy Sternal cleft types
of Fallot or diverticulum from the left ventricle). Partial superior form 67%
Surgical correction is possible, and long-term Complete form 19.5%
survival rate is more frequent than that of other Partial inferior form 11%
ectopia cordis. The first step is skin closure to Sternal foramen 2.5%
avoid infections and mediastinitis and omphalo-
cele excision. The correction is required early
with primary closure or prosthetic mesh closure. Sternal clefts are classified into complete or
The rectus muscles are distant with difficulties in partial [52]. The partial form can be superior or
obtaining a good primary closure. inferior: the partial superior SC is usually iso-
lated and relatively easy to repair; the partial infe-
rior SC is often associated with complete sternal
9.6.4 Sternal Cleft or Bifid Sternum fissure resulting in ectopia cordis. Other associ-
ated defects are vascular dysplasia, PHACES
The sternal cleft (SC) is caused by a defect in the syndrome, midline fusion defects, and pentalogy
fusion process of mesenchymal cells that starts at of Cantrell (heart, pericardium, diaphragm, ante-
around the 6th week of gestation. The effect is an rior abdominal wall defects) (Fig. 9.10).
anomaly in which the heart is in the orthotopic PHACE(S) syndrome is a neurocutaneous dis-
position in the thoracic cavity but the sternum is order of unknown etiology. The acronym refers
clef or partially fused over the heart (Fig.  9.9). to the commonest features of PHACE: posterior
The skin coverage is normal and the pericardium fossa malformations, large facial hemangiomas,
is intact. The condition is idiopathic and accounts cerebral arterial anomalies, cardiovascular anom-
for 0.15% of all chest deformities with a female alies, and eye anomalies. When ventral develop-
preponderance (Table 9.3). mental defects such as sternal clefting or
9  Congenital Thoracic Deformities 131

Older patients present respiratory symptoms

such as dyspnea, cough, respiratory distress, and
recurrent respiratory tract infections.
Asymptomatic patients usually have partial defects
Sternal malformation/ PHACES syndrome
Vascular dysplasia and require repair to provide protective coverage
for the heart (high risk of trauma-related injuries).
Several associations are seen, the most com-
STERNAL CLEFT mon being the bandlike scars from the umbili-
cus to the inferior part of the defect
(supraumbilical raphe) that represent only a
cosmetic anomaly, cardiac defects (22%) and
Midline fusion Cantrell’s pentalogy vascular anomalies (9%).
defects Early repair in infancy is important because
the chest is more flexible and primary closure is
the preferred treatment. The primary closure can
be challenging or impossible due to a stiff thorax.
Alternatives include the use of prostheses (pros-
Fig. 9.10  The relationship between sternal cleft and thetic materials such as Gore-Tex or Gore,
other rare syndromes/associations (From Torre et  al.
DualMesh, calcium phosphate cement (Fig. 9.11),
Phenotypic spectrum and management of sternal cleft:
literature review and presentation of a new series. Eur J polyester, or various autologous grafts such as
Cardiothorac Surg. 2012;41(1):4–9) bone graft interposition, muscle flap interposi-
tion), partial or total thymectomy [53], cartilage
resection, sliding chondrotomies, and clavicle
supraumbilical raphe occur, the PHACES acro- dislocation.
nym may be used. The hallmark feature of In most series the primary repair is performed
PHACE is the presence of one or more large within the 3rd month of life. The first year of age
facial infantile hemangiomas that occupy at least is considered a favorable age for repair.
one facial segment. Cerebral vascular anomalies The preoperative evaluation should exclude
are probably the most common extracutaneous associated anomalies that can lead to major com-
feature. Given that several organ systems are plications and should define the thoracic anatomy.
involved, a multidisciplinary approach to disease Some anomalies are evident (maxillofacial heman-
surveillance and treatment is advised. In particu- giomas, cleft lip or palate, pectus excavatum, pre-
lar the assessment of affected babies should cordial skin tags, supraumbilical raphe,
include the endoscopic evaluation of upper air- gastroschisis, connectival nevus of the anterior tho-
ways and cerebral MRI. racic wall). Other defects (cardiac anomalies, aor-
Intrinsic cardiac defects are rare. The presence tic coarctation, eye abnormalities, posterior fossa
of a fusion defect in the middle part of the ster- anomalies, hidden hemangiomas) require investi-
num is called sternal foramen. SC determines gations. Preoperative examinations include the
paradox movements during respiration with risk study of the chest with X-ray and CT (Fig. 9.12)
of mediastinal viscera damage. Therefore the and cardiologic evaluation (electrocardiogram and
correction in neonatal age should be recom- echocardiography). Neuroradiologic imaging and
mended. The difficulty in repairing the defect is ophthalmologic exams are performed in selected
related to the fact that the chest is small and can- cases. Genetic evaluation completes the screening.
not accommodate the heart with the risk of car- Prior to surgery, laryngo-tracheo-bronchoscopy
diovascular failure. might identify subglottic hemangiomas.
Some neonates are asymptomatic but present For surgery, the midline vertical incision
a paradoxical midline thoracic bulging due to the extends from the jugular notch to the end of the
protrusion of viscera during expiration. defect (Fig. 9.11). The dissection proceeds down-
132 G. Riccipetitoni et al.

a c

Fig. 9.11  Sternal cleft (a) repair (c, d) with a prosthesis in calcium phosphate cement (b)

ward to expose the sternal bars. Vertical strap lies have unfavorable events related to the
neck muscles are divided at their insertion on the underlying disease. No recurrences have been
sternal upper margins and the two sternal halves described.
are freed from the underlying pleura and pericar- The required follow-up is a close one since
dium. A U-shaped incision is performed in the patients can develop other congenital wall mal-
inferior part of partial SC to facilitate the closure. formations (e.g., pectus excavatum).
The sternal bars are approximated on the midline
and closed with nonabsorbable sutures when pos-
sible (Fig. 9.13). 9.7 Clavicle-Scapular Anomalies
Reported complications are pericardial or
pleural tears during sternal dissection, retroster- Clavicle-scapular malformations represent 0.5%
nal seromas, and pneumothorax. In females, of all the CWM. They are divided into malforma-
care should be taken not to injure the mammary tions of the clavicle, malformations of the scap-
gland. Patients with severe associated anoma- ula, and combined malformations.
9  Congenital Thoracic Deformities 133

a b

Fig. 9.12 (a) US showing “V-shaped” sternum with proximal diastasis; (b, c) CT evaluation of the sternal deformity:
diastasis of the middle and proximal portion of the sternum, costal hypoplasia

Fig. 9.13  Postoperative pictures after sternal cleft repair with a prosthesis in calcium phosphate cement
134 G. Riccipetitoni et al.

9.7.1 Clavicular Malformations of the thoracic wall. It is more common in women

(4:1 ratio). It occurs sporadically, but an apparent
They originate from alterations in the growth or pattern of autosomal dominant inheritance has
structure of the clavicle that can be aplastic, been sometimes noted. The affected scapula is
hypoplastic, or dysmorphic, on one or both sides. hypoplastic, with decreased vertical diameter and
Clavicular malformations can be isolated (sim- apparent increase of its horizontal width. The
ple) or part of a syndromic association. They usu- muscles connected to the scapula can be altered,
ally cause very little functional alteration, except most commonly the trapezoid, the deltoid, the
when associated with other malformations of the rhomboid, the elevator of the scapula, and the
scapula and/or upper ribs. Several syndromes, serratus anterior, so that the amplitude of shoul-
such as pseudohypoparathyroidism (Albright), der movements may be limited.
Holt-Oram, and Pierre-Marie syndrome, among Scapular malformations can also be part of
others, can present clavicular abnormalities as the Klippel-Feil syndrome, in association with
part of their clinical picture, usually associated anomalies of the cervical spine, a characteristic
with other skeletal deformities. The chest of these short neck with movement limitations, dorsal
children is narrow in its upper part, with decreased and lumbosacral vertebral malformations, anom-
lateral diameter. Functionally, this facilitates the alies of the ribs, malformations of the upper and
realization of atypical movements, such as the lower limbs, and rarely cardiovascular
approximation of the shoulders in front of the malformations.
thorax. The muscles of the area can also be Chest X-ray in front and profile projections
involved, presenting developmental and inser- and CT with 3D reconstruction of the chest wall
tional anomalies. In the neonatal period, respira- are the imaging techniques of choice. MRI is car-
tory disorders can appear due to the narrowness ried out when intramedullary alterations are sus-
of the chest. Chest X-ray shows the absence or pected. Differential diagnosis includes other
hypoplasia of one or both clavicles. Clavicular causes of shoulder asymmetry, such as scoliosis,
malformations can be associated with pectus car- asymmetry of lower limbs, and obstetric paraly-
inatum or excavatum. sis of the brachial plexus.
The goals of surgical treatment are to improve
the function and the esthetic appearance of the
9.7.2 Scapular Malformations shoulder. When indicated, surgery is recom-
mended between 9 and 18 months of life.
These anomalies are characterized by alterations
in development and position of the scapula with
variable joint mobility. The deformities occur at 9.7.3 Combined Malformations
birth and their severity is variable; they are usu-
ally unilateral. They are classified as simple, They are the most frequent variant and are char-
with hypoplastic or winged scapula, or syn- acterized by the association of different types
dromic. Syndromes that favors scapular winging both clavicular and scapular defects. They can be
are, for example, muscular dystrophies or other unilateral or bilateral, and they comprise the sim-
conditions with muscular hypoplasia such as ple subtypes of each group of malformations.
Poland syndrome. It can be associated with PE,
PC, scoliosis, vertebral, and rib deformities.
Sprengel deformity is characterized by an ele- 9.8 Associated Spinal
vated anomalous position of one or both scapu- Deformities
lae, with variable disorders of joint mobility. The
deformity is the result of a failure in the descent The normal development of the vertebral column
of the scapula from its fetal position in the neck includes the longitudinal and axial growth of the
to its normal position on the posteroexternal face vertebrae [54] that requires:
9  Congenital Thoracic Deformities 135

1. The skeletal growth (the growth of the axis for (a) Of the wall: costal resections, costal
muscular development). fusions
2. The symmetrical growth of the spine in the (b) Of the content: retraction after empyema,
longitudinal and axial plane, preventing the pulmonary resections, diaphragmatic palsy
development of deformities (scoliosis). The
scoliosis is the spinal lateral deviation of more Hemivertebra is a type of vertebral anomaly
than 10° with vertebral body rotation. and results from a lack of formation of one half
According to their origin, the scoliosis can be of a vertebral body. It can be a common cause
classified into idiopathic, congenital, neuro- of a congenital scoliosis. The curve progres-
muscular, osteopathic, and neoplastic. sion and the ultimate severity of the curve
3. Protection of neural elements, ensuring that depend on the type of hemivertebrae, the loca-
the child reaches adulthood without neuro- tion, the number of hemivertebrae, and their
logical complications. relationship with each other. It falls under the
4. The development of physiological spinal cur- spectrum of segmentational anomalies and can
vatures, which allow proper balance in the involve one or multiple levels. Recognized
standing position. associations are many and include Aicardi syn-
drome, cleidocranial dysostosis, gastroschisis,
The spine is intimately associated with the Gorlin syndrome, fetal pyelectasis, Jarcho-
thoracic cage and any alteration of these two ele- Levin syndrome, OEIS complex, VACTERL
ments is reflected in the other. Under normal con- association, and mucopolysaccharidosis.
ditions, the development of the thorax is a
dynamic process that involves the sternum, the
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 Mediastinal Masses
10
Mario Lima and Michela Maffi

10.1 Introduction (65–72%) of the illnesses are malignant, and

about 40% of children are under the age of 2. The
The mediastinum is defined as the thoracic region mediastinum can be divided into three compart-
limited by the pleural spaces laterally, the ster- ments: anterior, middle, and posterior. Anterior
num anteriorly, the vertebral column posteriorly, mediastinal tumors account for approximately
the thoracic inlet superiorly, and the diaphragm 46% of mediastinal lesions, neoplastic lesions of
inferiorly. The mediastinum contains different the middle mediastinum account for 20%, and
types of tissue including the thymus gland, part posterior mediastinal tumors account for 34% [1,
of trachea and esophagus, the great vessels, the 8–10].
heart, lymph nodes, fat, and nerves. Mediastinal
masses can derive from each of those tissue and
can be malformative, neoplastic, or infective [1– 10.3 Embryology
5]. Table 10.1 illustrates the different origins of
mediastinal masses. The embryology of the mediastinum is closely
linked to the development of the organs con-
tained within it. In the embryo, the mediasti-
10.2 Incidence num is still not formed, and the chest and the
abdomen are not separated. During the fourth
Congenital mediastinal malformations are rare gestational week, the coelomic cavity becomes
entities, with estimated incidences of 1  in a closed cavity partially separated into two
20,000–30,000 live births [6, 7], while the most parts by the transverse septum. The primitive
common are the masses of neoplastic origin. The pericardial cavity superiorly and the perito-
34% of the mediastinal masses are neurogenic neal cavity inferiorly communicate with each
tumors, followed by lymphomas (24%), foregut other through two wide dorsolateral channels,
malformations (14%), germ cell tumors (11%), called pericardio-­peritoneal canals. At the end
mesenchymal tumors (7%), thymic masses (6%), of the fourth week, the pulmonary buds grow
and vascular anomalies (4%). Mediastinal tumors in the cavity. As the lungs grow, it also
include a wide spectrum of pathologies. Most increases the cavity that contains them that
takes the name of pleural cavity. Initially, the
pleural cavity communicates with both the
M. Lima (*) · M. Maffi pericardial cavity and the peritoneal cavity.
Department of Pediatric Surgery, S.Orsola Hospital,
University of Bologna, Bologna, Italy
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 139

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_10
140 M. Lima and M. Maffi

Table 10.1  Anatomical classification of mediastinal the primitive lungs. The fusion of these folds
masses
occurs at the end of the fifth week and perma-
Anterior mediastinal masses nently separates pericardial cavity from pleu-
Solid lesions ral and peritoneal cavity. The communication
   1.  Normal thymus
between these two cavities remains until the
      (a)  Prominent thymus (pseumass)
seventh week when the diaphragm separates
      (b)  Ectopic thymus
   2.  Thymic hyperplasia the chest from the abdomen. Different malfor-
   3. Thymoma mative frameworks may occur during these
      (a)  Noninvasive thymoma complex phases, while tumors may also result
      (b)  Invasive thymoma from migration alteration of cellular precur-
   4.  Thymic carcinoma sors as in the case of germ cell tumors. These
   5. Lymphoma are derived from precursors of germ cells that
      (a)  Hodgkin lymphoma undergo early differentiation near the region
      (b)  Non-Hodgkin lymphoma of the primitive cephalic pole and migrate to
   6. Teratoma
the lumbar region. During this migration,
Cystic lesions
   1.  Thymic cyst
these elements may prematurely interrupt mat-
   2.  Lymphatic malformation uration and become teratomas.
Fatty lesions
   1. Lipoma
   2. Thymolipoma 10.4 Clinical Implication
Middle mediastinal masses
Vascular lesions Mediastinal masses can cause a wide spectrum of
   1.  Double aortic arch signs and symptoms ranging from being asymp-
   2. Right aortic arch with aberrant left subclavian
tomatic to causing compressive symptoms such
artery
   3. Left aortic arch with aberrant right subclavian artery
as coughing, dyspnea, dysphagia, superior vena
   4.  Pulmonary artery sling cava syndrome, and Claude Bernard-Horner syn-
   5.  Duplicated superior vena cava drome [11].
Nonvascular lesions The severity of symptoms depends on local-
   1.  Congenital foregut duplication cysts ization, structures involved or infiltrated, and size
      (a)  Bronchogenic cyst of the mass.
      (b)  Esophageal duplication cyst In asymptomatic cases, diagnosis is mostly
      (c)  Neurenteric cyst occasional during a radiograph performed for
Lymphadenopathy
other reasons.
   (a) Neoplasm
         •  Primary (i.e., lymphoma)
         •  Metastatic disease
   (b) Infection 10.5 Prenatal and Perinatal
Posterior mediastinal masses Management
Sympathetic ganglion tumors
   1. Neuroblastoma By prenatal screening, many lesions are already
   2. Ganglioneuroblastoma suspected during fetal life. An accurate prenatal
   3. Ganglioneuroma diagnosis can highlight the risk or the presence
Nerve sheath tumors of airway obstruction and allow for taking mea-
   1. Schwannoma
sures during pregnancy or at delivery. A com-
   2. Neurofibroma
   3.  Malignant peripheral nerve sheath tumor
prehensive evaluation includes prenatal
morphology ultrasound to further detect addi-
tional associated abnormalities, karyotype,
During the fifth week, the lateral walls of the echocardiogram, and fetal magnetic resonance
body form the pleuropericardial folds that face imaging (Fig.  10.1). Fetal MRI provides
each other, interposing between the heart and detailed information about the mass and the
10  Mediastinal Masses 141

10.5.1 EXIT Procedure

The ex utero intrapartum therapy procedure aims

to ensure placental uterine flow for a prolonged
period, so that a procedure on the fetus can be
safely performed.
It is a complex procedure involving a multi-
disciplinary team that takes care of the mother
and the fetus at the same time. The procedure
consists of a hysterotomy to allow the delivery of
the upper part of the fetus. During the procedure,
it is essential to maintain the uterine relaxation
that is achieved with tocolytics and inhalation
anesthetics and an adequate uterine volume that
is maintained by continuous replacement of the
amniotic fluid with warmed physiological solu-
tion. Once the patient is partially delivered, an
intravenous access is obtained, and the fetus is
strictly monitored with a pulse oximeter and
echocardiography. The first step is to secure the
Fig. 10.1  Fetal MRI can be useful in evaluation of tho-
racic lesions fetal airway through endotracheal intubation or
tracheostomy if clinically indicated. The range of
procedure that can be performed during an EXIT
entity of the associated obstruction compared procedure includes different maneuvers both
to ultrasound [12]. diagnostic and therapeutic. When the respiratory
Also during pregnancy, mass effect depends and cardiac stability of the fetus have been
on location and size. Compression on the esopha- reached, the delivery is completed.
gus may lead to polyhydramnios; compression Exit procedure was firstly described for air-
on the mediastinal lymphatics, great vessels, and way stabilization in fetuses that had undergone
heart may lead to hydrops, heart failure, and fetal tracheal occlusion for CDH, but currently, any
demise if not treated; compression on lung tissue fetus with a potential airway impairment or car-
may lead to pulmonary hypoplasia and respira- diorespiratory instability at birth can be a candi-
tory failure after birth. date for EXIT procedure [13, 15–18].
Treatment options depend on the nature of
the complication and the age of the fetus at the
time the complication occurs. Early in gestation 10.6 Diagnostic Tools
when a cystic mass is present and causes
hydrops and heart failure, treatment options 10.6.1 Laboratory
include percutaneous decompression or thora-
coamniotic shunt [13]. The laboratory data can help the diagnosis in
Most mediastinal lesions diagnosed prenatally cases of malignancy. In patients with a mass
can be managed after birth; however, if the fetus located in the paravertebral site, it is important to
develops hydrops before viability, prenatal sur- evaluate catecholamine catabolites (homovanillic
gery may be the only option to avoid fetal demise. acid and vanillylmandelic acid) in urine produced
Recently, successes have been reported in the by neurologically active tumors. In case of germ
management of upper airway obstruction in cer- cell tumors, common markers are beta-HCG and
vical teratoma [14]. It is advisable to be cautious, alpha-fetoprotein, which must be interpreted by
but fetal surgery will probably play a role in treat- knowing age-related values as they are normally
ing these patients. elevated in the neonatal age.
142 M. Lima and M. Maffi

10.6.2 Imaging 10.6.2.4 Upper Gastrointestinal Tract

X-Ray
10.6.2.1 Chest X-Ray If an esophageal duplication is suspected, upper
Chest radiographs (frontal and lateral views) are GI tract X-ray highlights the deviations and pos-
usually the first diagnostic imaging for evaluating sible communication between the mass and the
mediastinal masses in infants and children esophagus (Fig. 10.3).
(Fig.  10.2). CXR are sensitive (97–100%) for
detecting mediastinal masses depending on the 10.6.2.5 Computed Tomography
size and location of the mass but has a low diag- CT is the method of choice to permanently char-
nostic specificity (36%). For this reason, addi- acterize a mediastinal lesion (Fig. 10.4).
tional imaging studies (i.e., US, CT, or MRI) are It can provide high diagnostic accuracy (88%)
mandatory in order to further characterize a mass in diagnosing the nature, size, location, and
and narrow the differential diagnosis [1, 19]. involvement of other organs by mediastinal
masses, and it yields additional diagnostic infor-
10.6.2.2 Ultrasounds mation (82%) and affects clinical management
US can be useful in infants younger than (65%). However, a cautious use of CT is appro-
12 months. The unossified sternal and costal car- priate especially in neonatal and pediatric patients
tilages allow evaluation of anterior mediastinal who may necessitate repeat imaging during life,
structures and detection of masses. US has the
advantage to avoid ionizing radiation exposure
but is operator dependent [20].

10.6.2.3 Echocardiography
It is useful to differentiate mediastinal masses
from other intracardiac or pericardic lesions.

Fig. 10.2  Chest X-ray is the first-line imaging technique

in suspected mediastinal masses. It typically shows an Fig. 10.3  Upper GI tract X-ray highlights deviations of
enlargement of mediastinal profile or in some cases a esophagus or communications between the mass and the
well-defined opacity digestive system
10  Mediastinal Masses 143

plete evaluation of lymphoma in the pediatric

population [23–27] .

10.7 Esophageal Duplications

Intestinal duplications are esophageal in approxi-

mately 20% of cases. They can occur anywhere
along the esophagus, although the cervical
esophagus is most affected and most of these
Fig. 10.4  CT scan plays a central role in defining diagno- occur on the right side of the thoracic esophagus;
sis of mediastinal masses they usually are a round, well-defined cystic
lesion and may cause extrinsic compression of
keeping in mind the harmful potential of high the trachea with respiratory symptoms or
radiation exposure [21, 22]. pneumonia.
As an esophageal duplication may contain
10.6.2.6 Magnetic Resonance gastric mucosa in about half of cases, they can
Imaging cause hematemesis or anemia.
Magnetic resonance has a sensitivity slightly lower Esophageal duplication cysts should be con-
than TC. It finds particular utility on the study of sidered in the differential diagnosis of any medi-
vascular anomalies, evaluates posterior mediasti- astinal mass; in 20% of cases, spinal cord
nal neurogenic tumors with possible intraspinal communication has been described.
extension, and assesses foregut duplication cysts Among the congenital anomalies associated
with high attenuation on non-­contrast CT. with esophageal duplication, the most common
MRI provides a superior soft tissue character- are esophageal atresia and vertebral anomalies.
ization in comparison with other currently avail- Once suspected a duplication on the basis of
able imaging modalities. However it has the chest X-ray, it is usually necessary to perform a
disadvantages of image artifacts caused by car- TC or MR. It is also useful to perform abdominal
diac and respiratory motion and the need for ultrasound, as a high percentage of patients
sedation in newborns and infants [2, 4]. (about 25%) with esophageal duplication also
have intestinal duplication.
10.6.2.7 Positron Emission The scintigraphy with 99mTC pertechnetate
Tomography (PET) allows to diagnose the presence of gastric mucosa
Positron emission tomography (PET) is a nonin- within the mediastinal cyst.
vasive imaging modality using 2 fluoro-2-deoxy Differential diagnosis includes thyroglossal
(18 fluorine)-D-glucose (18 FDG). PET is cur- duct cysts, bronchial cysts, cystic hygroma, cer-
rently not used as an initial imaging modality for vical lymphadenopathies, and a variety of cervi-
evaluating mediastinal masses in infants and cal solid tumors.
children, but it can be useful for staging and fol- Although most of the esophageal duplication
low-­up of patient with lymphoma including is adjacent to the esophagus wall, in the literature
detection of tumor involvement in normal-sized are also described esophageal duplications in the
lymph nodes, discrimination of fibrous scar and right pleural space, detached from the
necrotic tissue from active tumor in residual esophagus.
masses after treatment, and evaluation of disease Esophageal duplications require removal by
involvement in extra-nodal sites (e.g., liver or thoracotomy or thoracoscopy (Fig. 10.5). If bone
bone marrow). communication is present, it is advisable to per-
In addition, PET/CT provides both functional form a bone section and, possibly, a laminectomy
and anatomic information necessary for a com- in collaboration with the neurosurgeon [28–30].
144 M. Lima and M. Maffi

a b

c d

Fig. 10.5 Large esophageal duplication removal. removed (c). In case of communication with the esopha-
Preoperative CT scan shows a large fluid-filled cystic gus, the residual defect should be sutured (d)
lesion (a) that can be reduced by puncture (b) and totally

10.8 Bronchogenic Cyst Also in this case surgical removal is required

which can be performed with toracotomic or tho-
Bronchogenic cysts are uniloculated cavities racoscopic access. Radicality is mandatory to
containing mucoid material, sometimes in com- avoid recurrences [31, 32].
munication with the bronchial lumen, located in
the mediastinum, tongue, neck, chest wall, peri-
cardium, pancreas, and adrenal gland. They can 10.9 Lymphangiomas
cause bronchial obstruction resulting in second-
ary lobular emphysema. The clinical course can Lymphangioma is a congenital anomaly of the
be asymptomatic or associated with the develop- lymphatic system. It is usually present at birth
ment of respiratory infections or tracheobron- (60%), and 80–90% of cases are symptomatic
chial compression symptoms. The first level under 2 years of age. Typical symptoms include
imaging is chest X-ray that can reveal rounded dyspnea, cough, chest pain, acute respiratory
homogeneous opacity with well-defined margins distress, and respiratory failure. This lesion is
associated with compression on the esophagus, usually located in the head and neck, while the
trachea, or bronchi. axilla and mediastinum are the second frequent
Ultrasound is a noninvasive, economical, and location site. Although it is a benign lesion, it
non-irradiating method. Nonetheless, preoperative can lead to complication because of its infiltrat-
diagnosis and evaluation requires TC and RM. ing nature, indefinite demarcation, and the
10  Mediastinal Masses 145

involvement of vital structures. Lymphangiomas

are classified morphologically as macrocystic,
microcystic, and mixed. Ultrasounds, CT scan,
and MRI are all used to evaluate a patient pre-
operatively. Typical CT appearance is a well-
circumscribed cystic mass with compression of
surrounding structures. MRI visualizes cystic
component with multilocular aspect, low signal
intensity on T1W1 and high signal intensity on
T2W1.
Surgical therapy consists of complete resec-
tion, but radicality can be difficult because of
high risk of damage to the surrounding struc-
tures. For this reason, sclerotherapy is mostly
used. Several sclerosing agents are available, but Fig. 10.6  Thoracoscopic biopsy allows to obtain neo-
the most commonly used are bleomycin and the plastic tissue to perform molecular studies
Ok-432 [33–36].
spaces. CT and MRI are the imaging techniques
of choice in assessing these lesions.
10.10 Neurogenic Tumors Surgery plays a key role in the treatment at
diagnosis and after chemotherapy. The goals of
Tumors derived from neural crests are the most surgery at onset are to define the diagnosis,
common lesions of the posterior mediastinum. acquire tissue for biological studies, and
These neoplasms arise from the sympathetic remove the tumor with minimal morbidity
chain and vary from benign ganglioneuroma to (Fig.  10.6). Since complete excision is the
malignant neuroblastoma. main goal of the intervention, this should not
Twenty percent of neurogenic tumors are be “tempted” before chemotherapy if any of
located in the posterior medium. Neuroblastoma, the risk factors, such as a tumor that encloses
a malignant neoplasm of the autonomic nervous large vessels (aorta and vein veins) or nerve
system, originates from the neuroectodermal plexus, are present. The treatment includes
cells of the primitive neural crest that migrate in chemotherapy and radiotherapy depending on
the course of embryonic life, giving rise to the the type of lesion. Surgical resection is the
sympathetic ganglia and adrenal medulla. treatment of choice and is curative for benign
Neuroblastoma is the most common solid tumor lesions [37–41].
in subjects <5 years old.
Ganglioneuroma, on the other hand, is a tumor
composed mainly of schwannian stroma with 10.11 T
 eratomas and Germ Cells
completely differentiated ganglionic cells Tumors
(mature ganglioneuroma) or incompletely differ-
entiated (immature ganglioneuroma). It affects Germ cell tumors are the second most common
older children and adolescents and manifests as neoplasm in newborn accounting for 35–40% of
asymptomatic lesions, which are sometimes acci- all tumors in the first month of life. In the new-
dentally identified with chest radiography. They born period, the majority of GCTs are extrago-
can appear anywhere along the paravertebral nadal (mainly sacrocoggygeal) but are located in
spaces and are usually encapsulated and quite mediastinum only in 3% of cases.
easily resectable. Most teratomas are located in the anterior
Symptoms of compression can be associated mediastinum, intrapericardial and intracardiac
to a large mass or to masses infiltrating spinal locations are described.
146 M. Lima and M. Maffi

Only 5% of germ cell tumors in neonatal age Important markers for germ cell tumors are
are malignant. They are more common in females α-FP and β-HCG.
with ratio F:M = 3:1 which is again a reversal of Surgical resection by thoracotomy, median
the ratio seen in the rest of childhood. Children sternotomy, or thoracoscopy (Fig.  10.7) is usu-
with anterior mediastinal teratoma usually have ally curative, although the detection of malignant
respiratory symptoms (distress, coughing), but in elements within the lesion may require further
older patients, teratoma may also be an acciden- therapies. Thoracoscopic removal is generally
tal finding at chest X-ray. Other symptoms not indicated for tumors with signs of
include erosion of thoracic wall, hemoptysis, due malignancy.
to erosion of a bronchus or cardiac failure. Patients with signs of malignancy should
TC is the imaging technique of choice in eval- receive neoadjuvant chemotherapy. Benign
uating these injuries, as it can define the extent of tumors or persistent masses after chemotherapy
the lesion and possible tracheal compression. should be resected aggressively [42–45].

a b

c d

Fig. 10.7  Left mediastinal teratoma removal. After the mass identification (a), parietal pleura is opened and the mass
removed (b, c, d)
10  Mediastinal Masses 147

10.12 Thymic Tumors the most common lesions even if in pediatric age
they occur primarily in the anterior and middle
Masses derived by thymus include thymic cyst, regions. Along with Burkitt’s lymphoma, large
thymic hyperplasia, and thymoma. B-cell lymphoma, and large-cell anaplastic lym-
These masses represent less than 5% of medi- phoma, lymphoblastic lymphoma is one of the
astinal tumors in children. Thymic hyperplasia most common non-Hodgkin lymphomas (LnH)
can take the form of a lymphoid follicular hyper- of the pediatric age. They account for about
plasia, which is often present in myasthenia gra- 10–15% of all malignant neoplasms of the
vis and associated with a good response to ­pediatric age, thus forming the third most com-
thymectomy; this lesion can also be found in thy- mon group in the Western countries. LnHs show
roid pathologies (hypothyroidism, hyperthyroid- a steady increase in age.
ism). Thymomas are rare in children when Hodgkin lymphoma (LH), on the other hand,
compared with adults, with only 2% that appears accounts for about 6% of the pediatric neoplasms.
in the first two decades of life. These lesions are It shows a predilection for the male, especially in
usually benign and appear in the anterior medias- the younger age and a bimodal distribution of
tinum or at the base of the neck. incidence, with a peak between 15 and 30 years
Although thymic cancers can be large in size, of age and a second after 50 years. LH is rare in
they generally compress the surrounding struc- individuals <10 years of age. The incidence var-
tures rather than invade them. The main symp- ies significantly in different geographic areas and
toms are respiratory distress (respiratory distress, populations.
cough) and/or superior vena cava syndrome. Children with LH may have systemic symp-
Occasionally they are associated with myasthe- toms such as fever, malaise, weight loss, night
nia gravis. TC is the imaging technique of choice illness, and rarely pleural effusions. In most
in evaluating these lesions, as it can define the cases, the diagnosis is transmitted through lymph
extension. node biopsy, as often babies have involvement of
Surgical resection is curative and recurrence is cervical or supraclavicular lymph nodes that are
rare (2%). Malignant thymomas are usually easily accessible to biopsies. Diagnostic evalua-
aggressive, and surgical resection is complex, tion also includes chest X-ray, which is the first
and the response to chemotherapy and radiother- routinely used imaging technique, and the tho-
apy is limited. The pleura, lung, diaphragm, racic TC that establishes localization, consis-
superior vena cava, and pericardium resections tency and mass architecture, and the relationship
may be required to achieve complete surgical with adjacent structures.
removal [46–48]. Mediastinal locations are often extended over
the original site, and other organs such as the
pleura, the pericardium, and the bone marrow are
10.13 Lymphoid Tumors affected.
Children with LnH often have symptoms due
Various lymphoid tumors may affect the medias- to local compression of the upper respiratory
tinum; lymphoma is the most common tumor of tract or compression of the superior vena cava.
the middle mediastinum and represents about Systemic symptoms such as fever, malaise,
60% of all mediastinal lesions in pediatric age. weight loss, nighttime awakenings, and pleural
Two-thirds of mediastinal lymphomas are non-­ effusions are often present. In most cases, the
Hodgkin lymphomas; one third are Hodgkin diagnosis is performed through lymph node
lymphomas. Lymphomas are quite rare in neona- biopsy. Diagnostic evaluation includes chest
tal age. X-ray and thoracic CT.
Lymphomas can involve all the mediastinal Treatment of such neoplastic lesions (LH)
compartments. Lymphoblastic lymphomas are involves chemotherapy and radiotherapy. The
148 M. Lima and M. Maffi

prognosis is good, with overall survival rates of agement and outcome of congenital mediastinal
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Puligandla PS, Nguyen LT, St-Vil D, et  al. 2012;17(4):222–30. https://doi.org/10.1016/j.
Gastrointestinal duplications. J Pediatr Surg. siny.2012.05.004. Epub 2012 May 28.
2003;38:740–4. 45.
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31. Achiron R, Hegesh J, Yagel S. Fetal lung lesions: a spec- D. Mediastinal germ cell tumors. Semin Diagn Pathol.
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 Pneumothorax and Chylothorax
11
Sebastiano Cacciaguerra, Pieralba Catalano,
Enrica Antonelli, and Salvatore Arena

11.1 Introduction involves the right lung and between 15% and
25% of nPTX cases are bilateral [4].
Pneumothorax (PTX) is the most common air In general, the most common classification
leak occurring when air accumulates in the pleu- system divides PTX into:
ral space [1]. Especially during the neonatal
period, PTX is considered life-threatening and is • Spontaneous (non-traumatic)
associated with high mortality and morbidity [2, –– Primary spontaneous—no predisposing
3]. Neonatal PTX (nPTX) was defined as radio- lung disease or history of thoracic trauma
logically verified PTX occurring up to the 28th –– Secondary spontaneous—underlying lung
day of life. Despite the high incidence, just 0.5% abnormality is present
of cases of nPTX are symptomatic [2, 4]. nPTX • Traumatic
is more frequently observed in neonates (1–2%), –– Iatrogenic—caused by invasive medical
and in particular in very low birth weight (3–9%) procedures, e.g., central vein cannulation,
[5, 6], than in older children (1.2–28 per 100,000) fine needle aspiration and baro-trauma due
[2, 3, 7] and the rate can increase to up to 30% in to mechanical ventilation
patients who have concurrent underlying lung –– Accidental—following direct injury to the
disease or requiring mechanical ventilation [2, thorax, e.g., penetrating chest injury and
7]. Rates may change due to obstetrical, perina- laceration of visceral pleura by a fractured
tal, clinical course, and management strategies rib [9, 10]
[8]. Furthermore, PTX can develop due to high
transpulmonary pressure generated at the onset Pneumothorax may also be classified as:
of respiration.
PTX can be classified as uni- or bilateral and • Simple pneumothorax—no shift of the heart
with or without the presence of tension. It has or mediastinal structures
been reported that two-thirds of unilateral nPTX • Tension pneumothorax
• or
• Open—“sucking” chest wound
• Closed—intact thoracic cage [10]
S. Cacciaguerra (*) · P. Catalano
Department of Paediatric Surgery,
A.R.N.A.S. Garibaldi, Catania, Italy
E. Antonelli · S. Arena
Department of Paediatric Surgery, University of
Messina, Messina, Italy

© Springer Nature Switzerland AG 2019 151

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_11
152 S. Cacciaguerra et al.

11.2 Risk Factors positive influence on the pulmonary system in

neonates. Specifically, nPTX was significantly
It has been reported that incidence of nPTX is more frequent after cesarean section than after
more frequent in males and is improved in vari- vaginal delivery. After an elective CS, the baby is
ous pulmonary disorders, such as respiratory not stressed and often has “wet lungs” followed
distress syndrome (RDS) and meconium or by forced respiration that may lead to
blood aspiration syndrome [3, 11–13]. In par- PTX.  Moreover, cesarean section increases the
ticular, incidence of nPTX of 5–20% was found need for mechanical ventilation, and, among neo-
in infants with RDS, with and without the use of nates delivered by cesarean section at term or
assisted ventilation, and of 20–50% in term moderately preterm, the incidence of nPTX and
infants affected by meconium aspiration syn- respiratory distress has been reported to be sig-
drome [14]. Single-lung ventilation, high peak nificantly increased [22].
inspiratory pressure, high positive end-expira- As far as potential maternal risk factors for
tory pressure application, and ventilator non- nPTX are concerned, there was not found a sig-
conformity are among the factors that can nificant difference in the proportion of infants
induce nPTX during mechanical ventilation [2, with maternal diabetes mellitus, with different
15, 16]. Although there are some conflicting maternal ethnic groups, different gender groups,
results, nPTX was also found to be associated and different places of birth or born with multiple
with the use of continuous positive airway pres- pregnancies [21].
sure (CPAP) and positive pressure ventilation
[11, 17, 18]. The risk is also shown to increase
in certain conditions including low birth weight, 11.3 Sign and Symptoms
prematurity, low Apgar score, vacuum extrac-
tion, and elective cesarean delivery before Many infants in PTX are asymptomatic [22].
39 weeks [11, 19, 20]. When symptoms do occur, they can include:
In a Malaysian study, although 42% of the
affected infants were of birth weight >2500 g, • Difficult breathing, use of accessory muscles
the incidence of nPTX was highest (7.3%) in to breathe, tightening of the neck muscles, and
the extremely low birth weight (<1001  g) use of the chest and abdomen to aid breathing
infants. Among infants of birth weight between (retraction).
1001  g and 1500  g, the incidence was only • Faster breathing. In particular, an increase of
3.4%. In a similar manner, the incidence of at least 10 per minute above the baseline in the
nPTX was a more common complication in the respiratory rate is a reliable parameter with
extremely preterm infants, being 6.8% in 77% sensitivity and 90% specificity to help
infants of gestation 26  weeks, 5.8% in the determining the development of nPTX.
27–29  weeks group, 3.4% in those of gesta- • Cyanosis/bluish discoloration of the skin as
tional age 30–32 weeks, and 3.4% in infants of well as of the nails and tongue. This is
gestation 33–36 weeks [21]. ­considered an important symptom of nPTX
The Apgar score at 5th minute is also consid- and one of the vital signs to be noted.
ered an important parameter in evaluation of the • Flaring of the nostrils.
nPTX.  A low Apgar score in 50% of non-­ • Grunting with breathing.
survivors and in only 12% of survivors has been • Irritability.
found in patients complicated by nPTX [14]. • Restlessness [22].
Furthermore, there is a strong association
between modes of delivery and the incidence of The time between onset of nPTX and a defini-
nPTX, in particular in preterm neonates. It has tive clinical diagnosis was found to range from 1
been suggested that vaginal delivery might have a to 10 h [5, 11, 23].
11  Pneumothorax and Chylothorax 153

In the supine patient, air in the pleural space

will usually be most readily visible at the lung
bases in the cardiophrenic recess and may
enlarge the costophrenic angle (the deep sulcus
sign). Artifacts can mimic the presence of a
PTX and should be born in mind during the
evaluation of a chest X-ray. The medial border
of the scapula can imitate a lung edge but once
considered can be traced in continuity with the
rest of the bone. Skinfolds overlying the chest
wall can simulate a visceral pleural line.
However, skinfolds are usually seen to pass
outside the chest cavity, are straight or only
minimally curved, and do not run parallel to
the chest wall as with a true visceral pleural
line [24].

11.4.2 Sonography

The use of ultrasound for detection of nPTX had

been shown to be particularly sensitive and in
fact some studies reported that it is comparable to
chest X-ray [26].
The main ultrasonic features of nPTX are as
follows:

Fig. 11.1  Supine projection showing a large right-sided

• Lung sliding disappearance. In a PTX, there is
pneumothorax with an evident visceral pleural line air present that separates the visceral and pari-
(arrow) etal pleura and prevents visualization of the
visceral pleura. In this situation, lung sliding
is absent. The accuracy and reliability of the
11.4 Diagnostic Tools lung sonographic signs of lung sliding disap-
pearance in diagnosing PTX were to be found
11.4.1 Chest X-Ray up to 100% in sensitivity, 100% in specificity,
and 100% in positive predictive value.
Radiographic diagnosis of PTX is usually However, lung sliding could be abolished in a
straightforward [24]. However, a nPTX can be variety of conditions other than PTX, includ-
missed easily on supine position chest radio- ing acute respiratory distress syndrome
graphs and, as a consequence, the diagnosis may (ARDS), pulmonary fibrosis, large consolida-
be made even later [11, 25]. tions, pleural adhesions, atelectasis, right
A visceral pleural line is seen without distal mainstem intubation, and phrenic nerve paral-
lung markings (Fig.  11.1). Lateral or decubitus ysis [27–30].
views are recommended for equivocal cases. On The negative predictive value for lung sliding
standard lateral views, a visceral pleural line may is reported as 99.2–100%, indicating that the
be seen in the retrosternal position or overlying presence of sliding effectively rules out a
the vertebrae, parallel to the chest wall [24]. nPTX [31–33].
154 S. Cacciaguerra et al.

“Comet-tail artifacts” or “B-lines”: Ultrasound ing. Power Doppler is very sensitive and picks up
demonstrates the loss of “comet-tail artifacts” subtle flow and movement. If there is lung sliding
in patients with a PTX.  These reverberation present, power Doppler will light up the sliding
artifacts are lost due to air accumulating pleural line with color flow.
within the pleural space, which hinders the The “lung pulse” refers to the rhythmic move-
propagation of sound waves and eliminates ment transmitted to the lung pleura in synchrony
the acoustic impedance gradient [34]. In addi- with the cardiac rhythm. The “lung pulse” is a
tion, “comet-tail” artifacts are generated by result of cardiac vibrations being in poorly aer-
the visceral pleura, which is not visualized in ated lung. Cardiac activity is essentially detected
a PTX [33]. The negative predictive value for at the pleural line when there is absent lung slid-
this artifact is high, reported at 98–100% [28, ing [28].
33, 35].
• “A-lines” are other important thoracic artifacts
that can help in the diagnosis of pneumotho- 11.4.4 Transillumination
rax. These are also reverberation artifacts
appearing as equally spaced repetitive hori- Transillumination consists in the placement of a
zontal hyperechoic lines reflecting off of the cord fiber-optic light source next to the infant’s
pleura. The space in between each A-line cor- skin that should transilluminate the whole hemi-
responds to the same distance between the thorax in the presence of a large PTX. It should
skin surface and the parietal pleura. In the nor- be compared to the other side of the chest for ref-
mal patient, when “B-lines” are present, they erence [37]. Transillumination is most useful in
extend from the pleural line and erase small babies.
“A-lines,” as they emanate out to the edge of In particular, the physician should lower the
the screen. “A-lines” will be present in a lights in the room to enable hyperlucent areas to
patient with a PTX, but “B-lines” will not. If be seen (if present) and place the transillumina-
lung sliding is absent with the presence of tor along the posterior axillary line on the side on
“A-lines,” the sensitivity and specificity for an which the air collection is suspected. Large
occult PTX is as high as 95 and 94%, respec- infants require a bright source and a very dark
tively [33]. room for transillumination to be visible, there-
• Lung-point sign. The “lung-point sign” occurs fore this thechnique is only useful if it is posi-
at the border of a PTX. It is due to sliding lung tive. The transilluminator may be moved up and
intermittently coming into contact with the down along the posterior axillary line and above
chest wall during inspiration and is helpful in the nipple to detect any areas of increased trans-
determining the actual size of the PTX.  The mission of light. Moreover, transilluminator
“lung-point sign” is 100% specific for PTX should be placed in the third or fourth intercostal
and defines its border [28, 36]. The location of space on the left midclavicular line and angle the
the lung point is beneficial in determining the light toward the xiphoid process to detect any
size of the PTX.  Although the specificity is areas of increased transmission of light. In a neg-
high, the sensitivity of the “lung-point sign” is ative result, a halo of light appears around the
relatively low (reported at 66%) and is not light source only. A false-negative result may
seen in cases of total lung collapse [36]. occur in infants with a thick layer of subcutane-
ous fat, small air leaks, a weak light source, or a
bright room. A false-­positive result may occur
11.4.3 Other Signs with severe subcutaneous chest wall edema, pul-
monary interstitial emphysema, or pneumomedi-
The “power slide” refers to the use of power astinum. Reported sensitivity is 87–100% and
(angiography) Doppler to help identify lung slid- specificity 95–100% [37].
11  Pneumothorax and Chylothorax 155

11.5 Management or 25 gauge) or an angiocatheter (18–24 gauge). If

using an angiocatheter, the plastic catheter can be
nPTX may be managed with a variety of left in situ [1, 39].
approaches, including observation (“watchful Chest tube (10 or 12 French size) insertion is
waiting”), simple needle aspiration (thoracente- usually obtained in the anterior pleural space
sis), or insertion of a chest tube (chest tube (Fig. 11.2). After the preparation of the skin with
placement). antiseptic solution and a local anesthesia of the
For asymptomatic patients who had PTX subcutaneous tissues, a small incision is made
occupying less than 15% of hemithorax, no sur- through the skin in the midaxillary line in the
gical intervention is usually required. Mild PTX sixth intercostal space, the subcutaneous tissue is
may be treated conservatively; the rate of sponta- dissected, and a subcutaneous track to the inter-
neous reabsorption is about 1.2% of the volume costal space is made. A trocar might be used to
of the hemithorax per 24 h and patients should be facilitate the penetration of the tube, even if this
followed up with radiographs once daily. In this technique may be associated with an increased
way, for example, if a patient has a 20% PTX, it risk of lung perforation. The chest tube is passed
will take approximately 16  days to resolve [2]. into the pleural opening, turned anteriorly and
Differently, for symptomatic patients who had directed to the location of the PTX, and then con-
PTX occupying less than 15% of hemithorax or nected to a Heimlich valve or an underwater seal
patients with PTX more than 15%, irrespectively with continuous suction at a pressure of 10–20
of the symptoms, a drainage is suggested. cmH2O. A less traumatic approach consists of the
Thoracentesis may be the only intervention use of pigtail catheters, which are usually smaller
needed in an infant who is not mechanically venti- (8–10  French) and possibly more suitable for
lated and may be a temporary measure in an infant preterms. Pigtail catheters can be placed with a
who requires ventilation [3, 38]. Thoracentesis Seldinger technique [39].
consists in the insertion of a needle into the second Both the procedures can be performed under
or third intercostal space in the midclavicular line, radiological or ultrasonographic guidance.
passing just above the top of the rib in order to A post-drainage chest radiograph is essential
reduce the risk of lacerating the intercostal artery. to document resolution of the PTX, detect com-
Flow of air into a syringe confirms that the PTX plications, and ensure a satisfactory drain posi-
has been reached by the needle, which should not tion. After satisfactory resolution of the PTX, the
be inserted further to avoid lung damage. Air could drainage catheter can be removed and a further
be aspirated with a 10–20 ml syringe (usually 23 follow-up radiograph obtained to detect recur-
rence. A straight radiopaque line is occasionally
seen here along the line of the removed tube,
known as a “drain track.” This may be
misinterpreted as a recurrent air leak, but its
­
straight course and precise relation to the drain
position on the radiograph before removal are
usually conclusive [24]. Fibrin glue is an effec-
tive treatment for intractable PTX, but this proce-
dure has significant risk [40].
The literature does not clearly define which is
the best option for the treatment of PTX, espe-
cially if hemodynamically stable. There is insuf-
ficient evidence to determine the efficacy and
Fig. 11.2  Latero-lateral projection displaying a chest
tube draining the anterior pleural space in a right-sided safety of the two techniques. Mortality rate did
pneumothorax not differ between the two groups [24].
156 S. Cacciaguerra et al.

11.6 Outcome pleural effusion can compromise normal lung

maturation and progress to fetal hydrops, result-
Although nPTX is one of the few treatable causes ing in pulmonary hypoplasia and premature birth,
of respiratory difficulty in the early days of life, with high rate of perinatal mortality [50, 51].
the mortality rate remains high, ranging between Generally, chylothorax resolves with nonopera-
13% and 65% in the literature [14, 40–42]. The tive measures (respiratory and life support, diet
variance in mortality is probably large due to dif- restriction, and medical therapy), but, if sponta-
ferences in gestational age, underlying diseases, neous healing does not occur, surgical treatment
and advances in neonatology. becomes necessary [52, 53]. Recently prenatal
nPTX is also associated with significant mor- therapies have been proposed for congenital chy-
bidity. In this regard, it has been reported that lothorax in order to improve the perinatal out-
59% of the neonates affected by PTX required come [54–56].
drainage, and about half needed mechanical ven-
tilation. The majority of the nPTX in the non-­
drainage treatment group could be managed with 11.7.2 Embryology and Anatomy
nasal CPAP and oxygen [43].
Because neonates with RDS and hypoxemia The lymphatic system, essential for fluid homeo-
are managed by increasing the inflating pressure stasis, immune responses, and fat absorption, is
and application of positive end-expiratory pres- an endothelium-lined network of blind-ended
sure, the potential for tension nPTX is increased. capillaries found in nearly all tissue, draining via
Additionally, nPTX during respiratory distress is collecting vessels into large trunks that eventu-
associated with increased risk of intraventricular ally empty into the blood circulatory system [57].
hemorrhage, chronic lung disease, and subse- This system begins its development in the sixth
quent death [14, 44, 45]. gestational week through a centrifugal budding
process starting from six different outpouchings
of the venous endothelium: two jugular sacs, two
11.7 Chylothorax femoral sacs, a retroperitoneal sac, and the cis-
terna chyli. These sacs grow longitudinally and
11.7.1 Introduction link together by the ninth gestational week, form-
ing a bilateral system of lymphatic trunks con-
Chylothorax is a rare condition, characterized by nected by numerous horizontal and diagonal
chyle collection in the pleural space, secondary anastomoses. The final thoracic duct is the result
to leakage from lymphatic system. Although it of resorption of the superior portion of the right
rarely represents the cause of pleural effusion in trunk and the inferior portion of the left trunk
children [46], it is the most frequent cause in [58]. This explains the potential for anatomical
newborn age [47–49]. Chylothorax can be con- variations in lymphatic pathways presenting in
genital, as isolated malformation or associated 35–50% of the population [46, 59, 60].
with other abnormalities, or acquired, as iatro- From the lacteals, lymphatic fluid is collected
genic or traumatic. Clinical manifestation in the cisterna chyli, located at the level of the
depends on the amount of accumulated chyle, second lumbar vertebra, from which it passes
ranging from asymptomatic patients or with only into the thoracic duct and then reaches the venous
mild respiratory distress to life-threatening con- system. The duct passes through the aortic hiatus
ditions that require urgent drainage and other of the diaphragm and ascends in the posterior
resuscitative management. Moreover, because mediastinum to the right of the midline between
chyle is composed of fats, immune cells, and pro- the azygous vein and the descending aorta. At the
teins, persistent losses may be associated with fourth to sixth thoracic vertebrae, the duct crosses
malnutrition, immunodeficiency, and metabolic to the left and continues its ascent into the left
acidosis. In congenital chylothorax, severe fetal neck, where it forms an arch that rises 3–4  cm
11  Pneumothorax and Chylothorax 157

above the clavicle. It then drains into the left sub- ties associated with chylothorax, but the atresia
clavian vein near the junction of the subclavian of the thoracic duct may be another cause [75,
and left internal jugular veins [61]. 76]. Congenital chylothorax may be discovered
in the antenatal period and can be associated with
hydrops fetalis, whose presence is the most
11.7.3 Physiopathology important predictor of outcome, decreasing the
overall survival from 75% to 24% [77–79]. Other
Chyle is a milky fluid produced by mucosal cells associations with uncommon disorders, such as
of the small bowel during digestion and consists mediastinal neuroblastoma and thyrotoxicosis,
of emulsified fats (especially triglycerides and have been reported in newborn [80, 81].
cholesterol), electrolytes, proteins, glucose, and Acquired chylothorax results from iatrogenic
cellular elements, most of which are small lym- or traumatic injury of the thoracic duct. It occurs
phocytes (≥80%). At birth or after fasting, chyle as a postoperative complication after surgery
is clear because it is lacking in fats. The thoracic involving structures in the neck and thorax, espe-
duct transports about 1.4  mL/kg/h of chyle, but cially after repair of cardiovascular anomalies,
the flow varies depending on different factors, congenital diaphragmatic hernia, and esophageal
particularly fatty meals may increase up to ten atresia [82–85]. Other causes are catheterization
times the basal flow [62, 63]. Chyle loss can of the subclavian vein, thrombosis of the superior
result in a serious state of depletion characterized vena cava or subclavian vein secondary to central
by hyponatremia, hypoproteinemia, metabolic venous catheters [86, 87], chest tube insertion
acidosis, and lymphocytopenia [64, 65]. [88], and traumatic delivery with trunk hyperex-
tension [89]. Furthermore, cases of abuse leading
to rupture of the thoracic duct have been reported
11.7.4 Etiology in infants [90, 91].

There are several causes of pediatric chylothorax,

grouped into two main categories: congenital and 11.7.5 Clinical Manifestations
acquired.
Congenital chylothorax is the most common The onset symptoms of chylothorax are usually
form of pleural effusion in the first few days of related to accumulation of lymphatic fluid within
life [47]. The studies have reported an incidence the pleural cavity. Then, symptoms of respiratory
range from 1:5775 to 1:24000 in live-born neo- distress such as tachypnea, dyspnea, cyanosis,
nates, a predominance of male patients with a and chest retraction develop in association with
male-to-female ratio of 2:1 [48, 51, 66], and a signs of pleural effusion (dullness on percussion
prevalence of bilateral forms. However, right-­ and reduction of breath sounds on the affected
sided chylothorax has been described as more side, mediastinal shift to the opposite side) [48].
frequent in unilateral presentations, because of Timing of the clinical manifestations varies
the anatomy of the thoracic duct [47, 50]. according to the type of chylothorax. Congenital
Congenital chylothorax may occur alone, sec- chylothorax, antenatally discovered, can alter
ondary to malformation of the lymphatic system normal lung development, resulting in a respira-
or in combination with genetic syndromes (Down tory distress at birth; however, in absence of pul-
syndrome, Turner syndrome, and Noonan syn- monary hypoplasia, symptoms become evident
drome) and chromosomal anomalies [67, 68]. within 2  weeks of life. In acquired chylothorax
Pulmonary lymphangiomatosis (focal prolifera- an interval of 1–2  weeks generally occurs
tion of well-differentiated lymphatic tissues) between the injury and the appearance of pleural
[69–71] and lymphangiectasia (diffuse dilatation effusion. Lymphatic fluid extravasation, in fact,
of the interlobular and subpleural lymphatics) collects first extrapleurally in the posterior medi-
[72–74] are the two major lymphatic abnormali- astinum and only after mediastinal pleural rup-
158 S. Cacciaguerra et al.

ture accesses to the pleural space producing

pulmonary compression. The time is shortest
when there is a direct injury to the thoracic duct
(5–7 days) and longest when there is high pres-
sure or thrombosis of the vena cava
(10–14 days).
The effects of prolonged loss of chyle may
include malnutrition, fluid and electrolyte imbal-
ance, metabolic acidosis, and finally immunologi-
cal compromise because of lymphocyte depletion
and hypogammaglobulinemia with high risk of
nosocomial infections and sepsis [92].
Fig. 11.4  Sagittal view of pulmonary ultrasound demon-
strating the presence of pleural effusion
11.7.6 Diagnosis

Chest radiograph can reveal signs of pleural effu-

sion: opacification of one or both hemithoraces
with compression of lung and displacement of
mediastinal structures in unilateral chylothorax
(Fig.  11.3). However, in premature babies the
diagnosis is not simple, because of concurrent
pulmonary disease. In these cases ultrasound is a
useful diagnostic method of detecting chylotho-
rax (Figs. 11.4 and 11.5). Nevertheless, diagnosis
must be confirmed with the analysis of drained
pleural fluid. Initially the pleural fluid is serous
and becomes chylous when milk feeding is
started. Typical chyle is composed of elevated

Fig. 11.5 Transverse view of pulmonary ultrasound

demonstrating the presence of pleural effusion

total protein, albumin, and electrolyte levels,

presence of white blood cells with a predomi-
nance of lymphocytes, and elevated triglycerides,
cholesterol, and total fat levels. Total fat more
than 400  mg/dL with triglycerides greater than
110  mg/dL and lymphocyte count 80–100% of
white blood cells are useful diagnostic tool in dif-
ferentiating chylothorax from other types of
pleural effusions. However, in unfed newborn fat
content of the fluid is low and the amount of pro-
Fig. 11.3  Chest X-ray showing opacification of the left teins and electrolytes is similar or inferior to the
hemithorax serum. Therefore, in a fasting neonate, the most
11  Pneumothorax and Chylothorax 159

useful test for diagnosis of chylothorax is to per-

form a complete blood cell count and differential
on the fluid and, when lymphocytes exceed
80–90% of the white blood cells, a lymphatic
effusion can be confirmed [93]. If making a posi-
tive diagnosis of chylothorax is easy by examina-
tion of pleural fluid, its mechanism and the
integrity of thoracic duct and its branches are dif-
ficult to determine.
Lymphoscintigraphy is a useful test for etio-
pathogenetic diagnosis in refractory chylothorax.
This diagnostic tool can be combined with single-­
photon emission computed tomography-­
computed tomography (SPECT-CT), providing
more specific anatomical information [94]. Fig. 11.6  Pleural effusion resolution after chest tube
placement

11.7.7 Therapy recommended more aggressive treatment in the

case of high output or persistent leak [51, 66]. In
Supportive and conservative methods (effusion fact chest tube insertion for a long period of time
drainage, mechanical ventilator support, and results in hypoproteinemia, electrolytes loss,
dietary restriction) are considered as first-line lymphopenia, and prolonged ventilator use with
treatment in patients with chylothorax, account- high risk of morbidities and mortality [65].
ing more than 80% of successful cases [46]. Therefore, if the site of leaking is identified and
Surgical therapy should be kept into account if the amount of daily drainage is high, early sur-
medical treatment fails to decrease chyle flow gery is suggested, because it shortens the dura-
and allow thoracic duct healing [95]. Most tion of chest tube insertion, reducing the risks of
authors recommend at least 2–4 weeks of non- its complications [98].
operative therapies, before surgery is considered Nutritional support aims to provide adequate
[96, 97]. However, these series are not specifi- caloric intake preventing malnutrition and to
cally congenital cases, in which medical man- minimize chyle production waiting for leakage to
agement has been associated with mortality heal; it ranges from aggressive fasting with total
rates up to 20% [51]. Then, if the infant’s nutri- parenteral nutrition (TPN) to medium-chain
tional or metabolic status declines measurably ­triglyceride (MCT)-enriched formula. MCT are
during that time, surgical intervention should be absorbed directly into the portal venous system,
undertaken. bypassing lymphatic drainage and so not contrib-
Management of chylothorax primarily uting to chyle flow; however even water intake by
involves aspiration of the pleural fluid (thoracen- mouth and a formula containing MCT can cause
tesis) for diagnostic purpose and immediate relief reaccumulation of pleural effusion [46, 63, 99].
of respiratory failure. In severely ill patients, Most reports indicate little difference in outcome
assisted ventilation may be necessary. Chest tube between parenteral nutrition and high MCT
insertion for continuous drainage of the pleural enteral nutrition, as initial therapy, with about
space is indicated if the effusion causes respira- three-fourths of patients responding to these
tory symptoms or if the effusion recurs [46]. It measures and chest drainage alone [100].
keeps the lungs fully expanded, which is neces- Nevertheless, the generally suggested approach
sary for sealing chyle leakage (Fig. 11.6). Time consists in the use of TPN until the drainage is
to cessation of drainage generally ranges from 1 minimal, followed by enteral nutrition with a for-
to 4  weeks, although more recent authors have mula high in MCT and eventually by normal
160 S. Cacciaguerra et al.

feeding. Close monitoring of reaccumulation of tion alone [108]. Another agent used in the treat-
pleural fluid must be performed either by chest ment of chylothorax is nitric oxide. Some case
tube drainage or ultrasound [99]. Supplementation reports described its use for the successful man-
of lost electrolytes and proteins, such as albumin, agement of refractory postoperative and congeni-
gamma globulin, fibrinogen, and fat-soluble vita- tal chylothorax in neonates with pulmonary and
mins, is frequently needed. central venous hypertension. Nitric oxide
A recent additional treatment to the medical decreases the pulmonary artery pressure that
options is represented by the pharmacological causes functional systemic venous obstruction
therapy with somatostatin or octreotide [101– and then persistence of chylous leak [109, 110].
105]. Somatostatin is an endogenous hormone Recently, oral sildenafil, a specific inhibitor of
with actions that include inhibitory effects on the phosphodiesterase-5, was reported to be effective
release of growth hormone, insulin, and gluca- in resolving a case of congenital chylothorax sec-
gon. Octreotide is a synthetic somatostatin ana- ondary to congenital pulmonary lymphangiecta-
logue more widely used because of its longer sia in a late preterm infant, in whom octreotide
half-life period, greater potency, and the option was unsuccessful. Its action mechanism involves
of subcutaneous administration without necessity generation of new lymphatic vessels, allowing
of continuous infusion. They act on gastrointesti- resolution of lymphatic obstruction and then chy-
nal receptors to reduce intestinal blood flow by lothorax [111].
vasoconstriction of the splanchnic vessels, If conservative treatment fails, surgical ther-
decrease motility, and inhibit gastric, pancreatic, apy is performed. No treatments have been sub-
and biliary secretions, thus reducing fat absorp- jected to a randomized controlled trial, and then
tion and the amount of chyle production [102, there are no standardized guidelines. Some cen-
106]. These drugs have been used in the treat- ters use daily drainage as a guide for clinical
ment of both the acquired and the congenital chy- improvement or failure, with >10  ml/kg/day
lothorax, appearing to be a safe and effective draining failure after 4  weeks of nonsurgical
adjuvant therapy in cases resistant to dietary management [96]. Actually, there is no defined
measures. However, a 2010 Cochrane review amount of output that suggests nonresolution, but
[105] was unable to draw any conclusions regard- drainage that does not gradually decrease or that
ing its use, and in a following study [103], the fluctuates is less likely to respond to nonopera-
authors felt that the decrease of pleural effusion, tive management [98]. Surgical options, often
observed in their patients, might reflect the natu- used in combination, include thoracic duct liga-
ral history of congenital chylothorax, not identi- tion, pleuroperitoneal shunt placement, pleurode-
fying a consistent effect of octreotide. In a recent sis, and pleurectomy. If the site of leakage can be
relatively large group of neonates with congenital identified, ligation of the thoracic duct represents
chylothorax, somatostatin/octreotide treatment a definitive treatment of chylothorax. Fibrin glue
significantly reduced the volume of pleural drain- and argon beam coagulation have also been used
age and the need for respiratory support without as an adjunct for ill-defined areas of leakage,
side effects and without need for surgical proce- especially in small premature infants [112, 113].
dure in any patient [107]. Nevertheless, there is The traditional surgical technique involves a pos-
no consensus on the optimal timing of introduc- terolateral thoracotomy and attempt ligation of
tion, route, dosage, and duration of treatment, the thoracic duct, where it passes into the chest.
due to the small numbers of reported cases and This area is hard to visualize, especially in an
the need for randomized controlled trials. infant. Thoracoscopy has several advantages,
Moreover, a current retrospective review, con- including a magnified view that may aid in iden-
ducted in order to develop an evidence-based tification of the duct and the site of chyle leak.
management algorithm for infants with chylotho- Moreover, this minimally invasive approach sig-
rax, concluded that octreotide has no advantage nificantly reduces the postoperative pain and
over complete enteric rest/total parenteral nutri- avoids future chest wall deformity. The possibil-
11  Pneumothorax and Chylothorax 161

ity of combining direct sealing, local pleurodesis, success rates [96]. A recently proposed safe and
and fibrin glue application results in high rate of successful option is thoracoscopic parietal pleu-
successful sealing of the leak [114]. ral clipping [98], a relatively easy technique,
Pleuroperitoneal shunt is a method to treat chylo- resulting in rapid control of the chylothorax with
thorax that connects the pleural space to the peri- drop in chest tube output. An alternative described
toneal cavity, providing chyle drainage without method is the mass ligation of the thoracic duct
losing the fluid. Shunts have been used with suc- and surrounding tissue between the aorta, azygos
cess in children refractory to conservative treat- vein, and esophagus, adjacent to the vertebral
ment and also in preterm infants and in fetuses body [122]. Another method to manage chylotho-
[77, 115]. However, this procedure is less per- rax is fluoroscopically guided percutaneous
formed today in neonates because of severe com- embolization of the thoracic duct, a successful
plications, such as shunt occlusion and interventional strategy even in children as well as
displacement, reported in 30–50% of cases [116]. in adults [123, 124]. However, literature regard-
Pleurodesis can be performed either chemically, ing pediatric lymphangiography with thoracic
instilling sclerosing agents (povidone-iodine, duct embolization is limited to some case reports,
OK-432, tetracycline, talc) into the pleural cavity because results a challenging procedure, espe-
through the chest tube, or surgically mechanical cially in infants. In fact in a series of six children
irritating the parietal pleura, possibly in associa- aged 9  months or younger, central lymphatics
tion with pleurectomy. This procedure has been were visualized in only two cases, both success-
used in cases where medical therapies failed and fully treated. The authors concluded that in these
duct ligation was not performed. During the last smaller children, technical success is decreased,
years, chemical pleurodesis has been proposed as given recommended low dosages of contrast and
an alternative to surgery in young infants, in the small size of lymphatics [125].
order to limit aggressive procedures in these
patients. Oxytetracycline has been described as
effective in the treatment of chylothorax in a pre- 11.7.8 Prenatal Management
mature baby [117]. OK-432 has been used as an
effective sclerosing agent in neonates and in Congenital chylothorax occurs in 1  in every
fetuses affected by severe chylothorax associated 12,000–15,000 pregnancies and is the most com-
with nonimmunologic hydrops [118, 119]. mon cause of pleural effusion in the neonatal
Povidone-iodine is reported as a safe and effec- period [126]. Because the normal mean percent-
tive option to treat refractory chylothorax in new- age of lymphocytes in the fetal blood is >80%,
borns, and, considering reported results (success this parameter cannot be used prenatally to
up to 80% of cases, no mortality and side effects ­characterize an effusion as chyle; therefore the
manageable without long-term sequelae), it term hydrothorax is used indifferently [54]. With
seems to be the agent of choice for chemical the advent of prenatal ultrasound, chylothorax
pleurodesis, although multicenter randomized has been diagnosed with increasing frequency,
studies are needed [120]. Infants with congenital presenting variable natural history, ranging from
chylothorax are exposed to significant fluid shift cases with spontaneous resolution to cases show-
and potential serious metabolic, immunologic, ing progression to hydrops that can be life-­
and nutritional complications [121]. The high threatening [127]. Overall mortality has been
risk of nosocomial infections in these patients reported to be between 22% and 53% based on
suggests the need for early surgical intervention. associated findings (abnormal karyotype, con-
However, in congenital cases, the thoracic duct genital anomalies, and hydrops fetalis), gesta-
can be more difficult to locate and ligate because tional age, and chylothorax duration and severity
of the variations in the course, shunts malfunc- [99]. Secondary causes of hydrothorax, including
tion because of fibrinous clotting or unfavorable chromosomal anomalies, infections, cardiac mal-
pressure gradients, and pleurodesis has variable formations, and other structural abnormalities,
162 S. Cacciaguerra et al.

have a higher rate of fetal demise and neonatal fetal pleural effusion has been proposed [54], but
mortality [126]. Chylothorax has a much better no consensus has been reached regarding the
prognosis when diagnosed after birth than when management of congenital chylothorax in the
discovered in utero, since during fetal life pleural prenatal period. Although the antenatal manage-
fluid can act as a space-occupying mass resulting ment is still a matter of debate, early diagnosis,
in lung growth impairment and then pulmonary prenatal thoracocentesis, and aggressive nonop-
hypoplasia [128]. erative postnatal treatment seem to decrease the
With advances in fetal therapy, fetuses with mortality rate.
severe pleural effusions seem to have an improved
outcome [129]. Prenatal interventions, such as
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 Congenital Pulmonary Airway
Malformations: From the Prenatal 12
Diagnosis to the Postoperative
Follow-Up

Arnaud Bonnard

12.1 Introduction 12.2 Histopathology and Lung

Development
Since a couple of years now, several things
evolved and changed for congenital pulmonary Congenital pulmonary malformations encompass
airway malformations (CPAM). From the under- all the cystic lung diseases which found an origin
standing of the malformation to the prenatal during the morphogenesis. This includes congen-
diagnosis and the rising place of the minimally ital cystic adenomatoid malformation (CCAM),
invasive surgery, CPAM became a subject of pulmonary sequestration, bronchogenic cyst, and
interest for all pediatric surgeons all over the pulmonary pneumoblastoma (PPB). The forma-
world. Most of the recent publications are related tion of cysts may be responsible of prenatal com-
to the surgery itself and the growing place of plications principally related to the volume of the
minimal invasive surgery helped by new instru- cyst (hydrops, fetal distress) and the compression
ments pushing further the indications. This does of the surrounding organs. Although many genes
not have to hide the recent progresses made in the have been identified to explain and better under-
comprehension of the pathology of these malfor- stand the lung morphogenesis, the main reason of
mations and especially the closed relations CPAM occurrence remains unknown.
between CPAM and pleuropulmonary blastoma
(PPB). In the first part, we will talk about the
classification and the pathology of these malfor- 12.2.1 Lung Development
mations. Then, we will move to the prenatal diag-
nosis and specifically the prenatal procedures The classical lung organogenesis has been
sometimes required in the severe form of described in five overlapping steps [1]. During
CPAM. At last, we will talk about surgery and the the embryonic phase (26–52 days of gestation),
follow-up. an endodermal outgrowth derived from the
primitive foregut divides and forms the early
tracheobronchial tree. In the pseudoglandular
phase (52  days to 16  weeks of gestation), the
A. Bonnard (*) primitive airway epithelium begins its differen-
Department of General Pediatric Surgery, tiation in neuroendocrine, ciliated, and goblet
Robert Debre Children University Hospital, APHP,
Paris, France cells, while cartilage and smooth muscle cells
e-mail: [email protected] emerge from the mesenchyme. The airway

© Springer Nature Switzerland AG 2019 167

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_12
168 A. Bonnard

branching pattern is completed in the canalicu- 12.2.2 Genes’ Involvement

lar or acinar phase (16 to 24–26 weeks of gesta-
tion), and the ­prospective gas-exchange region The discovery of numerous genes involved in
is developing: the respiratory bronchiole lung malformation revolutionized the idea that
increases, vascularization of peripheral mesen- congenital lung malformation was coming from a
chyme increases, and distal cuboidal epithelium simple incident occurring during one of the five
differentiates into alveolar types I and II cells steps previously described. Moreover, these
with the start of the surfactant production. genes share a common molecular pathway
Development of the distal pulmonary circula- between different malformations either the cystic
tion by vasculogenesis with capillaries is pres- adenomatoid disease or the PPB making the deci-
ent at 20  weeks. The saccular phase (24–26 to sion to be active for the surgeon instead of con-
36 weeks of gestation) is characterized by matu- servative crucial.
ration of the surfactant system, growth of the The current idea gives a preponderant role on
pulmonary parenchyma, and thinning of the bud elongation, bud induction, and bud arrest under
connective tissue or interstitium, going with an the influence of different signaling pathway [2].
important capillary network development. The Fibroblast growth factor (FGF) signaling pathway
alveolar phase extends from 36 weeks of gesta- appears to play an important role with its tyrosine
tion to at least 18 postnatal months in which true kinase receptor allowing to stimulate migration,
alveoli, with increased acinar complexity and proliferation, differentiation, and survival. In this
increased gas-exchange surface area, are family, the role of FGF10 and its receptor FGFR2 in
formed. This important point is considered lung branching is of particular interest (Fig. 12.1).
when the pediatric surgeon is dealing with a It appears as a driving force for branching capable
CPAM and especially when the time to undergo to induce epithelial proliferation and budding in
for surgery has to be decided. lung organ cultures. Thus, the hypothesis that

FGF10 FGF10
chemoattraction

FGF10 TGFβ FGF10

PTCH1
HIP1 Fn/αSMA
FGF10 FGFR2b FGFR2b
2b

FG
FR
chemoattraction

FR

SHH
FG

2b

SPRY2
BMP4
WNT
TGFβ YY1
FGFR2b cell
proliferation αSMA/
αSMA
ECM
MEK/ERK
cell proliferation / cell survial

Bud induction Bud elongation Bud arrest Cleft formation and

-inhibition of FGF10 expression de novo bud induction
-inhibition of cell proliferation

Fig. 12.1 Lung branching morphogenesis. From: elongates, the expression of SPRY2 and SHH increases.
O.  Boucherat. Paediatr Resp Rev 19 (2016) 62–68. Both act in a negative feedback loop that modulates
Reproduced with the permission of the authors. FGF10 expression and activity leading to inhibition of
Mesenchyme is depicted in gray and the epithelium in bud outgrowth. Subsequently, new foci of high FGF10
orange. FGF10 is expressed dynamically in the mesen- concentration emerge and induce bud tip bifurcation and
chyme. Epithelial cells, expressing the receptor FGFR2b, cleft formation. In this area, the synthesis of ECM compo-
respond to the FGF10 gradient by bud formation and bud nents induced by TGFb and WNT signaling pathways pre-
extension toward the local source of FGF10. As the bud vents further budding
12  Congenital Pulmonary Airway Malformations: From the Prenatal Diagnosis to the Postoperative… 169

FGF10 controls the directional outgrowth of lung been reported in literature [7]. In a personal non-
buds during branching morphogenesis has been published series, 37 patients were diagnosed pre-
established [3, 4]. Different signaling pathways natally with 12 pulmonary sequestration, 20
(sonic hedgehog (SHH), etc.), with feedback con- cystic adenomatoid malformation, and 5 hybrid
trol and inhibition control, are playing also an lesion. Twenty-four (65%) decrease in size, and
important role in this phenomenon. Mouse knock- 11% increase, while 24% remained stable and
out has been used to demonstrate this hypothesis. neither progressed nor regressed. This allows
This underlined the similar molecular pathway predicting the prenatal evolution and the clinical
shared by lung morphogenesis and pleuropulmo- presentation at birth. A serial US monitoring is
nary blastoma (PPB). Based on findings gained in necessary to detect any sign of fetal distress or
animal models and microscopic similarities predict a neonatal respiratory distress immedi-
between CCAM and type I PPB, it is tempting to ately after birth, meaning the mother should be
speculate that CCAM and PBB constitute distinct transferred to a level 3 pediatric center before
but related diseases whose etiology derives pre- delivery.
dominantly from the deregulation of SHH-FGF10
signaling. The majority of the research studies have
been done on surgical specimens; thus, data on 12.3.2 Are There US Findings
human fetus are lacking, and it is still difficult to Predictive of Neonatal
strictly relate these two entities. Nevertheless, this Respiratory Distress?
must stay in the surgeon’s mind when he/she is
dealing with pulmonary malformation. Different US findings have been reported in the
literature to predict this postnatal evolution [8].
Measurements of mass-to-thorax ratio (MTR),
12.3 Prenatal Diagnosis congenital pulmonary airway malformation vol-
ume ratio (CVR), and observed-to-expected
Progress has been made in both diagnosis and lung-to-head ratio (o/e LHR) were conducted and
prenatal intervention on fetus diagnosed with correlated to fetal or neonatal morbidity and mor-
congenital pulmonary malformation. In 2009, the tality and/or the need for prenatal intervention.
incidence has been reported to be between Fetuses with a CVR of <0.91 were significantly
1/11000 and 1/35000 [5]. There is an increasing less likely to experience adverse outcome or need
awareness of clinicians and the universal use of for prenatal intervention with good sensitivity,
latest ultrasound technology making the diagno- specificity, and positive/negative predictive value.
sis more frequent. Recently, the incidence has A MTR (mass-to-thorax ratio) of <0.51 had a
been reported to be 1/7200 [6]. negative predictive value of 0.96 of adverse
Two principal US findings are described pre- events with a sensitivity of 0.95. The o/e LHR
natally when a pulmonary malformation is sus- was reported to be less sensitive with sensitivity
pected usually on the second ultrasonography of 0.84 and specificity and positive predictive
screening: hyperechogenic lung or cystic lung. value of 0.73, 0.68, and 0.52, respectively. MRI is
Bronchogenic cyst is usually diagnosed easily not always necessary, but for bilateral lesion, it
showing an isolated cystic mass in the chest. can help to decide for future management.
Several questions are coming then for an ade- Basically, the size, the mediastinum shift per-
quate prenatal management. sistent during the third trimester, and the associa-
tion with hydrothorax are good indicators for in
utero transfer before delivery in a level 3 center
12.3.1 What Term Is It? with NICU and pediatric surgery available. In
this case, the risk for a neonatal respiratory dis-
It’s well known that these malformations used to tress is high and very predictive of an early neo-
decrease in size along the gestation. This has natal surgery.
170 A. Bonnard

12.3.3 Are There Any Signs of Fetal 12.3.4 What Prenatal Workout
Distress? Should Be Done?

Prenatal surgery may be required in case of severe The main question is about the possibility to have
neonatal distress. If a hydrops fetalis developed associated lesions and malformations in fetus
during pregnancy, indications to do something diagnosed prenatally with CPAM. Although rare
is  principally based on the type of CPAM. cases of CPAM associated with tracheo-esopha-
Macrocystic form with hydrops is a good indica- geal fistula or corpus callosum anomalies have
tion of drainage [9]. It may improve the neonatal been reported [13], included in the new 5 types of
survival rate (P < 0.005). Drain can migrate and be Stocker’s classification [14] where Type I and
dislodged. For this reason, a serial monitoring is Type III were described to be associated some-
needed after drain placement to make sure that the times with renal hypoplasia and cardiac abnor-
hydrops is resolving and the drain is still in place. malities, prenatal amniocentesis for karyotype is
Sometimes, an iterative drainage is required. not usual. Ultrasound large screening looking for
In case of microcystic form (hyperechogenic other malformations should be done anyway rou-
lung), drainage is not indicated. Steroids have tinely as a “non-CPAM” fetus. In contrary, look
been reported to be efficient in this indication for prenatal factors predictive of postnatal respi-
[10]. In this retrospective study, all patients ratory distress, and patients needing early surgery
referred to the center with CPAM were reviewed. are required. MRI has been proposed and reported
Betamethasone was given to 13 patients with in this indication. In our current practice, the
microcystic form of which 9 presented with a MRI is not done systematically but only for fetus
nonimmune hydrops. Hydrops resolved in seven presented with bilateral lesion, and/or important
(77.8%) of nine patients. Not all fetuses respond mediastinal shift persistent during the 3rd trimes-
to a single course of steroids, and, sometimes, ter with an important volume. Zamora and Coll
multiple courses might be indicated [11]. In this studied and reported in 2014 the need for the lung
retrospective study, single-course recipients dem- mass volume ratio (LMVR), observed/expected
onstrated a reduction in lesion size and resolution normal fetal lung volume (O/E-NFLV), and the
of hydrops in 82% and 88% of patients, respec- lesion-to-lung volume ratio (LLV) [15]. LMVR
tively, compared to 47% and 56% in recipients of was the strongest predictor of fetal hydrops (OR,
multiple steroid courses. Survival of multiple-­ 6.97, 1.58–30.84; P  =  0.01) of NNRD (OR,
course patients (86%) was comparable to that of 12.38, 3.52–43.61; P ≤ 0.001), and its value >2.0
single-course patients (93%) and improved com- predicted worse perinatal outcome with 83% sen-
pared to non-treated historical controls. Multiple-­ sitivity and 99% specificity (AUC  =  0.94;
course recipients demonstrated an increased need P < 0.001).
for open fetal surgery and may be predictive of
postnatal surgery at a younger age.
At last, fetal surgery has been purposed for 12.3.5 Do Parents Need a Prenatal
some cases [12]. A retrospective review of fetuses Counseling?
undergoing either open fetal surgery or steroids
for predominantly microcystic CPAM with Every parent should be seen for a CPAM diag-
hydrops fetalis was conducted. Thirteen patients nosed prenatally. Explanation on the CPAM,
were treated with steroids, and 11 patients got type, predictable evolution along the pregnancy,
open fetal surgery. In the steroid group, 12 (92%) management at birth, surgery, and long-term out-
survived to delivery versus 9 (82%) in the open come has to be discussed with them. To date, no
fetal surgery group. Only five (56%) in the open paper have been published reporting the effect or
fetal surgery group survived to neonatal dis- the influence of the prenatal CPAM diagnosis on
charge compared to ten (83%) in the steroid the outcome. Recognition of prenatal factors
group. The authors concluded that steroids should predictive of neonatal respiratory distress as
­
be considered for first-line therapy in these cases. described before is a crucial point and certainly
12  Congenital Pulmonary Airway Malformations: From the Prenatal Diagnosis to the Postoperative… 171

may play a role on the good outcome of such done before the surgery to plan the type of resec-
malformation with the level 3  in utero transfer, tion and give an accurate explanation to the par-
allowing a quick postnatal management for these ents (Fig.  12.3). Usually, postoperative courses
babies. are simple allowing to discharge back home the
baby after few days, depending essentially on the
term of birth, his/her weight, and the possibility
12.4 Postnatal Management to wean the mechanical ventilation off. We have
to keep in mind that babies with severe CPAM
12.4.1 At Birth with macrocyst diagnosed prenatally would
require for most of them prenatal procedures
Because more than 90% of babies diagnosed pre- such as repeat puncture and thoracoamniotic
natally with CPAM are doing great, these are shunt placement. Both are at risk of preterm
only managed by the pediatrician without even
being seen by the surgeon. A chest X-ray should
be done to rule out any mediastinal shift related
to an emphysema or a large cyst which can be
complicated by a pneumothorax (Fig.  12.2).
Usually, this X-ray is not showing something in
particular, and the baby is sent back home before
being followed up in an outpatient clinic. In our
center we used to perform a CT scan between 1
and 3 months old.
About 10% of patients present a neonatal
respiratory distress requiring for the worse cases
of mechanical ventilation and an admission in an
intensive care unit [16]. A discussion between a
pediatrician, a surgeon, and an anesthesiologist is
important to decide whether or not to undergo for Fig. 12.2  Chest X-ray at 1 day of life – cyst in the right
surgery and about the timing. A CT scan is often chest

Fig. 12.3  Chest X-ray and CT scan showing a large cyst. This baby required a surgery within 10 days of life for respi-
ratory distress
172 A. Bonnard

delivery. Hydramnios if present can increase this results of this meta-analysis showed that total
risk. This make sometimes the fetus at risk for morbidity (number of patients who experienced
preterm delivery making the postnatal manage- postoperative complications) was significantly
ment difficult with a preterm baby requiring an higher when surgery was performed after symp-
admission in NICU, eventually needing mechani- tom development compared to resection when
cal ventilation, and with complications related to patients were asymptomatic (OR 4.59, 95% CI
the preterm delivery (membrane hyaline disease, 1.40–15.11, P = 0.01). No death was reported.
brocho pulmonary dysplasia) [17]. Once you decide to operate, the question is
Rarely, thoracoamniotic shunt is completely should I perform a radical lobectomy or a
internalized and required a neonatal surgery to segmentectomy?
remove it because it is at risk for complication Multiple arguments are available in the litera-
[18]. This can be done thoracoscopically. ture in favor of both sparing surgery and radical
lobectomy. The surgeon should do what he/she
used to. In the area of mini invasive surgery, seg-
12.4.2 Treatment mentectomy is obviously more difficult to per-
form, and for the majority of this kind of surgery, a
For the majority of the patient, as previously pure anatomical segmentectomy is rarely done,
mentioned, the postnatal course from the respira- and a wedge resection using stapler or coagulation
tory wise is uneventful. A CT scan is done devices is performed. The CT performance to
between 1 and 3 months to confirm the diagnosis detect adenomatoid lesion extension within the
of CPAM, type, localization, and the presence of lobe was reported [19]. All patients who had
a systemic artery, allowing planning the surgery undergone a thoracoscopic lobectomy for CCAM
or the conservative treatment. located to one pulmonary lobe were reviewed ret-
Do all CPAM prenatally diagnosed should be rospectively. A thoracic radiologist performed a
treated surgically or conservatively?Infectious single-blind review of all preoperative computed
complications and malignancy with a risk of mis- tomographic (CT) scans, mentioning the presence
diagnosing a PPB in balance with the low postop- or absence of distant lesions from the main cysts of
erative complication rate after pulmonary CCAM within the pulmonary lobe. The patholo-
resection often make the surgical decision in these gist who analyzed the pulmonary lobectomy spec-
patients. This question has also been raised by 18 imen was aware of the diagnosis but not the CT
experts questioned on what could be the most rel- report. The median age at surgery was 12 months
evant question about CPAM treatment [18]. A (range, 2–24  months). On 12 patients diagnosed
response has been reported in this article by a with CPAM, the preoperative CT showed only two
review and a meta-analysis conducted on ten arti- cases with distant lesions within the affected pul-
cles selected on the criteria that can be analyzed monary lobe, whereas the histologic study of the
based on the primary outcome of interest which surgical specimen identified six cases. The sensi-
was postoperative morbidity including respiratory tivity to detect distant lesions of the CT scan was
distress, respiratory infection, pneumonia, pneu- low, 33%, whereas its specificity was high, 100%.
mothorax, and death and the secondary outcome Furthermore, the preoperative CT negative predic-
of interest which was the length of stay in hospital tive value was 60%. Because of poor sensitivity
following surgery. One hundred sixty-eight and very poor negative predictive value (60%) of
patients were asymptomatic at birth. Seventy the preoperative CT to determine distal adjacent
(41.7%) underwent elective surgery with seven lesions, lobectomy has our preference.
(10.0%) cases of postoperative complications. More important is the risk of residual disease
The 98 remainder patients were managed expec- left in place after the surgery. Furukawa T published
tantly (58.3%), with 64.3% developing symptoms his data and evaluated the risk to be 11% [20]. In a
between 1 month and 7 years of age and conse- paper presented to the EUPSA annual congress in
quently requiring surgery. Twenty of these experi- Limassol in 2017, this rate has been reported to be
enced postoperative complications (31.8%). The 17% [21]. Once you decide to undergo for surgery,
12  Congenital Pulmonary Airway Malformations: From the Prenatal Diagnosis to the Postoperative… 173

explanations given to parents should be clear and [22]. If for some reason, mini invasive surgery is
talk about this risk. Thus, in case of sparing paren- not the preferable surgical approach and the team
chyma surgery, monitoring has to be done, and all want to start a MIS program in pulmonary resec-
children would require a postoperative CT scan to tion, the results at least have to be reported as
evaluate the presence or absence of this residual good as the open approach. In a study from 2015,
disease. If it’s present, a redo surgery should be pro- on univariate analysis, thoracoscopic resection
posed to complete the resection. was associated with decreased postoperative
Should I prefer mini invasive surgery (MIS) or complications (9.8% vs. 25.3%, P = 0.001) and
classical open thoracotomy surgery? length of stay (3 vs. 4 days, P < 0.001). However,
Obviously, development of 2, 3, or 5  mm after adjusting for similar patient and operative
instruments is making the mini invasive surgery characteristics, no significant differences were
required for the congenital pulmonary malforma- encountered between techniques. In this paper,
tion. A 3 mm coagulation device and a 5 mm sta- both techniques provide comparable 30-day out-
pler are now available to help the surgery comes and safety in the management of congeni-
(JustRight Surgical, Boulder, Colorado, USA) tal lung malformations [23] (Fig. 12.4).

a b

c d

Fig. 12.4  Thoracoscopic removal of CCAM. Thoracoscopic view of the malformation (on the left) (a); resection with
5 mm stapler (b, c); final view after removal (d)
174 A. Bonnard

Most importantly, MIS associated with multi- using a CT scan every year for congenital cystic
modal analgesia allowed to treat patients with a malformation which is raising the risk of cumu-
fast-track way. The length of stay is reduced to lated doses of irradiation in the child. Extra-lobar
1 day for lobectomy, and even some patients with sequestration is theoretically not at risk for infec-
extra-lobar sequestration are operated on as day tious complication, but leaving in place this
case surgery [24] (Fig. 12.5). lesion for a long time period is certainly some-
Does all the congenital lung malformation thing risky as it can grow and develop and cause
have to be operated? complications in adulthood [25]. Emphysema
If macrocystic CPAM, bronchogenic cyst, and has also been treated conservatively. Langer [26]
intralobar sequestration are lesions which reported 14 children managed without surgery
required a surgery without any doubt, surgical doing well but with a median follow-up of
resection of small cystic lesion less than 3  cm, 2.5 years (range, 0–8 years). Significant medias-
emphysema, or extra-lobar sequestration is still a tinal shift was observed at diagnosis in seven of
matter of debate. The reflection is based on the them, and two demonstrated collapse of adjacent
profit and risk balance of the surgery. As we have lobes or segments. Follow-up imaging showed no
seen, the risk of MIS in experienced hands is very significant radiological change in 12, making dif-
low. In contrast, in case of conservative manage- ficult to know what will occur on the adjacent
ment, a serial monitoring has to be done, mostly lobe with a longer period time of follow-up.

a b

c d

Fig. 12.5  Thoracoscopic removal of extra-lobar pulmonary sequestration (a). Thoracoscopic view of the sequestration:
ligature of feeding vessel with two endoloops (b, c); section of the vessels (d)
12  Congenital Pulmonary Airway Malformations: From the Prenatal Diagnosis to the Postoperative… 175

12.5 Conclusion disease? Result of a prospective registry with uni-

versal antenatal screening program. Pediatr Surg Int.
2017;33(1):105–8.
At the light of what has been said and published, 7. Shanmugam G, MacArthur K, Pollock JC. Congenital
for all lesions diagnosed prenatally, we proposed lung malformations--antenatal and postnatal evalua-
a CT scan between 1 and 3 months of life and a tion and management. Eur J Cardiothorac Surg.
2005;27(1):45–52.
surgery if the lesion is confirmed between 2 and 8. Hellmund A, C B, Geipel A, Bludau M, Heydweiller
4  months. Mini invasive surgery is the surgical A, Bachour H, Müller A, Müller A, Gembruch
approach of our choice allowing to operate as a U. Prenatal diagnosis and evaluation of Sonographic
day case surgery for bronchogenic cyst and intra- predictors for intervention and adverse outcome in
congenital pulmonary airway malformation. PLoS
or extra-lobar sequestration or with a 1-day length One. 2016;11(3):e0150474.
of stay for noncomplicated CPAM. Follow-up is 9. Knox EM, Kilby MD, Martin WL, Khan KS. In-utero
done by a combined team with a pneumonologist pulmonary drainage in the management of primary
and a surgeon, principally based on the clinical hydrothorax and congenital cystic lung lesion: a
systematic review. Ultrasound Obstet Gynecol.
evolution and the clinical exam, every 3 months at 2006;28:726–34.
the beginning and every 6 months or year if the 10. Curran PF, Jelin EB, Rand L, Hirose S, Feldstein VA,
patient is doing well. For other lesions (symptom- Goldstein RB, Lee H. Prenatal steroids for microcys-
atic at birth, complicated, etc.), attitude can be tic congenital cystic adenomatoid malformations. J
Pediatr Surg. 2010;45(1):145–50.
changed from the time to undergo for surgery to 11. Peranteau WH, Boelig MM, Khalek N, Moldenhauer
the surgical approach, the length of stay, etc. mak- JS, Martinez-Poyer J, Hedrick HL, Flake AW, Johnson
ing this pathology i­nteresting by all the varieties MP, Adzick NS. Effect of single and multiple courses
that it can offer to the pediatric surgeon. of maternal betamethasone on prenatal congenital
lung lesion growth and fetal survival. J Pediatr Surg.
2016;51(1):28–32.
12. Loh KC, Jelin E, Hirose S, Feldstein V, Goldstein
References R, Lee H. Microcystic congenital pulmonary airway
malformation with hydrops fetalis: steroids vs open
fetal resection. J Pediatr Surg. 2012;47(1):36–9.
Lung Development 13. Pizzi M, Fassan M, Ludwig K, Cassina M, Gervasi
MT, Salmaso R.  Congenital pulmonary airway mal-
1. Warburton D, El-Hashash A, Carraro G, Tiozzo formation (CPAM) [congenital cystic adenomatoid
C, Sala F, Rogers O, De Langhe S, Kemp PJ, malformation] associated with tracheoesophageal fis-
Riccardi D, Torday J, Bellusci S, Shi W, Lubkin SR, tula and agenesis of the corpus callosum. Fetal Pediatr
Jesudason E. Lung organogenesis. Curr Top Dev Biol. Pathol. 2012;31(3):169–75.
2010;90:73–158. 14. Stocker JT.  Congenital and developmental diseases.
2. Boucherat O, Jeannotte L, Hadchouel A, Delacourt In: Dail DH, Hammar SP, editors. Pulmonary pathol-
C, Benachi A.  Pathomechanisms of congenital ogy. 3rd ed. New York: Springer; 2008. p. 154–80.
cystic lung diseases: focus on congenital cystic 15. Fetal Zamora IJ, Sheikh F, Cassady CI, Olutoye OO,
Adenomatoid malformation and Pleuropulmonary Mehollin-Ray AR, Ruano R, Lee TC, Welty SE, Belfort
Blastoma. Paediatr Respir Rev. 2016;19:62–8. MA, Ethun CG, Kim ME, Cass DL. MRI lung volumes
3. Bellusci S, Grindley J, Emoto H, Itoh N, Hogan are predictive of perinatal outcomes in fetuses with con-
BL. Fibroblast growth factor 10 (FGF10) and branch- genital lung masses. J Pediatr Surg. 2014;49(6):853–8.
ing morphogenesis in the embryonic mouse lung.
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4. Sekine K, Ohuchi H, Fujiwara M, Yamasaki M,
Yoshizawa T, Sato T, Yagishita N, Matsui D, Koga Y, Postnatal Management
Itoh N, Kato S. Fgf10 is essential for limb and lung
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P, Lista G, Zirpoli S, Napolitano M, Riccipetitoni
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17. Law BH, Bratu I, Jain V, Landry MA.  Refractory
5. Master IB.  Congenital airway lesions and lung dis- tension pneumothorax as a result of an internally dis-
ease. Pediatr Clin North Am. 2009;56(1):227–42. placed thoracoamniotic shunt in an infant with a con-
6. Lau CT, Kan A, Shek N, Tam P, Wong KK.  Is con- genital pulmonary airway malformation. BMJ Case
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18. Kapralik J, Wayne C, Chan E, Nasr A.  Surgical

22. Rothenberg S.  Thoracoscopic lobectomy in infants
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2016;51(3):508–12. SD, Cilley RE, Dillon PW. Comparing 30-day outcomes
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tic adenomatoid malformation? J Pediatr Surg. from NSQIP. J Pediatr Surg. 2015;50(10):1716–21.
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 Congenital Diaphragmatic Hernia
13
Mario Lima, Michela Maffi, Giovanni Parente,
and Chiara Cordola

13.1 Introduction chromosomal anomalies (13, 18, 21 trisomy and

chromosomal deletions) [1–6].
Diaphragmatic hernia of the newborn is a con- The current classification of congenital dia-
genital malformation due to an anomaly in the phragmatic hernia (CDH) is based on the anat-
diaphragm’s development causing the herniation omy of the defect:
of the abdominal viscera into the thorax.
Birth prevalence of this condition is estimated • Posterolateral hernia (Bochdalek’s hernia):
to be 1 per 3300 live births with no differences accounts for more than 90% of all CDHs; in
between geographical regions or race. 80% of the cases the left side of the diaphragm
The development of intensive neonatal care and in 15–20% the right side is affected. A
changed the natural history of this condition bilateral posterolateral defect is extremely
decreasing the mortality rate from 50% to 60% in rare (Fig. 13.1a).
the 1970s to 20% at present, even though the dis- • Anterior hernia (Morgagni–Larrey): 2% of all
ability burden in survivals is still high. CDHs; it involves the parasternal or retroster-
The etiology of this congenital defect is still nal part of the diaphragm (Fig. 13.1b).
unknown. It is considered a sporadic malforma- • Central hernia: central tendon defect of the
tion, although about 40% of the cases have asso- diaphragm, 1% of all cases (Fig. 13.1c).
ciated anomalies, most frequently of the • Diaphragmatic eventration: abnormal eleva-
cardiovascular system followed by the genitouri- tion of the diaphragm, which appears intact
nary (23%), gastrointestinal (14–17%), central but thinner, allowing the protrusion of the
nervous (14%), and musculoskeletal systems abdominal viscera upward (Fig. 13.1d).
(10%). Far from identifying a gene responsible
for this malformation, some series talk about a
multifactorial etiology involving both genetics 13.2 Embryology
and the environment. It can occur as part of a syn-
drome (Fryns, Donnai–Barrow, Beckwith– The diaphragm formation determines the separa-
Wiedemann, Denys–Drash) in addition to tion of the abdominal cavity from the thoracic cav-
ity, and is completed at gestational week 8. Four
different structures are required for this process:
M. Lima (*) · M. Maffi · G. Parente · C. Cordola
Department of Pediatric Surgery, S.Orsola Hospital,
• Septum transversum
Bologna University, Bologna, Italy • Pleuroperitoneal membranes
e-mail: [email protected] • Esophageal mesentery

© Springer Nature Switzerland AG 2019 177

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_13
178 M. Lima et al.

a b

c d

Fig. 13.1 (a) Posterolateral hernia. (b) Anterior hernia. (c) Central hernia. (d) Eventration

• Muscle fibers from the thoracic intercostal posterolateral body wall running medially and
muscle groups ventrally to fuse with the septum transversum
and the esophageal mesentery obliterating the
The septum transversum, destined to become pleuroperitoneal canals. The right side closes
the central tendon of the diaphragm, forms at before the left side, and the entire process is
gestational week 4 from the inferior portion of complete at gestational week 8. At this moment,
the pericardial cavity and represents the first but myoblasts migrate from the thoracic intercostal
incomplete separation of the abdomen from the muscle groups, and the muscularization of the
thorax and defines the pleuroperitoneal canals. diaphragm takes place.
At about the sixth week of gestation, the pleu- An anomaly at various levels of the described
roperitoneal membranes start to grow from the process results in CDH formation [1–6].
13  Congenital Diaphragmatic Hernia 179

13.3 Diagnosis and Clinical lateral ventricles. The LHR can be measured using
Features either ultrasound or fetal MRI, and for values
lower than 0.8, mortality is almost 100%, whereas
13.3.1 Antenatal a value higher than 1.5 gives a good prognosis.
As the LHR is strictly dependent on gesta-
Currently, more than 56% of CDHs are diag- tional age, it has nowadays been replaced by the
nosed prenatally during routine ultrasound, more reliable observed/expected LHR (O/E
which can reveal the presence of the defect from LHR) obtained by dividing the LHR calculated
gestational week 14. for the mean LHR of the respective week of
Sonographic signs that should lead the clini- gestation.
cian to the diagnosis of CDH are: All fetuses with a prenatal diagnosis of CDH
should undergo a chromosomal evaluation with
• The presence of cystic images or heteroge- fetal karyotyping [12–17].
neous echoes on the fetus thorax
• An interrupted hypoechoic line separating the
thorax from the abdomen 13.3.2 Neonatal Period
• A gastric bubble above the diaphragm
• An abdominal circumference below the Owing to pulmonary hypoplasia, these patients
expected values for gestational age experiment varying degrees of respiratory
• A mediastinal shift that may lead, if remark- distress.
able, to fetal hydrops A peculiarity of the disease is an initial
moment in which these babies present with
In severe right CDH with herniation of the almost adequate ventilation and oxygenation
liver, its identification in the chest cavity could be (“honeymoon”) followed by a quick worsening
difficult owing to the very similar echodensity of respiratory function due to the occurrence of
between the lung and liver itself. permanent pulmonary hypertension with regres-
A reduced amount of lung tissue seen on sion to the antenatal pattern of blood circulation
ultrasound from the 18th week onward may be that leads to hypoxia, hypercarbia, and acidosis,
another sign of CDH. exacerbating in a vicious cycle the pulmonary
Polyhydramnios, even if nonspecific, could be hypertension itself.
a sign of CDH as its presence depends on the her- The situation becomes even more critical as
niation of the stomach kinking the esophagogas- the neonate starts to swallow air, which distends
tric junction, making the fetus unable to swallow the intrathoracic viscera, worsening lung com-
the amniotic fluid. pression and thus function.
Differential diagnosis includes all intratho- At the clinical examination, the neonate shows
racic isolated lesions such as congenital cystic signs of respiratory distress (tachypnea, tachy-
adenomatoid malformation, sequestration, and cardia, chest wall recession, nasal flaring) with
foregut duplications. decreased or absent respiratory sounds ipsilateral
If available, fetal magnetic resonance imaging to the hernia together with a clearly visible barrel
(MRI) helps clinicians to give a better assessment chest and a scaphoid abdomen.
of lung volume and organ herniation and guides The diagnosis is confirmed with a chest X-ray,
them to differential diagnosis [7–11]. which typically shows:
A recently introduced parameter, called the
lung-­to-­head ratio (LHR), could be evaluated as a • Intrathoracic intestinal loops
prognostic value. The LHR could be obtained by • Nasogastric tube up in the thorax
dividing the area of the contralateral fetal lung at • Absence of a diaphragmatic profile
the level of a four-chamber view of the heart for • Contralateral mediastinal shift
the fetal head circumference at the level of the • If herniated, an intrathoracic liver segment
180 M. Lima et al.

13.3.3 Misdiagnosed CDH A nasogastric tube should be placed to decom-

press the stomach and the intestinal loops
There are sporadic cases of CDH diagnosed in herniated.
infancy or childhood that had been previously Monitoring is essential and requires:
asymptomatic.
Occasionally, it is diagnosed by a chest X-ray • An umbilical artery catheter to evaluate sys-
done for reasons other than suspected CDH temic arterial pressure
(respiratory infections, reactive airways disease, • A vesical catheter to obtain a reliable urine
dyspnea on exertion), but frequently it becomes output
symptomatic as a result of intestinal loop incar- • Preductal pulse oximetry (right arm)
ceration or even a volvulus. • Postductal pulse oximetry to evaluate the
entity of right-to-left shunting

13.4 Management Echocardiography should be performed to

study cardiac function and diagnose cardiac
13.4.1 Antenatal anomalies.
In the literature there is evidence for pulmo-
If a CDH is suspected, it is strongly recom- nary immaturity and surfactant deficiency; exoge-
mended to refer the parents of the future baby to nous surfactant is thus immediately administered.
a center that can guarantee a multidisciplinary As pulmonary hypertension is one of the most
team of physicians (neonatologists, geneticists, significant causes of mortality, its treatment plays
pediatric surgeons). a remarkable role in postnatal management.
Fetal karyotyping should be routinely per- Inhaled nitric oxide (iNO) has been introduced
formed to exclude chromosomal anomalies. with great results as it effectively reduces the ven-
Prenatal treatment of CDH is focused on con- tilation/perfusion mismatch with a selective action
trasting pulmonary hypoplasia and based on fetal on alveolar capillaries and it is quickly degraded
tracheal occlusion. The best tolerated method once it reaches the systemic circulation. Moreover,
with fewer adverse events (tracheomalacia, tra- iNO does not appear to have any major side effects.
cheomegaly, tracheal ring injury) consists in the Unfortunately, tachyphylaxis often occurs.
endoscopic placement of a balloon in the fetus’ If conventional ventilation with gentle pres-
trachea (fetoscopic tracheal occlusion, FETO) sure (it is important to avoid barotrauma) is not
creating an obstruction that contributes to lung sufficient, the passage to high-frequency oscilla-
development. The timing of the procedure is tory or jet ventilation should be considered.
extremely important: FETO is performed If adequate control of hypoxia, hypercapnia,
between 28 and 30 weeks’ gestation, and the bal- and pulmonary hypertension is not reached,
loon is removed 4–6  weeks later. Nevertheless, extracorporeal membrane oxygenation (ECMO)
FETO is associated with a significant risk for pre- is indicated [9, 18–28].
maturity, and current reported survival rates are
on average around 50%. As only a few trials are
evaluating the benefits of FETO, it should not be 13.5 Surgical Repair
used until more significant results are available
[11]. 13.5.1 Surgical Timing

In the past, CDH was considered a surgical emer-

13.4.2 Postnatal gency; nowadays, even though the debate around
the perfect timing is still open, delayed surgical
The priority for this type of patient is to guaran- repair is widely practiced.
tee adequate ventilation; therefore, most need The latest guidelines of the Canadian
endotracheal intubation. Congenital Diaphragmatic Hernia Collaborative
13  Congenital Diaphragmatic Hernia 181

emphasize the importance of medical stabiliza- At this point, the diaphragmatic defect can be
tion and suggest that the following physiological examined: in about 20% of patients a hernia sac
criteria should be met before surgery: can be found, formed of the parietal pleura and
the peritoneum, and this sac has to be excised to
• Urine output >1 ml/kg/h allow complete healing and to reduce the risk of
• FiO2 <0.5 mmHg recurrence.
• Preductal oxygen saturation between 85% and If there is enough tissue after mobilizing the
95% anterior and posterior edges of the defect, it can
• Normal mean arterial pressure for gestational be primarily closed with simple or mattress
age sutures. The posterior edge may be deficient; in
• Lactate <3 mmol/L this case, the surgeon should try to expose it bet-
• Estimated pulmonary artery pressure less than ter by sharply incising the overlying peritoneum
systemic pressure or suturing the anterior rim directly to the chest
wall, placing sutures around the ribs.
However, the failure to meet these criteria During this process, the surgeon should take
within 2 weeks should not prevent an attempt at a care not to cause a chest deformity because of the
surgical approach, which still remains the only closure attempt was too aggressive.
treatment that gives a chance of long-term If the native diaphragm is not enough to close
survival. the defect, several techniques for overcoming the
The perfect timing is a subtle equilibrium lack of tissue have been described in the litera-
among the potential improvements in pulmonary ture: using a muscular flap, prerenal fascia, or a
hypertension that can occur when delaying sur- rib structure (Fig. 13.2e, f). However, the use of
gery, the risk of pulmonary injury associated with prosthetic material to close the gap has gained
prolonged ventilation, and the possible suffering consensus, and the latest recommendations on
of herniated viscera [29–33]. CHD suggest the use of tension-free polytetraflu-
oroethylene/GORE-TEX patches; bio-prosthetic
materials can be used too, but because of a higher
13.5.2 Open Transabdominal Repair risk of recurrence, they are not recommended.
The chosen patch has to be carefully cut to
Laparotomy is usually performed with a subcos- resemble the shape and size of the defect and
tal incision on the side of the hernia approxi- then fixed with interrupted sutures to the edges of
mately one fingerbreadth below the costal margin the diaphragmatic defect.
(Fig. 13.2a). After closing the diaphragm, accurate control
The diaphragmatic defect is exposed by of the bowel and other herniated viscera has to be
retracting the upper portion of the wound in a managed to identify any sign of suffering or other
cephalic direction (Fig. 13.2b). Then, the abdom- anomalies that must be corrected before com-
inal viscera are gently reduced in the abdomen to plete closure.
avoid trauma (Fig. 13.2c, d). The abdomen is closed in layers when possi-
In the case of small defects, extraction of the ble. If primary closure generates significant
viscera should be performed in the following order: abdominal pressure, it should be avoided so as not
to cause an abdominal compartmental syndrome.
1. Left CDH: stomach, small intestine, cecum, These situations require either a simple clo-
ascending colon, transverse colon, and spleen. sure of the skin delaying that of the abdominal
2. Right CDH: the liver has to be replaced last wall or the use of a temporary prosthetic material
after the small intestine and colon. such as a GORE-TEX patch.
A chest tube can be placed in the side of the
The reduction of the abdominal viscera repair depending on the surgeon’s preference and
requires a careful check of the orientation of the on the presence of bleeding or possible air leak-
mesentery. age [34–37].
182 M. Lima et al.

a b

c d

e f

Fig. 13.2  Open transabdominal CDH repair: (a) subcostal incision; (b–d) reduction of viscera into the abdomen; (e, f)
closure of the defect (GORE-TEX patch)
13  Congenital Diaphragmatic Hernia 183

13.5.3 Video-Assisted Thoracoscopic If there is a hernial sac, the insufflation itself

Repair reduces the organs in the abdomen; the stomach
and intestinal loops are reduced first, followed by
Video-assisted thoracoscopic surgery (VATS) the spleen, which should always be the last organ
combines great visual clarity with less postopera- to be repositioned (Fig. 13.4b–d).
tive pain and better cosmesis. Despite these sig- Next step is the correction of the defect,
nificant advantages, thoracoscopic CDH repair is which should be closed using nonabsorbable
afflicted by a higher risk of recurrence; thus, the interrupted sutures (the author prefers Ethibond
author recommends that VATS should be per- 2/0 or 3/0).
formed only by expert teams well trained in mini- If the posterior edge is difficult to obtain, a
mally invasive surgery and in a restricted selected patch of GORE-TEX should be placed instead of
population of patients. performing direct closure. The author suggests
The patient is placed in a lateral, slightly semi-­ the introduction into the chest cavity of a piece
prone position (Fig.  13.3); the surgeon is at the of sterile glove that can be cut to the size and
patient’s head with the monitor in front of him/her. shape of the defect (Fig. 13.4e). Once extracted,
The assistant stands in front of the patient and the the glove is used as a template for the GORE-
scrub nurse at the end with the baby. TEX, which can be placed to close the diaphrag-
Thoracoscopic repair requires the placement matic gap (Fig. 13.4f).
of three trocars: We suggest a chest drain (aspiration,
5–10  mmHg), which may help lung expansion
• An optic port (5-mm trocar), below the tip of [38–40].
the scapula
• An anterior working port (3-mm trocar), fifth
intercostal space on the anterior axillary line 13.5.4 Complications
• A posterior working port (3-mm trocar),
fourth intercostal space between the optic port • Recurrence represents the main complication
and the spinal column of CDH repair. It accounts for 10% of oper-
ated patients, especially those who needed a
Once the optic port is correctly allocated, prosthetic patch. It mostly occurs within the
insufflation of CO2 is started taking care not to first year of life.
expose the baby to prolonged insufflation and • Adhesion-related bowel obstruction.
high pressure (4–8 mmHg and intermittent insuf- • Chylothorax due to lesions to the thoracic
flation are generally safe). At this point, the lung duct.
collapses, and the surgery can begin (Fig. 13.4a).

13.5.5 Outcome

Nowadays, the overall survival rate is 67% and

61% of those receiving ECMO survive.
The main causes of CHD mortality are pulmo-
nary hypoplasia and hypertension.
Children who have undergone CDH repair are
likely to suffer from gastroesophageal reflux,
exercise intolerance and wheezing, scoliosis, and
chest wall asymmetry.
Fig. 13.3  Patient position and trocar placement for per-
forming a thoracoscopic CDH repair. The orange dot indi-
Nonisolated CDH carries all the morbidity
cates the site of the optic port and the blue dots indicate and mortality of the associated syndromes and
the two working ports accompanying anomalies [41–50].
184 M. Lima et al.

a b

c d

e f

Fig. 13.4  Thoracoscopic CDH repair. (a) CDH presentation; (b, c) viscera reduction; (d) diaphragmatic defect; (e)
modeling of a sterile finger glove as a template for the patch; (f) GORE-TEX patch
13  Congenital Diaphragmatic Hernia 185

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 Esophageal Atresia
and Tracheoesophageal Fistula 14
David C. van der Zee, Maud Y. van Herwaarden,
Stefaan H. Tytgat, Michela Maffi, and Mario Lima

14.1 Definition 14.3 Pathogenesis

Esophageal atresia (EA) with or without tracheo- EA-TEF occurs early (22–23 days) in foetal life
esophageal fistula (TEF) represents a congenital when the endodermal epithelium, shaped as a
developmental anomaly. It is the most common tube that runs from the oral ectoderm to the cloa-
congenital malformation of the esophagus char- cae, undergoes morphologic changes that pre-
acterized by an esophageal discontinuity (the cede the development of the respiratory and
upper esophagus terminates in a blind-ending digestive tracts. In normal development, the
pouch) and a possible tracheoesophageal connec- proximal part of the endodermal tube, that is, the
tion [1–3]. foregut, branches starting from two ventral evagi-
nations generating either the tracheobronchial
tree and the lungs (proximal) or the ventral pan-
14.2 Epidemiology creas, biliary system and the liver (distal). The
respiratory system develops by the separation of
The reported incidence is between 1 in 2500 and the anterior part of the foregut from the posterior
1 in 4500 live births with males having a slight component (future esophagus). In this model, the
increased incidence. Mothers of white ethnicity single foregut tube divides longitudinally in two
have a higher prevalence of EA with or without by the progressive development of two lateral
TEF. The great majority of cases occur as a spo- epithelial ridges.
radic phenomenon although an increased inci- The division of the respiratory and esophageal
dence in twins is described. The advancement of tracts is complete by the time that the embryo is
surgical techniques and neonatal intensive care 6–7 weeks old. The exact pathogenesis of con-
has increased the survival rate up to 90% [1–3]. genital EA-TEF remains unknown and no single
unifying theory has been proposed. The first
abnormal embryogenetic event seems to be a late
D. C. van der Zee · M. Y. van Herwaarden separation of the respiratory component of the
S. H. Tytgat
Department of Pediatric Surgery, University Medical foregut related to defective epithelial-­
Center Utrecht, Wilhelmina Children’s Hospital, mesenchymal interactions. The upper pouch
Utrecht, The Netherlands seems to be the result of degeneration or atrophy
e-mail: [email protected] of the digestive half of the foregut. The notochord
M. Maffi · M. Lima (*) is abnormal at the level of the atresia playing an
Department of Pediatric Surgery, S.Orsola Hospital,
Bologna University, Bologna, Italy
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 187

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_14
188 D. C. van der Zee et al.

important role in the separation process. The aeti- Feingold syndrome, AEG (anophthalmia,
ology of EA-TEF is likely multifactorial esophageal, genital), x-linked Opitz syndrome,
­including environmental, genetic and epigenetic Goldenhar syndrome and Fanconi anaemia.
factors. Most of the cases are related to de novo Specific chromosomal disorders are found in up
mutations, while familial recurrence rate is 1%. to 10% of cases. All these rates are higher in
Studies of mouse and rat models have led to the patients with pure EA than in patients with
assumption that several molecular pathways are EA-TEF.
involved in the separation of the primitive foregut The other 50% of patients have non-syndromic
tube into dorsal and ventral components: vitamin associations: heart and great vessels are involved
A seems essential for proper foregut develop- in 24%, the digestive tract in 21%, the skeletal
ment; hedgehog pathway (including the family system including the vertebral column in 14%
components shh, dhh, ihh and the zinc-finger and the central nervous system in 7%.
transcription factors Gli1, Gli2, Gli3) plays an
integral role in foregut morphogenesis allowing
proper tracheoesophageal separation and foregut 14.5 Classification
development [1–4].
In 1929 Vogt recognized and classified EA based
on radiological findings. After the first successful
14.4 Clinical and Syndromic surgical approaches, various new anatomical
Associations classifications were proposed. In 1944 Ladd
introduced a classification system that was later
EA-TEF is associated with a very high inci- used by Gross in 1953 replacing the Roman
dence of congenital anomalies, affecting other numerals with alphabets. Later, Swenson returned
parts of the alimentary canal or other systems to a numeric classification with Arabic numbers
of the body and impacting both treatment and (1962) and Kluth added a list of EA variations
outcome. Anatomic malformations are that lead to ten separate classes and additional
described in more than 50% of cases. Half of all subclasses (1976). The anatomic classification is
EA-TEF-associated anomalies can be included still the most used (Fig. 14.1).
in recognizable syndromes: the most common In particular the malformation may present in
are those within the VACTERL spectrum (ver- five forms:
tebral anomalies, anorectal atresia, congenital
heart lesions, tracheoesophageal defects, renal –– Type I EA = esophageal atresia without fistula
and limb abnormalities); other genetic syn- (pure atresia) is the second most frequent
dromes are CHARGE (coloboma, heart defects, anomaly (8.4%) and consists of two blind
choanal atresia, growth and mental retardation, esophageal ends with a “long-gap” between
genito-urinary defects, ear abnormalities), the two pouches. It should be differentiated by

Type I Type II Type III Type IV Type V

Fig. 14.1  EA-TEF anatomic classification

14  Esophageal Atresia and Tracheoesophageal Fistula 189

type II EA as there is often a “missed fistula” culties, barking cough, expiratory stridor and
between the upper pouch and the trachea. cyanotic spells. Tracheomalacia may sustain
–– Type II EA = esophageal atresia with a proxi- respiratory symptoms unresponsive to medi-
mal tracheoesophageal fistula is an uncom- cal treatment and may impair clearance of
mon anomaly (2.1%). The abdomen is airless, secretions. The diagnosis is established by
and their anomaly is frequently misdiagnosed bronchoscopy. Most infants do not require
as type I EA unless accurate endoscopic eval- surgical corrections as the situation improve
uation or contrast studies are performed. with time. In case of life-threatening events,
–– Type III EA  =  esophageal atresia with distal the operation of choice is aortopexy that con-
tracheoesophageal fistula is the most common sists of suturing up the aortic arch and the
abnormalities (82.2%). It occurs when the ascending aorta to the posterior surface of the
upper esophagus ends blindly, the distal sternum after partial thymectomy. The opera-
esophagus opens in the trachea (about 1  cm tion is performed through a left anterior medi-
above the carina or rarely in the left/right main astinotomy, anterolateral thoracotomy,
bronchus) as an end-to-side fistula and there is cervical incision or thoracoscopy. In case of
a 1–2  cm long-gap between the two esopha- failure, airway stent can be considered as
geal stumps. Variations of this type include a alternatives, and tracheostomy is the final
wider or shorter gap that can be more than treatment.
2  cm long or absent (a membrane interrupts
the lumen, and the muscular layers of the In 1962, in addition to the reported classifica-
esophagus are in continuity). tions, Waterston proposed a risk-based stratifica-
–– Type IV EA = atresia with double (proximal tion of patients with EA-TEF considering birth
and distal) tracheoesophageal fistula is found weight, the presence of pneumonia and associ-
in 3.4% of cases. ated congenital anomalies (Table  14.1). This
–– Type V EA = tracheoesophageal fistula with- scheme permits the identification of factors that
out atresia (H-type, 3.3% of cases) may predict the prognosis and guide the management.
­present in older children with cough, recurrent Infants with “low” risk (A) undergo immediate
pulmonary infections and abdominal surgical repair, “moderate”-risk (B) patients were
distension. operated on after a period of adequate stabiliza-
tion, and “high”-risk (C) patients were treated
Patients with EA-TEF have also other ana- with staged repair. Some authors questioned the
tomical features that influence the clinical picture validity of this classification scheme and searched
and the prognosis: for others factors related to survival. Randolph
(1989) included the evaluation of the overall
–– Hypertrophy of the proximal pouch related to
foetal amniotic fluid swallowing and tracheo-
Table 14.1  Waterston classification
esophageal adhesion at the level of the pos-
terolateral wall of the trachea. Waterston risk-based classification
Survival
–– Hypoplastic distal esophagus and fistula due Group (%) Waterston classification
to the absence of a functional challenge. A 100 Birth weight > 2500 g and otherwise
–– Tracheomalacia that is a condition related to healthy
the reduction of the cartilage amount with a B 85 Birth weight 2000–2500 g and well
relative increase of the muscular component Birth weight > 2000–2500 g with
moderate associated anomalies
in the tracheal wall. The effect is the tracheal
(noncardiac anomalies plus patent
collapse and obstructive respiratory difficulty. ductus arteriosus, ventricular septal
The prevalence of tracheomalacia is estimated defect and atrial septal defect)
to be 5–15% (half patients require surgical C 65 Birth weight < 2000 g or higher with
correction). Symptoms include feeding diffi- severe associated anomalies
190 D. C. van der Zee et al.

Table 14.2 Okamoto modification of the Spitz malformation and duodenal atresia), and it may be
classification
absent in patients with EA-TEF and renal affec-
Okamoto-Spitz classification tions. The absence of the stomach is non-­specific
Description Risk Survival as well, and it is not described in some cases of
Class (%)
EA-TEF because the fistula permits enough fluid
I No major cardiac Low 100
anomaly, birth passage to fill the stomach. It is estimated that only
weight ≥ 2000 g 1/3 of cases have both a small-­absent fluid-filled
II No major cardiac Moderate 81 stomach and polyhydramnios, but when both pres-
anomaly, birth ent, the positive predictive value is 39–56%.
weight < 2000 g
Another EA-TEF predictive parameter is the US
III Major cardiac anomaly, Relatively 72
birth weight ≥ 2000 g high detection of the blind-ending upper pouch that
IV Major cardiac anomaly, High 27 may be identified late in gestation and seems to
birth weight < 2000 g correlate with a higher risk of trisomy 18. The
accuracy of antenatal US is between 75 and 91%
in case of pure EA, but it is lower with other types
physiologic status to establish the management. of EA-TEF, and in all cases it remains a challenge.
Poenaru proposed to use severe pulmonary Foetal MRI still has limited use although it has a
dysfunction, preoperative need of mechanical
­ significant positive predictive value. Once the
ventilation and severe associated anomalies as diagnosis is suspected, chromosomal anomalies
risk factors, and Brown and Tam tried to establish (karyotype) and associated defects (foetal ECHO)
long-term outcomes on the base of the esopha- should be excluded in order to provide an accurate
geal gap length. In 1992 Spitz suggested the counselling. After birth, in case of prenatal poly-
assessment of birth weight and major cardiac dis- hydramnios with or without prematurity (that is
ease to predict survival (Table 14.2). According common in infants with EA-TEF), the suspicious
to Okamoto, major cardiac disease plays a key should always rise in order to avoid feeding and
role in assessing prognosis. aspiration pneumonitis [1–3].

14.6 Diagnosis and Clinical 14.6.2  Diagnosis at Birth

Findings
The newborn infant usually has symptoms before
The diagnosis of EA-TEF is usually made within or during the first feed because it is unable to
the first 24  h of life. Prenatal diagnosis has swallow saliva and requires repeated suctioning.
increased since the introduction of the antenatal He may choke and cough and may have emesis,
US screening. Delayed diagnosis is described in cyanosis and respiratory distress. Those with dis-
case of type V esophageal atresia. tal fistula may have distended abdomen, while
the abdomen is usually scaphoid in patients with
pure EA. The respiratory symptoms worsen and
14.6.1  Prenatal Diagnosis become more evident when there is a delay in
diagnosis. Pulmonary compromise is related to
Antenatal diagnosis was first described by Farrant gastric fluid reflux through the fistula, spillage
(1980) who reported polyhydramnios and absent into the trachea and lungs with chemical pneu-
stomach in a 26 weeks foetus. The obstruction of monitis and diaphragmatic elevation after gastric
the esophagus means that the foetus cannot swal- distension. Aspiration manoeuvres exacerbates
low the amniotic fluid in a proper way with conse- the respiratory distress. The diagnosis is con-
quent polyhydramnios. Polyhydramnios is a firmed by passing a 10Fr gastric tube beyond
non-specific feature (it is also associated with 10–13 cm from the lips (if the esophageal lumen
myopathies, neurological defects, congenital dia- is patent the tube easily reaches the stomach)
phragmatic hernia, congenital cystic adenomatoid (Fig.  14.2). The use of smaller or bigger tubes
14  Esophageal Atresia and Tracheoesophageal Fistula 191

determine the presence of associated anomalies.

In this light an ECHO and renal US are used as a
routine investigation in children appearing clini-
cally normal. The assessment should be more
carefully conducted when there is the suspicion
of associated anomalies (cardiologic evaluation,
genetic counselling, etc.).
Preoperative bronchoscopy is increasingly used
to detect the fistula in the upper pouch and to find
additional defects (fistula from a main pulmonary
bronchus, laryngeal cleft, vallecular cyst) [1–3].

14.6.3  Delayed Diagnosis

A delay in the diagnosis is more common in case

Fig. 14.2  X-Ray evaluation shows the stop of the naso-
gastric tube in the upper esophagus of “H- or N-type fistula”. Patients have coughing
episodes during feed, recurrent pneumonia, chok-
ing spells with feeding and intermittent abdomi-
should be discouraged since they may curl in the nal distension with excessive flatulence.
upper pouch or pharynx and they may cause Symptoms are usually present from birth, but
esophageal perforation. The tube should be taped severity may vary. The diagnosis is made by upper
once a resistance is felt and plain x-rays of neck, gastrointestinal study and airways endoscopy.
chest and abdomen taken. A few millilitres of air
can be injected through the tube and used as a
contrast agent. The tip of the tube lies at the fun- 14.7 Management
dus of the upper pouch. The lateral film gives
information regarding the level of the pouch Following diagnosis, the baby should be stabi-
related to the thoracic inlet. The pouch usually lized and resuscitated. A double-lumen Replogle
reaches the second–third thoracic vertebra; if tube is used to suction secretions from the upper
higher, a type II EA should be suspected. The pouch reducing the risk of aspiration. Placing the
absence of air below the diaphragm suggests that head slightly elevated helps the drainage of secre-
there is no distal fistula although it is not conclu- tions. These interventions avoid chemical pneu-
sive (narrow or occluded distal fistula). monitis and respiratory distress that is the most
The presence of a double bubble may indicate critical preoperative problem. Intravenous fluid
duodenal obstruction, a known associated anom- therapy is started to maintain fluid, electrolyte
aly. The heart size should be checked, as well as and glucose balance. Intubation and ventilation
the pulmonary spaces to exclude the presence of may increase gastric distension leading to respi-
congenital heart disease and pneumonitis. ratory embarrassment and perforation with con-
Skeletal abnormalities may indicate a syndrome sequent pneumoperitoneum. The endotracheal
(VACTERL, CHARGE). Esophagograms are tube should be placed beyond any distal fistula,
useful to establish size and location of the proxi- and the ventilation should be based upon low
mal pouch and to visualize the proximal fistula, pressures. Biochemical and haematological
but they may cause serious complications and ­studies are performed to assess the homeostasis
should be performed only in centres with high of the baby. Blood is grouped and crossmatched.
radiological expertise. Vitamin K is given. Physiotherapy is instituted
Investigations are used not only to confirm the and prophylactic antibiotics are given. The tim-
diagnosis but also to provide additional informa- ing of surgery is established when the baby is
tion guiding the surgical management and to stable [1–3].
192 D. C. van der Zee et al.

14.8 Surgery of foregut-­associated anomalies, and it may help

to define the esophageal gap. The definition of the
The surgical correction of EA-TEF aims at inter- gap is important to choose the proper surgical
rupting any trachea-esophageal connections and approach (Fig. 14.3).
establishing end-to-end esophageal continuity.
The approach varies depending on the type of
anomaly and the general clinical conditions of the 14.8.1  Esophageal Atresia
baby (including the presence of associated anom- with Distal
alies): immediate operation is carried out when Tracheoesophageal Fistula
the baby is stable (a few hours after the admission, (Type III EA, Short Gap)
usually in the first few days of life), delayed repair
is the optimal strategy when the baby’s conditions Primary repair is now achieved in the majority of
can be improved after a period of intensive care, patients. Surgery is preceded by TBS that gives
and the staged approach is advocated in case of the possibility of probing the fistula facilitating
long-gap malformations in unstable patients with its identification during the operation (Fig. 14.4).
respiratory distress and other associated congeni- The standard approach remains the right pos-
tal abnormalities. The staging approach includes terolateral thoracotomy (the baby is placed on its
the establishment of a gastrostomy and the place- left side, with the right arm draped over the head)
ment of a central line in order to feed the baby and in the fourth interspace, adopting an extrapleural
start a proper support therapy towards an improved approach (Fig.  14.5). This approach avoids an
respiratory status. The fistula can be ligated and empyema in case of anastomotic leaks. The
divided during the same operation. Associated curved excision extends from the anterior axillary
anomalies may be treated or palliated (e.g. colos- line to the paravertebral region, passing about one
tomy in case of anorectal malformation). In some finger below the inferior angle of the scapula.
cases (long-­gap) the proximal pouch is mobilized Subcutaneous tissue and muscles are divided
and opened as an end cutaneous cervical esopha- with electrocautery (the operative field is created
gostomy. Prior to surgery a tracheobronchoscopy between the latissimus dorsi and the serratus
(TBS) is performed to evaluate the presence of a anterior muscles in case of muscle-sparing thora-
proximal TEF, and it offers the possibility to eval- cotomy); the scapula is elevated, and the fourth
uate vocal cord motility and to assess the presence intercostal space is identified. The extrapleural
dissection (that consists of stripping the parietal
pleura off the ribs and intercostal spaces) is per-
formed with a “peanut” swab or the finger until
there is enough space to put a rib retractor. During
this phase, small pleural tear can be repaired
whereas large defects involve a transpleural
approach. Figure 14.6 shows the steps of the pro-
cedure. The dissection proceeds permitting the
exposure of the azygos vein (it can be ligated and
divided) and of the posterior mediastinum after
medial lung retraction. The upper pouch, distal
TEF, trachea and vagus nerve are then identified.
The descending aorta may hide the lower esopha-
geal pouch, and care should be taken to avoid the
mobilization of the artery mistaken for the esoph-
agus. The mobilization of the distal segment,
using a silk suture, tape or a vessel loop passed
Fig. 14.3  Prior to surgery the gap is measured in order to around it, helps identifying the fistula. The fistula
establish the best surgical approach
is then ligated and divided.
14  Esophageal Atresia and Tracheoesophageal Fistula 193

Fig. 14.4  Preoperative bronchoscopy permits the identification of the fistula and the placement of a probe that will
facilitate the surgical repair

help by pushing and moving the tube placed in

the upper pouch. Once identified, a traction
suture is placed on the tip of the pouch to help its
mobilization. The dissection should be extensive
(ischemic injuries are rare as the vascular supply
is excellent), and the esophagus should be sepa-
rated from the trachea minding their intimate
relation in the esophageal antero-medial part (do
not open the membranous trachea). Once the
abovementioned steps are completed, the end-to
end esophago-esophageal anastomosis is per-
formed using 5-0 or 6-0 absorbable sutures. The
Fig. 14.5  The baby lies on its left side with the right arm suture should include all layers (especially the
elevated. A roll is placed under the chest in order to obtain mucosa) starting from the posterior wall and
a better exposure of the operative field
inserting the entire back row of suture before
tying them. It is of help to the passage of a feed-
The residual stump is ligated with 4-0 non-­ ing tube under vision across the anastomosis into
absorbable sutures. Leaving excessive amount of the stomach to ensure patency and start early
esophagus on the tracheal end may lead to tra- enteral feeding. Once the suture is completed, a
cheal diverticulum but not leaving enough tissue chest tube can be placed in the retropleural space.
may cause tracheal stricture. Filling the thorax The use of minimally invasive surgery (MIS)
with warm saline and looking for bubbles during has increased in children with AE-TEF, and it has
positive pressure ventilation test the airtightness. been supported by many centres reporting the
The distal esophagus mobilization proceeds same results as for open surgery.
using two stay sutures in order to ensure a pri- Thoracoscopic repair uses three 5 mm trocars
mary tension-free anastomosis although it should and a 5  mm camera. The TEF is identified and
be minimized to avoid nervous or vascular dam- clipped or ligated, the proximal esophageal
ages. The next step is to visualize and mobilize pouch is mobilized, and an end-to-end esophago-
the proximal pouch: the anaesthesiologist can esophagostomy is performed (Fig. 14.7).
194 D. C. van der Zee et al.

a b c

d e f

Fig. 14.6  Identification of the tracheoesophageal fistula pouch and exteriorization of the probe (d). The primary
after ligation of azygos vein (a). Mobilization of the upper esophago-esophageal anastomosis is then performed (e, f)
pouch (b) and the lower stump (c). Opening of the upper

After surgery the baby is admitted to the intensive anomalies that may represent a priority over
care unit for mechanical ventilation (when required: esophageal surgery, delayed between 3 days and
premature infants and anastomosis performed under 3  months) and surgery-related issues (airways
tension). The feeding starts after 48  h through the and esophageal anatomy and redo surgery).
nasogastric tube unless there is concern about the Prematurity is the factor that has the major
anastomosis. Ten days after surgery, the anastomotic influence in timing surgical correction. Very low
site is visualized during contrast X-ray that is fol- birth weight neonates usually develop respiratory
lowed by the removal of the drain and nasogastric distress requiring mechanical ventilation. The
tube. Oral feeding is then carefully started as there is inflated air easily passes through the fistula
a mandatory anastomotic relative stenosis of the towards the esophagus (low-resistance) instead of
anastomosis due to the different diameters above reaching the lungs that have lost their compliance
and below the EA. In most cases it will improve with determining a high-resistance system. The effect
feeding and do not require dilatation [5–7]. is the gastric distension with consequent wors-
ened respiratory distress, gastroesophageal reflux,
inhalation and risk of gastric perforation. Several
14.8.2  Difficult Cases approaches have been described to manage this
problem including gastric division, banding of
Difficult cases are related to general patient’s the gastro-esophageal junction, distal positioning
characteristics, such as prematurity or associated of the endotracheal tube, fistula occlusion with a
anomalies (life-threatening cardiac and bowel Fogarty balloon, water seal gastrostomy and
14  Esophageal Atresia and Tracheoesophageal Fistula 195

a b

c d

e f

Fig. 14.7  View towards the thoracic inlet during thora- pouch is mobilized and opened exteriorizing the probe
coscopy: the mediastinal pleura is opened, and the fistula (d). The anastomosis is performed with interrupted
is identified (a), sutured and divided (b, c). The upper stitches (e, f)

h­ igh-frequency ventilation. Urgent thoracotomy In case of right aortic arch (5% of cases), the
and fistula division seems to be the best approach, suggestion is to perform a left thoracotomy or at
followed by delayed primary anastomosis (the least paying attention not to mistake the aorta for
esophageal tissue is often too fragile to try a direct the esophagus. Right thoracoscopy is an alternative
suture). that gives a good view on the esophagus and the
196 D. C. van der Zee et al.

aorta. It is also important to notice that this condi- and the anastomosis is attempted once it is less
tion is usually associated with cardiac anomalies. than two vertebral bodies.
Other associations that make EA-TEF man- Various techniques have been proposed to
agement difficult include congenital diaphrag- deal with long-gap EA when spontaneous growth
matic hernia (that carries a very poor prognosis) fails. They consist of gradual traction of esopha-
and chromosomal anomalies, found in up to 10% geal segments in order to favour growth and
of patients (trisomy 21, 18 and 13). reduce the gap. There are also techniques used to
reduce the anastomotic tension (flaps and
myotomy).
14.8.3  Long-Gap Esophageal
Atresia –– Upper pouch bougienage (traction an
growth): a weighted bougie is inserted through
It includes patients with a high upper pouch and the mouth into the upper pouch, and daily pres-
a long distance between the esophageal segments sure is applied for 6–12 weeks; traction can be
that limits the possibility to perform an anasto- applied also to the lower pouch; the use of an
mosis with acceptable tension. The condition is electromagnetic field, hydrostatic pressure and
occasionally seen in case of EA with TEF, but it nylon thread bridge has been described for the
is frequent in case of pure EA.  Unfortunately same purpose. All these procedures have never
there is no consensus regarding the definition and gained widespread popularity.
the measurement of the “long gap” that remains a –– External traction:  traction sutures can be
subjective condition. However, preoperative placed in both the proximal and distal pouches
evaluation of the esophageal gap remains a criti- in order to exit them form the chest and apply
cal part of assessment. The gap can be measured an opposite traction (Foker technique). Time to
by inserting a tube in the proximal pouch and an achieve esophageal repair is almost 10–14 days.
endoscope in the lower pouch through the gas- Early complications include anastomotic leak
trostomy and performing a X-ray evaluation; (50% of patients, mostly minor), major disrup-
some surgeons prefer measuring directly the gap tion and need for ­reoperation (15%) or for
during the operation or using a TBS evaluation esophageal replacement (14%).
(X-rays are taken after a radiopaque tube is –– Extrathoracic elongation: the upper esophagus
inserted in the upper pouch and the tracheo- is mobilized and brought out as an end cervi-
scope’s tip is placed at the level of the tracheal cal esophagostomy that is progressively
opening of the fistula). The literature would sug- moved down along the anterior wall (Kimura
gest that a distance of four or more vertebral bod- technique). The procedure permits to maintain
ies defines the long gap. Once the long gap has the native esophagus, early oral feeding and
been confirmed, efforts should be made in order short hospital stay. The esophagostomy is
to maintain the native esophagus. preferably created on the right side of the
Placing a feeding gastrostomy is part of the neck. Long-term outcomes are limited.
management in case of pure EA, followed by a –– Upper esophageal flap: anterior full-­thickness
period of observation (anatomical investigations flap of the upper pouch to bridge the long gap
and management planning). This gastrostomy can (Gough, Bianchi). It is an elongation tech-
be difficult to perform as the non-used stomach nique of the proximal pouch. Complications
can be very small. The gap shortens during the first include leaks (27%), strictures (87%), gastro-
several months of life (3–6 weeks or until the baby esophageal reflux (20%), recurrent TEF (13%)
is 3.5–4  kg), and waiting may be sufficient to and esophageal motility incoordination (60%).
achieve enough length for the anastomosis. This –– Myotomy: circular myotomy of the upper part
process is facilitated by the administration of bolus of the esophagus is advocated by Livaditis to
gastrostomy feedings that promotes spontaneous gain length for primary anastomosis. It is an
growth by meal and gastric reflux into the lower elongation technique of the proximal pouch.
esophagus. The gap is measured every 15  days, Complications include esophageal leak,
14  Esophageal Atresia and Tracheoesophageal Fistula 197

impaction of food and ballooning (pseudodi- intrathoracic passage) is still the most used seg-
verticulum) of the myotomized segment. ment as it guarantees adequate calibre and length.
–– Elongation of the distal pouch:  during surgery Complications of surgery are stenosis (22–26%)
there is the possibility to elongate the distal pouch and leak (19–30%) related to the precarious circu-
in order to reduce the distance between the lation. There are also problems associated to the
esophageal segments. This can be obtained with reduced peristalsis (interposed colon redundancy).
the cardiac and gastric fundus mobilization  – The stomach (total pull-up or partial tubulisation)
“gastric pull-up” suggested by Spitz. The proce- is appreciated for the rich vascularization and acid
dure is performed along with the fundoplication. resistance. On the other hand, it gives constant
acid reflux damaging the upper esophagus and air-
Once the methods of esophageal elongation way. It has a delayed emptying, as for the colon.
used to preserve the native esophagus have failed, The jejunum is rarely used because of the precari-
the esophagus may need to be replaced. The ous vascularization, despite some favourable fea-
esophageal substitution is performed around 1 tures (adequate calibre and peristalsis) [3, 8, 9].
year of age. During this time a cervical esophagos-
tomy is used to drain secretions, and a gastrostomy
helps feeding the baby. The indications for esoph- 14.8.4  T
 ype V Esophageal Atresia
ageal replacement include long-gap esophageal (H-Type Isolated
atresia, peptic and caustic stenosis. The ideal Tracheoesophageal Fistula)
esophageal substitute should permit a valid oro-
gastric passage of food to satisfy the need of the It is a congenital TEF without EA. It gives symp-
baby, avoid the acid gastric reflux and be acid- toms in the first days of life or in older children:
resistant, do not interfere with cardiac and respira- repeated chokes during feeding, cyanotic spells,
tory function and grow with the baby ensuring its intermittent abdominal distension and recurrent
function also in adult life. Unfortunately there is pneumonia. Chest X-ray shows the signs of infec-
not an optimal esophageal substitute, and the pro- tion and gastric distension. The fistula is missed in
posed substitutes partially adapt to the abovemen- more than 50% of cases on contrast X-ray.
tioned requirements. The colon (retrosternal or Bronchoscopy (Fig.  14.8) and ­ esophagoscopy

Fig. 14.8  This child has recurrent respiratory infections esophagus (left). The latter is regularly patent, as shown
and coughing during feeding. Endoscopic evaluation by the insertion of a nasogastric tube, visible through the
shows a large communication between the trachea and the trachea (right)
198 D. C. van der Zee et al.

confirm the diagnosis and allow the positioning of 14.9.2  Esophageal Stricture
a guidewire through the fistula that helps its iden-
tification during surgery. The operation is per- It is a common complication reported in more
formed through a right-sided low cervical incision. than 80% of patients (40% being clinically sig-
The sternocleidomastoid muscle is retracted, and nificant). Risk factors include poor surgical tech-
the dissection proceeds to the carotid sheath. The nique (excessive tension of the anastomosis, etc.),
inferior thyroid artery and middle thyroid vein are long-gap, ischemia, GERD and anastomotic leak.
divided. Care should be taken to spare the recur- Symptomatic strictures (dysphagia, recurrent
rent laryngeal nerve. Once the fistula has been respiratory problems from aspiration or foreign
identified, traction sutures are placed on the esoph- body obstruction) are treated by endoscopic dila-
agus thus avoiding its rotation. The fistula is tations. The Savary-Gilliard dilators permit an
divided after suturing [3, 10]. anterograde dilatation over a guidewire. Balloon
dilators offer the advantage of a radial and uni-
form force applied over the stricture instead of a
14.9 Complications shearing axial force. Stenting has been proposed
as an alternative method. Recalcitrant strictures
The standard of paediatric care in patients with require resection and reanastomosis or esopha-
EA-TEF is good, and the overall quality of life is geal replacement. Mitomycin C application has
favourable. However, many patients suffer from recently been used to reduce stricture formation.
chronic long-term problems or develop early In the treatment of strictures is also important to
postoperative complications. The rate of compli- reduce GERD that prevent dilatation to be effec-
cations is higher in premature babies and after tive and worsen the stricture.
complex operations. Predictors of complications
are twin birth, low birth weight (<2500 g), preop-
erative intubation, long-gap atresia, anastomotic 14.9.3  Chylothorax
leak, long postoperative intubation (>4 days) and
inability to feed after the first month. It is related to thoracic duct damage during sur-
Short-term complications include anastomotic gery. It requires prolonged hospitalization, sus-
leak, sepsis, esophageal stricture and chylotho- pension of oral feeding, total parenteral nutrition
rax, and they are usually managed conservatively. and thoracic drainage. Surgical correction (tho-
Recurrent tracheoesophageal fistula may instead racic duct closure, pleuroperitoneal shunt,
require surgical correction. pleurodesis) is advocated in case of persistent
chylothorax after 2–5  weeks of conservative
treatment.
14.9.1  Anastomotic Leak

It occurs in 13–16% of patients and most of 14.9.4  Recurrent

them are successfully managed conservatively Tracheoesophageal Fistula
(drainage and nutritional support). A stenosis
may form after leak healing. Major leaks It occurs in 3–14% of cases and it is related to
account for 3–5% of cases and are diagnosed anastomotic leak, inflammation and erosion. A
early after surgery requiring a surgical revision preventive manoeuvre is the use of flaps (pleural,
(drainage and toilette, repair of the anastomosis pericardial, azygos) interposed between the
or esophagostomy and delayed esophageal esophagus and the trachea. Recurrent fistula usu-
replacement). Risk factors are poor surgical ally occurs as an early complication, but it can be
technique, ischemia, myotomy and excessive misdiagnosed and identified later. The baby pres-
tension of the anastomosis. ents with cough and cyanosis during feeding and
14  Esophageal Atresia and Tracheoesophageal Fistula 199

Table 14.3  Long-term complications in patients affected 14.9.6  Gastroesophageal Reflux

by EA-TEF
(GER)
Active long-term conditions
Condition Prevalence (%) The reported prevalence of GER symptoms is
Dysphagia 50.3
18.2–62.9% (mean 40.2%). The aetiology of
GERD (±esophagitis) 40.2
GER is based on congenital factors and surgical
BE 6.4
Cancer (squamous cell carcinoma) 1.4 effects (in particular surgical techniques applied
RTI 24.1 to preserve the native esophagus favour the onset
DDA 22.3 of GER). At the base of GER, these are the fol-
Persistent cough 14.6 lowing factors: abnormal esophago-gastric junc-
Persistent wheeze 34.7 tion, reduced intra-esophageal length, His angle
GERD gastroesophageal reflux disease, BE Barrett’s widening, esophageal dysmotility, increased
esophagus, RTI respiratory tract infections, DDA doctor-­ lower esophageal sphincter relaxation and
diagnosed asthma
impaired nervous control.
GER is related to the onset of esophagitis (that
recurrent pulmonary infections. This complica- is present in over half the patients) and Barrett’s
tion requires surgical or endoscopic correction. esophagus. The latter is a long-term morbidity
Long-term complications (Table  14.3) repre- that is more frequent in patients older than
sent chronic long-term problems with implica- 35 years of age and with severe GERD symptoms
tions on the adulthood management. (>3 times per week). The Barrett’s esophagus is
the replacement of normal squamous esophageal
epithelium with columnar epithelium containing
14.9.5  Dysphagia and Esophageal goblet cells (intestinal metaplasia). It is a prema-
Dysmotility lignant condition. The treatment consists of
aggressive medical management (thickening of
Half of patients experience dysphagia with a feedings, positioning the baby in the upright pos-
reported prevalence of 18.2–84.2% (mean 50.3%). ture, administering acid reduction agents) and
Dysphagia is associated with a poorer quality of often surgery (fundoplication).
life. The anomaly is related to the abnormal esoph-
ageal development (impaired and interrupted
innervations and anatomy) and to the surgical iat- 14.9.7  Persistent Respiratory
rogenic damage. It has been recently noticed the Symptoms
absence of peristalsis at the site of the anastomosis
and a lower esophageal sphincter hypotony in Respiratory symptoms are common and may be
patients with EA-TEF. Dysphagia and dysmotility significant into adulthood. The aetiology is mul-
are risks factors for GER and subsequent metapla- tifactorial: (1) developmental and anatomical
sia and a common cause of respiratory symptoms anomalies of the upper airways (e.g. tracheoma-
(inability to protect the airways during swallowing lacia, abnormal innervation, vocal cord problems,
and pooling of secretions). Some infants require a etc.), (2) gastrointestinal problems (chronic
gastrostomy to facilitate feeding and adequate GERD, esophageal dysmotility, esophageal stric-
growth in the first years of life. Although improved, tures, etc.), (3) recurrent aspiration and (4) lower
symptoms of dysphagia remain very common in airway abnormalities (bronchomalacia, airway
children and adults after AE-TEF repair. Strategies hyperresponsiveness, associated chest wall defor-
used to improve swallowing are chewing slowly, mities, etc.). Respiratory symptoms include
avoiding meat and drinking fluids to promote the cough, wheeze, recurrent infections and asthma.
bolus propulsion. A common consequence of dys- A quarter of patients have a diagnosis of asthma
motility is food impaction. even if it would be better to speak about “asthma-­
200 D. C. van der Zee et al.

like symptoms” because bronchial inflammation

in EA-TEF patients does not lead to extensive
remodelling present in asthma patients [11–16].

14.10 Focus on Thoracoscopic

Management of Esophageal
Atresia and Congenital
Stenosis

14.10.1  Introduction
Fig. 14.9 Monitoring cerebral perfusion with NIRS
Esophageal atresia has always been the hallmark (near-infrared spectrometry)
of paediatric surgery. With better perinatal inten-
sive care, survival has significantly improved to the cerebral blood perfusion decreases in a linear
approximately 90–95% [17, 18]. Therefore, way. On the other hand, an increase in CO2 tension
focus nowadays has shifted from survival to mor- gives rise to vasodilatation, which may give some
bidity and long-term follow-up [19–24]. compensatory effect [31, 32].
With the introduction of minimal invasive sur- Since 2012, brain monitoring using near-­
gery (MIS), also an increasing number of neona- infrared spectrometry (NIRS) has become a stan-
tal procedures can now be performed using MIS, dard procedure in all neonates undergoing
including esophageal atresia [25–27]. surgery in our institution [31] (Fig. 14.9).
A recent study described a deterioration of the Esophageal atresia is not just a congenital
physiologic status of the neonate during thoraco- anomaly with an obstruction of the esophagus but
scopic repair of esophageal atresia and congenital is a lifelong anomaly with sequelae such as dys-
diaphragmatic hernia [28, 29]. The drawback of motility, gastroesophageal reflux disease (GERD)
this study, however, was the fact that very high and airway pathology [17, 19–23, 33–36]. The
pressures of CO2 insufflation, up to 10 mm Hg had approach to esophageal atresia should therefore be
been used. In an animal study using 4 kg piglets, multidisciplinary in close collaboration with the
intrathoracic insufflation pressures of 5 and 10 mm following departments: paediatric gastroenterol-
Hg were compared. This study confirmed the ogy, paediatric pulmonology, paediatric ENT,
adverse effects due to high insufflation pressures genetics, nutrition, physiotherapy, psychology and
when using 10  mm Hg, while insufflation with paediatric cardiology, paediatric urology and
only 5  mm Hg caused no adverse effects [30]. orthopaedics. The Department of Pediatric Surgery
Consecutively, a prospective study in patients with in Utrecht is a centre of expertise for esophageal
esophageal atresia demonstrated no adverse effects atresia and forms part of a centre for upper gastro-
from CO2 insufflation with 5  mm Hg [31]. It is, intestinal (GI) and airway pathology, recognized
however, of paramount importance to have a con- by the Dutch government. The department is also
tinuous monitoring of brain perfusion in neonates a centre of expertise for minimal invasive surgery.
before, during and after surgery, whether open or
by MIS [32]. Neonates are particularly sensitive to
hemodynamic changes causing fluctuation in brain 14.10.2  C
 entre for Upper GI
perfusion. This is due to the fact that, contrary to and Airway Pathology
adults and older children, neonates have no or only
immature cerebral autoregulation. Variation may 14.10.2.1 Esophageal Atresia
be induced by changes in arterial saturation, end- When there is suspicion of esophageal atresia on
tidal CO2, mean arterial blood pressure, haemoglo- antenatal ultrasound, the patient is presented at the
bin levels, mean airway pressure and glucose multidisciplinary meeting with the departments of
levels. When the arterial blood pressure decreases, gynaecology, paediatric surgery and neonatology
14  Esophageal Atresia and Tracheoesophageal Fistula 201

[37, 38]. In case of VACTERL association, the gist, ENT and other specialists depending on
paediatric cardiology, paediatric urology, geneti- associated anomalies. Details on the surgical pro-
cist and/or neurology are consulted. cedure and estimated adverse events are dis-
After birth, patients are admitted to the neona- cussed extensively. Principally, all neonates can
tal intensive care unit (NICU) with a Replogle tube tolerate thoracoscopy [40].
placed in the proximal esophagus and arterial and After induction of anaesthesia, the procedure
venous access (Table 14.4). In case of respiratory is started with a tracheoscopy, while the patient
insufficiency, the neonate is intubated. NIRS sen- breathes spontaneously. This is to locate the fis-
sor and a-EEG electrodes are placed for continu- tula, either distal and/or proximal, and to deter-
ous monitoring. A preoperative ultrasound of the mine the presence and extent of tracheomalacia,
brain is performed. Postoperative follow-up cere- anteriorly due to weakness of the tracheal rings
bral ultrasound will be performed in all patients, as and/or posteriorly because of a floppy pars mem-
well as a MRI of the brain [31, 32, 39]. branacea [41, 42].
Preoperatively ultrasound of kidneys and heart The patient is then positioned into a left 3/4
is performed to determine major anomalies and prone position at the left side of the table.
the position of the descending aortic. The rest of During thoracoscopy, good collaboration
the VACTERL diagnostics can be performed between the paediatric surgeon and anaesthesi-
postoperatively. ologist is essential to successfully perform the
Surgery is performed semi-electively and is procedure. After open introduction of a 5  mm
preceded by a multidisciplinary meeting between trocar approximately 1 cm below and anterior to
paediatric surgeon, neonatologist, anaesthesiolo- the tip of the scapula, CO2 is insufflated with a
pressure of 2–3 mm Hg and a flow of 1 lt/min. to
collapse the lung. The anaesthesiologist usually
Table 14.4  Workup on admission in NICU increases the breathing frequency up to 40–60/
• Preoperative workup min while maintaining the same minute volume.
 – IV drip, arterial line, lab Only after the neonate has adjusted to the new
 – Replogle tube drainage situation the procedure is continued. NIRS
 – Near-infrared spectrometry (NIRS), a-EEG monitoring is performed continuously and when
 – X-thorax/abdomen, ultrasound kidneys indicated by the NIRS, ventilation settings are
 – Consultation paediatric cardiologist +
adjusted, extra fluids are given and cardiotonic
echocardiogram
 – Consultation genetics drugs can be administered. The haemoglobin
 – Consultation ophthalmologist level is important as an O2 carrier. The surgical
 – Other investigations depending on concomitant procedure has been extensively described previ-
anomalies ously and will only be summarized here [26, 27,
• Preoperative multidisciplinary consultation on 31, 41]. In many patients the distal esophagus
intended procedure
lies beneath the azygos vein and taking down
• After induction preoperative rigid
trachea-bronchoscopy
this vein facilitates the mobilization of the distal
• Operative thoracoscopic correction esophageal fistula. We emphasize to place a transfixing
atresia, i.e. under NIRS and a-EEG control suture through the wall of the fistula flush on the
• Postoperative ventilation for 24–48 h on indication tracheal side to prevent slipping of the suture
• Start Ranitidine during manipulation of the trachea postopera-
• Start feeding through nasogastric tube after 24 h tively, for example, when re-­ intubation is
• Start oral feeding when no saliva and/or infectious needed. Sometimes the endotracheal tube pref-
symptoms
erentially goes into the fistula opening. After
• Transfer to ward when stable and spontaneous
breathing cutting the distal fistula, the proximal esophagus
• MRI brain after 1 week can be mobilized. A first suture is placed poste-
• Life support course parents riorly with the proximal esophagus still closed
• Discharge from hospital when on full enteral feeds to facilitate the approximation of the proximal
and no other sequelae and distal esophagus. After tying this suture, it
202 D. C. van der Zee et al.

can be led outside to stabilize the position of the 14.10.2.2 Esophageal Stenosis
two ends to facilitate the actual anastomosis. A differentiation should be made between con-
After opening the proximal esophagus, a second genital and acquired esophageal stenosis.
suture is placed on the anterior side and tied. Congenital stenosis usually is part of the spec-
Now either interrupted sutures can be used for trum of esophageal atresia, in which cartilage
the posterior wall or the needle can be brought remnants in the esophageal wall cause obstruc-
inside for a running suture up to the first suture tion and food impaction [43]. However, these
on the posterior side. This usually creates a cartilage remnants are not always present; in
waterproof anastomosis. After bringing out the these cases muscular fibrosis may be found on
needle again, the two threads can be tied off. A pathology [44]. Endoluminal ultrasound may
transanastomotic tube can be advanced into the provide an indication to the cause of obstruction.
stomach, and the anterior wall can be anasto- MRI often is not conclusive. Sometimes the con-
mosed, again, either by interrupted or continu- genital esophageal stenosis can occur together
ous sutures. Principally, a chest tube is not with esophageal atresia. If the transanastomotic
necessary. tube hitches while introducing, alertness is war-
Postoperative feeding can be started through ranted to exclude a distal stenosis.
the nasogastric tube as of day 1, and an H2 The approach for congenital stenosis is thora-
antagonist is started routinely immediately after coscopic and similar to the repair of esophageal
surgery. Ventilation can be reduced depending atresia [44]. Depending on the level of the steno-
on clinical signs and morphine medication. sis, the esophagus can be approached from the
When there is no oral retention of mucus, the right or left side. After mobilization of the esoph-
patient can be extubated. Oral feeding is usually agus while sparing the vagal nerves, the stenosis
started 1  day after extubation, which is usually can either be resected circumferentially (in case
around the fifth postoperative day. Contrast stud- of cartilage remnants) or incised longitudinally
ies are only performed on indication. VACTERL and closed transversely (muscular fibrosis) [41].
diagnostics, postoperative ultrasound and MRI Acquired esophageal stenosis is usually due to
of the brain are completed, and parents receive a gastroesophageal reflux disease (GERD), caustic
life support training before discharge after ingestion or eosinophilic esophagitis (EE).
7–10  days. Follow-up is according to standard Management for EE is primarily by medication
protocol at the multidisciplinary outdoor clinic [45]. Initially GERD may be managed with antire-
(Table 14.5). flux medication. However, if GERD is refractory,
laparoscopic antireflux surgery in indicated [46].

Table 14.5  Follow-up protocol patients with esophageal 14.10.3  Long-Gap Esophageal
atresia
Atresia
Follow-up
Follow-up after 2, 4, 8 weeks or earlier when indicated
In case of long-gap esophageal atresia, nowadays,
• Consultation with dietician (by telephone)
most often a gastrostomy is performed with a
• Consultation with paediatric pulmonologist (yearly,
antibiotic prophylaxis during winter if necessary, lung Replogle tube in the proximal esophagus, and
function test at 6 years) delayed primary anastomosis is carried out after
• Consultation neonatologist (3, 6, 9, 12, 18, 2–3 months [47, 48]. In a recent position paper, a
24 months when Bailey test) uniform definition for long-gap esophageal atresia
• Consultation paediatric gastroenterologist
was finally determined, taking away the confusion
(esophagoscopy in case of stenosis or reflux; standard
Barrett’s investigation at 12 and 17 years) what should be called long-gap esophageal atresia:
• Consultation paediatrician “Any esophageal atresia (EA) that has no intra-
• Consultation other specialists on indication abdominal air should be considered a long gap”,
• Regular follow-up at 3, 6, 9, 12 months, then every 2 i.e. type A and B according to Gross [47]. When
years thereafter anastomosis is not possible, alternative replace-
14  Esophageal Atresia and Tracheoesophageal Fistula 203

ment techniques are available, such as jejunal usually be managed with a simple chest tube.
interposition, gastric pull-up or colon interposition Esophageal stenosis is believed to be related to
with a preference to jejunal interposition [47]. In gastroesophageal reflux [57]. If, despite repeated
our institution, we use the thoracoscopic traction dilatations, the stenosis is refractory, then lapa-
technique directly after birth without a gastros- roscopic antireflux surgery is warranted. [46] In
tomy. Principally, within 5–6 days a delayed pri- our department, indwelling balloon catheters
mary anastomosis can be performed in all children. are used to treat recurrent esophageal stenosis.
Term neonates without concomitant anomalies In many patients, we have been able to success-
can usually be discharged after 3–4 weeks [49]. fully treat the recurrent stenosis without resec-
tion [58]. Recurrent fistula is described in
approximately 5–10% of the patients [55]. In
14.10.4  Airway Anomalies some cases, endoluminal sclerosing or injecting
fibrin glue may be successful [55], but usually
Both the esophagus and upper airways develop surgical management is necessary to close the
from the primitive foregut. It seems logical that if fistula [41, 55].
a malformation of the esophagus occurs, hamper- Long-term sequelae mainly consist of esopha-
ing of the development of the upper airways is geal dysmotility, GERD and pulmonary restric-
most likely. The majority of children with esopha- tion [19, 21–23, 33–36, 41, 45, 50, 51, 57, 59].
geal atresia also have airway problems [50, 51]. Esophageal atresia is a lifelong condition.
As mentioned before tracheomalacia is an anom- Patients with esophageal atresia will always have
aly frequently encountered in children with to drink with their meals. They have to pay atten-
esophageal atresia and may give rise to a wide tion to what they are eating and may need medi-
range of symptoms, varying from minimal com- cation to support motility of the distal esophagus
plaints to life-threatening events due to a collapse [21, 57]. Silent or asymptomatic gastroesopha-
of the trachea and/or bronchi. If the malacia geal reflux occurs frequently and may ultimately
extends into the bronchi, these children need to be lead to Barrett’s esophagus [60]. Transition into
ventilated with positive airway pressure to keep adult follow-up is, therefore, mandatory. Many of
the airways open. Often, they need a tracheos- the patients with esophageal atresia experience
tomy until they outgrow the danger of collapsing pulmonary restrictions and may be susceptible to
of the airways. More recently, there have been pulmonary infections [33, 61]. Dedicated support
some developments regarding external stenting and management is important to improve quality
with bioresorbable scaffolds, based on 3D prints of life in these patients [35, 36, 57].
from CT scans, but it will take some more years In conclusion, esophageal atresia is a lifelong
before they will become commercially available condition requiring support by a dedicated team
[52]. If the malacia is more restricted to the tra- of multidisciplinary specialists, preferably in a
chea, there are treatment options, depending on centre of expertise [41].
the location and extent of the collapse [41, 53,
54]. Both the anterior and posterior approach can
be performed thoracoscopically [41, 53]. References
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 Part IV
Gastrointestinal
 Gastroesophageal Reflux
in the First Year of Life 15
Juan A. Tovar

15.1 Introduction 15.2 W

 hy GER Is So Frequent
in Newborns and Young
Gastroesophageal reflux (GER) is a frequent phe- Babies
nomenon consisting of the retrograde passage of
the gastric juice into the esophagus and, occasion- The stomach is located in the abdomen where
ally, its expulsion through the mouth. The main positive pressures are permanent and reinforced
harmful consequences of GER are the loss of by gastric peristalsis. In contrast, the esophagus
nutritional intake and the damage to the esopha- is mostly into the thorax where negative pres-
geal mucosa. The larynx, the tracheobronchial sures are present during each inspiratory move-
tree, and the lung can also be affected, and other ment. As a consequence of this, a GER-driving
complications may arise. However, although GER pressure gradient from the stomach to the esoph-
is extremely frequent, particularly in young agus exists in normal individuals, and only the
babies, most of them do not suffer from any of presence of an efficient anti-reflux barrier fights
these complications. Therefore, to a certain extent, this phenomenon. The barrier has two main com-
GER is “normal” in them, and only when such ponents: The first is the “lower esophageal
harmful effects arise the phenomenon is desig- sphincter” (LES) resulting from the permanent
nated gastroesophageal reflux disease (GERD). contraction of the distal smooth muscle fibers of
In the present chapter, the causes and mecha- the esophagus at the gastroesophageal junction.
nisms of GERD during the period of life between The second is a sort of “external sphincter” cre-
birth and the end of the first year are addressed ated by the phasic contractions of the striated
together with the sequence of diagnostic proce- muscle of the crural sling of the diaphragm
dures and the rationale of the currently recom- formed by the pillars of the hiatus. These contract
mended therapeutic measures. A particular during inspiration and lengthen the intra-­
analysis of the comorbidities that accompany abdominal segment of the esophagus while
GERD at this age will be made. accentuating the angle of His. The synergic play
of these two components closes the distal esopha-
gus, particularly when the GER-driving forces
are stronger. Swallowing is possible because the
J. A. Tovar (*) barrier opens at this moment during which inspi-
Department of Pediatric Surgery, Hospital
Universitario La Paz, Madrid, Spain ration ceases and the LES relaxes allowing the
passage of the bolus into the stomach. Esophageal
Department of Pediatrics, Universidad Autonoma de
Madrid, Madrid, Spain peristalsis is regulated by intrinsic and extrinsic
e-mail: [email protected] innervations that coordinate propulsive

© Springer Nature Switzerland AG 2019 209

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_15
210 J. A. Tovar

c­ ontractions with simultaneous relaxations of the is obvious that a spitting, well-nourished, and
sphincter. Peristalsis itself constitutes the second happy baby is normal and does not need investi-
anti-reflux barrier because it is able to clear gations or treatments. However, when some
refluxed material form the esophagus. digestive or respiratory symptoms occur, the sus-
However, the barrier function is not 100% effec- picion of GERD is reasonable, and some action
tive, and GER occurs rather frequently, specially should be undertaken. GERD induces several
after meals, even in normal individuals. Some GER symptoms that can manifest themselves simulta-
is therefore “normally” possible at different times neously or not in the same individual:
of the day particularly in newborns and young
babies who often spit or vomit. They spend long 1. Vomiting: Babies with GERD, in contrast

time lying flat and receive large-­volume feeds. A with adults, usually vomit and/or spit. This
certain immaturity of the LES mechanism was pro- vomiting is more often post-prandial, but it
posed as the main mechanism for the failure of the may occur at any time. Its content is gastric
barrier and the frequent occurrence of GER in juice with remains of feedings and very rarely
young babies [1]. However, modern manometric with coffee ground staining or bile. In contrast
methods demonstrated that the barrier is efficient with that of pyloric stenosis, vomiting tends
[2] even in the premature [3]. When sophisticated not to be projective and total.
miniaturized manometric probes became available, 2. Failure to thrive: The loss of nutritional intake
it was understood that rather than decreased or due to repeated vomiting may impair weight
abolished LES pressure, which only happens gain and development. Vomiting and stunting
rarely, the main mechanism of these episodes of may be the first signs of GERD requiring
GER at all ages [4], including young children [5, attention by the pediatrician who should rule
6], was the occurrence of non-deglutitory transient out other multiple causes.
lower esophageal sphincter relaxations (TLESR). 3. Irritation, discomfort, and “abdominal pain”:
In some cases the anatomy of the gastroesophageal Repeated exposure of the esophageal mucosa to
junction and its relationship with the hiatus are refluxed gastric juice leads to esophagitis. A
abnormal, mainly by ascent of the junction and part baby with heartburn, dysphagia, or pain can
of the stomach into the thorax and then it is appro- only demonstrate his symptoms indirectly by
priate to diagnose hiatal hernia. crying and/or being irritated, unhappy, and
If GER is frequent in infants and less frequent unfriendly [7]. Of course, these symptoms can
in grown-up children, a spontaneous tendency to be related to many other conditions, but they
improvement at this age should be acknowledged. should arise the suspicion of reflux esophagitis.
Since “maturation” of the anti-reflux barrier has 4. Anemia and iron deficiency: Macroscopic

not been demonstrated, other explanations should bleeding due to esophagitis is rare at this age,
be sought. The main one is the acquisition of the but microscopic blood loss may lead to micro-
standing position, and it is generally admitted that cytic anemia and low iron levels. Again, other
babies who spit or vomit improve progressively diseases may cause this, but GERD should be
during infancy and get rid of these symptoms actively sought after in these cases.
when they are able to stand up most of the day. 5. Repeated respiratory tract infection, bronchial
reactivity, and pneumonia may be related to
micro-aspiration or massive aspiration in
15.3 GERD in Newborns ­children with GER. GERD should be investi-
and Toddlers Without gated in them in the absence of other reason-
Concurrent Diseases able explanations like cystic fibrosis or
(Comorbidities) immune deficiencies.

If GER is “normal” to a certain extent in new- Most of these symptoms are caused by a
borns and young babies, when should we suspect variety of pediatric conditions, and pediatri-
GERD and start diagnostic tests and treatment? It cians should rule these out before investigating
15  Gastroesophageal Reflux in the First Year of Life 211

GERD [8]. However, given the prevalence of babies are often difficult to feed because of
GER in infancy, a high index of suspicion is jus- deglutition disorders, choking, or bottle
tified. Fortunately, peptic ulcers, stenosis, or refusal. The irreversibility of these circum-
major hemorrhages are not seen anymore, or stances in brain-damaged children makes
very seldom, in refluxing infants. Many years spontaneous improvement of GERD over
ago, Carre pointed out the naturally benign clini- time unrealistic and the benefits of medica-
cal course of what was known at that time as tions limited.
“minor” hiatal hernia during infancy [9]. 2. Patients with respiratory tract disease.
According to him, two thirds of patients would There are several circumstances that facilitate
be asymptomatic (even without specific treat- GER in patients with respiratory tract disease
ment) after the first 18  months of life, but the that is particularly frequent during the first
remaining third will remain symptomatic or may months of life: This may either enhance posi-
eventually have serious complications. These are tive intra-abdominal pressures or accentuate
the patients that require active treatment. negative thoracic pressures (or both) thus rein-
forcing GER driving forces. Premature and
newborn babies with bronchopulmonary con-
15.4 GERD in Newborns ditions are particularly prone to undergo
and Toddlers with GERD.  Upper airway obstruction, positive
Concurrent Conditions airway pressure ventilation [14, 15], medica-
(Comorbidities) tion with xanthines [16], nasogastric tubes
[17], and other reasons account for this as well
Pediatricians and pediatric gastroenterologists as micro-aspiration or esophago-bronchial
are mainly concerned with children belonging to reflexes [18]. Weaning off ventilator may be
the above-discussed category of refluxers. impossible until GER ceases [19]. At this age
Pediatric surgeons, however, have to deal more it is particularly difficult to determine whether
often with patients in which congenital or respiratory tract disease causes GER or con-
acquired concurrent diseases cause or facilitate versely, if GER (aspiration, bronchoconstric-
GERD.  Herewith we discuss these conditions tive reflexes, reflux laryngitis or sensitization
and how they impact on the pathogenesis of to allergens after aspiration) accounts for the
GERD and its natural course: respiratory disease.
A particular case is that of babies with
1. Brain damage: Congenital or acquired dis- apparent life-threatening events (ALTE),
eases of the central nervous system and par- (pauses of apnea or cardiorespiratory arrests)
ticularly cerebral palsy are frequently that might be related to GER. Whether these
accompanied by GERD. There are many rea- episodes are caused by GER or not is an open
sons for this: neurologic impairment may trig- issue. pH tracings, polysomnographic record-
ger the vomiting center and damages the ings [20, 21], and pH-MII recordings [22, 23]
coordination of digestive motility, both at the clarified only in part this issue. ALTE could be
sphincter and peristalsis levels causing failure related to both acidic and non-acidic reflux
of the barrier [10, 11] and defective clearance. episodes [24], but a clear link between both
TLESRs seems to have less importance in the phenomena is not convincingly demonstrated
pathogenesis of GER in these children than in [25, 26].
regular refluxers [11, 12] who, on top of this, 3 . Patients previously treated for esophageal
are often recumbent, scoliotic, spastic, consti- atresia (EA) with or without tracheoesoph-
pated, and affected by frequent respiratory ageal fistula (TEF): This is a rare malforma-
tract infections. GER is facilitated by all these tion (1:3500 newborns) consisting in the
circumstances, and it may be occasionally majority of cases of the interruption of the
aggravated by alkaline duodeno-gastric reflux upper esophagus behind the trachea and
[13] and salivary loss by drooling. These the  presence of a fistula connecting the
212 J. A. Tovar

t­rachea with the lower end of the esophagus. 4. Patients previously treated for congenital
This is the more common type, but about 10% diaphragmatic hernia (CDH): This is
of the patients have no fistula, and the two ends another rare condition (1:3500 newborns)
of the interrupted organ are quite far apart consisting of a posterolateral defect of either
(long-­gap cases). Smaller proportions have side of the diaphragm allowing the passage of
other uncommon varieties of the malforma- intra-abdominal viscera into the thorax. The
tion. Current overall survival of about 90% lungs are more or less hypoplastic, and persis-
[27, 28] makes lifelong follow-up and quality tent pulmonary hypertension threatens sur-
of life important issues for these patients and vival even with the best prenatal and neonatal
GERD a problem since 25–60% of survivors care. In addition, these babies may bear other
suffer it [29, 30] with increasing prevalence malformations or malrotation due to the dis-
with time [31]. Swallowing difficulties may be torted anatomy of the fetal abdominal organs.
related to the structural anomaly of the esopha- Ultrasonography allows prenatal diagnosis
gus itself, but reflux esophagitis is found upon and in some cases treatment. The more sophis-
endoscopic and biopsy assessments in high ticated support measures (vasoactive drugs,
proportions ranging between 20% [32] and nitric oxide, oscillatory ventilation, ECMO,
53% [33], and postoperative anastomotic ste- etc.) are necessary after birth in order to keep
noses refractory to dilation are in part related these babies alive. Survivals close to 70–80%
to the repeated exposure to gastric juices [34]. can be expected in high volume centers if hid-
Barrett esophagus is diagnosed in a growing den mortality (prenatal deaths, terminations,
number of these patients during adolescence etc.) is excluded. Long-term follow-up and
and adulthood [35], and the risk of esophageal quality of life became also a priority in this
cancer in the long run is considered manyfolds condition [46]. That GERD was associated
higher than in the regular population [36]. with CDH was pointed out long ago [47] after
Vomiting, heartburn, apneic spells, and respi- a dilated esophagus was found in babies with
ratory tract disease may be related to GER in CDH [48]. GERD is more frequent in those
these children and deserve attention and treat- with large hernias [49] and in those who
ment during the first year. require ECMO [50, 51]. It causes problems in
There are several explanations for the high up to 54% of cases [31, 52] and produces
incidence of GER in survivors of EA/TEF esophagitis in about 50% and Barrett’s esoph-
repair: the muscle and mucosal layers of the agus in some of them [53].
reconstructed esophagus are definitely abnor- In these babies, the play of pressures
mal. The esophagus is shortened because between the abdomen and the thorax is abnor-
anastomosis always involves some tension mal due to lung hypoplasia and tight abdomi-
[37] and the extrinsic and intrinsic innerva- nal closure [54, 55]. The hiatus is under tension
tions that regulate motility are defective [38– due to surgical repair or to replacement of one
40]. The LES is often ascended and of its rims by a synthetic patch. The esophagus
functionally poor [41, 42], and, in addition, has poor motility as a result of abnormal inner-
gastric motility may be abnormal as well, and vation [56], and gastric emptying may be
duodenal emptying may be slow in cases with slowed due to seemingly abnormal innervation
associated malformations or malrotation. All and to malrotation or adhesions [49].
these dysfunctions are more relevant in long-­ GER is frequent during the first year after
gap cases and particularly in those without CDH repair [57, 58], and it tends to taper off
fistula in which the anastomosis is always in the ensuing years [31]. Apparently, only a
under important tension and GER is practi- small proportion of patients maintain sphinc-
cally constant [35, 43–45]. teric and peristaltic dysfunctions over the
15  Gastroesophageal Reflux in the First Year of Life 213

years [59]. Feeding difficulties, prolonged do not collaborate, require miniaturized equip-
respiratory difficulties, and vomiting may ment, and, above all, might benefit from the
require active treatment of GERD. spontaneous tendency to improvement.
5. Patients previously treated for anterior ASPGHAN and ESPGHAN recommenda-
abdominal wall defects (AAWD). These are tions extensively review the diagnostic methods
congenital malformations consisting of ante- used in children [8]. In short, contrast meal is
rior body wall defects that may be of two widely available, but it is irradiating, scarcely
varieties: Omphalocele or exomphalos sensitive, and definitely unspecific. However, it
(1:4000 newborns) is an embryonic condition may show stenosis, hiatal hernia, or malrotation
in which a part of the periumbilical wall is and give some information about gastric empty-
replaced by a gelatinous sac containing the ing. Ultrasonography is too operator-dependent
bowel and the liver. Gastroschisis or laparos- and is of no common use for this purpose.
chisis (1:8000 newborns) is a fetal, acquired Extended pH monitoring is probably the
defect in which there is right-sided paraum- accepted “gold standard,” but it only informs
bilical abdominal wall orifice that allows for about acid reflux and has “normal” values that
the bowel and other organs to eviscerate into vary too much with age. Extended multiple
de amniotic fluid. In both cases, surgical intraluminal impedance measurements coupled
repair involves reintegration of viscera into a with pH monitoring (MII-pH) is currently the
reduced abdominal space and closure of the more informative tool since it is able to detect
wall that to a variable extent causes increased non-acidic or alkaline refluxes as well as acidic
abdominal pressure [60]. In addition, there is ones. However, the equipment is expensive, the
always non-rotation or malrotation due to the tracings are difficult to analyze, and computer-
extra-abdominal position of the bowel during ized measurements may be misleading. Isotopic
fetal life, and these, together with deficient studies are more specific and less irradiating
innervation and interstitial Cajal’s cell den- than contrast meal, but they do not provide the
sity [61, 62], delay intestinal transit postop- same morphologic information. Manometry in
eratively facilitating GER and hiatal hernia. all its varieties, pull-through sphincteric mea-
GER often accompanied by esophagitis has surements, micro-­catheter-­perfused and sleeve
been demonstrated in 43% of patients with sensor-prolonged sphincteric and esophageal
omphalocele and in 16% of those with gas- body measurements, and high-resolution
troschisis [63]. manometry, is too complicated and expensive
(in terms of equipment and time consumption)
to be routinely used for diagnosis at this age.
15.5 H
 ow and When to Use Endoscopy and biopsy require sedation or anes-
Diagnostic Tests for GERD thesia at this age, and although they inform
in Newborns and Toddlers about some morphologic features of the esopha-
gus and the stomach, their main focus is the
Since GER is to some extent a “normal” phe- mucosal consequences of GER that may be
nomenon, diagnosis of too frequent or exces- absent in refluxers with apneic spells or respira-
sively prolonged episodes becomes a tory symptoms. Finally, laryngoscopy and stud-
quantitative issue, and this explains the variety ies of lipid-laden macrophages or pepsin in
of the diagnostic procedures applied. Most of bronchial aspirate are only used in cases of
them are relatively invasive and costly, and respiratory tract disease of highly suspected
therefore, their use is withheld until well- GER origin.
grounded suspicion of GERD is established. A recent review shows clearly the limitations
This is particularly true for young babies who of diagnostic tests for GER in children [64].
214 J. A. Tovar

15.5.1 How to Test Children Below 15.5.2 How to Test Children Below
1 Year Without Comorbidities 1 Year with Comorbidities

Most infants with suspected GER or GERD do Newborns and small babies with concurrent con-
not need any diagnostic procedure and can be ditions require a different approach. In many of
managed expectantly under the more usual them, GER may seriously threaten their health
dietary, postural, and eventually antacid mea- and even their life. The expectancy of a spontane-
sures (see below). Only those who do not respond ously favorable outcome is unrealistic in them
to these simple measures, who keep vomiting, due to the persistence of the mechanisms of GER
fail to gain weight, emit blood in their vomit, or (posture, spasticity, scoliosis, structural anoma-
have alarming respiratory symptoms, require lies of the esophagus and/or the hiatus, innerva-
diagnostic tests. Contrast meal is widely avail- tion defects, malrotation, delayed gastric
able, but it is doubtful that it should be used at all emptying or jejunoileal transit difficulties, etc.).
in these cases because its “normality” does not It is therefore reasonable to perform GER diag-
exclude GERD and the presence of GER upon it nostic procedures once the suspicion is
is not diagnostic of GERD. pH monitoring is reasonable.
probably the first line of diagnosis. It is scarcely Contrast meal is probably the first and more
invasive, does not require collaboration, and accessible one in this group. In spite of its scarce
informs reliably about excessive acid exposure. sensitivity and specificity, it depicts the anatomic
However, it has some limitations since babies distortions caused by the concurrent condition
fed five or six times per day have the gastric (hiatal hernia, flattening of the angle of His, mal-
juice buffered to pH >4 for 2 h after each meal rotation, gastric emptying, etc.) that should be
and this “blinds” the esophageal electrode for known in case of surgery. pH monitoring should
almost half the duration of 24 h. Normal values probably be performed next, and the use of two
of acid exposure (reflux indexes) are set at higher electrodes (one esophageal and other one gastric)
values than at other ages, but this does not totally helps to detect alkaline reflux and delayed gastric
compensate for the insufficiencies of the method. emptying [13]. It is generally available and
It is true that the number of episodes and the tim- scarcely invasive. The interpretation should take
ing of acid refluxes are well displayed and can into account not only the reflux index but also the
confirm that GERD is present. Most probably number of episodes of GER and the tracings of
impedance studies will replace standard pH both the esophageal probe and the gastric one (if
metering in the future because the nature of the available). MII-pH will probably replace pH
information provided by this procedure is much metering in the near future, but it is not yet avail-
richer. However, there are still limitations that able everywhere.
have been mentioned already. Endoscopy and Endoscopy-biopsy is the best procedure to
biopsy are probably indicated in babies without detect esophagitis. It is probably indicated in
comorbidities that are extremely irritated and in cases with blood in the vomit or iron deficiency.
those with either blood in the gastric content or In summary, our approach to diagnosis in chil-
with microcytic anemia. Manometric studies are dren with comorbidities should be proactive but
not routinely used in the clinical setting at this limited to contrast meal, pH monitoring (or
age. Of course, they may show insufficient LES MII-pH), and endoscopy-biopsy in selected cases.
pressures, excessive number of TLESR, or dis-
turbed motility, but all these will not impact on
the therapeutic attitudes, and therefore it can be 15.6  ools for the Treatment
T
concluded that it should be reserved for the of GERD in the First Year of Life
investigation of the phenomenon rather than for
its diagnosis. Isotopic GER and gastric emptying If GER is a consequence of the failure or tran-
studies are probably not necessary in most of sient relaxation of the anti-reflux barrier allowing
these patients. acid and/or alkaline exposure of the esophageal
15  Gastroesophageal Reflux in the First Year of Life 215

mucosa, the treatment of GERD should be antacids like magnesium or aluminum hydroxide
directed to one or several of these factors: may be absorbed and increase aluminum serum
Non-operative treatment: This cannot rees- levels. Surface protective medications like algi-
tablish a failing anti-reflux barrier, and it rather nate or sucralfate are effective for on-demand
aims at decreasing the pressure gradients, at lim- decreasing acid exposure, but their prolonged use
iting the harmful effect of the refluxed juice on may also increase serum aluminum, and there are
the esophagus, and at facilitating esophageal no studies on their long-term effects in babies.
clearance. However, all these aims are hard to Inhibitors of histamine-2 receptors (H2RAS) like
reach in young infants. cimetidine, ranitidine, or famotidine are effective
Lifestyle changes are limited at this age. in reducing acid exposure and help to heal esoph-
Postural treatment pursues reducing GER by agitis, but after some time, their effect decreases
gravity and thus minimizing direct contact of the (tachyphylaxis). They also have some side
esophagus with gastric juices. Maintaining the effects, and they are being progressively replaced
baby in an upright position with a chair or crib is for proton pump inhibitors (PPI) like omepra-
of little help. The prone position that was recom- zole, lansoprazole, and esomeprazole. These are
mended years ago was abandoned because of the definitely more effective for acid suppression,
increased risk of sudden death, and therefore, the decrease of acid exposure, and healing of esopha-
preferred position is supine with the head ele- gitis. However, they have some side effects at this
vated [8]. age like gastroenteritis, respiratory tract infec-
Thickening of the feeds with vegetal products tions, parietal cell hyperplasia with gastric pol-
like rice cereal, corn or potato starch, or various yps, enterochromaffin cell hyperplasia, and
bean gums decreases regurgitation but does not others [66]. In addition, they are not approved for
impact either on the episodes of GER or acid use at this age in which the evidence of their ben-
exposure [8, 65]. AR formulas are based on these efits is not fully convincing [8, 67, 68].
additions, and they are designed to avoid exces- Surgical treatment: In turn, surgery that has
sive caloric intake. These formulas should be no effect on motility, acid secretion, alkaline
routinely used as first treatment, together with exposure, or gastric emptying (except in a few
some postural help, in babies who regurgitate or selected cases) can rebuild the failing anti-reflux
vomit but maintain weight gain. barrier in a quite efficient and permanent way.
Helping the esophagus to get rid of the gastric The aims of anti-reflux surgery are to relocate the
juice whenever this is refluxed seems a good gastroesophageal junction below the diaphragm
idea, and prokinetic drugs were introduced to if it is elevated, to lengthen the intra-abdominal
enhance clearance and hasten gastric emptying. segment of the esophagus to allow the positive
However, there is no convincing evidence of the abdominal pressures to play on it, to accentuate
efficacy of these drugs, and, on top of this, the the angle of His, and to create a full or a partial
more popular of them, Cisapride, had to be with- (anterior or posterior) wrap with the gastric fun-
drawn from the market because of cardiac risks. dus able to compress the distal esophagus and act
Other drugs like metoclopramide, domperidone, as a valve when the stomach is full. In some cases
erythromycin, or bethanechol cannot be recom- in which feeding problems are predominant, the
mended at this age because there is no evidence procedure may be accompanied by a gastros-
of their benefits and also because they may have tomy. In rare instances when there are demon-
serious secondary effects [8]. strated gastric emptying problems, a
Decreasing the number and duration of pyloromyotomy or pyloroplasty may be a useful
TLESRs was the reason for the introduction of a adjunct. All these operations are currently per-
new drug, baclofen, that has some success in formed by laparoscopy except when local factors
adults, but it is not approved for young patients [8]. make this approach more difficult.
Finally, neutralizing or decreasing the acid The gold standard of anti-reflux operations is
contained in gastric juice would reduce its harm- the complete fundal wrap-around first described
ful action on the esophageal mucosa. Buffering by Nissen [69]. It decreases acid (and alkaline)
216 J. A. Tovar

exposure, reestablishes a pressure barrier, and In cases with comorbidities, proactive treat-
reduces the frequency and duration of TLESRs ment should be undertaken once GERD has been
[70–73]. However, this operation reduces gastric demonstrated. Long-term administration of PPIs,
compliance leading to early fullness and some- although with scarce evidence, remains the first
times to “dumping” syndrome; it may cause tran- tool. It is recommended in neurologically
sient dysphagia and can have other surgical impaired patients [85] and in those previously
complications. Anterior hemi-fundoplications, as operated for EA/TEF [86] although their effects
described by Ashcraft [74] or Boix Ochoa [75], on the latter were not fully conclusive. With the
may work well [2, 76, 77] but are less effective in same lack of evidence, they are used in children
patients with comorbidities [2, 78]. Posterior fun- operated upon for CDH [87]. It is certainly more
doplication, according to Toupet [79], is quite questionable to rely on acid suppression in cases
similar to an incomplete Nissen wrap-around, with respiratory tract disease although the contri-
and its results should be more or less similar [80, bution to this of esophago-bronchial reflexes
81]. It is interesting to notice that the institutions could be minimized. There is no room for proki-
where Ashcraft’s or Boix-Ochoa’s operations netic treatment in these cases with comorbidities
were developed finally embraced Nissen’s opera- given the structural origin of dysmotility.
tion since laparoscopic approach was introduced. The role of surgery is certainly limited in the
This demonstrated that finally complete wrap-­ first year of life. In fact, the proportion of patients
around was not as bad as pretended by the intro- operated upon for GER below 2 years is small at
ducers of these alternative techniques. least in Europe. American series show that a
In a few desperate cases (particularly in neuro- more aggressive surgical approach is often
logically impaired children), esophagogastric dis- accepted on the other side of the ocean [88–92].
connection may be an alternative to repeated In babies without comorbidities, anti-reflux
failures of fundoplication [82–84]. However, this surgery is indicated when non-operative treat-
operation is rarely indicated in the first year of life. ment fails in symptomatic patients (growth fail-
ure, persistent esophagitis, or stenosis) and in
some cases with respiratory manifestations of
15.7 Treatment of GERD GER and particularly in those with recurrent
in the First Year of Life pneumonia due to aspiration [8]. In exchange,
surgery is frequently used for the treatment of
In children without comorbidities, the recom- children with GERD and concurrent conditions.
mendations of the NASPGHAN-ESPGHAN The most questionable indication for surgery
[8] are more than well founded and should be is the presence of repeated episodes of ALTE that
followed. Happy spitters do not need any treat- can be put in relationship with episodes of GER
ment (except perhaps AR formula if they are after profound study with polysomnographic and
bottle fed). Infants with persisting vomiting pH monitoring or MII-pH monitoring [20–23].
and other symptoms, like insufficient weight Non-acidic reflux episodes are frequent in young
gain, bleeding, or recurrent respiratory tract infants [93], and ALTE could be related to both
disease, in which investigation demonstrated acidic and non-acidic ones [24]. However, there
GER require thickening agents and acid sup- is no agreement on this interpretation [25, 26,
pression with either H2RAS or PPIs. However, 94]. Nevertheless, since the association of GER
it should be pointed out that the limitations and and ALTE may be deadly, anti-reflux surgery
scarce solid evidence of the beneficial effects might be indicated in a few cases.
of both changes in lifestyles and medications at Neurologically impaired patients that are
this age throw the suspicion that the unques- undernourished due to obvious feeding difficul-
tionable success of these recommendations ties may certainly benefit from anti-reflux opera-
might be based in most cases on the spontane- tions often accompanied by a gastrostomy. In
ous favorable course of events during this fact, close to 50% of indications in the USA cor-
period of life. respond to this group of patients [95]. The issue
15  Gastroesophageal Reflux in the First Year of Life 217

of whether a Nissen should be added if gastros- cal concerns, lack of collaboration, and age and
tomy is indicated has not been resolved, but it is size diversity preclude (or make very difficult)
reasonable to accept that gastrostomy alone may the performance of randomized controlled trials
improve the status of the patient if GERD has not (RCTs). Not many have been published on the
been demonstrated [96–100]. On the contrary, if efficacy of PPIs to treat esophagitis [108] or on
a Nissen is necessary to treat GERD in a neuro- the benefits of prokinetics [109–111]. In fact, the
logic patient, addition of a gastrostomy may be a lack of really “normal” controls at this age is a
useful adjunct. barrier difficult to overcome. And thus, as stated
Babies previously treated for EA/TEF benefit by the ASPGAHN/ESPGAHN recommenda-
from anti-reflux surgery when their GERD tions, no much solid evidence is available about
remains symptomatic for several months. the benefits of most of the non-operative treat-
Anastomotic stenosis refractory to repeated dila- ments proposed for individuals this young [8].
tions, recurrent pneumonias, or insufficient Moreover, the evidence is even less solid when
weight gain may improve after surgical creation considering the long-term effects of medications
of an anti-reflux valve. However, the particular like PPIs or others in infants. The risks of changes
anatomy of the esophagogastric junction in these in the microbiota, neoplasia, and others are some-
cases (high junction, small stomach, no angle of times discussed but have not been studied.
His) makes surgery more difficult and less effec- Nevertheless, the issue is not whether or not these
tive [30, 101]. treatments should be administered or not (proba-
Up to 15% or 20% of babies operated upon for bly they should) but whether or not they add sub-
CDH may require anti-reflux surgery during the stantially to the spontaneous improvement of
first year [57, 58, 102, 103] and definitely less in GERD at that particular age.
the ensuing years [31, 59]. Sometimes they can For the same reasons, surgical treatment of
only be extubated after a fundoplication, and more GERD should be applied cautiously during the
often surgery is offered on the basis of unmanage- first year of life. The objective evidence of its ben-
able respiratory situations accompanied by diffi- efits is weak, and the few published RCTs about
culties for oral feeding. Also in this case, the local this matter are restricted to compare two modali-
anatomy (distorted hiatus, patch, etc.) may make ties of operation [92, 112, 113] or details of the
surgery difficult. Preventive fundoplication during same operation [90] but not to clarify the key
CDH repair has been proposed [104, 105], but its issue of whether operation itself is better than no
benefits are not fully proven [106]. operation at this age. Of course, it is beyond doubt
The contribution of GERD to the problems of that some patients benefit from anti-reflux sur-
babies operated at birth for AAWD corresponds gery, but they cannot be compared with ­similar,
rather to later months of the first year. Difficulties non-operated patients, and this casts doubts about
in transit due to malrotation, adhesions, or mal- the appropriateness of such operations.
position of the hiatus cause GERD that becomes And surgery has an additional problem that is
bothersome later. Fundoplication in both ompha- easily linked to the operation itself: complica-
locele and gastroschisis may be indivated in up to tions [91]. If a child treated chronically with PPIs
50% of cases, and its performance during abdom- acquires an infection or a tumor, many explana-
inal wall closure has been proposed [107]. tions can be found for these. However, if a child
having a fundoplication has dumping syndrome,
ascent of the wrap into the thorax, failure of the
15.8 Results of the Treatment new valve or even dysphagia, wound infection, or
of GERD adhesive obstruction, the operation itself will be
blamed at once, and this is why pediatricians and
The main problem with the assessment of the pediatric gastroenterologists are so reluctant to
results of non-operative treatment of GERD in propose indications for surgery [114, 115].
children is the lack of consistent evidence on the Even if the surgeon is convinced after
effects of these measures at an age in which ethi- many years of practice and critical observation of
218 J. A. Tovar

his/her own results of the benefits of surgery for tions. Endoscopic surveillance for life is proba-
treating GERD in children below 1  year with bly warranted in all them.
comorbidities (and a few without them), it is fair Babies operated upon for CDH and surgically
to inform objectively their families about the treated for GERD have also a considerable pro-
potential complications and the expectations of portion of wrap failures but certainly smaller than
success than can be summarized as follows. the neurologically impaired or EA/TEF ones.
In children without comorbidities, a good Babies who require fundoplication are usually the
Nissen holds well in the vast majority of cases, more severe cases in which respiratory, neurocog-
and a normal life without dysphagia or early sati- nitive, or nutritional issues are predominant.
ety after the first weeks following the operation The experience with babies operated upon for
can be foreseen. AAWD and GER is limited, but it does not seem
Neurologically impaired children reunite the for the proportion of failures to be higher than in
conditions for long-term failure of the wrap (not regular refluxers.
to talk about the outcome of the primary disease).
A proportion of 25% after the first 12  months
[116] is a reasonable figure. In many cases, the 15.9 Conclusion
benefits of the wrap are obvious as demonstrated
by parent satisfaction [117] and reduced readmis- GERD is a serious problem during the first year
sions [118]. On these bases, reoperation is accept- of life in some patients without concurrent condi-
able when necessary. However, more than two or tions and in many of those who suffer them. It
three failures may indicate other strategies like would be naïf to believe that this complex phe-
chronic PPIs or esophagogastric disconnection. nomenon can be approached only by suppressing
Children with respiratory symptoms of GERD acid secretion. But it would be as naïf to believe
respond well after operation when the problem is that surgical creation of a new anti-reflux mecha-
repeated aspiration (recurrent pneumonias and nism will suffice in all cases. A balanced approach
atelectasis) but less well when the respiratory dis- is mandatory, and it should be taken into account
ease is bronchoconstrictive like asthma or that patients without comorbidities tend to
asthma-like bronchitis. In these cases, the pat- improve during the first year of life. The use of
terns of nocturnal episodes of GER can orient the medication at this particular age lacks evidence
prediction of success of the operation [119]. In and so does anti-reflux surgery. Every effort
general, in the presence of “asthma” and GER, should be made to design RCT to answer these
the surgical indications should be limited to cases uncertainties.
refractory to all medical treatments with long
nocturnal episodes of reflux [8].
The majority of children requiring surgery for
GERD after repair of EA/TEF are improved by
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 Hypertrophic Pyloric Stenosis
and Other Pyloric Affections 16
Mirko Bertozzi, Elisa Magrini,
and Antonino Appignani

16.1 Hypertrophic Pyloric Additionally they recommended reducing oral

Stenosis intake, gastric lavage, and atropine usage for the
initial treatment and suggested surgery for refrac-
16.1.1 History tory disease [4].
In 1912, Conrad Ramstedt simplified the
The history of what is referred to as infantile Fredet procedure by omitting the transverse
hypertrophic pyloric stenosis (IHPS) dates back suturing, leaving the mucosa exposed in the lon-
to the 1600s. Hildanus (1627) [1] and Blair gitudinal subserosal defect. “Ramstedt” opera-
(1717) [2] have been attributed with earlier tion was successful, and its essential elements
descriptions of HIPS. have remained virtually unmodified ever since
Nevertheless our understanding of this condi- [6, 7].
tion comes largely from Hirschsprung’s seminal The operative approach to the pyloromyotomy
work in 1888 [3]. has undergone to modifications in the last
Formerly, in order to release pyloric muscle decades. Up until the 1990s, most of surgeons
spasm, gastric lavage, and electrical stimulation, approached the pylorus through either by a right
dietary and drug treatments had been used. upper quadrant or upper midline incision. These
During this period, gastroenterostomy, which approaches provide excellent access to the pylo-
was performed as a desperate remedy, had a high rus, but frequently the cosmetic result was
mortality rate up to 50% [4]. unsatisfactory.
In 1907, Henry Dufour and Pierre Fredet In 1986 Tan and Bianchi reported the use of
defined the surgical correction including splitting circumumbilical incision [8].
of pyloric muscle until submucosa with trans- Although cosmetically superior, the downside
verse closure of the muscle [4, 5]. to this approach occurs when difficulty in deliv-
In 1910, Fredet and Guillemot reported the ering the pylorus is encountered. In some cases,
clinical signs of pyloric stenosis enclosing pyloric there is a risk of serosal tear, and the incision may
tumor, increased gastric peristalsis, projectile need to be extended.
vomiting, and weight loss, as well as the high fre- Intracavitary pyloromyotomy has also been
quency of the pyloric stenosis in boys. described and avoids the need to extend the skin
incision to accommodate the pylorus [9, 10].
More recently, laparoscopic pyloromyotomy
M. Bertozzi (*) · E. Magrini · A. Appignani has been reported with a wide diffusion in many
S.C. di Clinica Chirurgica Pediatrica, S. Maria della
Misericordia Hospital, University of Perugia, pediatric surgical units as well as other evolving
Perugia, Italy techniques.

© Springer Nature Switzerland AG 2019 225

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_16
226 M. Bertozzi et al.

16.1.2 Epidemiology and neurotensin. However, their role has not been
substantiated [5].
The incidence of IHPS ranges from 1.5 to 4 per Levels of vasoactive intestinal polypeptide
1000 live births in Caucasian infants [5] but is and neuropeptide Y which are responsible for
lower in African and Asian populations [1]. peptidergic innervation, as well as nitric oxide
Males are more commonly affected than (NO) synthase which produces the nitrergic
females with a ratio of at least 5: 1.4 although the innervation mediator NO that all have relaxation
explanation for this remains unclear [11]. effect on pyloric muscle, are found to be
Recently, a dramatic rise in incidence among decreased in patients with IHPS. This inability of
male infants but not for females was reported, so pyloric muscle relaxation and subsequent pyloro-
that rates for the two sexes were 6.2 and 0.9 per spasm is supposed to be effective on IHPS devel-
1000 infants per year [12, 13]. opment [16, 17].
Mothers under the age of 20 have been Also expression of neural cell adhesion mole-
reported to have 40% more risk of having a child cule that has an important role in the initial con-
with IHPS than the older ones [14]. The disorder duct, between neural and muscle cells, has been
often occurs in first-born boys [6]. Only 11% of significantly found low in IHPS [5, 18].
the infants with IHPS are preterm, while most of In case of IHPS, a defect of intramuscular inner-
infants with HIPS are term. vations has been demonstrated. Nerve-­supporting
Additionally breast-feeding infants have been cells of enteric neuronal system between hypertro-
reported to have lower risk of IHPS [15]. phied circular and longitudinal muscle fibers of
IHPS strongly aggregates in families, even pylorus are absent or extremely rare. Nerve-
among distant relatives, and there is a high con- supporting cells are responsible for a good order
cordance between monozygotic twins [13] for and arrangement among processes of neurons and
that heredity is supposed to be polygenic [5, 14]. cell bodies, essential for a good neuron function.
Decrease of neuron-supporting cells corresponds
to the absence or reduction of peptidergic, nitrer-
16.1.3 Etiology gic, cholinergic, and adrenergic neural fibers.
Interstitial cells of Cajal (ICC) are the pace-
Despite many researches were conducted about maker of gastrointestinal smooth muscles, pro-
possible associated etiological factors and patho- viding effective distribution of electrical activities
physiological mechanisms, the etiology of IHPS and mediating neurotransmission. ICC helps
is still unclear. inhibitory neurotransmission also by producing
The pylorus has an elevated high-pressure NO. Absence or deficiency of ICC within IHPS
zone that relaxes with the peristalsis of antrum resulting in abnormal motility, secondary to
and contracts as a response to duodenal stimula- decrease in slow wave occurrence, has been
tion. This mechanism prevents retrograde move- reported [19–21].
ment of duodenal contents back to stomach. In the case of IHPS, an increase of an extracel-
It is well known that pyloric sphincter func- lular matrix protein synthesis (type I procolla-
tions are under control of some kind of hormones gen) within circular muscle fibers and connective
such as gastrin, cholecystokinin, and secretin. tissue septa between fibers has been demon-
Formerly numerous gastrointestinal peptides or strated, suggesting that the hypertrophied circu-
grow factors have been implicated as having a lar muscle of HIPS is actively synthesizing
causal relationship with pyloric hypertrophy such collagen [22, 23]. This composition appears to be
as high gastrin levels, substance P, epidermal responsible of the characteristic structure of
grow factor (EGF), transforming growth factor-­ pyloric tumor. Furthermore, smooth muscle cell
alpha (TGF-alpha), somatostatin, enteroglucagon, abnormalities were found in IHPS [19].
16  Hypertrophic Pyloric Stenosis and Other Pyloric Affections 227

In the recent years, some authors demon- 16.1.5 Clinical Presentation

strated the increasing of some kind of growth fac-
tors in IHPS such as insulin-like growth factor I, The typical onset of symptoms occurs at
platelet-derived growth factor-BB, and trans- 2–8  weeks of age with a peek occurrence at
forming growth factor-β. Growth factors have 3–5 weeks [5]. In a study conducted by Schärli
been thought to be responsible for smooth muscle et  al. on 1215 patients with IHPS, they have
hypertrophy [18, 24, 25]. revealed the initiation of vomiting after delivery
The possibility of an infectious etiology for in 20%, 1–2  weeks of age in 60%, and after
IHPS has also been discussed [26]. 4 weeks of age in 20% of the patients [36, 37].
Since there is a strong familial trend in develop- Commonly non-bilious vomiting is the first
ing IHPS, genetic factors have been implicated in clinical sign. At first there is only regurgitation of
its etiology: regions on chromosomes 2, 3, 5, 7, 11, feed, but over a period of several days, it becomes
and 12 have been investigated and implicated [27– characteristically projectile at almost every feed-
30], and several susceptible loci have been identi- ing. In a little percent of patient, the vomitus may
fied [31]. Nevertheless a specific gene responsible contain fresh or altered blood as a result of gastri-
for IHPS has not yet been discovered. tis or esophagitis.
Variations in the incidence of IHPS and vari- Owing to inadequate fluid and calorie intake
ous environmental and mechanical factors sug- and in addition to a delay of diagnosis, dehydra-
gest that it could be an acquired condition rather tion and weight loss become apparent [19].
than congenital. Maternal smoking increase dou- In some patients with a significant delay in
bles the risk for IHPS [32]. diagnosis, a lethargic condition may be present
Young maternal age has been related to IHPS together with disappearance of subcutaneous fat
as risk factor [13] as well as breast milk feeding and wrinkled skin.
in early pyloric stenosis [33]. Usually stools become infrequent, scanty, dry,
Another extrinsic factor such as the usage of and firm. However, some infants have diarrhea.
erythromycin which is a motilin agonist inducing Jaundice is encountered in 2–5% of infants
gastric and pyloric contractions has been blamed with IHPS and characterized with indirect hyper-
to increase the risk for IHPS [34] as well as a bilirubinemia due to glucuronyl transferase defi-
neonatal transpyloric feeding [35]. ciency [5, 37].
Severe hypokalemic, hypochloremic meta-
bolic alkalosis caused by vomiting in IHPS may
16.1.4 Pathology result in apnea-like events [38].

Muscular tunica of the stomach is composed of

three-layer muscle fibers with different directions. 16.1.6 Physiopathology
In peripheral layer, muscular fibers are distributed
longitudinal, circular in middle, and oblique in the In the case of IHPS, continuous vomiting results
inner layer. Commonly circular muscular fibers in dehydration and metabolic disorders. Gastric
thicken at the pyloric level forming the pyloric fluid includes sodium, chloride, and potassium.
sphincter. In IHPS the muscle complex becomes Prolonged vomiting causes electrolyte loss rich
hypertrophied causing narrowing of the lumen. in hydrogen and chloride and poor in sodium and
Furthermore in addition to muscle hypertrophy, a potassium, and then a hypochloremic metabolic
worsening of the narrowing of pylorus is caused alkalosis develops. As a response to metabolic
by submucosal edema and lymphocyte infiltration alkalosis, renal tubules excrete sodium and
[18, 21]. All these conditions are cause of a pro- potassium to ensure the maintenance of hydro-
gressive obstruction of gastric outlet. gen ions within the body. If the vomiting goes
228 M. Bertozzi et al.

on, hypovolemia activates renin-angiotensin sys- Associated anomalies are found in 6–20% of
tem resulting in aldosterone secretion that pro- patients [41, 42]. Anomalies associated with
vides sodium and water absorption through renal IHPS are:
tubules and stimulates potassium and hydrogen
excretion. Because of decrease of chloride via • Esophageal atresia
gastric fluid loss resulting in bicarbonate absorp- • Malrotation of the bowel
tion from renal tubules with sodium, metabolic • Hirschsprung’s disease
alkalosis gets worse. A hypokalemic, hypochlo- • Anorectal anomalies
remic metabolic alkalosis is established. When • Cleft lip and palate
hypokalemia is increased, renal tubules tend to • Urological anomalies
keep potassium and excrete hydrogen ion from
renal tubules. Thus, development of paradoxical
aciduria is an indicator of deepened hypokale- 16.1.8 Diagnosis
mia. In case of delayed diagnosis, hypoglycemia
and hypoalbuminemia may also be encountered Infants having weight loss with non-bilious pro-
[39, 40]. jectile vomiting with a hypokalemic, hypochlore-
mic metabolic alkalosis should be considered for
IHPS. On physical examination, abdominal dis-
16.1.7 Differential Diagnosis tention and gastric peristaltic waves due to gas-
and Associated Anomalies tric outlet obstruction may be visible on left
upper quadrant.
Pylorospasm and gastroesophageal reflux may be Palpation of the hypertrophied pyloric muscle
difficult to differentiate from IHPS without fur- (“olive”) just above the umbilicus at the lateral bor-
ther imaging evaluation. Other medical and sur- der of the rectus muscle below the liver edge is
gical conditions causing non-bilious vomiting deemed diagnostic and has been previously reported
described below are to be considered [5, 31]: as having a 99% positive predictive value [43].
Surgical conditions to be considered in differ- When the clinical findings are equivocal, the
ential diagnosis of IHPS are: diagnosis can be confirmed by ultrasonography
(US) or barium meal. Nevertheless US has become
• Gastric volvulus the most common and standard technique for the
• Antral web diagnosis of IHPS. The US sensitivity and speci-
• Preampullar duodenal stenosis ficity approach 100% in experienced hands [44].
• Duplication cyst of the antropyloric region The generally accepted criteria for a diagnosis
• Ectopic pancreatic tissue within the antropy- of IHPS using US study are a pyloric muscle
loric muscle thickness ≥3.5–4  mm and a pyloric channel
length ≥15 mm [5, 44] (Fig. 16.1).
Medical conditions to be considered in differ- For the infants younger than 30  days, 3  mm
ential diagnosis of IHPS are: pyloric muscle thickness is assumed as boundary
value [45].
• Pylorospasm Contrast meal study is still a highly sensitive
• Gastroesophageal reflux examination for the diagnosis of IHPS. UGI may
• Gastroenteritis be used following a non-diagnostic US in a
• Increased intracranial pressure patient with a non-palpable “olive.” Water-
• Metabolic disorders soluble contrast is generally preferred compared
• Food allergy with barium to avoid the chemical pneumonitis
• Adrenogenital syndrome should aspiration occur [5].
16  Hypertrophic Pyloric Stenosis and Other Pyloric Affections 229

citation regimen for fluid and electrolyte replace-

ment [46].
Bicarbonate values higher than 30 mEq/L may
cause myocardial dysfunction and central respi-
ratory depression. Respiratory depression and/or
apnea due to metabolic alkalosis in IHPS has
been reported [38].
Fluid treatment is performed under control of
urine output and serum electrolyte values of the
infant. The aims of fluid treatment are improving
dehydration and achieving potassium and chloride
values close to normal [5, 40]. Usage of H2-receptor
antagonists has been reported to improve metabolic
alkalosis more quickly in IHPS [47, 48].
Fig. 16.1  Elongated and narrowed pyloric channel on US Decreasing of serum bicarbonate value less
than 30 mEq/L represents improvement of alka-
To have a diagnosis of IHPS by contrast meal, losis [5].
it is necessary for the contrast to pass through the Nevertheless in the case of IHPS, thanks to
pyloric channel. In this case, contrast meal study early suspect and fast hospitalization nowadays,
may demonstrate elongation and narrowing of many babies with pyloric stenosis do not show
pyloric channel giving “string” or “double track” any clinical evidence of dehydration on admis-
caused by compressed invaginated folds of sion, and their serum electrolyte levels are usu-
mucosa in the pyloric canal [19]. If contrast does ally normal [19].
not leave the stomach, it is not possible to con- Oral feeding should be discontinued.
firm the diagnosis of IHPS because pylorospasm Generally, there is no complete obstruction in
can also produce transient complete gastric outlet IHPS; thus, infant may tolerate its own gastric
obstruction [5]. However, it is possible to differ- secretion. The placement of a nasogastric tube
entiate the two entities by taking sufficient time may cause additional fluid and hydrochloric acid
during an intermittent fluoroscopy [5]. loss; thus, nasogastric tube is not needed whether
infants with IHPS that do not vomit following
oral intake is stopped [5]. Usually a nasogastric
16.1.9 Management tube is passed to keep the stomach empty imme-
diately prior to the general anesthetic, to reduce
16.1.9.1 Preoperative Preparation the risk of aspiration of gastric contents. Being
The surgical management of HPS is not an emer- not an emergency, the operation for pyloric ste-
gency and should be deferred until the infant is nosis should never be undertaken until serum
appropriately resuscitated because persistent electrolyte levels have returned to normal.
vomiting in these patients results in chloride
depletion and metabolic alkalosis. The length of
preparation depends on the severity of the fluid 16.1.10  Operative Treatment
and electrolyte abnormalities. Most infants with
IHPS should be able to be resuscitated within 16.1.10.1 Open Procedure
24-h period [5]. Intravenous administration of Pyloromyotomy for IHPS is one of the most
0.45% or 0.9% sodium chloride with 5% dex- important operations of the twentieth century.
trose and 10–20 mmol/L of potassium chloride at For the first time in 1907, Pierre Fredet who was
a rate of 150 mL/kg/day may be an optimal resus- a French surgeon from Paris performed Heineke-­
230 M. Bertozzi et al.

Mikulicz pyloroplasty (a longitudinal cut through as the pyloric vein of Mayo distally and onto the
both muscle and mucosa that was then sutured in anterior surface of the antrum of the stomach
a horizontal fashion) on an infant suffering from proximally resulting in a 2–3 cm incision [6]. A
vomiting for 1-month period. The infant died due gentle pressure with a blunt instrument into the
to abundant hematemesis 1  day after operation; incision allows splitting of the hypertrophied
thus, later he performed pyloroplasty by extramu- muscle fibers down to the submucosa that appears
cosal fashion. In 1912, Conrad Ramstedt per- white and glistening. Twisting movements of the
formed extramucosal pyloroplasty on an infant instrument cause a distal and proximal extension
with IHPS, but did not close the muscular layer, of the split, widening the incision [6]. To ensure
and left it open [7]. that all muscle fibers have been divided through-
This technique is still in use for the surgical out the length of the incision, the edges of the split
treatment of IHPS and called as Fredet-Ramstedt muscle are spread apart with a pyloric spreader
pyloromyotomy. Although the approach to the permitting to the submucosa to bulge into the inci-
abdomen has continued to evolve, the pyloromy- sion [6] (Fig. 16.3). Special care must be taken at
otomy itself has remained relatively unchanged the pyloroduodenal junction, particularly vulner-
over the past century. able, to avoid perforation. At this point, a simple
In the case of open surgical approach, many test to evaluate possible perforations is necessary.
types of incisions have been described: Via the nasogastric tube, an amount of 20 mL of
air is introduced into the stomach. The air is then
• Lateral oblique muscle-splitting incision gently milked through the pylorus into the duode-
• Transverse right upper quadrant incision num, and a gauze is placed on the incision to
• Upper midline incision detect any bile staining. If there is no sign of bile
• Right semicircular umbilical incision leak, the intervention is considered completed.
• Supraumbilical semicircular incision Any detected perforation of the mucosa should be
closed by direct interrupted fine suture and a por-
Once the hypertrophic pylorus is delivered tion of omentum placed over this site [5].
from the abdominal incision (Fig. 16.2), it is pos- Alternatively the pyloromyotomy is closed com-
sible to point out the vein of Mayo that marks the pletely, and a redo myotomy on the opposite side
distal extent of the tumor. There is a relatively of the pylorus may be performed [6]. At this point,
avascular plane in the middle of the anterior sur-
face, and in this line, the serosal incision should
be made. The incision should be extended as far

Fig. 16.3  Fredet-Ramstedt pyloromyotomy (hypertro-

phied muscle fibers are separated in midline to both sides
Fig. 16.2  Intraoperative appearance of “olive” in a fashion allowing for mucosal prolapse)
16  Hypertrophic Pyloric Stenosis and Other Pyloric Affections 231

the pylorus is reintroduced in the abdominal cav- also limited to small, retrospective case series
ity, and the fascial layers and the abdominal wall [54]. Modifications of the single-incision laparo-
are closed with an interrupted or running suture. scopic pyloromyotomy technique have also been
The skin is closed with subcuticular suture. reported in the literature with the aim of reducing
complications and operating times [51] such as
16.1.10.2 Laparoscopic Procedure the single-port laparoscopic-assisted pyloromy-
Laparoscopic pyloromyotomy was described for otomy, where a laparoscope is used to facilitate
the first time by Alain et al., in 1991 [49]. delivery of the pylorus through an umbilical
LP has become increasingly popular over wound [55, 56].
time, although the risks and benefits of this pro-
cedure, when compared with open pyloromyot- 16.1.10.4 Single-Port Laparoscopic-­
omy, are still widely debated. Assisted Pyloromyotomy:
Usually, 5 mm laparoscopic port and laparo- Operative Technique [55]
scope are placed in the umbilical fold. A prophylactic dose of intravenous antibiotic
Pneumoperitoneum is established with CO2 at (ceftriaxone, 50 mg/kg) is administered 30 min
pressure of 6  mmHg. Two additional ports are before surgery. A roll is positioned under the
placed in the left and right mid-clavicular line baby’s back to expose the high quadrants of the
just below the costal margin under direct vision abdomen. Umbilical cleansing with povidone-­
with the camera. The duodenum is grasped with iodine is provided before the surgical proce-
atraumatic forceps just distal to the pylorus olive dure. The infant is placed in anti-Trendelenburg
to stabilize it. A 3 mm diathermy hook is passed position. The access to the abdominal cavity is
into the abdomen to initiate the pyloromyotomy. performed according to Alberti et al. [57] with
Some prefer to use a retractable, arthroscopic a right semicircular umbilical skinfold
knife instead. The muscular layer is then sepa- incision.
rated with an endoscopic spreader. A satisfactory Once the peritoneum is opened, a 10–12 mm
pyloromyotomy is evidenced by ballooning of Hasson trocar with pneumostatic anchorage is
the intact mucosa. The absence of mucosal per- inserted. After establishing a pneumoperito-
foration is checked by insufflations of air in the neum (to a pressure of 6  mmHg––flow 0.5  L/
nasogastric tube; if the absence of perforation is min), an operative telescope is introduced, and a
seen, the instruments and ports are removed. The complete exploration of the abdominal cavity is
umbilical fascia is closed with absorbable suture, performed. After the pylorus is spotted
and the skin of all the wound is reapproximated (Fig.  16.4), using an atraumatic instrument
with subcuticular absorbable sutures [31].

16.1.10.3 Evolving Techniques

Endoscopic pyloromyotomy, single-incision lap-
aroscopic pyloromyotomy, and microlaparo-
scopic pyloromyotomy have been described. The
data regarding endoscopic pyloromyotomy is
limited to several case series [50, 51].
Data concerning single-incision laparoscopic
pyloromyotomy is limited to small sample retro-
spective analyses; nevertheless it appears similar
to traditional laparoscopic pyloromyotomy out-
comes [52, 53].
Microlaparoscopic pyloromyotomy is per-
formed using 2 mm instruments and 1.7–2.4 mm Fig. 16.4  The “olive” is spotted during the single-port
laparoscopes. Data regarding this technique is laparoscopic-assisted pyloromyotomy
232 M. Bertozzi et al.

Fig. 16.6  The air test performed during the single-port

laparoscopic-assisted pyloromyotomy to check
Fig. 16.5  The stomach is grasped laparoscopically proxi- perforation
mal to the pyloric tumor during the single-port laparoscopic-­
assisted pyloromyotomy intervention for IHPS
16.1.11  Postoperative Care

The timing of reintroduction of feeds continues to

introduced through the operative channel of the be controversial [60–62]. Nevertheless in the
laparoscope, the stomach is gently grasped lapa- majority of infants, feeding can be started within
roscopically proximal to the pyloric tumor 4–6 h after surgical procedure, and complete oral
(Fig.  16.5) and exteriorized through the right intake can be achieved within 24 h. First oral feed-
umbilical incision; the trocar is removed. With ing may be delayed to 12 h for the infants having
this simple maneuver, often the tumor is exteri- hematemesis during preoperative course due to
orized from the abdominal wall. In case of dif- gastritis. Usually the authors of this chapter prefer
ficulty, taking the stomach in two fingers, a to reintroduce nutrition 6 h after the intervention
gentle traction is performed to pull out the following an increasing scheme, discharging the
hypertrophic pylorus from the umbilical inci- patients only 24 h later the first full meal.
sion; then a Ramstedt’s pyloromyotomy is per-
formed. Once conventional intervention is done,
the pylorus is reintroduced in the abdomen. A 16.1.12  Nonoperative Treatment
reintroduction of the 12 mm trocar is performed,
and a new pneumoperitoneum is created. After Although this treatment to IHPS has been applied
the individuation of the pyloromyotomy, a mini- in the past, the only nonoperative treatment for
mal irrigation with a Nelaton catheter 14 ch HPS currently available is atropine sulfate [46].
introduced in the operative channel of the tele- The atropine suppresses muscular contraction
scope is done, and an air test by insufflating and gastric peristalsis which potentially reduces
50 ml of air through a previously placed naso- the muscular spasm reputed to be the cause of
gastric tube is performed to exclude any muco- IHPS. Despite some authors have reported a suc-
sal leakage (Fig.  16.6). If no perforation is cess rate in resolving the IHPS ranging from 75%
detected, after a careful control of the hemosta- to 88%, nowadays this way of treatment is only
sis, the trocar is removed. considered for extremely high-risk infants who
The wound is closed meticulously: 4-0 Vicryl cannot be operated due to other medical condi-
interrupted fascia sutures are used, and skin tions or should be reserved only for the treatment
suture is performed using 2-octyl cyanoacrylate of or for parts of the world where it is not safe to
[55, 58, 59]. perform neonatal surgery [63–67].
16  Hypertrophic Pyloric Stenosis and Other Pyloric Affections 233

Balloon dilatation of pyloric channel has been 16.2 Pyloric Atresia

tried for nonoperative treatment of IHPS.  The
first reported study with balloon dilatation that 16.2.1 Introduction
has been tried on six patients with IHPS, only one
dilatation of pyloric channel resolved the prob- Congenital pyloric atresia (CPA) is a very rare
lem, but a mucosal rupture occurred [68]. condition, representing less than 1% of all atre-
Afterward, an infant who had developed IHPS sias of the gastrointestinal tract [76] with an
following c­losure of a giant omphalocele was incidence of 1:100.000 live births [77]. The
reported to be improved after two pyloric dilata- first author describing CPA has been Calder in
tions [69]. There are some articles suggesting 1749 [78]. CPA may occur as isolated lesion or
balloon dilatation of pyloric channel for recurrent in association with other congenital hereditary
pyloric stenosis after IHPS operation [70] and for anomalies: aplasia cutis congenita and multi-
the hypertrophic pyloric stenosis that has late ple gastrointestinal tract atresias. Nevertheless
onset [71]. the most common hereditary anomaly associ-
ated with CPA is the epidermolysis bullosa
[79–83].
16.1.13  Complications

Nowadays, mortality after pyloromyotomy is 16.2.2 Etiology

almost not encountered, and morbidity is also
extremely rare [4, 5]. Etiology is not exactly known. Vascular theory
Perforation of duodenal mucosa is the most and failure of canalization theory have been pro-
severe surgical complication during pyloromyot- posed, but there is inadequate embryological evi-
omy. The risk perforation is reported to range dence in support of either. CPA is thought to
from 0.4% to 10% in laparoscopic surgery and result from developmental arrest between the 5th
from 0% to 6% in open surgery [5, 72]. and 12th weeks of intrauterine life. Mucosal des-
During postoperative 24  h, vomiting may be quamation has been suggested to play a role,
encountered caused by gastric atony, and vomit- mainly in patients with associated epidermolysis
ing caused by pyloric edema may be prolonged to bullosa [84]. Mutations in the genes encoding the
several days. For vomiting continuing after two subunit polypeptides integrin alpha 6 beta 4
postoperative days, incomplete myotomy should (ITGA6 and ITGB4) have been identified in sev-
be considered. Incomplete myotomy is generally eral patients with epidermolysis bullosa and
caused by insufficient splitting of muscle fibers of pyloric atresia. [85] There is no sexual predilec-
pylorus on gastric side. In this case, endoscopic tion but most CPA can be associated with low
balloon dilatation of pylorus could be tried, or birth weight.
pyloromyotomy should be performed [70, 71].
The ratio of postoperative wound infection is
reported ranging from 0% to 6% in laparoscopic 16.2.3 Pathology
group and from 0% to 7% in open surgical
approach [5, 73, 74]. Three recognized varieties of CPA are known
Postoperative hemorrhage, wound dehiscence, [76]:
and incisional hernia are rare complications [73,
74]. A recent meta-analysis concerning compli- • Type A, membranous pyloric obstruction
cations of pyloromyotomy has indicated major (57%)
complication rates 4.9% for laparoscopic and 2% • Type B, longitudinal segmental atresia (34%)
for open surgery, respectively [75]. • Type C, pyloric aplasia (9%)
234 M. Bertozzi et al.

16.2.4 History and Physical Type A (membranous pyloric obstruction):

Examination excision of diaphragm and Heineke-Mikulicz
pyloroplasty.
Oligohydramnios, large gastric bubble, and the Type B (longitudinal segmental atresia): when
presence of echogenic material in amniotic fluid the atresia is short, a Finney pyloroplasty can be
(elevated alpha-fetoprotein and acetylcholines- carried out [92]. For longer atresias, the proce-
terase) [86] on antenatal ultrasonography in the dure is the same with type C.
second trimester may be predictive signs of Type C (pyloric aplasia): gastroduodenal end-­
pyloric atresia [87]. Prenatal diagnosis of pyloric to-­
end anastomosis. Gastrojejunostomy should
atresia and epidermolysis bullosa can be per- be avoided.
formed in pregnancies at risk for recurrence of
this syndrome. Prenatal magnetic resonance
imaging has been used to confirm the diagnosis, 16.2.8 Operative Technique
but its utility remains unclear [88].
After a preoperative preparation (insertion of
nasogastric tube, i.v. infusion, central line for
16.2.5 Presentation parenteral nutrition, and medical treatment),
the patient is ready for surgery. Surgery can be
The typical presentation of CPA is non-bilious performed either with open or laparoscopic
vomiting soon after birth with upper abdominal technique.
distention. Scaling and blistering of the skin are A supraumbilical right transverse incision is
found if epidermolysis bullosa is associated. made. The abdominal cavity is opened, and care-
Respiratory symptoms such as dyspnea, tachy- ful exploration and search for other intestinal
pnea, cyanosis, and excessive salivation are atresias are performed.
often associated. CPA is common in infant with During the procedure, a gastrostomy can be
low birth weight [89]. In the case of associated helpful to identify the exact disease. Another way
colonic atresia on account of accumulation of to find the exact location of the web avoiding a
bile in the bowel between pyloric and distal gastrostomy can be achieved by placing a 12–14
atresia, the abdomen can be distended [90]. ch nasogastric tube, to be advanced up to the
region of the obstruction [92].
This procedure is indicated for membranous
16.2.6 Diagnosis pyloric obstruction (type A) and short atresia
(type B).
The diagnosis of CPA is suggested by an abdomi- After identification of the pylorus, a longitudi-
nal X-ray which shows a large single gastric air nal incision is made with cutting diathermy or
bubble and gasless non-distended abdomen [91]. scissors, starting from the gastric side of the pylo-
Contrast study or endoscopy can confirm the diag- rus to the duodenum. The total length of the inci-
nosis. There are three important radiological signs: sion should be 1.5–2 cm, extending approximately
(1) the single gas bubble sign, (2) the absence of 1 cm on the gastric side and 1.5–1 cm on the duo-
beak sign, and (3) the presence of the pyloric dim- denal side of the pylorus; it should be performed
ple sign on a contrast study. The ultrasonographic on the midline between the greater and lesser cur-
examination may be helpful for differential diag- vatures of the stomach and superior and inferior
nosis with hypertrophic pyloric stenosis [92]. borders of the duodenum. The membrane is
excised circumferentially and the mucosa approx-
imately with 5–0 absorbable sutures. The duode-
16.2.7 Management nal lumen is inspected, and a catheter is pushed
down to exclude further distal atresias. The longi-
The treatment of CPA is surgical and depends on tudinal incision is then closed transversely in two
the anatomical type [93]: layers [92].
16  Hypertrophic Pyloric Stenosis and Other Pyloric Affections 235

Gastrostomy is generally not necessary. The We have three groups of patients: a neonatal
abdomen is closed and a nasogastric tube is left group, childhood group, and adult group [97].
in the stomach. The most important symptom in neonatal
Laparoscopic approach to pyloric atresia group is non-bilious vomiting with apnea, cyano-
could be an alternative option to the conventional sis, and no weight gain.
open procedure. However, the procedure should In the childhood group: vomiting, abdominal
not significantly differ from that performed with pain, fullness after eating and bloating.
the conventional laparotomic approach [92]. In adult group: episodic cramping, epigastric
pain, fullness following meals, intermittent
vomiting.
16.2.9 Prognosis

The prognosis of isolated CPA is excellent. The 16.3.3 Diagnosis

mortality depends on the postoperative care of
neonates and co-existing morbidities and anoma- The diagnosis of pyloric obstruction is made by a
lies. In these last cases, mortality may be up to plain radiograph which reveals a large distended
50% [78, 82, 94]. stomach with no air distal to it.
Contrast meal study allows accurate diagnosis
of an antral web in 90% of cases [100].
16.3 Prepyloric Antral Diaphragm Diagnosis of an antral web can also be estab-
lished with ultrasound when performed by a skilled
16.3.1 Definition operator. Another diagnostic technique described
in literature is endoscopy that can confirm the pres-
Antral web represents about 1% of all gastroin- ence of an antral web or other gastric pathologies
testinal tract obstruction [94]. There is a male such as peptic diseases or adhesion [97].
predominance. It is a thin septum, composed of
mucosa and sottomucosa, soft and pliable with a
thickness of 2–4  mm, located 1–3  cm from the 16.3.4 Management
pylorus [95].
It typically projects into the gastric lumen per- In the case of symptomatic antral web, gastric
pendicular to long axis of the antrum [96, 97]. outlet obstruction surgery remains the primary
The etiology of the antral web is still contro- treatment method [100].
versial. It may originate from incomplete canali- It can be managed with an incision to excise the
zation of the foregut during the 5–6 weeks of the web. Endoscopic transection or laser lysis of the web
embryonic age, as an incomplete form of mem- has also been described [101]. In addition to resec-
branous atresia [96–98]. tion of the web, antropyloroplasty was also necessi-
Associated abnormalities are noted in 30% of tated. Complications are similar to pyloric atresia.
children, including the gastrointestinal tract and
cardiovascular system.
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 Gastric Volvulus
17
Ascanio Martino, Francesca Mariscoli,
and Fabiano Nino

17.1 History geal junction with the pylorus, volvulus is

termed organoaxial, the most frequent form
Gastric volvulus (GV) consists in the rotation of (Fig.  17.1a); if instead the rotation axis is the
at least 180° of the stomach on itself, resulting in line joining the greater with the lesser gastric
partial or total foregut obstruction. curvature, volvulus is called mesentericoaxial
The first autoptic description of an adult case (Fig.  17.1b); the rarest form is combined or
of GV was reported in 1866 by Berti [1]; in 1897 mixed volvulus, that is defined when there is a
Berg [2] performed the first surgical correction; biplanar rotation.
in 1899 Oltman [3] described the first pediatric Based on the etiology, GV may be primary or
case and in 1904 Borchardt [4] defined the classic idiopathic, due to failure of gastric fixation
triad presentation of acute gastric volvulus: vio- (absence or laxity of one or more gastric anchors:
lent nonproductive retching, severe epigastric the gastrophrenic, gastrosplenic, gastrohepatic,
distension, and inability to pass a nasogastric and gastrocolic ligaments). Volvulus is defined
tube. In 1940 Singleton [5] classified the disorder secondary when it is associated with anatomical
on the basis of type, degree, and direction of rota- or functional gastric disorders (e.g., hourglass
tion and on the basis of the etiology and of the stomach, gastric outlet obstruction) or with
mode of presentation. defects of adjacent organs (diaphragmatic hernia,
hiatal hernia, wandering spleen, asplenia, intesti-
nal malrotation).
17.2 Classification According to its location, GV can be classified
in abdominal and intrathoracic; in the majority
The GV can be classified in several ways [6– of cases, the stomach remains in the abdomen
10]. By the axis on which the rotation takes cavity, whereas, more rarely, in presence of dia-
place, if the revolution is realized according to phragmatic defects, it can migrate and rotate into
the longitudinal axis joining the gastroesopha- the chest. GV associated with hiatal herniation of
the entire stomach into the chest has been called
upside-down stomach [10].
A. Martino (*) · F. Mariscoli · F. Nino
Pediatric Surgery Unit,
Depending on its mode of presentation,
Salesi Children’s Hospital, Ancona, Italy GV  may be acute, intermittent or chronic and
e-mail: [email protected] acute-on-chronic.

© Springer Nature Switzerland AG 2019 239

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_17
240 A. Martino et al.

a b

Fig. 17.1 (a) organoaxial gastric volvulus. (b) mesentericoaxial gastric volvulus

17.3 Incidence and acute neurovegetative crisis (pallor, hypoto-

nia, ocular revulsion, up to cardiorespiratory
GV is an uncommon disorder in pediatric age, arrest).
although more frequent than reported, because Intermittent or chronic GV may cause nonbil-
the less serious forms can be misdiagnosed as ious emesis, feeding problems or failure to thrive,
gastroesophageal reflux, just sometimes sleep problems, and, less often, dyspnea or gas-
concomitant. troesophageal reflux disease, so that the differen-
The most extensive literature review [6] on tial diagnosis can be difficult, because of the
GV in pediatric age refers to 581 cases of infants similar clinical findings. Acute-on-chronic volvu-
and children; of these, 252 (43%) were acute lus [10] represents the acute form of infants and
cases, of which 69% secondary and 54% organo- children with a history of symptoms suggestive
axial type, while 329 (57%) were chronic cases, of chronic disorder.
of which 74% primary and 85% organoaxial
cases. 381 cases (66%) were children aged
≤12 months; of these, 166 (38%) were acute, of 17.5 Radiological Features
which 54 (37%) were neonates and 40 (27%)
were acute-on-chronic cases. Although radiologic investigation must include a
plain x-ray film of the chest and the abdomen, the
diagnosis of GV is performed by repeated upper
17.4 Clinical Presentation gastrointestinal contrast studies [6, 11]. Radiologic
evaluation should be done in supine as well as in
Clinical features depend on the degree of rotation upright position; the diagnosis is possible after the
and obstruction and may range from asymptom- first contrast study up to 83% of cases [12]. The
atic to life-threatening. Acute GV is a surgical radiological signs of organoaxial volvulus are
emergency, in relation to the evidence of vascu- horizontalness of the stomach with the greater
lar, ischemic disorders of the stomach. curvature above the lesser curvature, in front of
Symptoms are crying because of postprandial the lower esophagus, and pylorus pointing down-
abdominal pain, epigastric distension, persistent ward (Fig.17.2). In mesentericoaxial volvulus, the
nonbilious vomiting, and, less often, cyanosis, stomach may show double air-fluid levels
acute respiratory distress, hematemesis, apnea, (Fig.  17.3) and lies in an upright position, with
17  Gastric Volvulus 241

Fig. 17.2  Upper gastrointestinal series, organoaxial vol-

vulus, the pylorus is pointing downward, and the greater
curvature lies superiorly
Fig. 17.4  Upper gastrointestinal series, gastric volvulus
with hiatal paraesophageal hernia

In the secondary GV imaging studies may

show the associated anomalies (e.g., diaphrag-
matic hernia, deviation of the spleen) (Fig. 17.4).
Gastroesophageal reflux is detected in 12–23%
of cases [6, 12].

17.6 Treatment

The individualized treatment depends on the type

of GV, on the underlying etiology, and on the
presence of comorbidity. The management may
be medical or surgical.

17.6.1 Medical Treatment [12–14]

Fig. 17.3  Upper gastrointestinal series, gastric volvulus Conservative management is advocated in patients
with double air-fluid levels with intermittent or chronic volvulus; it consists
on diet modification (small amounts of thickened
meals) and keeping the patient in a prone or in a
pylorus above the gastroesophageal junction. In right recumbent position with the head raised
the intermittent volvulus, radiologic examination 30–45° for at least an hour after feeding. The
may be normal, due to its spontaneous reduction. advised positions allow rapid gastric emptying
242 A. Martino et al.

and prevent the torsion of the stomach. In fact in eliminate any concomitant reflux, by reforming
chronic GV the gastric contents are retained in the and stabilizing the angle of His.
fundus, while large amounts of air can pass Hiatal repair may be associated in patients
through the pylorus, causing an intestinal disten- with hiatal hernia. An additional antireflux proce-
sion, which can aggravate the volvulus pushing dure (fundoplication) may be performed in case
up the greater curvature. By keeping the patient as of persisting reflux disease.
already mentioned, the air will fill the fundus, and
this will reduce the intestinal distension, prevent-
ing the milk regurgitation into the esophagus. References
Drug therapy (prokinetics and anti-secretory
agents) may be useful. 1. Berti A.  Singolare attortigliamento dell’esofago col
Worsening of symptoms or their persistence duodeno seguito da rapida morte. Gazz Med Ital.
resulting in failure to thrive represents indication 1866;9:139–41.
2. Berg J. Zwei Faelle von Axendrehung des Magens:
for surgical approach. Operation; Heilung. Nord Med Arkiv. 1897;30:
1–18.
3. Kiel OH. Inaugural discussion; 1899, Cited in (16).
17.6.2 Surgical Treatment [10, 12, 15–18] 4. Borchardt M.  Zur Pathologie und Therapie des
Magenvolvulus. Arch Klin Chir. 1904;74:243–50.
5. Singleton AC.  Chronic gastric volvulus. Radiology.
Acute GV is a surgical emergency, because it can 1940;34:53–61.
be life-threatening for children. 6. Cribbs RK, Gow KW, Wulkan ML. Gastric volvulus
The delay in its recognition and management in infants and children. Pediatrics. 2008;122:e752–62.
7. Del Rossi C, Cerasoli G, Tosi C, et al. Intrathoracic gas-
can cause strangulation and ischemic perforation tric volvulus in an infant. Pediatr Surg Int. 1993;8:146–8.
of the stomach. 8. Al-Salem AH.  Intrathoracic gastric volvulus in
The surgical approach is recommended in vol- infancy. Pediatr Radiol. 2000;30:842–5.
vulus secondary to pathology of adjacent organs 9. Al-Salem AH. Congenital paraesophageal hernia with
intrathoracic gastric volvulus in two sisters. ISRN
as well as failure of conservative treatment of pri- Surg. 2011;2011:5. https://doi.org/10.5402/856568.
mary chronic type. 10. Stiefel D, Willi UV, Sacher P, Schwoebel MG, Stauffer
The goals of operative treatment are volvulus UG. Pitfalls in therapy of upside-down stomach. Eur J
reduction, recurrence prevention, and any associ- Pediatr Surg. 2000;10:162–6.
11. Elhalaby EA, Mashaly EM. Infants with radiological
ated anomaly correction. Prompt gastric decom- diagnosis of gastric volvulus: are they over- treated?
pression with a nasogastric tube can facilitate the Pediatr Surg Int. 2001;17:596–600.
reduction of the volvulus (the Borchardt’s triad is 12.
Bautista-Casasnovas A, Fernandez-Bustillo JM,
very rare in pediatric age) improving the clinical Estevez Martinez E, et al. Chronic gastric volvulus: is
it so rare? Eur J Pediatr Surg. 2002;12:111–5.
condition. 13. Hsu YC, Perng CL, Chen CK, et  al. Conservative
The surgical treatment of GV is still contro- management of chronic gastric volvulus: 44 cases
versial; several procedures have been proposed: over 5 years. World J Gastroenterol. 2010;16:4200–5.
simple reduction, gastrostomy for neonatal cases, 14. McCarthy LC, Raju V, Kandikattu BS, Mitchell

CS.  Infantile feeding difficulties: it is not always
anterior gastropexy, and double and triple gastro- reflux. Global Pediatric Health. 2014. https://doi.org
pexy, performed by open or laparoscopic /10.1177/2333794X14553624.
approach. 15. Samuel M, Burge DM, Griffiths DM. Gastric volvulus
Gastric fixation may prevent the recurrence and associated gastro-oesophageal reflux. Archiv Dis
Child. 1995;73:462–4.
and can be achieved by gastrostomy tube place- 16. Darani A, Mendoza-Sagaon M, Reinberg O.  Gastric
ment (open, laparoscopic, or endoscopic tech- volvulus in children. J Pediatr Surg. 2005;40:855–8.
nique) or by anterior gastropexy; both of the 17. Al-Salem AH.  Acute and chronic gastric volvulus

previous procedures can cause or worsen a gas- in infants and children: who should be treated surgi-
cally? Pediatr Surg Int. 2007;23:1095–9.
troesophageal reflux. 18. Behrens R, Lang T, Muschweck H, et al. Percutaneous
Fundal fixation and esocardiopexy may be endoscopic gastrostomy in children and adolescents. J
associated with anterior gastropexy in order to Pediatr Gastroenterol Nut. 1997;25:487–91.
 Bowel Atresia and Stenosis
18
François Varlet, Sophie Vermersch,
and Aurélien Scalabre

Congenital anomalies of the bowel can affect any 18.1 Epidemiology

portion of the gastrointestinal tract. Bowel atresia
and stenosis concern abnormal closure, disconti- The reported incidence of small bowel atresia
nuity or narrowing from the duodenum to sig- (SBA), i.e., concerning the duodenum, jejunum, and
moid colon, and the incidence is about 2/10,000 ileum, ranges from 1.3 to 2.8/10,000 live births [1].
live births. The pathogenesis was previously However wide variations have been noticed accord-
believed to be an embryologic trouble of bowel ing to the country, from 0.57  in Spain to
recanalization or a disruption compromising 6.6/10,000 in Japan [2]. The European Surveillance
small bowel vascular supply, but new genetic of Congenital Anomalies system (EUROCAT) col-
hypothesis emerges since a few years to explain lected 1133 SBA out of 5,126,164 live births during
the occurrence of bowel atresia and stenosis. a 16 years period (1990–2006) after exclusion of the
Prenatal diagnosis is common but remains cases associated with gastroschisis and teratogenic
difficult. The management of bowel atresia and syndrome which represent an overall incidence of
stenosis depends on many criteria such as birth 1.6/10,000  in Europe. Associated malformations
weight, the type and level of the atresia, the with SBA are frequent. Chromosomal and genetic
length of the remaining bowel, associated mal- syndromes are encountered in up to 20.6%. Among
formations, and the type of surgery. The results them Down’s syndrome is far more frequent in asso-
have improved dramatically since several ciation with duodenal atresia than with jejunoileal
decades due to enhanced medical support one. Other nonchromosomal malformations associ-
including intensive care management, total par- ated with SBA include all components of VACTERL
enteral nutrition (TPN), and new surgical and are significantly more frequent with duodenal
procedures. atresia. Details can be found in Table 18.1 [3].

F. Varlet (*) · S. Vermersch · A. Scalabre

Department of Pediatric Surgery, University Hospital
Centre, Saint-Etienne, 42055 Cedex 2, France
e-mail: [email protected];
[email protected];
[email protected]

© Springer Nature Switzerland AG 2019 243

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_18
244 F. Varlet et al.

Table 18.1 Most common associated malformations one [16–18]. It has been proposed to be an
with small bowel atresia [3]
autosomal recessive inheritance. They involve
Duodenal Jejunoileal atresia from the stomach to rectum and have a
Associated anomalies atresia (%) atresia (%)
very poor prognosis. Familial distal foregut
Cardiac 12.3 6.6
atresia due to an autosomal dominant inheri-
Intestinal (other 8 2.6
than SIA) tance was also described by Robinson [19].
Esophageal atresia 3.8 0.3 Experimentally Fourcade and Puri created mul-
Anorectal 3.8 1 tiple gastrointestinal atresia using Adriamycin
malformations in rats demonstrating that an ischemic process
Urinary system 6.5 2.4 was not involved [20].
Cleft (lip and/or 1.3 0.5
Many genes and the downstream morphoge-
palate)
Limb 6.9 1.3
netic events have been studied as possible causes
of bowel atresia. Cheng reported possible duode-
nal atresia in mouse by mutation of gene fibro-
blast growth factor 2IIIb (Fgfr2IIIb) or its ligand
18.2 Pathogenesis (Fgf10) leading to an increase in cell death and a
decrease proliferation specifically, and exclu-
The etiology of intestinal atresia remains unclear. sively, in the endoderm [21]. These endodermal
For Tandler a SBA was a lack of revacuolization cellular events precede any changes in the vascu-
of the solid cord stage during intestinal develop- lature by at least a full day in the mouse, leading
ment which occurs by Day 44–46 [4]. Against to atresia formation [22, 23]. Furthermore these
this hypothesis were evidences of bowel contents studies showed the mutation of Fgfr2IIIb and
appearing later during the organogenesis and Fgf10 resulted in both colonic and duodenal
found below the atresia or in the intermediate atresia, suggesting that the mechanism of forma-
parts of multiple SBA inconsistent with the tion of this atresia is the same. Other genetic dis-
revacuolization concept [5]. As early as 1904, ruptions of endoderm development were
Clogg, in reporting two cases of SBA, postulated described with disruption of hedgehog in mice
that torsion of the intestine could account for leading to duodenal stenosis and anorectal mal-
some of these cases [6]. Louw and Barnard sug- formation [24], or mutation of gene encoding
gested a mesenteric vascular accident could be Cdx2 transcription factor expressed exclusively
the cause of most jejunoileal and colonic atresias in the colonic endoderm after D12  in mice,
[7, 8]. However these theories do not explain how resulting also in intestinal atresia [25]. Johnson
a duodenal atresia occurs in Down’s syndrome, and Meyers reported 28 patients with SBA and
for instance. increased association in the allelic frequency
With the improvement of prenatal ultrasounds, factor V Leiden or R353R mutation of factor VII
more than 30 cases of intussusceptions have been [26]. More recently, Gupta studied 32 single
adequately documented in fetus, causing isch- nucleotide polymorphisms (SNPs): two had
emia and subsequent SBA [9–13]. Let’s mention increased risk of SBA (ITGA2 873  G/A and
that it has been hypothesized by Chiari as early as NPPA 2238 T/C), and three had reduced risk of
in 1888 [14], about a case in which intussuscep- SBA (SERPINE1 11,053 T/G, MMP3 (-1171)
tion of the fetal intestine was thought to be the A6/A5, and ADRB2 gln27glu) [27]. If genes and
cause. morphogenetic events are concerned in the
Hereditary multiple intestinal atresia, first occurrence of bowel atresias, the questions
reported by Guttman et  al. in 1973 [15] and raised are when do they occur, the number and
then by Puri in 1988, is a very rare form of mul- the type of genes involved, and what do these
tiple atresia that suggests a malformative pro- defects reveal about the normal processes of
cess could be involved rather than an ischemic intestinal growth and development [2].
18  Bowel Atresia and Stenosis 245

Besides experimental use of chemotherapy, must be proven. Without communication, other

maternal smoking and cocaine use have been diagnoses should be evocated such as duodenal
associated with intestinal atresia [28]. duplication or retroperitoneal cyst (Fig. 18.3).
Fetal movements associated with feeding have
been described in fetuses as early as 12–14 weeks
of gestational age (WGA) [29]. Should an obsta-
cle occur on the bowel, swallowing became
impossible to the fetus impeding clearance of
amniotic fluid thus accumulating in the uterine
cavity and leading to polyhydramnios. The more
proximal the obstacle is, the more important will
be the polyhydramnios. Hence any hydramnios
should cast suspicion of an obstacle on the bowel.

18.3 Duodenal Atresia and Stenosis

Duodenal atresias and stenosis are usually evi-

denced on routine ultrasounds (US). As a result
of fetal swallowing impairment, polyhydramnios
is present in about 40% and leads to 6% of death
in utero. Up to 40–50% of children are born pre-
maturely. The prevalence of associated anoma-
lies is higher in duodenal atresia than in any other
type of intestinal defect [3]. They involve chro-
mosomal anomalies, syndromes, and associated
structural malformations.

18.3.1 Prenatal Diagnosis Fig. 18.1  Double bubble sign

Duodenum is never visualized on normal prena-

tal ultrasounds. A “double bubble sign” is typi-
cally observed in the second trimester, although it
has been described since 20 WGA. This appear-
ance results from a distended stomach and duo-
denal bulb that are separated by a hypoechoic
gastric antrum. The word “bubble” has originated
from postnatal X-ray findings and is misleading
in the context of prenatal diagnosis as all fetal
cavities are filled with fluid and not with air. It is
often associated with a collapsed small bowel
and colon and maternal polyhydramnios [30].
The “double bubble” sign in prenatal diagnosis is
most often associated with duodenal atresia.
However patent communication between the Fig. 18.2  Communication between the stomach and duo-
stomach and duodenum (Figs.  18.1 and 18.2) denum (arrow)
246 F. Varlet et al.

Fig. 18.3 (a) Double

bubble sign at 20 WGA a b
and p­ renatal suspicion of
duodenal atresia (normal
karyotype). (b) Normal
neonatal appearance on
X-rays.
­(c–d) Retropancreatic cyst
on sonography and
MRI. Finally diagnosis
was a mature pancreatic
teratoma

c d

18.4 Classifications obstacle above the Treitz ligament and must be

subsequently investigated at birth using conven-
Difference should be done between duodenal tional X-rays. Should a double bubble sign appear
atresia and SBA. Mainly due to the fixation of the similar to that on prenatal diagnosis (Fig. 18.4),
duodenal frame and to the jejunoileal meso, the no further exam is needed. A gastric suction tube
forms of atresia differ and need for different and appropriate IV hydration and nutrition are
classifications. required awaiting for surgical treatment.
Three types of duodenal lesions were Without prenatal diagnosis, the baby vomits,
described by Gray and Skandalakis [31]: usually bilious, but sometimes water-like if the
obstruction is above the ampulla of Vater.
Type I: occlusion by a mucosal web with normal The abdomen is depressed, except in the epigastric
muscular wall area if the diagnosis is delayed. Plain abdominal
Type II: defect with a short fibrous cord bridging X-ray films are performed. If the double bubble is
the two blind ends of the duodenum isolated without air below (Fig. 18.4a), the obstruc-
Type III: complete gap between the atretic ends tion is total. The presence of small bubbles on the
lower abdomen (Fig.  18.4b) is related to partial
obstruction, i.e., to a diaphragm or a web with
18.5 Diagnosis at Birth hole, a stenosis with or without annular pancreas.
Unlike duodenal atresia, duodenal stenosis is
Prenatal ultrasonographic findings of a polyhy- compatible with partial or total oral feeding. Thus
dramnios of variable severity associated with a the age of discovery is extremely variable from
double bubble sign raise the suspicion of an first week of life to adult’s age according to the
18  Bowel Atresia and Stenosis 247

severity and symptoms of duodenal obstruction, Table 18.1. Among digestive anomalies, the asso-
mainly chronic vomitings. Duodenal stenosis ciation with annular pancreas (Fig.  18.6) and
occurs in about 20% of congenital duodenal malrotation (Fig. 18.7) must be highlighted as it
obstruction [32, 33]. Upper gastrointestinal con- is encountered from 11.5 to 35% [33–35].
trast study shows the duodenal stenosis (Fig. 18.5) Other associated digestive malformations
and leads to do endoscopy. are less common: esophageal atresia represents
3–9% and anorectal malformation 2–5%. A
second low intestinal atresia does not appear in
18.5.1 Associated Malformations more than 0.5% of cases, according to a recent
review of 408 patients [36]; subsequently,
Associated malformations are common with duo- ­systematic extensive exploration of the lower
denal atresia and stenosis. Down’s syndrome bowel during the cure of a duodenal atresia is
occurs in 25%. Other malformations are listed in no more required.

Fig. 18.4 (a) Total

obstruction with isolated
a b
double bubble. (b)
Partial duodenal
obstruction with
associated small bubbles
(arrows)

Fig. 18.5  3-year-old girl. Vomits since birth sometimes what she ate the day before. UGI and related drawing. Partial
duodenal diaphragm can be seen as a negative print below the second bubble
248 F. Varlet et al.

18.5.2 Surgical Treatment

Initially, duodenojejunostomies were performed to

cure duodenal atresia but were associated with
delayed anastomotic functional impairment and
sometimes with blind loop syndrome [33]. Today
the procedure of choice is a duodeno-­duodenostomy
with an evolution from a side-to-­side anastomosis
(Fig. 18.8) to a proximal transverse to distal longitu-
dinal (“diamond-­shaped”) anastomosis as described
by Kimura in 1990 [37] whose geometrical design
enlarges the anastomosis (Fig.  18.9). This can be
achieved through an upper transversal laparotomy or
a laparoscopy. Today the laparoscopic approach has
become a gold standard for those teams experienced
Fig. 18.6  Annular pancreas with neonatal minimally invasive surgery (MIS).

Fig. 18.7  Upper GI contrast study showing duodenal stenosis with malrotation (small bowel on the right)

Fig. 18.8 Side-to-side
anastomosis
18  Bowel Atresia and Stenosis 249

Fig. 18.9 Diamond-shaped
anastomosis

Kimura’s anastomosis requires a large mobili- early postoperative enteral feeding with or with-
zation of the duodenum using the Kocher maneu- out an orogastric tube for gastric decompression.
ver to approximate the two edges of the We avoid placing peripheral intravenous central
anastomosis without tension. The bilious leak catheters (PICC) or central intravenous catheter
appearing at the opening of the duodenum gives as a parenteral nutrition is almost never required.
the position of the ampulla above or below the Many patients have a very dilated proximal
stenosis or atresia. Thereafter, the surgeon must duodenum at the time of initial repair. In patients
identify the ampulla without touching it and note with an extensively floppy and distended duode-
its relationship to the web or to the gap because num, an antimesenteric tapering duodenoplasty
the medial portion of most of the defects is can be used to improve duodenal motility.
located close to the ampulla. In case of a web, its However in most cases, the proximal dilatation of
excision should proceed from the lateral duode- the duodenum resolves spontaneously with time
nal wall, leaving the medial third of the web as long as the anastomosis remains competent.
alone to avoid damaging the sphincter of Oddi or A web excision and duodenoplasty is also fea-
the ampulla. In patients with an annular pancreas, sible (Fig. 18.10).
pancreatic tissue should not be divided for fear of Recently, neonatal MIS developed dramati-
pancreatic fistula. Patients who present with cally and laparoscopic diamond-shaped anasto-
associated malrotation should undergo Ladd’s mosis can be performed safely and successfully
procedure at the time of duodenal repair. [38]. Three or four trocars are required, using
Gastrostomy tubes were often used in the past 3  mm instruments and a 5  mm–30° telescope.
with associated complications such as induced The fourth trocar is mandatory with an enlarged
gastroesophageal reflux. However it might be liver in front of the duodenum. As through an
performed in some circumstances (infants with open approach, the first step is to release the
trisomy 21 or neurological impairment or in right colon to visualize the duodenum. The atre-
some complex congenital heart disease). sia is easily seen if an annular pancreas is pres-
According to the surgeon’s preferences, a small ent. A transparietal suspension of the first
transanastomotic feeding tube (5F Silastic® naso- duodenum is done, giving a good exposure of the
jejunal feeding tube) can be placed to facilitate surgical area. It stabilizes and facilitates the
250 F. Varlet et al.

Fig. 18.10  Web resection and transverse suture

suture as well. The proximal transverse and lon- after MIS does not differ from that after open
gitudinal distal incisions are done. Then it is pos- surgery [42–44].
sible to check for the patency of the distal A few reports described endoscopic treat-
duodenum and proximal jejunum using a stent or ment of congenital duodenal web in infants or
a probe, even though the rate of distal web or
atresia is very uncommon [36]. The diamond- Table 18.2  Reported experiences comparing open and
shaped anastomosis is performed with inter- laparoscopic neonatal procedure [40, 41]
rupted or running resorbable sutures. Drainage is Authors N Open Laparoscopy
not mandatory but often performed. In the litera- Spilde 2008 [45] 29 14 15
ture, most laparoscopies were done in neonates Hill 2011 [46] 58 36 22
above 2000 g birth weight, but it has been proven Jensen 2013 [47] 64 44 20
possible from 1350 g [39]. The median time to Parmentier 2015 [44] 29 19 10
initiate oral feeding was around 8  days (Tables Chiarenza 2017 [41] 18 10 8
18.2 and 18.3) [40, 41], and the length of stay 198 123 75

Table 18.3  Meta-analysis employed to compare laparoscopic and open repair of duodenal atresia [40], added by
Chiarenza’s study [41]
Open = 123 Laparoscopy = 75 p
Median weight 2810 g 2590 g NS
Smallest weight 1100 g 1200 g NS
Down syndrome 23/60 (38%) 21/55 (38.2%) NS
Cardiac abnormality 24/60 (40%) 15/45 (33%) NS
Malrotation 10/46 (21.7%) 10/40 (25%) NS
Operative time 105 minutes 151 minutes p < 0.0001
Fistula 1/123 (0.8%) 0/65 NS
Stenosis 2/123 (1.6%) 3/65 (4.6%) NS
Death 1 sepsis 1 sepsis NS
Time to initial feeding Day 9.6 Day 6.8 NS
Time to full oral intake Day 17 Day 17 NS
Length hospitalization Day 22.2 Day 24.2 NS
Duodenal dysmotility >20 days 10/36 (27.7%) 4/22 (18.2%) NS
18  Bowel Atresia and Stenosis 251

later. In 1989 Okamatsu was the first to report low-up is too short to conclude definitely. In a
the endoscopic treatment of duodenal stenosis meta-analysis, Mentessidou and Saxena recently
in a 2-month-old baby with Down’s syndrome, compared laparoscopic repair of duodenal atresia
using balloon dilatations and high-frequency with the open approach (Tables 18.2 and 18.3), and
wave cutter on the web; the postoperative Chiarenza et al. also published a comparative study
course was uneventful, and the child was between open and laparoscopic treatment. They
doing well after 9  months [48]. In 1992, concluded MIS shows comparable safety and effi-
Ziegler reported the second case of endoscopic cacy with the open repair, although it is associated
treatment of duodenal diaphragm by YAG with significantly longer operative time [40, 41].
laser in 5-month-old baby but with recurrence
of vomitings a few days after the procedure;
surgery showed an annular pancreas explain- 18.7 Prognosis
ing the failure [49]. After 2006 several publi-
cations reported the endoscopic treatment of Finally, the prognosis of duodenal atresia depends
duodenal stenosis, and now 26 cases have been from associated malformations, especially car-
published (Table  18.4). Only three failures diac abnormalities and Down’s syndrome. A sur-
occurred, and 23 duodenal webs could be gical redo is sometimes required for stenosis or
treated successfully. Annular pancreas seems dysmotility. The rate of postoperative small
to be a cause of failure, occurring in two cases. bowel obstruction is an actual event, but it will
The procedures were variable from balloon decrease probably with the development of mini-
dilatation to resection by knife, cauterization, mal invasive surgery.
or laser.

18.8 Jejunoileal Atresia

18.6 Complications
Jejunoileal atresia occurs in approximately 0.7
The postoperative complications are frequent per 10,000 live births [3]. They are equally
(Table 18.5), especially when cardiac malforma- divided between the jejunum and ileum. However
tions are associated, with a high rate of death due associated congenital anomalies are less common
to cardiac failure [33, 34]. Escobar et al. reported with jejunoileal atresia than with duodenal atre-
5.9% deaths related to cardiac failures vs. 2.9% sia. Cystic fibrosis and malrotation are the most
from cerebral bleedings, anastomotic leaks, common associated malformations.
pneumonia, respiratory distress, and biliary
­atresia [33].
Anastomotic leaks may occur. The question 18.8.1 Prenatal Diagnosis
raised is whether they are related to the MIS proce-
dure. Van der Zee et  al. experienced leaks at the While duodenal atresia is commonly identified
beginning of their MIS procedures and stopped prenatally due to the presence of the “double bub-
doing duodenal atresia laparoscopically. After ble” sign, antenatal detection of jejunal and ileal
3 years of appropriate training, they restarted MIS atresia remains challenging. The discovery of
anastomosis without leaks proving they were small bowel atresia by prenatal ultrasound has
related to their learning curve [42]. Anastomotic been reported to be variable, and different sono-
strictures and dysmotilites can occur after laparo- graphic criteria for diagnosis have been described,
scopic surgery, requiring redo procedures and such as polyhydramnios, ascites, peritoneal calci-
sometimes taperings; laparoscopic tapering has not fications, meconium pseudocysts, and dilated
been described to date but seems feasible. No small bowel (Fig.  18.11) and stomach. Virgone et  al.
bowel obstruction has been described after laparos- reported in 2015 a meta-analysis with 640 fetuses
copy, unlike after open surgery (5.5%), but the fol- from 16 studies, and a highly variable detection
252 F. Varlet et al.

Table 18.4  Endoscopic treatment of duodenal web in the literature

Number of Results after
endoscopic endoscopic Follow-up
Author N Age Technique procedure procedure (months)
Okamatsu 1989 1 2 months Balloon + high-frequency 1 Good 9
[48] wave cutter
Ziegler 1992 [49] 1 5 months YAG laser 1 Failure:
annular
pancreas at
surgery
Van Rijn 2006 [50] 4 8–28 days Balloon dilatation 1 for 3 Good 15
1 with 3
procedures
Torroni 2006 [51] 4 8 days to Sphincterotome: 3 1 for 3 Good, 3 ?
66 months 1 impossible for Surgery, 1
annular pancreas
Barabino 2 1, 11 months Diathermic knife 1, 11 months Good, 1 6
2011–2012 [52] 1, 20 months 3, 20 months Surgery, 1
(1 bleeding and (recurrence)
stop—2
recurrences)
Bittencourt 2012 3 9–12 months Balloon dilatation and 1 Good 48
[53] membranectomy by
papillotome
Di Maio 2014 [54] 1 8 years Knife + argon laser 1 Good 12
Bleve 2015 [55] 1 11 months Electrosurgical knife 1 ? ?
Huang 2015 [56] 6 7 days to 5/6 balloon dilatation 1 Good 24
37 months 1/6 + electrocauterization
Poddar 2016 [57] 3 2–9 years Balloon dilatation 2–4 Good 6–9
(8–10 mm < 3 years and
18 mm > 3 years)
Total 26 7 days to Variable 1 = 21 Good, 23 21, 5
9 years 2–4 = 5 Surgery, 3
(2 annular
pancreas +1
bleeding)

Table 18.5  Postoperative complications and deaths after open surgery

N Down syndrome Complications Treatment Death (%)
Dalla Vecchia 1998 [34] 138 33 13, cardiac failure 14
4, stenosis 4, redo
6, dysmotility 5, duodenal tapering
7, pneumonia
13, small bowel obstruction 13, laparotomy
Escobar 2004 [33] 169 46 10, cardiac failure 5.9
1, stenosis 1, redo 2.9
7, dysmotility 3, duodenal tapering
2, fistula
4, small bowel obstruction 4, laparotomy

was noted from 10 to 100%. The overall predic- of amniotic fluid decreases progressively in the
tion of small bowel atresia was 50.6%, and the bowel due to intestinal reabsorption (Fig. 18.12).
detection rates were 66.3% for jejunal atresia and In case of suspicion of small bowel atresia before
25.9% for ileal atresia [58], because the amount the third trimester, an ultrasound after 32 weeks
18  Bowel Atresia and Stenosis 253

should be done, and John et al. demonstrated that been well characterized, but recently several
the presence of both polyhydramnios and bowel studies showed lesions similar to intestinal neu-
dilatation upper than 17 mm has a sensitivity of ronal dysplasia with an important decrease of the
66% and specificity of 80% [59]. The bowel con- density of myenteric interstitial cells of Cajal in
tent is hypoechoic when it is a jejunoileal atresia proximal and distal bowel [62, 63]. Wang et al.
contrary to a colonic one with hyperechoic con- tested the expression of proteins in the atretic
tent [60]. A volvulus can be suspected or proven if bowel wall, as calretinin, glial cell-derived neu-
a whirlpool sign is seen close to the dilated bowel rotrophic factor (GDNF), bone morphogenetic
or mass, but this sign is difficult to find [61]. protein 2 (BMP-2), c-kit, α-smooth muscle actin
(α-SMA), and S-100 Protein. A significant
decrease of these six proteins was noted with
18.8.2 Pathology return to normal at 15 cm proximal and at 3 cm
distal to the atresia site (Fig. 18.13) [64]. Then,
The nature and the extent of damage to the
smooth muscle in small bowel atresia have not

3cm
m
15c

Fig. 18.11  Prenatal US (third trimester) of a jejunal atre-

sia type IV. Note the bowel distension and the hypoechoic Fig. 18.13  Length of decreasing of expression of pro-
content teins [64]

a Intestinal
reabsorption
Amount b
of
amniotic
fluid

Dilated Less
loops dilated
= loops
US ++ =
US ±

Fig. 18.12 (a) Amount of amniotic fluid in small bowel. (b) Huge dilatation in proximal jejunal atresia and slight one
in ileal atresia (US ++, sonographic dilatation; US ±, no or slight sonographic dilatation)
254 F. Varlet et al.

the surgeon ideally should theoretically do a (1955) [7] to include the apple peel syndrome
proximal resection of 15  cm and distal one of and multiple atresia. Four types are described
3 cm before performing the anastomosis to avoid (Figs. 18.17 and 18.18):
postoperative dysmotility. Furthermore, every
newborn should be tested for cystic fibrosis
because the incidence is about 10%.

18.9 Diagnosis at Birth

Bilious vomitings and abdominal distension are

the main symptoms at birth. There is commonly
no or grey meconium. Neonatal X-rays show one
or multiple dilated bowel loops (Fig. 18.14) or cal-
cifications due to prenatal perforation and meco-
nial peritonitis. Ultrasonography helps to identify
complications such as peritoneal effusion or bowel
ischemia of the dilated loops and a whirlpool sign
if a volvulus had occurred. Enema using nonionic
hydrosoluble contrast is usually not necessary but,
if done, can show an unused microcolon and the
cecum location (Figs. 18.15 and 18.16).

18.9.1 Classification
Fig. 18.15  Unused microcolon
The classification of jejunoileal atresia was
­initially proposed by Louw [65] and then later by
Martin and Zerella [66]. The current classifica-
tion of small bowel atresia is the Grosfeld modi-
fication (1979) [32] of the Louw Classification

Fig. 18.14  Dilated bowel loops Fig. 18.16  Cecum location

18  Bowel Atresia and Stenosis 255

I II IIIa

IV

IIIb

Fig. 18.17  Classification of small bowel atresia [32]

I II IIIa

IIIb IV

Fig. 18.18  (I) Atresia type I. No bowel interruption, but note atretic bowel. (IIIa) Atresia type IIIa. Note the V-shaped mes-
a difference between the caliber of the proximal enlarged por- enteric defect. (IIIb) Atresia type IIIb. Apple peel form: the
tion of the ileum and the small post-atretic one. (II) Atresia ileum is wrapped around its vessel. (IV) Atresia type IV. At
type II. Note the fibrous band between the pre- and the post- least five interrupted segments of bowel can be seen
256 F. Varlet et al.

Type I: occlusion by a mucosal web or diaphragm

and an intact mesentery.
Type II: total defect with a bridge of fibrous cord
between the two blind ends. No defect of the
mesentery.
Type IIIa: total defect between the two blind
ends. V-shaped mesenteric defect.
Type IIIb: the so-called apple peel syndrome in
which there is a total defect between the two
blind ends. The loop distal to the defect is twisted
in a spiral around a single retrograde vessel.
Type IV: multiple atresia.

This classification system is also applied to

colonic atresia.
From 233 cases of small bowel atresia, the
Fig. 18.19  Exteriorization of a small bowel atresia type
rate of each type was 23% type I, 25% type II, IIIa (arrows) through the umbilical wound. Note the huge
21% type IIIa, 8% type IIIb, and 23% type IV difference in diameters between the proximal enlarged
[34, 67]. The rate of stenosis should be about 5%, bowel and the thin distal one
but it is not correctly specified in these papers.
18.9.3 Anastomosis

18.9.2 Surgical Treatment The main challenge in an atresia is the approxi-

mation of the two ends of the bowel. Due to the
After intensive care unit preparation, surgery can lack of continuity, the bowel content is stopped
be performed. The conventional approach is a at the level of the atresia. Thus the proximal part
transverse laparotomy. However, today MIS is pro- of the bowel enlarges, while the distal part does
posed to decrease the size of the approach and not develop resulting in a huge difference in
minimize the effects of a large laparotomy on the their diameter. The surgical challenge is to
neonatal abdominal content. Through a circular establish the continuity between two tubes of
umbilical laparotomy, the umbilical vein and arter- different size. The ratio between the two parts
ies are ligated and divided. Then the umbilical stalk can be up to 1:6. The first step is to resect the
is excised. A 2.5 cm sagittal mid-­abdominal inci- two edges of the atresia. A transverse section
sion is created, which can be expanded by severing above the most dilated part of the proximal edge
the linea alba cranially and caudally. It is always will reduce its diameter. Usually this dilated
possible to enlarge the fascia or skin incision if the part does not recover normal movements and
bowel exposure is not sufficient. At the end of the can be favorably resected. An oblique section of
procedure, an umbilicoplasty is performed [68, the distal end will enlarge the suturing line, the
69]. Laparoscopy-­ assisted surgery was first mesenteric side being longer than the antimes-
described by Lima et al. in three cases in 2009. The enteric (Fig. 18.20).
procedure was an explorative laparoscopy to iso- Unfortunately this may not be sufficient. An
late the atretic bowel. Then in a second step, the end-to-side anastomosis is not wise as it may
resection and the anastomosis were performed out- impair the intestinal flow. A tapering of the
side the abdomen [70]. Since then, many authors dilated upper pouch gives better results
[71, 72] including ourselves have proceeded using (Fig. 18.21). It must be done on the antimesen-
such laparoscopy-assisted surgery (Fig. 18.19). teric side of the bowel.
18  Bowel Atresia and Stenosis 257

18.9.4 Enterostomies Historically the double barrel enterostomy as

described by Mikulicz was used by Fockens who
It is wiser to perform a temporary enterostomy first successfully treated a case of SBA in 1911
followed by a second look than to spoil a segment (Fig.  18.22a) [73]. It can always be performed.
of bowel that could have recovered. The more The disadvantages are that the bowel content
distal the enterostomy is placed, the better will be does not fill the distal limb to increase its diame-
the enteric refeeding, i.e., an i­leostomy carries a ter and that closure requires a laparotomy [74].
better outcome than a jejunostomy. The problems related to small bowel enteros-
Several enterostomies and their modifications tomies are the fluid and the electrolyte losses.
can been used according to the first priority The more proximal is the enterostomy, the more
(Fig. 18.22). severe are the losses. As to allow partial refilling
of the distal limb without impeding the proximal
emptying, Gross and Willital have suggested
modifications of Mikulicz’s double barrel enter-
ostomy. Initially Gross used a specially designed
spur-crushing clamp that was applied to gradu-
ally cause necrosis of the common wall between
the two limbs [30]. Willital has replaced the
clamp by a stapler shot to sever the septum
between the two barrels away from the vessels
either when performing the stomy or later
(Fig. 18.23) [75].
In 1956 Bishop and Koop described a “Roux-­
Fig. 18.20  Oblique section of the distal end to enlarge en-­Y” anastomosis to be used in case of meco-
the suturing line nium ileus. Their purpose was to avoid spillage of

Fig. 18.21  Tapering of

the dilated upper pouch

a b c

P P P

Fig. 18.22  Surgical options for SBA (P) for proximal limb. (a) Double barrel Mikulicz enterostomy. (b) Bishop-Koop
enterostomy. (c) Santulli enterostomy
258 F. Varlet et al.

Fig. 18.23  The Willital

technique to improve a
double barrel Mikulicz
enterostomy with
staplers

pancreatic enzymes (Fig.  18.22b) [76]. Since becomes patent enough, the enterostomy can be
then, this enterostomy has been widely used for closed extraperitoneally.
bowel atresia as it allows distal refeeding as well. To summarize the differences between these
The thin distal loop is exteriorized in a single techniques and to help with decision, let us say
limb enterostomy, and the enlarged proximal one that the double barrel enterostomy according to
is anastomosed intraperitoneally very close to the Mikulicz is the simplest and the fastest procedure
stomy by 3–4  cm. It is expected that when the but may induce an important loss of fluids and of
bowel distal to the anastomosis becomes patent, electrolytes. The modification brought by Willital
the ileostomy ceases to loose stools. If not, an partially solves the problem but with a vascular
easy extraperitoneal closure is performed later risk. The Bishop-Koop procedure favors refilling
on. Nowadays the Bishop-Koop enterostomy has into the distal bowel but may fail to empty the
lost popularity. However it is still in use and has proximal one, while the Santulli anastomosis is
been proven safe and efficient especially when more efficient when proximal decompression is
the stomy has to be performed proximally [77]. needed [78].
Using the Bishop-Koop procedure, Santulli In case of high flow through the enterostomy
and Blanc found too many anastomotic leaks in (high-output stoma ≥50 mL/kg/d) and with a pat-
their series. They believed it was related to a ent distal bowel, a reinfusion procedure should
poor passage through the distal bowel and look be initiated. It is known under various names:
for an immediate relief of obstruction by a succus entericus reinfusion, continuous extracor-
dependable and effective method. Then they poreal stool transport (CEST), and mucous fis-
described a new technique bringing the dilated tula refeeding. This is not an easy technique, and
proximal limb to the skin, the small distal one one of the available protocols must be carefully
being anastomosed intraperitoneally by 3  cm followed in a PICU.  But it is highly beneficial.
above the level of the skin (Fig. 18.22c) [5]. At The reinstillation of the proximal bowel content
first the enterostomy is left open in order to into the distal one diminishes per se the proximal
decompress the proximal bowel, and then a flow by up to 30% [79]. Additionally it improves
nutriment can be instilled into the distal one the bowel movements, increases the distal diam-
through a catheter. This supplies fluid, electro- eter, stimulates absorption of nutriments, and
lytes, and nutriments but also induces a progres- diminishes the risk of mucosal atrophy and of
sive enlargement of the distal intestine. Once the bacterial translocation [80, 81].
baby’s conditions have improved, a clamp is According to the patient’s conditions, different
placed across the enterostomy to the edge of the procedures are performed to treat a small bowel
indwelling catheter. This intermittent occlusion atresia: resection and anastomosis, with or with-
forces the passage through the anastomosis and out proximal tapering, jejuno- or ileostomy, and
can be used for weeks. Once the anastomosis delayed anastomosis [34, 64, 67, 82] (Table 18.6).
18  Bowel Atresia and Stenosis 259

Table 18.6  Different procedures to treat a small bowel atresia

Author N A RA TA WE O BK
Dalla Vecchia [34] 127 45 23 5 54
Sato [82] 88 23 49 + 9 multiple 7
Stollman [67] 114 70 9 5 30
Wang [83] 81 37 11 8 25
Total 410 138 95 50 10 92 25
33.7% 23.2% 12.2% 2.4% 22.4% 6.1%
N number of cases, A anastomosis, RA resection and anastomosis, TA tapering and anastomosis, WE web excision, O
jejuno or ileostomy, BK Bishop-Koop procedure

Table 18.7  Postoperative complications

Author N Fistula Wound abscess Sepsis Stricture Necrosis Prolonged ileus
Dalla Vecchia [34] 127 5 6 11
Sato [82] 88 4 2
Stollman [67] 114 8 4 9 1 3
Wang [83] 81 1 12
Total 410 18 10 9 3 3 23

Postoperative complications are listed in 18.10.2  D

 iagnosis at Birth
Table  18.7 with their ratio. Prolonged ileus is and Classification
reported only by two authors and raises the ques-
tion of a redo procedure with tapering [34, 83]. All newborns with isolated colonic atresia
The average of full oral intake without TPN is by develop delayed vomitings and huge abdominal
15 days (limits 12.5–17 days) and appears to be distension. No patients pass meconium. Plain
longer with TPN between 32.4 and 88 days [67, abdominal X-rays show bowel obstruction
82]. Late complications were represented by (Fig. 18.24). A contrast enema must be done to
small bowel obstruction in 48 from 410 children evidence the (micro) bowel distal to the obstruc-
(11.6%) and deaths in 51 (12.4%), especially due tion and precisely state the level (Fig.  18.25).
to short gut syndrome and TPN, but also by pre- However, the diagnosis is most often done during
maturity and infection. surgery. The classification used for colonic atre-
sia is that of small bowel (Grosfeld classifica-
tion). Among 227 cases, the types of atresia
18.10 Colonic Atresia reported are type I 14.5%, type II 12.8%, type
IIIa 62.1%, and type IV 10.6%. The atresia is
Colonic atresia and stenosis are extremely rare more frequently located on the right colon
conditions with an approximate incidence of (71.7%) than on the left one (28.3%) [34, 86–88].
1:20000 births [84, 85]. Colonic stenosis alone without atresia has been
reported only in less than 20 cases [89–92].

18.10.1  Prenatal Diagnosis

18.10.3  Associated Malformations
The prenatal detection of colonic atresia is
uncommon, and three cases have been suspected Associated anomalies were found in 106 chil-
because they were associated with small bowel dren from 227 cases found in the literature [34,
atresia [85]. 86–88]: 40 had gastroschisis, 37 jejunoileal atre-
260 F. Varlet et al.

18.10.4  Treatment

Due to this very unusual anomaly, there is no con-

sensus to treat colonic atresia, and the same proce-
dures as for jejunoileal atresia can be done.
Classically, from the proximal right colon to the
splenic flexure, primary anastomosis is indicated,
sometimes protected by ileostomy, and beyond a
colostomy is done followed by a delayed anasto-
mosis after a few weeks. But the final decision
must be taken according to the newborn’s condi-
tion, presence of a sepsis or not, surgical school,
and type of lesions found at surgery. The rate of
death is significantly higher when the baby is
­managed beyond 72 h of obstruction, and the prog-
nosis is also depending on associated small bowel
atresia, the absence of ileocecal valve, bowel perfo-
Fig. 18.24  Colonic atresia and neonatal X-rays ration, and associated Hirschsprung’s disease [86].
Rectal and/or colonic biopsies during surgery seem
to be an important step to improve the knowledge
and the management of colonic atresia.

18.11 Conclusion

Duodenal and jejunoileal atresia rates differ

according to the countries, but an incidence of
1.6/10,000 births seems to be accepted.
Arguments for a genetic origin have become
more important to explain the pathogenesis of
atresia, even if the vascular origin remains a valid
hypothesis. Minimal invasive surgery can treat
numerous cases with less invasive procedures
and good results. The associated malformations,
such as cardiac anomalies, Down’s syndrome,
short gut syndrome or Hirschsprung’s disease,
play a significant role in the prognosis, the func-
tional result, and the final outcome.

Fig. 18.25  Stop of contrast enema in right flank Acknowledgements  Thank you to Olivier Reinberg for
reviewing this chapter.

sia, 36 malrotations, 19 Hirschsprung’s diseases,

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with balloon dilatation in four children. Eur J Radiol. imal incision surgery. J Pediatr Surg. 2014;49:1605–9.
2006;59:29–32. 69. Sawai T, Yonekura T, Yamauchi K, et  al. A novel
51. Torroni F, De Angelis P, Caldaro T, et al. Endoscopic approach to neonatal abdominal surgery via a circular
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 Meconium Ileus
19
Philip Corbett and Amulya Saxena

19.1 Introduction bowel and a type 3 atresia at birth, or it causes the

peritoneum to thicken and in some cases calcify.
Meconium ileus (MI) is neonatal intestinal The resulting fluid-filled cavity is called a meco-
obstruction caused by protein-rich, inspissated nium pseudocyst. Occasionally a perforation can
meconium in the terminal ileum. This viscid heal without obstruction, and evidence of the pre-
meconium adheres to the bowel wall, causing an vious injury is discovered incidentally as perito-
intra-luminal obstruction (sometimes referred to neal calcification on x-ray much later (Fig. 19.1).
as obturator-type obstruction). Its incidence is MI has been reported by some studies to be an
approximately 1:10,000 live births [1] within the indicator of poor growth and respiratory function
white population but lower in other races. later in life, suggesting that MI represents a more
Historically, MI has been almost exclusively severe phenotype of CF [6, 7]. However, subse-
associated with cystic fibrosis (CF); however this quent large multicentre retrospective studies and
dogma has been challenged by some published matched control studies have shown no differ-
series that report 21–46% of their cases did not ence in long-term outcomes [8, 9].
have CF [2, 3]. 10–20% of children born with CF
present as MI [4, 5].
MI is classified as ‘simple’ or ‘complex’ with 19.2 Cystic Fibrosis
roughly half of cases falling into each category.
Simple MI is a pure obstruction with a distended CF is an inherited autosomal recessive disease
terminal ileum filled with sticky meconium and with a carrier rate of up to 5% in the general pop-
unused distal bowel containing small pellets of ulation and an incidence of about 1:2500 live
grey stool. Complex cases have undergone a per- births amongst white babies in Europe and North
foration in utero, often secondary to a segmental America. Amongst black and Asian babies, the
volvulus, resulting in bowel wall necrosis. This incidence is much lower [10]. The condition is
causes a sterile, chemical peritonitis, which either caused by mutations in a gene which codes for a
settles entirely with resorption of the damaged protein known as the cystic fibrosis transmem-
brane regulator (CFTR) and is situated on the
long arm of chromosome 7 (7q31) [11]. CFTR
regulates the passage of Cl− and HCO3− ions
P. Corbett · A. Saxena (*) across epithelial cell apical membranes. An
Department of Pediatric Surgery, Chelsea Children’s abnormality results in abnormal electrolyte con-
Hospital, Chelsea and Westminster NHS Foundation
Trust, Imperial College London, London, UK centrations and desiccation of secretions which
e-mail: [email protected] can block epithelial-lined tubes such as bronchi,

© Springer Nature Switzerland AG 2019 265

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_19
266 P. Corbett and A. Saxena

a b

Fig. 19.1 (a) Meconium obstruction in terminal ileum. (b) Segmental volvulus secondary to obstruction with isch-
aemia and perforation. (c) The injured bowel is reabsorbed, resulting in type III atresia
19  Meconium Ileus 267

vasa and pancreatic and biliary ducts. The defec- formed on children over 2 kg and 2 weeks of age.
tive excretion of HCO3− and its role in the Sweating is induced by placing electrodes on an
­pathogenesis of CF have only recently been dis- area of skin and running a very small electrical
covered. Normally mucus is secreted into the current through them (iontophoresis). One of the
bowel lumen in a tight matrix formation, held in electrodes contains pilocarpine, a muscarinic ago-
place by Ca+ ions. The ions are chelated in a pro- nist. The current draws the drug into the skin,
cess involving the HCO3− which allows the stimulating perspiration. The sweat is collected
matrix to spring open, absorb water and become on a piece of gauze and sent for analysis; a con-
normal mucus [12, 13]. The failure of this mech- centration of sodium in excess of 60  mmol/L is
anism is now thought to be the cause of the considered diagnostic, whilst concentrations
obstruction which affects neonates. Previously it below 30 mmol/L are expected in a child under 6
was believed that pancreatic insufficiency played months [19]. A result between these two values is
a role in this process, but since 1992, numerous non-diagnostic and needs repeating.
animal models have shown that obstruction can
occur with a normally functioning pancreas [14].
There are currently more than 2000 documented 19.3 Prenatal Diagnosis
mutations in the CFTR gene although not all of
these result in CF [15]. The most common muta- Hyperechoic bowel contents, dilated bowel and
tion worldwide is F508del, which is identified in up non-visualisation of the gall bladder have all been
to 66% of CF sufferers (although the incidence is reported as suggesting MI, but they are extremely
over 80% in Northern American and Northern insensitive and nonspecific. In a series of 289 cases
European whites). Less than 20 other mutations are of hyperechoic bowel identified at the second tri-
responsible for the vast number of cases of CF, but mester scan, only 7.6% had CF, whilst 24.6% had
they vary depending on the location and ethnicity other pathologies including trisomy-­21 and cyto-
of the carrier meaning screening for ‘common’ megalovirus infections. 67.8% had no pathology
mutations must be tailored accordingly [16]. at all [20]. If hyperechoic bowel is identified, its
Interestingly, the F508del mutation predisposes to relevance can be determined by testing parents for
meconium ileus with homozygous carriers having common CF mutations. If one or both parents are
a 25% chance of presenting with MI and those with carriers, the pregnancy is considered ‘high risk’,
other mutations having a 12.5% chance [17]. and the positive predictive value of this sono-
Furthermore it appears that genes other than CFTR graphic sign jumps to 52% from 6.4% in pregnan-
affect the phenotype, with one study showing an cies where neither parent is a carrier [21].
82% concordance for MI in monozygotic twins Dilated bowel and absent gall bladder also
which dropped to 22% in dizygotic twins [18]. suggest a wide range of diagnoses including nor-
There are various methods of testing for CF. In mal pregnancy. In short, antenatal ultrasound
some countries (e.g. the UK), routine blood spot scan is only helpful when both parents are identi-
screening is employed. A neonate with CF cannot fied as CF carriers. In this instance, the parents
readily excrete pancreatic trypsinogen via the may be offered amniocentesis with counselling
duct and so it builds up in the blood. This rise in as a positive diagnosis would mean considering
‘immunoreactive trypsin’ (IRT) can be detected in termination or referral to a tertiary centre.
the first 8  weeks of life by a heel-prick test. A
level greater than 80 μg/L is indicative and should
be confirmed by further investigation. Increasingly, 19.4  resentation, Initial
P
genetic testing for the most common mutations Management and Investigation
has become commonplace, but it should be noted
that a negative result does not necessarily exclude Simple MI presents as abdominal distension
the diagnosis. The gold standard test for cystic within the first with bilious vomiting and non-­
fibrosis remains the sweat test. To ensure an ade- passage of meconium. Complicated MI may
quate sample is obtained (100 μg), the test is per- present identically or have the addition of an
268 P. Corbett and A. Saxena

inflamed, tender abdomen if the meconium peri-

tonitis is still active. In most cases, the presenta-
tion will be difficult to differentiate from other
causes of distal bowel obstruction such as
Hirschsprung’s disease or distal ileal atresia.
Examination should include assessment of the
child’s breathing, perfusion, temperature and gly-
caemic control with immediate correction as
needed. A detailed examination of the abdomen
should identify palpable bowel loops, exclude
incarcerated hernias and ensure that the sacrum
and anus are normal. A per rectal examination
should exclude atresia and presacral mass. A lim-
ited rectal washout with 20 mL/kg of warm 0.9%
saline introduced with a soft rubber catheter may
be both therapeutic and diagnostic as most cases
of Hirschsprung’s disease will see some decom-
pression of the abdomen with effective rectal
washouts but usually MI will not.
The immediate priorities are as with any neo-
natal obstruction, i.e. intravenous hydration, Fig. 19.2  Plain abdominal radiograph showing ‘soap
bubbling’, also known as Neuhauser’s sign
nasogastric tube decompression and appropriate
antibiotic cover. In addition to blood tests which
are needed to direct fluid management and does not rule out complex meconium ileus. In 1
exclude clotting problems, blood should also be series of 58 neonates, 27 (47%) required laparot-
taken and stored for future genetic analysis omy and resections for complex MI, but only 8
(should the child receive a blood transfusion, (30%) of those had radiographic evidence of cal-
subsequent genetic tests may be unreliable cification preoperatively [22].
because of the presence of the donor’s genetic
material).
After initial resuscitation, plain abdominal 19.5 Conservative Management
x-ray is a useful first-line imaging request. Simple
MI appears as unequal distension of proximal Whilst clinical or radiological suspicion of com-
bowel loops containing swallowed air and meco- plex MI mandates surgery, simple MI can poten-
nium with a characteristic ‘soap bubbling’ tially be relieved conservatively. Since Noblett
appearance (Fig. 19.2). This feature is due to the first described its use in 1969, per rectal adminis-
presence of small air bubbles trapped in the tration of Gastrografin enema under fluoroscopic
exceptionally viscid meconium which also means control has been the most popular method of
that air-fluid levels are usually absent. Complex relieving obstruction caused by inspissated
MI can be distinguished from simple by the pres- meconium [23].
ence of a large intra-abdominal mass displacing Although there is no uniformity of practice,
bowel loops and sometimes containing an air-­ typically, a soft catheter is passed rectally, and
fluid level. This ‘meconium pseudocyst’ men- contrast medium is introduced slowly, whilst its
tioned previously may also show visible progress is monitored by intermittent x-ray
calcification varying from faint flecks to a clear screening. The goal of this process is to observe
curvilinear rim, delineating the edge of the lesion. contrast passing from the unused ‘micro-colon’
Whilst evidence of a pseudocyst on plain x-ray is (Fig. 19.3) and terminal ileum to distended small
an indication for laparotomy, the absence of signs bowel. If this is achieved, passage of the obstruct-
19  Meconium Ileus 269

a b

c d

Fig. 19.3 (a) Instillation of contrast enema under fluoro- and entry of the contrast media in the small bowel. (d)
scopic control. (b) Passage of the meconium through the Contrast enema reaching the ileal loops of bowel which is
colon which has a ‘nonused’ appearance. (c) Successful filled with impacted meconium
instillation of contrast enema beyond the ileo-caecal valve

ing meconium is almost always observed shortly rated by intervals of a few hours [24]. Failure to
thereafter. If one treatment does not relieve relieve obstruction may result from the inability
obstruction and no adverse effects are observed, of contrast to reach the distended bowel or because
some clinicians advocate repeated attempts sepa- the patient has an unrecognised complex MI.
270 P. Corbett and A. Saxena

Gastrografin is a water-soluble, iodine-­ ate injury or mural necrosis resulting in delayed

containing contrast agent designed to be given perforation. Type of contrast and size of catheter
enterally. Its active ingredients are sodium ami- have no influence on perforation rates, but anec-
dotrizoate and meglumine amidotrizoate in water dotal evidence suggests the use of inflated bal-
with flavourings and an emulsifying agent, poly- loon catheters in the rectum increases the risk
sorbate 80 (Tween 80). It has an osmolarity of [28]. Studies assessing the toxic effects of meglu-
1900 mOsm/L, which is approximately six times mine amidotrizoate and polysorbate 80 on
that of extracellular fluid [25]. The rate of suc- colonic mucosa in animal models have produced
cessful decompression has been reported in older strongly conflicting results, but in the experience
series to be between 50 and 66% of neonates with of the authors, there is no direct irritant effect
simple MI [24, 26]. However, the most recent observed [29, 30]. The osmotic diarrhoea caused
series published in 2009 reported a success rate by undiluted contrast can result in distributive
of only 22% [27]. The success of Gastrografin shock secondary to third space fluid losses.
has been attributed to two of its physical Experienced radiologists will either dilute the
characteristics: contrast with water or ensure that the child is
receiving appropriate replacement for the
1. Its high osmolarity draws large quantities of expected losses during the procedure.
water from the bowel wall into the lumen,
hydrating and liquefying the meconium result-
ing in an osmotic diarrhoea. 19.6 Operative Management:
2. The polysorbate 80’s action as an emulsifier is Simple Meconium Ileus
presumed to reduce the viscosity of the meco-
nium directly. The indications for surgery are:

A survey of the American Society of Pediatric 1. Failure of conservative measures to relieve the
Radiology in 1993 demonstrated that Gastrografin obstruction
was more effective than other contrast media but 2. Complication of conservative measures, e.g.
revealed no significant difference in success rates perforation
between those who used pure Gastrografin to 3. Evidence of complicated MI, suggesting an
those who diluted the contrast to serum osmolar- atresia
ity [28]. The same survey showed a statistically
higher success rate for radiologists who included Since 1948, the simplest method of surgical
additives (like extra polysorbate 80) to their relief of obstruction has been laparotomy and
Gastrografin, but more recently, animal and meconium disimpaction using saline via a tube
in vitro studies of human meconium have shown enterostomy at the site of obstruction coupled
no advantage of polysorbate 80 over normal with a limited bowel resection as necessary [31].
saline in relieving constipation or reducing vis- Typically, a right-sided supra-umbilical trans-
cosity [29]. Therefore, whilst Gastrografin is verse abdominal incision is made, and the
shown to be effective, exactly why it is remains a peritoneum is entered safely. The midgut can
­
matter of debate. then be gently expressed through the wound and
Failure to relieve obstruction is not the only inspected for signs of injury or atresia. Such
complication of Gastrografin enema. Perforation exposure of the viscera will result in rapid loss of
of the bowel occurs in approximately 3% of ene- heat and fluid, requiring the surgeon to be quick
mata although there is significant variation in this in their inspection before returning the majority
from series to series. The majority of perforations of the bowel to the abdominal cavity. In simple
are identified at the time of the study [27, 28]. MI, the site of intra-luminal obstruction is usu-
The mechanism is almost certainly mechanical ally quite clear with a marked change in bowel
over distension of bowel either causing immedi- diameter somewhere in the terminal ileum. The
19  Meconium Ileus 271

benefit from doses of mucolytics (administered

orally and rectally) post-operatively until they
start opening bowels for themselves.
Many irrigation solutions have been used from
0.9% saline to Gastrografin [33] and even hydro-
gen peroxide [34]. N-Acetylcysteine (NAC) has
been used as an intraoperative irrigant since the
early 1960s [35]. It depolymerises glycoproteins
in mucus by hydrolysing the disulphide bonds
Fig. 19.4  Enterotomy is used to remove the highly vis-
that link the mucin monomers [36]. Despite its
cous meconium from the intestinal loop, as manual milk-
ing of the meconium through the intestine can lead to widespread use and successes reported anecdot-
serosal tears of the bowel loops (see right top loops in ally in the literature, there is relatively little evi-
image) dence that it is more effective than saline. An
in  vitro study of normal human meconium
upstream small intestine is grossly distended due showed that, saline is superior to 4% NAC at
to the long-standing nature of the obstruction, immediately reducing viscosity (84% reduction
whilst the distal bowel is collapsed and firm, con- versus 69% reduction) [29]. The same study did
taining puttylike pellets of meconium which can note a 99% drop in viscosity with NAC after 6 h
be indented with pressure. An enterotomy is of incubation, suggesting that it has a place as an
made on the anti-mesenteric border through effective mucolytic but perhaps not in the operat-
which a soft tube can be passed and manoeuvred ing theatre.
both proximal and distal to the site of obstruction Once decompression has been achieved, the
(Fig. 19.4). Some authors advocate the placement surgeon faces a choice as to how to complete the
of a purse-string suture to prevent spillage of operation, and on this, there is no consensus. The
bowel contents and peritoneal contamination, but decision should be made based on the condition
in our experience, the enterotomy needs to remain of the bowel, the patient and the experience of the
open and be large enough to allow expression of surgeon.
the abnormally viscid bowel contents [32]. An
irrigation solution can then be instilled to dilute 1. Closure of enterotomy can be performed if
the inspissated meconium and gently distend the the proximal bowel is minimally distended
bowel which has the action of freeing the sticky and the surgeon is very confident that she has
substance from the mucosa. The irrigation solu- completely cleared all trace of meconium
tion and meconium are then gently expressed obstruction distally.
along the bowel lumen to the enterotomy and 2. Resection and anastomosis is possible if
removed. This process must be repeated until the there is a segment of small bowel that the sur-
proximal bowel is free of thick meconium and geon feels is too dilated to recover its propul-
the distal bowel contents have been clearly irri- sive ability. This too relies on complete
gated into the colon to exclude the possibility of clearance of the meconium obstruction as a
distal ileal obstruction. Ideally, some of the irri- high distal intra-luminal pressure will result in
gation fluid and pellets of grey meconium are dis- anastomotic leak. Proponents of primary
charged from the anus during the operation to anastomosis point out that no further anaes-
demonstrate patency throughout. However, it is thetics are needed for stoma closure and the
well recognised that many neonates exhibit con- risks of anastomotic leak are acceptable [37].
tinuing symptoms of obstruction post-operatively 3. Formation of a tube enterotomy. By bring-
even when full decompression is achieved at the ing the enterotomy to the skin and leaving a
time of surgery. Whether this is due to a pro- tube in situ, it is possible to continue washouts
longed post-operative ileus or the reaccumulation of the distal bowel until such time that the
of viscid secretions is not clear, but there may be baby achieves normal bowel transit. Some
272 P. Corbett and A. Saxena

authors have proposed creating an appendi- Credible arguments can be made for most of the
costomy for the same purpose. One centre that options outlined above, and it is essentially a bal-
routinely uses this technique reported com- ance of risk between the formation of an anasto-
pleted decompression in all eight reported mosis in a system where some element of distal
cases, allowing the tube to be removed obstruction may remain and the complications
12–14  days later on the ward. All enteroto- and extra anaesthetics associated with stomas.
mies closed spontaneously within 24 h of tube We identified six large retrospective reviews of
removal [38]. MI management from single centres since
4. Formation of a stoma. Concerns about anas- 1990 in the world literature [42–47]. Collectively,
tomotic leak have led many surgeons to opt for they reported the results of the operative manage-
an ileostomy. Many types of stoma have been ment of 79 cases of simple MI (they also reported
used over the years with some now confined to outcomes for use of Gastrografin enema and
the history books (see also Chap. 18.9.4). complicated MI separately). None of the papers
(a) Mikulicz stoma. This technique, popula- had sufficient numbers for statistical analysis,
rised by Gross in 1953, involved bringing and in their conclusions, two favoured simple
the distended loop to the wound and enterotomy [42, 43], washout and closure, two
suturing its afferent and efferent limbs to favoured stoma’s in all cases [44, 45], one paper
the abdominal wall as for a stoma. When was non-committal [46] and the last concluded
the abdomen was closed, the distended that it would no longer use Bishop-Koop or
loop was resected just above the skin, Santulli stomas due to three of their ten stomas
leaving a double-barrelled stoma which developing problems at the end-to-side anasto-
was converted to a single orifice by the mosis requiring re-laparotomy [47].
application of a crushing clamp to the
common wall [39]. This procedure has
largely been superseded by others. 19.7 Complex Meconium Ileus
(b) Bishop-Koop stoma. In 1957 these two
doctors proposed performing an end-to-­ As stated previously, a diagnosis of complicated
side anastomosis of the proximal bowel to meconium ileus is an indication for laparotomy,
the distal and then bringing a ‘chimney’ but the intra-abdominal findings will influence
of distal bowel to the skin as a stoma and the rest of the operation. If active peritonitis is
catheterisable channel through which irri- found from a recent perforation, lavage and for-
gation could be performed [40]. When the mation of a stoma is the simplest, safest manage-
distal bowel had recovered sufficiently, ment. Similarly, the presence of an established,
the faecal stream would start to pass pref- thick-walled pseudocyst will necessitate decorti-
erentially towards the terminal ileum and cation and stoma.
colon, and the stoma output would drop. However, if the obstruction is due to a seg-
(c) Santulli stoma. Four years after Bishop mental volvulus which has not perforated, resec-
and Koop, Santulli suggested an adapta- tion of the volved segment and primary
tion of their stoma in which it was the anastomosis can be considered. If the volvulus
proximal limb which was brought to the has resulted in a pure atresia (3a or 3b) but no
skin rather than the distal [41]. He felt this evidence of chemical peritonitis remains, anasto-
configuration would improve proximal mosis could also be attempted then. Whenever
bowel decompression. anastomosis is attempted, the relative discrep-
(d) Simple divided ileostomy. This has the ancy in size between the huge proximal segment
advantage of being relatively simple to and the collapsed distal segment will have to be
form, has no internal anastomosis and still resolved. If sufficient small bowel is present that
provides a catheterisable channel to irri- some might be excised without compromising
gate the distal bowel. absorption, then the most distal, distended part of
19  Meconium Ileus 273

the proximal bowel may be excised to make the in 1988 comparing CF Centres in Toronto and
anastomosis simpler. Alternatively, a discrepancy Boston showed median survival was 30 years in
may be reduced by opening the distal bowel at an Toronto, but 21 years in Boston. The only signifi-
oblique angle, increasing its circumference. cant difference between the groups was nutri-
Various methods for tapering the proximal side tional status—the Canadian patients were taller
of the anastomosis are also described. and weighed more than their American counter-
We, like other authors [32, 48], feel that in the parts [51]. More recently a prospective, observa-
majority of cases of complicated MI, a stoma is tional study of 3142 children demonstrated that
appropriate. Only one retrospective series in the those with weight at or above the 50th centile
last 10 years has treated all the cases of compli- early in life had significantly better pulmonary
cated MI with resection and anastomosis [49]. In function and survival rates than those below the
a series of 13 patients, 4 (31%) had surgical com- 10th centile [52]. Based on such evidence, guide-
plications requiring a repeat laparotomy, and 1 of lines issued by the Cystic Fibrosis Foundation
those died. The authors concluded that primary recommend that the target weight for any CF
anastomosis was still their favoured method for infant should be above the 50th centile [53].
managing complicated MI. Neonates not reaching this centile should have
their calorific intake increased from 100 kcal/Kg/
day to 115–130  kcal/Kg/day. Nutritional guide-
19.8 Post-Operative Management lines published by the CF Foundation [54] and
the European Consensus on Nutrition in Patients
Fluid and electrolyte homeostasis is the primary with CF [55] recommend human milk feeding
goal of management in the immediate post-­ but accept that the evidence for this is not strong.
operative period. Ileus secondary to the surgery A prospective cohort study found no difference in
will exacerbate the pre-existing gut hypomotility weight or length between exclusively human
caused by a long period of obstruction. Therefore, milk-fed infants with CF and those who were
third space and nasogastric losses will have to be exclusively formula-fed [56].
replaced in addition to maintenance fluids. If the There are several challenges common amongst
child has a stoma, this is also a potential source of babies presenting with meconium ileus that make
fluid and electrolyte loss and should be consid- adequate weight gain difficult. If bowel resection
ered in fluid balance calculations. or a stoma has left the child with short gut, a nor-
Four percent NAC can be instilled via naso- mal enteral feeding regime will be insufficient.
gastric tube (or via stoma, if present) to help Continuous enteral feeding with a predigested
break down any residual meconium. 5 mL given formula is recommended until such time as a rou-
three times per day is recommended by the tine feed is tolerated. However, if sufficient
British National Formulary [50] and can be con- enteral feeds cannot be absorbed, parenteral
tinued until ileus resolves. Most surgeons would nutrition must be employed.
prescribe a short post-operative course of antibi- Neonates with MI should be assumed to have
otics, but prophylaxis beyond this is not required. pancreatic insufficiency until it can be confirmed
Stomas are typically closed early at approxi- by measurement of faecal elastase levels
mately 6 weeks to limit nutrition, fluid and elec- (<100ug/g is diagnostic) which is now consid-
trolyte difficulties. ered the ‘gold standard’ [57]. Since this test can-
not be performed on ileostomy effluent, children
with a stoma can only be tested after closure.
19.9 Nutrition Whenever enteral feeds are started, pancreatic
enzyme replacement therapy (PERT) should
The importance of nutrition to life expectancy in commence. This includes feeding with predi-
cystic fibrosis sufferers has been known for gested formulas [58]. Dosing of PERT is based
decades. A major cross-sectional study published on historical precedent as no formal studies have
274 P. Corbett and A. Saxena

been undertaken to determine optimal dosing Therefore, respiratory bodies recommend com-
[59]. A widely recommended dosing regimen is mencing daily percussion and postural drainage
2500 lipase units per kilogramme per feed in the first few months of life [66, 67]. The addi-
(assuming a feed of about 120 mL) with a maxi- tion of a bronchodilator (albuterol) has been
mum daily dose of 10,000 lipase units per kg per shown to enhance the effect of the physical ther-
day [60]. Although PERT contains protease and apy [68, 69]. They only caveat is that head down
amylase, dosing is always based on lipase units. posture may exacerbate GERD and so is to be
PERT needs to be tailored to each patient based avoided [70, 71].
on response; too low a dose can result in malab-
sorption, failure to thrive and constipation,
whereas excessively high dosing has been shown 19.11 Other Complications
to cause fibrosing colonopathy, a condition pre- of Cystic Fibrosis
senting as obstruction due to multiple colonic
strictures [61–63]. Distal intestinal obstruction syndrome (DIOS),
Infants with cystic fibrosis secrete large formerly known as meconium ileus equivalent, is
amounts of sodium in their sweat, and this can caused by increased viscosity of intestinal con-
lead to a total body deficit which is not reflected tents and occurs most commonly in teenagers
by the serum sodium [64]. A urine sodium con- and young adults. The aetiology is unclear, but
centration of less than 20 mEq/L suggests that the some cases are certainly due to poor compliance
child’s kidneys are actively retaining sodium with pancreatic enzyme replacement therapy
because of sodium depletion. These losses are which is a problem in this age group. Presenting
exacerbated by the presence of a stoma. 2–4 mmol symptoms are most commonly abdominal pain
of sodium chloride can be added to each feed and distension, which can cause some diagnostic
[50]. Babies with meconium ileus can also have difficulty as other pathologies associated with CF
deficiencies of fat-soluble micronutrients, i.e. also present similarly in this age group, i.e. intus-
vitamins A, D, E and K and zinc. For this reason, susception, appendicitis and fibrosing colonopa-
it is recommended that they receive vitamin sup- thy. Cross-sectional imaging is sometimes
plementation as standard and zinc supplementa- required to clarify the diagnosis. Treatment is
tion if there is unexplained poor weight gain [54]. hydration and administration of a strong osmotic
Gastroesophageal reflux disease (GERD) has laxative containing polyethylene glycol (Klean-­
an increased prevalence in infants with CF with Prep®, Golytely®). Failure of this therapy would
up to 50% displaying symptoms and having mean surgery, but this is a rare outcome [72].
abnormal pH studies [65]. Proton pump inhibi- In addition to intussusception, viscous stool
tors or histamine-2 receptor antagonists can be increases the possibility of rectal prolapse
used as a first line if the child is symptomatic. In although there is very little concerning this in the
addition, they can be given empirically as an literature. A single retrospective review suggests
adjunct to PERT which is inactivated if the stom- there is a 3–4% incidence of CF in children pre-
ach’s pH is very low. senting with rectal prolapse [73]. Biliary disease
resulting in hepatic failure is a very serious but
thankfully rare complication of CF.  End-stage
19.10 Respiratory Support liver disease requiring transplant does occur but
usually in adulthood [74]. Fertility is severely
Although respiratory symptoms tend not to mani- impacted in men with 98% being infertile due to
fest in the first year of life, it is perceived that occlusion or absence of the vasa. Epididymal
commencing airway clearance therapy as soon as sperm aspiration is possible but only rarely prac-
possible reduces complications later in life. tised [75].
19  Meconium Ileus 275

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No. 486: update on carrier screening for cystic fibro-
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their results with enterotomy and irrigation, Identification of the cystic fibrosis gene: genetic anal-
meconium ileus was a fatal condition. Numerous ysis. Science. 1989;245:1073–80.
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 Gastrointestinal Tract Duplications
20
Carmelo Romeo, Patrizia Perrone,
and Pietro Antonuccio

20.1 Introduction 20.2 Pathogenesis

Gatrointestinal tract duplications (GTDs) are rare Various theories have been proposed to explain
congenital anomalies that can occur in any por- the origin of these lesions, but none adequately
tion of the gastrointestinal tract from mouth to explains all intestinal duplications. The primitive
anus but are more commonly encountered in the foregut gives rise to the pharynx and its deriva-
small intestine. The term intestinal duplication tives, the respiratory tract (the trachea and lungs),
was first used by Calder in 1733 and later by Fitz esophagus, stomach, and duodenum to the level
in 1884 but was not widely used until it was pop- of the ampulla of Vater. No single embryological
ularized by Ladd in 1937, with further classifica- theory explains the spectrum of anomalies cov-
tions by Gross in 1953 [1–3]. ered by the heading “foregut duplications.” The
Gastrointestinal tract duplications have an split notochord theory is an attractive explanation
incidence of 4500–12,500 live births [4], and for some alimentary tract and spinal anomalies,
recent studies report that duplications are more e.g., neurenteric canal, but does not explain the
common in males than in females [5]. They can full spectrum of lesions observed. The notochord
present at any age, but 80% of cases present appears to have a pivotal role to play in foregut
within the first 2 years and the majority within development as the organizer of paraxial organo-
the first 3 months of life, with antenatal diagnosis genesis. There is some evidence emerging that
made in a significant number of cases [6, 7]. altered expression of the sonic hedgehog gene by
The distribution of alimentary tract duplica- the notochord affects the Shh-­GLi signaling path-
tions shows that the most common location is in way and may contribute to a spectrum of broncho-
the midgut (more than 64%). It is reported in the pulmonary, alimentary tract, and associated
literature that most of these duplications are anomalies [8]. It would appear that the cystic
located in the terminal ileum, but recently Rattan duplications develop secondary to an altered split
et al., reporting their case histories regarding 17 notochord mechanism, and instead, tubular dupli-
neonates, found that the major site involved in cations could develop secondary to a partial twin-
intestinal duplications was the mid-ileum rather ning of the fetus. According to the split notochord
than the terminal ileum [5]. theory, early in embryonic life, the neurenteric
canal is formed connecting the primitive neural
C. Romeo (*) · P. Perrone · P. Antonuccio tube with the developing intestine. During closure
Department of Human Pathology in Adult and
Developmental Age “Gaetano Barresi”, Unit of
of the neurenteric canal, remnants of developing
Paediatric Surgery, University of Messina, Messina, Italy intestine may be left anywhere from the intraspi-
e-mail: [email protected] nal space to the chest and abdominal cavities.

© Springer Nature Switzerland AG 2019 279

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_20
280 C. Romeo et al.

According to the theory of incomplete twinning, Esophageal duplication cysts have a double
the type of duplication that occurs most com- layer of surrounding smooth muscle, are lined by
monly involves the hindgut causing duplications alimentary (squamous or enteric) epithelium and
of the colon, rectum, and anus. Bremer’s theory of are attached to the esophagus in either a parae-
incomplete recanalization has also been consid- sophageal or an intramural fashion [11].
ered; according to this the error occurs during the Gastric duplication cysts are usually single
recanalization phase of the intestine with forma- and, in general, do not communicate with the
tion of a long continuous tube. Errors in this pro- gastric lumen. Histologically, the cyst wall can
cess can leave cystic structures composed of consist of mucosa, subepithelial connective tis-
intestinal remnants in addition to the normal gut. sue, a layer of smooth muscle and an outer fibrous
These duplications are usually of the cystic type capsule. The mucosa is typically lined by gastric
[9]. Finally, the literature reports on environmen- foveolar epithelium, but most of the cystic wall is
tal stress on the fetus, even during different gesta- lined with a pseudostratified columnar ciliated
tional times, and in this regard, Mellish and Koop epithelium. Sometimes, small intestinal or
hypothesized that traumas and hypoxia could lead colonic mucosa can be also found. Gastric dupli-
to the formation of duplications. cation cysts may also contain ciliated cells, pro-
Cystic duplications may be associated with spi- teinaceous debris, crystal formations or engulfed
nal cord and vertebral anomalies, and tubular dupli- histiocytes. Bronchogenic duplication cysts are
cations may be associated with urinary tract, spine, lined with respiratory epithelium (which is usu-
and central nervous system anomalies. Foregut ally ciliated pseudostratified columnar in nature)
duplications probably occur during the normal divi- and may contain cartilage/bronchial glands in
sion of the foregut into respiratory and esophageal their wall. Bronchogenic duplication cysts can
structures and may therefore contain elements of also contain one or more layers of smooth mus-
respiratory tract, such as cartilage and bronchial cle. Most are located in the mediastinum around
epithelium (bronchogenic cyst), elements of the the tracheobronchial tree or within the pulmo-
esophagus such as smooth or striated muscle and nary parenchyma.
squamous epithelium (esophageal duplication), or Small bowel duplication cysts can be associ-
elements of both (foregut duplication) [7]. ated with all three small bowel subtypes: duode-
nal, jejunal, and ileal. In general, the wall of
small bowel duplication cysts can contain two
20.3 Pathology mucosal layers sharing a common muscle layer.
More specifically, duodenal duplication cysts
Gastrointestinal tract duplications may be single, consist of submucosa, muscularis propria, a duo-
multiple, or complex and can be classified denal epithelial lining, and intimate attachment
according to morphology into cystic or tubular to the GI tract. Jejunal duplication cysts consist
masses with the presence of an intimate attach- of submucosa and muscularis propria and are
ment to the GI tract, a layer of smooth muscle in lined with jejunal mucus glands. Similarly, ileal
the wall and an epithelial lining resembling some duplication cysts consist of submucosa and mus-
part of the GI tract (islets of gastric mucosa, pan- cularis propria and are lined with ileal mucous
creatic tissue, and respiratory ciliary epithelium). glands and can contain heterotopic gastric
These are located on the mesenteric board of the mucosae.
intestinal canal with which they share the muscu- In 33% of colonic duplication cysts hetero-
lar layer and vascular axis but with a mucosal lin- topic gastric mucosa may be found; these cysts
ing. Duplications may be communicating or can contain multiple layers of the bowel wall
noncommunicating with the intestinal lumen, including mucosa, submucosa, and muscularis
although most duplications do not communicate propria. They can contain at least one outer mus-
with the adjacent bowel [10]. cular layer with an inner gastrointestinal mucosal
The most common duplication is usually cys- lining. Colonic duplication cysts can also contain
tic (80%) and is located on the mesenteric aspect well-organized layers of smooth muscle with
of the small or large intestine (midgut 64%). intimate attachment of the common wall to the
20  Gastrointestinal Tract Duplications 281

colon and fibrosis, inflammatory cells, lymphoid forated ileal duplication; dysuria and hematuria
aggregates, necrosis, and calcification. syndrome, attributed to the presence of gastric
Multiple duplications are seen in about 10% mucosa in the cyst in an infant with retroperito-
of patients. As many as 30% of patients with tho- neal duplication; and vaginal bleeding in an
racic or thoracoabdominal duplications have unusual anterior tubular rectal duplication [16].
additional duplications below the diaphragm.
Some cases lack anatomical association with
the normal GI tract, and they are called isolated 20.5 Diagnosis
enteric duplication cysts (IEDCs). Prenatal vas-
cular accidents, torsion, and heterotopic tumors The imaging modalities commonly used to
may be considered the etiological mechanism of investigate duplication cysts are ultrasound,
IEDCs. This type of tumor has been reported abdominal X-ray, barium studies, CT, and mag-
in locations including the tongue, pleural space, netic resonance imaging (MRI) as they are help-
liver, pancreas, biliary tree, and retroperitoneum. ful in defining the anatomical borders of a
Only 17 cases of retroperitoneal IEDCs have duplication [17].
been described in the literature, many of which The characterization of enteric duplications is
have a unilocular or multilocular shape [12]. not simple given that there is a large range of
anatomical variability. The differential diagnosis
to be considered in a fetus with an intra-abdomi-
20.4 Clinical Presentation nal cyst includes neurenteric cyst, anterior
myelomeningocele, mesenteric cyst, chole-
Symptoms are usually related to age, site, size, dochal cyst, and ovarian cyst. The first prenatal
presence of ectopic mucosa and communications detection of an enteric duplication was reported
with the native bowel; in fact, the clinical presen- by Van Dam in 1984 at 20 weeks’ gestation by
tation is quite diverse and often mimics other ultrasound [18]. Since then, large ultrasound sur-
intra-abdominal conditions, thus posing a great veys have shown that there are two sonographic
challenge for pediatric surgeons to arrive at a signs highly suggestive of enteric duplication:
clinical diagnosis preoperatively. the “double-wall” sign and the presence of peri-
Oral and esophageal lesions may cause rashes, stalsis [19, 20].
respiratory distress due to pressure on the bron- Indeed, enteric duplication cysts may be sus-
chi or lung, cough, cyanosis, retrosternal pain, pected on sonographic demonstration of an intra-­
and a mass effect with dysphagia, and also hem- abdominal cystic mass in the second or third
orrhage and peptic ulceration when an ectopic trimester of gestation [21], with the typical
gastric mucosa is present. Mediastinal enteric “double-­ wall” sign characterized by a hyper-
cysts are often associated with vertebral anoma- echoic inner mucosal layer correlating with the
lies such as vertebral fusion, scoliosis, anterior mucosa-­ submucosa and an outer surrounding
and posterior spina bifida, diastomyelia, and the hypoechoic layer reflecting muscularis propria.
absence of vertebra [13]. Gastrointestinal dupli- Duplication cysts may contain thick mucinous
cations may lead to nausea, vomiting, obstruc- material, septations, fluid levels, and debris, and
tion, hemorrhage, or perforation [14, 15]. In ileal they may also contain detached ciliary tufts,
and jejunal duplications, the most common which could be diagnostic. In addition, duplica-
symptoms were palpable mass, abdominal dis- tion cysts can have peristalsis, which appears as
tension, pain, and bleeding. Colonic and rectal ring contractions with a concentric contraction of
duplications are mostly accompanied by consti- the cystic wall. Peristalsis in a juxta-enteric cyst
pation and bleeding [4]. In a few cases intussus- is specific for a duplication cyst and can be a
ceptions and volvulus may occur in which the diagnostic feature [11]. However, prenatal diag-
adjacent cystic mass would represent the lead nosis is often difficult, and ultrasound identifies
point. Jehangir et  al. have also described some only 20–30% of lesions [22]. When an enteric
peculiar presentations, such as unexplained per- duplication (or any other malformation) is found
sistent metabolic acidosis in a neonate with a per- in a fetus on a surveillance ultrasound, a prenatal
282 C. Romeo et al.

MRI and echocardiogram are indicated. As fetal Surgical treatment involves open and minimally
MRI technology has advanced, MRI is more invasive techniques depending on surgeon expe-
accurate than ultrasound in delineating many rience, lesion localization, and resilience
aspects of fetal anatomy [23]. On fetal MRI, criteria.
enteric duplications appear hyperintense on To begin with, laparoscopy and thoracoscopy
T2-weighted images and hypointense on played merely an explorative role aimed at the
T1-weighted images. Despite this, ultrasound is definition of the location and nature of the lesions;
considered the first-choice imaging modality that nowadays, the lesions can be resected or enucle-
allows a fast postnatal treatment strategy, reduc- ated with a purely laparoscopic/thoracoscopic or
ing the risk for potential complications [24, 25]. a laparo-/thoracic-assisted approach [26]. Should
Contrast study demonstrates a submucosal an enucleation compromise the vascularization
mass with mass effect extending into the lumen of the remaining bowel, a resection followed by
of the GI tract. CT and MRI are not used rou- an end-to-end anastomosis is recommended.
tinely, but are quite helpful in difficult cases such
as esophageal, duodenal, and rectal duplications.
Radionuclide scanning with technetium-99  m 20.7 Esophageal Duplication
sodium pertechnetate can be used in cases in Cysts
which the presence of heterotopic gastric mucosa
is suspected [5]. Faced with a mediastinal enteric cyst, thoraco-
scopic surgical excision of the cyst is the main-
stay of treatment with comprehensive supportive
20.6 Treatment care. But when esophageal or vertebral connec-
tions or large cysts are present or expertise in tho-
In asymptomatic patients, surgical resection is racoscopy is not available, a thoracotomy is the
controversial. Although some authors advocate a approach to follow; in particular, large esopha-
resection owing to possible malignant degenera- geal duplications can be resected, leaving the
tion of the duplication cyst, others have advo- esophageal mucosa intact and closing the left
cated active observation. As there have been case muscular defect (Fig.  20.1). Another treatment
reports of stable duplication cysts on endoscopic strategy is observation in asymptomatic individu-
ultrasound surveillance, this may be a suitable als. Indeed, some authors, such as Versleijen,
method of outpatient follow-up and surgical argue that removing an asymptomatic cystic
resection can be considered if the patient lesion can lead to long-­term complications, such
develops symptoms. In any case, surgical versus as heartburn and gastroesophageal reflux with
nonsurgical management of asymptomatic dupli- esophagitis and can lead to mortality in up to 1%.
cation cysts is likely to remain controversial until Versleijen et  al. described a case in which a
we understand more about the time course and patient with an asymptomatic esophageal dupli-
risk factors associated with their malignant cation cyst with a diameter of 1.1–4.1  cm was
degeneration. followed for 13  years and routine endoscopic
The surgical approach varies according to the ultrasound did not show cyst growth [27].
localization and type of the duplication, rather
than on the duplication size. From a treatment
perspective, surgical removal/enucleation is the 20.8 Gastric Duplication Cysts
treatment of choice in most symptomatic cases.
In asymptomatic patients, surgical treatment Gastric duplication cysts make up between 4 and
should be performed to avoid complications such 9% of all intestinal duplication cysts [28]. Unlike
as ulcers or perforations or neoplastic degenera- other duplications, a female predilection is seen.
tion, although some authors prefer conservative They are usually single and in general do not
attitudes and clinical-instrumental monitoring. communicate with the gastric lumen. Most cystic
20  Gastrointestinal Tract Duplications 283

b c

Fig. 20.1  Esophageal duplication. (a) Scheme of surgical treatment. (b–d) Intraoperative thoracoscopic view

duplications of the gastric or pyloric curvature removed by resection of a stomach margin fol-
can be completely removed by subtracting the lowed by a double-layer gastric suture (Fig. 20.2);
cysts with subsequent repair of the seromuscular large or complex duplications may require partial
defect. Small gastric duplications can be simply gastrectomy.
284 C. Romeo et al.

Fig. 20.2  Gastric duplication (scheme of surgical treatment)

20.9 Bronchogenic Duplication 20.11 Small Bowel Duplication Cysts

Cysts
Small cystic intestinal duplications can be sim-
Most bronchogenic duplication cysts are located ply removed via a laparoscopic approach with
in the mediastinum around the tracheobronchial the adjacent bowel (Fig.  20.3). As intestinal
tree or within the pulmonary parenchyma. With duplications are situated on the mesenteric side
regard to treatment, surgical enucleation is the of the intestine, it is not possible to resect them
treatment of choice in symptomatic cases. In without compromising the blood supply of the
asymptomatic cases, surgical resection has been adjacent normal bowel. Long tubular duplica-
suggested owing to the rare development of com- tions can also be removed, unless the amount of
plications or malignancy, but many of these adjacent bowel that has to be sacrificed is con-
lesions can be safely observed [29]. sidered too much for the welfare of the patient.
In these cases, the seromuscular layer of the
duplication can be opened, and the mucosa can
20.10 Pancreatic Duplications be stripped from the entire length of the duplica-
tion (Fig. 20.4).
The rarest form of alimentary tract duplications The seromuscular cuff can be resected and
is pancreatic, with only a few cases reported in closed over the area of denuded epithelium.
the literature. Anatomically, the pancreatic head Resection can be limited to the area where the
is the most common location (51%), with the duplication communicates with the intestine.
remainder equally distributed in the body and Alternatively, the duplication and adjoining
tail. At operation, the presence of a smooth mus- bowel can be anastomosed over a long length to
cle lining on frozen section distinguishes pancre- ensure free drainage.
atic duplications from pseudocysts. Treatment The principles of management include bowel
ranges from cystectomy to more complex proce- preservation, mucosectomy, internal drainage,
dures, including cystojejunostomy, pancreatico- and staged operations where indicated to achieve
duodenectomy, or partial pancreatectomy, the best possible outcome for each individual
depending on the location. child.
20  Gastrointestinal Tract Duplications 285

a b

c d

e f

Fig. 20.3  Small bowel cystic duplications. (a–d) Scheme of surgical treatment. (e, f) Intraoperative view
286 C. Romeo et al.

20.12 Colonic Duplications 20.13 Rectal Duplications

The treatment of colonic duplications varies Treatment varies from marsupialization through
depending on the type and extent. Cystic duplica- a transanal approach, division of the s­eptum
tions are managed with resection and anastomo- between the duplication and the rectum, or exci-
sis (Fig.  20.5). Small cystic duplications can sion using a posterior sagittal approach. An initial
sometimes be enucleated. Tubular duplications colostomy may be needed in some patients. Ileal
are usually more challenging. For symptomatic and colonic tubular duplications vary in length
tubular duplications, resection is preferred, if and complexity [30].
possible. If resection is considered too aggres-
sive, a distal communication between the dupli-
cation and the native colon can be created to 20.14 Complications
relieve the obstruction. For large tubular duplica-
tions that are asymptomatic and with a distal The potential complications of an intra-­abdominal
­communication, conservative management with enteric duplication are numerous and can be fatal.
stool softeners is appropriate. Pain is one of the most frequent forms of

a b

c d

Fig. 20.4  Long tubular bowel duplications. (a–d) Scheme of surgical treatment. (e–h) Intraoperative view
20  Gastrointestinal Tract Duplications 287

e f

g h

Fig. 20.4 (Continued)

presentation and is usually attributed to high pres-

sure inside the duplication because of the accu-
mulation of secretions. Intussusception is another
complication in which the duplication serves as a
lead point. Intestinal obstruction because of the
extrinsic compression of the adjacent bowel has
been reported as well. However, perhaps the most
dangerous complications are those associated
with the presence of gastric mucosa, such as
ulceration, perforation, and hemorrhage. Finally,
malignant changes can occur in the mucosa of an
enteric duplication, regardless of the mucosal
type and the anatomical location [31].
In the literature, from 1955 to 2012, 67 cases
of malignancies have been reported arising from
alimentary tract duplications near the esophagus
(n=6), stomach (n=10), small intestine (n=19)
[duodenal (n=3), jejunum (n=3), ileum (n=12),
not described (n=1)], appendix (n=1), and large
intestine (n=31) [cecum (n=5), colon (n=13), and
rectum (n=13)]; of these, 39 occurred between
Fig. 20.5   Colonic duplications (scheme of treatment) 1990 and 2012. The age of presentation ranged
288 C. Romeo et al.

from 12 to 88  years, but most patients were nomas, and common adenocarcinomas. Owing
between the ages of 40 and 60 [32]. Although to the rare presentation with unspecific symp-
enteric duplications occur most often in the small toms, tumors are commonly diagnosed when the
bowel, a higher incidence of the tumor arising they are greater than 4 cm and so more invasive
from a large intestine duplication was noted com- and at an advanced stage with metastatic disease
pared with other sites, especially the colorectum [32]. If malignant change is found in small
[33]. There are also reports about carcinomas bowel duplications, the high rate of lymph node
arising in ­duplications of the duodenum and the metastases should be considered. Curative
stomach. Female predominance of 3:1 is found in resections are rarely performed. The prognosis
the colorectum site. Malignant transformation is generally poor once malignant change has
should be suspected if any abnormal solid com- occurred (Tables 20.1, 20.2, and 20.3) [25].
ponent is found within the duplication or if the
serum carcinoembryonic antigen (CEA) or car-
bohydrate antigen 19e9 (CA19e9) level is ele-
Table 20.1  Case series of gastrointestinal tract duplica-
vated. Indeed, although CA19e9 is not clearly tion in the last 25 years (1990–2015)
associated with malignancy, the prognostic value
Author Year Number of patients
of CA19e9 levels in colorectal cancer has been
Rattan et al. 2017 17 (2001–2015)
reported and could be of interest in the diagnosis Erginel et al. 2016 40 (1990–2015)
and management of intestinal duplications. More Jehangir et al. 2015 35 (2003–2014)
authors think that serum levels of CEA may serve Okur et al. 2014 32 (2000–2013)
as a valuable index for predicting tumor progress Haifen et al. 2012 39/67 (1990–2012)
arising from GI duplication. Lima et al. 2012 22 (1995–2010)
Carcinomas arising in duplication cysts Laje et al. 2010 18 (2001–2009)
include carcinoid tumors, squamous cell carci- Schalamon et al. 2000 12 (1989–1999)
Table 20.2  Characteristics of the numerical prevalence of duplications for sex, site, and morphology
First author n.D–n.Pz F-M T-A Esophagus Stomach Duodenum Jejunum–ileum Cecum Colon Rectum Morphology
20  Gastrointestinal Tract Duplications

Rattan, 2017 [5] 18–17 4–13 / 1 2 0–13 1 1 / 18 cystic

Erginel, 2016 [34] 40 12–28 2 2 3 3–21 4 5 / 40 cystic
Jehangir, 2015 [16] 38–35 11–24 3 + 1a 6b 3 1 0–17 / 6 1 22 cystic–16 tubular
Okur, 2014 [4] 32 23–9 2 1 2 5 3–11 2 + 2d 3 1 25 cystic–7 tubular
Haifen, 2012 [32] 39 24–15 4 5 2 3–10c 3 6 6 6 tubular–33 cystic
Lima, 2012 [35, 36] 22 6–16 6 3 / 0–10 / 2 1 20 cystic–2 tubular
Laje, 2010 [10] 18 8–10 / 3 4 0–10 / / / Cystic
Schalamon, 2000 [14] 13–12 Nd / 3 1 2–6 / / 1 Nd
Case series of gastrointestinal tract duplications in the last 25 years (1990–2015)b
n.D number of duplications, n.Pz number of patients, T-A thoracoabdominal, Nd not described
a
Other site
b
Six are mediastinic
c
One of the ten described was localized in the appendix, one in the small intestine
d
Two duplications were localized in the appendix
289
290 C. Romeo et al.

Table 20.3  Prevalence as a percentage of duplications 15. Karnak I, Ocal T, Senocak ME, Tanyel FC, Buyukpa-­
for morphology, sex, and localization Mukcu N.  Alimentary tract duplications in chil-
dren: report of 26 years’ experience. Turk J Pediatr.
Total cases Cystic Tubular Morphology Nd
2000;42:118–25.
220 80% 14% 6% 16. Jehangir S, Ninan PJ, Jacob TJ, Eapen A, Mathai J,
Total cases F M Sex Nd Thomas RJ, Karl S.  Enteric duplication in children:
220 40% 52% 8% experience from a tertiary center in South India. J
Total cases Foregut Midgut Hindgut Indian Assoc Pediatr Surg. 2015;20:174–8.
220 25, 45% 64, 10% 10, 45% 17. MacPherson RI.  Gastrointestinal tract duplications:
clinical, pathologic, etiologic, and radiologic consid-
Nd not described
erations. Radiographics. 1993;13:1063–80.
18. Van Dam LJ, de Groot CJ, Hazebroek FW, et al. Case
report. Intrauterine demonstration of bowel duplica-
tion by ultrasound. Eur J Obstet Gynecol Reprod Biol.
References 1984;18(4):229–32.
19. Segal SR, Sherman NH, Rosenberg HK, et  al.

1. Fitz RH. Persistent omphalomesenteric remains: their Ultrasonographic features of gastrointestinal duplica-
importance in the causation of intestinal duplica- tions. J Ultrasound Med. 1994;13:863–70.
tion, cyst formation and obstruction. Am J Med Sci. 20. Kangarloo H, Sample WF, Hansen G, et al. Ultrasonic
1884;88:30–57. evaluation of abdominal gastrointestinal tract duplica-
2. Ladd WE. Duplications of the alimentary tract. South tion in children. Radiology. 1979;131:191–4.
Med J. 1937;30:363. 21. Puligandla PS, Nguyen LT, St-Vil D, et al. Gastroin­
3. Gross RE.  Duplications of the alimentary tract. In: testinal duplications. J Pediatr Surg. 2003;38(5):
The surgery of infancy and childhood. Philadelphia, 740–4.
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4. Okur MH, Arslan MS, Arslan S, Aydogdu B, Turkcu Intestinal obstruction due to ileal duplication cyst and
G, Goya C, et  al. Gastrointestinal tract duplica- malrotation in a preterm neonate. J Neonatal Surg.
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2014;18:1507–12. 23. Quinn TM, Hubbard AM, Adzick NS. Prenatal mag-
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tion: an experience of 15 years at tertiary care centre. 24. Barr LL, Hayden CK Jr, Stransberry SD, Swischuk
J Neonatal Surg. 2017;6:5. LE.  Enteric duplication cysts in children: are their
6. Master VV, Woods RH, Morris LL, Freeman J. Gastric ultrasonographic wall characteristics diagnostic?
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7. Somme S, Langer JC. Duplications of the alimentary Adenocarcinoma arising in a cystic duplication of
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12. Momosaka D, Ushijima Y, Nishie A.  A retroperito- of the mediastinum. Results in 20 consecutive sur-
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 Mesenteric and Omental Cysts
21
Mario Lima and Neil Di Salvo

21.1 Introduction entery more frequently), followed by large bowel

mesentery (especially sigmoid mesentery) and
A mesenteric cyst is defined as any cyst that is retroperitoneum. The fluid contained inside the
located in the mesentery and may or may not cyst can be serous, chylous, haemorrhagic or
extend into the retroperitoneum; histologically, purulent (if infected). The fluid is generally chy-
the inner surface of the cystic wall presents a rec- lous when the cyst is located in the proximal
ognizable lining of epithelium (cuboidal/colum- small bowel mesentery and serous when it
nar), endothelial or mesothelial, depending on involves the ileal mesentery or the mesocolon.
the embryologic origin of the cyst. According to This could be related to a possible communica-
this definition, intestinal duplications, being most tion of these cysts with the absorption system of
commonly cystic and located on the mesenteric the intestinal wall. Another aspect that confirms
aspect of the small or large intestine, may be part this idea is the progressive dimensional increase
of this group. However, we will consider them in that is often observed in the natural history of
this chapter only for the differential diagnosis. these cysts.
Furthermore, in this chapter we will only con- Since the first description of a mesenteric cyst
sider cysts that interest the neonatal or infancy reported by an Italian anatomist in 1507,
period, that is, the congenital ones. In older chil- Benevieni, many authors have tried to classify
dren and adults, other cysts of an acquired nature these lesions on the basis of different criteria: eti-
do exist. These have an infectious (e.g. hydatid ology, histology or origin. Because these cysts
cyst) and neoplastic (e.g. teratoma) etiology and share common characteristics, thus the evalua-
are excluded from this context. tion and therapeutic objectives are the same, and
Mesenteric cysts are located anywhere in the a simple classification is the one that refers to
mesentery; more commonly they are localized origin. There are then cysts of lymphatic origin
close to or even adjacently to the intestine. They (lymphangioma, simple lymphatic cyst), meso-
may also extend from the base of the mesentery thelial origin (mesothelial cysts) and enteric ori-
into the retroperitoneum. The most common gin (bowel duplication cysts or simple enteric
localization is small bowel mesentery (ileal mes- cysts). Mesenteric and omental cysts are consid-
ered similar in origin and histological structure.
The most common type of mesenteric or omental
M. Lima (*) · N. Di Salvo
Department of Pediatric Surgery, S.Orsola Hospital,
cyst is lymphangioma, followed by intestinal
University of Bologna, Bologna, Italy duplication cysts, mesothelial cysts and enteric
e-mail: [email protected] cysts [1, 2].

© Springer Nature Switzerland AG 2019 293

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_21
294 M. Lima and N. Di Salvo

Lymphangiomas are very well known vascu- 21.2 Symptoms

lar congenital malformations of the lymphatic
system. Their volume can increase all of a sud- Mesenteric and omental cysts have a wide range
den, so as related symptoms, usually after viral of clinical presentations; they are often asymp-
infective episodes or traumas. Pathologically, tomatic and can be discovered as an incidental
lymphangiomas are large, thin-walled, cystic finding during a radiological study such as an
masses that are usually multiloculated. The fluid ultrasound, a CT or MRI done for other pur-
contents are predominantly chylous but may be poses; they can also be incidentally noticed dur-
serous or haemorrhagic. Lymphangiomas can be ing a surgical procedure (laparotomy or
closely attached to the bowel wall. They have an laparoscopy) for another condition. Nowadays,
endothelial cell lining, foam cells and thin walls these cysts in the majority of cases are discov-
that contain lymphatic spaces, lymphoid tissue ered, thanks to routine screening ultrasounds,
and smooth cells. Mesenteric lymphangiomas are during pregnancy; the prenatal suspicion is then
usually localized within the leaves of the mesen- frequently confirmed at birth by ultrasonogra-
tery, but they can also be pedicle (in this case phy. Depending on the data from the study, the
very easy to resect). clinician will decide whether to start a sono-
Simple lymphatic cysts presumably originate graphic follow-up of the cyst or undertake a
from benign proliferation of ectopic lymphatics second-line imaging study such as an MRI or
in the mesentery; they have a recognizable lining proceed with surgery. Even if mesenteric and
of endothelial cells and lack smooth muscle cells. omental cysts can pass as asymptomatic during
Cystic intestinal duplications present a thick a whole lifetime, it is also true they may mani-
wall composed of all the normal intestinal wall fest as a life-threatening acute abdomen. The
layers; part of the muscle layer is shared with the most common symptom, related to complica-
adjacent intestinal tract to which the duplicated tions of the cyst, is abdominal pain; this can be
part is intimately attached, in the mesenteric side secondary to intestinal obstruction with or with-
of the bowel. They are therefore localized within out volvulus. In the first case, compression of
the mesentery; the inner surface presents a gas- adjacent bowel will cause abdominal distension,
trointestinal mucosa, not necessarily of the same vomiting and constipation; if a volvulus occurs,
type to the adjacent normal bowel. Contents are besides the abovementioned symptoms, bloody
usually serous. stool, bowel perforation due to necrosis and a
Enteric cysts are lined with gastrointestinal rapid decay of general clinical conditions will
mucosa (hence enteric). They differ from dupli- progressively take place. Abdominal pain can
cation cysts because there is no reduplication of also set in with no obstruction or volvulus. In
all the intestinal wall layers. Enteric cysts result these cases, pain is due to torsion, rupture of the
from migration of a small bowel or colonic diver- cyst or the quick increase of cystic dimension
ticulum into the mesentery. Pathologically, they for intracystic bleeding. These conditions rarely
are thin, smooth-walled cysts, usually unilocular, occur following an abdominal trauma (the so-
with serous contents. They are lined with enteric called detector trauma). Other extremely rare
epithelium and have a thin fibrous wall without complications reported in literature are infec-
muscle layers. tion of the cyst or anaemia from intracystic
Mesothelial cysts are thin-walled unilocular bleeding. The cyst can be so enormous to give
cysts with a mesothelial cell line on the inner an abdominal distension (with no obstruction);
surface. They usually contain serous material sometimes the mass can simulate ascites. An
[2, 3]. older patient can even perceive the presence of
21  Mesenteric and Omental Cysts 295

an abdominal mass even with no pain associ- cystic nature of the lesion and gives informa-
ated; in these cases, the mass can also be pal- tion on dimension (Fig 21.1). Contents can be
pated by the patient or by a physician during an anechoic or hypoechoic. Cysts can present
examination; when palpable the mass is usually hyperechoic material in the inside; this aspect
movable in the abdomen [3, 4]. is probably determined by haemorrhage and/or
infection residuals and cyst debris. Ultrasounds
can also help determine if the mass is actually
21.3 Diagnosis movable or not in the abdomen, considering,
for differential diagnosis, movable cysts are
As said in the previous paragraph, the cysts can more likely to be mesenteric and not movable
be found as an incidental finding in an ultra- when of ovarian origin. The differentiation
sound. Nowadays it is very common to detect between intestinal duplication cysts and mesen-
these cysts during routine prenatal screening teric cysts may be problematic because both are
ultrasounds. In the prenatal period, it is very often intimately attached to the normal bowel
difficult to distinguish the nature of these cysts, wall. The former share a common blood supply
and therefore a differential diagnosis will have and muscular layer with the adjacent bowel and
to be undertaken in the postnatal phase: ovarian have a well-defined mucosal layer that meso-
cysts including cystic teratomas, intestinal thelial or simple enteric cysts lack. Therefore,
duplications, dilated bowel for other types of sonographically intestinal duplications are
intestinal obstructions (intestinal atresia, for anechoic with a thick wall composed of multi-
instance) and huge hydronephrosis. Before ple layers, resembling a normal bowel wall.
describing the different contributions that imag- While lymphangiomas appear as cystic and
ing studies can give when dealing with a prena- multiseptated masses with lobules, enteric and
tally suspected abdominal cyst, we want to mesothelial cysts only occasionally are seen
express our conviction that a precise preopera- with septations. A plain abdominal radiograph
tive diagnosis is not generally possible neither shows a gasless, homogeneous, water-dense
actually necessary. Any abdominal cyst with a mass that displaces bowel loops around it.
diameter superior to 5 cm, independently of its Omental cysts may compress bowel loops pos-
origin or anatomic attachment, must be explored teriorly, whereas mesenteric cysts may be sur-
for its associated risk of complications, being rounded by bowel loops. Fine calcifications can
an intestinal volvulus or an ovarian torsion in sometimes be seen. MRI and CT add minimal
the worst hypothesis. In this case performing an additional information, although they can
MRI in a newborn in order to have a better ana- reveal that a cyst is not arising from another
tomic definition would only mean giving an organ such as the kidney, pancreas or ovary.
extra general anaesthesia for something that They can also give more detailed information
will have to be surgically explored anyway. of the cystic wall and contents. For instance if
Different is the case of a cyst <5 cm or in case this imaging reveals a cystic mass with a thick
of older children. We suggest anyways dosing, wall that enhances after contrast material is
in the preoperative assessment, oncologic injected, we are more likely dealing with an
markers for ovarian tumours in the unlikely intestinal duplication and not a simple lym-
event of finding a cystic ovarian teratoma. This phatic, enteric or mesothelial cyst where the
is done only for post-operative follow-up pur- wall is not really discernible. Differences can
poses. Abdominal ultrasonography is the first- also be noted with regard to the cystic content
line imaging study in these cases: it shows the [2, 5] (Fig. 21.2).
296 M. Lima and N. Di Salvo

a b

Fig. 21.1  Abdominal ultrasounds in a newborn with pre- week later, the cyst moved to the left; furthermore, some
natal suspicion of intraabdominal cyst. Postnatal ultra- declivous sedimentations could be noticed (b, c). Surgical
sound confirmed the presence of the 4.6 cm cyst, anechoic, exploration later demonstrated a simple enteric cyst of the
uniloculated, thin-walled, in the right abdomen (a). One mesentery

a b

Fig. 21.2  MRI showing fluid-filled and thin-walled enormous mass (12 × 13 × 6.5 cm) extending from the hypogas-
trium to the pelvis (a, b, c); a mesenteric cyst was suspected
21  Mesenteric and Omental Cysts 297

Fig. 21.2 (Continued)

21.4 Treatment small laparotomy or via an extended umbilical

incision (Fig. 21.3). Enucleation or resection and
With increasing awareness of the potentiality anastomosis are then performed with an open
these cysts have in leading to severe complica- approach. Whether to drain the cyst during the
tions such as bowel obstruction or, worse, intesti- laparoscopic phase because the excessive size of
nal volvulus with loss of vital intestine, once the the cyst does not allow the passage through the
suspicion of a mesenteric cyst is confirmed post- abdominal incision is still debated because the
natally, indication for surgical intervention has to surgeon could be in front of a bowel duplication
be given. It is not possible to determine the exact with possible communication with bowel lumen
timing, but it is our opinion to proceed as soon as and eventual spillage of intestinal content in the
possible during early infancy. They can be abdominal cavity. A laparoscopic intracorporeal
removed with no bowel resection by shelling technique has been described but not in neonatal
them out from between the two leaves of the mes- cases; the small working space and the long dura-
entery (enucleation). Any resulting mesenteric tion of pneumoperitoneum are the major limits in
defect must be closed to prevent an internal her- newborns for such technique. If enucleation or
nia. If mesenteric vessels are damaged with resection is not feasible, basically due to a retro-
impairment of intestinal blood supply, a concom- peritoneal extension of the cyst, an option is par-
itant bowel resection with a primary end-to-end tial excision with marsupialization of the
anastomosis is required. Obviously, this principle remaining cyst into the abdominal cavity. The
does not apply to omental cysts, which can there- remaining cystic surface in this case should be
fore be removed without resecting the adjacent sclerosed; different sclerosing agents have been
transverse colon or the stomach. All of the above- used: 10% glucose solution, electrocautery or
mentioned surgical procedures can now be per- tincture of iodine. Recurrence is a possibility; it
formed even in the newborn with a happens in patients who undergo only partial
laparoscopy-assisted approach. The cyst can be excision, eventuality that occurs often in cysts
localized laparoscopically, and the affected mes- located deep from the root of the mesentery to the
entery with the intestine is brought out through a retroperitoneum [3, 5].
298 M. Lima and N. Di Salvo

a c

Fig. 21.3 (a–c). Laparoscopy-assisted transumbilical procedure on the cyst seen in Fig. 21.2. The cyst is seen during
laparoscopic exploration (a), punctured, drained and then removed through the umbilical access (b, c)

4. Belhassen S, Meriem B, Rachida L, Nahla K, Saida

References H, Imed K, Sana M, Amine K, Lassad S, Mongi M,
Mohsen B, Abdellatif N. Mesenteric cyst in infancy:
1. Peterson EW.  Mesenteric and omental cysts. Ann presentation and management. Pan Afr Med J.
Surg. 1932;96(3):340–9. 2017;26:191.
2. Stoupis C, Ros PR, Abbitt PL, Burton SS, Gauger 5. Saxena AK.  Mesenteric and omental cysts in
J. Bubbles in the belly: imaging of cystic mesenteric children. https://emedicine.medscape.com/
or omental masses. Radiographics. 1994;14:729–37. article/938463-overview.
3. Ricketts RR. Mesenteric and omental cyst. In: Coran
AG, editor. Pediatric surgery. 7th ed. Mosby: Elsevier;
2012.
 Surgical Necrotizing Enterocolitis:
Early Surgery - The Key to Live 22
Bowel and Quality Life

Adrian Bianchi

22.1 Introduction midgut volvulus from malrotation and gastros-

chisis, SNEC is a major cause of the short bowel
The term necrotizing enterocolitis (NEC) has state that commits the child to long-term paren-
been used to cover diverse neonatal illnesses [1] teral nutrition, autologous gastrointestinal
of altogether different prognosis e.g. spontane- reconstruction [4], and possible bowel or liver-
ous ileal perforation, such that it has been diffi- bowel transplantation.
cult to accurately ascertain the true incidence, The extent of the residual functional bowel,
appropriate management, and long-term out- so relevant to long-term survival with good
come. Better referred to as surgical necrotizing quality life, depends not only on the severity
enterocolitis (SNEC), it is an acquired postnatal of the disease but also on the timing and
condition of considerable mortality and morbid- nature of surgical interventions as determined
ity that affects primarily premature infants. The by the child’s medical carers. The increasing
long-­term prognosis for survivors is good, but number of very premature infants requires a
the quality of life will depend on the complica- dedicated ‘specialist neonatal team’ that
tions of prematurity (chronic pulmonary dyspla- includes at its core a neonatologist, a neonatal
sia, blindness from retinal infiltration, ischaemic surgeon, and a committed anaesthetist for
brain injury) and on the absorptive and immu- early, better, and co-ordinated management.
nological capabilities of the residual bowel. Bell’s Staging (Table  22.1) has been a poor
Management has been largely determined by guide for determining the timing of surgery.
Bell’s criteria [2, 3] that were developed to stage Most importantly the surgeon should not alter
the progress of the disease (Table  22.1). This the proven accepted surgical criteria for man-
essentially conservative approach with surgery agement of the acute abdomen and should not
figuring at a late stage is associated with 30–50% be deterred by prematurity or the size and
mortality from sepsis (abscess, peritonitis, per- weight of the child from early and effective
foration) and multiorgan failure, and with a sig- intervention, while the child is still in rela-
nificant risk of functionally damaged and/or tively good condition and before irreversible
short bowel in survivors. Indeed, along with bowel injury has occurred.

A. Bianchi (*)
Royal Manchester Children’s Hospital,
Manchester, UK

© Springer Nature Switzerland AG 2019 299

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_22
300 A. Bianchi

Table 22.1  NEC staging system

Stage I (suspect)
 (a) Any one or more historical factors producing
perinatal stress
 (b) Systemic manifestations—temperature
instability, lethargy, apnoea, bradycardia
 (c) Gastrointestinal manifestations—poor feeding,
increasing pre-gavage residuals, emesis (may be
bilious or test positive for occult blood), mild
abdominal distension, and occult blood may be
present in stool (no fissures)
 (d) Abdominal radiographs show distension with
mild ileus
Stage II (definite)
 (a) Any one or more historical factors
 (b) Above signs and symptoms plus persistent
occult or gross gastrointestinal bleeding, marked
abdominal distension
 (c) Abdominal radiographs show significant intestinal
distension with ileus, small bowel separation
(oedema in bowel wall or peritoneal fluid),
unchanging or persistent ‘rigid’ bowel loops,
pneumatosis intestinalis, and portal vein gas
Stage III (advanced) Fig. 22.1  NEC abdominal distension
 (a) Any one or more historical factors
 (b) Above signs and symptoms plus deterioration of
vital signs, evidence of septic shock, or marked rapid incremental rate. The natural chymotrypsin
gastrointestinal haemorrhage curdles the milk protein (casein) which the imma-
 (c) Abdominal radiographs may show ture small bowel of the premature baby finds dif-
pneumoperitoneum in addition to others listed in IIc
ficult to digest and to progress through the bowel.
Source: Bell MJ, Ternberg JL, Feigin RD, Keating JP, Curd stasis causes obstruction and eventual
Marshall R, Barton L, Brotherton T. Neonatal necrotizing
enterocolitis. Therapeutic decisions based upon clinical mucosal inflammation particularly in the lower
staging. Annals of Surgery 1978; 187(1): 1–7 ileum, at the ileocaecal valve, and in the right
colon leading to reduced peristalsis and progres-
sive small bowel gaseous distension (Fig. 22.1).
22.2 Pathophysiology of NEC Inflamed oedematous bowel is tender, is often
palpable on abdominal examination, and is iden-
Surgical NEC is an acquired postnatal condition tifiable on Doppler ultrasound as a ‘ring’ hyper-
affecting primarily premature infants <30 weeks’ perfusion [8] (Fig. 22.2) of thickened often static
gestation with immature gut of reduced absorp- loops that are typical of Bell Stage I–II [2, 9].
tive and immunological ability, but may affect Eventually mucosal necrosis and bacterial
also ‘stressed’ babies of greater gestation e.g. infiltration are detectable radiologically and
intrauterine growth retardation, babies of diabetic ultrasonologically as intramural (Fig. 22.3a) and
mothers, babies with congenital heart disease, intraportal gas (Fig.  22.3b) bubbles (Bell Stage
and those given indomethacin therapy for closure II) [2, 9].
of a patent ductus arteriosus. The cause of SNEC Increasing bowel gas from ingested air and
remains unclear, and it is not the intention of this from curd fermentation raises intraluminal pres-
chapter to discuss the diverse aetiological theo- sure that impairs perfusion to the antemesenteric
ries [5–7] but rather to concentrate on aspects of border (Fig. 22.4a) of the tightly distended loops
care that are immediately amenable to beneficial that is detectable as the Y-sign (Fig.  22.4b) on
change. Although rare in unfed babies and less Doppler ultrasound [8–12], causing ischaemic
common in breast-fed infants, there is a signifi- necrosis and eventual perforation.
cant association with formula-milk feeds, partic- Early accumulation of intraperitoneal fluid
ularly of larger volume and administered at a (Fig.  22.5a) and later local or general bowel
22  Surgical Necrotizing Enterocolitis: Early Surgery - The Key to Live Bowel and Quality Life 301

Fig. 22.2  US ring sign of hyperperfusion (Adapted from

Epelman et al. [8])

a b

Fig. 22.3 (a) NEC intramural gas. (b) NEC static loops intraportal gas
302 A. Bianchi

a b

Fig. 22.4 (a) Necrotic loops—no perf. (b) US Y-sign of absent antemesenteric perfusion (Adapted from Epelman et al. [8])

a b

Fig. 22.5 (a) NEC fluid - ground-glass appearance. (b) NEC perforation with free gas
22  Surgical Necrotizing Enterocolitis: Early Surgery - The Key to Live Bowel and Quality Life 303

perforation with collection of free gas and definition of the muscle planes of the abdominal
bowel content (Fig. 22.5b) are clear ultrasono- wall (Fig.  22.5a). The constant unaltered pres-
logically and on X-ray of the abdomen. Septic ence of gas within a static oedematous ‘sentinel
­intraperitoneal fluid undergoes dialysis with the loop’ (Fig. 22.3b) suggests serious inflammation
systemic circulation across the peritoneum and if not a local perforation. Mucosal inflammation
is associated with overwhelming septicaemia. and hyperperfusion are followed by necrosis and
bacterial infiltration, with intramural gas bubbles
becoming increasingly evident (Fig.  22.3a).
22.3 T
 he Clinical Picture: Ultrasonological findings of a reduction in bowel
Diagnostic Features wall thickness and reduced perfusion, detectable
by Doppler as the Y-sign, affect primarily the
The baby, initially in good condition and active, antemesenteric aspect of the bowel loops and
develops non-specific features of ill-health. indicate ischaemia and likely irreversible muco-
Carers often report that they are ‘unhappy’ with sal and bowel wall necrosis [8–10]. Intraportal
the child who is ‘not as well as previously’ dem- gas may become evident within the liver. The
onstrating lethargy and reduced activity, an child demonstrates all the clinical features of a
unstable temperature, and apnoeic spells (Bell generalized septicaemia with a significant drop
Stage I [2]). Biochemical parameters and sepsis in blood pressure requiring inotrope support of
markers may not yet have altered; however the cardiac and renal function. A severely low plate-
need for respiratory support is a significant dete- let count from platelet consumption and marrow
rioration. It is at this earliest stage of alteration in depression increases the risk of debilitating or
general health and developing abdominal signs fatal intracerebral bleeding. Blood, platelet, and
that constant joint review by the core specialist clotting factor transfusions and difficult fluid and
neonatal team (neonatologist, neonatal surgeon, electrolyte management are necessary to manage
committed anaesthetist) is crucial to determining anaemia, coagulation problems, metabolic aci-
an integrated pre-, intra-, and postoperative man- dosis, and severely disturbed electrolytes.
agement plan designed to optimize the timing Abdominal wall discolouration and cellulitis
and nature of surgery to ensure child survival and (Fig.  22.6) and the presence of an abdominal
specifically to limit bowel loss. mass, free fluid, and gas within the peritoneal
A developing metabolic acidosis and a distur- cavity are late features related to intraperitoneal
bance in the serum electrolyte profile with a sepsis and perforation and are of poor prognosis
reduction in serum sodium levels are of increas- for both the bowel and the child. Increasing intra-­
ing relevance. Some babies will pass foul stools abdominal pressure with diaphragmatic splinting
containing mucus and blood that, along with a impairs ventilation even despite the child being
drop in the platelet count, are ominous prognos- paralysed and mechanically ventilated and,
tic signs (Bell Stage I–II [2]). Abdominal fea- together with overwhelming septicaemia and
tures are initially minimal, and assessment eventual multiorgan failure, significantly com-
demands expertise from clinicians (neonatolo- promises survival. Surgery, even at this late stage,
gist and neonatal surgeon) of major experience. may be successful in rescuing the dying child by
Progressive distension [13] and tenderness to helping to control sepsis but is usually far too late
palpation become increasingly evident. Palpable for salvage of sufficient functional bowel. Indeed,
oedematous bowel loops or the presence of an extensive removal of necrotic, autolysing, and
abdominal mass is significant. As SNEC pro- irreversibly damaged bowel is unavoidably nec-
gresses, the child’s general condition steadily essary for survival.
deteriorates. With fluid accumulation within the Even following aggressive-but-conservative
peritoneal space, the abdominal X-ray shows a surgery retaining all potentially viable bowel,
ground-glass appearance with loss of the normal surviving children face the prospects of bowel of
304 A. Bianchi

the milk protein curds from chymotrypsin-treated

freshly expressed breast milk may be the only means
of providing a degree of immunological support as
well as nutrition.
Any deterioration in the general condition of
an ‘at-risk’ child, however non-specific, and
particularly when associated with abdominal
tenderness and distension, should alert the car-
ers and the specialist neonatal team to the likeli-
hood of SNEC. Enteral feeding is stopped, and
free gastric drainage with frequent aspiration
commenced through a large 8F naso-/oro-gas-
tric tube, to avoid further small bowel distension
from swallowed air. Positive pressure nasopha-
ryngeal support is contraindicated since swal-
lowed gas further distends the stomach and
small bowel, and respiratory support should
only be offered endotracheally. At this early
stage, a colonic washout is usefully undertaken
with a dilute 4% chlorhexidine gluconate solu-
tion (Hibiscrub, MediSupplies Ltd) and an equal
volume of air, delivered through an 8F feeding
tube that is slowly advanced through the anus.
Fig. 22.6  Abdominal wall cellulitis Concomitant abdominal massage along the
course of the colon helps to clean out the whole
impaired absorptive and immunological function, colon through to the caecum. There should be
of further resection of significant lengths of ste- no fear of perforation of live colon, and any sus-
notic bowel (Fig. 22.7) and the short bowel state. picion of perforation is indicative of necrotic
bowel for which urgent abdominal drainage and
exploration are required. Routine sepsis investi-
22.4 Management (Table 22.2) gations are undertaken, and conservative man-
agement commenced with blood and other
Nutrition, for infants considered to be at risk of factors (red cells, platelets, coagulation factors)
SNEC, should be largely provided parenterally with and initially with broad-spectrum antibiotics,
specific emphasis on replacement or limitation of later guided by bacteriological evidence from
soya-based lipids that contain high liver-toxic plant stool and blood cultures.
phytosterols, with omega-3 fish oil. Combinations At this early stage, abdominal radiology may
such as SMOFlipid (Fresenius Kabi, Uppsala, be less helpful, showing only a generalized dis-
Sweden) containing reduced soya lipids, medium- tension of bowel loops (Fig. 22.1) that on Bell’s
chain triglycerides, olive oil, and fish oil are also criteria is not considered to be a definitive sign of
proving acceptable. Enteral feeding is commenced SNEC.  Thus, it is relevant to frequently serially
at minimal volumes and at a very slow incremental assess perfusion in dilated bowel loops with
rate with low residue feeds that are preferably Doppler ultrasound [8]. Reduced or absent peri-
immunologically competent (derived from fresh stalsis, thickening of the bowel wall from oedema,
breast milk). During the first days, freshly expressed and hyperperfusion, noted as a ‘ring’ pattern on
maternal colostrum containing high levels of IgM is Doppler sonography, indicate inflammation in
particularly valuable. Subsequently, low residue bowel that is potentially still viable [8]. These
feeds supplemented with the whey after removal of findings, together with clinical deterioration and
22  Surgical Necrotizing Enterocolitis: Early Surgery - The Key to Live Bowel and Quality Life 305

Fig. 22.7  Multiple stenoses and damaged bowel in a survivor

Table 22.2  SNEC management

features of an ‘acute abdomen’ (tenderness, pal-
Early SNEC pable loops) in a child who is still in reasonable
Large 8F nasogastric tube on free drainage and 15 min
aspiration
condition, are definite indications for urgent early
Respiratory support only endotracheally laparotomy for control of sepsis, and of particular
Blood products, fluids, and electrolytes relevance to limit the extent of bowel injury by
Antibiotics—broad spectrum, but later guided by deflating the distended bowel and improving loop
blood and stool cultures perfusion. There is nothing to be gained, and
Ultrasound monitoring of bowel loops for perfusion indeed it is contraindicated to wait for the appear-
—Ring and Y-sign
ance of intramural gas bubbles, localized or free
Progressive disease
gas in the peritoneal space, reduced bowel wall
Paralysis and ventilation
Inotropes thickness, and poor or absent perfusion of the
Large tube drain to peritoneal space —14F Argyle antemesenteric surface of the dilated loops,
intercostal drain detectable as the ‘“Y” pattern’ [8] on Doppler
Peritoneal wash and dialysis —1.36% normal sodium sonography, as these are late features indicative of
with 4 mmol/L KCL ischaemia, mucosal loss, and severely damaged
306 A. Bianchi

bowel. Early rather than later surgery is indicated, assessment should follow the time-proven crite-
and it is inappropriate to await these late ‘definite ria for any patient presenting with deteriorating
indications for surgery’. general health and a suspicion of intra-abdomi-
A tight abdomen from maximal fluid and gas- nal inflammation.
eous distension that indeed cannot distend further, Drainage: An unwell child with a tender abdo-
and paralysis for ventilatory support, make clini- men, palpable bowel loops, and increasing
cal abdominal assessment much more difficult abdominal distension from intraperitoneal fluid
and uncertain and tend to delay surgery! Other and gaseous loop distension should be regarded
less specific features suggesting ­ deterioration as suffering from SNEC, and is an indication for
acquire greater relevance. These include unstable early surgical intervention while the child is still
temperature, poor respiratory parameters, occult in an acceptable general condition. Radiological
or manifest blood in the stools, disturbed electro- and ultrasound evidence of thickened bowel
lytes, metabolic acidosis, reducing platelet count, loops showing increased perfusion, and free fluid
and the need for inotropes to support the circula- with hyperechoic debris within the peritoneal
tion and maintain renal function. Such major space (Fig.  22.5a), are strong indications for
deterioration and evidence of severe sepsis are abdominal drainage and peritoneal lavage, to
very late stages in SNEC and are indications of a enhance the child’s general condition in prepara-
major intra-abdominal catastrophe requiring tion for a laparotomy. A large bore tube, e.g.
immediate surgical intervention for survival. It is 12–16F Argyle intercostal tube drain (Medtronic/
unfortunately likely that the opportunity for Covidien, UK), should be passed through the
bowel-sparing surgery will have been missed. right iliac fossa along the peritoneal surface of
the anterior abdominal wall towards the left
hypochondrium (Fig. 22.8). There should be no
22.5 Indications for Surgical
Intervention (Table 22.3)

On suspicion of SNEC and during the initial

critical hours of conservative management and
monitoring, the child deserves the immediate
and constant attention of the specialist neonatal
team. Prematurity is incidental, and surgical

Table 22.3  Indications for surgery

Early: Tender distending abdomen
Palpable bowel loops
Foul, bloody stools
Deteriorating general condition and
biochemical parameters
Doppler US ‘Ring’ sign — hyperperfusion of
thickened bowel
Increasing intraperitoneal fluid
Late: Doppler US ‘Y’-sign — absent perfusion
Reduced bowel wall thickness and absent
peristalsis
Intramural gas bubbles
Intraperitoneal fluid, especially with
echogenic material
Intra-abdominal mass
Local or free gas in peritoneal space Fig. 22.8  NEC large abdominal drain
22  Surgical Necrotizing Enterocolitis: Early Surgery - The Key to Live Bowel and Quality Life 307

concern regarding possible loop perforation dur- supraumbilical incision, gives good access to the
ing drain insertion since laparotomy is likely to whole of the small and large bowel. Alternatively,
follow, and any iatrogenic perforation can be a transverse supraumbilical incision is less aes-
managed. Indeed, the reduction in intraluminal thetic but practical. Distended loops are exterior-
pressure following loop perforation can act ized and an enterotomy performed preferably in
favourably to enhance bowel salvage by reducing the lower ileum or as dictated by the necrotic pro-
intraluminal pressure and allowing better loop cess. An intraluminal bowel washout is under-
perfusion. Peritoneal lavage is undertaken with a taken with a mixture of air and 4% chlorhexidine
warm isotonic 1.36% normal sodium gluconate solution (Hibiscrub, MediSupplies
(136 mmol/L) solution (Baxter, UK) with added Ltd) diluted in warm 1.36% normal sodium dial-
4  mmol/L of potassium chloride, as is used for ysate (Baxter, UK) with added 4  mmol/L KCl,
peritoneal dialysis. The fluid is infused to a vol- infused through an 8F catheter that is advanced
ume that is tolerated without ventilatory or circu- distally towards the caecum until fluid and air
latory compromise, the abdomen gently massaged exit through the anus, and retrogradely along the
to help with peritoneal cleansing and decompres- small bowel until aspirated from the stomach.
sion, and drainage allowed by gravity. The initial Gentle bowel massage and suction ensure thor-
cleanout is followed by 20-min washout cycles ough cleansing and complete collapse of all the
with the dialysate infused over 5 mins, retained small and large bowel from necrotic material,
for 10 mins to allow equilibration with the circu- with evident return of perfusion to live bowel.
lation, and drained by gravity over 5  mins. The enterotomy may be closed or brought out as
Repeated cycles over a few hours help to improve a double-barrelled stoma, and there is little role
the child’s general condition, circulation, renal for a widely split stoma that will later require an
function, and electrolyte profile. Laparotomy is extensive laparotomy for closure. In the event of
considered when the child’s condition is maxi- widespread or more severe disease, only obvi-
mally improved. ously necrotic, irretrievably damaged bowel is
Abdominal Surgery: Even though SNEC is a resected, with emphasis on preserving all ‘ques-
life-threatening condition, the surgeon should tionable’ but potentially viable bowel. Several
remain conscious of the fact that ‘it is the survivor segmental resections and multiple anastomoses
who is interested in an aesthetic abdomen’. It is may be necessary. It is most important to appreci-
therefore relevant to consider an aesthetic approach ate that even short lengths of 1–5  cm of viable
with scars placed appropriately in skin creases bowel are worth preserving, since the added total
when possible. Laparoscopic intervention has may be sufficient to avoid the short bowel state.
become more popular and has a place particularly The collapsed, better perfused bowel is more eas-
in early SNEC when abdominal distension is less ily replaced and the abdomen closed without ten-
marked and bowel inflammation is limited and sion and with adequate drainage, or with a large
less severe. Peritoneal lavage and drainage, limited tube drain if further washout/dialysis is contem-
loop resection of irretrievably damaged (autolys- plated postoperatively.
ing, necrotic) bowel, and small bowel deflation The child and stoma are carefully monitored,
with consideration of a stoma, commonly a low and further ‘housekeeping’ laparotomies should
ileostomy possibly placed at the umbilical port, be liberally entertained for peritoneal cleansing
form the basis of laparoscopic management. and for bowel review and management. This is
More extensive disease and difficulties with particularly relevant to those with bone marrow
laparoscopic intervention are stronger indications depression and a low white cell count who toler-
for open laparotomy that allows extensive perito- ate ongoing sepsis poorly. It is axiomatic at every
neal (subhepatic, subdiaphragmatic, pelvic) stage to preserve as much bowel as possible. At
cleansing and careful inspection of all the bowel. this point, the immediate prognosis remains
An aesthetic Pfannenstiel incision, with the guarded. Even survivors may have sustained suf-
occasional addition of a second circum-­ ficient mucosal injury for the residual bowel to
­
308 A. Bianchi

have lost its absorptive and immunological func- cialist neonatal team for the early management of
tions, or to require extensive resection because of the increasing number of very premature babies
stenosis(es) (Fig.  22.7) culminating in the short that are a high-risk cohort for SNEC.
bowel state. It is worth noting that mortality and morbidity
(short bowel state) in SNEC do not relate to the
operative intervention, but rather to the lack of
22.6 Discussion essential surgery at an early enough stage when
the bowel is still viable. The high mortality and
The adage ‘prevention is better than cure’ is par- morbidity relate to the severity of the illness and
ticularly suitable to the premature ‘at-risk’ child, the extreme condition of the child when surgery
such that all factors known to increase the possi- is undertaken, often as a last resort and when all
bility of SNEC should be avoided. Nutrition is other therapeutic options are failing. Surgical
primarily parenteral, avoiding phytosterol liver assessment should follow the time honoured and
toxicity from soya-based lipid solutions and proven criteria for management of any ill patient
favouring omega-3 fish oils or combinations with with a tender ‘acute’ abdomen and a suspicion of
reduced soya such as SMOFlipid (Fresenius intra-abdominal inflammation. The child’s pre-
Kabi, Uppsala, Sweden). During the first days maturity and size are incidental and should not
of bowel bacterial colonization, the child and influence or delay essential surgery. The tradi-
bowel should be assisted immunologically with tional ‘irrefutable indications for surgery’ are far
the mother’s fresh colostrum. Small-volume too late and, together with Bell’s criteria, have
no-­residue enteral feeds should be introduced been superseded and should no longer be used to
only very gradually and supplemented with determine the timing of operative intervention.
immunologically competent expressed fresh
­ Judicious early surgery before major bowel
breast milk or preferably the whey leftover fol- injury is crucial to maximal bowel salvage that
lowing chymotrypsin coagulation of the breast avoids the short bowel state, to survival of the
milk protein. As enteral feeding progresses, great child, and to the quality of long-term life. It is
relevance should be given to alterations in the time for change, and further prevarication can
child’s general state. Non-specific features such only lead to unnecessary additional child morbid-
as temperature instability and apnoeic episodes, ity and mortality.
particularly if associated with abdominal tender-
ness and progressive distension, should alert the
specialist neonatal team to the possibility of early
SNEC.  In addition to increased clinical review, References
frequent serial Doppler ultrasound monitoring of
1. Gordon PV, Swanson JR, Attridge JT, Clark
bowel motility, bowel wall thickness, and partic- R. Emerging trends in acquired neonatal intestinal dis-
ularly bowel wall perfusion should be instituted. ease: is it time to abandon Bell’s criteria? J Perinatol.
Palpable tender bowel loops, accumulating intra- 2007;27(11):661–71.
2. Bell MJ, Ternberg JL, Feigin RD, Keating JP,
peritoneal fluid, and ultrasound evidence of
Marshall R, Barton L, Brotherton T. Neonatal necro-
hyperperfusion are indicative of inflammation of tizing enterocolitis. Therapeutic decisions based upon
viable bowel and should lead to consideration of clinical staging. Ann Surg. 1978;187(1):1–7.
early surgery, while the child is in better condi- 3. Kliegman RM, Walsh MC.  Neonatal necrotiz-
ing enterocolitis: pathogenesis, classification,
tion, to drain the peritoneum and to deflate and
and spectrum of disease. Curr Probl Pediatr.
clean out the bowel lumen before the onset of 1987;17(4):213–88.
severe bowel injury. 4. Bianchi A. From the cradle to enteral autonomy: the
Neonatal anaesthesia and neonatal surgery are role of autologous gastrointestinal reconstruction.
Gastroenterology. 2006;130(2 Suppl 1):S138–46.
now well-developed specialties, and the neonatal
5. Nowicki PT.  Ischemia and necrotizing enteroco-
surgeon and committed anaesthetist together litis: where, when, and how. Semin Pediatr Surg.
with the neonatologist form the core of the spe- 2005;14(3):152–8.
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6. Caplan MS, MacKendrick W. Inflammatory mediators Smith C, Gerstle T, Kim JH. Necrotizing enterocoli-
and intestinal injury. Clin Perinatol. 1994;21(2):235–46. tis: assessment of bowel viability with color Doppler
7. Vieten D, Corfield A, Carroll D, Ramani P, Spicer US. Radiology. 2005;235(2):587–94.
R. Impaired mucosal regeneration in neonatal necrotis- 1 1. Urboniene A, Palepsaitis A, Uktveris R, Barauskas
ing enterocolitis. Pediatr Surg Int. 2005;21(3):153–60. V.  Doppler flowmetry of the superior mesenteric
8. Epelman M, Daneman A, Navarro OM, Morag I, artery and portal vein: impact for the early prediction
Moore AM, Kim JH, Faingold R, Taylor G, Gerstle of necrotizing enterocolitis in neonates. Pediatr Surg
JT.  Necrotizing enterocolitis: review of state-of-the-­ Int. 2015;31(11):1061–6.
art imaging findings with pathologic correlation. 12. Kim WY, Kim WS, Kim IO, Kwon TH, Chang W,
Radiographics. 2007;27(2):285–305. Lee EK.  Sonographic evaluation of neonates with
9. Aliev MM, Dekhqonboev AA, Yuldashev early-stage necrotizing enterocolitis. Pediatr Radiol.
RZ. Advantages of abdominal ultrasound in the man- 2005;35(11):1056–61.
agement of infants with necrotizing enterocolitis. 13. Daneman A, Woodward S, de Silva M.  The radiol-
Pediatr Surg Int. 2017;33(2):213–6. ogy of neonatal necrotizing enterocolitis (NEC). A
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Manson DE, Mohanta A, Moore AM, Hellmann J, 1978;7(2):70–7.
 Hirschsprung’s Disease
23
Maria Grazia Faticato and Girolamo Mattioli

23.1 Introduction have been described in an attempt to restore nor-

mal bowel in HSCR [6–11].
The initial description of Hirschsprung’s disease HSCR is a relatively common cause of intesti-
(HSCR) or the so-called congenital megacolon nal obstruction in the newborn and has always
was attributed in 1691 to Frederik Ruysch, a been one of the most interesting topics for pediat-
Dutch anatomist who described a 5-year-old ric surgeons due to its intriguing features and
dying from an intestinal obstruction [1]. Similarly, challenging treatment.
Domenico Battini in Italy, in 1800, described a
child affected by congenital megacolon [2].
In 1886 Sir Harald Hirschsprung, a Danish 23.2 Etiology and Pathogenesis
pediatrician, described for the first time two
young patients who died of septic shock and HSCR is a congenital rare disease which occurs
turned out to have huge colonic dilatation at post- in roughly 1  in 5000 live births; the incidence
mortem assessment. This was the first clinical varies significantly among ethnic groups (e.g.,
description of congenital megacolon or rectosig- higher in Asian population) [12] with a male to
moid aganglionosis that was subsequently named female ratio of roughly 4:1. The male preponder-
Hirschsprung’s disease [3]; however, Ehrenpreis ance is less evident in long-segment HRSC,
first diagnosed the disease in a neonate later, in where the male to female ratio is about 1.5–2:1.
1946, and realized that aganglionosis was the Recurrence risk to siblings depends on the child
cause of congenital megacolon [4]. In 1948 the sex affected and also on the extent of agangliono-
first successful operation for HSCR was per- sis. However, the risk is substantially higher in
formed by Swenson who understood that the clue siblings of children with total intestinal
of the disease was to resect the spastic and nar- aganglionosis.
rowed colon down to the anal canal with preser- HSCR is a congenital abnormality of the
vation of the sphincteric structures [5]. Since enteric nervous system (isolated neurocristopa-
then, many other patients have been treated suc- thy) characterized by distal bowel aganglionosis
cessfully, and a variety of surgical procedures with variable proximal involvement in both sub-
mucosal and myenteric plexus of the hindgut
[13]. The ganglion cells derived from the neural
crest and coordinate muscular activity balancing
M. G. Faticato (*) · G. Mattioli the motor effects of the preganglionic cholinergic
Paediatric Surgery Unit, Istituto Giannina Gaslini,
DINOGMI University of Genoa, Genoa, Italy fibers and inhibitory influence of postganglionic
e-mail: [email protected] adrenergic fibers. The disease is a consequence of

© Springer Nature Switzerland AG 2019 311

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_23
312 M. G. Faticato and G. Mattioli

premature arrest of craniocaudal migration of HSCR is a complex genetic disease, and sev-
neural crest cells in the hindgut during 5th–12th eral genes have been identified as involved in the
gestational weeks. development of the enteric nervous system: in
The earlier the arrest of cells migration, the 1994, mutations affecting the RET proto-­
longer will be the aganglionosis segment. HSCR oncogene on chromosome 10q11.2 were identi-
can be classified based on the length of the agan- fied in HSCR patients; this gene is also involved
glionosis into four subgroups: in different diseases such as multiple endocrine
neoplasia types 2A and 2B and sporadic and
• Rectosigmoid: the aganglionic segment does familial medullary thyroid carcinoma. These
not extend beyond the upper sigmoid (80%). mutations are detected in up to 50% of familiar
• Long-segment: aganglionosis extends to the and in 10–15% of sporadic cases [23–27]. A
splenic flexure or transverse colon (10%). number of minor HSCR susceptibility genes have
• Total colonic aganglionosis: the aganglionic been identified to date, namely, GDNF, EDN3,
segment extends to the colon and a short seg- EDNRB, NRTN, ECE1, PHOX2B, SOX10, and
ment of terminal ileum (10%). ZFHX1B.
• Total intestinal aganglionosis: the absence of The involvement of heterogeneous genetic
ganglion cells from duodenum to the rectum pathways and pluripotent cell lineage explains why
(extremely rare form of HSCR) [14]. HSCR disease can be associated to malformations
basically involving all organs and systems.
A hypothesis to explain the obstruction RET is crucial for the embryologic develop-
caused by ganglionated dilated bowel is the role ment also of other organs, including the kidneys
of the enteric nervous system (ENS), which is and urinary tract [28], and this could explain why
essential for normal propulsive intestinal motil- Hirschsprung’s disease is also associated with a
ity. ENS is the intrinsic innervation of the bowel number of syndromes or diseases: Waardenburg-­
and named “gut mini brain”; ENS coordinates Shah syndrome, congenital central hypoventila-
movements, immune functions, and secretion of tion syndrome (Ondine syndrome), MEN 2B,
the gut. ENS is independent and functioning in Goldberg-Shprintzen syndrome, Smith-Lemli-­
the absence of input from the brain or spinal cord Opitz syndrome, neurofibromatosis, neuroblas-
and can mediate reflexes, even when it is isolated toma, pheochromocytoma, and a variety of other
from the central nervous system. It is important congenital anomalies.
to emphasize that the aganglionic bowel in
HSCR is not denerved; in fact many authors sug-
gested that aganglionic portion may be hyperin- 23.3 Diagnosis
nervated by catecholaminergic and cholinergic
nerve fibers [15, 16]. What is therefore essential The diagnosis of HSCR is usually based on clini-
for the mediation of reflexes are the cell bodies cal aspects, radiological evaluation, and in par-
of ENS, not nerve fibers. There are also recent ticular on histological examination, histological
studies which suggest that the ganglionic bowel and immuno-histochemical examination of the
in patients with HSCR has abnormalities in rectal wall biopsy specimens.
innervation [17–22].
The classic pathological feature in HSCR is
dilation and hypertrophy of the proximal colon 23.3.1 Clinical Aspects
with abrupt or gradual transition to normal or
narrow distal bowel. Although the degree of dila- The usual presentation of neonate affected by
tion and hypertrophy increases with age, the HSCR is an intestinal obstruction characterized
cone-shaped transitional zone from dilated to by abdominal distension, bilious vomiting, and
narrow bowel is usually evident in the newborn. feeding intolerance suggestive of distal intestinal
23  Hirschsprung’s Disease 313

obstruction during the first few days of life. of HAEC remains poorly understood. HAEC rep-
Delayed passage of meconium beyond the first resents a clinical entity determined by a combi-
24  h is characteristic, but it is evident only in nation of various dysfunctions and/or disruptions
approximately 64% of children with HSCR [29]. of intestinal homeostasis. The assessment of the
In many cases of neonates with abdominal dis- histological abnormalities observed in the gut of
tention, a rectal examination or rectal irrigation patients suffering from HAEC has provided
causes passage of meconium or may demonstrate understanding regarding the pathogenesis of the
a tight anal sphincter and explosive discharge of disease. From a histological point of view, HAEC
stool and gas [30, 31]. is characterized by the presence of cryptitis, with
Approximately 10–25% of neonates with a huge inflammation and neutrophilic infiltration
HSCR present with fever, abdominal distention, of the crypts. These findings have been described
and diarrhea due to Hirschsprung-associated in both ganglionated and aganglionated bowel,
enterocolitis (HAEC), a serious complication suggesting a mechanism that goes beyond the
which can basically occur from birth to adult- simple absence of ganglia. One of the theories of
hood, regardless of the length of aganglionosis. pathogenesis of HAEC is partial obstruction, due
HAEC is an inflammatory colitis which can lead to the aganglionosis itself or surgical issues that
to bacterial translocation, sepsis, and death. determine a persistent state of fecal and bacterial
Though great advancements in HSCR treat- stasis. This lack of bowel emptying leads to bac-
ment have been made in the past 20 years, due to terial overgrowth, bowel dilatation, bowel wall
early diagnosis, rectal decompression and appro- stretching, impaired blood flow to the mucosa,
priate vigorous resuscitation and antibiotic ther- and subsequent increased permeability with bac-
apy, HAEC pathophysiology is largely unknown, terial translocation. The abnormal development
and predisposing factors as well as specific pre- of the enteric nervous system plays a pivotal role
vention strategies have not been determined yet. in the pathogenesis of HAEC. In fact, the ENS is
Various hypotheses regarding the etiology have of utmost importance in gut homeostasis and
been postulated. Based on experimental and clin- commensal microflora with a complex neuroim-
ical studies, several contributory factors have mune modulation effect. When ENS is compro-
been identified that may help to explain its mised, the integrity of epithelial barrier is at risk;
development. the neuroimmune dysfunction may thus lead to
HAEC can occur either preoperatively or after the propagation of the inflammatory vicious cir-
radical surgery. Owing to improved and prompt cle of HAEC.
diagnosis, the incidence of preoperative HAEC Abnormalities in the intestinal microbiote
(ranging between 6 and 26% of cases) has have been also implicated in the development of
decreased over the past decades [32, 33]. Also HAEC [36–39]. Clostridium difficile and
mortality rate has markedly decreased, thanks to Rotavirus have been frequently detected in
the advancements in its recognition and prompt patients with HAEC, even if no specific organism
management. HAEC occurs postoperatively in has been found to consistently cause HAEC. In
between 5 and 42% of patients [33]. The risk of particular, a cytopathic toxin of Clostridium dif-
postoperative HAEC is significantly increased by ficile has been found in the stools of a consis-
mechanical factors related to anastomotic com- tently high percentage of patients with
plications and intestinal obstruction [34]; other HAEC. Although this toxin has been detected in
factors which may have an influence on postop- patients with severe clinical manifestations of
erative HAEC is a previous (preoperative) epi- HAEC, the majority of healthy neonates and
sode of HAEC or associated anomalies such as infants younger than 1  year of age carry
Trisomy 21. Mortality rate decreased to nearly 10 Clostridium difficile in their stools. However, the
to 0% though the average mortality rate in the last relationship between Clostridium species and the
20 years is around 3% [35]. The pathophysiology development of HAEC remains controversial, but
314 M. G. Faticato and G. Mattioli

this aspect suggests that the toxin itself is not The most reliable clinical grading system
enough to trigger an HAEC episode [39]. The developed for HAEC is from Elhalaby that strati-
knowledge of microflora before, during, and after fied HAEC severity into three major categories
and HAEC episode may help in establishing pre- [33]:
ventive and therapeutic strategies. Metagenomics
studies have amply demonstrated the existence of • Grade I: mild explosive diarrhea, mild to
an alteration and a predisposition microflora in moderate abdominal distension, and no sig-
patients with recurrent HAEC as well as the exis- nificant systemic manifestations
tence of similar protection microenvironments. • Grade II: moderately explosive diarrhea and
These studies suggested that the occurrence and moderate to severe abdominal distension asso-
recurrence of enterocolitis may be associated ciated with mild to moderate systemic mani-
with a specific distribution of intestinal flora, festations (e.g., fever and tachycardia)
which is influenced by the use of antibiotics. The • Grade III: explosive diarrhea, marked abdom-
factors described above may create a dysfunc- inal distension, and shock or impending shock
tional environment in the “acceptable” gut micro-
biome, with a decreased colonization of The initial symptoms of HAEC may be indis-
bifidobacteria and lactobacilli, a probiotic organ- tinguishable from acquired infective gastroen-
ism that maintains a microbial equilibrium. teritis. Nonetheless, as HAEC can progress
Disruption of these mutually beneficial relation- rapidly and even result in death, most pediatric
ships could result in HAEC. However, the mech- surgeons will treat all patients regardless of uni-
anism is still uncertain [40, 41]. vocal HAEC diagnosis, in order to avoid delayed
The genetic of HSCR is complex, and it is treatment or misdiagnosis.
possible that a genetic predisposition to HAEC Conditions that can mimic HSCR in the neo-
may exist. Many investigators have identified natal period include cystic fibrosis, meconium
certain predisposing factors associated with the plug syndrome, small left colon syndrome, hind-
development of HAEC: gut atresia, anorectal malformations, ENS imma-
turity of the preterm, hypothyroidism, and
• Age at presentation: early symptoms onset chronic intestinal pseudo-obstruction [31, 42].
seems to correlate with HAEC severity and Hirschsprung’s disease is associated with a vari-
susceptibility. ety of other congenital abnormalities like malro-
• Associated anomalies and syndromes: Down tation, genitourinary anomalies, ocular disorders,
syndrome, central nervous system anomalies, congenital heart disease, limb abnormalities,
and congenital cardiac malformations have cleft lip and palate, hearing loss, mental retarda-
been considered strong risk factors by many tion, and dysmorphic features. These conditions
authors. should increase suspect diagnostic. Other causes
• Postoperative issues: all complications or sur- of intestinal neonatal occlusion should be consid-
gical issues leading to bowel obstruction or ered, such as intestinal atresia, meconium ileus,
impaired bowel emptying increase the likeli- meconium plug syndrome, and other less com-
hood of HAEC development. mon conditions.
• Personal history (previous HAEC episodes):
patients who previously developed HAEC are
at higher risk of recurrence in a sort of predis- 23.3.2 Rectal Biopsy
position/susceptibility.
• Extent of aganglionosis: patients with ultra-­ The gold standard for the diagnosis of HSCR is
long HSCR (i.e., total colonic aganglionosis) rectal suction biopsies (RSB) [43, 44] (Fig. 23.1).
have a higher likelihood of developing HAEC The development of histochemical and immuno-
both preoperatively and postoperatively with histochemical staining techniques using rectal
an overall incidence approaching 50% [33]. suction biopsies for the diagnosis of HSCR rep-
23  Hirschsprung’s Disease 315

The diagnostic accuracy of RSB is close to

100% after 1 month of age but must be taken with
care in the newborn or preterm who can only par-
tially express all diagnostic features. Usually the
rectal suction biopsy in a preterm is not recom-
mended because first of all the ganglion cells
should be difficult to detect for the pathologist
due to their intrinsic immaturity and also because
the pediatric surgeon could not obtain enough tis-
sue to allow the diagnose without increasing the
complications in a small baby. So, it is better to
decompress the distal colon with multiple and
daily irrigations and performed the diagnostic
Fig. 23.1  Solo-rectal biopsy tool [44]
procedure when the child is closer to term. The
rectal biopsy shows the absence of ganglion cells,
resents a considerable advance in the investiga- but in many cases there are no hypertrophic
tion of this disease, particularly in the newborn. nerves or abnormalities of acetylcholinesterase
RSB is a safe and painless procedure that can staining (long segment).
be carried out at the bedside without the use of Worldwide, two approaches are currently used
general anesthesia with an incidence of for the specimen evaluation: (1) analysis of
­complications (bleeding, perforation) lower than hematoxylin eosin-stained paraffin sections with
1% [44–46]. RSB is the standard method for col- or without frozen sections stained for acetylcho-
lection rectal tissues; however, it often results in linesterase (AChE)-enzyme histochemistry or (2)
smaller tissue specimens compared with full-­ evaluation of frozen sections stained enzyme his-
thickness biopsy; though larger tissue specimens tochemically for neuronal markers including that
may be obtained, full-thickness biopsy requires to AChE.
general anesthesia. Alternatively a single or multiple snap-frozen
Because there is a usual paucity of ganglion biopsies can be cut for hematoxylin eosin-stained
cells in the area 0.5–1  cm above the pectinate frozen sections and AChE preparations. After
line, the first biopsy should be taken at least 1 to completion of these, the remainder of the biopsy
1.5–2  cm above it and should contain enough can be thawed, fixed in formalin, and processed
submucosa tissue that properly assess the ENS. into paraffin sections.
Ideally, an adequate biopsy is 3–4  mm in A potential alternative to the use of AChE is
diameter and 1–2 mm deep with a minimum of a the Calretinin, an immunohistochemical marker.
third of the biopsy represented by submucosa. Calretinin is present normally in the perikarya
Two or three adequate specimens all containing and nerve processes of a subset of enteric gan-
submucosa area are typically collected to enable glion cells, including small nerves in the superfi-
the pathologist making a confident diagnosis. cial submucosa and muscularis propria.
Identification of ganglion cells excludes the Immunoreactivity in the latter sites is lost in the
diagnosis of HSCR.  Lack of submucosal gan- aganglionic segment of HSCR.
glion cells, particularly when accompanied with Other types of techniques include alpha-­
hypertrophic submucosal nerves and/or an abnor- naftylesterase, NADPH-diaphorase, succinic and
mal acetylcholinesterase-staining pattern, is suf- lactic dehydrogenases, and nitric oxide synthase.
ficient evidence to establish the diagnosis of However, AChE histochemistry is the most
HSCR.  In aganglionic rectum, the density and widely employed technique and has a very high
thicknesses of AChE-positive nerves in the mus- reported accuracy rate in the detection of HRSC
cularis mucosa and typically also in the lamina (greater than 99%) in laboratories with signifi-
propria are increased [47]. cant experience.
316 M. G. Faticato and G. Mattioli

23.3.3 Radiological Evaluation and retention of contrast in the colon on a 24-h

postevacuation film.
For the neonate with a strong suspect of HSCR, a In the presence of enterocolitis complicating
plain abdominal radiograph may show a dilated HSCR, contrast enema may demonstrate spasm
small bowel or proximal colon and fluid levels. and, in occasional cases, mucosal edema, and
Subsequently, the first step in the radiological ulceration. A plain abdominal radiograph can
evaluation diagnostic pathway is contrast enema. show, in HAEC patient, the typical intestinal
This exam may demonstrate a transition zone or “cutoff sign” in the rectosigmoid colon with
change in caliber, created by distention of the absent distal air, dilated loops of bowel, air fluid
normally innervated bowel proximal to the nar- levels, and even free abdominal air in case of
rowed and functionally obstructed aganglionic perforation.
segment (Fig. 23.2). The transition zone is com- In the presence of enterocolitis complicating
monly a common absence in neonates (approxi- HRSC, contrast enema may demonstrate spasm
mately 10%) though it may still be present due to and in occasional cases mucosal edema, and
a short aganglionic segment and indefinitely in ulceration. A plain abdominal radiograph can
patients with total colonic disease. However, the show, in HAEC patient, the typical intestinal “cut-
rectal transition zone is the most evident in the off sign” in the rectosigmoid colon with absent
lateral radiologic view. Other findings on the con- distal air, dilated loops of bowel, air fluid levels,
trast enema that are suggestive of Hirschsprung and even free abdominal air in case of perforation,
disease include a reversed rectosigmoid index indicating toxic megacolon. In some cases ultra-

a b

Fig. 23.2 (a) Contrast enema demonstrating a transition zone at the splenic flexure. (b) Lateral view
23  Hirschsprung’s Disease 317

sonography can be used to identify peritoneal washouts, flatus tubes, and bowel decompression
ascites or internal septations that are suggestive ofshould be performed as soon as possible, with 2–4
peritonitis or intestinal inflammation. times daily irrigations with saline until the efflu-
Other suggested diagnostic tools include US of ent is clear. Usually it is possible to continue twice
the kidney and urinary tract for the high percentage daily until symptoms settle. At the beginning of
of CAKUT in HRSC patients [48]. Other investiga- HAEC treatment, the patients should be kept fast-
tions, like audiological evaluation, heart US, cere- ing. Feeding should be allowed once symptoms
bral US, and ophthalmologic assessment should be improve. Depending on the severity of the dis-
performed basing on clinical features [49]. ease, in particular when Clostridium difficile is
detected in the stools, HAEC can be effectively
treated with oral or intravenous metronidazole.
23.3.4 Anorectal Manometry Inability to adequately decompress the bowel
or severe and uncontrolled septic shock may be
Anorectal manometry demonstrates the absence an indication for urgent bowel diversion with a
of recto-anal inhibitory reflex (reflex relaxation levelling colostomy (or ileostomy in patients
of the internal anal sphincter in response to rectal with total colonic aganglionosis) fashioned prox-
distension) present in normal children but absent imally to the transitional zone (intraoperative his-
in children with Hirschsprung disease. Contrast tochemistry) [50].
enema and anal manometry are similar in sensi- Ideally, the best treatment for HAEC is the
tivity and specificity, and it is necessary to con- prevention. The main foresight is rectal washout,
sider that anorectal manometry is not widely especially preoperatively in the newborn.
available for neonates. Immediate diversion should be strongly consid-
ered for patients presenting with sepsis or severe
HAEC, especially in newborn when this is the
23.4 Treatment initial presentation.
Radical surgery (pull-through) should be per-
Once the diagnosis of HSCR has been confirmed, formed as soon as possible. In fact, most of the
the patient must be prepared for surgery. It is nec- severe cases of HAEC do occur preoperatively
essary to distinguish the preoperative manage- being surgery mostly event-free. Preoperative
ment of healthy newborns from those with and postoperative probiotics use recently failed
enterocolitis. Healthy newborns with undistended to demonstrate a beneficial or protective role over
colon and rectosigmoid HSCR can benefit a pri- HAEC likelihood and severity.
mary surgery. Rectal irrigations must be per- Severe and fatal HAEC are more likely to
formed daily prior to surgery in order to wash and occur in patients with syndromes or congenital
empty the bowel. heart diseases. On the ground of these consider-
The treatment of newborn with HAEC is: ations, patients with congenital heart disease
should undergo prophylactic stoma fashioning in
1. Resuscitation in case of impending shock order to minimize the risk of HAEC and conse-
2. Decompression of the gastrointestinal tract quently possible fatal complications [29, 35].
3. Antibiotics, directed mostly against Gram-­ Nonetheless, although enterostomy could con-

negative and anaerobic species sider protective toward the development of
HAEC, it cannot prevent cardiocirculatory prob-
A key aspect in the management of an acute lems or issues related to pre-existing syndromes,
HAEC episode is a good fluid resuscitation, close and HAEC could potentially occur also after
hemodynamic monitoring, and in some severe stoma formation.
case, ventilatory support and admission to inten- The main goal in the treatment of patients with
sive care unit. In case of prolonged disease, a par- Hirschsprung’s disease is to remove aganglionic
enteral nutrition support may be indicated. Rectal bowel radically and to identify normoganglionic
318 M. G. Faticato and G. Mattioli

bowel with intraoperative seromuscular biopsies De la Torre-Mondragón and Ortega [11], in

for intraoperative assessment in order to identify 1998, reported a modified Soave procedure, a
the correct site of anastomosis. single-stage transanal endorectal pull-through
The radical resection of the aganglionic bowel performed totally through a transanal approach.
can be performed either with an endorectal This technique reduces the risk of complications
(Soave), retrorectal (Duhamel), or perirectal like damage to pelvic nerves.
(Swenson) approach. For many times, surgical The advent of minimally invasive surgery has
treatment of HSCR involved staged procedures, modified the surgical approach, and HSCR and
but in recent years many surgeons are now per- classic pull-through techniques were modified
forming one-stage pull-through operations in the and improved with laparoscopy, leading to the
newborn with minimal morbidity rates and advantages of reduced pain and improved cosme-
encouraging results [51–54]. sis [9, 10, 55, 58–61]. As a result of the obvious
Swenson provided the first description of a advantages of laparoscopic-assisted pull-through
surgical approach to Hirschsprung disease in the operations, the Soave-Georgeson technique [10],
late 1940s. The procedure involves the mobiliza- which embraces the advantages of the endorectal
tion and resection of aganglionic bowel with end-­ pull-through and those of the minimally invasive
to-­end anastomosis of normal colon to the anal surgery, has gained much popularity [62].
canal. The operation was originally done through The Soave-Georgeson procedure involving
a laparotomy, with the anastomosis being per- laparoscopic biopsy to identify the transition
formed from a perineal approach after eversion zone, laparoscopic mobilization of the rectum
of the aganglionic rectum. below the peritoneal reflection, and a short muco-
The Duhamel procedure (first reported in sal dissection through a perineal approach.
1960) [7, 55] implicates bringing the normal Preoperative intravenous antibiotic is given on
colon down through the bloodless plane between call in the operating room. The patient is posi-
the rectum and the sacrum and joining the two tioned on the operating table in the lithotomy
walls to create a the rectum instead of removing position to allow for access to both the abdomen
it with less pelvic dissection and the presence of for trocar placement and the perineum for the
a “reservoir” makes it the rectum instead of transanal dissection. Biopsy site is selected by
removing it with less pelvic dissection and the observing the apparent transitional zone; a sero-
presence of a “reservoir” makes it appealing for muscular biopsy is taken along the antimesen-
patient with longer aganglionic segments. teric surface; the sample is promptly sent to
Rehbein’s procedure is one of the techniques pathologist for examination. In the meantime the
mostly used in Europe for the past 25 years [56]. colon is isolated, and the peritoneum is divided
The procedure provides resection of the agangli- around its lateral and anterior reflection from the
onic colon only up to the upper rectum (2  cm rectum, exposing the muscle coat of the rectum.
below the peritoneal reflection) followed by dila- Once the endoscopic dissection has been com-
tation of the remaining rectum and anus, after pleted, the perineal dissection is started. The rec-
performing colostomy immediately proximal to tal mucosa is circumferentially incised using the
the aganglionic segment. cautery, approximately 5 mm from the pectinate
In 1964, Soave described an endorectal pull-­ line; the rectal muscle is then incised circumfer-
through procedure doing a submucosal endorec- entially, and the endorectal dissection is carried
tal dissection and placing the pull-through bowel to a point above the peritoneal reflection. The
within a “cuff” consisting of aganglionic muscle entire rectum and part of the sigmoid colon can
an excised exteriorized bowel; the anastomosis is be delivered through the anus. When the transi-
done at a second operation several weeks later. tion zone is reached, the anastomosis is done
Subsequently Boley modified this procedure per- from below (after histopathological confirmation
formed in a single stage. The concept of the of ganglionic specimen).
Soave procedure is to prevent extensive pelvic A transanal approach can also be used if the
dissection outside the rectum [57]. patient has already had a colostomy, by using the
23  Hirschsprung’s Disease 319

stoma as the end of the pull-through bowel and dered motility in the proximal colon or small
performing the rectal excision using the transanal bowel, internal sphincter achalasia, or functional
technique. In patients with a more proximal tran- megacolon caused by stool-holding behavior.
sition zone, laparoscopy can be used to mobilize Mortality rate for HSCR is relatively low; the
the left colon and/or splenic flexure to achieve patients died preoperatively due to complica-
adequate length. tions, like enterocolitis or associated anomalies,
This procedure is associated with excellent like congenital heart disease, but rarely died
clinical results and permits early postoperative postoperatively.
feeding, early hospital discharge, and no visible The family should be educated about the signs
scars. and symptoms of enterocolitis, and the family
Recently, robotic surgery was introduced in must be told to bring the child to the hospital if
the pediatric surgery but may play a role in the there are any signs suggestive of this problem
treatment of older patients with HSCR [63]. because children can become very sick and even
die from enterocolitis.

23.5 Postoperative Management

and Outcome References
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Patients undergoing a laparoscopic approach for
vation by Frederick Ruysch--1691. J Pediatr Surg.
HSCR can be fed immediately, and most can be 1970;5:1–3.
discharged within 24–48 h. It is important to cali- 2. Fiori M.  Domenico Battini and his description of
brate the anastomosis with an appropriately sized congenital megacolon: a detailed case report one
century before Hirschsprung. J Peripher Nerv Syst.
dilator or finger 1–2 weeks after the procedure.
1998;3:197–206.
Postoperative complications including anasto- 3. Hirschsprung H. Constipation of newborns as a result
motic stricture, rectal obstruction due to long rec- of dilatation and hypertrophy of the colon. Jhrb f
tal cuff in endorectal procedure, or long spur in Kinderh. 1888;27:1–7.
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Enterocolitis, constipation, failure to thrive, 9. Soave F. Hirschsprung’s disease: a new surgical tech-
nique. Arch Dis Child. 1964;39:116–24.
fecal soiling, and incontinence are the most fre-
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quent complaints after surgery [59, 66]. In par- laparoscopic-­assisted endorectal colon ­pull-­through
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the outcome of the bowel function could be influ-
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than 4  years of age, he may not be considered disease in Japan: analysis of 3852 patients based
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Persistent obstructive symptoms following a
13. Tomuschat P, Puri P. RET gene is a major risk factor
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tion, recurrent or acquired aganglionosis, disor- Surg Int. 2015;31:701–10.
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 Anorectal Malformations
24
Kristiina Kyrklund and Risto Rintala

24.1 Introduction mal disturbance to the existing continence

mechanisms. As ARMs represent relatively rare
Anorectal malformations (ARMs) comprise a disorders, definitive repair should be performed
spectrum of congenital defects with an inci- in experienced tertiary units to ensure optimal
dence of 1:2500 that range in severity from healthcare outcomes.
mild anal stenosis alone to complex malforma-
tions involving the anorectum and urogenital
tract. Both males and females are equally 24.2 Embryology of ARMs
affected, and a detailed understanding of the
anatomy of these defects is essential for the In early embryology, the caudal region of the
provision of optimal surgical care during the normal hindgut is called the cloaca. During the
neonatal period. Improvements in neonatal and 7th week of gestation, cloacal division into ven-
surgical care over the past decades have reduced tral and dorsal components occurs with descent
mortality in ARM patients to around 3% in of the urorectal fold, forming the urogenital
units with modern technology [1], and mortal- tract ventrally and the anorectal tract dorsally.
ity is usually the result of uncorrectable associ- The urorectal fold ultimately forms the perineal
ated anomalies rather than the ARM.  Apart body between them. The dorsal part of the cloa-
from cloacal abnormalities, prenatal suspicion cal membrane (CM) ends at the position of the
of ARMs is uncommon, and the diagnosis is future anal opening at a fixed point near the tail
usually made shortly after birth. Because asso- groove in the normal rat model (Fig. 24.1) [2].
ciated defects affect over half of patients, man- In ARMs, the critical factor for development
agement in the neonatal period involves prompt may be an abnormally shortened cloacal mem-
screening based on a set algorithm. The modern brane (Fig. 24.2) [2], which could lead to aber-
operative management of ARMs involves ana- rant siting of the bowel termination during
tomical reconstruction of the defect with mini- cloacal subdivision in ARMs, including urogen-
ital connections. The site where the anal orifice
should be, as marked by the location of the
external sphincter apparatus in humans, is
already established at a fixed point in the mouse
K. Kyrklund · R. Rintala (*) model prior to cloacal subdivision [2]. In nor-
Department of Pediatric Surgery, Children’s Hospital, mal development, the cloacal membrane disin-
Helsinki University Central Hospital,
Helsinki, Finland tegrates where it meets the tip of the descending
e-mail: [email protected]; [email protected] urorectal fold posteriorly, forming the anal ori-

© Springer Nature Switzerland AG 2019 323

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_24
324 K. Kyrklund and R. Rintala

a b c

W U
W
HG A
A

A HG S HG

C
CM C
CM C

TG
TG TG
CM

Fig. 24.1  Normal cloacal development in the rat model. Schematic diagram of a normal (a and b) and an abnormal
(c) cloaca

Fig. 24.2  Model of

abnormal cloacal a b
W
development. Schematic
W
diagram of a normal (a) and
an abnormal (b) cloaca. In the
abnormal embryo, the cloacal
membrane (CM) is too short
(arrow). The cloacal
membrane does not extend to U U
the region of the tail groove
(grey area). The dorsal cloaca A A
is missing. In the normal
embryo (a), the cloacal
membrane is of normal length
and extends to the region of HG HG
the tail groove (grey area).
Reproduced from Fig. 7 in C
Kluth [2]. Embryology of
anorectal malformations. CM G
Semin Pediatr Surg 2010, 19:
201-208 and reproduced with CM
kind permission from
Elsevier

fice [3]. This initially closes with the ectoderm

24.3 Etiologic Factors
and is recanalized 2 weeks later. Abnormalities
of recanalization of the anal orifice during the
The etiologic basis of ARMs is based on genetic
9th week of gestation could assist to explain
and environmental influences. The most fre-
mild ARMs, including stenotic and membra-
quent chromosomal associations involve micro-
nous defects [3].
24  Anorectal Malformations 325

deletion of chromosome 22q11.2 (also known 24.3.2 Normal Anatomy of the Pelvic

as DiGeorge or CATCH-22 syndrome) and Floor
Down syndrome (trisomy 21). A chromosomal
abnormality is observed in approximately Knowledge of the normal anatomy of the pelvic
10% of cases [3]. Townes-Brocks, Pallister- floor and anal canal is necessary for understanding
Hall, Opitz-Kaveggia, Johanson-Blizzard, the pathologic anatomy of ARMs. The pelvic floor
Kaufman-McKusick, Lowe, oculo-auricular- comprises a sheetlike diaphragm of striated mus-
vertebral (Goldenhar), fragile X and trisomy 8 cles that support the pelvic organs and abdominal
syndromes are other reported associations [4]. viscera. These muscles insert into the pubic bone
A genetic aetiology is supported by a familial anteriorly, the most inferior part of the sacrum pos-
occurrence in up to 8% of cases [5] and among teriorly and the obturator membrane, ischium and
monozygotic twins. Autosomal dominant inher- ischial spine laterally. The ventromedial aspect
itance of mutations in HLXB9 is responsible forms a funnel-like sling around the urethra, vagina
for 50% of patients with Currarino syndrome. and anorectum, with fibres fusing medially at the
Environmental risk factors for ARMs include perineal body and serving to close the urogenital
prenatal exposure to caffeine, alcohol or drugs and anorectal hiatuses by contraction [9]. The
as well as maternal factors such as diabetes and superior part of this muscle funnel is called the
epilepsy. Assisted reproductive techniques, pri- levator muscle, and its inferior fibres are continu-
miparity, pre-eclampsia and maternal fever in ous with the deep fibres of the external anal sphinc-
early gestation have also been implicated [6]. ter. Contraction of the puborectalis sling fibres of
the levator complex maintains the anorectal angle
(Fig. 24.3), preventing faecal descent during sud-
24.3.1 Associated Anomalies den increases in intra-abdominal pressure [10].

Malformations of the VACTERL (vertebral, anal,

cardiac, tracheo-esophageal, renal, limb) and 24.3.3 Anatomy of the Anal Canal
CHARGE (choanal atresia/coloboma, anal, renal,
gastrointestinal and ear/hearing) sequence are rec- The voluntary or external anal sphincter (EAS)
ognized, non-random associations of ARMs. Over muscles of the anal canal are continuous superi-
half of all patients with ARMs have at least one orly with the fibres of the levator muscles, form-
other associated congenital malformation, and ing a striated funnel comprising of deep,
these may affect over 90% of patients with severe superficial and subcutaneous components
ARMs. Approximately 10–15% fulfil the criteria (Fig.  24.4). The EAS provides approximately
for VACTERL association [6–8], having three or 15% of resting continence but becomes activated
more anomalies from this sequence. A recent epi- during physical activities that increase the intra-­
demiological survey identified a prevalence of abdominal pressure. It receives its motor and
13% for cardiac defects (mainly atrial septal sensory supply from the inferior rectal branches
defect, ventricular septal defects and tetralogy of of the pudendal nerve and the perineal branch of
Fallot), 15% for skeletal defects, 10% for tracheo- S4, which is also sensory to the skin of the anal
oesophageal fistula, 25% for urologic abnormali- canal to approximately 1 cm proximal to the den-
ties (most commonly vesicoureteric reflux, renal tate line [10]. The internal anal sphincter (IAS)
agenesis and dysplastic kidney), 13% for limb fibres provide the remaining 80–85% of resting
defects and 13% for genital anomalies [4, 7]. anal canal pressure and represent a thickened
Uterine and vaginal abnormalities are common in continuation of the inner smooth (visceral) mus-
cloaca patients and occur less frequently in cle of the rectum [10]. The tone of the IAS is
females with milder types of ARMs. Additionally, maintained by sympathetic pathways from the
craniofacial abnormalities including cleft palate hypogastric plexus. The rectoanal inhibitory
are present in approximately 5% of patients. reflex of the IAS is principally intramural and
326 K. Kyrklund and R. Rintala

Fig. 24.3  The normal

anorectal angle, formed by
the puborectalis sling,
which is part of the levator
muscle complex

Rectum

Puborectalis Anorectal
angle

Anus

tures involved in continence are displaced to

varying degrees. In all ARMs, the levator mus-
Rectum cles and external sphincter apparatus are more
or less normally sited, but the bowel termination
is increasingly displaced with increasing sever-
ity of malformation. Higher malformations are
also associated with greater hypoplasia of the
Levator structures involved in faecal continence.
Anal
fibers
columns Functional IAS tissue is present in the bowel
IAS termination of all ARMs, and the fistula con-
tains all components of a normal anal canal,
EAS
including stratified columnar epithelium, anal
Anus
glands and anal columns [12]. In mild or ‘low’
malformations, the bowel termination is at least
Fig. 24.4  Normal anatomy of the anal canal: the levator partially within the voluntary sphincter funnel,
fibres are continuous with the deep portion of the external and the levator muscles are nearly normally
anal sphincter (EAS); the internal anal sphincter (IAS) is developed.
a thickened continuation of the smooth muscle of the
rectum

24.3.5 Classification of ARMs

mediated by nitric oxide synthase-containing
neurons [11]. The main purpose of classification systems in
ARMs has been to provide a platform for
describing the anatomy, operative treatment
24.3.4 Pathologic Anatomy and functional outcomes for different types of
in Anorectal Malformations malformations. Several systems have been used
over the past decades (Table 24.1), of which the
Most of the structures observed in normal most recent is the clinically oriented
infants are present in anorectal malformations, Holschneider (2005) [13] classification. This is
but the anatomical relationships between struc- a simplification of earlier models that divides
24  Anorectal Malformations 327

Table 24.1  Classification systems for ARMs

Holschneider (2005) [13] Peña (1995) [14] Stephens (1986) [15]
Major clinical Rare/regional Males Females Males Females
groups variants
Perineal Pouch colon Perineal fistula Perineal fistula High High
(cutaneous) Rectal atresia/ Rectourethral Vestibular fistula Anorectal Anorectal
fistula stenosis fistula: Persistent cloaca: agenesis agenesis
Rectourethral Rectovaginal Bulbar <3 cm common Rectoprostatic Rectovaginal
fistula: fistula Prostatic channel fistula fistula
Bulbar H-type fistula Rectovesical >3 cm common No fistula No fistula
Prostatic Others (bladder neck) channel Rectal atresia Rectal atresia
Bladder neck Imperforate anus Imperforate anus Intermediate Intermediate
Vestibular fistula without fistula without fistula Bulbar fistula Rectovaginal
Cloaca Rectal atresia Rectal atresia Anal agenesis fistula
No fistula Low Rectovestibular
Anal stenosis Anocutaneous fistula
fistula Anal agenesis
Anal stenosis Low
Rare Anovestibular
malformations fistula
Anocutaneous
fistula
Anal stenosis
Cloaca
Rare
malformations

ARMs into major clinical groups and rare/ 24.3.7 Mild ARMs
regional variants. The preceding Peña [14]
classification was based on the surgical 24.3.7.1 A  nterior Anus with or
approach and included division of ARMs into Without Anal Stenosis
male and female groups. The Wingspread clas- Present exclusively in females, anterior anus rep-
sification (1986) [15] considered anomalies resents the mildest type of ARM and is character-
based on the location of the rectal termination ized by a normal-looking anus that is anteriorly
in relation to the levator plate. The major clini- sited (Fig. 24.5). In approximately half of patients,
cal groups described in the Krickenbeck clas- mild anal stenosis may be present. The bowel ter-
sification are covered herein; the rare and minates natively mostly within (≥70%) the exter-
regional types are uncommon, but the princi- nal sphincter complex. Anterior anus may be
ples of surgical treatment are the same as for associated with a perineal groove, which is a
other types of ARMs. mucosa-lined median cleft between the ­vestibulum
and anus (Fig. 24.5) [16]. A perineal groove may
also be present in the absence of an anorectal
24.3.6 Clinical Features of ARMs anomaly and in itself requires no treatment. The
mucosal surface epithelializes gradually over time.
In this communication, ARMs from the
Krickenbeck classification with a bowel termina- 24.3.7.2 P  erineal Fistula and Anal
tion mostly within the external sphincter complex Stenosis in Males
are considered mild types, and those with a bowel In males, perineal fistula (Fig. 24.6) and anal steno-
termination outside the EAS are considered sis essentially constitute variants of the same type of
severe anomalies. mild ARM [17]. In a male perineal fistula, there is a
328 K. Kyrklund and R. Rintala

superficial subcutaneous tract in the midline for a

variable distance along the perineum or scrotal
raphe through which meconium extrudes (arrowed).
The bowel termination is natively mostly within the
external sphincter funnel, for which reason a peri-
neal fistula in a male is considered to be a mild
ARM. The bowel termination may be covered by a
median bar or an anal membrane that is usually situ-
ated at the level of the dentate line [16]. Complete
anal membranes are uncommon (2% of cases) and
could also represent the least severe form of imper-
forate anus without a fistula [18].

24.3.8 Severe ARMs

24.3.8.1 P  erineal or Vestibular Fistula

in a Female
In contrast to a perineal fistula in a male, in
females with a perineal or vestibular fistula, the
bowel termination is anterior to and outside the
Fig. 24.5  Anterior anus with perineal groove. Reprinted
support of the external sphincter funnel on the
from Fig. 3 Pakarinen and Rintala [16], with kind permis-
sion from Springer Science & Business Media perineum (Figs. 24.7 and  24.8) [16, 19] or ves-
tibulum (Fig.  24.9 and   24.10) [20]. Therefore,
these are not considered mild ARMs. Rectovaginal
fistula is a very rare variant, and most cases in
which this is suspected are actually vestibular fis-
tulas on careful clinical examination. In perineal
and vestibular fistula, there are separate and usu-
ally normal openings for the urethra and vagina.

24.3.8.2 Cloaca
The most severe form of ARM in females is cloaca,
which is characterized by a single perineal opening
(Figs.  24.11 and 24.12). The urethra, vagina and
anorectum terminate into a single common channel
of variable length. Flat buttocks and natal cleft are
suggestive of a longer common channel. Prenatal
diagnosis of cloaca may be suspected in the pres-
ence of significant hydrometrocolpos. Nearly all
cases of cloaca have associated anomalies.

24.3.8.3 Rectourethral Fistula

In males with no opening on the perineum
(Fig. 24.13), the diagnosis is usually a rectoure-
thral fistula, which is the most severe form of
Fig. 24.6  Perineal fistula in a male (arrowed). There is a
subcutaneous tract from the site of the bowel termination ARM in males. The fistulous connection of the
within the external sphincter complex terminal anorectum is most often at the level of
24  Anorectal Malformations 329

Fig. 24.9  Vestibular fistula in a female.

Fig. 24.7  Perineal fistula in a female (arrowed) reprinted
from Pakarinen and Rintala [16], with kind permission
from Springer Science & Business media

Fig. 24.10  Vestibular fistula in a female; Reprinted from

Fig. 5 in Levitt and Pena [20], with kind permission from
BioMed Central
Fig. 24.8  Perineal fistula in a female; The diagram (black
and white) from Levitt and Pena [19], with kind permission
from BioMed Central
24.3.8.4 Imperforate Anus Without
the bulbar or prostatic urethra but may be as high a Fistula
as the bladder neck (Fig.  24.14). Some patients Imperforate anus without a fistula is usually associ-
may pass meconium via the urethra, which is ated with well-developed sphincters, and this type of
diagnostic. Higher rectal terminations are associ- ARM occurs in males and females and is the most
ated with more significant hypoplasia of the common type of ARM present in patients with Down
native continence mechanisms, which is clini- syndrome. When the rectal termination is below the
cally apparent from a relatively flat and feature- dentate line and immediately subcutaneous to the
less bottom as with females with cloaca. The anal pit, the anomaly is termed anal agenesis. Less
differential diagnosis when there is no perineal commonly, the anus may be normal-looking but ter-
opening in males is imperforate anus without a minates blindly at 1–3 cm of depth. In this type of
fistula. Nearly all males with rectourethral fistula ARM, termed rectal atresia, the rectal pouch com-
have associated anomalies. monly terminates above the levator plate [21].
330 K. Kyrklund and R. Rintala

Fig. 24.12  Cloaca, single perineal opening; Reprinted

Fig. 24.11  Single channel cloaca.
from Fig. 7 in Levitt and Peña [19], with kind permission
from BioMed Central

Fig. 24.14  No perineal opening in a male: usually recto-

bladder neck or rectourethral fistula. Reprinted from
Fig. 6 in Levitt and Peña [19], with kind permission from
Fig. 24.13  No perineal opening in a male is usually a BioMed Central
rectourethral fistula

on the perineum or vestibulum, or as a single chan-

24.3.9 Initial Assessment nel cloaca. If there is any uncertainty in distinguish-
ing an anterior anus from a perineal fistula in a
Clinical examination is often sufficient to make a female, electrical muscle stimulation under anaes-
provisional diagnosis of the severity of the ARM. In thesia can clarify this [16]. In anterior anus, the anus
females, the diagnosis can be made from careful is calibrated using Hegars (normal in a full-term
examination of the perineum to demonstrate the site neonate is Hegar 12–14). In males, meconium
of the termination of the anal canal: within the exter- extruding onto the perineum indicates a mild ARM
nal sphincter complex in anterior anus, or fistulously with a low rectal termination. If no fistula is appar-
24  Anorectal Malformations 331

ent, a nasogastric tube is passed, and the patient is

kept nil by mouth. If there is still no meconium after
24–48 h of observation and gentle probing, it is safer
to assume a high ARM as the working diagnosis and
to proceed with a double-barrelled colostomy.
Cross-table lateral X-rays and perineal ultrasound
have limitations in their diagnostic sensitivity with
regard to the level of the defect. Antimicrobial pro-
phylaxis is appropriate in suspected urogenital con-
nections or if there is vesicoureteric reflux.

24.3.10  Screening for Associated

Anomalies

It is important to rule out serious associated malfor-

mations as part of the initial management. Normal
passage of a nasogastric tube rules out oesophageal
atresia, which is not uncommon in ARM patients.
Cardiac and renal tract ultrasound and a chest/
abdominal X-ray should be performed promptly for
high anomalies. Screening investigations, during the
hospitalization period include a micturating cysto-
urethrogram, spinal column radiography (Fig. 24.15)
and spinal ultrasound to assess for tethering.
Chromosomal assessment and genetic consultation
is indicated if a syndrome is suspected. Spinal cord
magnetic resonance imaging can be performed at a
later stage to rule out intraspinal anomalies.

24.4 Initial Surgical Management Fig. 24.15  Spinal column radiograph of a patient with a
rectourethral fistula showing an extra vertebra with rudi-
24.4.1 Mild ARMS mentary ribs between T12 and L1 and four sacral segments

24.4.1.1 Anterior Anus 24.4.1.2 P  erineal Fistula, Anal

No operative management is indicated for patients Stenosis or Incomplete Anal
with anterior anus because the anal canal terminates Membranes in Males
natively mostly within the external sphincter funnel. In mild ARMs in males, the anal canal is usually
If anal stenosis is present, this usually responds well located mostly within the external sphincter com-
to serial Hegar dilatations up to Hegar 14, increas- plex, and patients have a nearly normally devel-
ing the Hegar size at weekly intervals. Parents are oped anal canal [16]. In males with perineal
taught to perform Hegar dilatations twice a day at fistula, the skin overlying the subcutaneous tract
home, attending outpatients for Hegar changes by a can be laid open over a thin probe inserted from
paediatric surgeon. In the absence of anal stenosis, the tip of the fistula to the centre of the sphincter
observant, expectant management is sufficient. The complex to uncover the anus proper under gen-
long-­term continence outlook with appropriate eral anaesthesia (Fig. 24.16), usually on the first
aftercare is good/normal in most cases [22]. day of life. Anal sphincter fibres are not divided
332 K. Kyrklund and R. Rintala

a b c

Fig. 24.16  Minimally invasive management of a perineal of the external sphincter complex; (c) anoplasty of the
fistula in a male: (a) introduction of a thin probe through bowel terminus to the skin edges with a few absorbable
the subcutaneous fistula tract; (b) the skin overlying the interrupted sutures
fistula canal is laid open using diathermy up to the centre

during this procedure. The centre of the external 24.4.1.3 Anal Dilatation Programme
sphincter complex may be delineated with elec- Parents are taught to perform twice daily dilata-
trostimulation. Standard anoplasty to suture the tions with weekly outpatient visits for Hegar
bowel termination to the skin edges is performed changes. Upon reaching Hegar size 14, a
using a few interrupted absorbable sutures. “2 + 2 + 2” programme is subsequently followed,
Posterior sagittal anorectoplasty is also practised comprising dilatations twice a day for the first 2
for males with perineal fistula, but there is no evi- weeks, then every other day for 2 weeks and twice
dence to suggest superior outcomes compared to a week for the last 2 weeks. Anal strictures after a
simply laying open the fistula tract. Urologic successful dilatation programme occur in only 2%
injuries should also be completely avoided with of cases, and the likelihood requiring other anorec-
this minimally invasive approach. tal surgery is low [17]. Funnel anus, a distinct type
If a mild ARM in a male is associated with a of anal stenosis characterized by a deep skin-lined
median bar or ‘bucket handle’ defect that inter- funnel up to a stenotic ring (Fig.  24.17), is an
feres with faecal outflow, this should be excised. exception [16]. As late presentation is common
Males with anal stenosis and/or partial anal mem- and although these patients may also be treated
branes can be treated with gradual Hegar dilata- with serial dilatations, many go on to require exci-
tions, which can usually be performed without sion of a megarectum. Funnel anus is most com-
general anaesthesia. Complete anal membranes monly associated with Currarino syndrome.
require surgical incision. If the patient has under-
gone a primary colostomy due to initial suspicion
of a higher ARM, it is possible to incise the mem- 24.4.2 Severe ARMs
brane under endoscopy control through the distal
colostomy to transluminate the skin over the 24.4.2.1 Perineal and Vestibular
membrane [16]. The colostomy can be closed Fistulas in Females
during the same procedure. Following anoplasty The principles of surgical management of ARMs
for perineal fistula, the anus usually approxi- with an anal canal termination outside the external
mates to Hegar 7–8 immediately post-­operatively. sphincter comprise restoration of the normal ana-
Males with mild ARMs undergo a standard Hegar tomical relationships between structures with mini-
dilatation programme over 6 weeks up to Hegar mal interference to existing continence
14, beginning 2 weeks post-operatively. mechanisms. Anterior sagittal anorectoplasty
24  Anorectal Malformations 333

Posterior sagittal anorectoplasty is also practised

for females with perineal and vestibular fistulas
with comparable results to ASARP.  Anal cutback
has also been used to treat females with perineal
fistula, but this does not equate to an anatomical
repair as it leaves the external sphincter complex
anteriorly deficient and the perineal body greatly
shortened. Other procedures used in the past have
been largely superseded by sagittal repairs.

24.4.2.2 Rectourethral Fistula

The current ‘gold standard’ approach to high uro-
genital connections including rectourethral fistula
is posterior sagittal anorectoplasty (PSARP),
which was first introduced by De Vries and Peña
Fig. 24.17 Funnel anus. Reprinted from Fig.  2  in in 1982 [26]. PSARP largely modernized the
Pakarinen and Rintala [16], with kind permission from
Springer Science & Business Media safety and technical standards of the repair of
severe ARMs by introducing an operative tech-
nique for anatomical reconstruction under direct
(ASARP), also termed limited posterior sagittal vision. Serious operative complications reduced
anorectoplasty, is a well-established and minimally from 10 to 30% in classical operations of the past
invasive operation for both perineal and vestibular to 2% after PSARP [27]. Following a primary
fistulas in females [23]. In ASARP, a squash-racket double-barrelled sigmoid colostomy in the imme-
incision is made around the fistula, extending this diate neonatal period, PSARP may be performed
in the midline up to the centre of the external electively for rectourethral fistula at approximately
sphincter complex as marked pre-­operatively by 2–3  months of age but later if other congenital
electrostimulation. The terminal anorectum is then anomalies require repair first. The colostomy
carefully mobilized from its surrounding struc- should be proximal enough to the retroperitoneal
tures, taking particular care not to injure the poste- connections of the descending colon to reduce the
rior vaginal wall. Conservation of the fistula canal, risk of prolapse but most importantly so that
which contains internal anal sphincter tissue in enough length of distal bowel is left to reach the
ARMs, is practised by the authors. perineum during the definitive repair [20].
In ASARP, sufficient mobilization of the termi- The level of the defect is ascertained pre-­
nal anorectum to enable tension-free anastomosis to operatively as precisely as possible. The mictur-
the centre of the external sphincter complex is tech- ating cystourethrogram can demonstrate the
nically important. The perineal body is then recon- fistula and its level of entry into the urogenital
structed in layers using absorbable sutures. ASARP tract (Fig.  24.18), and a distal colostogram is
may be safely performed as a single-stage proce- complementary to this purpose. Filling the bowel
dure in otherwise well infants during the neonatal with sufficient pressure to permit passage of con-
period [24, 25]. A covering sigmoid colostomy is trast into the bladder through the fistula is techni-
currently advisable for older patients. Intravenous cally important. Failure to demonstrate a urethral
antibiotic prophylaxis is advisable during the imme- connection, however, does not completely rule
diate post-operative period. Most wound complica- out the possibility of one.
tions relating to ASARP are superficial infections Classical PSARP involves a strict midline
that respond well to local hygiene and antibiotics. sagittal approach through the levator muscles
Patients undergo a standard anal dilatation pro- and external sphincter with the patient in the
gramme up to Hegar 14 beginning 2  weeks post- prone position to access the bowel termination.
operatively as for males with perineal fistula. Although nearly all urethral fistulas are acces-
334 K. Kyrklund and R. Rintala

Fig. 24.18  Micturating cystourethrogram showing a rectourethral fistula at the level of the prostatic urethra (a) and the
distal colostogram of the same patient (b) demonstrating the entry of contrast into the bladder through the fistula
(arrowed)

sible through the posterior sagittal approach

alone [20], laparoscopy is an attractive option
for accessing high urogenital connections and
permits excellent visualization of the fistula
(Fig.  24.19). A combined technique, involving
laparoscopic ligation of the fistula and a poste-
rior sagittal incision for anastomosis of the
bowel in the centre of the external sphincter
complex, represents our current practice for
patients’ recto-­prostatic or recto-bladder neck
fistulas. In rectourethral bulbar fistulas, the pos-
terior sagittal incision alone provides optimal
access. Laparoscopic division are both anatomi- Fig. 24.19  Laparoscopic ligation of a high rectourethral
cally challenging in these cases and may be (prostatic) fistula
complicated by a posterior urethral diverticulum
due to incomplete excision of the fistula. As a internal anal sphincter tissue, has been demon-
limited modification of PSARP, the most distal strated to be present in most patients post-oper-
part of the external sphincter may be conserved atively with this technique [28]. After PSARP, a
during posterior sagittal incisions. As with ves- standard anal dilatation programme is followed
tibular and perineal fistulas, an internal anal up to Hegar 14, after which colostomies can be
sphincter-­ saving technique that preserves the closed.
entire fistula canal is practised [27]. The recto- Almost fully laparoscopic repairs for urethral
anal inhibitory reflex, indicative of functional fistula are also practised in some centres [29].
24  Anorectal Malformations 335

This technique involves laparoscopic dissection described previously. Colostomy closure can be
of the fistula and pull-through of the bowel via a performed at the same time. In imperforate anus
small 1 cm incision at the centre of the external without a fistula, the sphincter muscles are usu-
sphincter complex. Although minimally inva- ally quite well developed, and the continence out-
sive, laparoscopic pull-throughs continue to be comes are mostly favourable.
complicated by a high rate of rectal prolapse,
and there are no long-term studies to suggest
improved functional results. A benefit of the 24.4.3 Cloaca
posterior sagittal incision is that it enables
reconstruction of the normal anorectal angle Cloaca is a rare and complex type of anorectal
through anatomical positioning of the bowel malformation that requires considerable expe-
within the support of the sling muscles, which rience in its surgical management. In the
may be important for preventing rectal prolapse. immediate neonatal period, other life-threaten-
Minor anal mucosal ectopy, which occurs in a ing anomalies, including obstructive uropathy,
few patients in the mid to long term after cardiac anomalies and tracheo-oesophageal fis-
PSARP, is usually amenable to local corrective tula, should be ruled out. Pre-operative investi-
surgery. gations of the cloacal malformation should aim
to establish the length of the rectourogenital
24.4.2.3 Imperforate Anus Without confluence and the urethra and the anatomy of
a Fistula the bladder and gynaecologic structures for
The posterior sagittal approach is appropriate for planning the reconstruction. Ultrasound of the
patients with an imperforate anus without a fis- urinary tract and imaging with contrast through
tula. In rectal atresia, the principles of operative the perineal opening may assist in this purpose
management are otherwise the same as for ure- (Fig.  24.20). However, not all structures may
thral fistula. However, if a complete anal mem- be visualized, and accurate interpretation of
brane is present (anal agenesis), this can be the findings is dependent on the experience of
treated minimally invasively by incision as the radiologist.

r r

v v b
v

u
c

Fig. 24.20  Contrast study of a patient with a cloaca showing the rectum (r), duplex vagina (v), bladder (b), urethra (u)
and urogenital confluence (c)
336 K. Kyrklund and R. Rintala

Endoscopy through the cloacal common chan- 24.4.4 Definitive Reconstruction

nel using a paediatric cystoscope and warm flush-
ing fluid is performed to measure the length of The timing and nature of the definitive reconstruc-
the common channel and urethra and visualize tion in cloaca patients are based on the clinical
the number and size of vagina(s) and the position judgement and experience of the surgeon. The
of the rectourogenital connection. A high-­ objectives include enabling faecal continence, uri-
confluence cloaca is considered one with a com- nary continence and a functional genital tract.
mon channel length in excess of 3 cm. Patients should be stable from a cardiovascular and
With regard to the initial colostomy, if there is urologic perspective, >5  kg of weight and over
(1) clear anatomy and (2) a patent vagina with no 6 weeks of post-gestational age. Through a poste-
expectation of a possible need for vaginal recon- rior sagittal approach, the first structure to be opened
struction, a double-barrelled sigmoid colostomy in cloaca is the rectum, which is split in the midline;
may be performed. The colostomy should aim to the vaginal and urethral communications are identi-
leave as much distal bowel as possible for the fied through the rectal opening. In high rectal com-
definitive repair, so that the bowel can reach the munications, a laparotomy may be required. If there
perineum without tension. If there is (1) a very is a long common channel and a short proximal ure-
high confluence and (2) uncertainty of the need for thra, it may be opted to retain the common channel
sigmoid vaginal augmentation or (3) the anatomy as the urethra, particularly if it is not too wide. The
is simply unclear, a transverse colostomy should rectum and vagina are separated from their sur-
be performed. A transverse colostomy does not rounding structures and pulled down to their ana-
preclude the later use of the sigmoid colon for tomical positions on the perineum. The rectum is
vaginal reconstruction or hinder the subsequent ­transected flush to the vaginal wall. The most diffi-
pull-through. A contrast study of the distal bowel cult part of a cloacal repair this way is separation of
prior to the definitive repair should be performed the vagina from the urethra. Total urogenital mobi-
and combined with the results of neonatal imaging lization, which was first introduced in 1996 [31], is
when planning the definitive surgery. an attractive option for cases with a short common
Hydrometrocolpos is commonly present in channel for this reason. It involves mobilization of
cloaca patients, because urine may first pass into the urethrovaginal junction en bloc and bringing
the vagina before being evacuated via the com- this down to the perineal skin, thereby only requir-
mon channel [30]. Catheterization of the bladder ing separation of the rectum. In low confluences,
is usually not possible without endoscopic aid, as posterolateral mobilization of these structures is
the junction of the proximal urethra with the sufficient, but in higher confluences, anterior retro-
common channel is sharply angulated towards pubic dissection is also required. When required,
the pubic bone [30]. Catheter decompression of vaginal reconstruction may be performed using
the hydrometrocolpos should be attempted as it bowel segment transposition with the (1) sigmoid
can relieve urinary obstruction and prevent sep- colon or (2) ileum.
sis. If intermittent catheterization of either the
bladder or vagina for urinary drainage is not fea-
sible and severe urinary outflow obstruction or 24.4.5 Basic Principles of Aftercare
upper tract dysfunction is present, a vesicostomy During the First Year of Life
is indicated. A colpostomy is only indicated in
large hydrometrocolpos and often decompresses Adequate aftercare of patients with ARMs is at
the upper urinary tract. However, a colpostomy least as important in securing optimal functional
may also preclude a posterior sagittal approach outcomes as a successful primary repair. Patients
and total urogenital mobilization for vaginal should be cared for in centres that are also able to
pull-through. provide high-quality, multidisciplinary manage-
24  Anorectal Malformations 337

ment of both the ARM and associated anomalies. with increasing level of fistula. They are good in
In terms of bowel function, a tendency to consti- approximately 40%, with the remainder reporting
pation is a central feature that affects all types of varying degrees of residual symptoms. Although
ARMs. The aetiology may relate to developmen- the majority of patients with high bladder neck fis-
tal factors or to corrective surgery. The onset is tulas achieve social continence with modern care,
commonly around the time the child begins to secondary measures for bowel management such
take solids, around 3–6 months of age. After sur- as an antegrade continence enema (ACE) conduits
gical repair, patients should be reviewed in outpa- are likely to be required [27]. Secondary interven-
tients at regular intervals to ensure satisfactory tions aim to enable weaning from diapers before
stooling, and parents should be educated on the primary school and to ensure normal social inte-
importance of attending to constipation. Most gration during childhood. In cloaca, approximately
constipation in ARMs responds well to oral laxa- half of patients attain faecal and urinary conti-
tives that include bulking agents (macrogols), nence, and the remainder stay clean or dry by
lactulose and stimulant laxatives (natrium pico- adjunctive measures, including bowel manage-
sulphate). Treatment should be continued until ment, continent urinary diversion or intermittent
the tendency to constipation completely resolves, catheterization [32]. However, most patients with
which may not be for several years in some cases. ARMs report a normal quality of life after contem-
Failure to address constipation can lead to severe porary treatments in the long term [32, 33].
complications, including megarectosigmoid from
faecal impaction and secondary overflow inconti-
nence [19]. Apart from an increasing level of the
malformation, other negative prognostic factors
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Wakhlu A, Kureel SN, Tandon RK, Wakhlu
13. Holschneider A, Hutson J, Peña A, Bekhit E,
AK.  Long-term results of anterior sagittal anorecto-
Chatterjee S, Coran A, et al. Preliminary report on the plasty for the treatment of vestibular fistula. J Pediatr
International Conference for the development of stan- Surg. 2008;44:1913–9.
dards for the treatment of anorectal malformations. J 25. Kumar B, Kandpal DK, Sharma SB, Agarwal LD,
Pediatr Surg. 2005;40:1521–5126. Jhamiraya VN.  Single-stage repair of vestibular and
14. Peña A.  Anorectal malformations. Semin Pediatr
perineal fistulae without colostomy. J Pediatr Surg.
Surg. 1995;4:35–47. 2008;43:1818–952.
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16. Pakarinen MP, Rintala RJ. Management and outcome RJ.  Long-term bowel functional outcomes in rec-
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RJ. Bowel function and lower urinary tract symptoms 28. Kyrklund K, Pakarinen MP, Rintala RJ. Manometric
in males with low anorectal malformations. An update findings in relation to functional outcomes in differ-
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 Congenital Pouch Colon
25
Devendra K. Gupta, Shilpa Sharma,
and Kashish Khanna

25.1 Introduction 25.3 Anatomical Criteria

Congenital pouch colon (CPC) is a type of ano- CPC most commonly fits in the following ana-
rectal anomaly where a pouch-like dilated and tomical criteria [1, 2]:
shortened colon is associated with the anorectal
malformation (ARM). It is reported widely from 1 . There is anorectal agenesis.
the South Asian subcontinental countries India, 2. The total length of the colon is short.
Pakistan and Bangladesh with anecdotal cases 3. The colon has a pouch of varying length

from other parts of the world [1, 2]. (5–15 cm) and form (saccular or diverticular)
CPC comprises of around 5–15% of all cases of with collected meconium or faecal matter.
ARM in Northern India, 8–10% in Pakistan and 4. The pouch has an abnormal blood supply. It is
1.7% in Bangladesh. Its incidence is as higher in usually supplied by the branches from the
tertiary centres especially in high ARM to the tune superior mesenteric artery, which form a leash
of one fifth to one sixth of the cases [3]. It is more of vessels around the pouch.
common in males than in females (3:1–7:1) [2, 4]. 5. It has a uniformly thick and muscular colonic
wall with hypertrophied mucosa.
6. In females, the pouch opens into the genito-
25.2 Definition urinary tract via a wide, long and muscular
fistula, closely adherent to the bladder wall
Pouch colon is a type of anorectal agenesis in either open into the vaginal wall, the vaginal
which the whole or a part of the colon is replaced septum between two hemi-vaginae, bladder or
by a pouch-like dilatation that communicates dis- rarely in the perineum. In males, there is a
tally with the urogenital tract by a large fistula. short fistula that communicates with the blad-
This supralevator anomaly is associated with a der usually opening in the dome or posterior
colonic pouch of variable length and diameter. It wall of the bladder.
has a short and poorly developed mesentery, 7. There is no transitional zone between the
absent taenia coli and no appendices epiploicae pouch colon and the normal bowel, and the
or haustrations and usually has a very thick wall. bowel pattern changes suddenly and
abruptly.
8. CPC frequently has other associated major
D. K. Gupta (*) · S. Sharma · K. Khanna
Department of Pediatric Surgery, All India Institute of anomalies especially the genitourinary
Medical Sciences, New Delhi, India anomalies.

© Springer Nature Switzerland AG 2019 339

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_25
340 D. K. Gupta et al.

25.4 Classification In female newborns with CPC often muco-

sal folds radiating inwards and upwards from
In 1984 Narasimharao et al. suggested the name the margins of the vestibule may be seen
CPC syndrome and classified it into types I–IV (Fig. 25.3).They may usually have a short wide
based on the length of the normal colon proxi- urethra, deficient bladder neck, small bladder,
mal to the colonic pouch [5]. Wakhlu et  al. poorly developed trigone and laterally placed
(1996) classified it into types A and B based on ureteric orifices [10, 11]. These features may
the need for coloplasty [6]. It was in 2005 that be responsible for the higher incidence of uri-
Gupta and Sharma modified this classification nary incontinence (around 85%) seen in these
based on the management of CPC into incom- patients [10].
plete and complete varieties and CPC was rec- Rarer varieties of pouch colon have been
ognized as rare/regional anomalies in the described with double pouch with associated rectal
Krickenbeck classification of ARM [1, 7, 8]. atresia, pseudoexstrophy bladder and associated
The classification was based on the feasibility to duplicated exstrophy bladder [12–14]. The embry-
use the remaining colon while performing the ologic basis of the association of pouch colon with
pull-through. duplicate bladder exstrophy has been proposed as
The Gupta and Sharma (2005) classification malposition of allantoic diverticulum with the yolk
has been described (Fig. 25.1) as: sac resulting in anorectal malformation or seques-
Complete: There is either none or little normal tration of a part of the allantois, infraumbilically
colon left that is insufficient for performing the and improper mesodermal progression giving rise
pull-through. to duplicate bladder exstrophy [14].
Incomplete: The length of the normal colon is Gupta and Sharma operated a newborn with a
adequate enough to perform the pull-through patent pouch colon opening at the umbilicus and
without the need for doing a coloplasty. connected to the bladder via a fistula with no
normal intervening colon. The ileum opened into
the pouch-like structure. The baby had an associ-
25.4.1 Characteristics of Subtypes ated bifid scrotum and meningomyelocele [15].
Short colon has been described by Chiba as a
Complete CPC: A large, dilated, thick-walled shortened length and a narrow calibre of left
pouch occupies most of the left side of the abdo- colon without associated ARM in babies usually
men. Cecum, if present, almost always opens into born to diabetic mothers [16].
the sac from the right side. It may be associated
with an absent, rudimentary or double appendix.
The pouch is usually supplied by the superior 25.5 Embryopathogenesis
mesenteric artery on the superior and right side and Aetiology
and an arcuate extension of superior mesenteric
artery on the left side [9]. CPC is a complex congenital anomaly thought to
Incomplete CPC: The pouch usually occupies have resulted due to error during the partitioning
the left half of the abdomen with adequate length of cloaca at around 4–6 weeks. During develop-
of the normal colon which opens into the pouch ment, a coronal wedge or ridge of mesenchyme,
from the right. Apart from the branches of superior the urorectal septum (URS), forms in the angle
mesenteric artery, the pouch in its lower half may between the allantois and the hindgut. As the URS
be supplied by the inferior mesenteric artery [1]. grows caudal towards the cloacal membrane, it
With growing awareness of the anomaly, divides the cloaca into an anterior portion, the
incomplete pouch colon is more commonly rec- primitive urogenital sinus, and a posterior part,
ognized [2]. the anorectal canal. By 7 weeks of age, the URS
The genitourinary fistula opens at various lev- reaches the cloacal membrane and fuses with it.
els in males and females (Fig. 25.2). Thus, the failure of rostrocaudal growth of the
25  Congenital Pouch Colon 341

a Superior
Superior
mesenteric
mesenteric
artery
artery

Caecum
Ileum

Pouch
colon

Urinary
bladder

Complete pouch colon

Ileum Caecum
Superior
mesenteric
Normal
artery
colon
Inferior
Superior mesenteric
mesenteric artery
artery
Pouch Ileum
colon
Pouch colon

Urinary Urinary
bladder Caecum bladder

Incomplete pouch colon

b c

Fig. 25.1 (a–c): (a) Modified classification of congenital sufficient length of the normal colon. (c) Operative photo-
pouch colon (incomplete and complete CPC). (b) graph of complete pouch colon with the ileum seen enter-
Operative photograph of incomplete pouch colon showing ing into the pouch from the right side

URS would cause an arrest of cloacal septation The earlier the timing of arrest, the more are the
with hindgut opening above the level of Wolffian chances of complete pouch. Various theories have
duct in males and at a similar level in females. been proposed for the same [15] (Table 25.1).
342 D. K. Gupta et al.

a b

Pouch
Pouch colon
colon Uterus
Urinary Urinary
bladder bladder
1 1
Colovesical Vagina
fistula 2 3
3
2
4

CPC fistula in males CPC fistula in females

1 - Colovesical fistula
2 - Colocloacal fistula
3 - Colovaginal fistula
4 - Colovestibular fistula

Fig. 25.2 (a, b): Showing site of fistula. (a) In males, above the bladder neck (3). (b) In females, common sites
colovesical fistula in males opens either in the posterior of fistula are colovesical (1), colocloacal (2), colovaginal
wall of the bladder (1), near the bladder base (2) or just (3) and colovestibular (4)

Table 25.1  Theories of faulty embryogenesis in CPC

Proposed by Theory
I Dickinson Aborted hindgut development
following obliteration of the
inferior mesenteric artery early in
foetal life [17]
II Chatterjee Improper development of the
postaxial midgut or presplenic gut
due to a primary disorder of the
proximal end of the hindgut or
postsplenic gut [18]
III Wu Faulty rotation and fixation of the
colon leads consequently to a
disturbed longitudinal growth [19]
IV Wakhlu The anomaly is a stage in the
development of cloacal exstrophy and
is the combined effect of defective
development of the splanchnic layer
of the caudal fold and failure of
Fig. 25.3  External examination of a girl with common rotation of the gut causing defective
cloaca and incomplete CPC, showing wide vestibule with longitudinal growth of the colon [9]
folds radiating inwards
V Gupta and Role of pesticides, micronutrients or
Sharma the vitamin deficiency in a largely
[2007] vegetarian community with poor
The major aetiological factors currently pro- socioeconomic status, affecting the
posed to be involved are [15]: vascular supply in the growing
hindgut of the foetus at a critical
window period of gestation [2]. Any
• Vascular: The blood supply to the pouch is genetic link, though suggestive of a
always abnormal and is mainly from the strong geographical distribution,
branches of the superior mesenteric artery. still needs to be confirmed
25  Congenital Pouch Colon 343

The absence of inferior mesenteric artery in mal peristaltic activity mandate its removal for a
50% of the cases points towards early vascular better functional outcome when feasible, espe-
insult during the foetal period. cially in incomplete pouch colon. Gangopadhyaya
• Environmental: The high density of cases in et al. concluded from their study on histopatho-
the northern parts of the Indian subcontinent logic evaluation that the pouch is an abnormally
strongly suggests a possible association with developed tissue and needs to be resected for bet-
deficiency of micronutrients (iodine, vitamin ter functional outcome of the remaining gut [23].
B and zinc) and the liberal use of pesticides
and fungicides which may affect the pregnant
mother during organogenesis. 25.7 Clinical Presentation
• Genetic: Recent reports in the literature
have shown that germline mutations/dele- Most cases present early within the first 7 days of
tions of genes encoding the proteins of sig- life with an absent anal opening and gross abdom-
nalling pathways (NOTCH, Wnt gene and inal distension [1]. Meconuria may be present in
Hedgehog) of the normal colon result in its up to half of the cases. There may be associated
malformation. Maudar et  al. reported an bilious vomiting. In case the pouch perforates, the
­immunohistochemical study of colonic pouch newborn may present with pneumoperitoneum,
tissue that revealed an enhanced expression of peritonitis and sepsis. Abdominal distension may
beta-catenin, Ihh, Notch1 and HMGA1 and not be marked in incomplete pouch and in female
commented on the expression of molecules patients decompressing well via colocloacal fis-
from all three embryonic signalling pathways tula. Such patients may present late.
[20]. However, more biochemical and molec-
ular studies are still required.
25.8 Investigations

25.6 Histopathology In addition to the clinical examination and the

endemic disease pattern, an erect anteroposterior
Various studies have revealed abnormal histopath- skiagram helps to clinch the diagnosis in sus-
ological changes in the pouch. Gupta and Sharma pected cases of CPC. In cases of complete pouch
found disorganization of the muscle coat in an colon, a large bowel loop with a single air-fluid
arborizing manner as a salient feature [1]. It is not level occupying more than 50% of the abdominal
clearly differentiated into inner circular and outer width ending at a supralevatoric level with its
longitudinal muscles but is disarranged in a decus- apex positioned in the left hypochondrium is usu-
sating pattern. The circular muscle may be incom- ally seen. In cases of incomplete pouch, the apex
plete in 50% cases [15]. In the nerve plexus, the of the pouch may be in the right hypochondrium
ganglion cells are mature and present in all cases or variable in position [24]. On an invertogram,
with the presence of normal or occasionally hyper- the pouch is proximal to the pubococcygeal line
trophic nerve bundles. The pouch wall consists of (Fig. 25.4a, b). In case of perforated pouch, pneu-
normal ganglion cells though these maybe reduced moperitoneum may confound the diagnosis of
in number and smaller in size [2]. However, giant CPC.  Similarly in very wide CVF, the gas may
ganglia are also seen in 10% cases [15]. Nerve escape into the urinary bladder, and a cross-table
bundle hypertrophy has also been reported [8]. prone/lateral film will help to differentiate.
Varying degrees of submucosal fibrosis may be Before the child undergoes a definitive sur-
present [21–23]. Mucosal congestion and focal gery, an ultrasound of the abdomen, an intrave-
haemorrhages are seen commonly. Occasionally, nous urogram and voiding cystourethrography
heterotopic epithelium (gastric/pancreatic/small and an echocardiography should be done to rule
intestinal) has been reported [21]. out other associated anomalies. Examination
The typical histology of pouch and the under anaesthesia (EUA) and cystourethroscopy
mechanics of a grossly dilated colon with abnor- may help to confirm diagnosis in females. In
344 D. K. Gupta et al.

a b

Fig. 25.4 (a) X-ray abdomen erect (AP view) showing a large air-fluid level occupying more than 50% of the abdomen
suggestive of a pouch. (b) Invertogram with a large air-fluid level ending above the PC (pubococcygeal) line

males, cystourethroscopic examination shows

• ARM with a rectouterine fistula
that the CPC fistula usually ends above the blad-
• Localized pneumoperitoneum due to a sealed
der neck [10]. However, in endemic regions, the
perforation
diagnosis is almost confirmed on the anteropos-
terior film, and an abdominal exploration is
indicated directly without cystoscopic confir-
mation. In females, endoscopy may help to
25.9 Associated Anomalies
prognosticate about the urinary incontinence.
The genitourinary anomalies like vesicoureteric
Other causes which may mimic the diagnosis reflux, renal agenesis and bicornuate uterus, fol-
of CPC include: lowed by gastrointestinal anomalies like absent
appendix or double appendix are most commonly
• ARM with hugely dilated rectosigmoid associated with CPC. Table 25.2 summarizes the
• ARM with hydrometrocolpos other associated anomalies.
25  Congenital Pouch Colon 345

Table 25.2  Common asso- Type System Anomalies

ciated anomalies reported in I Genitourinary system Vesicoureteric reflux
literature [2, 15] Hydronephrosis
Renal dysplasia/agenesis/ectopia
Pseudoexstrophy bladder
Cryptorchidism
Hypospadias
Urethral anomalies—diverticulum, duplication,
megalourethra, stricture
Prune belly syndrome
Bicornuate uterus
Double uterus/vagina
Septate vagina
II Gastrointestinal Absent appendix
system Double appendix
Malrotation
Meckel’s diverticulum
Duplication of colon
Oesophageal atresia
III Vertebral and limb Sacral agenesis (partial/complete)
anomalies Hemivertebrae
Meningomyelocele
Congenital talipes equinovarus
IV Cardiovascular system Congenital heart disease

end colostomy followed later by abdominoperi-

25.10 Management neal pull-through. The other option is initial
window colostomy or a transverse colostomy
25.10.1  Preoperative Resuscitation followed by fistula division, pouch excision and
abdominoperineal pull-through later at
Initial management includes nasogastric tube 6–18 months with or without a protecting trans-
decompression, dehydration and electrolyte cor- verse colostomy.
rection, temperature maintenance, bladder cathe-
terization and proper antibiotic coverage. Surgery
should be aimed at preserving the available 25.10.3  Complete Pouch
length of the colon for ensuring adequate absorp-
tion, faecal storage and continence In complete CPC, tubularization of pouch till
­postoperatively. A staged management has been about 15  cm length is essential to preserve the
widely accepted for CPC. Single-staged surgery function of the colon [1, 2]. Hence fistula divi-
is not routinely advocated due to unacceptably sion, coloplasty, end colostomy and a proximal
high mortality rate [1, 2, 22]. ileostomy followed by an abdominoperineal
pull-­through of the tubularized colon later are
the preferred approach. Alternately a window
25.10.2  Incomplete Pouch colostomy/proximal ileostomy can be done as an
initial procedure depending upon the condition
In incomplete pouch, the preferred approach of the baby, technical skills of the surgeon and
consists of fistula division, pouch excision and the available facilities.
346 D. K. Gupta et al.

25.10.3.1 Management Algorithm of CPC

Preoperative Resuscitation

Incomplete Complete
congenital congenital pouch
pouch colon colon

Fistula division,
Transverse Fistula division, Window
pouch excision
colostomy coloplasty and colostomy/ proximal
and end
colostomy end colostomy ± ileostomy
proximal ileostomy

Fistula division,
Abdominoperineal pouch excision
Fistula division,
pull-through ± and
Abdominoperineal coloplasty and
Transverse colostomy Abdominoperin
pull-through ± Abdominoperineal
eal pull-through
proximal ileostomy pull-through ±
±Transverse
proximal ileostomy
colostomy

+/-Colostomy/ ileostomy closure

Window colostomy: An opening made in the End colostomy is the preferred procedure.
anterior surface of the pouch. Fistula is not Stoma-related complications like stomal retrac-
ligated. tion, prolapse, peristomal excoriation, bleeding,
Advantages anaemia, stomal diarrhoea and poor weight gain
are seen more in ileostomy and transverse colos-
• Simple procedure tomy than in end colostomy.
• Minimum anaesthesia required Coloplasty: In complete CPC, the pouch first
• Less operative time mobilized completely by dividing the inferior
• Provides adequate decompression mesenteric artery (if present). Thereafter, the
• Can be done in a sick neonate pouch is incised on the anti-mesenteric border,
preserving the vascularity, and a tube is fashioned
Disadvantages over a red rubber catheter to obtain a uniform cali-
bre. This coloplasty may be brought out as an end
• Complications: massive pouch prolapse, colostomy on the abdominal wall for a staged pro-
bleeding from prolapsed pouch, pouch reces- cedure and can be pulled down later during defini-
sion and stenosis tive procedure. In neonates though, a primary
• Incomplete decompression requiring regular pull-through is possible, but it is associated with
washouts high morbidity and even mortality [1] (Fig. 25.5).
• Recurrent urinary tract infection and entero- Advantages
colitis due to persistent fistula
• Pouchitis • Preserves adequate length of the colon for
• Adhesive obstructions functional purposes (about 15 cm)
• Septicaemia and failure to thrive • Less faecal incontinence and diarrhoea later as
• High mortality (15–20%) [15] compared to ileal pull-through cases
25  Congenital Pouch Colon 347

Superior Mesenteric Superior

mesenteric artery border Ileum mesenteric artery

Tubularized
colon
Ileum
Pouch
colon

Line of
incision

Antimesenteric
border

Red rubber
Fistula catheter

Fig. 25.5  Coloplasty is performed while preserving the vascular arcade to the pouch

Disadvantages Table 25.3  Complications related to pull-through sur-

gery in CPC
• Suture line leak Complications Management
• Wound dehiscence I Mucosal prolapse Mucosal excision
• Constipation II Anal stenosis Regular anal dilatation
starting 3 weeks after
• Re-dilatation pull-through
• High mortality if not performed as a staged III Colonic Redo surgery using
procedure re-dilatation of the shorter pouch length for
• Increases operative time during initial surgery coloplasty segment retubularization is
required sometimes
IV Shortened colon Adequate vitamin,
In case if the child presents with a severely length leading to mineral and dietary fibre
ischaemic/gangrenous pouch or a pouch with recurrent watery supplementation
multiple perforations, then pouch excision, fis- diarrhoea and poor
tula ligation and a proximal ileostomy remain the weight gain
V Faecal Bowel management and
safest option.
incontinence dietary modifications
Definitive surgery: It is usually performed
after 6–18  months when the child has gained
enough weight and has been evaluated c­ ompletely
for other associated anomalies. In incomplete A protective stoma (ileostomy/transverse
pouch, the abdomino-posterior sagittal anorecto- colostomy) is preferred during a pull-through
plasty approach (abdomino-PSARP)/abdomino- surgery. This could later be closed after
perineal pull-through (APPT) is performed with 3–6 months.
the child in supine lithotomy position. In com- Use of pouch in common cloaca: The pouch
plete pouch, the tubularized colon is pulled down can be used to reconstruct the vagina and the ano-
to create a neoanus by APPT. The complications rectum both at the same time by splitting it longi-
and the appropriate management of pull-through tudinally into two while preserving the blood
surgery are given in Table 25.3. supply of either segments [25].
348 D. K. Gupta et al.

25.11 Follow-Up with associated sacral anomalies and poor pelvic

musculature.
Initial follow-up examination is performed after Growth and development: In a study on func-
2 weeks and then after 1 month. Then 3-monthly tional outcomes of CPC patients, Puri et al. found
follow-up for the first year and 6-monthly follow- that all 13/22 (59.1%) patients with an ileal pull-­
­up for the next 3  years are required. Thereafter through had height and weight less than the 50th
the child can be followed up once in 2 years till percentile of the expected value for age [26].
adulthood to assess for long-term results. However, 9/22 (40.9%) patients with types III/IV
Initially the baby passes frequent liquid stools, CPC or type I/II CPC with pull-through after
but subsequently, the frequency decreases and coloplasty had near-normal growth patterns or
the consistency changes to semisolid and over parameters between the 50th and 80th percentile.
months to solid. Perineal excoriations and bacte- Nutritional outcomes: These patients require
rial and fungal infections are common in the ini- monitoring of nutritional status. Anaemia and
tial period. The colon on follow-up examination malnutrition are common in complete CPC
shows normal calibre in most of the cases; how- patients, and hence early dietary modification,
ever, dilatation of the tube coloplasty is rare but a high-protein consumption and micronutrient sup-
serious problem [1, 23]. plementation are important.
Colonic re-dilatation: Incidence reported
varies. This occurs primarily because the
25.12 Outcome and Prognosis colonic pouch has an abnormal histology and a
tendency to dilate. Hence, the use of a shorter
The mortality in patients of CPC has decreased segment of pouch for tubularization is now
from 30–40% to 10–20% with the growing recommended.
awareness and improved management of this dis-
ease [3]. Prognosis and results depend upon vari- 25.13 Future
ous factors:
Leads from the past will lead to the work in the
• The age at presentation future in the field of CPC. The exact aetiopatho-
• The weight of the child genic factors responsible for CPC still need to be
• Presence of sepsis and perforation explored. A genetic link though pointed by the
• Associated congenital anomalies typical geographic distribution of CPC needs to
• Complete/incomplete pouch colon be studied further. Environmental association
• Type of perineum and the muscle complex with micronutrient deficiency may provide a
• Surgical expertise and NICU care scope for prevention of this disease. Management
• Nutritional management of faecal incontinence and urinary incontinence
• Compliance to follow-up especially in girls still remains a challenge. Long-­
term follow-up studies of these patients till adult-
Babies with incomplete pouch colon fair bet- hood are required to form a proper management
ter than those with complete pouch colon. protocol and improve the quality of life of these
Faecal continence: Most patients have fairly patients [27].
good continence results by puberty. However,
around 60% of children with complete pouch
colon may have faecal incontinence in the initial References
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amide/diphenoxylate, daily colonic washes may 1. Gupta DK, Sharma S.  Congenital pouch colon. In:
improve the dry interval. Hutson J, Holschneider A, editors. Anorectal malfor-
mations, vol. 11. 1st ed. Heidelberg: Springer; 2006.
Urinary incontinence: Though not a common p. 211–22.
problem, it may persist in females with CPC 2. Gupta DK, Sharma S. Congenital pouch colon —then
associated with wide bladder neck or in those and now. J Indian Assoc Pediatr Surg. 2007;12:5–12.
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3. Sharma S, Gupta DK, Bhatnagar V, Bajpai M, 16. Chiba J, Kasai M, Askura Y. Two cases of coloplasty for
Agarwala S. Management of congenital pouch colon congenital short colon. Nihon Geka Hokan. 1976;45:40.
in Association with ARM.  J Indian Assoc Pediatr 17. Dickinson SJ.  Agenesis of the descending colon

Surg. 2005;10(Suppl 1):S22. with imperforate anus. Correlation with modern con-
4. Gupta DK. Congenital pouch colon: present lacunae. cepts of the origin of intestinal atresia. Am J Surg.
J Indian Assoc Pediatr Surg. 2007;12:1–2. 1987;113:279–81.
5. Narasimharao KL, Yadav K, Mitra SK, et  al. 18. Chatterjee SK.  Anorectal malformations, a surgeons
Congenital short colon with imperforate anus experience. Delhi: Oxford University Press; 1991.
(pouch colon syndrome). Ann Pediatr Surg. 1984;1: p. 170–5.
159–67. 19. Wu YJ, Du R, Zhang GE, Bi ZG.  Association of
6. Wakhlu AK, Wakhlu A, Pandey A, et al. Congenital imperforate anus with short colon: a report of eight
short colon. World J Surg. 1996;20:107–14. cases. J Pediatr Surg. 1990;25:282–4.
7. Holschneider A, Hutson J, Pena A, Beket E, Chatterjee 20. Maudar KK, Gandhi P, Varshney S, Budhwani KS,
S, Coran A, Davies M, Georgeson K, Grosfeld J, Ghritalaharery RK. Congenital pouch Colon: review
Gupta D, et al. Preliminary report on the International of current clinical and molecular studies. J Pediatr
Conference for the development of standards for the Neonatal Care. 2016;5(9):00227.
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2005;40:1521–6. Sharma A, Roy Choudhury S.  The histopathology
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Surg. 2005;10:79. 22. Gangopadhyay AN, Sharma S, Mohan TV, Gopal SC.
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10. Chadha R, Khan NA.  Congenital pouch colon. J
Upadhyaya VD.  Congenital pouch Colon associated
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Acharya H, et  al. The anomalous clinical anatomy 24. Mathur P, Saxena AK, Bajaj M, Chandra T, Sharma
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 Inguinal Hernia and Hydrocele
26
Ciro Esposito, Maria Escolino, Alessandro Settimi,
and Giuseppe Cortese

26.1 Introduction In particular, in small babies, this can be a

daunting procedure, due to the fragile hernia sac,
The incidence of inguinal hernia (IH) varies small anatomic region, and possible comorbidi-
between 1 and 5% in the pediatric population ties, so frequent in ex-preterms [11]. Similarly,
with a strong male preponderance [1]. Preterm the incidence of postoperative issues (recurrence
babies have a higher likelihood to develop ingui- and testicular atrophy) has a higher incidence in
nal hernia with an incidence that has been infants compared to the general pediatric popula-
reported to be as high as 30% [2, 3]. The inci- tion [12–14].
dence of incarceration in untreated hernias in Open herniotomy (OH) has always been the
young children has been reported to vary between standard procedure for this group of patients over
6 and 18%, but it can exceed 60% during the first years. During the last decade, laparoscopic IH
6 months of life [4]. Bilateral inguinal hernia is repair (or herniorrhaphy) (LH) has become a rou-
significantly more common in younger patients tine procedure in older children, but its use in
with an incidence of about 50% if patients are neonates and premature babies is still limited
less than 1-year-old [5]. [15–20]. Reported advantages of laparoscopic
As a consequence, inguinal hernia repair is hernia repair include excellent visual exposure,
one of the most common surgical procedures per- minimal dissection of vas deferens and spermatic
formed by pediatric surgeons [6, 7]. In pediatric vessels, fewer complications, comparable recur-
population, the traditional inguinal approach is rence rates, and improved cosmetic results com-
an excellent method for hernia repair [8]. pared to the traditional open approach [21, 22]. In
However, it has the potential risk of injury of the addition, laparoscopic approach allows diagnosis
spermatic cord and vas deferens, hematoma, and repair of contralateral patent processus vagi-
wound infection, iatrogenic cryptorchidism, tes- nalis (CPPV), uncommon types of hernias (femo-
ticular atrophy, and recurrence of hernia [9, 10]. ral, direct, combined hernia), and recurrent or
complicated hernias [4, 23]. During the first year
of life, the probability of finding a patent proces-
C. Esposito (*) · M. Escolino · A. Settimi
Department of Translational Medical Sciences, sus vaginalis (PPV) on the contralateral side may
Pediatric Surgery Unit, Federico II University, be up to 50% of cases [24], and the incidence of
Naples, Italy metachronous hernia ranges from 1 to 38% as
e-mail: [email protected] reported in different studies [25]. Recently, few
G. Cortese authors have reported successful treatment of
Department of Anesthesiology, Pediatric these infants through laparoscopy. Controversy
Anesthesiology Unit, Federico II University,
Naples, Italy remains about a possible increase in length of

© Springer Nature Switzerland AG 2019 351

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_26
352 C. Esposito et al.

operative time, costs, indications, and contraindi- a hydrocele, there is a painless swelling within the
cations and the need of orotracheal intubation for scrotum. It is larger in the evening than in the
anesthesia [26–28]. Difficulty in operative tech- morning. Clinical examination reveals a fluctuant
nique, comorbid conditions, and high anesthetic painless swelling, which may or may not be
risk in premature babies may be still the reasons reducible. Transillumination reveals a fluid-filled
for the preference of open repair in many centers scrotum, which may be bilateral above all in
[15]. Furthermore, the timing of IH repair in infants [33] (Fig. 26.2).
infants – early or delayed – still remains a matter
of debate.
26.2.2 Anesthesia

26.2 General Considerations The vast majority of infants and children under-
going surgical treatment of inguinal hernia
26.2.1 Diagnosis require pre-anesthetic medication and general
anesthesia [34].
As for the diagnosis of inguinal hernia, it is a clin-
ical diagnosis. In general, patients with hernia are
assessed by history and clinical examination [29].
Their history often reveals a sudden, intermittent
appearance of a bulge in the inguinal region or in
the scrotum during diaper change or after bathing.
This is also usually seen during crying or defeca-
tion [30]. In cases of hernia incarceration, it can
cause an intestinal obstruction, and the child may
have vomiting and abdominal distention. If the
hernia is incarcerated at the time of examination,
a mass is usually palpated in the inguinal region
[31] (Fig.  26.1). In girls, a small mobile mass
often appears in the groin or labia, which usually
represents an ovary [32]. The differential d­ iagnosis
of hernia from a hydrocele is important. In case of Fig. 26.1  A giant bilateral inguinal hernia in a newborn

Fig. 26.2  Transillumination, revealing a fluid-filled scrotum, confirms the diagnosis of hydrocele
26  Inguinal Hernia and Hydrocele 353

The anxiety of separation is enormously expe- respiratory function, while opioids produce a
rienced. The inherited, the personality, the previ- dose-dependent depression of medullary respira-
ous experiences, and the anxiety of parents are tory centers, also resulting in decreased respon-
the factors involved in the severity of the children siveness to partial pressure of carbon dioxide
anxiety. Recalling the early phases of anesthesia (PaCO2). For these reasons regional anesthesia is
which begins with the placement of anesthesia often used in combination with general anesthe-
mask and follows with the smelling of the anes- sia for pediatric surgery and has been shown to
thetic gas is an unpleasant experience. Some reduce general anesthetic requirements, opioid
medications such as benzodiazepines are used as use, postoperative nausea and vomiting, and pain
pre-anesthetic tranquilizers. Midazolam, in the [36, 37].
oral route, is a common pre-anesthetic medica- Pain is of the utmost concern in patient recov-
tion. Some studies reported the doses of 0.25 mg ery. By providing optimal pain management, pro-
to 1.0 mg/kg for midazolam, when employed as a viders can improve patient and parents’
pre-anesthetic tranquilizer. In regard to the gen- satisfaction, mobility, compliance, hemodynamic
eral anesthesia, it can be accomplished in many alterations from stress responses, and potentially
ways depending on the experience and prefer- even wound healing.
ence of the anesthesiologist. So the regional anesthesia is often used to
At the arrival in the operating room, in each supplement general anesthesia and provide post-
patient, pulse oximetry, heart rate, and noninva- operative analgesia. The most common forms
sive arterial blood pressure are monitored. used are regional nerve block or caudal anesthe-
Anesthesia is induced with sevoflurane 8% in sia performed after the induction of general anes-
oxygen 6  L/min via face mask. Sevoflurane is thesia [38].
currently one of the volatile agents of choice in As for the regional nerve block, the local anes-
pediatric anesthesia because of its acceptance for thetic is introduced at a puncture site 1 cm medial
inhalation induction. It is suitable because it has to the anterior superior iliac spine. Because the
a pleasant smell, it does not irritate the airways, nerves most commonly run below the external
and its blood-gas partition coefficient is slightly oblique, the needle is advanced until a “click” is
greater than that of desflurane or nitrous oxide. A felt as the needle passes through the external
vascular access is taken (22 or 24 gauge) after oblique, and the local anesthetic is injected.
loss of the eyelash reflex, and opioid is given to Caudal block is performed by injecting local
maintain a suitable depth of anesthesia. anesthetic into the epidural space via the sacral
Airway management using laryngeal mask or hiatus. Standard dosing provides neuraxial block-
endotracheal tube is an acceptable alternative ade of sensory input at and below the T10/umbili-
[35]. The relative ease of insertion and lower rate cal dermatome [39].
of airway complications compared to endotra- Finally, the intranasal use of clonidine to
cheal intubation make laryngeal mask use a logi- awakening is interesting [40].
cal choice, but the use of an endotracheal tube is Clonidine acts as an agonist at a2 adrenocep-
the safest strategy for the patient with a full stom- tors. The locus ceruleus (LC) is the site of action
ach and an irreducible inguinal hernia and for for the sedative effect of clonidine. The LC con-
laparoscopic surgery. tains a high density of a2 adrenoceptors.
Anesthetics produce dose-dependent and Following binding of clonidine to a2 adrenocep-
drug-specific changes in the mechanics and in the tors, hyperpolarization of noradrenergic signal-
central control of the respiratory center. Inhaled ing to the ventrolateral preoptic area (VLPO)
anesthetics decrease muscle tone within the air- occurs, thus producing sedation.
ways, chest wall, and diaphragm, in addition to The drug is rapidly absorbed by the nasal route
inhibiting central respiratory drive and respon- and peak plasma levels are reached within 10 min.
siveness to ventilatory stimulants such as carbon No sign of irritation or edema in the nasal cavity
dioxide. Intravenous anesthetics may also alter has been observed after a single dose. Intranasal
354 C. Esposito et al.

administration of drugs is an easy and minimally use of regional anesthesia (spinal, epidural, or cau-
invasive alternative route of administration: a rel- dal) has a role in decreasing the risk of a postop-
atively large surface area is available for drug erative respiratory complication as compared with
absorption, and a thin, very vascularized epithe- general anesthesia [36, 46]. Perhaps this decreased
lium ensures rapid absorption and onset of thera- risk may lead to a decreased need for inpatient
peutic action by avoiding the first-pass effect. postoperative monitoring in the ex-premature
infant after an inguinal hernia repair.

26.2.3 Anesthetic Risks in Premature

Infants 26.2.4 Timing of Repair

Premature infants are at a higher risk for develop- Surgery is indicated for all pediatric patients where
ing postoperative respiratory complications com- a diagnosis of inguinal hernia has been made [6,
pared with full-term and even older premature 7]. However, the timing of surgical repair in pre-
infants [29]. Steward reported that 33% of pre- mature infants is controversial [13, 29]. In a small
mature infants undergoing hernia repair devel- premature infant, the operation is technically more
oped respiratory complications, most commonly difficult and associated with a higher morbidity,
apnea [41]. All of the infants with apnea weighed including an increased incidence of testicular atro-
less than 3  kg at the time of surgery and were phy and recurrent hernias [14]. Furthermore, the
under 10 weeks of age. anesthetic risk is higher in a premature infant.
Allen and coworkers reported an association Some debate exists about the optimal time to
with the use of intraoperative narcotics and mus- repair the asymptomatic hernia found in a prema-
cle relaxants and the incidence of postoperative ture infant in the neonatal intensive care unit
apnea-bradycardia episodes in ex-premature (NICU). The factors that must be considered in
infants with a postconceptual age of <60 weeks making the decision when to operate include the
[42]. Warner and coworkers found that a history technical difficulties of a fragile hernia sac and
of apnea or respiratory distress syndrome signifi- higher risk of injury to the vas deferens or the tes-
cantly increased the chance of a postoperative ticular vessels, the presence of comorbid condi-
respiratory event in premature infants undergoing tions associated with prematurity, and the
herniorrhaphy [43]. A history of bradycardia or anesthetic risks in a premature infant. Because of
ventilatory support for 24  hours or more after the risks of surgery in the premature infant, many
birth was also a significant risk factor. surgeons used to discharge patients home from the
The anesthetic risk for former preterm infants is neonatal intensive care unit (NICU) and repair
inversely proportional to the postconceptual age. their hernia once they reached a certain age or
However, there is still some controversy about the weight. With recent advances in anesthesiology
minimum postconceptual age that reduces the and neonatal care, many surgeons have moved
chance of a postoperative anesthetic event. Several toward performing an early hernia repair before
studies have attempted to address this question, discharge from the NICU [3, 47, 48]. Proponents
leading to recommendations ranging from 40 to of immediate repair [31] justify the risk of an early
60  weeks postconceptual age [44, 45]. Although operation based on an increased risk of incarcera-
the postconceptual age has been shown to be the tion with a longer waiting period before surgical
major risk factor, the presence or absence of a his- repair. Others advocate waiting until an arbitrary
tory of preoperative apnea or the need for ventila- weight or age criteria has been met, thereby opti-
tory support also influences the safety of mizing some of the associated morbidities [49].
performing an outpatient procedure. Some studies Vaos in 2010 and Uemura in 1999 demon-
also show that the presence of anemia is an inde- strated that the sooner the patients are operated on
pendent risk factor for a postoperative apneic event upon diagnosis, the lower is the risk of complica-
[44, 45]. Recent literature has suggested that the tions [50, 51]. Conversely, Lautz and colleagues
26  Inguinal Hernia and Hydrocele 355

recently stated that delaying surgery of newborns 26.3.1 Open Inguinal Approach
and ex-preterms after discharge from the hospital
does not increase the risk of complications [52]. Open technique of inguinal hernia repair
Pini Prato et al. strongly recommended to per- requires an inguinal approach. An inguinal inci-
form herniotomies before discharge for neonates sion of about 3–4 cm is made on the ipsilateral
diagnosed during hospital stay and to schedule as side to the symptomatic inguinal hernia. The
soon as possible (within a month) those who procedure involves the separation of the hernia
present to the outpatient clinic [3]. sac from the surrounding cord structures, includ-
In our practice, we typically repair neonatal ing cremaster muscle, vas deferens, and the tes-
inguinal hernias before discharge from the ticular vessels or round ligament. This must be
NICU. If the family is reliable, however, and the done using atraumatic dissection without seizing
repair cannot be easily scheduled without pro- the vas and/or vessels as to avoid vas occlusion
longing the hospital stay, we perform the opera- or testicular atrophy. A ligature is usually applied
tion soon after the discharge. to the separated sac, and the distal sac is divided.
There is no evidence in the literature if it is pref-
erable to adopt a resorbable or a non-resorbable
26.3 Operative Techniques suture (Fig.  26.3). In general during the open
repair of a unilateral inguinal hernia, there is no
Inguinal hernia in children can be treated through check of contralateral patency. In the 1980s
either an open or laparoscopic approach. French pediatric surgeons described the tech-

Fig. 26.3  Open inguinal hernia repair requires an inguinal incision, separation of the hernia sac from the surrounding
cord structures, ligature, and division of the hernia sac
356 C. Esposito et al.

nique to check the presence of a contralateral The laparoscopic approach can be performed
peritoneal vaginal duct or hernia consisting in either transperitoneally or through a pre-­
the passage of a 45- or 70-degree angled tele- peritoneal approach (using special needles) with
scope through the hernia sac prior to ligation transperitoneal visualization [60].
(hernioscopy) [53]. This technique of contralat- The laparoscopic technique that we com-
eral video control requires the use of the laparo- monly adopt is the classic transperitoneal
scopic video column, the creation of the approach using three ports. The patient is always
pneumoperitoneum, and the use of the optic and placed in supine position with a 15°–20°
all laparoscopic equipment; for this reason this Trendelenburg inclination of the operative table
procedure is rarely adopted in the clinical to reduce the intra-abdominal pressure (IAP) and
practice. abdominal contents. The surgeon is positioned at
the head of the patient and the camera operator
contralaterally to the side of pathology, and the
26.3.2 Laparoscopic Approach screen is placed at the feet of the patient. Average
IAP is 6–8 mmHg in patients under 1 year of age.
Laparoscopic inguinal hernia repair (or hernior- The emptying of the bladder using a Nelaton
rhaphy) (LH) in children has been introduced as catheter is performed before surgery.
an alternative method to conventional open herni- A 0° telescope of 5–10 mm through an umbili-
otomy (OH) and first described by Montupet in cal port is used, allowing direct visualization of
1993 [26–28, 54]. Regarding the technical point the deep inguinal rings, followed by the use of
of view, there are many techniques now described two 3-mm trocars in triangulation to keep a good
for LH repair [55, 56]. The different repair ergonomics. As for the optic, the use of a 5- or
options can be categorized as either intracorpo- 10-mm optic gives the same invisible scar in the
real or extracorporeal/percutaneous. In regard to navel; for this reason the use of a 5- or 10-mm
intracorporeal repairs, in 1993 Montupet firstly optic depends on the instruments’ availability. As
described the technique, consisting in a purse-­ for the operative 3-mm trocars, the majority of
string suture performed on the periorificial peri- authors prefer to adopt screw trocars. The advan-
toneum at the level of the internal inguinal ring tage of using screw trocars is fundamental above
[26–28]. In 1998, Schier introduced his tech- all in infants under 10 kg; in fact, in these catego-
nique, consisting in an “N”-shaped suture on the ries of patients, the tissues and the skin are very
periorificial peritoneum [54]. In 2004, Becmeur thin, and the smooth trocars tend to slip out easily
and coworkers described the laparoscopic divi- creating a subcutaneous emphysema. Screw tro-
sion and resection of the hernia sac at the level of cars are more stable, and in addition you can
the internal ring with subsequent closure of the change instruments rapidly, without dislodge-
peritoneal edges [57]. ment of the trocars and without gas leaks
The extracorporeal techniques all involve the (Fig. 26.4). In case you have only smooth trocars,
placement of a suture circumferentially around you can put a piece of Nelaton catheter around
the internal ring and tying the knot using percuta- the cannula and then fix the piece of Nelaton
neous techniques [58]. Loads of variations of this catheter to the skin to stabilize the trocar
approach have been described. Recently, Ostlie (Fig. 26.4).
and Ponsky stated that there is no sufficient evi- Some surgeons prefer to use instruments with-
dence to support one approach or another [56]. out the assistance of trocars (stub incision); also
However, the addition of the peritoneal incision if using this technique, it may be difficult to
intentionally created at the level of the internal change instruments.
inguinal ring, as reported by Esposito, seems to The first step of the laparoscopic procedure
result in a more durable repair [6, 7, 59]. consists of checking the patency of the peritoneal
26  Inguinal Hernia and Hydrocele 357

10  mm or larger, it is preferable to perform a

a
purse-string suture according to Montupet’s tech-
nique, whereas in orifices of about 5  mm or
smaller, an N-shaped suture according to Schier’s
technique or a purse-string suture may be adopted
as well.
It is also important to well close the medial
part of the ring, in particular the peritoneum
between the inner spermatic vessels and the vas,
because this is the most frequent location of
b recurrences.
As for technical point of view, the needle has
to be introduced into the abdominal cavity trans-
parietally and then removed transparietally or
transumbilically. The preferred needle to use is
3/8 of circle with a 20–22-mm needle. To per-
form a unilateral closure, the length of suture has
to be 13–15 cm; for a bilateral repair, it has to be
15–20 cm, according to the surgeon’s preference.
The trocar orifice is closed with stitches or glue.
Fig. 26.4  Trocars used for laparoscopic hernia repair: (a) Percutaneous internal inguinal ring (PIRS)
smooth trocar with a piece of Nelaton catheter around the technique is the most common percutaneous
cannula to be fixed to the skin to stabilize the trocar; (b)
screw trocar method for inguinal hernia repair, and it was
firstly described by Patkowski in 2006 [61]. In
this method, after induction of pneumoperito-
vaginal duct as well as the inspection of the neum and visualization of internal inguinal ring,
­contralateral side for the presence of a contralat- a 2-mm stab incision is made to correspond to
eral patent processus vaginalis (CPPV). In case above the internal ring. An 18-G angiocath nee-
of incarcerated hernia, before closing the defect, dle with a 2/0 nonabsorbable monofilament
it is necessary to reduce the hernia by releasing suture loaded as a loop is passed on one side of
incarcerated elements like epiploon, intestinal the internal ring, entering and leaving the perito-
loops, appendix, or ovaries. The next step con- neal cavity several times. The loop is introduced
sists in circumferentially cutting the periorificial into the peritoneal cavity at the farthest opposite
peritoneum, distally to the internal inguinal ring, aspect that the needle allows. The 18-G angiocath
by using a monopolar hook. We consider the sec- is then introduced on the other side of the internal
tion of the periorificial peritoneum a key point of ring, entering and leaving the peritoneal cavity
the technique, because using this expedient there several times, once again passing to the farthest
is the collapse of the distal part of the sac and opposite side the needle allowed. The needle is
consequently there is no tension on the suture then passed through the previously introduced
line in closing the internal ring. The deep ring is loop. A 2/0 nonabsorbable monofilament suture
then closed, after sectioning the periorificial peri- is then passed through the needle. After removal
toneum, with a resorbable or non-resorbable of the needle, the loop is withdrawn, catching the
suture, performing either a purse-string suture as second suture and passing it out of the stab inci-
described by Montupet (Fig. 26.5) or an N suture sion. After manual reduction of gas from the her-
as described by Schier (Fig. 26.6). In general, if nia sac, the suture is then tied, obliterating the
the diameter of the inguinal orifice is of about internal ring (Fig. 26.7).
358 C. Esposito et al.

a b

c d

Fig. 26.5 Laparoscopic hernia repair according to (c) a purse-string suture is placed on the periorificial
Montupet’s technique: (a) the periorificial peritoneum is peritoneum; (d) the hernia defect is closed
sectioned; (b) the needle is introduced transparietally;

a b

Fig. 26.6  Laparoscopic hernia repair according to Schier’s technique: (a) an N-shaped suture is placed on the periori-
ficial peritoneum; (b) the hernia defect is closed
26  Inguinal Hernia and Hydrocele 359

Fig. 26.7  Percutaneous internal ring suturing (PIRS) technique

26.3.3 Tips and Tricks In very small babies, under 3  kg of weight,

of Laparoscopic Repair where the working space is extremely limited,
in Infants you can also place a balloon trocar in the umbili-
cus for the optic; in this way, during the interven-
From a technical point of view, the laparoscopic tion, the cameraman can lift up the trocar without
repair is more technically demanding in infants dislodging it, thus creating more working space
because of the visual restriction and the very into the abdominal cavity; or, alternatively, you
small working space available, due to bowel dis- can put a transabdominal stitch, passed transpari-
tension. For this reason, it is useful to perform a etally, and use it to lift up the abdominal wall.
bowel preparation the day before operation in In regard to trocar insertion, it is sometimes
such patients, with one or two enemas and safer to insert the working ports through the can-
simethicone per os in order to empty the intesti- nula of the umbilical optic trocar (“trocar in tro-
nal loops of gas and to allow the creation of a car”), considering the limited working space in
larger working space into the abdominal cavity newborns (Fig. 26.8).
[26–28]. Another important point of the technique in
In regard to port position, in small infants, we infants is to adopt 3-mm screw trocars that remain
do not have a true triangulation between the optic stable during the entire procedure, in particular
and trocars because the two working ports used during the change of instruments. In case you
for instruments are located higher compared with have only smooth trocars, you can put a piece of
the usual position. In fact, we prefer to place Nelaton catheter around the cannula and then fix
them on the umbilical line at the same level of the the piece of Nelaton catheter to the skin to stabi-
optic to create more distance between the ports lize the trocar (Fig. 26.4). As for the needle size,
and the internal inguinal ring [16, 18, 20]. it is difficult to manage large needle in premature
360 C. Esposito et al.

A nonreducible hernia in children requires opera-

tive exploration.
These hernias, unless treated, are likely to
progress to strangulation and infarction. The ini-
tial management of an incarcerated inguinal her-
nia without strangulation should be nonoperative
[62]. Analgesia or sedation can also be used to
aid the reduction of an incarcerated hernia.
Reduction may spontaneously occur prior to a
manual attempt, if the infant’s buttocks are ele-
vated slightly to assist in the reduction of hernia
contents. The hernia is palpated distally, while
the clinician’s fingers are located to the proximal
Fig. 26.8  In newborns, it is safer to perform insertion of neck of the hernia. Compression of the hernia can
working trocars through the cannula of the optic trocar then occur. The pressure is maintained slowly
(“trocar in trocar”) and consistently until the hernia is reduced.
Gentle compression is usually successful in 70 to
infants; probably the needle length has to be 85% of patients [63], and an elective repair can
maximum of 17–20 mm, because larger needles be performed in 24–48 h. This time allows some
are difficult to manage with a higher risk of resolution of the edema, minimizing the diffi-
complications. culty of the dissection and the risk of complica-
In addition, it is important to use a CO2 flow of tions. However, failure to reduce the hernia, even
1  L/min and to maintain the intra-abdominal with sedation, is an indication for an immediate
pressure (IAP) around values of 6–8  mmHg operation.
throughout the operation in order to avoid anes- The operative management is determined by
thesiologic problems during and after the the viability of the intestine. If the incarcerated
intervention. intestine is viable, the surgeon can simply reduce
In regard to the operative technique, it is also the hernia and perform a high ligation of the sac.
important to close well the medial part of the If the intestine is no longer viable, it should be
internal inguinal ring, in particular the perito- resected, either through the sac or through a sepa-
neum between the inner spermatic vessels and rate abdominal incision. An incarcerated hernia
the vas deferens, because this is the location of in an infant is more technically difficult and has a
most of recurrences [16, 18, 20]. higher complication rate since the hernia sac is
By adding these technical refinements, LH has typically edematous and fragile. The testicular
become an easy approach in tough repairs such as vessels and the vas are particularly susceptible to
neonatal inguinal hernias. injury because of the edema and often difficult
dissection.
It has been reported that probably one of the
26.4 Management of Incarcerated main advantages of laparoscopy is in the cases of
Inguinal Hernias nonreducible hernias [64]. In fact thanks to lapa-
roscopic traction and the manual pressure from
The incidence of inguinal hernia incarceration the outside, it is easy to reduce hernia content,
has been reported in the general pediatric popula- and in case of vascular damages of appendix or
tion to be between 6 and 18% [29]. However, the bowel loops, it is easy to exteriorize the specimen
risk of incarceration is higher in infancy, with a through the umbilicus and to perform a bowel
reported incidence of approximately 30% [62]. resection (Fig. 26.9).
26  Inguinal Hernia and Hydrocele 361

orchidism, testicular atrophy, incidence of

metachronous hernia, and contralateral patent
processus vaginalis (CPPV) (Table 26.1).

26.5.1 Recurrence

Recurrence rate was significantly higher after

OH compared with LH (2.6 vs. 1.9%, p = 0.001).
It has been reported that low gestational age
and specific comorbidities may be associated with
a higher likelihood of recurrence. However, con-
sidering the operative technique, the medial
Fig. 26.9  Laparoscopic view of a left incarcerated ingui-
nal hernia in a newborn
aspect of the internal inguinal ring is the most cru-
cial [16, 18, 20]. The great advantage of laparo-
scopic approach over open technique could be
26.5 O
 utcome Analysis of Open due to the better visualization of the medial aspect
and Laparoscopic Inguinal of the internal inguinal ring allowed by laparos-
Hernia Repair in Neonates copy. On the upper part of the internal inguinal
and Premature Infants ring, slightly more tissue is usually included, not
only in the peritoneum but also in some underly-
In the last decade, despite laparoscopic inguinal ing musculature. On the lower part of the ring,
hernia repair (or herniorrhaphy) (LH) becoming however, less tissue is present because more cru-
popular in older children, there are few reports in cial nerves and vessels are present. For this rea-
newborns. Most recently published series have son, it is important to put the most medial stitches
reported encouraging results [16, 18, 20, 21]. The as close as possible to the epigastric vessels and
use of LH in neonates is a technically demanding vas deferens. A tightened closure of the inguinal
procedure because intracorporeal suturing ring seems to reduce the recurrence rates [20, 21].
requires to be done in a very limited working In addition, the key of the success is the use of
space. However, open herniotomy (OH) in new- nonabsorbable suture, together with the section
borns is also considered a technically demanding of periorificial peritoneum, as long as the medial
surgery with an increased overall rate of postop- side of PPV is properly closed [6, 7].
erative complications (recurrence, testicular
hypotrophy/atrophy, high testis) compared to
older children [11]. Serious intraoperative com- 26.5.2 Wound Infection
plications such as bladder injury or rupture can
also occur in open surgery with excessive mobili- Studies focused on LH reported fewer wound
zation of the sac [20]. Miyano et al. reported the infection rates (range 0–1.6%) compared with the
need for sigmoidocolocystoplasty for bladder studies focused on the inguinal open approach
augmentation after a bladder injury caused by (range 1.1–2.3%). However, looking at the aver-
open herniotomy [65]. age values, the difference between the two groups
Analyzing literature reports focused on is not statistically significant (LH  =  0.8% vs.
open and laparoscopic inguinal hernia repairs OH = 1.1%, p = 0.66).
in newborns and/or premature infants, outcome In our opinion, the higher wound infection
parameters reported included postoperative rate following OH may be due to the fact that the
hydrocele, wound infection, iatrogenic crypt- laparoscopic scars are located higher on the
 362

Table 26.1  Outcome analysis of OH and LH series in neonates and premature infants
Acquired
cryptorchidism Testicular
Reference LH OH Recurrence requiring surgery atrophy Wound infections Hydrocele CPPV MIH
Turial et al. [20] 147 4 (2%) 7 (4.1%) 0 1 (0.4%) 0 61 (57%) 1 (0.4%)
Pastore et al. [21] 30 0 3 (10%) 0 0 0 12 (63%) 0
Esposito et al. [16, 18] 67 3 (4.4%) 4 (5.9%) 0 0 0 NR 0
Pini Prato et al. [3] 184 8 (4.5%) 1 (0.5%) 5 (2.7%) 2 (1.1%) 4 (2.2%) NR 13
(10.5%)
Chan et al. [15] 79 1 (1.3%) 0 0 0 0 52 0
(66%)
Choi et al. [66] 299 4 (1%) 1 (0.3%) 1 (0.3%) 5 (1.6%) 4 (1%) 136 (54%) 0
Hughes et al. [67] 408 8 (1.9%) 10 (2.4%) 2 (0.4%) 5 (1.2%) 1 (0.2%) NR 26
(6.3%)
Nagraj et al. [11] 221 5 (2.3%) 6 (2.7%) 6 (2.7%) 5 (2.3%) 0 NR NR
Marinkovic et al. [68] 144 3 (2%) NR 1 (1%) NR NR NR 7
(5%)
Krieger et al. [13] 24 1 (4.2%) NR 2 (8.4%) NR NR NR NR
Saha et al. [69] 30 1 (3.3%) 0 0 NR 2 (6.6%) 18 (66%) 0
Saha et al. [69] 32 2 (6.0%) 0 0 NR 1 (3.0%) NR 2 (7.4%)
Lin et al. [70] 24 0 NR NR NR NR 13 (65%) 0
Lin et al. [70] 31 1 (3.2%) NR NR NR NR NR 4 (18%)
LH laparoscopic herniorrhaphy, OH open herniotomy, NR not reported, CPPV contralateral patent processus vaginalis, MIH metachronous inguinal hernia
C. Esposito et al.
26  Inguinal Hernia and Hydrocele 363

abdominal wall compared with inguinal scars, at 1  year of age according to the guidelines for
which are inside the diaper area; for this reason management of undescended testis [16, 18].
they are subject to urine or fecal contamination, Postoperative hydrocele is recognized as a
which may lead to a higher infection rate. common complication but it has been rarely dis-
cussed. Some authors reported a higher incidence
of hydrocele following incarceration. The reason
26.5.3 Iatrogenic Cryptorchidism, for this association remains unknown; probably
Testicular Atrophy, severe inflammation and derangement of the
and Hydrocele tunica vaginalis surrounding the testicle may
explain this issue [3].
Incidence of testicular atrophy following OH in
infants and premature babies was significantly
higher compared with LH approach (1.5 vs. 26.5.4 Metachronous Inguinal
0.1%, p = 0.001). Hernia (MIH)
Acquired cryptorchidism requiring surgery did and Contralateral Patent
not show any significant difference between LH Processus Vaginalis (CPPV)
series (average 2.2%; range 0.3–10%) and OH
ones (average 1.6%; range 0.5–2.7%) (p = 0.30). Studies focused on OH reported an incidence of
Also postoperative hydrocele rates did not metachronous inguinal hernia (MIH) ranging
show any significant difference between LH from 5% [68] to 18% [70]. A paper focused on
series (average 0.8%; range 1–6.6%) and OH LH recorded one case of MIH (0.4%) [20].
ones (average 0.5%; range 0.2–3.0%) (p = 0.30). Six studies reported the coexistence of a uni-
The etiology of testicular atrophy and malde- lateral inguinal hernia with a contralateral patent
scending testes in infants following hernia repair processus vaginalis (CPPV), with an incidence of
is poorly understood. It has been reported that tes- contralateral patency between 54% [66] and 66%
ticular atrophy has the highest incidence after [15, 69].
incarceration [12]. It may be either due to prema- Considering the high incidence of CPPV in
turity and low weight at the time of surgery or patients with unilateral inguinal hernia under-
associated with demanding surgery [3]. During went LH, another clear advantage of laparoscopic
laparoscopic repair, the risk of complications repair is to treat bilateral inguinal hernia in the
associated with dissection is minimized. same operation or close a CPPV in order to pre-
Laparoscopic surgery approaches the internal ring vent future metachronous hernia [26–28, 72].
without any dissection of the abdominal wall or This is particularly important for newborn and
spermatic cord structures. This advantage is preterm babies, in whom the risk of MIH is
important, especially in neonates, in whom the higher, thus obviating the need for a second oper-
vas deferens and the vessels are very small and the ation and thus anesthesia and reducing both eco-
hernia sac is very friable and fragile [16, 18, 20]. nomic impact and risk to the patient [21].
Laparoscopic purse-string closure of internal
ring has been reported to cause holding up of the
testis by entangling its vaso-vasal pedicle. It is not 26.5.5 Other Advantages
very clear if the high-lying testis is the result of of Laparoscopic Inguinal
arrested normal descend or the result of testicular Hernia Repair in Infants
ascend following purse-string suture [71]. In our
experience, all patients who developed iatrogenic It has been reported that laparoscopy presents
cryptorchidism following LH presented a testis several other advantages over open surgery in the
located in high scrotal position at the moment of treatment of inguinal hernia in infants. First of
the operation, and we decided preoperatively all, laparoscopy permits to identify and treat rare
together with the parents to correct this condition and uncommon types of hernia, such as direct
364 C. Esposito et al.

hernias, femoral hernias, double hernias, and the

so-called hernia en pantalon [16, 18].
In case of direct hernia, a key point of the
technique is to remove the lipoma always pres-
ent in this pathology and to close the defect
using a purse-string suture or separated stitches.
In case of a huge hole, the lateral bladder liga-
ment can be adopted in order to reinforce the
closure [16, 18, 73].
In addition, laparoscopy is particularly helpful
in patients who experience a hernia recurrence
after initial repair, whether from previous open
surgery or a laparoscopic approach. In fact, in
those cases, the manipulation of the sac sur-
rounded by a thigh scar can be dangerous and Fig. 26.10  Cosmetic outcome 6  months after laparo-
harmful for the cord, whereas the intra-­abdominal scopic inguinal hernia repair
laparoscopic closure of the internal ring can be
less traumatic and even less technically demand- laparoscopy and inguinal approach is preferable
ing. In such cases laparoscopy permits to identify to repair an inguinal hernia in infants.
and treat the cause of recurrence [74]. Age, size, and weight of the child are not lim-
Another advantage of laparoscopy may be in iting factors for the laparoscopic approach in
the management of incarcerated hernias, espe- terms of surgical technique. Anesthetists tend to
cially in infants. In fact, the reduction of the object to laparoscopy for small children consid-
incarcerated loops can be facilitated using both ering the risk of opening right-to-left shunts due
laparoscopic reduction and with external manual to the increased intra-abdominal pressure.
reduction. The pneumoperitoneum may also help However, despite a steep learning curve for
to widen the internal ring, allowing an easier pediatric anesthesiologists, patient safety has
reduction. Immediate inspection of the incarcer- increased generally as laparoscopy has become a
ated bowel status is possible before closing the routine procedure. Only patients with clear con-
peritoneal vaginal duct (PVD), allowing resec- traindications with laparoscopy, including respi-
tion if necessary. Furthermore, the hernia could ratory distress syndrome, severe
be immediately repaired, perhaps avoiding the bronchodysplasia, or other medical conditions,
edematous tissues and decreasing the higher should be offered open herniotomy.
complication rate associated with incarcerated On the basis of our 20-year experience [55],
hernias [64, 75]. we believe that laparoscopic hernia repair is a
An improvement in the cosmetic outcome is safe and easy procedure to perform also in infants
another proposed advantage of laparoscopic and small babies and a strict collaboration with
technique (Fig. 26.10). anesthesiologist is fundamental for the good out-
Despite LH having always been considered a come of the procedure.
time-consuming procedure, more reports showed
that operative time of LH is not only comparable
with operative time of OH [76] but also, espe- 26.6 Current Management
cially in neonates and certainly in bilateral ingui- of Hydrocele
nal hernias, it could be shorter when the
laparoscopic surgeons have gained enough expe- When examining a child with an inguinal hernia,
rience [21, 26–28]. a hydrocele must be considered in the differential
It is clear that there is no definitive evidence in diagnosis. This determination can typically be
the literature about which technique between made by clinical examination. By palpation, one
26  Inguinal Hernia and Hydrocele 365

can feel the narrowing of the hydrocele neck at 4. Parelkar SV, Oak S, Gupta R, Sanghvi B, Shimoga
PH, Kaltari D, Prakash A, Shekhar R, Gupta A,
the external inguinal ring without extension into Bachani M. Laparoscopic inguinal hernia repair in the
the inguinal canal. Ultrasound can also be helpful pediatric age group—experience with 437 children. J
in making this distinction. The patent processus Pediatr Surg. 2010;45(4):789–92.
vaginalis spontaneously closes over a period of 5. Holcomb GW 3rd, Brock JW 3rd, Morgan WM 3rd.
Laparoscopic evaluation for a contralateral patent
1–2  years in most instances. Therefore, most processus vaginalis. J Pediatr Surg. 1994;29(8):970–
pediatric surgeons avoid operation within the first 3. discussion 974
1 to 2  years of life unless a hernia cannot be 6. Esposito C, Escolino M, Settimi A.  Laparoscopic
excluded. After the age of 2 years, the hydrocele pediatric inguinal hernia repair using purse-string
suture: technical recommendations after 20 years
is unlikely to resolve and an operation is required. experience. J Laparoendosc Adv Surg Tech A.
If the hydrocele shows signs of communication 2016a;26(9):748–9.
(frequently changing in size), then there is a sig- 7. Esposito C, Escolino M, Turrà F, Roberti A, Cerulo
nificant exchange of fluid between the peritoneal M, Farina A, Caiazzo S, Cortese G, Servillo
G, Settimi A.  Current concepts in the manage-
cavity and the hydrocele sac. Many pediatric sur- ment of inguinal hernia and hydrocele in pediatric
geons choose to repair a communicating hydro- patients in laparoscopic era. Semin Pediatr Surg.
cele earlier [29]. 2016b;25(4):232–40.
The surgical procedure is the same described 8. Misra D, Hewitt G, Potts SR, Brown S, Boston
VE.  Inguinal herniotomy in young infants, with
for the open inguinal hernia repair. A high liga- emphasis on premature neonates. J Pediatr Surg.
tion of the patent processus vaginalis is per- 1994;29(11):1496–8.
formed through a groin incision, and in case of 9. Esposito C, Montinaro L, Alicchio F, Scermino S,
communicating hydrocele, the distal fluid col- Basile A, Armenise T, Settimi A. Technical standard-
ization of laparoscopic herniorrhaphy in pediatric
lection should be emptied. This often requires patients. World J Surg. 2009;33(9):1846–50.
an incision distally, down to the scrotal tunica 10. Schier F. Laparoscopic inguinal hernia repair: a pro-
vaginalis, to release any residual fluid. In case of spective personal series of 542 children. J Pediatr
communicant hydrocele, laparoscopic repair Surg. 2006;41(6):1081–4.
11. Nagraj S, Sinha S, Grant H.  The incidence of com-
can be proposed. It is similar to laparoscopic plications following primary inguinal herniotomy
treatment of inguinal hernia, the fluid is aspi- in babies weighing 5 Kg or less. Pediatr Surg Int.
rated, and the PVD is closed with a purse-string 2006;22:500–2.
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However, at the moment, the preferred tech- 2001;5(2):92–6.
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In our practice, we recommend a groin explo- Pediatr Surg. 1994;29:978–82.
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Laparoendosc Adv Surg Tech A. 2014;24(3):194–8. niotomy in prematurely born infants. Med Pregl.
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R, Grandadam S, Lieber A, Toledano D.  A con- 69. Saha N, Biswas I, Rahman MA, Islam MK. Surgical
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in 3 pediatric surgical institutions. J Pediatr Surg. 71. Raveenthiran V.  Controversies regarding neonatal

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 Intestinal Malrotation
and Volvulus 27
Luisa Ferrero, François Becmeur,
and Olivier Reinberg

27.1 Introduction of the duodenum and wrote a reference article on

the treatment of malrotation, describing his surgi-
Intestinal malrotation is a common name for a large cal approach, the “Ladd’s procedure,” which still
variety of abnormalities of intestinal rotations and remains today the basic rules of good practice
attachments that occur during fetal development. [1]. By the 1950s Snyder and Chaffin [6] in the
United States and Grob [7, 8] in Switzerland have
done much to clarify our understanding of these
27.2 History malformations. Most of the available drawings
are reproductions of the initial drawings by Grob.
The first cases of malrotation were reported in the
literature in the mid-1700s [1, 2]. No progress
was made until normal intestinal embryology 27.3 Epidemiology
was first described by Meckel in 1817 [3] and
then later by Mall in 1897 who wrote the first The true incidence of malrotation remains
description of the embryology of the midgut [4]. unknown. According to literature it ranges from
In 1923, Dott applied the embryology to the 1/6000 [9, 10] to 1/200 [11] of all live births.
understanding of intestinal malrotations. Based Autopsy studies estimate that it may be as high as
only on five clinical observations, he correlated 1% of the total population [9, 12]. Males are
them with the sequences of embryological devel- more frequently affected than females with a
opment describing theoretically many of the ratio of 2:1 [6, 13, 14].
potential errors and their consequences without Case reports have suggested a strong concor-
having seen them [5]. In 1931, William E. Ladd dance of intestinal malrotation between identical
presented in a seminar five cases of obstruction twins and even between non-twin siblings.
Genetic factors may thus play some role in its
L. Ferrero pathogenesis [15–18].
Department of Pediatric Surgery, Regina Margherita Most cases of malrotation are discovered in
Children’s Hospital, Turin, Italy the first few months of life, and of those, most
F. Becmeur will present within the first week of life.
Department of Pediatric Surgery, University Approximately 90% are discovered before 1 year
Hospitals, Strasbourg, France
e-mail: [email protected] of age. However a significant percentage of
patients reach adulthood with an undiagnosed
O. Reinberg (*)
Department of Pediatric Surgery, Lausanne, malrotation [19]. Unfortunately, for those patients
Switzerland delays in diagnosis are common.

© Springer Nature Switzerland AG 2019 369

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_27
370 L. Ferrero et al.

27.4 Embryology cord with the SMA forming the axe of a U-loop
in the sagittal plane (Fig. 27.1a).
The final anatomic arrangement of the midgut As it protrudes, the midgut makes a first rota-
follows a complex series of events [6]. By the 4th tion of 90° counterclockwise, so its distal part
week of fetal life, the embryo is about 5 mm, and comes to the left, and its proximal part is to the
the primitive intestine is an almost straight tube, right. The loop is now in a horizontal plane. The
the same length as the ectodermal and mesoder- distal part of the loop develops a pouch that will
mal germ layers, and lays on the midline. It con- become the cecum. The proximal part of the loop
sists, cephalad-caudally, in the foregut, midgut, becomes tortuous. These loops still lie outside
and hindgut. the abdominal cavity (Fig. 27.1b).
Rotation of the midgut happens during the 2nd By 10 weeks, the body of the embryo is now
month of the fetal life, to become the medial part large enough for the bowel to develop inside the
of the gastrointestinal tract (GIT). At this stage abdomen, so the midgut reintegrates the abdo-
the midgut is in continuity with the vitelline duct men. The proximal part of the loop returns first. It
inside the umbilical duct and still connected to passes under the distal one and comes to the left
the yolk sac. The aorta gives blood supply to the making a second 90° counterclockwise rotation.
GIT through three arteries, respectively, the coe- Then the distal part follows it passing in front of
liac artery for the foregut, the superior mesenteric the proximal part and rotates to the right. This is
artery (SMA) for the midgut, and the inferior making the third 90° counterclockwise rotation.
mesenteric artery for the hindgut. With this development, the proximal part of the
The GIT develops faster than the coelomic midgut becomes placed posteriorly to the distal
cavity resulting in a lack of space. Thus by one that will become the transverse colon with
6 weeks, it forced to herniate inside the umbilical the SMA between them (Fig. 27.1c).

a b c

Fig. 27.1  Normal embryological development of the of 90° counterclockwise, so its distal part comes to the
midgut [23]. (a) The midgut has not rotated yet and left, and its proximal part is to the right. The loop is now
remains in a sagittal plane. The aorta gives blood supply to in a horizontal plane. The distal part of the loop develops
the GIT through three arteries, respectively, the coeliac a pouch that will become the cecum. (c) The second 90°
artery for the foregut (up), the superior mesenteric artery counterclockwise rotation. The proximal part of the loop
(SMA) for the midgut (middle), and the inferior mesen- returns first, passes under the distal one, and comes to the
teric artery for the hindgut (lower). It forms an U-loop left. The distal part follows it passing in front of the proxi-
around the SMA. (b) The midgut has made a first rotation mal part and rotates to the right
27  Intestinal Malrotation and Volvulus 371

At this time, both parts of the midgut have which errors occur during these organogenetic
rotated 270° in a counterclockwise manner. Then steps either by omission or by opposite rotation(s).
the period of fixation lasts until after birth. The Three main types are described, i.e., nonrotation,
descending and ascending colon mesenteries fuse partial malrotation, and reversed malrotation [6,
with the retroperitoneum, and the small bowel is 9–11, 13, 21–23].
fixed by a broad mesentery from the duodenoje-
junal junction in the left upper quadrant to the
ileocecal valve in the right lower abdomen. The 27.5.1 Complete Nonrotation
broad base of the small bowel mesentery stabi-
lizes its position and prevents volvulus. In nonrotation, only the initial 90° counterclock-
According to Kluth, this description of the wise rotation occurs so that the duodenojejunal
processes of rotation is schematic. It has been junction lies on the right side and the colon lies of
done in order to better explain the background the left side of the SMA. It is characterized by the
of the pathology of malrotation than to study the small and large bowel coursing vertically and a
embryology of the midgut. Using his technique common longitudinal mesentery [23]. This mal-
of scanning electron microscopy pictures of the rotation is often called “left-sided colon”
developing midgut in a series of rat embryos, he (Fig. 27.2).
demonstrated that the primum movens of the
process was not the rotations but the lengthen-
ing of the bowel, mainly the small bowel, in a 27.5.2 Partial (Incomplete)
small cavity. Thus the bowel components enter Malrotation
into a position where space allows [20].
Partial (incomplete) malrotation implies a failure
of the midgut loop to complete the final 90°
27.5 Classification counterclockwise rotation; thus, terminal ileum
enters the abdominal cavity first. This term is
The term malrotation comprises a range of ana- used in all cases of anomalies in the arrangement
tomical anomalies in the arrangement of GIT in of the midgut ranging from a nonrotation to a
the abdominal cavity, each reflecting the time at normal rotation. In the most common forms, the

a b c

Fig. 27.2  Nonrotation. (a) Pure form; (b) with colonic the ileocecal valve faces to the right (Drawings from Max
adhesion to the stomach; (c) with a right position of the Grob) [8]
proximal colon compressing the second duodenum. Note:
372 L. Ferrero et al.

a b

Fig. 27.3  Partial (incomplete) rotation: two forms (a and extrinsic obstruction. (b) This is one of the commonest
b). In form (a) the cecum lies below the pylorus and is malrotations. Counterclockwise rotations have stopped at
fixed to the posterior abdominal wall by peritoneal bands 180°. Note: the ileocecal valve faces to the left (Drawings
(“Ladd’s bands”) that cross over the duodenum and cause from Max Grob) [8]

cecum lies below the pylorus and is fixed to the 180°, and the duodenojejunal loop has failed to
posterior abdominal wall by peritoneal bands cross the midline and lies to the right of the
(“Ladd’s bands”) that cross over the duodenum SMA.  The caecocolic loop has rotated from
and cause extrinsic obstruction. The duodenum almost 180° but no further and lies anterior to the
and small bowel are located on the right side of duodenum and to the SMA. Congenital adhesive
the SMA and the cecum and colon on the left bands (“Ladd’s bands”) course from the cecum to
(Fig. 27.3). the parietal peritoneum usually obstructing the
second part of the duodenum [23] (Fig. 27.4).

27.5.3 Malrotation
27.5.4 Reversed Malrotation
This term refers to anomalies occurring during
the second rotation. Several types have been When rotation is clockwise, the result is said
described according to the degree of rotation reversed malrotation in which the duodenum lies
accomplished. In the commonest type, the rota- anteriorly to the colon. Small intestine lies on the
tion has stopped at some point just before the left and large intestine on the right. The cecum is
27  Intestinal Malrotation and Volvulus 373

a b

Fig. 27.4  Malrotations: (a) these are results from reverse right in front of the duodenum. A compressive Ladd’s
second rotation following the initial counterclockwise band compresses the second duodenum (Drawings from
rotation. (b) In this type of malrotation, the cecum came Max Grob) [8]
from behind the mesentery and has passed toward the

found in the midline. Duodenum lies in front of 27.6 Associated Anomalies

the SMA and transverse colon behind it, which
may cause an extrinsic colonic obstruction. This Malrotation may occur in association with
is a rare malrotation (Fig. 27.5). other congenital abnormalities or syndromes
In addition to these terms, defining malrota- with wide differences according to authors
tions and abnormal fixation of the mesentery ranging from 17 to 60% of patients [14, 22,
must be mentioned as it may cause intestinal 25]. The most common associated ones are
internal herniation (“hernia mesocolica”) [14, other gastrointestinal abnormalities, espe-
24] (Fig. 27.6). cially jejunal and duodenal stenosis or atre-
In individuals with malrotation, the mesenteric sia, annular pancreas, and Hirschsprung’s
attachment of the midgut, particularly the portion disease. Malrotation of the bowel is always
from the duodenojejunal junction to the cecum, is present in children with congenital abdomi-
abnormally short. The gut is therefore prone to nal wall defects (omphalocele and gastros-
twist counterclockwise around the SMA.  This chisis) or congenital diaphragmatic hernia in
condition is known as midgut volvulus (Fig. 27.7). whom the normal embryologic positioning of
374 L. Ferrero et al.

a b

Fig. 27.5  Two types of reverse completed 180° clock- right side of the abdomen. (b) The colon can be com-
wise rotation. (a) The transverse colon comes to lie behind pressed by the SMA (Drawings from Max Grob) [8]
the SMA, but the cecum and proximal colon are in the

Fig. 27.7  Boy 3 weeks old. Urgent laparotomy for acute

Fig. 27.6  “Hernia mesocolica”: abnormal fixation of the midgut volvulus in a partial rotation. Discoloration with-
mesentery may cause intestinal internal herniation out necrosis. No resection
27  Intestinal Malrotation and Volvulus 375

the developing gut was disrupted. But many volvulus becomes complicated by intestinal
other malformations have been occasionally gangrene, perforation, and peritonitis. A high
described in association with malrotations index of suspicion for midgut volvulus is based
such as absence of the kidney or ureter, on the history, physical examination findings,
esophageal atresia, biliary atresia, imperfo- and presence of metabolic acidosis. A delay in
rate anus, and intestinal pseudo-­o bstruction. diagnosis and treatment may result in small
Several syndromes are associated with mal- bowel necrosis, short gut syndrome, and depen-
rotations. It may be present in patients with dence on TPN. Mortality in affected newborns
heterotaxy syndrome (asplenia or right isom- was approximately 30% by the 1950s and 1960s
erism and polysplenia or left isomerism). but today has markedly decreased down to
Patients presenting with this syndrome should 3–5% [32].
be investigated for the possibility of malrota-
tion [26]. It has also been described in asso-
ciation with Cornelia de Lange, cat eye, 27.8 Diagnostic Imaging
Coffin-Siris, Marfan, Prune-Belly syndromes, Investigations
and trisomy 21 [27].
Clinical diagnosis of malrotation must be con-
firmed by investigations.
27.7 Clinical Presentation Plain abdominal radiographs (Rx) are neither
sensitive nor specific for intestinal malrotation
The prenatal diagnosis of malrotation can be sug- [25, 33, 34]. They are usually performed to evi-
gested by identification of its complications, such dence an occlusion (Figs.  27.8a and 27.9a). A
as bowel dilatation, ascites, or meconium perito- duodenal obstruction gives a typical image of the
nitis, that can be evidenced on ultrasounds (US). double bubble sign whatever the cause, i.e., duo-
With US it is possible to diagnose intestinal vol- denal atresia or high located volvulus [21, 25].
vulus in utero. Combined with Doppler it gives Plain abdominal Rx may yield hints of abnor-
information on the viability of the involved intes- mally located bowel, e.g., small bowel markings
tinal segment [28–30]. predominantly on the right and large bowel on
Various clinical presentations may result from the left. Such findings should prompt further
failure of normal intestinal rotation and fixation, investigations. However a patient with midgut
ranging from chronic abdominal pain to acute volvulus may have a normal radiograph.
midgut volvulus. The most common features in The upper GI series (UGI) remains the imag-
newborns are bilious vomiting with or without ing reference standard for the diagnosis of malro-
abdominal distention associated with either duo- tation with or without volvulus [21, 22, 25, 35].
denal obstructive bands or midgut volvulus [13, Normally the duodenum descends to the right
25, 31]. Clinical diagnosis of malrotation with of the midline, courses transversely to the left,
volvulus is based on a high index of suspicion. and then ascends to the left of the midline at the
The major complications of malrotation is a level of the pylorus; thus the duodenojejunal
midgut volvulus and infarction of the bowel junction is located to the left of the vertebral body
that can be life-threatening if total or without at the level of the duodenal bulb on a standard AP
fatal issue can lead to a significant loss of bowel view [25], and the loops of the proximal jejunum
with a subsequent short bowel syndrome and are seen on the left of the midline. On a lateral
dependence on total parenteral nutrition (TPN). view, the duodenojejunal junction is located pos-
The infant presents in a shocked and collapsed teriorly [25]. However, variations of the normal
state with bilious vomiting (which often con- location may appear, particularly on frontal views
tains altered blood), abdominal tenderness with in the upper GI series, that mimic malrotation
or (more commonly) without distension, and [25, 36]. A grossly distended stomach may dis-
the passage of dark blood rectally. Edema and place the bulb. Then the stomach must be emp-
erythema of the abdominal wall develop as the tied and the position of the flexure reassessed.
376 L. Ferrero et al.

a b

Fig. 27.8 Boy D5. Partial rotation with obstructive that fails to cross midline looking down below the level of
Ladd’s bands. (a) Plain abdominal Rx performed to evi- the duodenal bulb. The proximal jejunal loops are in the
dence an occlusion showing gastric distension. Note that right abdomen. (c) UGI lateral view; the duodenojejunal
some gas has passed below the duodenum. (b) UGI AP junction has an anterior location
view; abnormal position of the duodenojejunal junction
27  Intestinal Malrotation and Volvulus 377

a b

c d

Fig. 27.9  Boy D15. Nonrotation type and volvulus. (a) that fails to cross midline looking down below the level of
Plain abdominal radiographs performed to evidence an the duodenal bulb. (d) The proximal jejunal loops are in
occlusion showing bowel distension. (b and c) UGI AP the right abdomen
view; abnormal position of the duodenojejunal junction

In infants, an inferior displacement of a normal In malrotation, the distal duodenum has an

duodenojejunal junction is a common variation abnormal course. On a strict AP view, this appears
seen on AP views. This is even more common in as an abnormal position of the duodenojejunal
prematures. It could be due to a relative mobile junction that fails to cross midline and is located
ligament of Treitz [36]. to the right of the vertebral body and, in some
378 L. Ferrero et al.

cases, below the level of the duodenal bulb torsion, described as “bird’s beak,” “corkscrew,”
(Figs.  27.8b and 27.9b, c). The duodenojejunal “twisted ribbon,” or “coiled” in appearance
junction may have an anterior location that can according to authors [21, 25, 37].
be depicted on a lateral view (Fig.  27.8c). In The sensitivity of the UGI series for the diag-
addition, in some malrotations, the duodenojeju- nosis of malrotation has been reported as
nal flexure may disappear making its localization 93–100%, but a sensitivity of only 54% was
difficult. Without occlusion, the contrast media reported for the diagnosis of midgut volvulus
demonstrates the presence of the proximal jeju- [25, 37].
nal loops in the right abdomen (Fig. 27.8d). The By 1987, ultrasounds (US) has been intro-
cecum is abnormally positioned in 80% of duced as an alternative for the diagnosis of mal-
patients with malrotation [21, 25, 35]. A midgut rotation, with emphasis on the relationship of
volvulus produces an obstruction of the descend- the superior mesenteric vessels and in the detec-
ing distal duodenum or the proximal jejunum tion of the so-called “whirlpool sign” in cases of
with the appearance of extrinsic compression and volvulus [38–42] (Fig. 27.10a, b). This is due to

a b

Fig. 27.10  Boy D12. Nonrotation type and volvulus. (a, b) US, whirlpool sign. (c) Peroperative view of the volvulus
27  Intestinal Malrotation and Volvulus 379

the rotation of the superior mesenteric vessels display the relationship between SMV and
associated with the twist of the bowel. Normally SMA as well as signs of volvulus such as the
the superior mesenteric vein (SMV) lies to the “whirlpool” sign. CT and MRI can also depict
right of the superior mesenteric artery (SMA). the location of both small and large bowel. An
In malrotation the SMV is coiling around the additional advantage of these imaging tech-
artery coming left to the SMA and more anteri- niques is that other abnormalities, in associa-
orly. The highest sensitivity is achieved when tion with syndromes or anomalies, can be
the “whirlpool sign” is shown, several studies illustrated. However CT is not considered to be
suggesting it to be diagnostic in 100% of the the first imaging modality of choice due to the
cases [12, 21, 37, 43–45]. related irradiation and should be restricted to
US has the potential benefits of portability and some unusual cases.
lack of radiation. Although US is an excellent
imaging modality, the results are strongly opera-
tor dependent. Additionally, due to the superim- 27.9 Treatments
posed intestinal air, both the SMV and the SMA
are not always clearly detectable. Orzech et  al. The surgical treatment of a malrotation includes:
reported sensitivity of 86.5%, specificity of 75%,
positive predictive value of 42%, and negative • Careful inspection of the bowel and of the
predictive value of 96% for US [31]. Several mesenteric root in order to recognize the type
studies have suggested that inversion of the supe- of malrotation. A precise description is better
rior mesenteric vessels, (i.e., the SMV to the left than the use of a classification type.
of the SMA), is diagnostic of malrotation in • Detorsion of the volvulus counterclockwise if
100% of the cases [12, 37, 43, 44]. Consequently, present.
an abnormal US study requires further radiologic • Lysis of all abnormal bands and adhesions of
and clinical investigation. peritoneum, the so-called Ladd’s bands,
However, it has been shown by other authors between the cecum and the duodenum. This is
that inversion of the SMV/SMA relationship can known as the “Ladd’s procedure” [1]
also be seen in patients with normal midgut rota- (Fig. 27.11).
tion [12, 21, 43] and in patients with abdominal • Straightening and freeing of the duodenum
masses and distal ileocolic intussusception [46]. such that it descends directly into the right
Furthermore, not all cases of malrotation have lower quadrant.
abnormal SMV/SMA orientation on US [47]. • Broadening of the base of the small bowel
Because of the lower sensitivity and specificity of mesentery by severing its serosal leaves as to
US compared with UGI, and because of the fact create the longest distance between the duode-
that US cannot estimate the length of the mesen- nojejunal junction and the ileocecal one.
teric base (which determines the risk of midgut • Placement of the bowel in a nonrotation posi-
volvulus), UGI has remained the gold standard tion in the abdomen with the duodenum and
diagnostic modality [31, 48]. upper jejunum on the right of the abdomen
Contrast enema (CE) has been used to demon- and the cecocolic loop in the left upper
strate the position of the cecum. However, CE is quadrant.
less reliable in identifying malrotation because
the position of the cecum and colon is highly The important steps are the broadening of the
variable and may even be normal [33]. Reversely mesentery which prevents recurrent volvulus and
20–30% of malrotations have a normally sited the freeing of the duodenum to relieve the gastro-
colon [42]. Today it is considered at suppress intestinal symptoms these patients have (emesis,
used in low diagnosis value used and is rarely reflux, failure to thrive). Turbid fluid at surgery is
used. almost always due to chylous ascites related to
Both computed tomography (CT) and mag- lymphatic congestion from partial volvulus and
netic resonance imaging (MRI) can be used to does not evidence a bowel perforation.
380 L. Ferrero et al.

resection has to be performed. It is wiser to wait

before resecting as reperfusion is frequently
observed after detorsion, warming, and observa-
tion. If viability is in question, it is better to plan
a second look procedure within 1 or 2 days than
to resect in haste.
In the absence of acute midgut volvulus,
patients with symptomatic malrotation can be
scheduled for an elective Ladd’s procedure.
The Ladd’s procedure can be performed open
or laparoscopically, but the steps remain the same
regardless of the approach.
If preferred, laparotomy is performed via an
upper abdominal, transverse, muscle-cutting
incision, extending mainly to the right side.
Exteriorization of the entire bowel is necessary,
avoiding traction to the mesentery, in order to
understand the anatomy. The volvulus is usually
untwisted by a counterclockwise rotation until
the transverse colon and cecum are brought ante-
riorly to the superior mesenteric pedicle. The
bowel is wrapped with warm moist pads until its
perfusion is returned to normal.
The use of minimally invasive surgical tech-
niques in the diagnosis and treatment of malro-
tation has been described in the literature since
Fig. 27.11  Division of obstructive Ladd’s bands the beginning of the 1990s [50–52]. Bax
reported nine cases of neonates being operated
laparoscopically between 1994 and 1997 for
Performing an appendectomy is debatable. A volvulus [50].
few decades ago, it was the rule. The argument For the laparoscopic procedure, the child is
put forward was that the appendix could be in an placed in a supine, anti-Trendelenburg, “frog”
unusual position, thus making the diagnosis of a position. The surgeon stands at the bottom end of
future appendicitis more difficult or even unrec- the table with the camera assistant to the left and
ognized. Today pediatric surgeons are more the scrub nurse to the right. The principal monitor
respectful of the appendix and avoid removing it is placed over the child’s head to face the surgeon
unnecessarily specially since the era of laparos- if possible or to the right of the patient’s head.
copy that makes its search easier. Much has been Three trocars are used: the first trocar is inserted
written about a pexy of the cecum to prevent in an open fashion through the inferior umbilical
future volvulus. There is no evidence that ceco- fold (Hasson’s technique) and will contain a ø
pexy improves outcomes or prevents from recur- 5 mm × 30° telescope, and two working trocars
rences [49]. Reversely it creates sites around are positioned, one pararectally on the right at
which a volvulus could occur. umbilical level and one in the left hypochon-
Patients with an acute abdomen require appro- drium. An extra cannula can be inserted subcos-
priate resuscitation and prompt operative explo- tally on the left to be used for retraction. Ladd’s
ration. If a segment of volvulized bowel is bands are divided, and the mesentery is widened
identified as ischemic, resection is not manda- laparoscopically using the same principles as
tory. Only in case of certainly necrotic segment, with the open technique [50, 53–56].
27  Intestinal Malrotation and Volvulus 381

They are major challenges in the laparoscopic lives. So the question raised is, should we perform
procedure for malrotation. In case of occlusion, preventive surgery? In 1993, Schey et  al. retro-
the bowel distension in an already limited field spectively reviewed 53 cases of pediatric and
reduces the surgeon’s vision as also does a adult malrotations and categorized them into 5
chylous ascites or inflammatory mesentery
­ distinct patterns based on relative positions of the
resulting from bowel suffering. At the end of the duodenojejunal junction and the cecum. They
procedure, the small operating field in a neonate suggested that configurations involving an abnor-
makes the assessment of the proper position of mal position of the duodenojejunal junction were
the bowel difficult. The use of laparoscopy is safe at highest risk for acute midgut volvulus and
and effective, and the number of reports in litera- should be surgically corrected, even if asymptom-
ture increases significantly. However a high rate atic. Configurations involving malrotation of the
of conversion is noted ranging from 12 to 33% cecum bear also a risk for volvulus but with less
[14, 54, 56, 57]. catastrophic consequences due to the smaller vas-
The debate between open and laparoscopic cular distribution involved. According to Schey,
approaches on Ladd’s procedure is still open. The these patients should not be operated unless
comparative studies between open and laparo- symptomatic [58]. In 2002, Mehall et  al. retro-
scopic approaches are limited by the small num- spectively reviewed 201 cases of pediatric malro-
ber of cases and subsequently by the lack of tation. They classified them into three groups
prospective randomized design [14, 53, 55]. In a based on the location of the duodenojejunal junc-
series comparing 2 similar groups of 20 neonates, tion. The junction was described as “typical” if it
each suffering malrotations and being operated was located right to the midline, “low” if it was
either open or by laparoscopy demonstrated that located left to the midline and below the vertebra
the laparoscopic group recovered full diet shortly T12, and “high” if it was located left to the mid-
and left the hospital earlier. Rehospitalization due line and above T12. Operative findings of volvu-
to recurrence of occlusive symptoms occurred in lus were more common in the “typical” cases as
30% of patients in the laparoscopic group versus compared with the other groups, namely, “low”
40% in the open group [14]. Additionally, what is and “high” cases. Operative complications and
believed to be an advantage of laparoscopy (less persistent symptoms after surgery occurred more
postoperative adhesions) could not be either one frequently in the “low” and “high” cases than in
if the bowel does not stay in the nonrotation posi- the “typical” cases. Given the lower risk of volvu-
tion at the end of the Ladd’s procedure. If malro- lus, higher operative morbidity, and lower success
tation cannot be excluded from imaging, rate, they concluded that consideration should be
laparoscopy is an ideal tool to look at the position given to nonoperative management of asymptom-
of the bowel and the appearance and the width of atic patients with duodenojejunal junctions classi-
the mesentery [56]. fied as “low” or “high” [59].
Malrotation that is discovered at the time of
operation raises an interesting dilemma with
respect to consent. Should the malrotation not be 27.10 Postoperative Course
involved in the disease process, its treatment
would be considered an additional procedure The postoperative course depends upon the indi-
except if consent can be given by the parents dur- cations for surgery and the intraoperative find-
ing the course of operation. ings. Dilatation of the duodenum and vascular
Another dilemma is the asymptomatic malro- compromise of the bowel might cause prolonged
tation discovered fortuitously. Asymptomatic ileus. It should be managed with expectant pol-
midgut volvulus bears a risk of sudden dramatic icy, maintaining gastric decompression through a
event with vascular compromise. No mean can nasogastric aspiration and IV fluids. Patient hav-
predict it. On the other hand, there are adult ing an extensive bowel injury with or without
patients who remain asymptomatic for their entire resection should benefit of a TPN.
382 L. Ferrero et al.

During the postoperative course of malrota- 16. Beaudoin S, Mathiot-Gavarin A, Gouizi G, et  al.

Familial malrotation: report of three affected siblings.
tions, intussusception may occur. The incidence is Pediatr Surg Int. 2005;21:856–7.
higher (3.1%) than for other laparotomies (0.05%) 17. Smith VL, Long F, Nwomeh BC. Monozygotic twins
[60]. The incidence of postoperative adhesive ileus with discordant intestinal rotation. Pediatr Radiol.
is 4%. The incidence of recurrent volvulus ranges 2006;26:1–3.
18. Touloukian RJ, Smith EI.  Disorders of rotation and
from 0.5 to 1.3% according to literature [23]. fixation. In: O’Neill JA, Rowe MI, Grosfeld JL, et al.,
editors. Pediatric surgery. 5th ed. St Louis: Mosby;
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laparoscopic Ladd’s procedure can safely be per- 713–5.
 Part V
Liver and Biliary Tract
 Biliary Atresia: New Developments
28
Filippo Parolini and Mark Davenport

28.1 Introduction and North America, the incidence ranges from

about 1 in 15–20,000 [2, 4]. Although rare, BA is
Biliary atresia (BA) is an idiopathic neonatal the most common cause of severe chronic pro-
hepatobiliary disease characterized by progres- gressive liver disease in childhood and is still the
sive fibrosing obstruction of the intra- and extra- leading indication for liver transplantation in
hepatic biliary tree [1]. Although there have been childhood (about 50%) [5, 6]. This disproportion
some changes in modern management, its prin- can be gauged by considering that in the United
ciples have been largely unchanged since the States, $77 million (2003 figures) is spent annu-
1980s involving an initial attempt at restoration ally on paediatric liver transplantation-related
of bile flow with the Kasai portoenterostomy costs, i.e. about 2% of total healthcare expendi-
(KPE), and if this is unsuccessful or complica- tures for only 0.0006% of the entire paediatric
tions ensue, then liver transplantation is offered population [5].
[2–7]. Nowadays, long-term survival with a nor-
mal life is possible with either KPE or a function-
ing liver transplant, in most centres, for more 28.1.2 Macroscopic Classification
than 90% of patients [1–3]. Here, we review the
recent advances in basic research and clinical The Japanese classification of BA describes the
progress in these diseases, as well as the diagnos- macroscopic appearance of the extrahepatic ducts
tic assessment and therapeutic approach. and is based on the level of the most proximal
obstruction of the extrahepatic biliary tree [1, 7]
(Fig. 28.1):
28.1.1 Epidemiology and Burden
of Disease • Type 1 (5%): level of common bile duct
(CBD) and often associated with a cyst which
The incidence of BA varies dramatically accord- therefore should contain bile.
ing to geography, with the highest rates being • Type 2 (2%): level of common hepatic duct
reported from Taiwan, Japan and China (1  in (CHD). Transection of the proximal porta
5–10,000 live births) [2–5]. In the UK, Europe hepatis should show both right and left ducts
with bile present.
• Type 3 (>90%): Transection of the porta hepa-
F. Parolini · M. Davenport (*) tis should not show any remnant bile ducts, as
Department of Paediatric Surgery, Kings College
Hospital, London, UK these if present are microscopic. Typically
e-mail: [email protected] there is a solid dense fibro-inflammatory

© Springer Nature Switzerland AG 2019 387

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_28
388 F. Parolini and M. Davenport

28.1.3 Aetiopathogenesis
and Phenotypic Classification

The true aetiology of BA is unknown, although

developmental and infective hypotheses have
been suggested and fashions change [1, 2, 8].
Certainly, BA is not a single uniform disease and
Type I
at least four different variants with a different
pathological background are identifiable from
clinical observation alone (Fig. 28.2).

• Syndromic BA, typically the biliary atresia

splenic malformation syndrome, but there are
others such as the cat eye syndrome [9, 10]
• Cystic BA [11]
• Cytomegalovirus (CMV) IgM + ve BA [12]

The others, for which we use the term “iso-

lated BA”, lack any real clue to their aetiology
Type II and account for the majority of cases.
“Developmental” BA is a term used to include
patients with BASM and cystic BA, where the
onset is certainly during prenatal life and evident
at the time of birth and usually where there is the
clear female predominance.

28.1.4 Development
of the Extrahepatic Bile Ducts

The extrahepatic bile duct begins as a diverticu-

Type III lum from the duodenum around 20 days’ gesta-
tion. It is enveloped by the amorphous hepatic
primordium and forms its own diverticulum—the
gallbladder. Throughout this phase, ending about
45 days, it retains a lumen. It is lined by cholan-
Fig. 28.1  The Japanese classification of biliary atresia
giocytes expressing transcription factors com-
mon to the pancreas and duodenum (e.g. PDX-1,
PROX-1, HNF-6) [1, 13]. This is occurring paral-
­roximal remnant at the porta hepatis. The
p lel with key changes in visceral rotation, cardiac
distal duct may be atrophic, absent or rela- and splenic development and evolution of the
tively well preserved, if so, usually in connec- portal and inferior vena cava. Bile duct maldevel-
tion with a mucus-filled gallbladder. opment at this stage could explain the biliary
atresia splenic malformation (BASM) syndrome,
Intrahepatic bile ducts are always non-dilated a subset noted in 10% of European BA cases and
and if visualized (rarely) are grossly abnormal that encompasses splenic malformation (usually
with perhaps a myriad of ductules coalescing at polysplenia), situs inversus, malrotation, absence
the porta hepatis. of the inferior vena cava and a preduodenal portal
28  Biliary Atresia: New Developments 389

1st trimester 2nd trimester 3rd trimester Post-natal

Genetic Epigenetic Genetic Susceptibility

Virus-initiated
e.g. CFC-1 e.g. diabetes Cystic BA e.g. ADD3

Other syndromic
e.g. Cat-Eye BASM e.g. CMV, REOvirus

Developmental Inflammatory
Cholangiopathy

Class II antigen exposure

ICAM, VCAM activation
Environmental Isolated T reg deficit

e.g. biliatresone

Key
Biliary Atresia
Mechanism

Clinical Features

Fig. 28.2  Possible aetiological pathways in biliary atresia

vein [10]. Some of these infants seem to come extrahepatic systems. These infants also have a
from an abnormal intrauterine environment (e.g. better outcome following surgery, probably
maternal diabetes and thyrotoxicosis). because of this more mature intrahepatic bile sys-
Postnatally, infants with BASM have absence tem [6, 11].
of the CBD, an atrophic gallbladder and a normal
appearing liver at the time of birth [10, 14].
Mutations in the CFC-1 gene, encoding for 28.1.6 Cytomegalovirus-Associated BA
CRYPTIC protein which is also related to disor-
ders of heterotaxy and cardiac anomalies, at least In 1974, Benjamin Landing proposed that BA
in mice, have been identified in 50% of a French could be caused by the effects of a virus [16].
series of infants with BASM [15]. Since then DNA and RNA from a range of candi-
date viruses (e.g. reovirus, rotavirus and CMV)
have been isolated from clinical cases although
28.1.5 Cystic BA not consistently so [17, 18].
One of the candidates, CMV, is a double-­
Cystic BA accounts for about 10% of cases and is stranded DNA virus from the Herpesviridae fam-
caused by extrahepatic cyst formation in an oth- ily that has the capability to infect and injure bile
erwise obliterated biliary tract [11]. The cyst may duct epithelia, and serological evidence of
be filled by mucus or bile and can be detected infection in the infant (CMV IgM  +  ve) has
­
antenatally. Cystic BA may lead to diagnostic been shown in up to 50% of BA patients in
confusion with early obstructed cystic chole- some Chinese series [12, 17–19]. Nevertheless,
dochal malformation though both need urgent whether the biliary damage is related to a direct
exploration. We speculate that this variant occurs cytopathic effect of the virus or to secondary auto-
relatively late in gestation beyond the period of immune reaction triggered by viral exposure still
initial bile production at 12 weeks with at least in remains unclear. Patients with CMV IgM + ve BA
some luminal integrity between intrahepatic and (about 10% of cases in our series) showed several
390 F. Parolini and M. Davenport

distinct clinical and histological features com- and Th17 effector profile [19]. This systemic
pared to CMV IgM-ve BA infants such as an older response to hepatobiliary inflammation can be
age at KPE, a greater degree of splenomegaly and detected as increased levels of cellular adhesion
a greater degree of inflammation and fibrosis in the molecules (ICAM and VCAM) and pro-inflam-
liver even if age-matched [12]; further quantifica- matory cytokines such as interleukin-2 (IL-2),
tion of the T cell infiltrate also suggested a Th-1 IL-18 and tumour necrosis factor-α (TNF-α)
predominance [19]. These patients have also a [23].
poor outcome in terms of response to KPE and a
higher mortality compared to those who were
CMV IgM-ve [12, 20, 21]. 28.2.1 Initiators of Cholangiopathy

A number of extrinsic factors have at one time

28.1.7 Isolated BA been suggested as triggers to the inflammatory
process whereby the end product is bile duct
Whatever remains, termed “isolated BA”, lack damage and obliteration. Viruses, particularly
any real clue to their aetiology, though its onset CMV, may play a role but other mechanisms have
must be after those with BASM given the lack of been suggested. Thus recently a toxin has been
other affected systems [3]. We also know that for- isolated and named biliatresone for its property
mation of the intrahepatic bile duct system only of causing either damage or developmental arrest.
begins beyond about 7 weeks gestation and has to Figure 28.3 illustrates the story behind this piece
be essentially complete and linking with the of biological detective work.
extrahepatic bile ducts at the porta hepatis by
12  weeks [13]. One obvious speculation is that
this linkage phase is incomplete—so-called 28.3 Clinical Features
“interface” BA.
Alternatively there is normal formation of a Antenatal detection of those with cystic BA
functional duct system but later obliteration as a (<10%) is possible on the maternal ultrasound
secondary phenomenon. scan, usually between 18 and 22 weeks’ gestation
[11, 24]. For the remaining patients, the disease is
usually suspected soon after birth with persistent
28.2 Cellular Kinetics conjugated jaundice, acholic stools and dark urine
and Inflammation in an otherwise healthy neonate. Most infants
eventually demonstrate a degree of failure to
In about 40% of cases of BA (possibly with the thrive due to reduced fat absorption, and certainly
exception of BASM), there is a marked inflam- fat-soluble vitamin deficiency is common (A, D,
matory process with mononuclear cell infiltrate E and K) [25]. Liver fibrosis and cirrhosis are sec-
and expression of a variety of adhesion molecules ondary features which depend on the age of the
on intrahepatic biliary and vascular surfaces [1, child, whilst ascites and hepatosplenomegaly are
22]. The immunohistochemical appearance is not usually seen until after about 3 months [1].
characterized by abnormal expression of Class II
antigens and cytokines such as intercellular adhe-
sion molecule (ICAM), predominantly on the 28.3.1 Diagnostic Assessment
biliary epithelium, and vascular cell adhesion
molecule (VCAM), predominantly on the sinu- Liver biochemistry is non-specific and shows a
soidal endothelium [22]. There is also an infiltra- conjugated hyperbilirubinemia, slightly raised
tion of activated CD4  +  ve lymphocytes and transaminases (AST and ALT) and significantly
CD56 + ve natural killer (NK) cells. Most studies raised γ-glutamyl transpeptidase (GGT). Protein
suggest polarization with a predominantly Th1 and albumin levels are usually normal. The
28  Biliary Atresia: New Developments 391

a b

OCH3
O
OH

OCH3 O

Biliatresone (1)

d c

Fig. 28.3  The Biliatresone story: In 1964 in the area sur- (c) subsequently born were affected by BA-like pathol-
rounding the Burrinjuck Dam in New South Wales, ogy. An isoflavonoid isolated in extracts of the Red
Australia (a), the silt foreshores of the dam became Crumbweed, now known as Biliatresone, has been clearly
exposed by declining water levels causing abnormal colo- demonstrated to cause biliary maldevelopment in
nization by a particular weed termed the red crumbweed Zebrafish larvae model (d). Picture reproduced with per-
(Dysphania glomulifera subsp. glomulifera) (b). This area mission from reference 13
was then used as grazing land by local farmers and lambs

­ ST-­to-­platelet ratio index (APRi) can also be

A specific though may include evidence of an atro-
calculated and has been used as a surrogate phic gallbladder or the so-called triangular cord
marker of liver fibrosis in larger studies even pre- sign, representing the appearance of the solid
dicting native liver survival [26, 27]. proximal biliary remnant in front of the bifurca-
Abdominal ultrasound is a key investigation in tion of the portal vein.
other possible surgical diagnoses characterized Radioisotope hepatobiliary imaging should
by intrahepatic or common bile duct dilatation show absence of biliary excretion in BA but is
(e.g. choledocal malformation, inspissated bile non-specific [28]. In the UK and North America,
syndrome). Actual positive signs of BA are less percutaneous liver biopsy is popular and has a
392 F. Parolini and M. Davenport

positive predictive value of >90% and typically option in some countries, but it should probably
shows the histological features of “large-duct only be a consideration in those presenting late
obstruction”, i.e. oedematous expansion of the (>100  days) or with obvious cirrhosis, ascites
portal areas, ductular proliferation, bile plugs and and portal hypertension and liver failure (increas-
portal fibrosis [29]. There is in some a marked ing INR and decreasing albumin). For the
inflammatory aspect with infiltration of activated remainder a KPE is indicated as attempt to retain
mononuclear cells, such as CD4+ T cells and NK the native liver.
cells. As the disease progresses, then monocytes/
macrophages also appear with progressive bridg-
ing fibrosis between portal areas [1]. 28.5.1 “Maximally Invasive” Surgery
Sometimes, direct cholangiography has to be
performed to prove (or disprove) the diagnosis. Conventional open portoenterostomy, first
This can be performed using endoscopic retro- described by Japanese surgeon Morio Kasai in
grade cholangiopancreatography (ERCP) or at 1957, still represents the gold standard of treat-
laparoscopy or indeed via a small incision ment. The key part of the procedure is the dissec-
directly over the gallbladder. tion at the level of the portal plate. Our practice is
to exteriorize the liver on the abdominal wall by
division of the left triangular and falciform liga-
28.4 Screening for BA ments. The gallbladder is then mobilized from its
bed and the distal CBD divided and then dis-
Population screening programmes for BA are sected back towards the porta hepatis (Fig. 28.4).
based on the provision of stool colour cards to Division of small veins from the back of the por-
parents of newborns in order to identify acholic tal confluence to the porta plate facilitates down-
stools and have been in use Japan [30], Taiwan wards traction of the portal vein and exposes the
[31], Switzerland [32] and Canada [33]. A large-­ caudate lobe. On the left side, there is often an
scale prospective study which enrolled more than isthmus of liver parenchyma (from segment III to
6000 Canadian families demonstrated the practi- IV) which may need division by coagulation dia-
cality and cost-effectiveness of the stool colour thermy to open up the recessus of Rex (where the
card [33], even if this success may be more lim- umbilical vein becomes the left portal vein). On
ited in countries without routine 30-day-old well-­ the right side, the division of the right vascular
child visits for review of the stool colour card pedicle into anterior and posterior branches
[34]. Recently, a pilot study on a mobile applica- should be visualized. The “width” of the tran-
tion that utilizes a smartphone’s camera and sected portal plate should extend from this bifur-
colour recognition software to analyse an infant’s cation into Rouviere’s fossa on the extreme right
stool in the perinatal period (PoopMD©) showed to the point where the left portal vein gives off its
that it may have value as a tool to help parents first branches to segment IV. A 40–45-cm retro-
identify acholic stools and provide guidance as to colic Roux-en-Y loop should be constructed. The
whether additional evaluation with their paedia- jejunojejunostomy lies about 10  cms from the
trician is indicated [35]. ligament of Treitz and can be stapled or sutured.
The proximal anastomosis must be wide (~2 cms)
and typically end-to-side.
28.5 Management

Following confirmation of the diagnosis, it is 28.5.2 “Minimally Invasive” Surgery

important to consider how far advanced the dis-
ease is. Primary liver transplant is uncommon in During the early years of the new century, there
Western series (<2% in the UK) and could be an was a brief flirtation with the concept of the
28  Biliary Atresia: New Developments 393

a b

c d

Fig. 28.4  Intraoperative picture of Kasai portoenteros- its bed and the distal CBD divided and then dissected back
tomy. (a) Exteriorisation of the liver and exposure of the towards the porta hepatis. (c) Exposure and transection of
porta hepatis. (b) The gallbladder is then mobilized from portal plate. (d) Reconstruction with Roux-en-Y loop

laparoscopic Kasai option. This procedure was likely to be because of the difficulties with por-
reported first by a Brazilian team in 2002 [36] tal plate dissection using laparoscopic instru-
and there have been small case series since ments, as delicate dissection and radical
[37]. It has become apparent that laparoscopic resection of all extrahepatic biliary remnants
KPE does not offer anything advantageous to are key features to maximize the results.
the child beyond a better scar. Clinically mean- Laparoscopic KPE is still being practised in a
ingful results are certainly not better and rarely few centres in Japan, but one team at least has
comparable to open surgery [38]. Two large reverted to a less extensive dissection and more
centres have reverted from laparoscopic to the superficial transection [41, 42].
open operation with restoration of their previ-
ous results [38, 39]. A recent systematic review
found no significant difference between the 28.6 Adjuvant Therapy for Biliary
laparoscopic and open KPE groups in terms of Atresia
operative time, early clearance of jaundice and
cholangitis, but the rate of 2-year survival with The success of the operation is gauged by clear-
native liver was significantly higher in the open ance of jaundice (within 6  months), and each
group than in the laparoscopic [40]. This is centre treating infants with BA will have its own
394 F. Parolini and M. Davenport

Table 28.1  Adjuvant postoperative therapy after KPE prednisolone (2 mg/kg/day) in two English high-­
Therapy Rationale volume centres in 73 infants [45]. This showed a
Corticosteroids Anti-inflammatory effect and statistically significant improvement in early
choleretic effect bilirubin levels (especially in the “younger”
Antibiotics Decreases risk of ascending
liver) in the steroid group but did not translate to
cholangitis
UDCA Establishes bile flow, possible a reduced need for transplant or improved over-
anti-inflammatory action all survival. The other study is the START trial
Ganciclovir/ Competitive inhibitor of [46]; this randomized 140 infants from 14 North
valganciclovir deoxyguanosine triphosphate American centres to a steroid arm using initially
(dGTP) of CMV
IV methylprednisolone 4 mg/kg/day for the first
Fat-soluble vitamin Restores intrinsic deficiency due
supplementation to impairment of bile flow 3 days followed by oral prednisolone (4 mg/kg/
Phenobarbitone Induces liver microsomal day till the second week, 2 mg/kg × 2 weeks, fol-
enzymes and thereby increases lowed by a tapering protocol over the next
bile flow 9-week period). Although there was a difference
MCT-based Effective maintenance of calorie in the clearance of jaundice from 49% in the pla-
formula milk intake, as MCT does not require
bile for its absorption in the
cebo group to 59% in the steroid group, this did
gastrointestinal tract not attain statistical significance. They also did a
Legend: UDCA ursodeoxycholic acid, CMV cytomegalo- subgroup analysis of infants <70  days at KPE
virus, MCT medium-chain triglyceride (n = 76) and showed that 72% (28/39) in the ste-
roid group cleared their jaundice compared to
57% (21/37) in the placebo group, unfortunately
postoperative regimen to try and maximize the still not statistically different (P = 0.36).
restoration of bile flow. Most will include a A follow-up study [47] to the original UK
­prolonged period of oral antibiotics, ursodeoxy- trial examined the use of a high-dose predniso-
cholic acid, fat-soluble vitamin supplementation, lone cohort (starting at 5  mg/kg/day) and
medium-chain triglyceride (MCT)-based for- reported the same beneficial biochemical effects
mula milk and usually steroids (Table 28.1). (now including a reduction in AST and APRi
levels) with a statistically significant higher pro-
portion of those who cleared their jaundice in
28.6.1 Corticosteroids the steroid groups. Later analysis showed that
the key appeared to be the age of the infant at
Steroids have been used for at least 30  years time of KPE [48]. In practice, all three of the
albeit delivered in an uncontrolled pragmatic English specialist centres (London, Leeds and
fashion [43]. The rationale behind the use of ste- Birmingham) use high-dose steroids albeit in a
roids maybe twofold: firstly, there is a pro- variety of regimens.
nounced inflammatory element in a proportion
of infants with BA, and steroids have many anti-
inflammatory properties. Moreover, steroids 28.6.2 Ursodeoxycholic Acid (UDCA)
have a positive choleretic effect which may
improve bile flow and keep open the primitive This is widely thought to be beneficial, but only if
bile ductule-Roux loop connection in the early surgery has already restored bile flow to reason-
postoperative phase [44]. There have been two able levels. UDCA “enriches” bile and has a cho-
prospective, double-blind, randomized, placebo-­ leretic effect, increasing hepatic clearance of
controlled trials. The first one used a low dose of supposedly toxic endogenous bile acids and may
28  Biliary Atresia: New Developments 395

confer a cytoprotective effect on hepatocytes. 28.7.1 Cholangitis

There is but a single study which looked at the
effect of UDCA on liver function in 16 children Ascending bacterial cholangitis are relatively
>1  year post-KPE how who had resolved their common and at least one episode is seen in up to
jaundice. Its crossover design looked at UDCA 50% of most large series. The CHiLDREN con-
(25  mg/kg/day in three divided doses) in an sortium reviewed 219 long-term survivors and
18 month period followed by 6 months washout reported an incidence of cholangitis of 17% in
and then resumption. All but two had sustained the preceding 12  months [52]. The risk is most
significant worsening in their liver enzymes that apparent in the first 2 years post-surgery although
on restarting UDCA reversed [49]. the reason for the diminution in risk is obscure,
though it could be related to some time-­dependent
change in  local immunologic defence within
28.6.3 Antiviral Treatment for CMV cholangioles. The key clinical features are
IgM + ve pyrexia, worsening jaundice and a change in liver
biochemistry. Following blood culture, episodes
Antiviral treatment with intravenous ganciclovir should be treated aggressively with broad-­
and/or its oral prodrug valganciclovir has been spectrum intravenous antibiotics effective against
­trialled and shown to be well-tolerated and effec- Gram–ve organisms (e.g. gentamicin, merope-
tive in prevention of long-term neurological dam- nem, piperacillin/tazobactam) [53].
age (e.g. hearing loss) in newborns with
symptomatic congenital CMV infection [50, 51].
The real potential for antiviral therapy in children 28.7.2 Portal Hypertension
with CMV IgM + ve BA (10% of cases) exists, and Oesophageal Varices
even if no convincing studies have been pub-
lished to date [20, 21]. In our own unpublished Abnormally raised portal venous pressure is seen
series of 37 consecutive IgM  +  ve BA patients, at the time of KPE in about 70% of BA infants. It
the group who received adjuvant antiviral postop- is caused by liver fibrosis and correlates with the
erative therapy (9 patients) presented a statisti- age at KPE, bilirubin level and ultrasound-­
cally significant higher clearance of jaundice measured spleen size [54]. However the initial
compared with those who did not receive such measured pressure is a poor predictor of outcome
treatment (89 vs. 41%). either in terms of response to KPE or more sur-
prisingly even in those who will go on to develop
varices. About 60% of children who have sur-
28.7 Postoperative Complications vived with their native liver beyond 2 years will
have definite varices visible at endoscopy, and of
The most common problem after KPE is that these about 20–30% will bleed. Upper gastroin-
there is no or ineffective restoration of bile flow; testinal varices take time to develop, and bleeding
jaundice therefore worsens and end-stage liver is unusual before 9 months of age and more usu-
disease and cirrhosis beckon. The key in these ally occurring from 2 to 3 years. Emergency treat-
infants is to prepare the way to a safe liver trans- ment of bleeding varices specifically includes the
plant by strict attention to nutrition, vitamin defi- use of vasopressin or somatostatin analogues and
ciencies and fluid management. There are some sometimes even a Sengstaken-Blakemore tube.
specific complications, which can occur indepen- Most can be treated endoscopically with banding
dently of this process though. or in the very young, injection sclerotherapy [55].
396 F. Parolini and M. Davenport

Recently we proposed a new prediction score These are:

associated with good specificity and sensibility in
the selection of children with clinically significant • Clearance of jaundice to a preset level (typi-
varices eligible for a screening endoscopy [56]. cally ≤20 μmol/L in Europe and < 1.5 mg/dl
Some children also develop haemorrhoids and in North America). This is influenced by type
anorectal varices later during childhood [57]. of BA, age at surgery, the experience of the
surgeon and the nature of the surgery per-
formed. A clearance rate higher than 50%
28.8 Miscellaneous should be expected in experienced surgeons
operating on infants <70 days of age.
Ascites is related to and caused by portal hyper- • Actuarial native liver survival (end-points of
tension in part, but there are other contributory death and liver transplant). This is influenced
factors which include hypoalbuminaemia and mostly by clearance of jaundice rate but also
hyponatraemia. Conventional treatment includes by postoperative complications and quality of
a low-salt diet, fluid restriction and the use of medical follow-up. Obviously, increased
diuretics particularly spironolactone. Often seen access to transplantation and softening of the
in settings of malnutrition, consideration should indications will reduce the native liver sur-
be given to nasogastric feeding to try and increase vival over time.
calorie and protein intake. • Actuarial true survival (end-point death). This
Hepatopulmonary syndrome (HPS) may reflects on not only the success of the original
develop even in anicteric children, especially in operation but also access and safety of the
those with BASM. The exact mechanism of HPS transplant procedure and minimization of
is still unknown, even though it may be a mani- postoperative risk. The burden of associated
festation of preexisting congenital vascular anomalies, mainly cardiac, should be also
anomaly. HPS can be diagnosed using arterial considered.
blood gas estimation with and without inspired
oxygen, and typically hypoxia is worse in the Centralization of the resources has been the
standing position (platypnea). This complication single most important public health measure and
is usually resistant to conventional therapy, and has changed the outcome of BA. Since 1999, the
liver transplantation appears to be the only spe- treatment of BA has been centralized to three
cific treatment. centres in England and Wales (London,
Malignant change involving both cholangiocar- Birmingham and Leeds), and the benchmark
cinoma and hepatocellular carcinoma (HCC) has study of outcome following this centralization
been reported in children post-KPE [58]. It is related has allowed publication of key national statistics.
to the underlying cirrhosis of most of the long-term In this cohort of 424 patients who underwent
survivors. Surveillance using regular serum alpha- KPE from 1999 to 2010, clearance of jaundice
fetoprotein levels and ultrasound are helpful but not was achieved in 55%, with a 5- and 10-year
absolute markers of the malignant change, and sus- native liver survival estimated in 47% and 43%,
picious nodules should be thoroughly investigated respectively [6]. Following this English experi-
with magnetic resonance imaging (MRI) or com- ence, encouraging results were achieved in
puted tomography (CT) and biopsy. smaller countries such as Finland [59] and
Denmark [60] and Switzerland [61]. The only
constraint is geography such as in the relatively
28.9 Outcome and Results low population density countries such as Canada
[62] and Australia [63]. Published national out-
In order to allow meaningful comparison between comes are given in Table 28.2. Essentially if your
series, it is important to use reproducible out- country is not listed, then its outcomes will be
come measures which accurately reflect perfor- worse. The recently launched online registry
mance and effective management of BA. “bard-online” (www.bard-online.com) might aid
28  Biliary Atresia: New Developments 397

Table 28.2  National outcomes in Biliary Atresia

Age at KPE, days Clearance of 4- to 5-year native 4- to 5-year true
Period N (mean/median) Jaundicea liver survival survival
Centralized national series
England and Wales 1999–2009 443 54 56% 46% 90%
[6]
Finland [59] 1987–2010 72 64 75% 75%b 92%b
Decentralized national series
France [64] 2003–2009 329 59 33–39% 33–39% 85–92%
Swiss [61] 1994–2004 48 59 39.5% 37% 91%
Netherlands [65] 1987–2008 214 59 38% 46% 73%
Canada [62] 1992–2002 230 64 n/a 39% 83%
Germany [66] 2001–2005 183 57 18% 20% 83%
Multicentre, not National
USA [67] 1997–2000 104 54 55% 46% 89%
Italyc 2001–2005 59 78 51% 38% 87%
National Asia
Japan [68] 1989–1998 1381 65 57–62% 52–62% 70–78%
a
Clearance of jaundice variably defined
b
Outcome at 2 years after KPE
c
Unpublished data from Italian Survey on BA including patients from five centres (Brescia, Bergamo, Modena, Naples
and Rome) (Alberti D, personal communication)
n/a: not available

in the collection of multinational data, including 3. Petersen C, Davenport M.  Aetiology of biliary atre-
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Origins of BA are mysterious, its diagnosis con- Kasai hepatoportoenterostomy and early postopera-
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will see improvements in understanding the basis transplant-free survival. Ann Surg. 2011;254:577–85.
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 Congenital Hepatic Cysts
29
Morven Allan and Mark Davenport

29.1 Introduction 29.2 Simple Hepatic Cysts

The incidence of congenital hepatic cysts is not The majority of antenatally detected liver cysts
known. A 10-year retrospective study of antenatally are simple in origin. The first one proving to be a
diagnosed abdominal cysts, carried out at a single simple liver cyst was described by Michel et al. in
Australian centre, showed that three hepatic cysts 1986 [4].
were detected in 22,000 live births during the period Their adult counterparts are regarded as a
January 1991–January 2002 [1]. However, with the common but usually incidental finding. So, one
increasing prevalence of antenatal ultrasonography, study identified a simple cyst in about 2.5% of an
it is inevitable that this incidence will increase. adult population, occurring most frequently in
Whilst the diagnosis can certainly be suspected the fourth and fifth decade of life [5], with an
antenatally, a precise diagnosis may be difficult due increased incidence in females (M:F 1: 4) [6].
to lack of specific features. Of course, this is true of However, antenatal diagnosis is infrequent with
any intra-­abdominal cystic lesion in a newborn fewer than 30 cases of simple liver cysts being
infant where the differential diagnosis includes reported in the literature [4, 5, 7–19]. The largest
mesenteric cyst, duplication cyst, haemangioma, single-centre series (n = 11) was reported by our-
teratoma, lymphangioma, cystic choledochal mal- selves in 2007 [18].
formation, renal cysts, ovarian cysts, etc. Histologically they can be defined as a fluid-­
Those antenatal cysts that can be seen to arise filled space lined by cuboidal or columnar epi-
from within the liver parenchyma can be divided thelium with a distinct lack of mesenchymal
into four possible categories: simple hepatic stroma and with an outer layer of fibrous tissue
cysts, mesenchymal hamartomas, ciliated foregut [12]. The majority (90%) are unilocular, ranging
cysts, and intrahepatic choledochal malforma- in size from mm to cm, the largest reported
tions (typically Type V) [2, 3]. Only the first three being >150  cm on postnatal imaging [16]
on this list will be discussed in any detail. (Fig. 29.1).

M. Allan · M. Davenport (*)

Department of Paediatric Surgery, Kings College
Hospital, London, UK
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 401

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_29
402 M. Allan and M. Davenport

a b

Fig. 29.1  Simple liver cyst antenatal detection on routine region of umbilical fissure (b). Contained 600 mls of bile-­
maternal USS from 24-week gestation. Confirmed on tinged (cyst bilirubin  =  100  μmol/L, probably reflecting
postnatal USS.  MR scan shows giant cyst occupying serum bilirubin as no bile connection) and was completely
entire right-side of abdominal cavity (T2 weighting)—(a). resected without incident
At operation, confirmed to be thin-walled rising from

29.2.1 Aetiology 29.2.3 Management

Their aetiology has been suggested to be an aber- These cysts seldom require intervention before
rant development of intrahepatic bile ducts due to birth. Percutaneous transuterine aspiration has
the cuboidal appearance of the epithelial lining been performed (up to five times in one case [13])
and location within the portal triad [11]. but only in the few cases [8, 13, 14, 18] where
Hypoplasia of the ducts is perhaps secondary to hydrops was present or where there was obvious
inflammation or obstruction, with the subsequent displacement of abdominal and thoracic organs
retention of fluid perhaps leading to cyst due to size. This of course is only a holding mea-
formation. sure as the cyst will reaccumulate shortly after.
It is our view that most simple cysts do not
require any intervention postnatally as the major-
29.2.2 Presentation ity stay asymptomatic and usually either remain
unchanged or undergo a diminution in size as
A successful antenatal diagnosis is challenging, detected by postnatal USS (Fig.  29.2). Larger
particularly in differentiating from a choledochal cysts may obstruct adjacent structures and can
malformation. On US, a simple liver cyst appears lead to bowel or biliary obstruction and in one
as an anechoic, unilocular fluid-filled space, most case IVC obstruction [17]. Infrequently they can
frequently originating within the right hepatic cause infection or haemorrhage [17]. Ito et  al.
lobe [6]. The cysts are most frequently picked up [13] reported one case where there had been five
in the third trimester although diagnosis has been repeated aspirations antenatally with a further
made as early as the 17th week of gestation [17]. successful postnatal aspiration on day 14. No fur-
Prenatal MRI can be performed and typically will ther intervention was required with resolution
show a high-intensity signal if T2-weighted [17]. until at least the time of the report at 21 months.
 29  Congenital Hepatic Cysts 403

10.0 Key 29.3 Mesenchymal Hamartoma

Simple cysts
(n = 10) Mesenchymal hamartoma (MH), although the sec-
7.5
Liver cyst size (cm)

Choledochal ond most common benign hepatic tumour in chil-

malformation
(n = 2) dren, remains rare. It usually presents as a large,
5.0 rapidly growing mass, occurring almost exclu-
sively within infancy and childhood (<2  years).
Antenatal diagnosis is infrequent, with fewer than
2.5 30 cases reported in the literature to date [18, 23–
44]. The first antenatal case to be reported was by
Foucar in 1983, when a woman was referred at
0.0
0 1 2 3 4 5 33  weeks of gestation with an inappropriately
Age (y) small uterus and maternal hypertension [23]. On
sonography several large hypoechoic masses
Fig. 29.2  Postnatal course of the antenatally detected
liver cysts of 12 infants that did not require surgery replacing the liver parenchyma were seen. Labour
[Reproduced with permission from Ref. 18] was induced the following week, resulting in a
stillborn female. Diagnosis of mesenchymal ham-
Surgical excision should be reserved for those artoma was confirmed at post-mortem.
with large lesions causing symptoms or mass MH can be defined as a benign overgrowth of
effect. Laparoscopic resection has been per- mature normal cells and stroma native to the
formed on simple liver cysts and shown to be safe liver. The majority are multicystic (75%) in
[19]. Ideally, complete resection should be nature, with the remaining being solid (echo-
attempted to avoid recurrence. However, this genic) or mixed. On histological appearance, the
depends on anatomical location as cystic component is composed of tortuous or cys-
marsupialization or subtotal excision has also
­ tic bile ducts and the degeneration of myxoid
been shown to be effective in our hands [15, 18]. stroma, with a lack of epithelial lining and instead
lined by loose connective tissue. The solid com-
ponent is predominantly hepatocytes but with
29.2.4 Prognosis proliferation of vessels [45].
Placental pathology has also been reported in
The prognosis is good, with only a handful of association with MH, typically a honeycombed
cases being reported in the literature associated multicystic enlargement which can be visualized
with squamous cell metaplasia arising from sim- by maternal USS. Several terms have been used
ple cysts. All of these cases were diagnosed in to describe this condition such as mesenchymal
adults (>30  years), and it is believed that such stem villous hyperplasia and placental mesen-
histological transformation is only likely to result chymal dysplasia. Histologically the placenta
from chronic inflammation [20, 21]. shows enlarged dysplastic villi, thrombosis of the
In the adult population, the risk of recurrence is chorionic vessels, and a multifocal cyst transfor-
reported to be high (>60%) in those treated with mation of the villi [18, 43].
aspiration or partial excision, and therefore total
excision with the lowest recurrence rate, is
favoured [22]. However, of the aforementioned 29.3.1 Aetiology
neonatal cases treated with surgical management
(partial or complete resection), no recurrences It has been hypothesized that there is an inade-
were reported, and of those which underwent ante- quate blood supply to the placenta which causes
natal aspiration, two of the three reaccumulated in aneurysmal dilatation of the chorionic vessels
the antenatal period but resolved postnatally. and hyperplasia of stem villi. Ischaemic lesions
404 M. Allan and M. Davenport

of the fetal liver occurs in response, although the gestation following intrauterine drainage of a
mechanism is unclear, but this results in large cyst and survived [29].
cystic masses seen by the second and third tri- There have been three cases reported where
mester [43]. antenatal aspiration of the cyst occurred. Bejvan
et  al. [29] undertook prenatal aspiration and
insertion of a pigtail drain at 27-week gestation;
29.3.2 Clinical Features however, in this case premature rupture of mem-
branes occurred and preterm labour at 30/40.
The most common presentation has been of an The infant then underwent a resection on day 21
abdominal mass detected by antenatal USS at of life with survival. In the second case, percu-
varying gestations (range 15–38  weeks). The taneous drainage of 110mls occurred just prior
larger lesions have been associated with polyhy- to an emergency Caesarean section for maternal
dramnios and foetal hydrops. Lesions have been hypertension. However, the infant needed an
reported to be in range of 5–14 cm, with the most urgent laparotomy on day 1 of life due to haem-
common site again being the right lobe of the orrhage from the puncture site [35]. The third
liver (50–75%) [46, 47]. Maternal α-fetoprotein case was more successful with three percutane-
and β-human chorionic gonadotrophin (HCG) ous aspirations occurring prior to a spontaneous
levels may also be seen to rise. vaginal delivery at 35  weeks gestation and a
A definitive diagnosis can be challenging in subsequent laparoscopic excision on day 1 of
the antenatal period and probably is not neces- life [36].
sary, but if the characteristic features can be dem- Definitive surgical resection is usually recom-
onstrated of a rapidly growing multiloculated mended, particularly in those who develop respira-
cystic lesion, then MH is probable. There are tory distress secondary to diaphragmatic splinting
only six cases reported of an antenatal diagnosis with the aim being to reduce volume. This occurred
of MH [27, 32, 35, 39, 40, 43], whilst the rest are in 17 of the 24 infants in the literature with sur-
content with “intra-abdominal cystic lesions” and vival in all. One infant underwent repeated cyst
postnatal confirmation. aspiration leading to regression [43]. There have
MRI can also be useful to identify liver tissue been six deaths. Of these, surgery was performed
and thus origin of the mass, since it is the only in one case despite a poor preoperative prognosis,
foetal organ to produce a hyperintense signal on with non-immune hydrops present in a neonate
T1 imaging [44, 45]. Whilst it has been used fre- born at 34-week gestation [36].
quently in the postnatal period, there are only two A laparotomy with partial or complete cyst
reports of its use antenatally [35, 39]. resection, with or without an associated segmen-
tectomy or lobectomy, is performed. There seems
to be no consensus on when surgery should occur
29.3.3 Management (range 1  day–5  months). However, those who
underwent laparotomy early in life were often
There have been a total of 24 cases of antena- due to neonatal respiratory distress, whilst in
tally detected MHs reported in the literature to those undergoing a delayed laparotomy, the indi-
date. cation was failure of cyst regression or increasing
Four cases developed fetal hydrops during the abdominal size.
second trimester [28, 29, 32, 36], and this has a There have been two infants reported where
very poor prognosis with two being stillborn and more conservative approaches have resulted in
a third dying shortly after birth. This is an indica- spontaneous regression of the cyst. In one case,
tion for expedited delivery to try and save such repeated postnatal percutaneous cyst aspiration
infants. The one survivor was born at 30-week was performed to relieve abdominal pressures
29  Congenital Hepatic Cysts 405

and improve pulmonary function. This led to sub- 29.4 Congenital Hepatic
sequent cyst regression despite formation of Foregut Cysts
intrahepatic calcification being noted [43].
Postsurgical cyst recurrence has been reported in Congenital hepatic foregut cysts (CFHC) are rare
two cases [35, 42]. However, both of these were lesions arising from embryonic foregut. Wheeler
only of moderate size and were seen to regress on and Edmonson first coined the term in 1984 and
subsequent imaging. defined their characteristics [48]. To date there have
As spontaneous regression is possible and the been only five cases of antenatally detected CFHC
likelihood is that these are histologically benign, reported in the literature (Table 29.1) [49–52].
then an initially conservative approach is reason- It has been hypothesized that these represent
able in otherwise asymptomatic infants. an abnormal foregut bud, arising from the thorax,
which becomes entrapped in the liver through
two patent pleuroperitoneal canals [50]. They
29.3.4 Prognosis have a histological relationship in this respect
with oesophageal and bronchogenic cysts.
Antenatally diagnosed MH has a mortality rate of
up to 20% and is higher than those presenting
later. Poor prognostic factors include the devel- 29.4.1 Histology
opment of non-immune hydrops and a rapidly
increasing cyst size with compression of thoracic The classic histological feature of CFHC is a cyst
and abdominal organs. composed of four layers: a pseudostratified

Table 29.1  Summary of the literature on antenatally diagnosed ciliated hepatic foregut cysts
Gestational
age at Location Size Squamous
Source Gender diagnosis (segment) (cm) Type Postnatal Surgery metaplasia
Stringer M 30 V, IV, VIII 7 Unilocular Aspiration Extended Y
[49] Day 5. right
hepatectomy
Betalli F 20 IV 3 Unilocular Biliary Resection, N
[50] obstruction 16 months
and
progressive
increase in
size
Guerin M 22 IV, V, VII 3 Multilocular Progressive Central N
[51] increase in hepatectomy
size and
Roux-en-Y,
11 months
Guerin F 22 V 2 Multilocular Central Y
[51] hepatectomy
and
Roux-en-Y,
14 months
Khoddami M 36 IV 2 Unilocular Re-presented Resection, N
[52] at 3 years— 3.5 years
abdominal
pain
406 M. Allan and M. Davenport

CA19–9, CEA and α-FP). However, none of

these cases were associated with metaplasia, and
those cases which did have associated metaplasia
had normal tumour markers [54]. This observa-
tion can thus be misleading and should be inter-
preted with care.

29.4.3 Treatment

Whilst some have suggested treatment with

Fig. 29.3  Ciliated hepatic foregut cyst. Classic histologi- sclerotherapy [54], surgical resection again is the
cal appearance of ciliated, pseudostratified, epithelial cyst
preferred method given the possibility for later
lining (haematoxylin-eosin) [By permission from Ref. 54]
malignant transformation. Some indications for
surgery have included increasing size, diame-
columnar epithelium composed of ciliated cells ter  >  4  cm, clinical symptoms, unexplained
with numerous goblet cells, a sub-epithelial con- abnormal liver function tests, or cyst wall abnor-
nective tissue layer, a smooth muscle layer, and a malities on imaging.
fibrous capsule [48] (Fig. 29.3). The presence of Like many central cysts, the intrahepatic bile
a liver lesion containing ciliated columnar cells is ducts are at risk during resection. Damage man-
pathognomonic for CHFC. These cysts do have a dates some form of biliary reconstruction [50],
malignant potential, but this is always deferred to and this may be a reason to defer surgery until
adult life. Squamous metaplasia (n = 6) and squa- 1 year of age as this can be quite complex.
mous cell carcinoma arising from the innermost
lining (n = 5) have been reported in adults with
the youngest being reported in a 21-year-old 29.4.4 Prognosis
male who had a diagnosis of liver cyst made in
infancy but never followed up [53, 54]. Overall prognosis is good with no reports of
recurrence post-surgery. Cysts have been seen to
enlarge following biopsy and may also recur after
29.4.2 Presentation sclerotherapy [54].

Imaging, both USS and cross-sectional, suggest

that these are predominantly unilocular with the 29.5 Conclusion
cyst fluid containing sediment (reflecting the
mucinous content). Mural calcification can be Most of the liver cysts that are diagnosed antena-
present, and they tend to be subcapsular and tally are incidental, innocuous with a relatively
located in the central liver segments, typically benign natural history. Nonetheless all deserve a
Couinaud segment IV. It had been suggested that full postnatal investigation work-up including
this predominance of segment IV is because it cross-sectional imaging (CT or MR as tolerated)
makes up most of the liver substance in the 4th– to make a diagnosis. Discrimination from type V
8th week of development [50]. Aspiration cytol- choledochal malformations is usually straightfor-
ogy may show the presence of ciliated columnar ward but may need radioisotope imaging
epithelial cells suspended in a mucinoid back- (Fig.  29.4). Virtually all the aforementioned
ground and again is pathognomonic. lesions have no isotope uptake and are “cold”,
Interestingly, one third of childhood and adult whilst isotope concentration should define a
cases have also raised tumour markers (e.g. “warm” or “hot” intrahepatic choledochal cyst.
29  Congenital Hepatic Cysts 407

a b

Fig. 29.4 (a) Antenatal detection with imaging at 1 year showing early radioisotope uptake. (b) Corresponding MR
image showing type V choledochal malformation [Reproduced with permission from Ref. 18]

10. Alcacay M, Dan U, Kessler A, Graif M, Shalev

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Briz A, et  al. Mesenchymal hamartoma of the liver 51. Guerin F, Hadhri R, Fabre M, et al. Prenatal and post-
in Beckwith–Wiedemann syndrome: the first reported natal ciliated hepatic foregut cysts in infants. J Pediatr
case. Pediatr Pathol Mol Med. 2000;19:455–60. Surg. 2010;45:9–14.
35. Kamata S, Nose K, Sawai T, et  al. Fetal mesenchy- 52.
Khoddami M, Aghdam MK, Alvandimanesh
mal hamartoma of the liver: report of a case. J Pediatr A.  Ciliated hepatic foregut cyst: two case reports in
Surg. 2003;38:639–41. children and a review of the literature. Case Rep Med.
36. Tsao K, Hirose S, Sydorak R, et al. Fetal therapy for 2013;2013:72017.
giant hepatic cysts. J Pediatr Surg. 2002;37:31–4. 53. Furlanetto A, Dei Tos AP. Squamous cell carcinoma
37. Mittermayer C, Bettelheim D, Horcher E, et  al.
arising in a ciliated hepatic foregut cyst. Arch Pathol
Prenatal sonographic detection of a giant multiseptate Lab Med. 1999;123:1115–7.
hepatic cyst in the third trimester. Ultrasound Obstet 54. Bishop K, Perrino C, Ruzinova M, et  al. Ciliated
Gynecol. 2002;20:97–8. hepatic foregut cyst: a report of 6 cases and a review of
38. Carta M, Maresi E, Giuffre M, et  al. Congenital
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hepatic mesenchymal hamartoma associated with https://doi.org/10.1186/s13000-015-0321-1.
 Choledochal Cyst and Congenital
Biliary Dilatation 30
Alessandro Settimi, Alessandra Farina,
Francesco Turrà, Maria Escolino, Mariapina Cerulo,
and Ciro Esposito

30.1 Introduction the biliary tree [3]. It can be diffused or confined

to a lobe (predominantly the left one) or to a seg-
Benign biliary diseases include a wide spectrum ment. Two types have been described, which may
of conditions, which may have similar clinical and represent different stages of the same disease:
laboratory findings, but they can differ signifi- Caroli’s disease, the “pure form,” with no liver
cantly with regard to etiopathogenesis, treatment, involvement, and Caroli’s syndrome when con-
and prognosis [1]. Imaging plays an important genital hepatic fibrosis coexists secondary to
role in diagnosis, differential diagnosis, treatment defective remodeling involving the entire intra-
decision and planning, and follow-up. They can hepatic bile duct tree [2].
be incidentally discovered in clinically asymp- Well-defined anechoic intrahepatic cystic
tomatic patients during either routine laboratory lesions are demonstrated at ultrasound, which may
tests or work-up for other diseases or alternatively also present with intra-cystic sludge or calculi [4].
during the diagnostic work-up in cholestatic Contrast-enhanced CT and MRI studies can dem-
patients [2]. Patient history may address the diag- onstrate the presence of the pathognomonic “cen-
nosis. We focus our attention in particular on two tral dot sign,” which corresponds to the
of these pathological conditions: congenital bili- fibrovascular bundle within the dilated cystic intra-
ary dilatation and choledochal cyst. hepatic bile duct, appearing as a hyper-enhancing
focus. Complications are related to bile stasis pre-
disposing to stone formation, recurrent cholangitis,
30.2 Congenital Biliary Dilatation secondary biliary cirrhosis, and, rarely, cholangio-
carcinoma. Magnetic resonance cholangiopancre-
Congenital biliary dilatation, or Caroli’s disease, atography (MRCPO) may be helpful in the
is a rare autosomal recessive congenital disorder differential diagnosis with polycystic liver disease
characterized by multifocal, nonobstructive, sac- or other conditions presenting with intrahepatic
cular, or fusiform dilatation of the large-sized bile duct dilatation by demonstrating the character-
intrahepatic bile ducts, which communicate with istic features of saccular dilatation of the intrahe-
patic bile ducts communicating with the biliary
tree. Moreover, MRI can be performed with hep-
A. Settimi · A. Farina · F. Turrà · M. Escolino ato-specific contrast agent, which confirms the
M. Cerulo · C. Esposito (*) biliary communication. Management depends on
Pediatric Surgery Unit, Department of Translational clinical presentation, localization, and stage of the
Medical Sciences, Federico II University, disease. Conservative treatment consists of antibi-
Naples, Italy
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 409

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_30
410 A. Settimi et al.

otics to treat cholangitis and hepatic abscess and increased risk for developing cholangiocarci-
ursodeoxycholic acid to prevent stone formation. noma, the recognition and proper management of
Radiological or endoscopic drainage procedures choledochal cyst disease are important.
are indicated in the case of biliary obstruction, Choledochal cysts are generally classified using
although related to high morbidity and mortality the Todani modification of the Alonso-Lej clas-
due to infectious complications. Partial hepatec- sification (Fig. 30.3) [8]. As the underlying etiol-
tomy is rarely recommended for localized disease, ogy of various subtypes of cysts remains
whereas liver transplantation may be a treatment unknown, the current classification may poten-
option when there is diffuse liver involvement [5]. tially be describing overlapping subtypes. We, as
other authors, have attempted to ask if type IV
choledochal cysts could be part of the disease
30.3 Choledochal Cyst progression of type I cysts. As for the surgical
management of this pathological condition, lapa-
A choledochal cyst is the congenital cystic dilata- roscopic surgery is safe and feasible in selected
tion of the extrahepatic and/or intrahepatic biliary patients, but it technically highly demanding. The
tree. It is a congenital anomaly usually found in short-­term complications of patients are gener-
the pediatric population (Fig.  30.1), and is esti- ally good, with an early complication rate of less
mated to occur in 1  in 5000 live births, with a than 5%. Recurrent strictures and intrahepatic
higher frequency in Asians. Common symptoms stone formations are well-known and well-
include abdominal pain and vomiting, but these described long-term complications, with the risks
are nonspecific, and therefore the condition is being forever present. The long-term complica-
usually difficult to diagnose during infancy. On tion rate is about 15%. There has been no malig-
the other hand, jaundice is a more specific symp- nancy documented so far in any of our patients.
tom, and the diagnosis is usually made early if the As antenatal ultrasound becomes more popular
jaundice is prolonged during the neonatal period and easily available in this era, more and more of
or related to the abnormal liver function test
because of cholestasis or cholangitis [6].
The presence of the triad of symptoms is the
classic description of a choledochal cyst, but it is
rare. The diagnosis is usually made in the first
few years of life; in particular more and more
patients have been diagnosed antenatally in
recent years (Fig.  30.2) [7]. As there is an

Fig. 30.2  Ultrasound-guided, contrast-enhanced trans­

hepatic cholangiographic images. The right and left main
hepatic ducts were dilated. Cystic dilatation of the proxi-
mal choledochal duct and transition of contrast media to
Fig. 30.1  A surgical aspect of a giant choledochal cyst the intestine were observed
30  Choledochal Cyst and Congenital Biliary Dilatation 411

IA IB

I II III

IC

IV-A IV-B V

Fig. 30.3  Todani classification

the diagnoses are made antenatally [9]. This mation [11]. Type I and type IV choledochal
allows us to have better communication with the cysts are two distinct entities according to the
parents. The parents are likely to have better Todani classification [8]. Type I cyst has no intra-
acceptance and be more prepared to agree to hepatic component, and the common hepatic duct
early surgical intervention for the patients. The proximal to the cyst is usually normal, whereas
common bile duct pathological condition can be type IV disease contains multiple cysts, with
detected antenatally as early as 15 weeks’ gesta- involvement of the intrahepatic bile ducts. In our
tion. All the patients diagnosed antenatally had experience, type I cysts occur more frequently in
been asymptomatic before the operation. Early those patients diagnosed earlier in their lives,
surgery greatly decreases the occurrence of whereas type IV cysts are usually found in older
disease-­related complications, for example, acute children [12]. The usual presenting symptoms for
cholangitis, acute pancreatitis, early formation of older children are the complications of chole-
biliary stone disease, biliary cirrhosis, liver cir- dochal cysts, that is, stone formation and acute
rhosis, and malignancy [10]. Although the post- cholangitis. Because of repeated cholangitis,
operative complication rates in the antenatal and there could be bile duct stricture formation. It
postnatal group did not show any statistical sig- would be possible to deduce that dilatation of the
nificance, possibly because of the small number, proximal segment takes time to develop and is a
we have experienced easier dissection during the gradual process. Hence, the diagnosis of a type
surgical procedure in antenatally diagnosed IV choledochal cyst could well be a result of the
patients as a result of decreased periductal inflam- chronic complications of a type I choledochal
412 A. Settimi et al.

cyst. The chronic inflammation may result in fur- due to infectious complications. Partial hepatec-
ther stone and stricture formation. The final result tomy is rarely recommended for localized dis-
would be the dilatation of the more proximal seg- ease, whereas liver transplantation is a treatment
ments and therefore the presence of multiple option when there is diffuse liver involvement.
cysts, that is, “type IV” choledochal cysts. In con- As for choledochal cysts, as they have been
clusion, choledochal cyst is a rare disease and is widely known to be extremely highly associated
commonly present in childhood. Antenatal diag- with pancreaticobiliary maljunction, Todani
nosis by means of routine ultrasound s­ creening is made his classification to include a concept of
possible and allows earlier surgical intervention, pancreaticobiliary maljunction in 1995.
which may prevent later complications [13]. According to the accumulation of case reports on
Laparoscopic surgery is feasible but is techni- congenital biliary dilatation from around the
cally demanding. Long-term follow-up is neces- world, it has been understood that most cases are
sary to identify those who are at risk for classified as either type I with local dilatation of
complications. the common bile duct or as type IV-A, which is
associated with involvement of the intrahepatic
bile duct. In addition, it has been clarified that
30.4 Discussion pancreaticobiliary maljunction is extremely
highly associated with types Ia, Ic, and IV-A;
Reported cases of dilated biliary tracts have a however, it is almost never associated with types
higher prevalence in Asia than in Western coun- Ib, II, III, IV-B, and V [8].
tries. In a nationwide survey of Korean children, The presence of the triad of symptoms is the
acquired biliary diseases and congenital hepato- classic indication of a choledochal cyst, but it is
biliary diseases were 7.6 and 12.6% of total hepa- rare. The diagnosis is usually made in the first
tobiliary diseases respectively [1]. Therefore, it is few years of life; in particular, more and more
important to define abnormal bile duct dilatation patients have been diagnosed antenatally in
because of its possible association with congeni- recent years [9]. Laparoscopic surgery is safe and
tal malformation and pathological conditions, feasible in selected patients, but it is technically
such as infection, calculi, biliary dysfunction, highly demanding [14]. The short-term compli-
and malignancy. Various kinds of pathological cations of patients are generally good, with an
conditions, such as flow disturbances of bile and early complication rate of less than 5% [15].
pancreatic juice, reciprocal reflux between bile Recurrent strictures and intrahepatic stone for-
and pancreatic juice, and malignancy of biliary mations are well-known and well-described
systems, can occur in the hepatobiliary system long-term complications, with the risks being
and pancreas secondary to bile duct dilatation forever present. In conclusion, biliary congenital
and pancreaticobiliary maljunction. pathological conditions are a rare disease, and
Ultrasound is a useful method of evaluating the patients with these conditions, according to inter-
biliary tract system in children. It is rapid and national guidelines, have to be sent to a national
noninvasive and does not involve radiation expo- referral center where there is a high level of
sure. As for congenital bile duct dilatation, com- expertise in their treatment, to obtain excellent
plications are related to bile stasis predisposing to results, also using in some cases a minimally
stone formation, recurrent cholangitis, secondary invasive surgical treatment.
biliary cirrhosis, and rarely, cholangiocarcinoma.
Conservative treatment consists in the use of anti-
biotics to treat cholangitis and hepatic abscess and
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Radiological or endoscopic drainage procedures 1. Santiago I, Loureiro R, Curvo-Semedo L, Marques C,
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2. Yonem O, Bayraktar Y.  Clinical characteris- 9. Howell CG, Templeton JM, Weiner S, Glassman M,
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3. Dhumeaux D. Congenital cystic diseases of the intra 1983;18(4):387–93.
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2005;29:878–82. choledochal cyst. Ann Surg. 1970;172(5):844–51.
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central dot sign in CT. Radiology. 1990;174:161–3. cyst excision with hepaticoenterostomy for chole-
5. Lai Q, Lerut J.  Proposal for an algorithm for liver dochal cysts and their surgical management in children
transplantation in Caroli’s disease and syndrome: versus adults. J Pediatr Surg. 1997;32(7):1097–102.
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Transpl. 2016;30:3–9. genital biliary cystic disease: special reference to
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Hiçsönmez A.  Choledochal cysts in children: intra- Hepato-Biliary-Pancreat Surg. 2003;10(5):340–4.
hepatic ductal dilatation does not indicate true intra- 13. Schroeder D, Smith L, Prain HC. Antenatal diagno-
hepatic biliary duct disease. Turk J Gastroenterol. sis of choledochal cyst at 15 weeks’ gestation: etio-
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2009;45:28–30. 2003;10(5):352–9.
8. Todani T, Watanabe Y, Narusue M. Congenital bile duct 15. Saing H, Han H, Chan KL, Lam W, Chan FL, Cheng
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of thirty-seven cases including cancer arising from ledochal cysts. J Pediatr Surg. 1997;32(11):1563–6.
choledochal cyst. Am J Surg. 1977;134(2):263–9.
 Part VI
Anterior Abdominal Wall Defects
 Gastroschisis and Omphalocele
31
Mikko P. Pakarinen, Antti Koivusalo,
and Janne Suominen

31.1 Introduction cles are separated to a variable degree above the

abdominal defect, and omphalocele may present
Gastroschisis and omphalocele are the most com- as a part of more extensive cephalo-caudal fold
mon congenital abdominal wall defects with an defects such as pentalogy of Cantrell and cloacal
unclear etiology. The incidence of gastroschisis exstrophy, which fall outside the scope of this
approximates 3–4.5/10000 live births and that of review.
omphalocele 2–3/1000 live births omphalocele The main goals of the management are prompt
2-3/10000 live births [1]. The incidence of gas- protective coverage of eviscerated organs and
troschisis continues to increase in the Western abdominal wall closure while avoiding iatrogenic
world. For example, in Finland, the birth preva- injuries. This is usually relatively straightforward
lence of gastroschisis has increased by 40% dur- in gastroschisis, and abdominal closure is accom-
ing the last 20 years. plished in most patients during the first week of
Gastroschisis refers to a small developmental life, whereas in patients with large omphaloceles,
abdominal defect almost always right to the the final fascial closure of the abdominal wall
umbilicus through which uncovered small intes- may be achieved only after several years follow-
tine and colon and occasionally stomach and ing skin grafting and multiple surgeries. In the
gonads eviscerate. The abdominal wall and mus- management of gastroschisis, one of the most
cles around the defect are normally developed. In significant challenges is caused by associated
omphalocele, the intestine and other abdominal intestinal dysmotility, which may require pro-
organs, including the liver, the spleen, and gonads longed parenteral nutrition, predisposing to com-
covered by the amniotic membrane, eviscerate plications of intestinal failure, including septic
through a large umbilical defect. The rectus mus- episodes and liver disease [2]. The risk of irre-
versible intestinal failure is further increased
when complications require significant bowel
M. P. Pakarinen (*) resections in patients with associated atresia and
Section of Pediatric Surgery and Pediatric Liver perforation of necrosis of the intestine or when
and Gut Research Group, Children’s Hospital,
University of Helsinki and Helsinki University there is congenital loss of the midgut in patients
Hospital, Helsinki, Finland with vanishing or closed gastroschisis [3–7].
e-mail: [email protected] Comprehensive treatment of omphalocele is
A. Koivusalo · J. Suominen often complicated by significant associated disor-
Section of Pediatric Surgery, ders, which need to be managed in carefully
Children’s Hospital, University of Helsinki and planned coordination with the abdominal wall
Helsinki University Hospital, Helsinki, Finland
e-mail: [email protected]; [email protected] defect for optimal outcomes [8].

© Springer Nature Switzerland AG 2019 417

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_31
418 M. P. Pakarinen et al.

31.2 Embryology methods can usually be considered in time before

and Pathophysiology labor [13]. Prenatal ultrasound (US) is the pri-
mary imaging modality during pregnancy
Even though the incidence of gastroschisis has because it is noninvasive and rapid and it allows
increased during past decades, the etiology and real-time fetal examination. Maternal serum
exact pathogenesis have remained unclear. alpha-fetoprotein (AFP) is usually elevated with
Normally, during the third week of gestation, the abdominal wall defects, although there is varia-
midgut becomes distinct from the yolk sac, and at tion between gastroschisis and omphalocele. In
sixth week the midgut elongates resulting in gastroschisis, maternal serum AFP is usually
physiologic development of an umbilical hernia. markedly abnormal, whereas in omphalocele
The lateral body wall folds form early in gesta- AFP is usually elevated more moderately with a
tion as a combination of the parietal layer of lat- much wider range. Current practice for antenatal
eral plate mesoderm and overlying ectoderm and surveillance in gastroschisis is variable, but regu-
move ventrally into the midline [9]. At 10 weeks, lar US monitoring aims to determine possible
the midgut returns rapidly to the embryonic bowel dilatation and thickening, amount of amni-
abdominal cavity, and the defect in the abdomi- otic fluid, and fetal growth and to detect any other
nal wall closes. In gastroschisis, the fusion of lat- associated malformations. Prenatal definition of
eral body folds fails to occur leading to an simple and complex (atresia, necrosis, perfora-
opening in the abdominal wall. Several hypothe- tion, or volvulus) gastroschisis is used in prenatal
ses leading to the formation of gastroschisis have counseling and planning postnatal medical and
been introduced [10, 11]. Young maternal age has surgical treatment. In antenatal US, intra-­
been linked to the incidence of gastroschisis in abdominal bowel dilatation and polyhydramnios
several studies as well as maternal smoking and are associated with an increased risk of bowel
drug usage implying a role for teratogens in the atresia, and gastric dilatation has been linked to
development of gastroschisis [12]. Ethnic back- the occurrence of death in the neonatal period
ground and body mass index may have a role as [14]. Doppler US has been used to determine the
well. Although compelling epidemiologic risk mesenteric circulation during late pregnancy, but
factors have been identified, the underlying this data is scarce to provide guidelines for the
pathogenesis of gastroschisis remains controver- timing of delivery. Usually antenatal magnetic
sial, and most likely the origin of this defect is resonance imaging (MRI) is not necessary in
multifactorial. fetuses with gastroschisis but should be used as
The exact pathogenesis behind omphalocele is an adjunct to provide better understanding on
also still unsolved. Omphalocele results from the anatomy if US reveals untypical findings. Fetal
failure of bowel to return to the abdominal cavity karyotyping is not necessarily indicated in gas-
following the physiological herniation of the umbil- troschisis, as neither single genes have been iden-
ical cord between the 6th and 11th week of develop- tified as responsible for the occurrence of
ment. Omphalocele is more often seen in gastroschisis nor recognized syndromes [15].
conjunction with syndromes that have genetic back- The risk of familial recurrence approximates
ground like Beckwith-Wiedemann suggesting dif- 2.5% [16].
ferent etiologies for the two congenital anomalies. As associated anomalies are more common
with omphalocele than with gastroschisis, MRI
should be done after US has revealed o­ mphalocele
31.3 Antenatal Screening with special emphasis on evaluation of cardiac
and Follow-up and central nervous system. Fetal echocardiogra-
phy and karyotyping should also be performed.
Gastroschisis and omphalocele are detected in Complex cardiac defects, nervous system anoma-
developed countries in over 90% of cases within lies, and chromosomal alterations define the
the second trimester of pregnancy, and delivery prognosis and mortality more strongly than the
31  Gastroschisis and Omphalocele 419

size and nature of omphalocele itself. Even if fetus with omphalocele whether the chosen mode
imaging modalities have evolved during the past of delivery is cesarean section or vaginal deliv-
decades, there is still remarkable proportion of ery. Cesarean section is, however, favored in
fetuses that appear to be isolated omphaloceles in fetuses with large defects containing an extra-­
antenatal scans but are found to have multiple abdominal liver [21].
anomalies postnatally, an important issue to be
discussed with parents during pregnancy.
31.5 Clinical Features
and Associated
31.4 Delivery Malformations

The most discussed issues concerning the deliv- 31.5.1 Omphalocele

ery of a fetus with an abdominal wall defect are
the facilities that manage the delivery, the timing In omphalocele, there is variable-sized defect in
of the delivery, and the mode of delivery. abdominal wall at the site of umbilical cord lead-
Contemporary evidence suggests that the deliv- ing to protrusion of intestines and sometimes the
ery of a fetus with an abdominal wall defect liver, spleen, and gonads through the defect.
should occur in a tertiary perinatal center. The Eviscerated organs are covered by a sac formed
high risk of preterm labor in pregnancies with of peritoneum, Wharton’s jelly, and amnion, and
gastroschisis and postnatal management of gas- this sac is normally intact. Abdominal wall mus-
troschisis closure and associated complications cles are usually intact but hypoplastic and dis-
such as intestinal atresia or perforation, as well as placed laterally. Variability in the size of the
the risk of respiratory compromise and associ- omphalocele is remarkable ranging from a small
ated cardiac defects in fetuses with omphalocele, loop of the intestine to giant omphaloceles where
requires immediate access to expert neonatal most of the intestines and abdominal organs
intensive care and pediatric surgical service [17, occur within the amniotic membrane outside the
18]. In fetuses without prenatally diagnosed poorly developed abdominal cavity. The size of
lesions, successful deliveries may, however, omphalocele together with associated malforma-
occur in lower-grade perinatal units, and with tions determines largely both the early treatment
appropriate postnatal care and timely transfer to a strategies and long-term outcomes. Associated
specialist center, good outcomes can be achieved. malformations among patients with omphalocele
Contemporary studies have failed to show any are common as over 75% of the patients have
significant difference in the outcome of fetuses been reported to have either chromosomal anom-
with gastroschisis after planned late preterm aly or defect in other organ systems than abdomi-
delivery (35–37 weeks) or delivery at a later date nal wall [22, 23]. If the sac covering omphalocele
(≥38 weeks). Because of the high risk of preterm is ruptured, this needs to be repaired in prompt
labor and associated neonatal death, pregnant fashion, but otherwise other malformations
women with a fetus with gastroschisis should be define the treatment more than omphalocele
alerted for the signs of preterm labor and be itself. Babies born with large omphalocele may
admitted to an appropriate maternity unit without have hypoplastic thoracic cavity associated with
delay. There is no evidence that US findings of pulmonary hypoplasia leading to severely
bowel distension should guide the timing of the compromised respiratory function soon after
­
delivery. In fetuses with gastroschisis, induced or birth. Up to one third of omphalocele patients
spontaneous vaginal delivery is safe and can be may have congenital heart defects [23].
attempted unless there are obstetric indications Interestingly, associated anomalies may occur
for cesarean section [19–21]. more commonly in minor rather than in large
Most infants with omphalocele are born at omphaloceles [24]. Chromosomal anomalies are
term. There is no difference in the outcome of a significantly more common in offspring of
420 M. P. Pakarinen et al.

women 35 years and older [22]. Live-born infants 31.6 Management

with trisomy 13 and trisomy 18 have omphalo- and Complications
cele in up to 7.5% of cases, and these chromo-
somal anomalies are more common; the earlier 31.6.1 Omphalocele
omphaloceles are detected during pregnancy,
whereas the association between trisomy 21 and After delivery infants with large omphaloceles
omphalocele is controversial [25]. When the with hypoplastic rib cage and pulmonary hypo-
diagnosis is made in early pregnancy, the propor- plasia may require intubation and ventilation.
tion of aneuploidy can increase up to two thirds. Nasogastric tube is inserted for gastric decom-
If molecular karyotype has not been assessed pression. Intravenous access is inserted and ade-
during pregnancy, it should be verified after the quate fluid resuscitation started. Coexisting
birth. Survival among neonates with isolated diaphragmatic defects can be seen in chest X-ray.
omphalocele ought to be over 90%, but associ- If the omphalocele is ruptured, the eviscerated
ated anomalies have impact on survival rates as organs are protected with cling film as in gastros-
especially chromosomal abnormalities worsen chisis, and intravenous antibiotics are started. If a
the prognosis. primary skin closure is not feasible, the ruptured
sac should be repaired by suturing, or cadaver
skin grafting should be done without undue delay
31.5.2 Gastroschisis [27, 28].
A detailed evaluation for associated anomalies
As the bowel remains eviscerated, it is not rotated including echocardiography, abdominal US for
normally, and also intestinal atresias among these renal anomalies, assessment of molecular karyo-
patients can be regarded as a consequence rather type, and external examination for other visible
than a true associated anomaly. Cryptorchidism anomalies should be made in all infants with
presumably develops secondary to bowel evis- omphalocele regardless of the size of the defect.
ceration and lack of intra-abdominal pressure. Postnatal hypoglycemia may indicate Beckwith-­
However, there is increasing evidence implying Wiedemann syndrome. In majority of infants
that up to one third of gastroschisis cases are with omphalocele, enteral feeding can be started
associated with a variety of anomalies [13, 23]. within days the period with parenteral nutrition
Cardiac anomalies have traditionally been linked and the need of central venous catheter is short;
to omphalocele but seem to be present in gastros- in many patients, insertion of central venous
chisis as well. Furthermore, it appears that fetuses catheter is unnecessary.
with gastroschisis that die in utero or are termi- Surgical management of the omphalocele
nated during pregnancy have more often associ- aims for complete fascial and skin closure of the
ated anomalies than surviving babies with defect. In infants with small omphaloceles, direct
gastroschisis [26]. Taken together, recent data closure of all layers can be accomplished during
supports careful evaluation of possible associated the first days of life. In larger defects, the obsta-
anomalies also in patients with gastroschisis. cles in the completion of the final repair include
The bowel that has floated freely on amniotic small abdominal cavity and lateral migration of
fluid is never quite the same as in healthy new- the margins of the abdominal musculature. In
borns. The bowel can be thickened and edema- infants with cardiac defects, lung hypoplasia, or
tous, is often covered with fibrinous peel, and in prematurity-elevated intra-abdominal pressure
15–20% of cases intestinal atresia is noted [23]. after even minor attempts of reduction, the con-
Even without atresia, the bowel length among tents of the sac may cause cardiopulmonary com-
gastroschisis patients is shortened compared with promise. In large defects with extracorporeal
healthy babies, and intestinal dysmotility to vari- liver, early reduction of the contents causes
able degree is always accompanied with abdominal compartment syndrome and is gener-
gastroschisis. ally not possible, and staged closure is advisable.
31  Gastroschisis and Omphalocele 421

Closure of a defect located high in the epigas- of age. It may be possible to close the defect with
trium may also be challenging because of prox- prosthetic mesh followed by serial excision of
imity of the costal arcs of the narrow belt of the mesh until apposition of the fascia margins is
abdominal musculature around the defect. achieved. Use of subcutaneously located pros-
If staged closure is chosen, the surgeon has thetic material can be complicated with dehis-
several options. There is no hurry to perform cence and infections and can be unsuitable for
complete closure. Covering the defect by widely long-term solution. If possible, it is better to per-
mobilizing the abdominal skin and suturing the form one well-planned operation instead of sev-
mobilized skin over the sac is possible in medium-­ eral incomplete attempts. In the planning of the
sized omphaloceles, but overt tension in the clo- final closure, the size of the contents of the sac in
sure may result in dehiscence, rupture, or large relation with the volume of the abdominal cavity
central scar. The epithelization of the sac can be is assessed. In this assessment, whole-body MRI
achieved by dressing with nontoxic topical agents imaging may be helpful, and the location of the
(e.g., silver sulfadiazine) or by covering the sac margins of the abdominal musculature can be
with cadaveric skin grafts. A recent small series verified. Small abdominal domain can be gradu-
described the use of vacuum suction device [29]. ally widened with the help of intra-abdominal
Omphalocele may be supported with a tethered tissue expander inserted through a Pfannenstiel
dressing for the first weeks of life. Complete mat- incision (Figs. 31.1, 31.2, and 31.3).
uration and epithelization of the scar may take Closure of the abdominal musculature can be
several months, during which time the relative achieved with component separation technique in
size of omphalocele usually grows smaller. which the abdominal wall surface is enlarged by
Despite a large remaining ventral hernia, infants translation of the muscular layers without com-
are able to develop motor skills appropriate for promising the innervation and blood supply of
age such as walking and climbing. the muscles [30]. Cooperation with a plastic sur-
Timing of the final closure of a large defect geon familiar with compartment separation tech-
depends on the infant’s general condition, and nique is advisable. If the need arises, the patient
treatment of associated anomalies and final clo- can be prepared for a pedicled latissimus dorsi
sure may occur anywhere between 1 and 7 years myocutaneous flap.

a b

Fig. 31.1  Axial (a) and sagittal (b) preoperative MRI images of a 1-year-old infant with omphalocele. Omphalocele
sac is epithelialized and contains the liver (L); defect diameter is 10 cm
422 M. P. Pakarinen et al.

a b

TE

L
TE

Fig. 31.2  Same patient as in Fig. 31.1. Widening of the abdominal domain with intra-abdominal tissue expander (TE)
in axial (a) and sagittal (b) MRI projections. (L) denotes the liver

Fig. 31.3  Same patient

a c
as in Figs. 31.1 and
31.2. Widening of
abdominal domain is
under way with
intra-abdominal tissue
expander in situ (a and
b) and the result after
removal of tissue
expander and final
closure of anterior
abdominal wall with
compartment separation
technique (c) b

Postoperative monitoring includes monitoring 31.6.2 Gastroschisis

of intra-abdominal pressure, central venous pres-
sure and diuresis, and serial measurement of blood After delivery, a baby with gastroschisis is trans-
lactic acid. In a well-planned repair without undue ferred to neonatal intensive care unit with lower
tension, abdominal compartment syndrome and body wrapped in transparent cling film or plastic
prolonged mechanical ventilation are avoidable. bag so that eviscerated intestines remain pro-
31  Gastroschisis and Omphalocele 423

tected, supported, and visible for inspection. In Primary abdominal closure is not usually safe in
addition to bowel protection, the initial care con- the presence of thickened, edematous bowel coated
sists of maintenance of body temperature and with fibrinous peel and a small abdominal domain.
fluid and electrolyte balance as well as respira- These cases are best treated by placing eviscerated
tory support when required. Bowel viability is bowel into a transparent s­pring-­loaded preformed
ascertained and checked for any mesenteric silo under adequate analgesia and sedation at bed-
twisting or restrictive compression against a side. Bowel is gradually reduced into the abdominal
small fascial defect. Intravenous fluid replace- cavity by daily reductions in silo usually within a
ment is guided by clinical signs of hypovolemia week followed by abdominal closure, which can be
to avoid excessive rehydration and undesirable performed by suturing or by simply stretching the
tissue edema. Venous access, preferentially using umbilical remnant over defect without fascial clo-
percutaneous jugular catheter, is established to sure (Fig. 31.5). The umbilical cord covered defect
allow several weeks of parenteral nutrition before contracts spontaneously in a few weeks and pre-
recovery of bowel function, and nasogastric tube serves aesthetically normal umbilicus [1].
is inserted to facilitate intestinal decompression.
The presence of associated malformations is
­routinely screened with US examination of the Surgery for simple gastroschisis
heart, head, and abdomen. Simple gastroschisis
The surgical care of gastroschisis aims for
bowel reduction and abdominal wall closure
without harmful increases in the intra-abdominal
non-reducable
pressure (Fig. 31.4). In some patients, this can be reducable Intra-abdominal pressure↑
achieved right after birth with primary abdominal
closure, while others require gradual bowel
reduction with silo and staged abdominal closure.
silo
Before final selection of the closure method, the primary closure (fascial patch)
intestine should be carefully examined for atre-
sia, perforation, or necrotic areas, which signifi- Fig. 31.4  Outline of surgical management principles of
cantly affect surgical treatment. isolated gastroschisis

at birth 4 days 7 days

Fig. 31.5  Gradual bowel reduction with preformed silo and staged abdominal closure
424 M. P. Pakarinen et al.

The most feared and devastating, although a Intestinal diversion and primary anastomosis are
rare complication of primary abdominal closure, combined either with primary abdominal wall
is abdominal compartment syndrome, which closure or staged silo closure depending on oper-
may lead to a massive intestinal resection and ative findings. Another surgical option with asso-
short bowel syndrome. Forceful reduction of the ciated intestinal atresia is to leave the atresia
intestine may result in an intolerable increase in initially untouched, continue parenteral nutrition
intra-­abdominal pressure. Resulting abdominal and intestinal decompression with nasogastric
compartment syndrome is a life-threating com- tube, and perform delayed atresia repair once the
plication characterized by decreased venous reduction has been completed. Delayed repair of
return, low cardiac output, ventilatory compro- intestinal atresia is most commonly performed in
mise, mesenteric ischemia, and renal hypoperfu- a separate laparotomy only several weeks after
sion that necessitates immediate decompressive abdominal wall closure has healed, and abdomi-
laparotomy to avoid intestinal necrosis. Removal nal inflammation has settled facilitating adhe-
of fascial sutures and placement of a circumfer- siolysis and identification of the dilated and
ential fascial patch or silo reduce intra-abdomi- dysmotile small intestinal segment above the
nal pressure efficiently. Measurement of bladder atresia. In vanishing gastroschisis, all the remain-
pressure through a Foley catheter or renal perfu- ing bowel should be preserved, and the dilated
sion with infrared spectroscopy is useful in mon- small bowel proximal to the atresia is dealt with a
itoring intra-abdominal pressure after primary suitable tailoring/lengthening procedure at the
closure and each repeated reduction during silo time of atresia repair.
treatment. Abdominal compartment syndrome is Once abdominal closure has been achieved,
efficiently avoided by using staged abdominal babies are weaned from ventilatory support, and
closure with silo whenever any concern of venti- enteral nutrition is instituted through nasogastric
latory or hemodynamic compromise arises dur- tube. Oral feeds, preferentially fresh breast milk,
ing attempted primary closure. are advanced according to individual tolerance.
There are several surgical options to manage Intermittent feeding intolerance is common
gastroschisis complicated by intestinal atresia, especially during the early postoperative period.
perforation, or necrosis (Fig.  31.6). The safest The possibility of missed intestinal atresia
option is to remove the diseased part of the should be ruled out with small intestinal contrast
­intestine and exteriorize both bowel ends as osto- study if bowel function has not recovered in
mies. If the patient’s general condition is good, 2–3 weeks.
and there is no significant abdominal contamina- The risk of intestinal failure is 12 times higher
tion, a primary anastomosis may be performed. in patients with complicated gastroschisis when
compared to isolated gastroschisis [3]. Because
Surgery for complex gastroschisis of the increased risk for developing intestinal
failure, management of complicated gastroschi-
GS + perforation/necrosis GS + atresia
sis in this respect should start from the very
beginning. Among other things, this includes the
primary Delayed
use of percutaneous tunneled single-lumen cen-
anastomosis enterostomy repair/stoma tral venous catheters with antimicrobial locks to
prevent septic episodes and novel parenteral lipid
Primary abdominal emulsions to prevent intestinal failure-associated
closure
Silo and delayed liver disease. When intestinal diversion is applied,
closure routine refeeding of the distal mucous fistula pro-
motes bowel function and minimizes the require-
Fig. 31.6  Outline of surgical management principles of ment of parenteral support while supporting
complicated gastroschisis physiological liver function.
31  Gastroschisis and Omphalocele 425

31.7 Early Outcomes most omphalocele survivors have similar quality

of life as their healthy peers [21].
31.7.1 Omphalocele

In live-born fetuses with omphalocele, infant mor- 31.7.2 Gastroschisis

tality of 25% can be expected (Table  31.1).
Associated congenital heart defects, central ner- Infants with complicated gastroschisis are prone to
vous system defects, prematurity, and chromo- face much more complicated clinical course than
somal defects increase the risk of infant death their counterparts with isolated disease. In isolated
2.4–7.7-fold [22]. Important predictors of mortality gastroschisis, average duration of mechanical ven-
include also respiratory insufficiency at birth tilation is 4–6  days, which is nearly doubled in
and  development of pulmonary hypertension. complicated gastroschisis [3, 4]. Gastroschisis is
Pulmonary hypertension is characterized by associated with different degrees of intestinal dys-
increased oxygen requirement and right ventricular motility, which delays return of propulsive peri-
pressures (>40  mmHg) in early echocardiogram stalsis and prolongs the need for parenteral support
and often observed in patients with giant omphalo- (Table  31.2). The gastroschisis-associated dys-
celes [32]. Isolated omphaloceles which comprise motility is resistant to medical therapy, and accord-
about 20–25% of all live-birth cases have the best ing a Cochrane review, there is no benefit of
prognosis with 7.8% infant death rate [22]. erythromycin on feeding tolerance in patients with
Neurodevelopmental dysfunctions have been gastroschisis. In patients with isolated gastroschi-
reported in half of survivors with giant omphalo- sis, mean duration of parenteral nutrition and
celes in whom the primary hospitalization is pro- length of h­ ospital stay is just over 1 month, while
longed and includes mechanical ventilation, a small percentage of patients develop intestinal
oxygen supplementation, delayed enteral feed- failure-associated liver disease, and around 4%
ing, and delayed closure of the abdominal wall. still die. The respective figures are markedly
Autism, hypotonicity, neurodevelopmental higher for patients with gastroschisis complicated
delays, and poor motor function are the most by intestinal atresia, perforation, or necrosis
often reported dysfunctions [33]. (Table 31.2). In these patients, length of stay, dura-
Long-term complications include failure to tion of parenteral nutrition, and incidence of intes-
thrive, gastroesophageal reflux, and intermittent tinal failure-associated liver disease are twice
abdominal pain. Cosmetic issues including the higher and mortality about four times higher than
missing umbilicus and extensive abdominal scar in patients with isolated gastroschisis [3, 4].
are common in all omphalocele patients regard-
less of the size of the defect. At young adult age, Table 31.2  Comparative outcomes of isolated and com-
plicated gastroschisis
Isolated Complicated
Table 31.1  Infant mortality among live-born fetuses gastroschisis gastroschisis
with omphalocele
Length of stay 36 (28–32) 76 (67–84)
Live Infant (days)
Author (year) Period births mortality (%) Duration of 34 (25–41) 72 (63–81)
Marshall et al. 1995–2005 1729 28.7 parenteral nutrition
[24] 2015, USA (days)
Corey et al. 1997–2012 1448 20.0 Intestinal failure-­ 12 (4–20) 28 (23–33)
[31] 2014, USA associated liver
Finnish Register 1993–2011 245 21.6 disease (%)
of Congenital Mortality (%) 4 (1–8) 15 (4–30)
Malformations Data are combined means (range) of four studies (Arnold
2011, Finland et al. [5], Bradnock et al. [6], Gover et al. [7], Lap et al.
Summary 4001 25 (average) [4]) including 5161 patients
426 M. P. Pakarinen et al.

Financial Support  Mikko Pakarinen was supported with 11. Chambers CD, Chen BH, Kalla K, Jernigan L, Jones
research grants by the Finnish Pediatric Research KL. Novel risk factor in gastroschisis: change of pater-
Foundation and the Sigrid Juselius Foundation. nity. Am J Med Genet A. 2007 Apr 1;143A(7):653–9.
https://doi.org/10.1002/ajmg.a.31577.
12. Jenkins MM, Reefhuis J, Gallagher ML, Mulle JG,
Hoffmann TJ, Koontz DA, et  al. Maternal smoking,
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 Omphalomesenteric Duct
and Urachal Remnants 32
Daniele Alberti and Giovanni Boroni

32.1 Introduction ing of the embryo. As a result the dorsal portion

of the yolk sac cavity is incorporated into the
Omphalomesenteric duct and urachus are two embryo to form the primitive gut, which main-
transitory structures, normally encountered dur- tains a connection with the extracoelomic portion
ing the embryonic development. The first usu- of the yolk sac through the omphalomesenteric or
ally disappears by the fifth to seventh week of vitelline duct. With the growth, the placenta
gestation, while the urachus progressively nar- becomes the primary source of nourishment for
rows and is obliterated by fibrous proliferation the fetus, and the extraembryonic yolk sac
during the fetal life. Remnants of these embry- regresses; the omphalomesenteric duct normally
onic structures account for a wide variety of obliterates between the fifth and the seventh week
abnormalities that may require surgical of gestation [1, 2] (Fig. 32.1).
correction. Meantime, on about day 16 of gestation, a fin-
gerlike outpouching, the allantois, forms from
the caudal wall of the yolk sac. In some lower
32.2 Normal Embryology vertebrates, this structure serves as a reservoir for
excretion products of the developing renal sys-
In the early stages of development, the disk-­ tem, but in humans, it remains rudimentary and
shaped trilaminar embryo presents the amnion has no known role. The cranial end of the blad-
located in a dorsal direction, whereas the yolk sac der, that develops from the ventral portion of the
occupies a ventral position. From the fourth week distal hindgut, the cloaca, initially opens into the
of gestation, the different growth of embryonic allantois at the level of the umbilicus. By the
tissues produces a cephalocaudal and lateral fold- fourth to fifth months, the bladder descends into
the pelvis, and its apical portion narrows to form
the urachus, a fibromuscular band that connects
the bladder with the allantois. The urachus is
finally obliterated by fibrous proliferation by the
D. Alberti (*) latter half of fetal life, giving rise to a fibrous cord
Clinica Chirurgica Pediatrica, Università degli studi
di Brescia, ASST Spedali Civili di Brescia, running from the inferior aspect of the umbilicus
Brescia, Italy to the dome of the bladder, the median umbilical
e-mail: [email protected] ligament [2, 3].
G. Boroni
Clinica Chirurgica Pediatrica, ASST Spedali Civili di
Brescia, Brescia, Italy

© Springer Nature Switzerland AG 2019 429

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_32
430 D. Alberti and G. Boroni

Fig. 32.1 Normal a b
embryology of the
omphalomesenteric
duct. (a) A 3-week
embryo; (b) a 4-week
embryo; (c) a 5-week
embryo. Explanation in
the text

32.3 Omphalomesenteric Duct vitelline duct from the ileum to the umbilicus and
Remnants is one of the least common variants (about 5%)
[5]. Usually it presents by fecal umbilical drain-
Failure of complete involution of the omphalo- age in the neonatal period, although a small fis-
mesenteric duct results in a heterogeneous vari- tula can occur with granulation tissue or umbilical
ety of anomalies, sometimes evident since birth, polyp and little or no secretion. Occasionally, the
which may require surgical correction. ileum can prolapse exteriorly through the patent
The commonest omphalomesenteric duct duct, leading to obstructive symptoms and isch-
remnant is the Meckel diverticulum, accounting emic damage of the incarcerated ileum. Even in
for 67% of all defects [4]; other pathologic vari- case of obvious diagnosis (fecal umbilical drain-
eties include umbilical fistulas, sinus, cysts, age), imaging workup should include ultraso-
mucosal remnants, congenital bands, and combi- nography and a fistulogram to identify the
nations of these entities (i.e., a fibrous band con- communication with the bowel [4]. The manage-
taining a cyst or a Meckel diverticulum attached ment of omphalomesenteric fistula requires sur-
to the umbilicus). gical excision from the umbilicus up to the ileum
An omphalomesenteric fistula (Fig.  32.2a) and should be done promptly after the diagnosis
occurs when there is a complete patency of the (Fig. 32.3a, b).
32  Omphalomesenteric Duct and Urachal Remnants 431

a b c

d e f

Fig. 32.2  Various omphalomesenteric duct remnants. (a) omphalomesenteric (umbilical) cyst; (e, f) Meckel diver-
Omphalomesenteric fistula; (b) omphalomesenteric sinus ticulum with and without fibrous band
with a fibrous band; (c) umbilical polyp with a band; (d)

Omphalomesenteric sinus (Fig.  32.2b) is An omphalomesenteric cyst (Fig.  32.2d) is

caused by the failure of obliteration of the outer caused by failed obliteration of an intermediate
portion of the vitelline duct; the ileal attachment portion of the vitelline duct. The cyst may be
may persist as a fibrous cord or be lost. Clinically, located under the umbilicus (umbilical cyst) or in
this condition may lead to the discharge of the context of the fibrous remnant. The cyst usu-
mucus; injection of contrast medium may be ally has columnar epithelium: gastric mucosa is
helpful in defining the diagnosis. During surgical the most common, but small intestinal, colonic,
removal, a full exploration is mandatory to iden- or pancreatic tissue can be present [4]. This con-
tify and remove any attachment to the small dition is typically asymptomatic, but the cyst can
bowel [2, 4]. become infected, leading to erythematous swell-
An umbilical polyp (Fig.  32.2c) represents ing at the umbilicus and sometimes spontaneous
exposed gastrointestinal mucosa at the umbili- external drainage with discharge of pus. Like for
cus. The most common ectopic mucosa encoun- the umbilical polyp, during the surgical removal
tered in this situation is of gastric or pancreatic of umbilical cyst, any associated remnant must
origin; acid secretion by the gastric mucosa can be looked for and removed.
lead to chemical dermatitis of the periumbilical The persistence of a fibrous band between the
skin. Sometimes the polyp is misdiagnosed as umbilicus and ileum, representing an obliterated
umbilical granuloma and treated by cauteriza- omphalomesenteric duct, possibly associated
tion with silver nitrate, without resolution. with other remnants (Fig. 32.2b, c, e), may cause
Surgical resection is required, with careful angulation, volvulus, herniation, or strangulation
identification of any remnant under the umbili- of intestinal loops, resulting in mechanical intes-
cus [4, 6]. tinal obstruction [2].
432 D. Alberti and G. Boroni

a b

c d

e f

Fig. 32.3  Various clinical presentations and complications a mesodiverticular band, leading to ischemic damage of the
of omphalomesenteric remnants. (a, b) Omphalomesenteric diverticulum and the adjacent ileum; (g) perforation of a
fistula cannulated at the beginning of the intervention and giant Meckel diverticulum secondary to peptic ulceration;
during the dissection; (c, d) inverted Meckel diverticulum (h) torsion of Meckel diverticulum
leading to intestinal obstruction; (e, f) internal hernia due to
32  Omphalomesenteric Duct and Urachal Remnants 433

g h

Fig. 32.3 (Continued)

32.4 Meckel Diverticulum In some textbooks, a mnemonic trick, known

as “the rule of two”, is cited: MD is found in 2%
Meckel diverticulum (MD) results from the of the population and becomes symptomatic
incomplete obliteration of the inner (intestinal) before 2  years of age, two times as common in
portion of the omphalomesenteric duct. The males, 2 ft. from the ileocecal valve, 2 inch. long,
German surgeon Wilhelm Fabricius Hildanus and 2  cm in diameter, containing two types of
first described this “unusual” diverticulum of the heterotopic tissue (gastric and pancreatic) [12].
small bowel in 1598, but this entity was no named
until 1908, when Johann Friedrich Meckel the
Younger published his research describing its 32.4.1 Pathology
anatomy, embryology, and clinical presentation
[7]. MD is the most common congenital malfor- MD is a true diverticulum, containing all three lay-
mation of the gastrointestinal tract and is found in ers of the intestinal wall, and receives its blood
1.2–3% of the population. In autopsy series, MD flow from the vitelline artery, a terminal branch of
was discovered in 386 of 31,499 autopsies, result- the superior mesenteric artery. It is usually located
ing in a prevalence of 1.23% [8]. The male-to-­ on the antimesenteric border of the ileum, but
female ratio is almost equal in asymptomatic sometimes it can be found on the lateral aspect or
patients, whereas the symptomatic cases are on the mesenteric border. These locations are
more frequently males, with a male-to-female explained by the presence of a short vitelline artery
ratio of 2–3:1 [9, 10]. Most cases of MD are iso- that fixes the tip of the diverticulum to the mesen-
lated, without other associated abnormalities. tery, determining the diversion away from the
Simms et  al. showed an increased incidence of mesenteric border during the growth of the intes-
Meckel diverticulum in children born with major tine [4]. Three-fourths of MD are unattached to the
malformation of the umbilicus, alimentary tract, abdominal wall and free-­floating within the perito-
nervous system, or cardiovascular system. They neal cavity (Fig.  32.2e, f). Most of the MD are
found MD in 24.5% of patients with small located within 100 cm of the ileocecal valve and
omphalocele, in 12% of patients with esophageal have a length of 2–3 cm. In a review of 100 cases
atresia, in 11% of those with imperforate anus, of symptomatic MD in pediatric age, the mean dis-
and, respectively, in 6, 4.6 and 4.2% of patients tance to the ileocecal valve was 47.58 ± 14.50 cm,
with neurologic abnormality, congenital cardio- the diverticular length was 3.72 ± 1.95 cm, and the
vascular abnormality, and duodenal atresia [11]. mean diverticular diameter was 1.65  ±  0.66  cm
434 D. Alberti and G. Boroni

[9]. In one study on adult patients, more than one- minimal painful gastrointestinal bleeding; up to
fourth of MD were located between 91 and 161 cm 70% of patients presents with massive bleeding
from the ileocecal valve. and requires blood transfusion [9]. Chronic
The presence of heterotopic mucosa is bleeding with isolated iron-deficiency anemia is
reported with an overall incidence of 15–50%, the presentation symptom in a small number of
with a great variability between symptomatic and patients and is seen more in adults than in
incidental cases. The most common type of het- children.
erotopia is gastric, followed by pancreatic The main mechanism of bleeding is the acid
mucosa, whereas other types are rare. Park, on secretion from ectopic mucosa, which leads to
1476 patients with Meckel diverticulum, reported ulceration of adjacent ileal mucosa; gastric het-
an overall incidence of heterotopic tissue of erotopia is described in at least 60% of bleeding
21.5%. In asymptomatic patients, the incidence diverticula and in some series up to almost 100%
was 11% in pediatric age and 14% in adults, [9].
whereas in symptomatic cases, it was, respec- Intestinal obstruction is the second most com-
tively, 59 and 43% in children and adults. In mon complication of MD in pediatric age, pri-
bleeding diverticula, gastric heterotopia was marily observed in older children, with several
present in 63% of adults and in 78% of pediatric possible mechanisms. MD can act as a pathologi-
cases [10]. Huang reported the presence of ecto- cal lead point for an ileoileal or ileocolic intus-
pic tissue in 73% of symptomatic children (61% susception. Most of these intussusceptions are
gastric, 2% pancreatic, 10% coexistence of gas- not reducible with pneumatic or contrast enema,
tric and pancreatic mucosa); ectopic gastric tis- and rarely preoperative imaging identifies the
sues was found in 97.7% of patients with underlying cause, which can only be suspected.
gastrointestinal bleeding, whereas the presence However, only 5–10% of patients with intussus-
of ectopic pancreatic tissue was more frequent in ception after 2  years of life have a MD [5].
patients with intussusception [9]. Fibrous cord from the tip of the diverticulum to
the umbilicus can cause volvulus, providing a
point of fixation for the bowel to twist around.
32.4.2 Clinical Presentation Fibrous remnants can also cause intestinal
obstruction favoring compression and kinking of
Most MD are clinicaly silent and often detected intestinal loops.
incidentally during surgery for some other indi- The presence of a mesodiverticular band, a
cations. They usually become symptomatic when remnant of vitelline vessels, that arises from the
a complication occurs. According to the original mesentery and implants on the diverticulum, can
papers of Johann Friedrich Meckel, the risk of create a loop which predisposes to internal hernia
complication of MD was 25%, but in the recent [13] (Fig. 32.3e, f). Adhesions due to inflamma-
literature, the estimated lifetime risk of symp- tory process may also result in obstruction. Rarer
toms ranges between 4 and 6% [5]. In children causes of obstruction are the inversion of the
gastrointestinal bleeding is the most common diverticulum (Fig. 32.3c, d), enteroliths, foreign
presentation, especially in those younger than bodies, or tumors within the diverticulum.
2  years, followed by obstruction and inflamma- MD may also be found within a hernia (Littre
tion. In adults the most frequent complications hernia) which may get incarcerated and obstructed
are obstruction, ulceration, diverticulitis, and per- [14]. During adulthood Littre hernia occurs typi-
foration [7]. Neoplasia becomes a more frequent cally in the inguinal region, whereas in pediatric
complication in the elderly. population, umbilical type is more common.
Gastrointestinal bleeding from MD is usually Meckel diverticulitis usually occurs in older
described as brick red, maroon, or less commonly children and is commonly misdiagnosed as
tarry; in neonatal population, bright red blood appendicitis because of the overlapping clinical
may be present, owing to the rapid intestinal tran- features. Inflammation of MD is secondary to
sit. Usually patients present episodic painless or acid secretion from ectopic mucosa or, similar to
32  Omphalomesenteric Duct and Urachal Remnants 435

appendicitis, can result in owing to obstruction of contrast studies, the classic finding is a single
the lumen by an enterolith or foreign body lead- diverticulum arising from the antimesenteric
ing to stasis and bacterial proliferation [4]. ­border of the distal ileum. On ultrasound and on
Intestinal perforation (Fig.  32.3g) is a very CT scan, uncomplicated MD can be seldom iden-
rare clinical manifestation and is secondary to tified as a round or tubular blind ending structure
diverticulitis, ischemia due to torsion of the originating from the ileum [17].
diverticulum (Fig.  32.3h), or peptic ulceration In case of gastrointestinal bleeding, the tech-
due to ectopic gastric mucosa [14]. netium-­ 99  m pertechnetate radionuclide study
Malignancies in MD are reported to account (“Meckel scan”) is widely used. Harper intro-
for only 0.5–3.2% of the complications. Several duced this study in 1962, but Jewett was the first
types of tumor of the MD have been described, to apply it clinically in 1970 [18]. 99MTc pertech-
and malignant tumors predominate, with carci- netate is taken up and secreted by the tubular
noids being the most common. Other pathologi- glands of the gastric mucosa in the stomach, but
cal types include adenocarcinoma, pancreatic also in ectopic gastric mucosa, which is present
carcinoma, intraductal papillary mucinous neo- in 70–100% of bleeding MD in children
plasm, gastrointestinal stromal tumor (GIST), (Fig. 32.4). In children the “Meckel scan” has a
leiomyosarcoma, lymphoma, lipoma, adenomy- sensitivity of 80–90%, a specificity of 95%, and
oma, and villous adenoma [15, 16]. Mean annual an accuracy of 90% [4, 7]. The accuracy of the
incidence rate of MD cancer is 1.8 per 10 million study is improved by the administration of penta-
person-years; incidence increases progressively gastrin (which increases gastric mucosal uptake
with age, reaching a peak in the eighth decade. and stimulates acid secretion), H-2 blockers like
Carcinoid is the most common pathologic type, cimetidine or ranitidine (which reduce the excre-
representing 76.5% of all MD cancer [15]. The tion of the isotope and increase cellular retention
average age of appearance of a carcinoid on a enhancing visualization), and glucagon (which,
MD is 55  years, with an incidence 2.5 times in by its antiperistaltic effect, allows the isotope to
men than women. The classic carcinoid syn- persist longer in the diverticulum) [17]. Causes of
drome, supported by serotonin secretion, usually false-positive results include intestinal duplica-
in patients with liver metastasis, is present in tion containing ectopic gastric mucosa, intussus-
10–20% of patients. Carcinoid tumors smaller ception, bowel inflammation, retention of tracer
than 1 cm have an incidence of 2% of metastasis; in the urinary system, vascular lesion such
lesions between 1 and 2 cm metastasize in 50% hemangiomas, arteriovenous malformations,
of cases and those bigger than 2  cm in 80% of and gastrointestinal bleeding unrelated to MD.
cases. The liver is the most common metastatic False-negative scintigraphy may result from
site, with a 5-year survival of 30% in patients absence or small size of gastric ectopic mucosa in
with hepatic metastases [16]. In more than 70% the diverticulum: at least a 1  cm [2] of ectopic
of cases, carcinoids originate at the distal extrem- tissue is required. Other factors include tracer in
ity of MD. In MD tumors, resection of the ileal the urinary bladder that may obscure a MD
tract containing the diverticulum and the corre- located in the pelvis, residual contrast in bowel
sponding mesentery is generally recommended. from previous barium study that attenuates
gamma radiation, and rapid dilution of the radio-
tracer from high bleeding rate or poor blood sup-
32.4.3 Diagnosis ply to the diverticulum [18]. Single photon
emission computed tomography (SPECT) has
Most of the uncomplicated MD are asymptom- been successful in identifying cases that are not
atic and discovered as incidental finding, usually visible using conventional planar imaging [17].
during laparotomic or laparoscopic procedures. Mesenteric angiography can be used to investi-
Rarely, owing to increase in the use of more sen- gate gastrointestinal hemorrhage associated with
sitive radiological tests, a MD can be suspected a MD, although a bleeding rate greater than
with imaging studies. On upper gastrointestinal 0.5 mL/min is required. In comparison a techne-
436 D. Alberti and G. Boroni

Fig. 32.4  Technetium-99  m pertechnetate radionuclide the right, intraoperative findings, with palpable ectopic
study, demonstrating a focus of uptake in the lower right mucosa at the tip of the diverticulum
abdomen in a case of bleeding Meckel diverticulum; on

tium-­99 m-labeled red blood cell scan is a more formed by the inverted Meckel diverticulum act-
sensitive test and can identify hemorrhage at ing as a lead point and the second target by the
rates as low as 0.1 mL/min, but it is not specific intussuscepting ileum [4, 14].
[17]. In presence of bleeding with typical charac- In patients with intestinal obstruction or diver-
teristics and a repeat negative scintigraphy, some ticular perforation, the radiologic findings are
authors suggest exploratory laparoscopy. usually aspecific: dilated bowel loops, air-fluid
Wireless capsule endoscopy is widely used levels, and free intraperitoneal gas.
in patients with obscure gastrointestinal bleed-
ing, with an incidence of positive findings
between 40 and 75% and diagnosis of MD in 32.4.4 Treatment
3–15% of patients [19]. Retrograde double bal-
loon enteroscopy was also successfully used for The treatment of choice for symptomatic MD is
diagnosis of MD in children with negative scin- the surgical resection, which can be done with
tigraphy [20]. open or laparoscopic techniques. Laparoscopy is
Inflamed MD appears on ultrasound as a increasingly used both for diagnosis and treat-
thick-walled, tubular, noncompressible lesion, ment of MD: in most cases the diverticulum is
with wall hyperemia on color Doppler; however identified, grasped, and exteriorized and then
these features often simulate those of acute removed extracorporeally. This can be achieved
appendicitis, leading to misdiagnosis. At CT either by simple diverticulectomy and transverse
scan, acute Meckel diverticulitis appears as a closure of the ileum or by segmental bowel resec-
blind-ending, tubular or cystic, thick-walled tion and reanastomosis. Diverticulectomy alone
structure, with wall enhancement and inflamma- can result in either retained mucosa or, in case of
tory changes of surrounding mesenteric fat [13, bleeding, a retained ulcer on the mesenteric
17]. In intussusception cases, rarely enema per- aspect of the bowel or in the neck of the diver-
mits to demonstrate a MD as a lead point, and ticulum. In patients with bleeding or inflamma-
usually the diagnosis is made intraoperatively. tory symptoms, resection of the ileal segment
Itagaki described an ultrasound sign, which he including the diverticulum may be the safest
named “double-target sign,” with one target option [5, 12].
32  Omphalomesenteric Duct and Urachal Remnants 437

The management of incidentally detected MD found, at autopsy, tubular urachal remnants in

remains controversial. The classic approach is in 38% of 122 specimens in adults [24]. Urachal
favor of resection, with the rationale to remove a remnants are diagnosed quite frequently since
potential cause of complications throughout life. abdominal ultrasonography is often used as a
In 1976, Soltero first argued that asymptomatic screening test, but the clinical significance of
MD should not be removed, demonstrating that these incidentally diagnosed remnants is unclear.
there was only a small asymptomatic diverticu- In 2003, Ueno reviewed the ultrasound reports of
lum causing disease in later life [8]. Other authors 3400 patients and found 56 children with urachal
recommended a “selective” approach, advising remnants, with an incidence of 1.6%; 36 of these
resection of incidentally detected Meckel in 56 cases were asymptomatic [25]. Recently
selected cases. For example, Park recommended Gleason reviewed abdominal imaging study of
removing all diverticula with any of the four fea- 64,803 patients younger than 18 years, during a
tures most commonly associated with symptom- 13-year period. Of those patients, 721 were
atic Meckel: age less than 50  years, male sex, radiographically diagnosed with an urachal
diverticulum length greater than 2  cm, ectopic anomaly (1.1%); only 54 of these urachal anoma-
tissue, or abnormal features within the diverticu- lies (7.5%) were symptomatic [26]. The inci-
lum [10]. Nevertheless, about the last point, the dence is slightly higher in males, with a
same author reported that a palpable mass was male-to-female ratio of 1.36:1 [23]. The most
identified during surgery only in 38% of the common type of urachal anomaly is the urachal
diverticula with histopathologic diagnosis of cyst (36–61%) (Fig. 32.5d), which develops if the
ectopic tissue [10]. A recent meta-analysis by urachus closes at both the umbilicus and bladder
Zani concluded that resection of incidentally site but remains patent between these two points.
detected MD has a significantly higher early Umbilical urachal sinus (Fig.  32.5c), a blind-­
complication rate than leaving it in situ (5.3% in ending remnant that opens at the umbilicus, rep-
the resected compared with 1.3% in the nonre- resents 16–49% of the anomalies; the patent
sected MD); the estimated lifetime chance of urachus (Fig. 32.5a), in which a persistent com-
complications requiring an operation is 2.9%, munication exists between the bladder lumen and
and 758 resections of asymptomatic diverticula the umbilicus, accounts for 10–23% of remnants
are required to prevent 1 death from MD [8]. [27, 28]. Urachal diverticulum (Fig. 32.5b), con-
sisting of outpouching of the bladder at the inser-
tion of the urachus, is very rare, representing only
32.5 Urachal Remnants 1–3% of urachal anomalies [3, 27].

Failure or delay in complete fibrous obliteration

of the urachus may lead to a variety of urachal 32.5.2 Clinical Presentation
remnants, including patent urachus, urachal sinus,
urachal cyst, and vesicourachal diverticulum. With the widespread diffusion of abdominal ultra-
sonography, the number of incidentally diagnosed
urachal remnants, without any symptom, is
32.5.1 Epidemiology increasing. In the symptomatic cases, drainage
and Classification from the umbilicus is the most frequent modality
of presentation. Pain, erythema and other signs of
Bartholomaeus Cabrolius first described the per- infection, palpable cyst or mass, and dysuria or
sistence of the urachus in 1550 [21]. Urachal urinary tract infection are other presenting clinical
anomalies have been historically considered rare; symptoms [27, 28]. Umbilical retraction with
even if their incidence at birth was formerly esti- voiding can be a sign of urachal anomalies [5].
mated to be 1 in 5000–8000 live births [22, 23], A patent urachus is usually associated with
the true prevalence is probably higher. Schubert urine leakage during the neonatal period. In
438 D. Alberti and G. Boroni

a b c d

Fig. 32.5  Various urachal remnants. (a) Patent urachus; (b) vesicourachal diverticulum; (c) urachal sinus; (d) urachal
cyst

addition it may be one of the causes of giant ranges between 43 and 61% [31]; local inva-
umbilical cord in the newborn [2, 3]. Umbilical sion and systemic metastases result in a 5-year
urachal sinus may be asymptomatic or may survival rate of 6.5–15% [3].
present with periodic discharge, usually asso-
ciated with an infection. Urachal cyst are
sometimes found as incidental masses during 32.5.3 Diagnosis
routine examination; they become symptom-
atic when they enlarge or when an infection Any child suspected to have an urachal abnor-
occurs, with symptoms such as acute abdomi- mality should undergo ultrasound evaluation as
nal pain, fever, urinary tract infection, and initial screening test. Ultrasound is diagnostic in
abdominal mass [29, 30]. Most of the vesicour- most of urachal cysts (82–100%) and in a vari-
achal diverticula are asymptomatic but may be able percentage of urachal sinus and patent ura-
complicated by urinary tract infection and chus, ranging, among the studies, between 33 and
intraurachal stone formation, particularly if 100%. In presence of drainage from the umbili-
they retain urine [3, 5]. Urachal anomalies are cus, a sinogram/fistulogram is useful to delineate
thought to be associated with an increased risk the anatomy of the defect and to exclude an
of urachal cancer. Malignant urachal neo- omphalomesenteric remnant [27]. Most authors
plasms are rare, accounting for 0.1–0.5% of all have suggested that voiding cystourethrography
bladder malignancies; adenocarcinoma, that is rarely informative and then not necessary in
represents the majority of cases (88–97% of all patients with suspected urachal anomalies.
urachal cancer), has an estimated incidence of Nevertheless a voiding cystourethrography
0.18/100,000 individuals yearly. The peak (VCUG) may be useful in the rare vesicourachal
median age at diagnosis is mostly in the fifth diverticulum to delineate the anatomy of the
and sixth decade, and the gender distribution diverticulum and in patent urachus to exclude
shows a tendency toward the male sex [26, 31]. posterior urethral valves or other bladder obstruc-
Urachal tumors are typically silent, and a large tion. Currently this association seems very rare,
proportion of patients presents with disease at but, in the past, posterior urethral valves have
stage pT3 or higher. The most frequent symp- been reported in about one-third of patients with
tom is hematuria, owing to the origin of 90% of patent urachus [3, 32]. In selected cases, when
carcinomas in the juxtavesical portion of the the ultrasound is not diagnostic, a CT scan or an
urachus. Five-year cancer-­ specific survival MRI can be proposed [27].
32  Omphalomesenteric Duct and Urachal Remnants 439

32.5.4 Treatment ­position [29]. Other placement techniques

involve placement of all the ports at the right or at
Traditionally urachal anomalies in children have the left of the midline: the first port in the upper
been removed, in order to avoid infection, as well abdomen; the second at the level of the umbili-
to prevent malignant degeneration later in life. In cus, laterally to the midclavicular line; and the
the recent literature, several authors propose con- third in the lower abdomen, on the midclavicular
servative management for the incidentally line [30]. A Foley catheter must be placed to ini-
detected urachal remnants and even in cases of tially empty the bladder, during the port place-
infected anomalies, especially in younger patients ment and the dissection of the urachal remnant.
[21, 23, 32]. This new trend in management of The bladder should then be inflated with saline
urachal remnant is justified by some evidences: solution or with vital dye diluted, allowing better
the increasing number of incidentally detected visualization of the borderline between the blad-
urachal remnants and the rate of spontaneous der and urachus and prompt recognition of any
resolution that can reach 80% in patients younger leakage after the removal of the urachus. After
than 6 months [28, 32]. Moreover, the exact role opening of the anterior parietal peritoneum, the
of urachal remnant resection in order to prevent urachal remnant is dissected off the transversalis
urachal cancer is unknown. Gleason calculated fascia, with hook, scissors, or harmonic scalpel,
that the number needed to treat to prevent a single and then divided at its superior end, near the
case of urachal adenocarcinoma is 5.721 urachal umbilicus. The dissection is carried down until
remnants and concluded that prophylactic surgi- the bladder, and the urachal remnant is then
cal excision is neither reasonable nor recom- ligated by an endoloop just above the dome of the
mended [26]. bladder and sectioned with a small pad of detru-
In patients with persistent symptoms despite sor. One or two additional stitches may be placed
appropriate conservative management, particu- to ensure complete closure of the bladder. The
larly if older than 1  year, resection of urachal urinary catheter should be left for 2–3  days in
remnant remains the most accepted treatment. In order to prevent urinary leakage [29, 30].
patients with infected urachal cyst, some authors
suggest a two-stage approach, first with drainage
and antibiotics, followed by excision [21]. References
The recommended surgical management
includes the radical excision of the urachal rem- 1. Sadler TW. Langman’s medical embryology. 10th ed.
nants from the umbilicus to the bladder dome, Philadelphia: Lippincot Williams & Wilkins; 2006.
with a cuff of the bladder wall: most urachal can- 2. Cilley RE. Disorders of the umbilicus. In: Coran AG,
Adzick NS, Krummel TM, Laberge JM, Shamberger
cers, in fact, occur at the distal part of the urachus RC, Caldamone AA, editors. Pediatric surgery. 7th ed.
[29]. The traditional open approach, via the Philadelphia: Elsevier Saunders; 2012. p. 961–72.
umbilicus, may need a lateral expanded incision, 3. Yu JS, Kim KW, Lee HJ, Lee YJ, Yoon CS, Kim
a midline vertical incision, or a hypogastric trans- MJ.  Urachal remnant diseases: spectrum of CT and
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doi.org/10.1067/j.cpradiol.2014.12.003. Epub 2015
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reports describe a three-port approach, with one malities and related anomalies. Semin Pediatr Surg.
port for a 30° telescope and two working ports. 2007;16(1):41–9. Review
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8. Zani A, Eaton S, Rees CM, Pierro A.  Incidentally et  al. Bleeding Meckel’s Diverticulum in children:
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9. Huang CC, Lai MW, Hwang FM, Yeh YC, Chen 21. Lipskar AM, Glick RD, Rosen NG, Layliev J, Hong
SY, Kong MS, et  al. Diverse presentations in pedi- AR, Dolgin SE, Soffer SZ.  Nonoperative manage-
atric Meckel’s diverticulum: a review of 100 cases. ment of symptomatic urachal anomalies. J Pediatr
Pediatr Neonatol. 2014;55(5):369–75. https://doi. Surg. 2010;45(5):1016–9. https://doi.org/10.1016/j.
org/10.1016/j.pedneo.2013.12.005. jpedsurg.2010.02.031.
10. Park JJ, Wolff BG, Tollefson MK, Walsh EE, Larson 22. Nogueras-Ocaña M, Rodríguez-Belmonte R, Uberos-­
DR.  Meckel diverticulum: the Mayo Clinic experi- Fernández J, Jiménez-Pacheco A, Merino-Salas
ence with 1476 patients (1950–2002). Ann Surg. S, Zuluaga-Gómez A.  Urachal anomalies in chil-
2005;241(3):529–33. dren: surgical or conservative treatment? J Pediatr
11. Simms MH, Corkery JJ.  Meckel’s diverticulum:
Urol. 2014;10(3):522–6. https://doi.org/10.1016/j.
its association with congenital malformation and jpurol.2013.11.010.
the significance of atypical morphology. Br J Surg. 23. Stopak JK, Azarow KS, Abdessalam SF, Raynor

1980;67(3):216–9. SC, Perry DA, Cusick RA.  Trends in surgical man-
12. Snyder CL.  Meckel diverticulum. In: Coran AG,
agement of urachal anomalies. J Pediatr Surg.
Adzick NS, Krummel TM, Laberge JM, Shamberger 2015;50(8):1334–7. https://doi.org/10.1016/j.
RC, Caldamone AA, editors. Pediatric surgery. 7th ed. jpedsurg.2015.04.020.
Philadelphia: Elsevier Saunders; 2012. p. p1085–92. 24. Copp HL, Wong IY, Krishnan C, Malhotra S,

13. Kotecha M, Bellah R, Pena AH, Jaimes C, Mattei Kennedy WA. Clinical presentation and urachal rem-
P.  Multimodality imaging manifestations of the nant pathology: implications for treatment. J Urol.
Meckel diverticulum in children. Pediatr Radiol. 2009;182(4 Suppl):1921–4. https://doi.org/10.1016/j.
2012;42(1):95–103. https://doi.org/10.1007/s00247- juro.2009.03.026.
011-2252-7. 25. Ueno T, Hashimoto H, Yokoyama H, Ito M, Kouda
14. Kotha VK, Khandelwal A, Saboo SS, Shanbhogue K, Kanamaru H. Urachal anomalies: ultrasonography
AK, Virmani V, Marginean EC, et  al. Radiologist's and management. J Pediatr Surg. 2003;38(8):1203–7.
perspective for the Meckel's diverticulum and its com- 26. Gleason JM, Bowlin PR, Bagli DJ, Lorenzo AJ,

plications. Br J Radiol. 2014;87(1037):20130743. Hassouna T, Koyle MA, Farhat WA.  A comprehen-
https://doi.org/10.1259/bjr.20130743. sive review of pediatric urachal anomalies and pre-
15. Thirunavukarasu P, Sathaiah M, Sukumar S, Bartels dictive analysis for adult urachal adenocarcinoma. J
CJ, Zeh H 3rd, Lee KK, et  al. Meckel’s diverticu- Urol. 2015;193(2):632–6. https://doi.org/10.1016/j.
lum—a high-risk region for malignancy in the ileum. juro.2014.09.004.
Insights from a population-based epidemiological 27. Yiee JH, Garcia N, Baker LA, Barber R, Snodgrass
study and implications in surgical management. Ann WT, Wilcox DT.  A diagnostic algorithm for urachal
Surg. 2011;253(2):223–30. https://doi.org/10.1097/ anomalies. J Pediatr Urol. 2007;3(6):500–4. https://
SLA.0b013e3181ef488d. doi.org/10.1016/j.jpurol.2007.07.010.
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28. Naiditch JA, Radhakrishnan J, Chin AC. Current diag-
Castellani E, Boselli C, Gemini A, Burattini MF, nosis and management of urachal remnants. J Pediatr
Covarelli P, Noya G.  Incidental finding of carcinoid Surg. 2013;48(10):2148–52. https://doi.org/10.1016/j.
tumor on Meckel's diverticulum: case report and liter- jpedsurg.2013.02.069.
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mended? World J Surg Oncol. 2014;12:144. https:// of urachal cysts. Transl Pediatr. 2016;5(4):275–81.
doi.org/10.1186/1477-7819-12-144. https://doi.org/10.21037/tp.2016.09.10.
17. Thurley PD, Halliday KE, Somers JM, Al-Daraji
30. Sato H, Furuta S, Tsuji S, Kawase H, Kitagawa

WI, Ilyas M, Broderick NJ. Radiological features of H. The current strategy for urachal remnants. Pediatr
Meckel’s diverticulum and its complications. Clin Surg Int. 2015;31(6):581–7. https://doi.org/10.1007/
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crad.2008.07.012. 31. Behrendt MA, DE Jong J, VAN Rhijn BW.  Urachal
18. Kiratli PO, Aksoy T, Bozkurt MF, Orhan D. Detection cancer: contemporary review of the pathological,
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useful diagnostic tool for diagnosing Meckel's diver- 03.105.
 The Bladder Exstrophy-Epispadias
Complex (BEEC) 33
Geoffroy de Sallmard, Omar Alhadeedi,
Delphine Demède, and Pierre Mouriquand

The BEEC complex is the result of a failed cavi- dias where the sphincteric mechanisms are
tation and separation of the pelvic organs and a involved and the child incontinent at various
failed closure of the pelvic ring. During the first degrees and anterior epispadias where the conti-
2  months of gestation, the embryo (germinal nence mechanisms are completely or partially
disc) is subjected to a complex process (delimita- respected but the genital tubercle remains abnor-
tion) [1] of cranio-caudal tubularization resulting mal. Epispadias exists both in males and females.
in the cavitation and connection of the pelvic Complex embryonic hypotheses have been
organs to the pelvic floor. This leads to the cre- described to explain these abnormalities. They
ation of separated urinary, genital and intestinal involve the formation and positioning of the cloa-
cavities independently connected to the perineal cal membrane which is situated at the caudal end
surface by distinct conduits and their correspond- of the germinal disc and occupies the infra-­
ing sphincter. If the delimitation process is inter- umbilical abdominal wall. Between the two lay-
rupted early, the distal bowels, the bladder and ers (ectoderm and endoderm) initially forming
the urethra are not individualized and appear as the cloacal membrane comes a mesenchymal
contiguous and often duplicated plates. This is a ingrowth [2] which will result in the formation of
cloacal exstrophy and is often associated with the lower abdominal muscles and the pelvic
other abnormalities. If the process halts later in bones [3]. The surrounding mesoderm will be at
the gestation, the bowels are properly formed and the origin of the genital tubercle. The 3D devel-
connected, but the bladder and urethra are both opment of the embryo progresses from the
widely open, presenting as a classical bladder cephalic to the caudal extremity and from the
exstrophy. Finally, when the process stops late, dorsum to the ventrum of the embryo. When the
only the urethra and the urethral sphincter are caudal delimitation is aborted, the mesenchymal
open and incompetent, presenting as an epispa- ingrowth between the ectodermal and endoder-
dias. Depending on the timing of the cavitation mal layers fails to progress, and the overstretched
failure, one should distinguish posterior epispa- cloacal membrane becomes fragile and subject to
a premature rupture leading to exstrophy (or non-­
cavitation) of the pelvic organs [4]. This “zip
G. de Sallmard · O. Alhadeedi · D. Demède down” process [5] explains the progressive clo-
P. Mouriquand (*)
Service de Chirurgie Uro-génitale de l’Enfant, sure of the pelvis and the cavitation of the pelvic
Hospices Civils de Lyon, Université Claude Bernard, organs from the back to the front and from the top
Lyon1, Hôpital Mère-Enfant, Bron, France to the bottom of the embryo. It is possible that the
e-mail: [email protected]; middle period of the cloacal delimitation is more
[email protected];
[email protected]

© Springer Nature Switzerland AG 2019 441

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_33
442 G. de Sallmard et al.

vulnerable than the early and late stages. This

would explain why bladder exstrophy is more
frequent than cloacal exstrophy and epispadias
[6]. Other embryonic hypotheses have been
reported [7–10].
Epidemiological data confirms that the inci-
dence of bladder exstrophy is between 2.15 and
3.3 per 100,000 births [11, 12]. The incidence of
epispadias is 1 per 101,000 [13] with a sex ratio
from almost equal to a marked male predomi-
nance of 5:1 [14]. The sex ratio of bladder exstro-
phy ranges from 1:1 to 6:1 with a male Classical bladder exstrophy
1- ureter 4- Bladder plate
predominance [15]. White children, in vitro fer- 2- Dorsal urethral plate 5- Corpus cavernosum
tilization [16] and socioeconomic status appear 3- Rectum
to be interacting factors. Significant genetic pre-
disposition remains uncertain considering the
small reported cohorts [17–19]. The recurrence
risk varies from 0.3% [20] to 2.3% [17–19].
1 3

33.1 Anatomy of BEEC (Fig. 33.1a,

b; Fig. 33.2a, b; Fig. 33.3; 4
Fig. 33.4a, b; Fig. 33.5a, b;
Fig. 33.6)
2
5
1. Bony anomalies include a rotation and separa-
tion of the two hemi-pelvises creating a gap
between the two hemi-pubis, a flattening of
the pelvic cavity, an ascent of the perineum
with an anteriorly positioned anus and vagina Fig. 33.1  Classical bladder exstrophy in a boy. Courtesy
in girls and a disorganization of the abdominal of: Mouriquand P., Vidal I.  Complexe Exstrophie
muscles with frequent inguinal hernias [21]. Epispade. Encyclopédie Médico-­Chirurgicale—Urologie.
Volume 18-208-A-10 2012. pp 1–18
The pelvic floor and the pubo-rectal sling are
subsequently stretched apart explaining fre-
quent genital prolapses in girls and occasional alies, omphalocele, short guts or anorectal
rectal prolapses [22]. malformation.
2. In the classical bladder exstrophy, the lower 4. In boys, the epispadiac penis is short and

urinary tract is exposed with an opened blad- broad with an abnormal distribution of the
der reservoir and urethra. The sphincteric penile skin. There is a dorsal curvature of the
mechanisms are deficient leading to a total penis due to an abnormal rotation of the cor-
urinary incontinence. The uretero-vesical pora cavernosa. Erection mechanisms are
junctions are abnormal with short ureteric respected. The urethral plate is wide open on
submucosal tunnels leading to vesicoureteric the dorsum of the penis. The glans is dorsally
reflux once the reservoir is closed. open and split in two. The neurovascular bun-
3. Variants exist with partial exstrophies (“split dles are divided in two wide strips leading to
symphysis variants”), duplicated pelvic each hemi-glans and positioned on the lateral
organs [23], myelomeningocele, spinal anom- aspects of each corpus.
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 443

Classical bladder exstrophy in a female

1- Hemi clitoris 4- Bladder plate
2- Ureter 5- 5 vagina
3- Rectum

1
5

Fig. 33.2  Classical bladder exstrophy in a girl. Courtesy of: Mouriquand P., Vidal I. Complexe Exstrophie Epispade.
Encyclopédie Médico-Chirurgicale—Urologie. Volume 18-208-A-10 2012. pp 1–18

hemi-clitorises are split on each side of the

urethral plate. The vaginal orifice is anteri-
orly positioned and often narrow. The sepa-
ration of the two hemi-­ pubes creates a
triangular hairless area between the two
hemi-mons [25].
7. In cloacal exstrophies, abdominal defects are
more severe with a possible omphalocele. The
bowels are also exstrophied separating two
hemi-bladders. The small bowel is short and
Fig. 33.3  Cloacal exstrophy the large bowel poorly developed (“hindgut”).
The genital tubercle in boys is very poor. The
child is incontinent of urine and faeces.
5. In rare cases, the epispadiac urethra is con-
cealed by a tight complete foreskin. The penis
is buried due to a congenital defect of the 33.2 Diagnosis of BEEC
penile skin shaft [24].
6. In girls, the urethra is also wide open expos- Prenatal ultrasound scan can alert on the diagno-
ing the bladder neck or the bladder reservoir sis of exstrophy from the 16th week of gestation
itself. The continence mechanisms are when a low implantation of the umbilical cord, a
therefore deficient as well [25]. The two non-visualized bladder, an inter-pubic gap and a
444 G. de Sallmard et al.

Male Epispadias
1- Pubic bone 3- Corpora cavernosa
2- Neurovascular bundles 4- Dorsal urethral plate

3
4

Fig. 33.4  Incontinent (posterior) male epispadias. Courtesy of: Mouriquand P., Vidal I. Complexe Exstrophie Epispade.
Encyclopédie Médico-Chirurgicale—Urologie. Volume 18-208-A-10 2012. pp 1–18

protrusion of the infra-umbilical wall are demon-

strated. In cloacal exstrophy, an omphalocele can 33.4 Two Major Treatment
be seen as well. The diagnosis is still often made Approaches Exist
at birth [26].
33.4.1 The Classic Stepwise
Approach
33.3 Management of BEEC
Described by Robert Jeffs in Baltimore [27], the
The objectives of the management of BEEC are three-step approach includes (1) a closure of the
to preserve renal functions, to achieve “social bladder plaque in the neonatal period with or with-
dryness”, to refashion the genital area, to help out osteotomy; (2) a reconstruction of the genital
future sexual life and future fertility and to pro- tubercle between 6 and 18 months of age with or
vide an ongoing psychological support all along without androgen stimulation, with or without oste-
childhood and adolescence. otomy; and (3) bladder neck surgery between after
4 years of age with or without bladder augmenta-
tion, with or without a Mitrofanoff diversion.
33.3.1 At Birth

The umbilical clamp should be removed and the 33.4.2 Closure of the Bladder Plate
cord sutured to avoid damage to the bladder sur- (Fig. 33.7a, b; Fig. 33.8; Fig. 33.9)
face. The bladder should be covered with paraf-
fin- or saline-soaked gauze or a protective silicone Once the ureters have been catheterized, the blad-
mesh, and the child should be transferred to a der plate is carefully dissected off the adjacent
dedicated department of paediatric urology. structures, following several important landmarks:
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 445

Female epispadias
1- Hemi pubis Fig. 33.6  Pelvic ring in an exstrophy with a significant
2- Hemi clitoris gap between the two hemi-pubis
3- Vaginal opening
4- Hairless area
5- Open urethra level of the bladder neck. The anterior muscular
abdominal wall is closed and the two hemi-pubis
sutured together with a strong stitch. This manoeu-
vre allows the relocation of the bladder and poste-
rior urethra inside the pelvic ring. The pelvic bones
4
are usually flexible enough soon after birth to
allow the closure of the pelvic ring. Some still pre-
1 fer to perform a pelvic osteotomy to facilitate the
joining of the two hemi-pelvises without osteot-
omy. In the first days of life, posterior pelvic oste-
2
otomies allow the insertion of pins and external
5 fixation as the bones are thicker posteriorly.
Anterior oblique osteotomies are feasible although
insertion of pins from the front is more difficult in
the newborn. The Bryant traction is then preferred.
3
The pros of neonatal osteotomy are the facilitation
of the abdominal and pelvic ring closure by reduc-
ing the tensions on the wound. It also helps the
relocation of the bladder and posterior urethra
inside the pelvis. Furthermore, it makes post-oper-
6
ative nursing care much easier. It increases, how-
ever, the magnitude of the procedure and the
morbidity in a period of life when the child loses
Fig. 33.5  Female epispadias. Courtesy of: Mouriquand weight and may be unfit for major surgery.
P., Vidal I. Complexe Exstrophie Epispade. Encyclopédie
Médico-­Chirurgicale—Urologie. Volume 18-208-A-10
2012. pp 1–18
33.4.3 Surgery of the Epispadiac
Genital Tubercle and Urethra
the medial edges of the straight muscles, the (Figs. 33.10, 33.11, 33.12, 33.13,
medial edges of each hemi-pubis until the pelvic 33.14)
floor is well exposed, the umbilicus and the perito-
neum. The bladder cavity is then closed with a Surgical repair of these genital anomalies is usu-
double layer of interrupted stitches down to the ally performed during the first 2 years of life.
446 G. de Sallmard et al.

Surgical landmarks in the male exstrophy

1- Incision line around the bladder plate 6- Rectus muscle
2- Veru montanum 7- Medial edge of the rectus muscle
3- Corpus cavernosa 8- Bladder plate
4- Dorsal urethral plate 9- Ureteric orifice
5- Umbilicus 10- Pubic bone

1 7

8
9

10
2
3

Surgical landmarks in a female

1- Ureteric orifice 4- Umbilicus 7- Hemi clitoris
2- Incision lines 5- Rectus muscle 8- Vaginal opening
3- Midline incision 6- Pubic bone 9- Anus

7
1

8
2
9

Fig. 33.7  Anatomical landmarks for bladder plate dissection in male and female exstrophies. Courtesy of: Mouriquand
P., Vidal I. Complexe Exstrophie Epispade. Encyclopédie Médico-Chirurgicale—Urologie. Volume 18-208-A-10 2012.
pp 1–18
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 447

Vertical ventral incision of the penis fascia

on each corpus cavernosum
1- Penis fascia
2- Albuginea of the corpus cavernosum
3- Spongiosum of the urethral plate

Fig. 33.8  Bryant traction

2 3

Fig. 33.9  External fixation after neonatal bladder closure Fig. 33.10  Ventral approach of the corpora cavernosa.
Courtesy of: Mouriquand P., Vidal I. Complexe Exstrophie
Epispade. Encyclopédie Médico-­Chirurgicale—Urologie.
(a) In boys, the aims of this surgery are (1) to cor- Volume 18-208-A-10 2012. pp 1–18
rect the dorsal curvature of the penis by de-
rotating the corpora cavernosa to obtain a is vertically opened along the entire ven-
dangling penis, (2) to relocate the recon- tral aspect of each corpus. This manoeu-
structed urethra on the ventral side of the penis vre permits the exposure of the albuginea
and (3) to redistribute the skin around the penis of each corpus. Dissection continues
to compensate the dorsal skin defect. Although under the fascia around the albuginea of
many procedures have been described over the each corpus medially to separate the vas-
years, the techniques of Ransley, Mitchell and cular tissues (spongiosum) leading to the
Kelly are probably the most commonly used urethral plate and externally to separate
today. Preoperative androgen stimulation of the wide strip of neurological fibres inner-
the genital tubercle makes surgery easier. vating the glans. Each neurovascular bun-
• In Ransley’s technique [28], the incision dle and the urethral plate with its
begins in the midline above the urethral spongiosal tissue are then separated from
opening and continues down on each side adjacent structures. The urethral plate is
of the urethral plate (backed by the corpus tubularized, and a plasty (IPGAM = reverse
spongiosum) and sweeps ventrally around MAGPI) of its distal end allows the ven-
the coronal sulcus separating the prepuce tralization of the future urethral meatus.
and ventral skin from the corpora. Once The corpora are then de-rotated medially
the ventral aspects of the corpora are fully by approximately 90° and maintained in
exposed, the fascia covering each corpus this new configuration by a proximal
448 G. de Sallmard et al.

Fig. 33.11 Derotation Derotation of the corpora cavernosa

of the corpora
1- Dorsal urethral plate 3- Neurovascular bundles
cavernosa. Courtesy of:
Mouriquand P., Vidal 2- Corpus cavernosum 4- Ventral reconstructed urethra
I. Complexe Exstrophie 1
Epispade. Encyclopédie
Médico-Chirurgicale—
Urologie. Volume 2
18-208-A-10 2012. 3
pp 1–18

caverno-­cavernostomy. This new anasto- tures, which allows a tubularization and

mosis between the corpora keeps the ure- ventralization of the entire urethra, and a
thra in its ventral position and gives the more complete release of the corporal
penis a dangling position when flaccid. rotation. The corpora cavernosa are com-
The skin shaft is covered with a transverse pletely separated from each other with
flap of ventral skin dissected with its ped- their corresponding hemi-glans. The ure-
icle and transferred to the dorsal side of thral plate is dissected off of the corporeal
the penis (reverse Duckett). bodies respecting its blood supply coming
• Mitchell’s technique [29, 30] is based on a from underneath. It is then tubularized
complete disassembly of the penile struc- and transferred ventrally. The corpora
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 449

Fig. 33.12 Dérotation Cantwell-Ransley procedure

of the corpora and skin 1- Pubic bone 4- Corpora cavernosa
cover of the dorsum of 2- Caverno-cavernostomy 5- Glans
the genital tubercle. 3- Neurovascular bundles 6- Urethral meatus
Courtesy of:
Mouriquand P., Vidal
I. Complexe Exstrophie
Epispade. Encyclopédie 1
Médico-Chirurgicale—
Urologie. Volume
18-208-A-10 2012.
pp 1–18

entirely separated and independent are (b) In girls, the open urethral plate extending
rotated to correct the dorsal chordee and from the bladder neck to the medial aspect of
sutured together. The glans halves are both hemi-clitoris anteriorly and to the ante-
subsequently brought together. rior vaginal edge posteriorly is separated
• The Kelly procedure, or radical soft tissue from the adjacent structures to the perineal
mobilization, is used by some [31, 32]. muscles and subsequently tubularized. The
The technique is described elsewhere [33] triangular hairless area separating both hemi-­
and may be a valuable alternative for pri- pubes is excised. The perineal muscles
mary or secondary penile reconstruction located in front of and between the neo-­
in EEC patients. The periosteum on the urethral conduit and the vaginal orifice are
inner side of the ischium and pubis with both sutured together which significantly
the attachment of the sphincter muscles, increases the bladder outlet resistance and
the pudendal vessels and nerves are mobi- provides social continence in most cases. A
lized on both sides so that the outstretched secondary plasty of the mons venus may be
muscles can help to reconstitute the mem- needed at puberty if the cosmetic appearance
branous urethra without osteotomy. of this area remains unsatisfactory. It is rec-
Others [34] have suggested a mobilization ommended not to dissect and suture together
of the crura from the pubic rami to get both medial aspects of the two hemi-clitoris
more penile length without the complete to avoid any damage of the clitoral sensitivity
Kelly mobilization. [35].
450 G. de Sallmard et al.

Fig. 33.13 Surgical Female epispadias repair

landmarks in a female 1- Hemi-clitoris
epispadias. Courtesy of: 2- Hairless triangular zone
Mouriquand P., Vidal 3- Open urethra
I. Complexe Exstrophie
Epispade. Encyclopédie
Médico-Chirurgicale—
Urologie. Volume
18-208-A-10 2012.
pp 1–18
2

1
3

33.4.4 Incontinence Surgery complex, coordinated active neuromuscular

(Fig. 33.15a–c) mechanisms, cannot be achieved by conven-
tional surgery. Surgery can only create a suffi-
All procedures aim at increasing the bladder cient static obstacle which, in the best cases,
outlet resistance to achieve social dryness (>3 h) allows the child to hold urine for at least 3  h
and allowing bladder emptying either via the without significant leakage. This is dryness
reconstructed urethra or via a continent conduit which implies passive mechanisms not always
(Mitrofanoff) [36]. Continence, which implies easily controllable.
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 451

Fig. 33.14 Urethroplasty Female epispadias repair

in a female epispadias.
Courtesy of: Mouriquand 1- Pre-urethral perineal muscles approximation
P., Vidal I. Complexe 2- Reconstructed urethra
Exstrophie Epispade.
Encyclopédie Médico-
Chirurgicale—Urologie.
Volume 18-208-A-10
2012. pp 1–18

(a) The peri-cervical injection of biocompatible

Although immediate results can be encouraging,
substance: It is the simplest option to increase continuous deterioration with increased leakage
the outlet resistance by injecting a bulking agent is common. It has been demonstrated that the
in the bladder neck region. Although not very efficacy of bulking agents is much increased
invasive, this procedure provides disappointing whilst used as a post-operative adjunct to blad-
results on a medium- and long-term basis. The der neck surgery than as an isolated treatment
most optimistic results [37] report 30–40% of [38]. It does not seem that the type of bulking
dryness with several years of follow-­ up. agents used makes much difference [39].
452 G. de Sallmard et al.

Bladder neck reconstruction Bladder reconstruction 2

1- Triangular bladder flaps 1- Mitrofanoff conduit
2- Ureter 2- Lengthening of the urethra
3- Reimplanted ureters (Jeffs technique) 3- Integration of the 2 triangular flaps
4- Bladder reservoir into the bladder reservoir

4
3

2
1

Fig. 33.15  Cervico-cystoplasty to increase bladder outlet resistance. Courtesy of: Mouriquand P., Vidal I. Complexe
Exstrophie Epispade. Encyclopédie Médico-Chirurgicale—Urologie. Volume 18-208-A-10 2012. pp 1–18

(b) The cervicocystoplasty: This surgery is usu- der capacity is big enough (>80 mL). It is the
ally performed in incontinent epispadias most hazardous part of this reconstruction as
after the age of 3 or 4 years when some col- it aims at increasing the bladder outlet resis-
laboration between the child and the medical tance to achieve intervals of dryness of at
team can be established and when the blad- least 3  h without compromising complete
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 453

bladder emptying and upper tract drainage. pressure bladder emptying [36]. If the
Experience shows that this challenge is rarely bladder capacity does not increase after ure-
achieved in the exstrophy group although throplasty, it is sometime necessary to aug-
results are better in the epispadiac group as ment the bladder capacity with a bowel
the bladder behaviour is probably more nor- segment. Finally, most EEC bladders are
mal. The principle of bladder neck plasty is associated with reflux, which is usually cor-
to narrow the bladder outlet and reintegrate rected at the time of the cervicocystoplasty.
the verumontanum inside the urethral lumen. Urinary diversions towards the distal colon
Bladder neck tightness is achieved by creat- [45] and their variants (Mainz Pouch II) have
ing a muscular muff which itself creates a the advantage of reducing the number of
static outlet resistance. Ureteric reimplanta- operations and achieving a reasonable level
tion is needed to prevent reflux which is of continence although they expose patients
almost constant once the bladder is closed to a high risk of severe retrograde urinary
and to create enough trigonal space to tighten infection and bowel cancer [46]. Non-­
the outlet. Bladder neck wrapping is based continent diversions (Bricker) are another
on the Young-Dees-Leadbetter procedure ultimate option.
and its multiple variants. This technique (f) Late procedures: Refashioning external geni-
often leads to “obstructive” micturition, i.e. talia and umbilicoplasty are often requested
high-pressure emptying which represents a in the adolescent group of BEEC.  The
threat for the bladder and the whole upper hairless triangle and the midline pubic
­
tracts. Trigonal dissection can also damage depression are often the source of concerns.
the genital tracts. These patients often have Rotation of hairy pubic flaps is then needed.
poor or retrograde ejaculations related to the Various techniques of umbilicoplasty have
deficient sphincteric area. been published. We favour Ransley’s tech-
(c) The artificial urinary sphincter: Insertion of nique which needs to be seen to be under-
an artificial sphincter cuff around the EEC stood. Introitoplasty and treatment of uterine
bladder neck has poor records although indi- prolapse are also common and challenging
vidual experience is always limited. There is procedures in female adolescents. Anchoring
a much higher risk of erosion in a recon- the uterus to the sacrum often fails, and radi-
structed bladder neck and urethra [40, 41]. cal surgery is sometimes needed after preg-
The artificial sphincter is therefore not a nancies. Finally, phalloplasty is the ultimate
frontline solution in the EEC group although option in case of complete penile failure.
silicone sheath placement has been reported This complex procedure should be performed
to facilitate the insertion of the cuff in in identified centres.
selected patients [42, 43]. (g) In cloacal exstrophy, procedures are similar
(d) The bladder neck closure: It is the ultimate although most patients require an intestinal
solution when all others have failed. It is a diversion from birth to separate the urinary
difficult operation as all cervical tissues have and intestinal compartments.
been previously dissected and the separation
of the trigone from the bladder neck region
can be tricky. This procedure although quite 33.5 C
 omplete Primary Repair
successful in terms of dryness is irreversible of Exstrophy (CPRE)
and obviously implies a concomitant
Mitrofanoff diversion [44]. Begun in 1989 by the Seattle group [47–49], a
(e) Complementary procedures: The unpredict- complete primary repair is based on early, one-­
able results of cervicocystoplasty often lead step treatment with or without pelvic osteotomy
to a combined Mitrofanoff continent diver- with a primary goal of achieving early blad-
sion which allows complete, regular and low-­ der  outlet resistance and bladder growth, thus
454 G. de Sallmard et al.

a­voiding the need for bladder neck reconstruc- ing of this condition [58–62]. The Mitchell penile
tion. The surgery is performed either within the disassembly [29, 30, 47, 63, 64] provides equiva-
first 3 days of life or between 6 and 8 weeks of lent results with possibly a higher risk of glans or
life and combines primary abdominal wall and hemi-glans necrosis. The Kelly procedure has
bladder closure with epispadias repair and partial strong supporters who have a solid experience of
tightening of the bladder neck. The most com- this difficult dissection associated with a signifi-
mon indication for delayed surgery is to allow for cant risk of penile loss [32, 65]. Skin coverage of
the growth of the small bladder plate, followed the reconstructed epispadiac penis aims at trans-
by delayed referral [50]. This technique may ferring the ventral skin to the dorsum. The post-­
decrease the morbidity associated with multiple operative cosmetic appearance may often be
operations and stimulate early bladder growth. disappointing with a penis which often looks
Many children however require surgery for small and buried. Attempts to improve this have
resulting hypospadias, persistent vesicoureteral been reported [66].
reflux, incontinence or failed primary closure
[51–54]. Wound dehiscence, bladder prolapse,
vesicocutaneous fistula and loss of penile tissue 33.6.2 Dryness
are associated with CPRE [55, 56]. Ultimately
74% of patients in the Seattle group achieved Functionally the primary reconstruction of the
social dryness; however, a disappointing 80% of urethra in both sexes is an essential first step
boys and 57% of girls required subsequent blad- which allows the bladder to grow. Social dryness
der neck repair [53]. More promising results is defined variably in the literature, although a gap
from Gargollo et al. report the need for bladder of 3 h of dryness is a generally accepted standard
neck repair after primary closure in only 43% of [67]. In the Baltimore group [68], social dryness
boys and 27% of girls [54]. However, long-term was achieved in approximately 75% of their
urinary continence with CPRE may be similar to exstrophy females compared to 87.5% of dry
staged repair of bladder exstrophy [53]. The need patients 15  years earlier. Our long-term results
for neonatal osteotomy is independent of the sur- [69], those from the Indianapolis group [70] and
gical approach, although a single-institution others [71] clearly showed a long-term deteriora-
experience demonstrated a feasibility of primary tion of dryness as well as serious complications
closure without osteotomy with successfully clo- related to “obstructive” micturition (infections,
sure in 95% of cases [57]. stones, bladder perforation, upper tract dilatation)
mostly in the exstrophy group. In our own series
of 25 incontinent epispadias, dryness was
33.6 Results achieved day and night in 28%, day only >3 h in
24%, between 1 and 3 h 16% and less than 1 h in
33.6.1 Cosmetic 8%. These results were better in this group than in
the exstrophy group (80 patients) where only 45%
Reported results are usually better in the epispa- presented with a dry interval of >3 h with trans-
diac group compared to the exstrophy group and urethral voiding. Complications related to
better in girls than in boys. Cosmetically, the out- “obstructive micturition” and other complications
come is satisfactory in girls although comple- were also significant with 48% of recurrent uri-
mentary surgery of the mons venus may be nary tract infections (vs. 65% in the exstrophy
requested at puberty. The repaired epispadiac group), 8% of stone (vs. 24%), 20% of upper uri-
penis is often short and broad with better result in nary tract dilatation (vs. 26%), 4% of bladder per-
isolated epispadias compared to the exstrophy foration (vs. 16%) and one patient with
group. Undoubtedly the Cantwell-Ransley penile adenocarcinoma in both groups [69].
repair has been a major step forward not only in Simplification of the technique of bladder neck
the surgical outcome but also in the understand- plasty has been reported [72]. The key issue is the
33  The Bladder Exstrophy-Epispadias Complex (BEEC) 455

growth of the bladder after increasing the outlet unpredictable with a significant morbidity.
resistance. The epispadiac bladder has a much Bladder neck closure is the ultimate solution
safer behaviour and therefore a better dryness out- especially in boys despite long-term complica-
come than the exstrophy bladder, which is essen- tions. Outcomes in adolescents and adults and
tially abnormal [73]. The role of endoscopic large series are lacking which should encourage
injection remains uncertain as published series are prospective multicentric studies.
short, retrospective and often mix neurological
bladder and EEC. It might be helpful to treat par-
tial urinary incontinence and to help bladder References
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 Prune-Belly Syndrome
34
Mario Messina, Francesco Molinaro,
and Rossella Angotti

34.1 Definition because none completely explains the whole con-

stellation of findings in the syndrome. The impos-
The term prune-belly syndrome (PBS) was sibility to test these theories, furthermore, due to
coined in 1901 by William Osier because of the the absence of experimental model contributes to
wrinkled appearance of the abdominal wall in consider them only conjectures [3–10].
affected patients. Prune-belly syndrome also is Three major theories are known:
known as the triad syndrome, because it has three
major manifestations and Eagle-Barrett syn- 1. Fetal outlet obstruction: This theory has been
drome. It is a rare congenital disorder character- proposed by Strumme in 1903. Urinary dilata-
ized by three major features: deficient abdominal tion and atrophy of abdominal wall are con-
wall musculature, urinary tract anomalies, and sidered as final result of early in utero posterior
bilateral cryptorchidism in males [1]. urethral obstruction that produces a signifi-
cant back pressure at a critical time during
development.
34.2 Epidemiology 2. Theory of mesodermal arrest: This theory

suggests that the etiology of prune-belly syn-
PBS occurs mostly in boys (>95%) and its annual drome is a primary defect of lateral plate
incidence is estimated between 1/30,000 and mesoderm. This is the precursor of the ureters,
1/50,000 live births. Females constitute about bladder, prostate, urethra, and gubernaculum
3–5% of known cases [2]. [13, 14]. Nevertheless, the mesodermal arrest
theory does not explain the male predomi-
nance of the syndrome. It also fails to explain
34.3 Pathophysiology the myriad associated anomalies and the pres-
ence of the abdominal wall abnormalities with
The exact pathogenesis of PBS is not clearly a normal urinary tract.
known as yet. Many theories have been proposed, 3. A yolk sac defect: This has been proposed by
but none of them have universal acceptance Stephens. It is based on an error in embryo-
genesis of the yolk sac and allantois. This
theory postulates that the yolk sac does not
M. Messina (*) · F. Molinaro · R. Angotti resorb. The abdomen closes around it, leaving
Division of Pediatric Surgery, Department of the abdominal musculature highly redundant.
Medical, Surgical and Neurological Sciences,
University of Siena, Siena, Italy
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 459

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_34
460 M. Messina et al.

34.4 Genetic [11–13]

No specific gene defect has been identified for

PBS to date, even if the high male-to-female
ratio, the occasional occurrence in male siblings
and cousins, and the increased occurrence in
twins suggest a genetic basis. Most cases are spo-
radic and have a normal karyotype. Some patients
have chromosomal abnormalities, including
Turner’s syndrome and trisomies 13 and 18. The
consensus, however, remains that an associated
chromosomal abnormality is the exception rather
than the rule [3].

34.5 Clinical Features [1, 3]

• Abdominal Wall Fig. 34.1  Abdominal wall in prune-belly syndrome

• The deficiency of abdominal wall muscles can
be partial or complete. The abdominal wall is also vary greatly from side to side in the
lax, thin, and protuberant (Fig. 34.1). It may same patient.
be associated with flaring rib margins, –– Ureters: The ureters are typically dilated,
depressed lower sternum, and kyphoscoliosis elongated, and tortuous. The lower third
in severe cases. The skin is wrinkly until older of the ureter is more affected than the
age when it can often become smoother. proximal portion. Their radiographic
Absence and muscular hypoplasia especially aspect is hallmark of the syndrome.
in the lower and central areas are the main his- Hydroureteronephrosis, usually nonob-
tological features of the abdominal wall. structive, is not correlated with the degree
Which is the clinical effect of all these charac- of renal dysplasia. Their architecture of
teristics of the abdominal wall? Firstly, cough walls is dysmorphic and their peristalsis is
mechanism in many of these children is inef- poor and ineffective. Vesicoureteral reflux
fective, exposing them to recurrent respiratory involves up to 85% of patients with
infections and worsening their pulmonary PBS.  Its degree can be difficult to estab-
condition; secondly, the absence of Valsalva lish by the conventional system of grading
maneuver contributes to the ineffective func- due to dysmorphism of the ureter, renal
tion of the bladder and the small intestine. pelvis, and calices. Histologic examina-
• Urinary Tract tion of the ureter shows a profound sub-
Urinary tract, in terms of upper and lower uri- verted architecture at level of the ureteral
nary tract, is all involved in many ways. wall that contributes to the poor ureteral
–– Renal: Renal dysplasia and hydronephrosis peristalsis. The dilatation and reduced
are common characteristics. peristalsis of the ureters interfere with the
The involvement of kidneys varies widely output of the bladder, cause a urinary sta-
from normality and dysplasia. Prognosis is sis, and increase the risk of urinary infec-
directly related to renal function and the tion that represents the greatest threat to
degree of renal dysplasia. The renal dyspla- the renal parenchyma.
sia is found in more than half of patients –– Bladder: Megacystis is typical of patients
and it is a major determinant of patients’ with PBS. The bladder is usually enlarged,
prognosis. The degree of dysplasia may with a thick and smooth wall, not
34  Prune-Belly Syndrome 461

t­ rabeculated; the dome is elongated similar didymis, travels via the inguinal canal, and
to a large diverticulum consisting of the attaches distally at the pubic tubercle.
urachal remnant and giving the bladder an Discontinuity between the ductuli efferentes
hourglass configuration. A patent urachus and rete testis and between the body of the
can be present, especially in association epididymis and testis is common. The vas def-
with urethral anomalies (atresia or micro- erens is thickened and may drain ectopically.
urethra). The ureteral orifices are often lat- The seminal vesicles may be dilated, atretic,
eral, dilated, and out of the trigone or absent. Verumontanum is small or absent
explaining the presence of massive reflux. and reflux into the vas deferens can be present.
Histologic examination of the bladder Prostate is hypoplastic and it is one of the eti-
demonstrates an alteration in the ratio of ologies of infertility in this syndrome.
connective tissue to smooth muscle caus-
ing a poor contractility even if the involve-
ment of the bladder is less than the ureter 34.6 Associated Anomalies
following in a good compliance. [1, 3, 14]
–– Urethra: The known anomalies of the ante-
rior urethra range from urethral atresia to Patients with prune belly syndrome are often
megalourethra. Urethral atresia, stenosis, affected from many associated conditions that
or microurethra is present in cases with influence their prognosis determining a long-­
poor prognosis, and survival of these term morbidity in 75% of them and mortality.
patients is related to the presence of a pat- Multidisciplinary approach is often mandatory to
ent urachus. care of these patients. Many associated anoma-
Megalourethra may be scaphoid or fusi- lies are known in patients with PBS as it is
form. The fusiform megalourethra, accom- reported in Table 34.1.
panied by deficient corpora cavernosa, is a
more severe defect frequently associated
with renal dysplasia and lethal anomalies. Table 34.1 Associated anomalies with percentage of
Scaphoid megalourethra is characterized as incidence [1]
a deficiency of the corpus spongiosum with Cardiac 10% Patent ductus arteriosus,
normal glans and fossa navicularis. The atrial septal defect,
ventricular septal defect,
aspect of VCUG like heart is typical.
tetralogy of Fallot
Urethral obstructions at the level of veru- Gastrointestinal 30% Malrotation, intestinal
montanum are present up to 50% of patients atresia, intestinal stenosis,
(posterior urethral valves in 10% of cases). volvulus, anorectal
• Testis, Epididymis, Seminal Vesicles, Prostate, agenesis, imperforate anus,
omphalocele, gastroschisis,
and Vas Deferens hepatobiliary anomalies,
Undescended testis is a needful feature in acquired megacolon
PBS.  As other mesenchyme-derived genito- Orthopedic 45– Congenital dislocation of
urinary organs, also epididymis, seminal vesi- 60% hips, chest wall deformity:
pectus excavatum
cles, and vas deferens can be involved in terms
Pectus carinatum, scoliosis,
of anomalies in PBS.  All of these findings genu valgum, talipes
contribute to the known infertility associated equinovarus, severe leg
with prune belly syndrome. Testicles are usu- maldevelopment:
arthrogryposis
ally intra-­abdominal, sited at the level of inter-
Pulmonary 50% Pulmonary hypoplasia,
nal inguinal ring, with increased risk of pneumothorax,
malignant degeneration. Gonads are small pneumomediastinum, lobar
with short vessels. The gubernaculum is usu- atelectasis, pneumonia,
ally attached proximally to the tail of the epi- chronic bronchitis
462 M. Messina et al.

34.7 Spectrum of Disease 34.8 Pseudoprune Syndrome

[1, 15, 16]
The term “pseudoprune” has been suggested to
Based on the many anomalies present in PBS, it define females and males, who do not have all
is understandable that there is a wide spectrum of features of prune belly syndrome (incomplete
clinical presentations. Classification systems syndrome).
based on this clinical spectrum have been formu- Incomplete Syndrome
lated by numerous authors, and all take into con- Abdominal wall features usually lack in the
sideration initial and subsequent renal function. incomplete syndrome, but the common uropathy
Three major categories of presentation in the and cryptorchidism are present. Many of these
neonatal period were described by Woodard as it patients risk to develop a renal failure probably
is reported in Table 34.2. because of the delay of diagnosis. Some of them
Category I includes patients with the most may present as late as adulthood with symptoms
severe form of the prune belly syndrome. of renal failure and hypertension. For these rea-
Oligohydramnios, pulmonary hypoplasia or sons, they require close observation, careful
pneumothorax, and several renal dysplasia are monitoring, and specific interventions [17].
present. Urethral obstruction or atresia, which Female Syndrome
represents the lethal form of PBS, may be pres- Three to five percent of PBS patients are
ent. Patients of this category usually die in the female; most of them have the abdominal wall
few days after birth due to pulmonary deficiency and the abnormal urinary tract, but it is
complications. known also the association between typical
Category II includes babies without pulmo- abdominal wall deficit and a normal urinary tract.
nary hypoplasia but with renal dysplasia of dif- They are often affected by omphalocele and blad-
ferent grades. They usually have no immediate der outlet obstructive lesions [18].
problems with survival.
Category III patients, who are the majority of
patients with PBS, have the typical external 34.9 Investigations
abdominal features and undescended testes, but
pulmonary and renal functions are preserved 34.9.1 Prenatal
despite the markedly dilated urinary tracts.
Prenatal diagnosis of prune belly syndrome can be
made from 11  weeks of gestation on ultrasound.
Table 34.2  Categories of presentation in the neonatal
Ultrasonic diagnostic accuracy varies from 30% to
period described by Woodard
85%. The importance of prenatal diagnosis is
Category
classification Clinical features
related to the possibility to make an in utero treat-
I Oligohydramnios, pulmonary ment known as the vesicoamniotic shunt proce-
hypoplasia, or pneumothorax. May dure. Sonographic findings include
have urethral obstruction or patent oligohydramnios or anhydramnios, hydroureter, a
urachus and clubfoot distended bladder, and a thin, attenuated abdominal
II Typical external features. Uropathy
wall. Megacystis megaureter syndrome, megacys-
of the full-blown syndrome but no
immediate problem with survival. tis-microcolon-intestinal hypoperistalsis syn-
May have mild or unilateral renal drome, vesicoureteral reflux, or posterior urethral
dysplasia. May or may not develop valves may have similar findings in fetal ultrasono-
urosepsis or gradual azotemia
gram. Although modern ultrasonic capabilities and
III External features may be mild or
incomplete. Uropathy less severe. visualization have improved, it can still be difficult
Stable renal function to establish a definite prenatal diagnosis.
Each of them includes specific clinical features and differ- Vesicoamniotic shunt: A double pigtail cathe-
ent postnatal management and prognosis [1] ter is inserted percutaneously via trochar and
34  Prune-Belly Syndrome 463

positioned to drain urine from the obstructed A voiding cystourethrogram (VCUG) must be
fetal bladder into the amniotic fluid. performed to show the presence of vesicoureteral
It is clear that this intervention can be made reflux (85% of patients with PBS) and to assess
only in specific cases (normal karyotype, severe the bladder emptying (Fig.  34.2). After initial
oligohydramnios, and predicted good renal func- evaluation, a technetium 99m (99mTc) diethyl-
tion) [19–26]. enetriaminepentaacetic acid (DTPA) renal scan
and a mercaptoacetyltriglycine (MAG3) renal
scan can be made to give functional and anatomic
34.9.2 Postnatal informations. It is performed at 4–6 weeks of age
to prevent difficulties in interpretation due to
The phenotype of patients with PBS is typical, transitional neonatal physiology.
and physical examination at birth doesn’t leave Urethrocystoscopy for evaluation of the ure-
little doubt regardless of prenatal suspicion. A thral pathoanatomy may be performed. Serial
multidisciplinary team must take care of the creatinine measurements are mandatory.
patient. The major initial concern is the manage- Although an initial creatinine determination is
ment of cardiac and respiratory issues. An imme- important in establishing a baseline, it is known
diate chest X-ray needs to exclude common that its level at birth reflects maternal renal func-
associated pulmonary abnormalities such as tion. The trend in creatinine levels over the course
pneumothorax, pneumomediastinum, and pul- of the early postnatal days or weeks is much more
monary hypoplasia, which often occur as a result predictive of long-term renal function. A progres-
of oligohydramnios. A renal ultrasound must be sive increase of serum creatinine over the first few
done to have informations on the state of kidneys weeks of life is related to a poor prognosis. If after
in terms of cortical thickness, the presence of 48–72 h the serum creatinine is >1.0 mg/dL in the
cystic changes, the renal size, and the degree of term infant or 1.5 mg/dL in the preterm infant, a
urinary tract dilation. degree of renal insufficiency can be diagnosed. If
Serial urinalysis and urine cultures are initial creatinine’s value is <0.7 mg/dL, a subse-
extremely important. quent renal failure is improbable. The serum and

a b

Fig. 34.2  VCUG showing bilateral high-grade reflux in both passive (a) and active (b) phases
464 M. Messina et al.

urinary electrolyte levels and analysis of serum valid urinary drainage, and delayed surgical
blood urea nitrogen (BUN) are useful to assess reconstruction, at 3  months of age or more,
for the potential systemic acidosis and electrolyte according to pulmonary maturation. Patients
imbalances that may be seen in renal insuffi- with preserved renal function (category III) are
ciency. Finally, the glomerular filtration rate usually managed by conservative approach.
(GFR) is initially low in the premature and full- Antibiotic prophylaxis is usually recommended
term infant and then rapidly increases. This is an to avoid urinary infections. Regular monitoring
important consideration before performing exam of urinary tract dilation (ultrasonography) and
with administration of intravenous contrast renal function (serum creatinine measurements)
agents, which can cause elevated plasma osmo- must be planned. Urologic surgery is not usually
lality, causing intraventricular hemorrhage as necessary and it should be reserved for those
well as further impairment of renal function. patients who have repeated urinary infections.
Specific exams based on associated malforma- These patients benefit from early orchidopexy
tions of patients are useful in the initial diagnosis and abdominoplasty [3, 16].
of patients. Finally, ultrasound of the heart and
abdominal and chest radiographs should be
obtained [1, 3]. 34.11 Surgical Management [1, 3]

Surgical management of children with PBS

34.10 Management includes three different possibilities: urological
surgery, abdominal wall reconstruction, and
The main goal of treatment of patients with PBS orchidopexy.
is to preserve renal function. The prognosis and
the postnatal management of these patients, 1. Urological surgery consists in two different
indeed, are closely related to it. The spectrum of options: temporary urinary diversion and uri-
therapeutic possibilities range from a “wait and nary tract reconstruction
see” approach to immediate or delayed urologic (a) Temporary urinary diversion usually is
surgery. It should be emphasized that surgery in not indicated. It can be necessary, as a
these infants should not be undertaken unless temporary measure to decompress the
expert anesthesiology and medical support are entire urinary tract for children with a doc-
available and the surgeon has extensive experi- umented site of obstruction. Cutaneous
ence doing such surgery. Furthermore, aggressive vesicostomy usually is the procedure of
approach must be considered with caution choice and it can be performed in inten-
because the surgery is difficult and the patients sive care. The Blocksom technique as
are vulnerable to pulmonary complications. modified by Duckett [27] is most com-
The neonates requiring an early surgical inter- monly method used to create a generous
vention are few. They are patients with bladder stoma and prevent stomal stenosis. A short
outlet obstruction, who usually die in the imme- transverse incision, halfway between the
diate postnatal period due to pulmonary compli- umbilicus and symphysis pubis, is made.
cations (category I). The vesicostomy or After dissection of the peritoneum from
cutaneous pyelostomy is needed in these cases to the dome of the bladder, a small circular
provide an immediate urinary drainage. Surgical hole in the bladder dome posteriorly is
approach, nevertheless, doesn’t modify their poor performed. This is important to ­minimize
long-term survival due to severe underlying renal the risk of prolapse of the posterior blad-
dysplasia. Patients with different renal dysplasia der wall through the stoma, resulting in
grades but without pulmonary hypoplasia (cate- obstruction. Quadrant sutures are placed
gory II) are managed with antibiotic prophylaxis between the anterior rectus sheath of the
at birth, urinary diversion if necessary to ensure a anterior abdominal wall and the bladder
34  Prune-Belly Syndrome 465

adjacent to the vesicostomy. The lateral anatomic obstruction of the urethra.

edges of the rectus sheath are closed with However, it is known that it is the sec-
interrupted absorbable sutures. An 18- to ond choice after considering intermit-
24-Fr Foley catheter is introduced into the tent catheterization if the urodynamic
bladder via the vesicostomy and should criteria of outlet obstruction are not
remain in situ for a few days postopera- present [29, 30]. Endoscopic urethrot-
tively to minimize the risk of prolapse or omy by hot or cold knife is usually per-
stenosis. Thereafter the vesicostomy formed with careful avoidance of the
should be left to drain freely into the urinary sphincter.
child’s nappy/diaper. If a large urachal • Anterior urethral reconstruction:
diverticulum is encountered during cre- Prune belly syndrome is associated
ation of the vesicostomy, it can be excised. with microurethra and megalourethra.
Rarely it is indicated a more proximal Progressive dilatation of the urethra
diversion like as cutaneous pyeloplasty can be used. If the anterior urethra is
that it is chosen. The proximal ureteros- not usable, urethroplasty techniques
tomy is usually avoided because it pro- combining skin flaps and grafts are
vides to worst upper tract drainage and necessary to bridge the anterior ure-
sacrifices a normal proximal ureter that thral defect. Megalourethra can be
might be useful in later reconstruction. repaired by application of hypospadias
(b) Urinary tract reconstruction is generally operative techniques [3, 31, 32].
performed in cases of progressive or severe • Reduction cystoplasty: Poor contract-
hydronephrosis, recurrent upper tract ibility and inefficient voiding are typi-
infections, and worsening renal function. cal aspects of the bladder in
Timing is quite controversial. Some experts PBS.  Reduction cystoplasty is per-
advocate immediate reconstruction, believ- formed to reduce volume and improve
ing that it reduces the risk of infection and emptying. A variety of techniques have
progressive renal failure. Other experts been proposed, from simple excision
recommend nonoperative management of the urachal diverticulum to the exci-
because urinary tract function often sion of redundant mucosa with the cre-
improves with age. However, extensive ation of overlapping flaps to improve
reconstructive surgery is not recommended contractibility. Reduction cystoplasty
before the age of 3–6 months [1, 3]. should be done only to remove the
• Ureteral remodeling: Ureteral tailoring larger urachal diverticulum or as part
and reimplantation are usually under- of a more extensive internal recon-
taken. The goal of ureteral remodeling struction. Intermittent catheterization
is to preserve the upper few centime- through the urethra or through an
ters of proximal ureter for reconstruc- appendicovesicostomy channel is
tion. Meticulous ureteral dissection is likely to afford better long-term blad-
needed. The distal, redundant, and der emptying and reduction of residual
ectatic ureter is excised, and common urinary volumes [33–35].
ureteral tailoring techniques are used to 2 . Abdominal wall reconstruction
decrease the size of the ureter. Ureteral Despite the mild degrees of abdominal
reimplantation into the abnormal and wall laxity which can mature, the potential
floppy bladder can be difficult because psychological crippling justifies the abdomi-
the creation of a submucosal tunnel is nal wall reconstruction.
challenging [28]. In addition to the cosmetic benefit, how-
• Internal urethrotomy should be consid- ever, it is known also its role in improvement
ered in the older patient with a true of bladder, bowel, and pulmonary function.
466 M. Messina et al.

The timing of abdominal wall reconstruction can be obtained with many techniques as
should be dictated by the need for other surgical Fowler-­Stephens orchidopexy, staged Fowler-­
interventions. If upper tract remodeling is not Stephens orchidopexy, and microvascular
anticipated, then the abdominal wall can be autotransplantation.
addressed at any time. Between many described
techniques of abdominoplasty in patients with
PBS, Monfort technique collects to date general 34.12 Long-Term Outcomes [49, 50]
consensus because it recognizes the best func-
tional and cosmetic results [35–40]. Prognosis of a child with prune belly syndrome is
After estimation of the amount of redun- directly related to renal function and the degree
dant abdominal wall, an elliptical incision that of renal dysplasia. Despite known management
extends from the tip of the xiphoid to the pubis of renal dysplasia, approximately 30% of patients
is done. A second incision is made around the presenting with impaired renal function at initial
umbilicus to preserve it in situ. evaluation will develop chronic renal failure dur-
The skin and subcutaneous tissue are sepa- ing childhood or in their adolescent years. When
rated from the attenuated fascia and muscle, the deterioration of kidneys develops in young
extending the dissection laterally to the ante- age, peritoneal dialysis often can be used tempo-
rior axillary line. Vertical fascial incisions are rarily until the child is of adequate size to accept
made lateral to the superior epigastric arteries, a transplant.
leaving a central fascial bridge. With this A normal growth and a normal pattern of sec-
approach the exposure of the urinary tract or ondary sexual development can be expected in
abdominal testes is perfect, and intra-­ most of the patients. Infertility of these patients is
abdominal surgery can be done. known. Many factors contribute to its etiology as
The lateral fascia is then advanced over the anatomical elements (prostatic hypoplasia; lack
central fascial bridge from both sides, alleviat- of continuity between the ductuli efferentes and
ing the redundancy and increasing the thick- rete testis; abnormally thickened vas deferens
ness of the abdominal wall. A recent and ectopic drainage; atretic, absent, or dilated
modification of the Monfort technique uses seminal vesicles; intra-abdominal location of the
laparoscopy approach. testes) and retrograde ejaculation related to an
3 . Orchidopexy [41–48] open bladder neck and hypoplastic prostate.
The early orchidopexy is mandatory in However, fertility with assisted reproductive
patients with PBS to permit a regular exami- techniques may be feasible in those who have
nation of testes in relation to potential risk of had successful early orchidopexy. The overall
testicular carcinoma and to ensure normal outlook for the PBS patient, both for survival and
hormonal function at puberty. These reasons for quality of life, has improved considerably,
justify early surgery although the fertility largely in the last years. The key to management
potential of the PBS patient is known to be is individualization of timing of care. Long-term
compromised. Transabdominal bilateral follow-up about the urinary tract is essential,
orchidopexy at about 6 months of age is cur- because it can change over time.
rently considered the approach of choice. This
approach is often used in conjunction with
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J Urol. 1984;2:266. pexy with laparoscopic clip ligation of the spermatic
42. Patil AA, Duffy PG, Woodhouse CRJ, Ransley
vessels in prune belly syndrome. J Pediatr Surg.
PG.  Long-term outcome of Fowler–Stephens orchi- 1995;30:870–2.
opexy in boys with prune-belly syndrome. J Urol. 48. Wacksman J, Dinner M, Staffon RA.  Technique of
2004;171:1666–9. testicular autotransplantation using a microvascu-
43. Gibbons DM, Cromie WJ, Duckett JW. Management lar anastomosis. Surg Obstet Gynecol. 1980;150:
of the abdominal undescended testicle. J Urol. 399–401.
1979;122:76–9. 49. Dreikorn K, Palmtag H, Rohl L.  Prune belly syn-
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1995;154:1148–52. 3:245–7.
45. Fowler R, Stephens FD. The role of testicular vascular 50. Reinberg Y, Manivel JC, Fryd P, et al. The outcome of
anatomy in the salvage of high undescended testes. renal transplantation in children with the prune belly
Aust NZ J Surg. 1959;29:92–6. syndrome. J Urol. 1989;142:1541–2.
Part VII
Tumors
 Neuroblastoma in Neonates
35
Matteo Carella, Riccardo Masetti,
Claudio Antonellini, Beatrice Randi,
Andrea Pession, and Mario Lima

In neonatal period, tumours, although very rare, and masses could have malignant potential if
represent an important cause of morbidity and untreated; nevertheless different tumours, with
mortality. The prevalence of neoplasms, within malignant histological features, have a benign
the first month after birth, occurs once in every clinical behaviour, or on the contrary certain
12,500–27,500 live births, and malignant tumours malignant tumours could regress in neonates
develop in approximately 40–50% of them. without treatment.
Diagnosis often occur during prenatal screening Management of malignancy in newborn com-
or during follow-up for a known cancer predispo- bines the expertise of paediatric surgeons to pae-
sition syndrome; in fact the presence of congeni- diatric medical oncologists because it represents
tal anomalies, multifocal or bilateral diseases and a difficult challenge due to vulnerability of this
cancer in close relatives is suggestive for an period which is characterized by rapid growth of
underlying cancer predisposition syndrome, and cells and tissues and a haematopoietic and
genetic counselling and testing should be consid- immune system not fully developed.
ered to investigate these possibilities. In neonatal solid tumours, surgery plays a central
Neonatal tumours differ from cancer in older role in diagnosis and treatment. Chemotherapy is
children because they arise generally from administered balancing the treatment most indicated
embryonic and immature tissue due to intrinsic with the risk of irreversible damage to the rapidly
dysfunction of cellular growth and proliferation; growing organs; drug doses should be calculated
for these reasons incidence, genetic, histological according to body weight than surface area and
features, clinical behaviour and treatment are dif- started at reduced levels and increased as well toler-
ferent in neonates. In newborn, benign tumours ated. The radiation instead is avoided due to risk of
irreversible damage of growth organs and tissues
M. Carella · R. Masetti · A. Pession (*) and the risk of secondary malignancies [1–3].
Department of Pediatric Hematology Oncology,
Sant’Orsola-Malpighi University Hospital,
Bologna, Italy 35.1 Introduction
e-mail: [email protected];
[email protected]; and Epidemiology
[email protected]
C. Antonellini · B. Randi · M. Lima Neuroblastoma occurs frequently in newborn
Department of Pediatric Surgery, Sant’Orsola-­ and represents the most common tumour diag-
Malpighi University Hospital, Bologna, Italy nosed in neonatal period, accounting for 7–8
e-mail: [email protected]; cases per million per year, with an incidence rate
[email protected]; [email protected]

© Springer Nature Switzerland AG 2019 471

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_35
472 M. Carella et al.

almost double that of leukaemia, the next most first in patients with congenital central hypoven-
prevalent malignancy occurring during the first tilation syndrome (CCHS). In many cases
year of life [4]. Hirschsprung’s disease is associated with CCHS
This neoplasm originates from neural crest because of migration failure of neural crest cell in
cells that will give rise to the development of the the gut wall. PHOX2B mutations were found also
peripheral sympathetic nervous system. The in families with neuroblastoma in which were
adrenal gland was the most common primary identified these other conditions [13].
tumour site, occurring in almost 50% of neuro- Neuroblastoma is also present in other cancer
blastoma cases, followed by connective tissue, predisposition syndromes like NF-1 (von
the retroperitoneum and the mediastinum [4]. Recklinghausen disease) because both disorders
Different cases have been detected during prena- result from defective development of the neural
tal screening, and some of these patients, together crest cells [14].
with those diagnosed in the first years of life, If we consider the pathogenesis of tumour dis-
have been observed to undergo spontaneous ease in the context of the embryonic development
regression even if metastatic [5]. of the neural crest, we can understand how the
clinical and pathological heterogeneity of neuro-
blastoma derives from alterations of molecular
35.2 Genetic and Risk Factors drivers which guide these cells during the differ-
ent maturation stages. Many genetic features of
Neuroblastoma arising in neonatal period sug- neuroblastomas have now been identified, which
gests a need to investigate exposure events before configure different subtypes of these tumours
conception and during gestation. Different stud- with distinct genetic abnormalities and clinical
ies correlate neuroblastoma with maternal alco- behaviour [14].
hol and tobacco use during pregnancy [6], MYCN amplification: Amplification of the
preconception parental occupation and prenatal MYCN oncogene at 2p24 occurs in about 20% of
exposure to drugs (e.g. codeine, oral contracep- all neuroblastomas, and of these, 90% are associ-
tives, anticonvulsant drugs) [7], ambient air tox- ated with poor clinical outcomes [15]. In neona-
ics [8] or maternal folate deficiency [9]. tal period MYCN amplification represents an
Most neuroblastoma occurs sporadically adverse prognostic factor, and treatment should
but inheritance should be considered in new- be intensified [5].
born. Germ line mutations in ALK and Allelic loss of 1p: Loss of heterozygosity of
PHOX2B are the most frequent genes involved 1p occurs in up to 35% of neuroblastoma and
in hereditary neuroblastoma which is occur- correlates with MYCN amplification and
ring in neonates [10]. advanced disease stage independently of age and
ALK, the anaplastic lymphoma kinase gene, stage [16, 17].
has been recently identified as the first Unbalanced 17q gain: This is the most fre-
neuroblastoma-­ predisposing gene. ALK is a quent genetic abnormality in neuroblastoma,
transmembrane receptor tyrosine kinase fre- occurring in up to 70% tumours [18].
quently expressed in the central and peripheral Allelic loss/imbalance of 11q: Those genetic
nervous system [11]. We can find ALK mutation abnormalities are reported in 40% of neuroblas-
in up to 10% of sporadic neuroblastomas and in tomas, and they are prognostic factors associated
many other neoplasm-like small-cell lung can- with poor outcomes in patients affected by neuro-
cers and anaplastic large-cell lymphomas, and for blastoma and without MYCN amplification.
these reasons, it represents an attractive therapeu- DNA index/ploidy: Hyperdiploid and near-
tic target [12]. triploid neuroblastomas showed a better out-
PHOX2B is a gene involved in normal sympa- come compared to diploid neuroblastomas,
thetic neuronal development and catecholamine this latter being associated to rapid tumour
synthesis. Germ line mutations were identified progression and a poor prognosis even in
35  Neuroblastoma in Neonates 473

infants and patients with lower stages of tinum, pelvic and neck. Neonatal neuroblastoma
­disease [5, 14]. occurs more frequently along thoracic and cervi-
cal tracts than the older children; abdominal
mass is often the more frequent clinical features;
35.3 Pathology pelvic tumours could alter bowel and bladder
habit. Flaccid leg paralysis, associated or not
Neuroblastoma generally is defined as lobulated with the bladder and bowel dysfunction, and
masses intimately related to the adrenal gland or Horner’s syndrome occur due to compression of
sympathetic chain delimited by delicate, mem- the spinal cord and neck sympathetic chain,
branous capsule covering soft, fleshy, grey, par- respectively [5].
tially haemorrhagic tumour. Two main cell In 42% of neonates, neuroblastoma could
populations are frequently recognized at micro- occur as a localized primary tumour associated
scopic exam: neuroblastic/ganglion cells and with multiple metastases which are limited to the
Schwannian stroma cells which different per- skin, liver and/or bone marrow. Subcutaneous
centage defines four groups of neuroblastic nodules (bluish and blanching with a ‘blueberry
tumours which are characterized by favourable or muffin’ appearance) and a rapidly enlarging and
unfavourable prognosis: diffusely involved liver, which may cause respi-
ratory compromise, renal impairment, bowel
• Neuroblastoma (Schwannian stroma-poor) dysfunction and coagulopathy, represent the
• Ganglioneuroblastoma, intermixed (Schwannian clinical features of neuroblastoma stage 4s/Ms
stroma-rich) [5, 20].
• Ganglioneuroma (Schwannian stroma-­dominant) Paraneoplastic syndromes can occur also in
• Ganglioneuroblastoma, nodular (composite neonates; opsoclonus-myoclonus syndrome
Schwannian stroma-rich/stroma-dominant and known as dancing eyes syndrome accounts for
stroma-poor [19] 2–3% of all neuroblastoma with a median age of
presentation of 18–22  months [21]. Vasoactive
Neuroblastic tumours such as ganglioneuro- intestinal peptide syndrome (VIP) known as
blastomas and ganglioneuromas are rare entity in ‘Kerner-Morrison’ syndrome is characterized nev-
newborn because maturation process needs ertheless by intractable secretary diarrhoea [22].
month to years to occur [5].

35.5 Diagnosis
35.4 Clinical Features
Ultrasound scanning is the first approach in a
Foetal neuroblastoma can be detected during neonate with an abdominal mass. MRI is the
screening in the third trimester, when an adrenal gold standard to evaluate paravertebral and pel-
mass with solid or cystic characteristics and foci vic tumours, and it is preferred than CT to avoid
of calcification could be seen at ultrasound. The the risk association with radiation exposure.
differential diagnosis includes adrenal haemor- Urinary catecholamines like homovanillic acid
rhages, enteric duplication cysts, subdiaphrag- (HVA) and vanillylmandelic acid (VMA) are
matic extralobar pulmonary sequestration, raised generally in >90% of children affected by
adrenal cytomegaly, adrenocortical tumours, neuroblastomas, but only 33% of neonates have
adrenal abscess and neuroblastoma. shown that increasing. Full blood count, bio-
Clinical features of neuroblastoma in children chemistry and lactate dehydrogenase levels
can be due to tumour primary localization along (LDH) in serum could be administered, but the
the sympathetic chain. Frequently neuroblas- evaluations of LDH, ferritin and NSE are only
toma could be detected in the adrenal glands, markers of tumour bulk but not specific to neuro-
paravertebral retroperitoneum, posterior medias- blastoma [5].
474 M. Carella et al.

123
I-meta-iodo benzyl guanidine (123I-mIBG) • Bone marrow aspirate or trephine biopsy con-
scintigraphy is highly sensitive and specific to tains unequivocal tumour cells, e.g. syncytia
neuroblastoma; it is important not only to resolve or immunocytological clumps of cells, and
differential diagnosis but also to evaluate metas- increased levels of urine catecholamines [24].
tases and then treatment response [23]. Frequently
perinatal neuroblastomas are mIBG avid [5].
According to the International Neuroblastoma 35.6 P
 rognostic Factors and Risk
Staging System (INSS) guidelines, a diagnosis of Stratification
neuroblastoma is established if either of the fol-
lowing sets of criteria are met: The new International Neuroblastoma Risk
Group stratification is based on prognosis, but
• Unequivocal pathological diagnosis made clinical behaviour, histological features and
from tumour tissue and immunohistology and genetic abnormalities play also an important role
raised urine catecholamines. If histology is to define the different three risk groups. The clin-
equivocal, genetics may help. ical features include the degree of resectability of

Image-defined risk factors in neuroblastic tumours [25]

Ipsilateral tumour extension within •  Neck-chest
two body compartments •  Chest-abdomen
• Abdomen-pelvis
Neck • Tumour encasing the carotid and/or vertebral artery and/or internal
jugular vein
• Tumour extending to base of the skull
• Tumour compressing the trachea
Cervico-thoracic junction • Tumour encasing brachial plexus roots
• Tumour encasing subclavian vessels and/or the vertebral and/or carotid
artery
• Tumour compressing the trachea
Thorax • Tumour encasing the aorta and/or major branches
• Tumour compressing the trachea and/or principal bronchi
• Lower mediastinal tumour, infiltrating the costovertebral junction
between T9 and T12
Thoraco-­abdominal • Tumour encasing the aorta and/or vena cava
Abdomen/pelvis • Tumour infiltrating the porta hepatis and/or the hepatoduodenal ligament
• Tumour encasing branches of the superior mesenteric artery at the
mesenteric root
• Tumour encasing the origin of the coeliac axis and/or of the superior
mesenteric artery
• Tumour invading one or both renal pedicles
• Tumour encasing the aorta and/or vena cava
• Tumour encasing the iliac vessels
• Pelvic tumour crossing the sciatic notch
Intraspinal tumour extension • More than one third of the spinal canal in the axial plane are invaded,
whatever the location provided that: and/or the perimedullary leptomeningeal spaces are not visible, and/or
the spinal cord signal is abnormal
Infiltration of adjacent organs/ • Pericardium
structures • Diaphragm
• Kidney
• Liver
• Duodeno-pancreatic block and mesentery
Conditions to be recorded but not • Multifocal primary tumours
considered IDRFs • Pleural effusion, with or without malignant cells
• Ascites, with or without malignant cells
35  Neuroblastoma in Neonates 475

the tumour as determined by its radiological 35.7.2 Intermediate Risk

appearance on MRI or CT.
This replaced the old international neuroblas- This risk group accounted for 20% of patients
toma staging system with L1 (stages 1 and 2) which affected by neuroblastoma and includes M infants
includes localized tumours that do not involve vital <12  months (with bone/lung/CNS metastases
structures as defined by the list of IDRF, L2 (stage without MYCN amplification) who have a 2-year
3) which includes locoregional tumours with one overall survival of 95% with modest treatment in
or more IDRFs, M (stage 4) which includes confront of older children with a poor outcome
tumours with distant metastatic disease and Ms who needed a more intensive treatment.
(stage 4s) metastatic disease in patients younger Chemotherapy in these patients based on carbo-
than 18  months with metastases confined to the platin associated with doxorubicin
skin, liver and/or bone marrow [25]. administration.
Surgical role in intermediate-risk patients is to
International Neuroblastoma Risk Group (INRG)
obtain the most complete tumour resection when
Staging System [22]
Stage Description
feasible taking in count the preservation of full
L1 Localized tumour noninvolving vital organ and neurologic function. This may lead fre-
structures as defined by the list of image-­ quently to leave residual disease adherent to criti-
defined risk factors and confined to one body cal anatomic structures.
compartment Radiation was administered in selected cases
L2 Local regional tumour with the presence of
one or more image-defined risk factors
with infants with 4s disease and respiratory insuf-
M2 Distant metastatic disease ficiency or patients with epidural disease and
MS Metastatic disease in children <18 month symptoms of spinal cord compression.
with metastases confirmed to the skin, liver
and/or bone marrow
35.7.3 High Risk

High-risk groups account for approximately 50%

35.7 Therapeutic Management of all neuroblastoma but only around 5% in neo-
nates who obtained only 30% 2-year overall sur-
35.7.1 Low Risk vival despite intensive multimodal therapy.
SIOPEN HR-NBL-1 is a European trial which
Low-risk category includes approximately 70% included infants <12  months with MYCN-­
of neonatal neuroblastomas which have an excel- amplified disease, and this shall comprise:
lent 5-year survival accounting for 95–100%.
Surgery alone is indicated for all localized, • Induction chemotherapy  – multi-agent
resectable (L1) tumours. In tumours which are cisplatin-­based dose-intensified chemotherapy
not resectable or biopsy is not feasible is indi- • Surgical resection of primary tumour
cated a follow-up with MRI because some of • Myeloablative therapy and autologous stem
these have a good chance to regress. cell rescue
Chemotherapy based on carboplatin administra- • Radiotherapy to site of primary tumour
tion is indicated in case of unresectable tumour • 13-cis-retinoic acid + anti-GD2 immunotherapy
(L2), stage 4s (Ms) or M (without bone, lung or (± IL-2)
CNS metastases) associated with clinical behav-
iour, e.g. due to spinal cord compression. In Despite the uncertainty of the role of surgery,
asymptomatic Ms patients without SCAs in fact, the COG high-risk protocol currently recom-
there is a high percentage of patient with sponta- mends attempting gross total resection of the
neous regression and a low risk of recurrence, primary tumour and locoregional disease in
­
and no treatment is needed. patients with high-risk neuroblastoma [2, 23].
476 M. Carella et al.

35.8 Surgery of Neonatal

Neuroblastoma

Surgical approach will depend upon the location

of the primary tumour. The majority of primary
tumours occur in adrenal glands (90%) followed
by the sympathetic chains of the posterior
mediastinum.

35.8.1 Primary Tumour from Adrenal

Gland
Fig. 35.2 Neuroblastoma arising from right adrenal
gland
The access is a long transverse supraumbilical
incision; the peritoneum is entered (Fig.  35.1).
The colon is mobilized medially incising the
attachments to the lateral abdominal wall.

35.8.2 Right Adrenal Gland (Fig. 35.2)

The duodenum and the head of the pancreas are

mobilized and retracted medially; the arterial
blood supply usually comes from vessels from
the right renal artery, aorta and diaphragmatic
vessels; venous drainage is directed to the infe-
Fig. 35.3  The blood supply of the tumour is controlled
rior vena cava. So the blood supply and venous
drainage are severed (Fig. 35.3), and the dissec-
tion of the tumour is completed. 35.8.3 Left Adrenal Gland

The spleen, pancreas and stomach should be

reflected to expose a left-side tumour; the arterial
blood supply usually comes from vessels from
descending aorta; the venous drainage is directed
into the left renal vein and subdiaphragmatic ves-
sels. So the blood supply and venous drainage are
controlled (Fig.  35.4), and the dissection of the
tumour is completed.

35.8.4 Mediastinal Neuroblastoma

(Fig. 35.5)
Fig. 35.1  Once the peritoneum is opened, tumour dis-
semination to the liver is clear in a 4s stage The access is a posterolateral thoracotomy inci-
neuroblastoma sion; the parietal pleura that covers the tumour is
35  Neuroblastoma in Neonates 477

Report of an international working group. Pediatr

Surg Int. 2003;19:509–19.
4. Alfaar AS, Hassan WM, Bakry MS, Qaddoumi
I. Neonates with cancer and causes of death; lessons
from 615 cases in the SEER databases. Cancer Med.
2017;6:1817–26.
5. Fisher JP, Tweddle DA.  Neonatal neuroblastoma.
Semin Fetal Neonatal Med. 2012;17:207–15.
6. Muller-Schulte E, Kurlemann G, Harder A. Tobacco,
alcohol and illicit drugs during pregnancy and risk of
neuroblastoma: systematic review. Arch Dis Child
Fetal Neonatal Ed. 2018;103(5):F467–73.
7. Cook MN, Olshan AF, Guess HA, et  al. Maternal
medication use and neuroblastoma in offspring. Am J
Epidemiol. 2004;159:721–31.
Fig. 35.4  Neuroblastoma arising from a left adrenal 8. Heck JE, Park AS, Qiu J, Cockburn M, Ritz B.  An
gland and the vascular control of the mass exploratory study of ambient air toxics exposure in
pregnancy and the risk of neuroblastoma in offspring.
Environ Res. 2013;127:1–6.
9. French AE, Grant R, Weitzman S, et  al. Folic acid
food fortification is associated with a decline in neu-
roblastoma. Clin Pharmacol Ther. 2003;74:288–94.
10. Tolbert VP, Coggins GE, Maris JM.  Genetic sus-

ceptibility to neuroblastoma. Curr Opin Genet Dev.
2017;42:81–90.
11. Chiarle R, Voena C, Ambrogio C, Piva R, Inghirami
G. The anaplastic lymphoma kinase in the pathogen-
esis of cancer. Nat Rev Cancer. 2008;8:11–23.
12. Mossé YP, Laudenslager M, Longo L, et  al.

Identification of ALK as a major familial neuroblas-
toma predisposition gene. Nature. 2008;455:930–5.
13. Trochet D, Bourdeaut F, Janoueix-Lerosey I, et  al.
Germline mutations of the paired-like homeobox 2B
(PHOX2B) gene in neuroblastoma. Am J Hum Genet.
2004;74:761–4.
Fig. 35.5  Mediastinal neuroblastoma 14. Brodeur GM. Neuroblastoma: biological insights into
a clinical enigma. Nat Rev Cancer. 2003;3:203–16.
15. Newman EA, Nuchtern JG.  Recent biologic and

incised, and the tumour is mobilized from the genetic advances in neuroblastoma: implications for
ribs. Vascular supply and drainage come from diagnostic, risk stratification, and treatment strategies.
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16.
Attiyeh EF, London WB, Mosse YP, et  al.
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riorly exposing the intervertebral extension. neuroblastoma. N Engl J Med. 2005;353:2243–53.
Mediastinal neuroblastoma often extends into the 17. Caron H, van Sluis P, de Kraker J, et al. Allelic loss
intervertebral foramina. Leaving small remnants of chromosome 1p as a predictor of unfavorable out-
come in patients with neuroblastoma. N Engl J Med.
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mosome arm 17q and adverse outcome in patients with
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19. Shimada H, Ambros IM.  Pathology of peripheral

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Plaschkes J. The epidemiology of neonatal tumours. myoclonus syndrome in neuroblastoma a report from
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a workshop on the dancing eyes syndrome at the 24. Brodeur GM, Pritchard J, Berthold F, et al. Revisions
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 Hepatic Tumours
36
Matteo Carella, Riccardo Masetti,
Claudio Antonellini, Beatrice Randi,
and Andrea Pession

Liver tumours account for only 5% of all tumours ing may be necessary to diagnosis or planning
in prenatal and neonatal period [1]. They include therapy in specific cases. Blood count, liver func-
a variety of benign and malignant neoplasms tionality parameters, infectious serology and the
with a different distribution than in older children tumour markers such as alpha-fetoprotein (AFP),
(Table 36.1). The most common are vascular neo- beta-human chorionic gonadotrophin (beta-­
plasm, of which infantile haemangioendotheli- HCG), lactate dehydrogenase and markers for
oma and cavernous haemangioma are the most neuroblastoma (catecholamine metabolites,
frequently types, and embryonal hepatic cell neuron-­specific enolase) may be essential to dif-
tumours such as hepatoblastoma. Mesenchymal ferential diagnosis. Neonates with hepatic neo-
hamartomas and germ cell tumours can occur plasm often have a clinical behaviour, and
very rarely, and the differential diagnosis of these laboratory tests which are not conclusive and
tumours could be very difficult. imaging results can be misleading, and for these
Many of these are diagnosed during prenatal reasons biopsy and histological exam may be
screening or in the first few weeks of life. necessary to correct diagnosis [2].
Ultrasound is the first exam which may be admin-
istered because it can often give information on
the type of neoplasm encountered. Staging and 36.1 Vascular Neoplasm
other important considerations need a computed
tomography (CT) scan or a magnetic resonance The most common hepatic tumours during neona-
imaging (MRI), which is preferred in neonatal tal period are vascular neoplasm such as hemangio-
period. Scintigraphy and vascular contrast imag- endothelioma which occur more frequently in the
newborn. These tumours are often diagnosed dur-
M. Carella · R. Masetti · A. Pession (*) ing prenatal US scan, or commonest are incidental
Department of Pediatric Hematology Oncology, findings in the first weeks of life. The pathogenesis
Sant’Orsola-Malpighi University Hospital, of these vascular lesions is currently unclear. In
Bologna, Italy 50% of cases, multiple haemangiomas on the skin
e-mail: [email protected];
[email protected]; and in other organs have been reported, and in a
[email protected] few cases, it could occur in associations with
C. Antonellini · B. Randi omphalocele and other congenital malformations.
Department of Pediatric Surgery, Sant’Orsola-­ Infantile haemangioendothelioma could pres-
Malpighi University Hospital, Bologna, Italy ent abdominal distension and hepatomegaly which
e-mail: [email protected];
could be complicated by severe arteriovenous
[email protected]

© Springer Nature Switzerland AG 2019 479

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_36
480 M. Carella et al.

Table 36.1  Malignant/benign tumours and tumour-like lesions in newborn

Malignant Benign
Hepatoblastoma Infantile haemangioendothelioma/cavernous
Hepatocellular carcinoma Mesenchymal hamartoma
Rhabdoid tumour Teratoma
Yolk-sac tumour Adenoma
Choriocarcinoma Focal nodular hyperplasia
Undifferentiated sarcoma Hepatic cysts
Rhabdomyosarcoma Liver abscess
Inflammatory pseudotumour

shunting with congestive heart failure, haemo­ sporadic, and the most frequent genetic abnormal-
dynamic anaemia, thrombocytopenia, coagulopa- ities associated to hepatoblastoma were founded in
thy, rupture with intraperitoneal haemorrhage and genes involved in the Wnt signalling pathway.
respiratory distress. Rapid growth or multiple Sometimes hepatoblastoma is associated with
lesions could deter a life-threatening status which genetic anomalies like trisomy 18/Edward’s syn-
develops in the first life weeks or sometimes even drome and cancer predisposition syndromes like
during the foetal period with a clinical behaviour Beckwith–Wiedemann syndrome, familial adeno-
characterized by hydrops fetalis and intrauterine matous polyposis coli and foetal alcohol syndrome
heart failure. [6]. Extremely premature neonates have an
Management of haemangioendotheliomas and increased risk to develop hepatoblastoma [7, 8].
haemangiomas is based on their clinical feature. Hepatoblastoma is characterized by malignant
Follow-up is recommended for asymptomatic epithelial cells with variable differentiation, most
lesions; if patient shows a gradual onset of con- often with embryonal or foetal characteristics.
trollable symptoms, medical treatment should be Mixed hepatoblastomas are a variant which is
considered; digitalis and diuretics are adminis- characterized by the presence of malignant mes-
tered for congestive heart failure, whereas admin- enchymal tissue with immature fibrous areas,
istration of blood products may be considered to spindle cells and cartilage-like osteoid. In neo-
correct anaemia and coagulopathy. Steroid ther- nates, the relatively differentiated, pure foetal
apy is also recommended (PDN 2–5 mg/kg/day) histology seems to predominate compared with
but often is not succesful [3]. Treatment with older children [9].
alpha-2A-interferon can be more effective, but Hepatoblastomas can be detected prenatally by
this is associated with potentially severe side US screening and may cause polyhydramnios and
effects [4]. In case of rapid onset of severe symp- stillbirth. Clinical behaviour may also differ:
toms, resection should be considered when tech- metastases, which are often systemic, arise earlier
nically feasible, but in case of a large diffusion of and bypass lung because of differences in the foe-
haemangioendotheliomas in the hepatic tissue, tal circulation [9]. Tumour rupture with massive
hepatic arterial ligation or radiological emboliza- haemorrhage is a possible life-threatening event in
tion should be preferred. Surgery in 80% of neonates. High values should be compared to nor-
patients is successful; however, in a few cases, mal ones for the age because AFP is still high in
the development of new vessels could be seen this period of life compared to older children [5].
within days from first surgery [5]. Tumour biopsy may be performed, but differ-
ent studies confirm that it may not be necessary
for children aged less than 3  years with a very
36.2 Hepatoblastoma high AFP level.
SIOPEL (Société Internationale d’oncologie
Hepatoblastoma is the most common liver tumour Pédiatrique) configures a pretreatment staging
of early childhood and in 10% of cases occurs dur- system, called PRETEXT, based on the anatomy
ing the neonatal period [2]. This neoplasm is often of the liver and the radiological findings at diag-
36  Hepatic Tumours 481

nosis; therefore, staging of the tumour should intermediate and low-risk patients, estimated at
include chest and brain CT. 80–90% in all groups of patients. Patients with
In the PRETEXT system, the liver is divided poor prognosis (high-risk tumours) were treated by
into four sectors: an anterior and a posterior sector COG and SIOPEL with increased dosages of plati-
on the right and a medial and lateral sector on the num-based therapy which reported an improve-
left. In this way, four PRETEXT categories are ment of their survival [8]. The SIOPEL 4 study,
identified (I–IV). The development of the disease using a weekly administration of cisplatin as intra-
beyond the liver is indicated using the following venous infusion in 24  h associated with monthly
letters: “V” if the tumour extends into the vena doxorubicin, reported an overall and event-free
cava and/or all three hepatic veins, “P” if the main ­survival at 3 years for patients with PRETEXT IV
and/or both left and right branches of the portal tumours by approximately 83% and 76%, respec-
vein are involved by the tumour, “C” if there is tively. Patients with lung metastases nevertheless
involvement of the caudate lobe, “E” if there is have an EFS and OS at 3 years by approximately
evidence of extrahepatic intraabdominal disease 79% and 77% [16]. A retrospective review reported
and “M” if there are distant metastases [10, 11]. that the outcome in neonates affected by congenital
The risk stratification system proposed by the hepatoblastoma is much better than those which
Children’s Hepatic tumors International were diagnosed at an older age [17].
Collaboration includes PRETEXT staging sys-
tem, patients age and AFP level serum.
Clinically relevant histologic subtypes are 36.3 S
 urgery of Hepatic Neonatal
also being incorporated into risk stratification; in Tumours
fact the Children’s Oncology Group (COG)
reported that complete tumour resection (stage I) Surgical treatment of a neonatal haemangioen-
associated with pure foetal histology configures dothelioma is required if the newborn is still
excellent outcome; different studies confirm symptomatic (significant haemodynamic shunt-
therefore that HBL patients presenting with low ing) despite the medical therapy (corticosteroids,
AFP levels (<100 ng/mL) and/or with undifferen- digoxin, diuretics, beta-blockade).
tiated histology have a poor outcome [12–14]. The surgical treatment includes the following:
Surgery plays a central role in the treatment;
standard−/low-risk patients in fact can safely • The hepatic artery ligation (the haemangioen-
undergo complete surgical resection associated or dothelioma becomes ischaemic because it is
not to neoadjuvant chemotherapy. Cisplatin and usually supplied by a hypertrophied hepatic
doxorubicin are used in different regimens, which artery rather than by the portal vein); it could
may reduce some extensive hepatoblastoma to an be performed also by embolization, if special-
operable size. Liver transplant could be considered ist interventional radiologists are available.
in absence of metastases that configure patients • The surgical resection: only if the tumour is
with very high-risk hepatoblastoma if present. unilobar and, however, if possible, the surgical
These patients with unresectable liver tumours can resection is to defer after the neonatal period.
undergo mastectomy associated to chemotherapy. • The liver transplantation is a therapeutic option
The Japanese Study Group for Paediatric Liver reserved to lesions that are not ­resectable and
Tumour showed that TACE (Transarterial chemo- are not suitable for l­igation/­embolization. An
embolization) with cisplatin or anthracyclines immediate preoperative radiological emboliza-
could represent an important option of treatment in tion is an alternative to decrease the blood flow
patient with PRETEXT IV non-metastatic tumour through the tumor and minimize the risk of
because of its equivalence and less toxicity in com- sharp bleeding during resection.
parison with systemic chemotherapy [14, 15].
Generally in children affected by hepatoblas- The treatment of a neonatal mesenchymal
toma, the 3-year EFS and OS (event-free survival hamartoma is the complete excision because
and oculus sinister) are similar between standard, this tumour has an uncertain natural history.
482 M. Carella et al.

hepatic vein. Each lobe is again divided into a

paramedian and a lateral portion by the right and
left hepatic veins. The four sectors are subdivided
into anterior and posterior segments.
Each of the eight segments is supplied by a
portal triad and drains into a hepatic vein. The
portal triad is composed of a branch of the portal
vein and hepatic artery and drained by a tributary
of the right or left main hepatic ducts.
The major hepatic resections include the
following:

• Left lateral lobectomy: removal of segments

Fig. 36.1 Hepatoblastoma
II–III.
• Left hepatic lobectomy (II, III, IV).
For the treatment of hepatoblastoma • Extended left hepatectomy (II, III, IV, V, VIII).
(Fig.  36.1), surgical treatment is indicated at • Right hepatic lobectomy (V, VI, VII, VIII).
diagnosis in patients with PRETEXT I and any • Extended right hepatectomy (IV, V, VI, VII,
unifocal PRETEXT 2 tumours. All other patients VIII).
will receive a diagnostic biopsy if necessary • Central hepatic resection (IV, V, VIII).
(open or preferably percutaneously), the place-
ment of a vascular access and preoperative che- Segment I receives inflow from both the right
motherapy. Chemotherapy is used to reduce and left branches of the hepatic artery and portal
tumour size in tumours that are unresectable at vein and drains directly into the inferior vena cava.
presentation. In those cases in which the tumour So, if necessary, the caudate lobe could be resected
remains inoperable, because of diffuse liver during extended right or left hepatectomy.
involvement, liver transplantation is considered. A major hepatic resection is often performed
The surgical treatment includes the following: through a trans-abdominal approach with total
liver mobilization to provide possible vascular
control (see below) (rapid access to the suprahe-
36.3.1 Atypical Resections patic inferior vena cava). For right hepatic
(Nonanatomic Resection) lesions, surgeon performs an upper abdominal
transverse incision, extending the incision across
Atypical or wedge resections are not recom- the costal margin into the seventh intercostal
mended because of the high risk of incomplete space, a left upper abdominal transvers incision
resection; the atypical resection could be applied with a vertical midline extension into the chest
only in rare form of pedunculated tumours or for left hepatic lesions.
small peripheral lesions. Mobilization of the liver is performed by the
division of the falciform ligament, right ligament,
coronary ligament and left triangular one.
36.3.2 Partial Liver Resection The hepato-duodenal ligament is isolated and
(Anatomic Hepatectomy) surrounded with a vascular loop to control the vas-
cular inflow, if necessary (Pringle manoeuvre).
Partial hepatectomies are based on the anatomic Then, in each type of major hepatic resection,
classification of Couinaud that allows to remove the first step is the control of vascular inflow
each segment without damaging any of the (branches of the hepatic artery and the portal vein)
others. and biliary structures (hepatic duct branches).
The liver is divided into the right and left lobe The vascular inflow and biliary control can be
by the main portal fissure containing the middle performed through an extrahepatic vascular con-
36  Hepatic Tumours 483

trol or intraparenchymal. The advantage of the 2. von Schweinitz D.  Neonatal liver tumours. Semin
Neonatol. 2003;8:403–10.
vascular control performed intraparenchymally is 3. Prokurat A, Chrupek M, Ko-ciesza A, et  al.
the protection of the other vascular pedicle, but Hemangioma of the liver in children-­ conservative
for tumours close to the hilum, the extrahepatic versus operative treatment. Surg Child Intern.
technique is necessary. 2000;3:202–7.
4. Deb G, Donfrancesco A, Ilari I, et  al.
Once the inflow and biliary control is achieved, Hemangioendothelioma: Successful therapy with
the surgeon moves to the outflow control (right, interferon-α. A study in association with the Italian
middle and left hepatic veins). The last step is the Pediatric Haematology/Oncology Society (AIEOP).
parenchymal resection. Med Pediatr Oncol. 2002;38:118–9.
5. Thompson PA, Chintagumpala M. Renal and hepatic
tumors in the neonatal period. Semin Fetal Neonatal
Med. 2012;17:216–21.
36.3.3 Liver Transplantation 6. Czauderna P, Lopez-Terrada D, Hiyama E, Haberle
B, Malogolowkin MH, Meyers RL.  Hepatoblastoma
state of the art: pathology, genetics, risk stratification,
Complete eradication of metastatic lesions by and chemotherapy. Curr Opin Pediatr. 2014;26:19–28.
chemotherapy or surgical resection is a prerequi- 7. Ikeda H, Matsuyama S, Tanimura M.  Association
site for transplantation. between hepatoblastoma and very low birth weight: A
When tumour resection by partial hepatec- trend or a chance? J Pediatr. 1997;130:557–60.
8. Aronson DC, Meyers RL.  Malignant tumors of the
tomy is incomplete or when intrahepatic relapse liver in children. Semin Pediatr Surg. 2016;25:265–75.
is observed after a previous partial hepatectomy, 9. Ammann RA, Plaschkes J, Leibundgut K. Congenital
performing a liver transplantation may be a rela- hepatoblastoma: A distinct entity? Med Pediatr Oncol.
tive contraindication because of the disappoint- 1999;32:466–8.
10. Roebuck DJ, Aronson D, Clapuyt P, et  al. 2005

ing results observed. PRETEXT: a revised staging system for primary
Early indications for liver transplantation are malignant liver tumours of childhood developed by
the following: the SIOPEL group. Pediatr Radiol. 2007;37:123–32;
quiz 249–50.
11. Aronson DC, Czauderna P, Maibach R, Perilongo G,
• Multifocal PRETEXT IV hepatoblastoma is a Morland B. The treatment of hepatoblastoma: Its evo-
clear indication for liver transplantation what- lution and the current status as per the SIOPEL trials.
ever the result of chemotherapy because of the J Indian Assoc Pediatr Surg. 2014;19:201–7.
high probability of microscopic neoplastic 12. De Ioris M, Brugieres L, Zimmermann A, et  al.

Hepatoblastoma with a low serum alpha-fetoprotein
cells despite the apparent clearance of one level at diagnosis: the SIOPEL group experience. Eur
liver lobe. J Cancer. 2008;44:545–50.
• Large, unifocal PRETEXT IV hepatoblastoma 13. Trobaugh-Lotrario AD, Tomlinson GE, Finegold

involving all four sections of the liver is an MJ, Gore L, Feusner JH.  Small cell undifferenti-
ated ­variant of hepatoblastoma: adverse clinical and
indication of liver transplantation only if the molecular features similar to rhabdoid tumors. Pediatr
tumour does not downstage after Blood Cancer. 2009;52:328–34.
chemotherapy. 14. Hiyama E.  Pediatric hepatoblastoma: diagnosis and
• Unifocal, centrally located PRETEXT II and treatment. Transl Pediatr. 2014;3:293–9.
15. Hishiki T, Matsunaga T, Sasaki F, et al. Outcome of
PRETEXT III involving main hilar structures hepatoblastomas treated using the Japanese study
or hepatic vein should be considered for liver group for pediatric liver tumor (JPLT) protocol-2:
transplantation because these structures pre- report from the JPLT. Pediatr Surg Int. 2011;27:1–8.
sumably will not become free of tumour after 16. Zsiros J, Brugieres L, Brock P, et  al. Dose-dense

cisplatin-­based chemotherapy and surgery for chil-
chemotherapy [1, 18]. dren with high-risk hepatoblastoma (SIOPEL-4):
a prospective, single-arm, feasibility study. Lancet
Oncol. 2013;14:834–42.
References 17. Trobaugh-Lotrario AD, Chaiyachati BH, Meyers RL,
et al. Outcomes for patients with congenital hepato-
blastoma. Pediatr Blood Cancer. 2013;60:1817–25.
1. Makin E, Davenport M.  Fetal and neonatal liver
18. Isaacs H Jr. Fetal and neonatal hepatic tumors. J

tumours. Early Hum Dev. 2010;86:637–42.
Pediatr Surg. 2007;42:1797–803.
 Wilms Tumor in Neonates
37
Matteo Carella, Riccardo Masetti,
Claudio Antonellini, Beatrice Randi,
and Andrea Pession

37.1 Introduction test administered for the study of genitourinary

and Epidemiology abnormalities or genetic syndromes associated to
early infancy [3].
Wilms tumor (WT) or nephroblastoma is the sec-
ond commonest neonatal renal tumor accounting
for 20% of cases and represents the most important 37.2 Genetic and Risk Factors
renal malignancy during childhood. This neoplasm
develops from the primitive metanephric blastema, The Wilms tumor 1 (WT1) gene is located at
the primitive tissue of normal kidney, but it may be 11p13, and its defects are associated with combi-
formed also by cell of nonrenal tissues. In neonates nations of Wilms tumor, genitourinary abnormal-
affected by nephroblastoma, only 16% of these are ities, and renal dysfunction. In these patients
being diagnosed antenatally, and the rest are identi- Wilms tumor arises earlier (median age 1  year)
fied during investigation for maternal polyhydram- than the other cases (median age 4 year).
nios, hydrops fetalis, or other congenital anomalies. WAGR syndrome is characterized by the asso-
Wilms tumor occurs in males and females equally, ciation of Wilms, aniridia, genitourinary abnor-
and in 1% of cases, there is a family history, and it malities, and mental retardation. It accounts for
is associated with various congenital syndromes [1, 7–8/1000 cases of Wilms tumor. Heterozygous
2]. A recent Associazione Italiana Ematologia constitutional microdeletions of WT1 (responsi-
Oncologia Pediatrica (AIEOP) study reports that ble of Wilms tumor and abnormalities of genito-
infants have a good prognosis than older children urinary tract) and PAX8 (responsible of aniridia)
affected by WT because of a biological diversity at 11p13 caused WAGR.
and an earlier diagnosis occurring during screening Denys-Drash syndrome is more strictly asso-
ciated with Wilms tumor than WAGR syndrome,
and, like these, it is caused by germline abnor-
M. Carella · R. Masetti · A. Pession (*) malities on WT1. This syndrome is characterized
Department of Pediatric Hematology Oncology, by the association of Wilms tumor, nephropathy,
Sant’Orsola-Malpighi University Hospital,
Bologna, Italy and genitourinary abnormalities in males in
e-mail: [email protected]; which phenotype differs for severity in the
[email protected]; [email protected] ­different cases, ranging from mild hypospadia to
C. Antonellini · B. Randi pseudohermaphroditism. Nephropathy is charac-
Department of Pediatric Surgery, Sant’Orsola-­ terized by mesangial sclerosis which lead to renal
Malpighi University Hospital, Bologna, Italy failure before the age of 10 years.
e-mail: [email protected]; beatrice.
[email protected]

© Springer Nature Switzerland AG 2019 485

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_37
486 M. Carella et al.

Children affect by Beckwith-Wiedemann syn- because of increasing of renin activity. A rapid

drome have an increased risk to develop Wilms enlarging of abdominal mass associated to ane-
tumor. This syndrome is caused by altered mia, hypertension, pain, and fever may be caused
expressions of cluster of gene regulated by two by subcapsular hemorrhage within the tumor [9].
imprinting control genes localized at 11p15. Wilms tumor must be suspected in children pre-
Defects in methylation of paternal and maternal senting clinical features known to be associated
alleles are involved in the development of this with predisposing syndromes.
syndrome. Wilms tumor occurs in 10% of
Beckwith-Wiedemann syndrome patients [4].
A moderately increased risk of Wilms’ tumor 37.4 Pathology
(5–20%) has also been demonstrated in children
affected by other overgrowth syndromes: Wilms tumor histologically is characterized by a
pattern of epithelial, stromal, and blastema com-
• Sotos syndrome, characterized by cerebral ponents. The proportions of these components
gigantism. configure different histological groups with favor-
• Simpson-Golabi-Behmel syndrome, charac- able prognosis in the current SIOP classification
terized by macroglossia, macrosomia, and of pediatric renal tumors [10]. The presence of
renal and skeletal abnormalities associated to anaplastic elements is found in a particular histo-
an increased risk of embryonal cancer. logical group associated with adverse outcome,
• Perlman syndrome, characterized by fetal especially in the cases with diffused anaplasia and
gigantism, renal dysplasia, Wilms tumor, islet advanced tumor stage; thus, its recognition is
cell hypertrophy, multiple congenital anoma- essential for the prognosis and treatment [11].
lies, and mental retardation. Nephrogenic rests are an abnormal cluster of
• Isolated hemihypertrophy, characterized by embryonic renal cell which are found in 35% of
abnormal growth of the bone, soft tissue, or unilateral Wilms tumor and in 100% of kidneys
both. with bilateral Wilms tumor [12, 13].
Nephroblastomatosis is the diffuse presence of
Loss of heterozygosity of chromosome 11p, these cluster of embryonal cells which are classi-
16q, and 1p has been identified in Wilms tumor fied based on the category of rest (intralobar or
and correlates with an increased risk of relapse perilobar nephrogenic rests) and their growth
and unfavorable outcome [5]. phase (incipient or dormant nephrogenic rests,
hyperplastic nephrogenic rests, and regressing or
sclerosing nephrogenic rests). Diffuse hyperplas-
37.3 Clinical Features tic perilobar nephroblastomatosis represents a
preneoplastic condition, and for this reason it is
Wilms tumor often arises asymptomatically; in generally treated, when it presents bilateral
neonates the majority of renal tumor patients lesions, with chemotherapy, to reduce the risk of
(79%) presents with an asymptomatic abdominal developing Wilms tumor [14]. Rarely extrarenal
mass, often found by relatives noticing during the nephrogenic rests may develop into extrarenal
bath an abdominal enlargement, followed by Wilms tumor [15].
microscopic or gross hematuria in 10% of cases
[6]. Rarely a newborn presenting with fetal
hydrops could be associated with congenital 37.5 Diagnosis
Wilms tumor [7, 8]. In older children affected by
Wilms tumor, malaise, pain, and hematuria are Ultrasonography is the technique used first to
found in approximately 20–30% of cases. evaluate an abdominal mass. This exam can also
Hypertension is present in 25% of children evaluate tumor extension and involvement of
37  Wilms Tumor in Neonates 487

contralateral kidney; genitourinary a­ bnormalities, suggests nephrectomy, followed by chemother-

the involvement of the inferior cava and liver apy basing on tumor staging; this approach nev-
metastases, must be considered during abdomi- ertheless could cause a higher incidence of
nal US exam. CT or preferably MRI scan of the surgical adverse events such as tumor rupture and
abdomen must be performed in children with intraoperative spillage. SIOP however promotes
suspected renal tumor; particularly MRI should the administration of neoadjuvant chemotherapy
be preferred if bilateral renal lesions are sus- followed by surgical resection to reduce compli-
pected to avoid radiation exposition in early age cations related to nephrectomy and consensually
children [16]. to evaluate treatment response; on the other hand,
this strategy could deter an overtreatment of
benign tumors and an undertreatment of high-­
37.6 P
 rognostic Factors and Risk risk renal tumors. Chemotherapy includes a com-
Stratification bination of vincristine, dactinomycin, and
doxorubicin in patient at any stage with favorable
COG (Cluster of Orthologous) group divides histology of disease; in addition anaplastic Wilms
patients in different groups, to assign every group tumor or high-risk patients requires administra-
to different treatment, based on stage, histology, tion of cyclophosphamide, etoposide, and carbo-
patient age, tumor weight, lung nodule response, platin [19, 20].
and loss of heterozygosity (LOH) at chromo- Recent studies suggest that, basing on tumor
somes 1p and 16q. SIOP (Société Internationale stage, children affected by WT and classified as
d’Oncologie Pédiatrique) risk stratification sys- very low risk (VLRWT) may be treated with
tem based on stage, histology, response to preop- nephrectomy alone. Although there is no differ-
erative chemotherapy, and tumor volume [17]. ence in overall survival in VLRWT patients who
AIEOP Wilms Tumor Working Group study receive surgery alone and patient who received
configured a more sensitive risk stratification sys- neoadjuvant chemotherapy, these patients have a
tem where patients were stratified into six classes 10–15% chance of relapse, which required sal-
based on age, criteria for stage III (separating vage chemotherapy.
cases with LN or caval involvement from the oth- Stage II and above are treated with chemo-
ers), and completeness of lung nodule response at therapy regimen depending on the extent of the
6 weeks in addition to stage and anaplasia histol- lesion and genetic risk factors. Chemotherapy is
ogy, which represented the most powerful adverse recommended in tumors associated with syn-
prognostic factor for WT. In this study children dromes, unilateral kidney tumors, or bilateral
aged less than 24 months and with stage II tumor tumors in which partial nephrectomy could be
are assigned in the very low-risk group. This associated with neoadjuvant chemotherapy. In
because 1p, 16q loss and 1q gain are uncommon conclusion, neonatal Wilms tumor can be suc-
in the first 2 years of life and Wilms tumor devel- cessfully treated with a combination of surgery
oped in this age is considered therefore a biologi- and neoadjuvant chemotherapy, which is admin-
cally/histologically favorable tumor [18]. istered, where indicated, with 50% dose reduc-
tion due to increased incidence of toxicity.
Radiotherapy is performed in high-risk patients
37.7 Therapeutic Management and avoided when it is possible because of long-­
term adverse events [6, 21]. Nevertheless in
Management of WT in children includes a com- infants less than 1 year of age, 50% dose reduc-
bination of nephrectomy, chemotherapy, and tion is recommended due to increased incidence
radiotherapy. Treatment strategies differ in the of toxicity, and radiation is avoided because of
two major study groups of Wilms tumor. NWTSG long-term adverse events.
488 M. Carella et al.

37.8 Surgery of Wilms Tumor

Neonatal Wilms tumors are usually low stage

(stage I or II) at diagnosis, so the treatment is sur-
gery, typically transabdominal nephrectomy.
Renal tumor must be resected through a gen-
erous transverse upper abdominal incision, from
the flank of the tumor side to the flank of the
opposite side (Fig.  37.1). A limited incision is
associated with a high risk of tumor rupture.
The peritoneum is opened and the small bowel
is delivered out of the peritoneal cavity. Then the
abdomen is explored for hepatic metastasis, and
Fig. 37.2  The retroperitoneal space is opened by an inci-
the renal vein and the inferior vena cava should sion made lateral to the reflection of the peritoneum of the
be palpated to assess for intravascular extension descending colon, and the colon is reflected medially to
of the tumor. Also contralateral kidney should be expose the tumor
controlled for synchronous lesions.
The retroperitoneal space is opened by an
incision made lateral to the reflection of the peri-
toneum of the ascending colon for a right-sided
tumor or lateral to the descending colon for a left-­
sided tumor. The colon is mobilized off the tumor
and reflected medially (Fig. 37.2).
It’s recommended the initial control of the renal
hilum, but this is not always feasible for large
tumors. For large tumors is necessary, first of all,
the mobilization of the mass to expose the hilum.
The renal vein is isolated, and a vascular sling
is passed around the vein to prevent the risk of
tumor embolization during surgery. Then the renal
artery and the ureter are mobilized (Fig. 37.3). Fig. 37.3  Control of the renal hilum: the renal vein (blue
vascular sling), the renal artery (red vascular sling), and
the ureter (yellow vascular sling) are isolated

The renal artery is ligated and divided before

the renal vein to avoid congestion of the tumor.
In cases with intravascular extension of the
tumor (renal vein or vena cava), the vessel is
opened by transverse incision between vascular
slings and clamps, and the thrombus is removed
with a suction cannula.
The para-aortic lymph nodes are sampled on
the tumor side and on the opposite side.
The ureter is divided as low down as possible
to avoid diverticulum.
Then the tumor is mobilized from the retro-
Fig. 37.1  A large neonatal left Wilms tumor approached
throughout a generous transverse upper abdominal peritoneal space. Any lymph nodes should be
incision included in the mobilization and removed with
37  Wilms Tumor in Neonates 489

the perinephric fat. Also lymph nodes of the renal 8. Glick RD, Hicks MJ, Nuchtern JG, Wesson DE,
Olutoye OO, Cass DL.  Renal tumors in infants less
hilum are included. than 6 months of age. J Pediatr Surg. 2004;39:522–5.
If the tumor involves the upper pole, the adre- 9. Davidoff AM.  Wilms tumor. Adv Pediatr. 2012;59:
nal gland is resected to achieve adequate margins 247–67.
around the tumor. In lower pole lesions, the adre- 10. Perlman EJ.  Pediatric renal tumors: practical updates
for the pathologist. Pediatr Dev Pathol. 2005;8:320–38.
nal gland may be preserved. 11. Popov SD, Sebire NJ, Vujanic GM. Wilms’ tumour—
Once removed, the tumor is sent fresh to histology and differential diagnosis. In: van den Heuvel-
pathology. The abdomen is closed in layers. Eibrink MM, editor. Wilms Tumor. Brisbane (AU):
The most frequent complication of Wilms’ sur- Codon Publications Copyright: The Authors; 2016.
12. Beckwith JB. New developments in the pathology of
gery is intestinal obstruction (6–7%) followed by Wilms tumor. Cancer Investig. 1997;15:153–62.
intraoperative hemorrhage (5–6%) and injuries to 13. Beckwith JB. Precursor lesions of Wilms tumor: clini-
other visceral organs (1–2%) [2, 20, 22, 23]. cal and biological implications. Med Pediatr Oncol.
Recently some 16 selected cases of WT have 1993;21:158–68.
14. Perlman EJ, Faria P, Soares A, et al. Hyperplastic peri-
been proven to be resected safely and totally by lobar nephroblastomatosis: long-term survival of 52
laparoscopy. The choice is based on strict imag- patients. Pediatr Blood Cancer. 2006;46:203–21.
ing preoperative criteria [24]. 15. Cooke A, Deshpande AV, La Hei ER, Kellie S,

Arbuckle S, Cummins G.  Ectopic nephrogenic rests
in children: the clinicosurgical implications. J Pediatr
Surg. 2009;44:e13–6.
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biology, diagnosis and treatment. Transl Pediatr.
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Surg. 2008;43:1587–95. 17. Dome JS, Perlman EJ, Graf N. Risk stratification for
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Group. Pediatr Blood Cancer. 2017;64 https://doi. the principles in management of Wilms’ tumour:
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NE. Clinicopathologic correlates of loss of heterozy- S.  Neoadjuvant chemotherapy in neonatal Wilms’
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Gynecol. 2000;16:80–3. 2014;10(3):500–5.
 Neonatal Ovarian Cysts
38
Gloria Pelizzo

38.1 Introduction eclampsia, and toxemia are generally recognized

as causes of NOCs (Table 38.1) [6–13].
Ovarian cysts are the most common intra-­ A decrease in maternal-placental estrogens
abdominal masses found in female fetuses and and β-hCG after birth and the baby’s neurologic
neonates. The estimated incidence of clinically maturation itself lead to spontaneous regression
significant ovarian cysts is 1/2500 live births. The of the cysts. After birth, since the infant’s FSH-LH
first neonatal ovarian cyst (NOC) was reported in levels continue to increase until the maturation of
1889 upon an autopsy in a preterm stillborn the gonadostat mechanism, cysts may continue to
infant [1, 2]. Nowadays, with advances in radio- enlarge for about 3 months [5, 6, 14, 15]. To date,
graphic techniques, and especially following the the prenatal detection rate for NOCs is more than
extensive use of ultrasonography, NOCs are eas- 30%. Although spontaneous regression occurs in
ily documented in fetuses, toward the end of the more than half of NOC cases prenatally detected
second trimester of gestation. [2–6, 16], complications of fetal ovarian cysts
The fetal and neonatal ovary is usually dor- include compression of other viscera, cyst rup-
mant, but follicular cyst development may occur ture, hemorrhage, and, most frequently, ovarian
before and after birth. Fetal ovarian cysts gener- torsion with consequent loss of the ovary.
ally manifest in the third trimester, and the most
widely accepted theory is that exposure to fetal Table 38.1  Etiology of fetal ovarian cysts
pituitary gonadotropins, placental human chori- Fetal hormonal stimulation
onic gonadotropins, and maternal estrogens stim- Fetal hypothyroidism
ulates the fetal ovary and causes follicle Congenital adrenal hyperplasia
production and maturation [2–6]. Hormonal Mutation of the G-protein α-subunit
stimulation in fetal hypothyroidism, congenital Preterm ovarian hyperstimulation syndrome
adrenal hyperplasia, mutation of the G-protein Maternal and placental hormonal stimulation
α-subunit, preterm ovarian hyperstimulation syn- Maternal diabetes
Rh iso-immune hemolytic disease
drome (a rare and self-limiting disease), maternal
Preeclampsia
diabetes, Rh iso-immune hemolytic disease, pre- Toxemia

G. Pelizzo (*)
Pediatric Surgery Unit, Children’s Hospital, ARNAS
Civico-Di Cristina-Benfratelli, Palermo, Italy

© Springer Nature Switzerland AG 2019 491

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_38
492 G. Pelizzo

Management includes watchful expectancy

during the pregnancy and postnatally and antena-
tal aspiration of large simple cysts, to prevent tor-
sion and ovarian loss. Prenatal monitoring of
recurrent complex cysts and postnatal follow-up
in the case of simple cyst recurrence are manda-
tory. Surgical intervention should be considered
only in symptomatic or complex cases [2–4, 17–
19]. When a surgical intervention is pursued, an
ovary preserving approach should be emphasized
for all types of cysts, regardless of size and
complexity.

38.2 Imaging Appearance

Neonatal ovarian cysts are unilateral in 95% of

cases. Cysts are classified with regard to their
ultrasonographic features as “simple” or “com-
plex” and with regard to their size as “small” Fig. 38.1  Simple anechoic ovarian cyst (5 cm)
(2.5–5 cm in diameter) or “large” (over 5 cm in
diameter) cysts [17, 20, 21] (Fig. 38.1). Simple
cysts are completely anechoic or may occasion-
ally contain a single septation. The complex cyst
may contain internal echoes, fluid levels, septa-
tions, or echogenic foci (Table 38.2, Figs.  38.2
and 38.3) [17, 22].
Cysts are usually unilateral and more often
intra-abdominal versus intrapelvic. An ovarian
cystic structure less than 20  mm in diameter is
considered physiologic rather than a pathological
maturing follicle. A cyst larger than 20  mm in
diameter is considered abnormal and should be
watched carefully [23–27].

Table 38.2  Pre- and postnatal sonographic appearance

of ovarian cysts
Simple cysts • Anechoic Fig. 38.2  Large ovarian cyst (8.5  cm), with internal
• Single septation echoes and normal ovarian vascularity and flow
Complex cysts • Thick walled
(torsion) • Double-wall sign
• Fluid-fluid level Most simple cysts measuring less than 4 cm do
• Heterogeneous echogenicity not develop complications and resolve within the
• Calcification and solid
first 6 months as hormonal stimulation decreases.
component
Complex cysts • Fluid-debris level Rarely, are they complicated; this depends on
(hemorrhage) • Retracting clot their size and pedicle length [5, 6, 8, 24].
• Septation with or without A complex heterogeneous ovarian cyst is
internal echoes defined by the presence of a fluid-debris level, a
38  Neonatal Ovarian Cysts 493

does not present signs related to ovarian torsion

[4, 5, 10, 15, 21, 23].
Various complications are associated with
ovarian cysts; torsion is the most commonly
reported complication bearing an incidence of
50–78% for all neonatal ovarian cysts, followed by
compression of other viscera, rupture of the cyst,
and hemorrhage. Torsion is more common in cysts
larger than 4–5 cm in size and may result in adhe-
sion of the necrotic ovary to the bowel or other
organs with possible intestinal obstruction or per-
foration, urinary obstruction, and even sudden
infant death [5, 6, 8, 24]. Large NOCs may cause
pain, irritability, vomiting, fever, and abdominal
distension in neonates and infants. Serial monitor-
Fig. 38.3  Complex neonatal ovarian cyst with multiple ing of a fetal ovarian cyst, by evaluating its resolu-
septations tion or changes in appearance, is mandatory for
making an early diagnosis of torsion [23]. US is
retracting clot, and multiple septation with or with- usually sufficient to determine ovarian torsion, but
out internal echoes, indicating hemorrhage within sometimes an MRI is also necessary to determine
the cyst. The most frequent and frightening compli- the age of the hemorrhage [22].
cation of simple cysts is torsion of the ovary [28,
29]. Cystic torsion occurs more often in the fetus
than in the neonate, and fetal sonographic appear- 38.4 Differential Diagnosis
ance of a calcified abdominal mass and a solid
component with or without wandering can be con- Once a cyst is detected, close US follow-up is
sidered an autoamputated ovary [28, 29]. necessary in order to make a differential diagno-
Complicated or complex ovarian cysts evaluated sis (Table 38.3). The differential diagnosis
by ultrasound (US) present with thick wall and het- includes choledochal, mesenteric, urachal, and
erogeneous echogenicity. Complex cysts are
thought to be the result of rupture, dystocia during Table 38.3  NOCs sonographic characteristics used to
birth, and pressure on nearby structures such as distinguish cysts from other cystic masses [22]
blood vessels, uterus, intestines, and urinary sys- Ovarian cyst Female fetus only; “daughter cyst”
tem [22, 30]. If a cyst presents with complex US sign (smaller cyst within a larger
ovarian cyst)
features from the beginning, there is a probability
Choledochal Unilocular cyst that communicates
of ovarian-vascular dysgenesis or a neoplasm [5, 8, cyst with the bile ducts; located in the
15, 28]. right upper quadrant of the
abdomen
Enteric “Gut signature” sign (cyst wall is
duplication cyst thick and layered)
38.3 Clinical Manifestations Urachal cyst Fluid-filled cyst restricted to the
and Complications anterior midline between the
bladder and umbilicus
When small cysts, prenatally or postnatally Hydrocolpos Fluid-filled midline pelvic mass
detected, start to grow rapidly and their US fea- posterior to the bladder; may be
associated with uterine dilatation
tures change, ovarian torsion should be consid- (hydrometrocolpos)
ered. Ovarian torsion, rare in the postnatal period, Lymphangioma Thin-walled multilocular cystic
is relatively more frequent in the intrauterine mass with multiple septations;
period (20–32%) and during delivery. At birth, in infiltrative; may involve the body
almost all cases, the neonate is asymptomatic and wall
494 G. Pelizzo

enteric duplication cysts and hydrometrocolpos than 40 mm, in order to reduce the risk of ovar-
[22]. Malignant tumors are rare in the neonatal ian torsion and other complications [34].
period, but benign cystic teratomas are common US-guided aspiration offers several advantages:
ovarian tumors [22, 30, 31]. Lymphangiomas it is a minimally invasive procedure, does not
also are counted among the hamartomatous require general anesthesia, and enables preser-
lesions of the fetal-neonatal ovary [22, 30]. vation of the ovarian tissues [34]. The procedure
is simple and safe, can be performed at the bed-
side, and may be repeated as required if the cyst
38.5 Treatment refills.
Even though US-guided aspiration has many
Treatment options include close follow-up with advantages, the condition of the ovary may not be
observation, cyst aspiration, laparoscopic interven- ascertained accurately, the adjacent organs may
tions, or laparotomy. Prenatally detected simple interfere with the approach to the target, and
cysts require watchful expectancy when the size is US-guided aspiration may be rather limited in
less than 4 cm in diameter; antenatal aspiration to septated or complex cysts. Moreover the risk of
prevent torsion loss is recommended when the size recurrence is high and careful ultrasonographic
is greater than 4 cm; in the neonatal period, resec- follow-up and repeated aspirations may be neces-
tion of all symptomatic, complex cysts is necessary sary, which increases the risk of bleeding and
to avoid ovarian loss [2, 3, 17, 19, 20]. Surgical infection in the cyst [22, 34–38].
treatment is essential in torsioned cysts [2, 3, 6, 32].
The major goal of both surgical and noninvasive
treatment by US monitoring is optimal ovarian 38.5.3 Laparoscopic Interventions
preservation even though long-term outcomes and
risks to future fertility are unknown [19, 30]. Laparoscopy, with its minimally invasive nature,
offers the advantages of prompt and good recov-
ery in newborns and smooth postoperative recov-
38.5.1 Expectant Management ery. The laparoscopic approach is preferred since
it affords a diagnostic opportunity, allowing the
As long as the prenatal simple cyst is small, does surgeon to visualize both ovaries. Aspiration of
not show a trend for rapid growth, and remains the cyst, cystectomy, stripping of cysts, and, if
asymptomatic, it should be monitored by serial necessary, oophorectomy are all possible with
US and expectant management [2, 3, 17, 19, 20, laparoscopy [39–43].
33]. Fetal cysts that are less than 5 cm in diameter Laparoscopic aspiration also overcomes all of
are unlikely to cause problems and can be the US-guided aspiration disadvantages. This
observed for spontaneous resolution. In the new- approach allows surgery without damaging the
born there is no consensus regarding the modality adjacent organs, which is the greatest concern
and timing of NOC monitoring. Postpartum during US-guided aspiration. Almost all fluid can
serial US examination should continue every be repeatedly aspirated from septated cysts via an
4–6  weeks until the cyst resolves, enlarges, approach from other directions. In addition, the
becomes symptomatic, or persists for more than ovary with torsion and the normal contralateral
6 months, and if a cyst is large (>5 cm), does not ovary may be visualized.
regress, or increases in size, it should be punc- The operation time for an aspiration-only pro-
tured or removed surgically [2, 3, 17, 19, 20, 33]. cedure takes less than 30 min and leaves minimal
scarring, since only a 3-mm trocar/camera port is
created. Surgeons may perform detorsion or cys-
38.5.2 Ultrasound-Guided Cyst tectomy at the same time if an ovarian torsion is
Aspiration discovered. The magnitude of the cyst size is not
a contraindication, since laparoscopic cyst punc-
US-guided cyst aspiration in newborns is only ture and aspiration allows sufficient reduction in
recommended for simple cysts that are larger size [39–42].
38  Neonatal Ovarian Cysts 495

Surgical excision is generally indicated for As illustrated in Fig. 38.5, three ports are usu-
cysts that are complex and symptomatic or increase ally used: a 3- or 5-mm umbilical port (camera)
in size and persist for more than 6 months. Early and two 3-mm ports in the right and left flank,
surgical intervention to exclude malignancy is also respectively (working ports).
possible. Although US is inadequate to distinguish The peritoneal cavity is insufflated with CO2
between a complicated cyst and an ovarian tera- at a pressure of 5–8 mmH.  The flow rate for
toma or other tumor, the presence of neonatal insufflation of CO2 ranges from 1 to 5 L/min.
ovarian tumors is anecdotal [30, 31]. The laparoscopic approach can be technically
When surgical treatment is indicated, every challenging in small children with large intra-­
attempt should be made to rescue as much of the abdominal cysts. First, it is often difficult to gain
gonadal tissue as possible. Indeed, even if no access to the peritoneal cavity for port placement
ovary is macroscopically visible, ovarian tissue and to dissect and manipulate the cyst because of
may still be present, and surgery should be lim- the limited space in smaller children and the need
ited to removal or unroofing of the cyst. for multiple instruments. Secondly, chemical
The stripping technique for enucleation of peritonitis may result from leakage of benign cyst
large benign cysts is also feasible in infants and fluid into the peritoneal cavity [45–48].
appears to be an organ-preserving procedure
when the ovarian tissue is not inadvertently
excided with the cyst wall [26].
In preparation for all laparoscopic procedures,
preoperative assessment is crucial in all children.
This can be a formal assessment in a dedicated
preoperative assessment clinic held by experi-
enced pediatric surgeons.
Positioning of the patient must allow adequate
exposure and safe access to the operating field.
The recommended alignment is to have the
­monitor, operating surgeon, and the patient or tar-
get organ in a straight line. During laparoscopic
neonatal gynecological surgery, the patient is
placed in a supine transverse position, across the
operating table, so that the surgeon and assistant
can work from the head of the patient, on the
right side of the table [43, 44] (Fig. 38.4). Fig. 38.5  Trocar positioning

Fig. 38.4  The room Surgeon Assistant

setup for gynecological Anesthesiologist
procedures in neonates
a
ca hesi

Scrub nurse
rt
t
es
An

S
W cru
or b n
k
st urs
at e
io
n

Laparoscopic
tower
496 G. Pelizzo

In order to address these issues, several lapa- tional laparoscopic surgery. Due to limited data
roscopic approaches and modifications have been regarding neonatal cysts and the effective cost
adopted. These include either drainage of the cyst analysis, the robotic surgery approach is not pro-
by US-guided paracentesis or drainage during moted in infants and neonate.
laparoscopy followed by excision or manipula-
tion of the cyst or extracorporeal cystectomy. For
drainage and manipulation of the cyst, different 38.6 Other Considerations
techniques have been described using a planned
trocar placement through the cyst, percutaneous The NOCs need to be managed by a multidisci-
gastrostomy introduction set, soft cup aspirator plinary team involving pediatric surgeons, pedi-
set, suprapubic catheter, extracorporeal drainage atric radiologists, gynecologists,
via a minilaparotomy, and aspiration and traction anesthesiologists, neonatologists, and pediatri-
through the port to facilitate dissection [45, 46]. cians. Adequate perioperative and operative facil-
These techniques provide controlled means of ities instrumentation for minimally invasive
aspirating the cyst and allow traction to the cyst surgery in infants are mandatory [51]. Counseling
wall to facilitate intracorporeal manipulation and prior to surgery is essential and should involve
dissection of the cyst. The needle hitch technique both parents. During this discussion the risks,
minimizes the need for additional instrumenta- benefits, and alternatives to surgery should be
tion and ports for traction and facilitates better conveyed and documented. Finally, sufficient
ergonomics for intracorporeal manipulation and pain management during the postoperative recov-
dissection of large cysts. ery is recommended.
In contrast with open surgical procedures,
laparoscopic treatment of ovarian cysts ends in Acknowledgments  The author thanks Dr. Calcaterra V.
only three punctiform scars, which give a satis- of the Pediatrics and Adolescentology Unit, Department
of Internal Medicine and Therapeutics, University of
factory cosmetic appearance for the entire life of Pavia, Italy, and Dr. Re A. of the Pediatric Radiology,
the patient. Shorter hospital stays and time to Children’s Hospital, ARNAS Civico-Di Cristina-
feedings, reduced pain, and quick return to nor- Benfratelli, Palermo, Italy.
mal activity (or parents to work) are additional
advantages of the laparoscopic approach.

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44. Schenkman L, Weiner TM, Phillips JD. Evolution of in the pediatric and adolescent populations: review of
the surgical management of neonatal ovarian cysts: perioperative and operative considerations. J Minim
laparoscopic-assisted transumbilical extracorporeal Invasive Gynecol. 2016;23:1033–9.
ovarian cystectomy (LATEC). J Laparoendosc Adv
Surg Tech A. 2008;18:635–40.
 Teratoma: Sacrococcygeal
and Cervical 39
Olivier Reinberg

39.1 General Considerations diseases and abnormalities, the first reported case
was on a Chaldean cuneiform tablet dated
Extragonadal teratoma is generally located all approximately 2000 BC [2].
along the midline. They are found in decreasing Circa 600  AD, the Archbishop Isidore of
incidence in the sacrococcygeal region (40%), Seville compiled the universal knowledge of that
pineal region (13.3%), cervical (13.1%), palatine time in the “Etymologiae” in which he gave the
and nasopharyngeal region (8%), heart (7.5%), first pseudoscientific descriptions of congenital
stomach (2.6%), mediastinum (2.6%), orbits anomalies. This book was the most popular com-
(2.4%), face (1.5%), placenta (1.5%), and other pendium in medieval libraries. By the fifteenth
very rare locations (3%) [1]. Today with the century, more than ten editions were published
improvement of ultrasounds (US), the diagnosis showing his continued popularity during the
is done prenatally. Sacrococcygeal teratoma Renaissance [Isidore of Seville, Etymologiae,
(SCT) although the commonest germ-cell tumor Liber XI: De hominibus et portentis (Of men and
in children is a rare fetal anomaly. The majority monsters)].
present at birth as an external sacral mass; how- From mid-sixteenth to mid-seventeenth cen-
ever, some intrapelvic SCT may be unapparent. tury, monstrous births with SCT and/or conjoined
A final paragraph will treat of the 10% cervical twins have been described and depicted in several
teratoma concerning the neck, the nasopharynx books by Jacob Rueff from Zurich in De con-
and/or the oropharynx. ceptu et generatione hominis (1554); by Ambroise
Paré from France in Des monstres et prodiges
(1573); by Fortunio Liceti from Rapallo, who
39.2 History worked in Bologna in De monstrorum natura,
caussis et differentiis libri duo (1616); and by
Many cases have been reported, depicted, and Ulisse Aldrovandi from Bologna in Monstrorum
drawn, but most of them are related to conjoined historia (1642).
twins as they impressed the observers and are dif- The term “teratoma,” from the Greek
ficult to distinguish from mature SCT. (τερατώδης  =  monstruous; τερας  =  monster),
According to JW Ballantyne, a Scottish eru- was coined by the German pathologist Rudolf
dite in ancient medical literature dedicate to fetal Virchow in 1869 to describe lesions which con-
tained a foreign tissue to the part in which they
arise [3].
O. Reinberg (*)
Department of Pediatric Surgery, Lausanne, Switzerland

© Springer Nature Switzerland AG 2019 499

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_39
500 O. Reinberg

In the modern era, the first large series of 40 Lagausie has described a case showing that fetus
infants and children with SCT was reported by in fetu can be a remarkably complex, well-­
Gross in 1951 [4]. differentiated, highly organized teratoma. Mature
SCT are derived from remnants of the three
embryonic developmental tissues (ectoderm,
39.3 Epidemiology mesoderm, endoderm) and demonstrate a lack of
organ specificity whether conjoined twins have a
Most authors report SCT incidences of 1:30,000– more advanced structural organization.
1:40,000 [5–9]. However these rates were based SCT occur near the coccyx where the greatest
on data obtained before the 1970s, and more concentration of germ cells is present for the lon-
recent studies have shown incidences up to gest period of time. Using immunohistochemis-
1:23,300 [10–13]. It seems that the number is try, Buchs showed that SCT come from remnants
increasing [14, 15]. SCT is possibly more fre- of the epiblast-like tail bud blastema. He demon-
quent in Northern Europe as reported in Sweden strated that they contain cells positive for embry-
(1/13,000 [14]) and in Finland (1:10,000 [13]). onic stem cell markers and may represent a novel
But higher incidence of SCT in Scandinavian source for human embryonic stem cells [29].
countries might be explained by the region’s use With the hypothesis of an abnormally placed set
of nationwide birth registries [14]. Most studies of stem or germ cells, they could migrate from
show a female to male preponderance of about the yolk sac to the gonad pathway, persist, dif-
4:1 (from 1.9:1 to 8.3:1) [9, 12, 16–19]. SCT ferentiate, and mature resting anterior to the coc-
seem to be sporadic. However familial forms cyx at the Hensen’s node. The growth of the
exist with different characteristics: they have an pluripotential cells could escape to the control of
autosomal dominant inheritance, show no sex the embryonic inductors and organizers, resulting
difference, and are presacral and usually benign in a teratoma. Rearrangements into the proto-­
with a low risk of malignancy [20–22]. Mature oncogene or in an abnormal regulatory sequence
teratoma is the most common [14, 15, 23, 24]. could result in molecular transformations of cells
Demography and ethnic origins could play a role foreign to that anatomical site [29, 30].
in the risk of malignancy [25].

39.5 Types and Classifications

39.4 Etiologies
All SCT are attached to the coccyx. They develop
The etiology remains unknown. SCT arise from outside the pelvis, into the presacral area, or
multipotential embryonic cells situated in both. Altman described a four-stage classifica-
Hensen’s node. It could be the failure of a twin- tion of SCT according to the relative amounts of
ing attempt or result from an abnormally placed intrapelvic and external tumor [5] (Fig.  39.1).
set of stem or germ cells. Altman also subclassified SCT into small
In the hypothesis of a twinning failure, the (2–5  cm diameter), moderate (5–10  cm), and
question raised is what is the difference between large types (more than 10  cm). This classifica-
a mature SCT with all organized tissue compo- tion has been adopted by the Surgical Section of
nents, conjoined ischiopagus or pygopagus twins, the American Academy of Pediatrics and then
or a fetus in fetu. A definition of fetus in fetu was worldwide. Type I are primarily external and
proposed by Gonzalez-Crussi [26] as “high have only a small presacral component (Fig.
organotypic development and presence of a ver- 39.1a and Fig. 39.2). Type II are predominantly
tebral axis with arrangement of tissue around this external but have a significant intrapelvic portion
axis.” Some authors raise the question whether (Fig. 39.1b). Type III are partially external and
highly differentiated teratoma and fetus in fetu predominantly intrapelvic with abdominal exten-
could be the same pathology [16, 27, 28]. De sion (Fig.  39.1c and Fig.  39.3). Type IV are
39  Teratoma: Sacrococcygeal and Cervical 501

a b

Type II
Type I

c d

Type IV
Type III

Fig. 39.1  Altman classification of SCT [5]

located entirely within the pelvis and abdomen mesoderm, endoderm) and thus reveal inhomo-
(Fig. 39.1d). This classification is related to the geneity with solid, cystic, and osseous parts. In
ease of surgical resection and prenatal detection mature SCT, any well-differentiated tissue can be
as well as the likelihood of malignancy. Type I present such as skin, bone, cartilage, and neural
are easy to detect and to resect with a very low tissue but also nails, teeth, and hair (Fig.  39.4).
incidence of malignancy. Reversely, SCT type SCT is said immature when undifferentiated
IV are difficult to diagnose with prolonged delay cells, especially from neuroepithelial tissues, are
of r­ecognition, are not amenable to fetal resec- dominant. Malignant SCT are mostly solid, while
tion, and are frequently malignant. Fortunately, immature are frequently cystic. Mature and
the majority of SCT are type I or II. immature teratomas represent 87–93% of cases,
Mature teratoma is multi-tissular with ele- while malignant tumors represent the other
ments coming from the remnants of the three 7–13% [15, 31–33]. Malignant changes are more
embryonic developmental tissues (ectoderm, common in males [5, 34].
502 O. Reinberg

a a

Fig. 39.2 (a, b) SCT Altman I in a female newborn on

Day 1. On close view (b) note the large superficial vessels
that may bleed and a superficial wound not correlated with
delivery (Cesarean section) (arrow head)

The Gonzalez-Crussi’s grading system for

SCT (1978) is based on histology [31]. Grade 0 Fig. 39.3 (a, b) SCT Altman III in a female newborn.
is totally mature and benign. Grade 1 is mainly MRI performed on Day 2
mature with rare foci of immature tissue and has
to be considered as benign. Grade 2 has Usually the SCT is well delimitated, but commu-
­significant parts of immature tissues, thus bear- nication with the urethra or with the rectum may
ing a potential for malignancy. In Grade 3 mul- occur [37]. Proteus syndrome can be associated
tiples, places of immature tissue are found with with a SCT [38].
or without yolk sac tumor and are considered to
be malignant; thus additional cancer staging
must be added. 39.6 Prenatal Diagnosis
Most SCT are benign (55–94%). Histological and Treatments
grading of SCT does not seem to correlate
directly with prognosis unlike that of ovarian SCT are usually evidenced on a routine
teratoma. Histology for malignancy increases US. They appear as caudal or intrapelvic mass
from 10% at birth to 50–70% at 2 months. and require for more investigations. Following
Unusual forms of SCT have been described, the diagnosis of a SCT, the parents need to be
such as SCT with intradural extension [35, 36]. referred to a tertiary center where a multidisci-
39  Teratoma: Sacrococcygeal and Cervical 503

a b

Fig. 39.4 (a, b) Mature SCT Altman I on a male newborn (a) and conventional plain Rx showing multiple limb-like
osseous components (b) on Day 1

plinary team has experience with this condition.

Parents should be reassured that the majority of
tumors are benign with a good prognosis and a
low recurrence risk if total resection is per-
formed in the neonatal period. However they
should be informed that a closed surveillance is
mandatory and that death may occur during
pregnancy or at birth.
Evaluation of SCT is best performed by MRI
to document its content and its extension
(Fig.  39.5). But 3D US with power Doppler is
an alternative [39, 40]. It should be comple-
mented by an echocardiography (EKG) with US
Doppler measurements. Once the diagnosis of
SCT is made, frequent evaluation (weekly ?) by
US and EKG is mandatory as cardiac failure
may occur.
The prenatal workup looks for anomalies
associated to SCT that range between 5 and 26%
[10, 12, 15, 41]. They are many and diverse and
have been described as associations with hydro-
cephalus, tethered cord, spinal dysraphism, ver-
Fig. 39.5  Prenatal MRI at 30 WGA (same patient as in
tebral anomalies, sacral agenesis and
Fig. 39.2)
meningocele, anorectal malformations, cleft lip
and palate, polydactyly, transposition of great
vessels, neurogenic bladder, bifid scrotum, hypo- associated with anorectal malformations and
spadias and epispadias, and ectopic kidney. SCT sacral anomalies. Urogenital anomalies seem to
can occur as part of the Currarino triad, when it is be more common in girls with SCT [42].
504 O. Reinberg

Vascular disruption defects refer to those before 24  weeks of gestational age (WGA). A
involving the interruption or destruction of some TFR  <  12 means a good outcome, while a
part of the fetal vascularization. A vascular dis- TFR > 12 has a poor outcome. The sensitivity of
ruption sequence has been mentioned by Atis the TFR ratio is >91% and his specificity is ≈
about a rare case of SCT causing multiple fetal 80% [47, 49].
disruption defects like cleft lip and palate, limb These ratio are helpful at diagnosis but must
amputations, and hydrops [43]. be followed during pregnancy to evaluate the
In most fetus, the prenatal course is unevent- growth rate of the SCT. A rapid growth (> 60 cm3/
ful. However in case of unfavorable evolution, week for Coleman; > 150 cm3/week for Wilson;
the fetus and the mother can be in danger. Close >8  mm/week for Hambraeus) bears a risk of
monitoring helps to predict and prevent these adverse outcome [14, 15, 19, 44, 50, 51] as has a
unusual outcomes. Several factors such as tumor preterm delivery [15]. After reviewing 18 studies
morphology (solid vs. cystic), vascularity, tumor including 420 cases, Ayed concluded that a SCT
growth rate, and the presence of hydramnios have diagnosed at >28 WGA with a delivery >34
been found to predict outcomes in prenatally WGA has a survival rate of 90% [19, 44, 51, 52].
diagnosed SCT [44–46]. The macro-microscopic appearance of the
Benachi suggested a prognostic classification SCT is also a part of the prognosis:
of prenatally diagnosed SCT related to their size, The prognosis is better in mature types (98%
vascularization, and macroscopic appearance on survival) than in immature (69% survival) and in
ultrasound with Doppler evaluation. SCT are cystic or mixed forms (73% survival) than in
classified into three prognostic groups: (A) tumor solid (45% survival) [15, 31].
diameter < 10 cm, absent or mild vascularity, and The effects of SCT on fetus are of two types:
slow growth; (B) diameter  >  10  cm with pro- the compressions due to the volume of the mass
nounced vascularity, high-output cardiac failure, that are more important in the internal types (i.e.,
and rapid growth; and (C) diameter of 10 cm or types III and IV) and the cardiocirculatory distur-
greater, predominantly cystic with absent or mild bances induced by the SCT itself. SCT may para-
vascularity and slow growth. Group A is associ- sitize blood supply usually from the mid-sacral
ated to good maternal and perinatal outcome. artery or sometimes from the internal and exter-
Group B is related to poor outcome, and the per- nal iliac systems. This causes abnormal high flow
centage of mortality as well as fetal and maternal through enlarged vessels that “steal” blood from
morbidity is high. Group C has a good prognosis the normal vascular stream. The highest risks for
although shunting or drainage of the SCT could fetal death are in the most vascularized tumors,
be necessary. Large fast-growing SCT with rich regardless of size [51]. Then the fetus may
vascularity are associated with a higher perinatal develop a high-output cardiac failure, an hydrops
mortality and morbidity than smaller lesions with fetalis, an hemorrhage inside or outside the
mild vascularity [23]. tumor, a polyhydramnios, and/or a placentomeg-
As it appeared that the size of the SCT was not aly. Should a hydrops appear after 30 WGA, the
significant enough, several ratios have been mortality risk is 25%, while appearing before 30
developed to make a better prognosis and a fol- WGA means 90% mortality [51]. Grossly said
low-­up during pregnancy: without hydrops fetalis and/or polyhydramnios,
The THR ratio is the ratio between SCT vol- SCT have 80% survival for a full-term delivery
ume and fetal head [46, 47]. In case of cystic but only 52% survival with a preterm delivery
SCT, only the volume of solid components is (before 34 WGA) [51].
taken into consideration. A THR  <  1 means no Inadequate placental flow has been reported to
death in utero, while a THR > 1 has a 61% risk of induce the release of vasoactive substances that
poor prognosis. can gain access to the maternal circulation. They
The TFR ratio is the ratio between SCT vol- induce endothelial cell damage and lead to mater-
ume and fetal weight [48, 49]. It is best done nal pseudotoxemia (Ballantyne syndrome). In
39  Teratoma: Sacrococcygeal and Cervical 505

this syndrome, there are signs and symptoms of coils, alcohol, or tissue adhesive (Histoacryl®)
preeclampsia including hypertension, protein- have been used [60].
uria, peripheral edema, pulmonary edema, nau- Adzick first used ex utero open fetal surgery
sea, and vomiting. for tumor ablation in 1997 which since then has
Last but not least, the external SCT have a sig- been followed by others [41, 64–67]. These pro-
nificant risk of dystocia and may require for a cedures are at risk for the fetus and for the mother
Cesarean section due to the size (>10 cm?) and to [59]. Thus mandatory criteria for fetal surgery
the risk of rupture of one of the major vessels run- must be followed: accurate prenatal diagnosis,
ning on its surface during labor (Fig. 39.2a, b). absence of other life-threatening or debilitating
Thus there is a ratio for fetal management in anomalies, and procedure without increased risk
selected cases. Should unfavorable evolution to the mother’s life or for her future fertility [65].
occur, the termination of pregnancy using a In addition the specific criteria for SCT are blood
Cesarean section has to be considered accord- volume represented by SCT circulation may have
ing to the WGA. Indications for Cesarean sec- exceeded the capacity of baby’s lungs to arterial-
tion are fetal (hydrops fetalis, cardiac failure) ize blood, large venous blood stream from the
or maternal complications. Early delivery as an SCT contributed to a low mixed venous PO2 and
alternative management strategy for selected pulmonary vasoconstriction, fetal ascites and
high-risk SCT must weigh the pros and the cons abdominal distension impairs lung development
among risk of death in utero and prematurity in utero, resulting in reduced lung volumes and
[53]. The EXIT procedure (ex utero intrapar- finally to presume that post birth the SCT volume
tum therapy) can be an alternative between 28 will impair diaphragmatic movements.
and 36 WGA for selected cases as long as there
is no maternal or placental compromise [54,
55]. The EXIT procedure requires the presence 39.7 P
 ostnatal Preoperative Cares
of maternal-fetal specialists, pediatric anesthe- and Surgery
tists, neonatologists, and pediatric surgeons at
delivery to secure stable airway access and ven- SCT bears a high risk of fatal issue during and
tilation to the baby before clamping the umbili- after delivery. It is said to be the “most common
cal cord. cause of neonatal mortality” [68]. Death during
Otherwise many techniques have been devel- the prepartum is related to heavy bleeding associ-
oped to reduce the volume of the mass or to mini- ated to trauma on the external vessels, while dur-
mize the risk of bleeding. In case of nonvascular ing the postpartum, major bleeding from deep
cystic SCT, percutaneous drainage/decompres- vessel injuries is involved [10].
sion can be performed under US guidance [56]. Preoperative assessments include postnatal
Laser coagulation of surface or deep vessels can MRI, complete assessment of the spine (mostly in
be done under fetoscopy, under US guidance, or type IV), and blood sampling for αFP, β-HCG, and
using radiofrequency ablation [57–60]. CA-125. Additionally cross-matched blood should
Radiofrequency ablation is done by a needle be done to ensure availability in the operating
inserted through the mother’s abdomen into the room with extensive coagulation tests as signifi-
tumor. Radiofrequency waves are sent through cant coagulopathies are associated with SCT.  In
this needle, producing heat into the tumor and case of ureteric compression with subsequent
destroying the blood vessels that supply it [61, hydronephrosis, renal functions should be done.
62]. However it is difficult to control the energy Treatment of SCT is mainly surgical.
released, resulting in severe collateral damage to Whenever possible, early excision within the 1st
the surrounding tissues. Complications have been week of life should be the aim as some undiffer-
reported such as severe orthopedic sequelae to entiated foci may proliferate with time and
the pelvis and sciatic nerve injuries [63]. become aggressive [51, 67]. Surgery should
Radiological techniques of occlusions using include total resection of the SCT and coccyx
506 O. Reinberg

removal. As to reduce the risk of sharp bleeding permits excision with significant reduction of
in case of enlarged vascularization, control of the bleeding. We have not required aortic control in
presacral artery is required. This can be done any of our patients, even with large tumors. The
radiologically using preoperative radiological dissection is carried on cranially surrounding the
embolization [69–71] or by clipping laparoscopi- upper pole of the tumor (Fig. 39.6b). At this point
cally the artery [72–78] if the child’s conditions we reach the posterior wall of the rectum that
allow it. If not possible, it has to be the first step must be dissected carefully. On either side, the
through an open laparotomy. gluteal muscles are spread away and sometimes
The patient is laid in a prone position, a pad difficult to identify. Then the safest way is to stay
being placed under the pubic symphysis. The in close contact with the tumor without opening
incision differs according to the surgeon and to it. The lower part of the dissection can be in close
the quality of the skin. Historically, the chevron contact with the anorectal muscular complex. It
incision has been used but leaves transverse scars is of major importance to avoid lateral dissection
causing unpleasant cosmetic results. Posterior to preserve from nerve injury. Skin is closed over
sagittal anorectoplasty (PSARP) has also been drainage(s), but buttock reconstruction after SCT
used [79]. Resecting the skin at that stage is not resection is difficult.
recommended as we don’t know yet how the Some surgeons prefer to perform a prelimi-
wound will be closed at the end of the SCT nary colostomy before combined ­abdominosacral
removal. Then the limit between the sacrum and excision of large type III and IV lesions to reduce
the coccyx is looked for and carefully cut trans- morbidity [80]. The use of ECMO and hypother-
versally (Fig. 39.6). The presacral artery lies just mic hypoperfusion [81, 82] or cardiopulmonary
under the sacrum (Fig.  39.7). It can be a major bypass and ECMO [83] has been described in
one and has to be ligated carefully. Its control large SCT resections.

Fig. 39.6 (a, b) Transverse section between the sacrum and the coccyx (arrows). After section of the coccyx, the
dissection goes cranially, surrounding the upper pole of the tumor (b)
39  Teratoma: Sacrococcygeal and Cervical 507

sion of the coccyx [84–86]. Most recurrences

occur within 2–3 years [10, 84].
Malignant SCT has a good overall prognosis
provided complete surgery is achieved and che-
motherapy is administered. A huge improvement
with neoadjuvant chemotherapy has been widely
described with 5-year survival rising from 49 to
83% [23, 33, 85]. Distant recurrence or metasta-
sis at first resection requires for risk-adapted che-
motherapy with a fairly good prognosis [85].
All presacral teratomas do not bear the same
risk of malignant evolution. This is the case when
comparing the risk of malignant transformation
Fig. 39.7  Peroperative view after section of the coccyx.
Note the large presacral artery (arrow) lying just below the of isolated SCT with that of presacral teratoma in
sacrum (asterisk) (same patient as in Fig. 39.2, operated Currarino syndrome. The evolution may differ
on Day 2) despite the similar position and appearance. The
malignancy-free survival of patients with isolated
SCT seems to be lower than for patients with a
39.8 Recurrences and Prognosis presacral teratoma associated with Currarino
syndrome (80 and 58% after 1 and 2 years in iso-
The overall prognosis after SCT removal is good lated SCT versus 100% after 2 years in Currarino
with >90% survival and free of recurrence at syndrome) [87].
5-year follow-up [10]. However it varies widely
according to several factors including early and
complete resection without spillage, size of the 39.9 Follow-Up
tumor, and histology. After total macroscopic
resection, the prognosis for benign histology is Long-term functional sequelae after resection of
good with 7–22% recurrences but is 37–49% SCT are relatively common. They mainly affect
after incomplete resection. However recurrences fecal and urinary continence interfering with the
have been described after macroscopically and quality of life. In most series, no anorectal or uro-
histologically radical tumor removal. Thus logic complications occurred in patients with
recurrences need for extensive histology. Altman type I SCT [88, 89]. But Dericks consid-
Recurrence rate is higher if surgery is delayed ers Altman classification, sex, histopathology,
(>50% recurrences when surgery is done incomplete resection, and age at diagnosis are not
2–4  months vs. 10–35% if performed before risk factors for functional sequelae [8].
1 month). A strong argument favors early resec- Fecal complications can be involuntary bowel
tion: a shift from initially benign histology movements, soiling, or constipation. Constipation
toward immaturity or malignancy has been fre- is encountered in 8–50% cases [8, 88, 90, 91].
quently described [10, 67, 84]. The histology of Soiling is present in 24–27% [8, 88–91]. In a
fetal SCT may change in utero and post birth. Swedish study on 34 SCT, 40% soiling were
Graf reported histological maturation in fetal found in spite of recto-anal inhibitory reflex pres-
SCT between the initial debulking procedure ent and normal. The authors could not determine
and subsequent definitive resection [67]. if anal incontinence was related to the surgery or
However in these cases, it is unclear whether this to the tumor itself [92]. A very long-term follow-
was the result of spontaneous in utero tumor ­up (mean 30  years) was reported by Rintala: if
maturation or transformation induced by fetal 88% of patients reported themselves with normal
surgery. Malignant recurrence after excision of fecal continence, only 27% had completely nor-
benign tumors has been reported despite exci- mal bowel habits. As in other reports, no correla-
508 O. Reinberg

tion was found between the impaired anorectal

functions and the degree of intrapelvic extension
of the tumor [91].
Urologic complications are underappreci-
ated sequelae of the mass effect of SCT and of
its resection. Most series report ≈ 30% com-
plaints [8, 88–92]. Patient may have no urinary
complaints after surgery, but urodynamic inves-
tigations reveal anomalies in 78% of cases
including neurogenic bladders specially in the
intrapelvic forms [88, 90, 93, 94]. Renal impair-
ment may follow obstructive findings on prena- Fig. 39.8  Cosmetic result 4  years post surgery (same
tal imaging related to ureteric compressions by patient as in Fig. 39.2)
the tumor [93].
Sexual activity after resection of SCT seems
to be normal. Males reported normal erectile mature and immature tumors [100]. The mean
functions and penetration ability with normal time required for markers to become normal is
ejaculations. However females had significant by 8–12 months after resection [100, 102]. With
lower Body Image Questionnaire results com- no decrease at 6 months, an MRI should be done.
pared to males [95]. Successful pregnancies were Thus, regular monitoring of αFP, β-HCG, and
reported, and neither of their children had SCT CA-125 is recommended in post-surgical fol-
[42]. Some authors mentioned obstetric difficulty low-up of SCT. However there is no consensus
due to rigid pelvic outlet in their patients [96, 97], on the frequency and duration of controls.
but in a series of 20 pregnancies in women after Several authors recommend that patients undergo
SCT, 17 children were born by vaginal delivery serum αFP monitoring every 3 months for more
and 3 required Cesarean section [98]. than 3  years after SCT resection [86, 101].
The common complaint among 40% patients Barreto evaluates monthly the αFP in the first
is a cosmetically unacceptable scar [8]. According 6  months, every 2  months in the following
to Derikx, the size of the tumor (>500 cm3) bears 6 months, and every 3 months in the second and
a significant risk factor for cosmetically unac- third years [102].
ceptable scar. Fishman has described a technique
to improve the cosmetic appearance of scar and
buttock after SCT resection [99]. However it 39.10 Cervical Teratoma
must be said that the poor quality of the skin and
the need for total resection sometimes impede Congenital cervical teratoma represents the sec-
performing a nice reconstruction and closure ond most frequent extragonadal teratoma loca-
(Fig. 39.8). tion after SCT. They are very unusual arising in
Orthopedic sequelae after SCT removal 1/20,000–40,000 live births [1, 54, 103]. The
have been described [96]. Most patients show term epignathus refers to those arising from the
normal gait pattern but abnormal kinetics of oropharynx or palate in the sphenoid region
some ambulatory muscles independently of called Rathke pouch [104].
tumor size. What has been said about SCT is valid for cer-
The role of alpha fetoprotein (αFP) and vical teratoma including cardiovascular compli-
human chorionic gonadotropin (β-HCG) in the cations and fetal hydrops. However according to
follow-­up of SCT is well known [85, 100, 101]. the location, their masses are likely to cause air-
Pauniaho demonstrated that αFP was useful in way or esophageal compressions. Closure of the
detecting malignant recurrences, while CA-125 esophageal lumen by external compression leads
was useful in early detection of recurrences of to polyhydramnios and risk of preterm delivery.
39  Teratoma: Sacrococcygeal and Cervical 509

Polyhydramnios and hydrops, associated with a 7. Leung AK, Rubin SZ, Seagram GF, et  al.
Sacrococcygeal teratoma. Aust Paediatr J. 1985;
large tumor size (>5 cm), have a poor prognosis 21:123–5.
[105, 106]. Teratoma arising from the face, the 8. Derikx JP, De Backer A, van de Schoot L, et  al.
pharynx, the palate, or the tongue may occlude Long-term functional sequelae of sacrococcygeal
the airway leading to respiratory distress at birth, teratoma: a national study in The Netherlands. J
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 Part VIII
Genitourinary
 Congenital Ureteropelvic
Junction Obstruction 40
Michela Maffi and Mario Lima

40.1 Definition between APD on prenatal ultrasound and the

likelihood of pathological dilation after birth,
Primitive or congenital hydronephrosis is a dila- taking into account the fact that the diameter of
tion of renal pelvis and intrarenal calyces mostly the renal pelvis increases with gestational age
due to an abnormality of the ureteropelvic junc- (GA). Mostly accepted thresholds are
tion (UPJ), which results in an inadequate drain- APD <4 mm in the second trimester and <7 mm
age of urine from the pelvis into the ureter. in the third trimester. The APD classification is
Increased intrapelvic pressure and urinary stasis resumed in Table 40.1.
in the collecting ducts cause progressive damage In 1993, the Society of Fetal Urology (SFU)
to the kidney. proposed a classification based on the appear-
ance of pelvis, calyces, and renal parenchyma
(Fig. 40.1) [2]. In case of monolateral hydrone-
40.2 Classification phrosis, parenchymal thickness reduction is
considered significant when it is less than half
Several classification systems for urinary tract of the non-affected kidney and in case of bilat-
(UT) dilation have been proposed over time, and eral hydronephrosis when it is less than 4 mm.
some of them are currently used. Perhaps the The SFU classification is summarized in
most basic is the traditional grading system, in Table 40.2.
which the grade of hydronephrosis is descrip- The SFU grading system finds a wide applica-
tively defined as mild, moderate, or severe [1]. tion; however, it emphasizes more intracalyceal
Obviously this is a highly subjective system and pelvic dilation and does not take into account
resulting in poor inter-rater reliability. A more APD measurement. To overshadow this limit, in
objective system is based on the measurement of 2008, the European Society of Pediatric
the anterior-posterior diameter (APD) of renal Radiology has proposed a revision of the SFU
pelvis during prenatal age. There is now ample classification which includes the introduction of
evidence that there is a significant correlation APD measurement [3, 4].
In 2014 a panel of eight societies with a spe-
cial interest in the diagnosis and management of
fetuses and children with UT dilation agreed to
collaborate on the development of a unified grad-
M. Maffi · M. Lima (*)
ing system for perinatal UT dilation (UTD sys-
Department of Pediatric Surgery, S.Orsola Hospital,
Bologna University, Bologna, Italy tem) and propose a standardize scheme for
e-mail: [email protected] follow-up evaluation [5]. This is a six-item

© Springer Nature Switzerland AG 2019 515

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_40
516 M. Maffi and M. Lima

Table 40.1 Definition of antenatal hydronephrosis grading system that considers the following ultra-
(ANH) by APD
sound findings in relation to age: ADP, calyceal
Degree of ANH Second trimester Third trimester dilatation, parenchymal thickness, parenchymal
Mild 4 to <7 mm 7 to <9 mm appearance, ureter visibility, and bladder aspect.
Moderate 7 to ≤10 mm 9 to ≤15 mm
A further prenatal item is represented by unex-
Severe >10 mm >15 mm
plained oligohydramnios. In normal fetuses,

a
b

Fig. 40.1  Ultrasonographic appearance of urinary tract fills extrarenal pelvis; major calyces dilated; (d) SFU
dilation according to SFU system. (a) SFU grade 0, no grade 3, SFU gr2 and minor calyces uniformly dilated and
splitting; (b) SFU grade 1, urine in pelvis barely split parenchyma preserved; (e) SFU grade 4, SFU gr3 and
sinus; (c) SFU grade 2, urine fills intrarenal pelvis/urine parenchymal thinning (segmental 4A or diffuse 4B)
40  Congenital Ureteropelvic Junction Obstruction 517

calyceal dilation is absent, renal parenchyma has 40.3 Embryogenesis

a normal thickness and appearance, ureter is not
visible, bladder is normal, and there isn’t oligo- At 4th week of GA, primitive structures such as
hydramnios. Normal APD measures <4  mm at cloaca and mesonephros have been formed. At
<28-week gestation, <7  mm at ≥28  weeks, 5th week of GA, the ureteral bud, an extroflection
and < 10 mm postnatally. When UTD is detected of the mesonephric duct, grows in cranial direc-
antenatally (denoted as A for antenatal), it’s pos- tion until penetrating the metanephric blastema.
sible to identify a low-risk group (UTD A1) and The interaction between these structures leads
an increased risk group (UTD A2-3). Postnatally to renal development. The ureteral bud induces
detected UTD is denoted by P, and patients are the metanephric blastema to form specialized
stratified in low-risk (UTD P1), intermediate-risk nephrons and is induced to form the pelvis, the
(UTD P2), and high-risk (UTD P3) groups. The calices, and the collecting ducts. From the 10th to
features of each group are summarized in the 12th week of GA, urine begins to be produced
Table 40.3. and to pass in the bladder [4].
From the 18th to the 20th week, virtually all
Table 40.2  The Society for Fetal Urology amniotic fluid is made up of fetal urine. Atypical
Hydronephrosis Grading System (http://www.uab.edu/ muscular cells, located in the minor calices, act as
images/peduro/SFU/sfu_grading_ on_web/sfu_grading_ pacemaker sites. The peristaltic wave propagates
on_web.htm) through the major calices and activates the mus-
Pattern of renal sinus splitting cles of the renal pelvis that push the urine in distal
SFU grade 0 No splitting direction. The UPJ represents the transition point
SFU grade 1 Urine in pelvis barely split sinus in which the pyelic peristaltic activity, character-
SFU grade 2 Urine fills intrarenal pelvis/urine fills
extrarenal pelvis; major calyces dilated
ized by short and frequent waves, turns into ure-
SFU grade 3 SFU gr2 and minor calyces uniformly teral peristaltic activity characterized by wide and
dilated and parenchyma preserved slow waves. When the endopyelic pressure over-
SFU grade 4 SFU gr3 and parenchymal thinning comes ureteral pressure, the UPJ initially opens,
(segmental 4A or diffuse 4B) pushing the urine toward the ureter, and then

Table 40.3  UTD classification system

Prenatal presentation Postnatal presentation
APD 16–27 ≥28 weeks 16–27 ≥28 >48 h APD >48 h APD >48 h APD
weeks 4 to 7 to weeks weeks 10 to ≥15 mm ≥15 mm
<7 mm <10 mm ≥7 mm >10 mm <15 mm
Calyceal dilation Central or no calyceal Peripheral calyceal Central Peripheral Peripheral
dilation dilation calyceal calyceal calyceal
dilation dilation dilation
Parenchymal Normal Abnormal Normal Normal Abnormal
thickness
Parenchymal Normal Abnormal Normal Normal Abnormal
appearance
Ureter Normal Abnormal Normal Abnormal Abnormal
Bladder Normal Abnormal Normal Normal Abnormal
Oligohydramnios No Unexplained – – –
oligohydramnios
UTD A1 UTD A2-3 UTD P1 UTD P2 UTD P3
Low risk Increased risk Low risk Intermediate High risk
risk
518 M. Maffi and M. Lima

closes, avoiding the ureteral contraction to cause with antenatal hydronephrosis are affected by
reflux into the pelvis. A premature stop of ureteral UPJ obstruction) [4]. It is most common in males
muscle development would lead to an adynamic with an M/F ratio of 2–3:1 and mostly affects the
segment without peristalsis at the UPJ level. left side (L/R  =  2:1). In 15–35% of cases, it is
bilateral [7–10].
UPJ obstruction may be associated with other
40.4 Etiology and genitourinary anomalies such as horseshoe kid-
Physiopathology [6] ney or be a component of a syndrome such as
CHARGE (coloboma, heart anomaly, choanal
UPJ obstruction can be dividend in intrinsic and atresia, retardation, genital and ear anomalies)
extrinsic forms. In intrinsic forms, a variable por- [11, 12].
tion of UPJ is stenotic or kinked as the ureter enters
the pelvis. The urothelial lining is normal but the
number of parietal smooth muscular cells is 40.6 Differential Diagnosis
reduced with an increased proportion of collagen
between muscle fibers, an increased proportion of UPJ obstruction belongs to congenital anomalies
elastin in adventitious, and a rearrangement in the of the kidney and urinary tract (CAKUT). All
orientation of muscle fibers, with predominant lon- these conditions may present in prenatal age with
gitudinal arrangement. This hypoplastic and ady- hydronephrosis as the main feature. CAKUT rep-
namic segment is able to discharge urine at low resent the cause of prenatal hydronephrosis in
pressures, but cannot adequately respond to an one third of patients [13]. UPJ obstruction is the
increase in workload with progressive dilation of most common cause of hydronephrosis, but sev-
renal pelvis. The high compliance of renal pelvis in eral other causes of hydronephrosis can be
the fetal age and in the first years of life explains identified:
the occurrence of severe hydronephrosis not asso-
ciated with high intrapelvic pressure and secondary • Megaureter
renal damage. Other rare forms of intrinsic obstruc- • Multicystic dysplastic kidney
tion are due to the presence of mucous valve or ure- • Ureterocele
teral polyps or the persistence of convoluted fetal • Posterior urethral valves
ureter. In 10–20% of patients, obstruction of the • Ectopic ureter
UPJ is extrinsic, mostly due to the presence of an • Prune-belly syndrome
inferior polar abnormal vessel that intersects the • Urachal cyst
UPJ anteriorly. Extrinsic compression causes a • Duplex collecting system
progressive alteration of the ureteral wall, decreas- • Urethral atresia
ing the number of myocytes, fibrosis and deposi-
tion of collagen with consequent stenosis of the
lumen. During correction of hydronephrosis due to 40.7 Clinical Manifestation
abnormal vessel, therefore, it is necessary to check
patency and function of UPJ after displacement of With the advent of fetal ultrasound, the diagnosis
the crossing vessel. Less frequently, extrinsic of hydronephrosis is basically prenatal. In
obstruction is caused by connective bands or adhe- patients without early diagnosis, symptoms can
sions between pelvis and ureter. be varied and complex. In the neonatal age, a pal-
pable abdominal mass can represent the first and
only clinical sign. Classical symptoms may be
40.5 Epidemiology urinary tract infection, hematuria, and food
refusal.
The UPJ obstruction has an incidence of 1:500 In older children, sometimes, the first episode
live births and represents the major cause of is a renal colic or a pain localized at flank. In
primitive hydronephrosis (10–30% of patients case of bilateral severe hydronephrosis or single
40  Congenital Ureteropelvic Junction Obstruction 519

kidney, clinical manifestation can be dominated is evaluated by calculating the T1/2, i.e., the time
by symptoms of renal failure. needed to eliminate 50% of the radionuclide. A
T1/2 greater than 20 min is indicative of obstruc-
tion, and a T1/2 between 15 and 20 min is con-
40.8 Diagnosis sidered doubtful. The T1/2 evaluation is
influenced by several factors: technique, hydra-
At birth, a diagnostic work-up is required to eval- tion status, renal function, and anatomy
uate the actual presence and entity of dilation, (Fig.  40.2). Renal scintigraphy should be per-
identify the underlying cause, and asses the renal formed at about 3–4  weeks of life, as kidney
function. The diagnostic tools essential to obtain immatureness of the newborn results in reduced
these information are represented by renal ultra- glomerular filtration and a lower diuretic
sonography (RUS), voiding cystourethrography response.
(VCUG), and diuretic renal scintigraphy.

40.8.3  Voiding Cystourethrography

40.8.1  Postnatal Ultrasound
Voiding cystourethrography (VCUG) consists in
Postnatal ultrasound should be performed by the acquiring radiographs after filling the bladder with
first week of life; RUS performed in the first 48 h a contrast medium through a transurethral catheter.
of life may underestimate the entity of hydrone- Adequate bladder filling can be used to detect ves-
phrosis due to transient dehydration status with ical abnormalities and the presence of passive
reduced glomerular filtration and diuresis restric- reflux. The voiding phase shows active VURs,
tion. RUS allows assessment of pelvic and caly- studies the urethral morphology, and evaluates the
ceal dilation, thickness of the renal pelvis, possible proper bladder emptying. Voiding urosonography
presence of ureteral dilatation, and the condition (VUS) is an alternative to VCUG. It is performed
of the contralateral kidney and urinary tract. It also by a trans-catheter injection into the bladder of an
provides information on the bladder. In case of eco-amplifier contrast medium that allows visual-
UPJ obstruction, the ureter typically has a normal ization of any reflux. It offers the advantage of
diameter and cannot be visualized during RUS. In avoid radiation exposure but has limits in provid-
case of hydroureteronephrosis, the concomitant ing morphologic informations of the urinary tract.
presence of ureteral dilation is classified according
to the ureteral diameter in grade 1 (<7 mm), grade
2 (7–10 mm), and grade 3 (> 10 mm). 40.8.4  Intravenous Urography

Intravenous urography allows, in doubtful cases,

40.8.2  Diuretic Renal Scintigraphy a better definition of anatomical details. In pedi-
atric age, it is currently underutilized because of
Diuretic renal scintigraphy is performed by high radiation exposure.
intravenous infusion of a radionuclide, 99mTc
DTPA (Tc99m-diethylenetriamine pentaacetic
acid) or preferably 99mTc-MAG3 (99mTc-­ 40.8.5  Magnetic Resonance
mercaptoacetyltriglycine), followed by the Imaging
administration of a diuretic (furosemide). While
being less accurate in defining renal function Magnetic resonance imaging of the urinary sys-
than DMSA scintigraphy, the diuretic renal scin- tem (Uro-RM) can provide accurate anatomical
tigraphy allows to evaluate urinary flow in and functional details. It has the advantage of not
response to diuretic administration, distinguish- using ionizing radiation but has the disadvantage
ing obstructing or non-obstructing forms of uri- of requiring general anesthesia in smaller patients
nary tract dilatations. The degree of obstruction [14–16].
520 M. Maffi and M. Lima

Fig. 40.2  Diuretic scintigraphy showing a persistent stasis of the radiopharmaceutical in the right pelvis

40.9 Postnatal Management Surgery is indicated in cases of DRF <40%

According to SFU with a further reduction of DRF >5% in patients
Classification with baseline differential renal function <40%.

40.9.1  S
 FU I and II Monolateral
Hydronephrosis 40.9.2  S
 FU III and IV Unilateral
Hydronephrosis
RUS during the first week of life (>48 h of life)
and VCUG at about 1 month. In the absence of RUS during the first week of life (>48 h of life)
VUR, RUS follow-up is performed every and VCUG at about 1 month. Antibiotic prophy-
3 months during the first year of life. If VUR is laxis and MAG3 diuretic renal scintigraphy are
diagnosed, antibiotic prophylaxis is set, and performed at 4–6  weeks. In presence of
scintigraphic examination to evaluate differen- DRF >40%, RUS will be scheduled every 3 months
tial renal function (DRF) is performed at and a MAG3 diuretic scintigraphy at 6 months. In
4–6 weeks. If DRF <40% or there is a worsening presence of DRF <40%, RUS and MAG3 scintig-
of the ultrasound findings, it may be useful to raphy at 3  months will be scheduled. In case of
repeat RUS and MAG3 diuretic scintigraphy at significant symptomatology, worsening of clinical
3 months. Conservative treatment is indicated in features, or reduction of DRF >10% compared to
small children with DRF >40% and good famil- the baseline value during follow-up, it is recom-
ial “compliance.” mended to undergo early surgery.
40  Congenital Ureteropelvic Junction Obstruction 521

40.9.3  Bilateral Hydronephrosis follow-up can be closer, with more than two
SFU III and IV prenatal RUS and early postnatal evaluation
(always at more than 48 h of life).
The management of bilateral hydronephrosis is
similar to that of monolateral hydronephrosis of
the same degree but varies in the execution time 40.10.2  Postnatally Detected
of the VCUG that must be performed during the Hydronephrosis
first 24–48  h of life, to exclude lower urinary
tract obstructions (LUTO). In addition, since In case of UTD P1, follow-up RUS is recom-
accurate assessment of differential renal function mended at 1–6  months. Antibiotic prophylaxis
in a bilateral hydronephrosis is difficult to define, and VCUG are at discretion of clinician, while
it is desirable to select lower DRF threshold val- functional scan is not recommended.
ues ​​to indicate surgical correction in order not to In case of UTD P2, follow-up RUS is recom-
further impair renal function. mended at 1–3  months. Antibiotic prophylaxis
and VCUG and functional scan are at discretion
of clinician.
40.9.4  Criteria for Surgical In case of UTD P3, follow-up RUS at 1 month,
Correction antibiotic prophylaxis, and VCUG are
­recommended, while functional scan is at discre-
The main criteria for surgical correction are: tion of clinician.
Further research will be needed to correlate
–– DRF <40% the UTD classification system risk stratification
–– Reduction of DRF >5% to other specific clinical outcomes such as surgi-
–– Worsening of hydronephrosis cal intervention, renal function, urinary tract
–– Severe monolateral hydronephrosis (AP infection, and others. Currently it’s possible to
diameter >50 mm) convert the existing grading system to the UDT
–– Severe hydronephrosis in single kidney classification. For example, SFU grade 1e2
–– Severe bilateral hydronephrosis (AP diameter would be equivalent to UTD P1, SFU grade 3 to
>30 mm) UTD P2, and SFU grade 4 to UTD P3.
–– Urinary tract infections, symptomatic
hydronephrosis
40.11 Surgical Treatment

40.10 Management In selected and extreme cases, antenatal decompres-

of Hydronephrosis sion of hydronephrosis can be considered to prevent
According to UTD System [5] dystocic delivery or fetal pulmonary compression.
While in most of cases, surgical treatment can
40.10.1  Antenatally Detected be delayed beyond neonatal age. Nevertheless,
Hydronephrosis following are reported the possible surgical
approaches to UPJ obstruction.
If UTD A1 is diagnosed before 32 weeks, a fur-
ther RUS at ≥32 weeks is recommended. If the
second RUS is normal, no further evaluation is 40.11.1  A
 nderson–Hynes Pyeloplasty
necessary. If UT is persistent after 32  weeks, a (Dismembered Pyeloplasty):
postnatal evaluation is recommended whatever is Open Approach
the risk group. After birth, two additional RUS
are recommended: the first between 48 h of life The almost universally used technique is a dis-
and 1 month and the second 1–6 months later. In membered pyeloplasty. It consists of excision of
case of UTD A2-3, the prenatal and postnatal the UPJ stenotic tract, part of the pelvis, and the
522 M. Maffi and M. Lima

proximal ureter. The classical approach is lombo- the pelvis is identified and isolated. The proce-
tomic extraperitoneal. The patient lays in lateral dure is then performed as in open approach. In
decubitus and an incision is made at the tip of the newborn, retroperitoneoscopic approach is lim-
12th rib. Parietal muscles are divided bluntly ited by the little working space.
according to fiber direction. This approach pro-
vides direct exposure of the renal hilum. A trac-
tion stich is placed in the anterior portion of the 40.11.4  Robotic Surgery
pelvis, proximal to the planned section line, and a
second traction stich is placed in the anterior por- Robot-assisted approach is similar to laparo-
tion of the upper ureter, distal to the stenotic tract. scopic approach, but it provides a greater preci-
These two stiches will act as landmarks to avoid sion and wider degrees of freedom than
the twisting of the anastomosis. The redundant conventional laparoscopic instruments.
pelvis is resected, the obstructed UPJ is removed, Nevertheless, robotic instruments are still too big
and the proximal ureter is spatulated on its infe- (8 mm for Da Vinci Xi and 5 mm for Da Vinci Si
rior (posterior) border in order to obtain a wide but with limited movements and variety of tools)
anastomosis. The anastomosis is performed by and require too much distance from each other (at
placing the first stitch between the inferior part of least 6–7 cm) to be placed in a newborn, so neo-
the spatulated ureter and of the transected pelvis natal experiences are still limited.
and proceeding up either side with running suture
using 6-0 or 7-0 monofilament absorbable
sutures. Before completion of the anastomosis, a 40.11.5  One–Trocar–Assisted
trans-anastomotic stent is placed [17]. Pyeloplasty (OTAP)

One-trocar-assisted pyeloplasty is a technique

40.11.2  Laparoscopic Approach that combines the principles of open approach
with those of retroperitoneoscopic minimally
The patient lays in slight lateral decubitus. The invasive surgery (Fig. 40.3). This technique pro-
first 5 mm trocar is placed in the umbilicus, and vides retroperitoneoscopic access to the renal
two additional 3–5 mm trocar are placed in epi- loggia using one 10  mm trocar for operative
gastrium (lower rib margin) and in the lower infe- optics, subsequent GPU identification, exterior-
rior quadrant (iliac crest) of the side to be treated. ization through the surgical incision, and pyelo-
The pelvis can be reached after mobilization of plasty following the Anderson-Hynes open
colic flexure or with transmesocolic approach. technique [18].
Once the pelvis is suspended, the pyeloplasty is The surgical incision, about 1  cm length, is
performed following the principles of the open made at the tip of the 12th rib. Through the inci-
technique. sion, the retroperitoneal space is reached, and the
Gerota fascia is opened. The self-anchoring
10  mm trocar is introduced, and CO2 is insuf-
40.11.3  Retroperitoneoscopic flated, with an 8 mmHg pressure and a 0.5 L/min
Approach flow. The working space is created with the help
of a laparoscopic swab; the ureter is identified
This approach follows the principles of the open and isolated using the psoas muscle as a land-
approach. The patient is placed in lateral decubi- mark. Following the ureter, the lower renal pole
tus. The skin incision, for the first 5 mm trocar, is and the pelvis are identified. A rubber band is
performed at the tip of the 12th rib. Two further introduced to surround the ureter, and it is exteri-
3 mm trocars are placed, at the spino-costal edge orized together with the UPJ. If the pelvic dila-
and immediately above the iliac crest, respec- tion is severe, it can be emptied by an evacuation
tively. The kidney is approached posteriorly, and puncture. The technique proceeds as in the open
40  Congenital Ureteropelvic Junction Obstruction 523

approach with the resection of the obstructed is then replaced in the retroperitoneal space, and
tract and the redundant pelvis followed by the the anastomosis is checked endoscopically.
suture with 6-0 or 7-0 monofilament absorbable If a pyelostomic or nephrostomic stent has
suture. Before the completion of anastomosis, a been placed, it will be removed, in the fifth post-
trans-anastomotic stent such as Mazeman-Porges operative day, while the J-J stent will be removed
or a J-J or Pippi-Salle stent is placed. The pelvis by cystoscopy after 4–6 weeks.

a b

Fig. 40.3  One-trocar-assisted pyeloplasty  – OTAP. (a) stenotic tract and starting of the anastomosis; (d) ureteral
Endoscopic view of the ureter that is identified and iso- stent placement; (e) endoscopic check of the pyeloplasty
lated; (b) exteriorization of the UPJ; (c) removal of the at the end of the procedure
524 M. Maffi and M. Lima

40.11.6  Postoperative Follow-Up 5. Nguyen HT, Benson CB, Bromley B, Campbell JB,
Chow J, Coleman B, Cooper C, Crino J, Darge
K, Herndon CD, Odibo AO, Somers MJ, Stein
RUS is indicated 4–6  weeks after surgery. If the DR.  Multidisciplinary consensus on the classifi-
investigation detects an improvement (reduction cation of prenatal and postnatal urinary tract dila-
of the hydronephrosis), seriated RUS is performed tion (UTD classification system). J Pediatr Urol.
2014;10(6):982–98. https://doi.org/10.1016/j.
at increasing time intervals (initially every jpurol.2014.10.002.
3  months, then annually, and every 2–3  years) 6. Shulam PG. Ureteropelvic junction obstruction. http://
[19]. If the follow-up RUS does not show any kidney.niddk.nih.gov/statistics/uda/Ureteropelvic_
improvement, a MAG3 scintigraphy is indicated Junction_Obstruction-Chapter09.pdf. Accessed 22
Apr 2010.
to evaluate the possible recurrence of obstruction. 7. Koff SA, Mutabagani KH.  Anomalies of the kid-
ney. In: Gillenwater JY, Grayhack JT, Howards SS,
Mitchell ME, editors. Adult and pediatric urology. 4th
40.11.7  Complications ed. Philadelphia: Lippincott Williams and Wilkins;
2002. p. 2129.
8. Liang CC, Cheng PJ, Lin CJ, et al. Outcome of prena-
Outcomes of open dismembered pyeloplasty are tally diagnosed fetal hydronephrosis. J Reprod Med.
excellent, with resolution of the obstruction in 2002;47:27.
90–95% of cases, including newborns [20, 21]. 9. Morin L, Cendron M, Crombleholme TM, et  al.
Minimal hydronephrosis in the fetus: clinical sig-
Among the possible early complications of inter- nificance and implications for management. J Urol.
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conservative with or without drainage and antibi- the clinical outcome of antenatally detected uni-
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otic coverage. The most significant long-term com- 2013;82:691.
plication is represented by the recurrence of 11. Cascio S, Sweeney B, Granata C, et al. Vesicoureteral
obstruction, which may require re-intervention reflux and ureteropelvic junction obstruction in chil-
(5% of cases). dren with horseshoe kidney: treatment and outcome. J
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12. Ragan DC, Casale AJ, Rink RC, et al. Genitourinary
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 Multicystic Dysplastic Kidney
41
Michela Maffi and Mario Lima

41.1 Introduction and Definition According to the first theory, pelvic-ureteral

atresia leads to severe obstruction with massive
Multicystic dysplastic kidney (MCDK) is the most hydronephrosis and MCDK, but according to
common cystic renal anomaly found in children others, the result would be a major hydronephro-
and the second cause of palpable mass in neonates sis and not cystic dysplasia [2].
after hydronephrosis. The kidney is characterized The second theory argues that MCDK derives
by the presence of multiple non-­communicating from an altered interaction between the ureteric
cysts in absence of normal parenchyma. bud and metanephric blastema [3].
The interaction between the metanephros and
the ureteric bud stimulates organogenesis that
41.2 Epidemiology hesitates in the formation of the nephrons and
collector systems. When this interaction is
The estimated incidence of MCDK ranges from altered, the final architecture of the renal paren-
1 in 1000 to 1 in 4300 live births, and males are chyma will be subverted.
slightly more affected than females (M/F = 2.4:1) A recent study identified some genes to be
[1]. The MCDK is generally unilateral with the mutated in children with MCDK: CHD 1L,
left side more affected than the right one, but ROBO2, HNF 1B, and SALL1 genes [4].
there are cases of bilateral MCDK which are Another less accredited theory attributes a role
mostly incompatible with life since renal tissue to exposure to teratogens such as viral agents
has minimal or no activity. In 60–80% of cases, it (cytomegalovirus, adenovirus, enterovirus) or
is diagnosed prenatally [1, 2]. medicaments during pregnancy (antiepileptics)
that can cause malformations of the urinary tract
among which MCDK [1].
41.3 Etiology

The etiology of MCDK is still not clarified; how- 41.4 Associated Anomalies
ever, there are two predominant theories.
The incidence of associated anomalies ranges
from 5 to 48% [1, 2, 6]. MCDK can be associated
M. Maffi ∙ M. Lima (*) with several anomalies involving the contralateral
Department of Pediatric Surgery, S.Orsola Hospital,
University of Bologna, Bologna, Italy urinary tract such as rotational or positional anom-
e-mail: [email protected] alies, hypoplasia, areas of dysplasia, vesicoureteral

© Springer Nature Switzerland AG 2019 527

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_41
528 M. Maffi and M. Lima

reflux (VUR) (7–26%), ureteropelvic junction 41.5.2 Postnatal Presentation

obstruction (UPJO) (1.5–5%), ureterovesical junc-
tion obstruction (2%), ureterocele, horseshoe kid- The patient may be totally asymptomatic, and the
ney, or genital anomalies [1, 2, 5–10]. diagnosis can be done occasionally during an
Extrarenal associated anomalies include heart ultrasound examination performed for other
defects, esophageal or intestinal atresia, neural reasons.
tube defects (myelomeningocele), and The most common clinical presentation is a
aneuploidy. palpable abdominal mass in the neonatal age.
The surface is typically irregular in contrast to
what happens in case of hydronephrosis or poly-
41.5 Diagnosis cystic kidney disease. The contralateral kidney, if
not dysplastic, is generally enlarged by compen-
41.5.1 Prenatal Diagnosis satory hypertrophy.

About 60–80% of cases of unilateral MCDK are

detected with prenatal ultrasound. The classical 41.6 Natural History
appearance of MCDK is an abdominal mass con-
sisting of multiple thin-walled cysts of different
The natural evolution of the MCDK is the spon-
size, not communicating with each other taneous involution. The complete involution may
(Fig.  41.1). The kidney is usually enlarged and
take place during fetal life and is greater in early
irregular, with no visible pelvis, atretic or absent
life. The rate of involution ranges from 35 to 62%
ureter, and small or absent renal artery. by 10  years of age, and if complete involution
Parenchymal tissue between the cysts is oftendoes not occur, the MCDK may decrease in size
hyperechogenic, and the kidney may reduce in (30–44%) or remain stable (13–34%). Initial size
size during pregnancy. less than 5–6 cm seems to be predictive of com-
Sometimes the ultrasonographic appearanceplete involution [1, 2, 6].
can be confused with an important hydronephro- The RVU, frequently present in the contralat-
sis, but in this case, the cysts communicate each
eral kidney, is in 90% of cases of low grade (<of
other and parenchyma can be seen. Rare case of
grade III) and very rarely requires treatment
Wilms tumor, multilocular cyst, or cystic meso-
[11].
blastic nephroma can have a similar aspect to The MCDK was once accused of being the
MCDK. cause of hypertension. In fact different studies
showed that only a very small proportion of
patients develop hypertension with a rate ranging
from 1.5 to 6% [2, 10, 12–14], but above all,
nephrectomy resulted in the resolution of hyper-
tension in 25–50% of cases [3].
Among the theoretical risks of MCDK is
malignant degeneration. In particular it has been
suggested an association with the occurrence of
Wilms tumor. Again, although some cases have
been reported, several reviews reported no
malignancies in patients with MCDK [2, 11,
15]. We can argue that the total risk of Wilms
tumor in MCDK is not increased if compared to
the general population and not sufficient to indi-
Fig. 41.1 RUS in MCDK showing multiple non-­ cate a prophylactic nephrectomy in a healthy
communicating cysts patient.
41  Multicystic Dysplastic Kidney 529

41.7 Management A possible algorithm recommends a postnatal

RUS and one at 1 year of age with any other imag-
According to these data, the most correct ing investigation guided by any abnormality of the
approach in case of MCDK is a conservative contralateral urinary tract, abnormal blood pressure,
management based on ultrasound monitoring of or increase in dimension of MCDK [2]. Another
the kidney and the management of associated more widely accepted algorithm recommends per-
anomalies of the contralateral kidney. Currently forming RUS at birth, 4 weeks, 2 years, 5 years, and
the debate regards imaging modality, frequency, 10 years of age [18]. In all cases, follow-up should
and duration of follow-up. In particular, the ques- be completed by routine blood pressure measure-
tioned topics involve the need for a confirmatory ment, urinalysis to detect proteinuria, and renal
renal scan and for a routine voiding cystourethro- function studies (e.g., serum creatinine) especially
gram (VCUG) and the frequency and duration of in patients with contralateral abnormalities that may
ultrasonographic follow-up. develop chronic renal disease [19, 20].
In the past years, a routine renal scan was per- Currently, nephrectomy is not part of the nor-
formed to confirm absence of function of the mal management of MCDK; however, it can be
affected kidney (Fig. 41.2). Recently, in order to indicated in selected cases:
avoid radiation exposure, several studies have
investigated the benefits of carrying out this • Symptoms caused by compression: large or
investigation, concluding that renal ultrasounds increasing in size MCDK, can lead to intesti-
(RUS) are able to diagnose almost all cases of nal compression. Although it has been called
MCDK, so renal scan should be reserved for into question the possible decompression,
doubtful cases [16]. nephrectomy is still one option for treatment.
Similarly, VCUG should be reserved to • Other symptoms: in a minority of cases, the
patients with contralateral hydroureteronephrosis patient may complain of pain, hematuria,
or signs and symptoms of a UTI as most cases of recurrent infections, and hypertension. This
VUR in MCDK with normal RUS are not clini- can also be an indication for surgery [21].
cally significant [2, 5, 17]. • Equivocal diagnosis: in case of uncertainty, it
should be considered that the patient may
have another potentially life-threatening dis-
ease such as cystic Wilms tumor [22].

41.8 Nephrectomy

The approach to the kidney is traditionally extra-

peritoneal although it can also be approached
transperitoneally. The nephrectomy can be per-
formed with open or minimally invasive surgery,
laparoscopic or retroperitoneoscopic, and robotic.
In the open approach, the patient lays in the
lateral decubitus with the shoulders rotated
slightly forward and the pelvis rotated slightly
back. The incision is performed at the apex of the
12th rib. Parietal muscles are divided by blunt
dissection following fibers direction. Then the
Gerota fascia is opened exposing the kidney.
Fig. 41.2  DMSA renal scan showing absence of function Vessels and ureter are then isolated and dissected.
of right kidney affected by MCDK disease The evacuation by puncture of the cysts can facil-
530 M. Maffi and M. Lima

a b

c d

Fig. 41.3  One-trocar-assisted nephrectomy: (a) patient position; (b) operative setup and trocar placement; (c) retro-
peritoneoscopic appearance of MCDK; (d) exteriorization of the MCDK

itate the identification of the hilum and thus the References

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peritoneoscopic with the patient in the prone dysplastic kidney. Curr Urol Rep. 2015;16:67.
2. Eickmeyer AB, Casanova NF, He C, et al. The natu-
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AL. Management and etiology of the unilateral mul-
of the open approach, and the incision is per- ticystic dysplastic kidney: a review. Pediatr Nephrol.
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but has minimum extension, just to allow the 4. Hwang DY, Dworschak GC, Kohl S, et al. Mutations
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identified and, after emptying the cysts, pulled F, Hall M. Routine voiding cystourethrography is of
out through the incision and removed as in open no value in neonates with unilateral multicystic dys-
plastic kidney. J Pediatr. 2005 Jun;146(6):759–63.
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eral RVU, it is essential to remove the ureter as multicystic dysplastic kidney-what followup is
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7. Guarino N, Casamassima MG, Tadini B, Marras E, https://doi.org/10.1016/j.jpurol.2014.03.011. Epub

Lace R, Bianchi M. Natural history of vesicoureteral 2014 May 2.
reflux associated with kidney anomalies. Urology. 17. Calaway AC, Whittam B, Szymanski KM, Misseri
2005;65(6):1208–11. R, Kaefer M, Rink RC, Karymazn B, Cain
8. Merrot T, Lumenta DB, Tercier S, Morisson-­ MP.  Multicystic dysplastic kidney: is an initial
Lacombes G, Guys JM, Alessandrini P.  Multicystic voiding cystourethrogram necessary? Can J Urol.
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genitourinary tract: experience in children. Urology. 18. Aslam M, Watson AR, Trent & Anglia MCDK Study
2006 Mar;67(3):603–7. Group. Unilateral multicystic dysplastic kidney: long
9. Atiyeh B, Husmann D, Baum M. Contralateral renal term outcomes. Arch Dis Child. 2006;91(10):820–3.
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10. Moralıoğlu S, Celayir AC, Bosnalı O, Pektaş OZ, Vermeulen A, Dekker-van der Meer IM, Bökenkamp
Bulut IK.  Single center experience in patients with A, Van Wijk JA.  Ambulatory blood pressure moni-
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 Vesicoureteral Reflux
42
Michela Cing Yu Wong and Girolamo Mattioli

42.1 Definition of reflux is statistically greater in girls (23%) than

boys (16%) for anatomical reasons [6]. Siblings
Vesicoureteral reflux (VUR) is an anatomical of children with VUR have a 27.4% (3–51%) risk
and/or functional disorder characterised by back- of also having VUR, whereas the offspring of
flow of urine from the bladder into the ureter and, parents with VUR have a higher incidence of
sometimes, in the renal collecting system. 35.7% (21.2–61.4%) [6].
Urinary tract infection (UTI) associated with Within children with UTIs, the incidence of
VUR predisposes the child to acute pyelonephri- VUR is much higher (30–50%, depending on
tis and possible subsequent renal scars, hyperten- age). UTIs are more common in girls than boys
sion and renal failure [1–3]. VUR can be primary due to anatomical differences [1]. By the age of
or secondary to a urethral obstruction (e.g. in 6  years, 2% of boys and 8% of girls will have
case of posterior urethral valves—PUVs). PUVs experienced a UTI [7]. Most infections occur
are a congenital obstruction of the posterior ure- during the first 2 years of life, with boys dominat-
thra and are considered one of the few life-­ ing during the first 6 months and girls thereafter
threatening congenital anomalies of the urinary [8, 9]. Specific risk factors for acute pyelonephri-
tract found during the neonatal period [4]. tis and renal scarring in patients with VUR
include a higher grade of reflux, dysfunctional
voiding/elimination, recurrent pyelonephritic
42.2 Epidemiology episodes and delayed initiation of antibiotic ther-
apy [10]. Untreated recurrent UTIs may have a
VUR is the most common urologic anomaly in negative impact on somatic growth and medical
children and affects 1% of children [1–3]. The status of the child. It is important to underline
true prevalence is hard to determine as VUR can that renal scarring in patients with VUR is the
also be asymptomatic. The prevalence of VUR in result of both the congenital dysplasia and
non-symptomatic children has been estimated at acquired postinfectious damage [10].
0.4–1.8% [5]. Among infants with prenatal Primary VUR is a disease with a good sponta-
hydronephrosis on ultrasonography (US), the neous resolution. It depends on age at presenta-
prevalence of VUR is 16.2% [6]. The prevalence tion, sex, VUR grade, laterality, mode of clinical
presentation and ureteral anatomy [11].
M. C. Y. Wong (*) · G. Mattioli Age <1 year at presentation, lower grade of reflux
Paediatric Surgery Unit, Istituto Giannina Gaslini, (grades 1–3), asymptomatic presentation with
DINOGMI University of Genoa, Genoa, Italy prenatal hydronephrosis or sibling reflux and
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 533

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_42
534 M. C. Y. Wong and G. Mattioli

single ureter are associated with significantly logic abnormality [19–21]. There is a significant
­earlier resolution of reflux. Spontaneous resolu- increase in risk per increasing degree of prenatal
tion is low for bilateral high-grade reflux [11]. hydronephrosis [20]. Several studies have tried to
Secondary VUR is usually caused by the pres- assess the threshold for diagnosing foetal hydro-
ence of PUVs. As this disorder develops early in nephrosis associated with persistent renal anoma-
gestation, the bladder and upper urinary tract are lies [22–24]. The most commonly accepted
exposed to high pressure throughout develop- values are those described initially by Corteville
ment. Despite optimal treatment, PUVs in chil- and colleagues: an anterior-posterior diameter
dren could result in renal failure in almost (APD) greater than or equal to 4  mm before
one-third of cases [12]. The incidence of PUVs 33 weeks’ gestation or 7 mm after 33 weeks’ ges-
has been estimated of 2.2 in 10,000 births, with tation allows the identification of 100% of foe-
up to 62% being diagnosed prenatally [4, 13]. tuses that ultimately will have impaired renal
Despite their rarity, PUVs present such a severe function or require surgery [24].
insult to the upper urinary tract that they account To characterise the dilatation of the collecting
for almost 17% of children with end-stage renal system and correlate foetal hydronephrosis with
failure [14, 15]. postnatal clinical relevance, the Society for Fetal
Urology (SFU) developed a grading scale for
foetuses older than 20  weeks’ gestation [25]
42.3 Clinical Presentation (Table 42.1):
and Diagnostic Pathway
• Grade 0: no hydronephrosis.
VUR clinical presentation could be variable. The • Grade 1: the renal pelvis only is visualised.
clinical pictures are [1]: • Grade 2: hydronephrosis is present when a
few but not all calices are identified in addi-
1. Prenatal hydronephrosis. tion to the renal pelvis.
2. Siblings and/or offspring of patients with
• Grade 3: hydronephrosis requires that virtu-
VUR. ally all calices are seen.
3.
Febrile urinary tract infections/ • Grade 4: hydronephrosis may have a similar
pyelonephritis. appearance of the calices as grade 3 but, when
compared with the normal side, the involved
kidney has parenchymal thinning.
42.3.1 Prenatal Hydronephrosis
Neither the SFU grading scale nor APD has
The detection of congenital anomalies has the ability to specifically identify pathological
increased because of the widespread use of rou- cases. They remain indicators of ‘potential’ dis-
tine second trimester US.  One of the most fre- ease [26].
quently detected abnormalities is the dilation of In the presence of PUVs, antenatal US com-
the foetal renal collecting system, affecting monly demonstrates a distended thick-walled
1–4.5% of all pregnancies [16–18]. The prenatal bladder and a dilated posterior urethra (key-
detection of pelvis dilation is not always associ- hole sign), associated with monolateral/bilat-
ated with pathological conditions; in fact, these eral hydroureteronephrosis and sometimes
findings may instead reflect normal physiology oligohydramnios. This disorder may account
[17]. It is important to distinguish prenatal sono- for up to 10% of all prenatally detected hydro-
graphically evident renal pelvis (SERP) from nephrosis [13].
hydronephrosis, which consists also in calices After the birth, physical examination is usu-
dilation [16]. ally normal. Basic serum laboratory exams, spe-
Up to 64–94% of foetuses with prenatal SERP cifically creatinine, are not necessary for children
will ultimately have no identifiable postnatal uro- with unilateral prenatal hydronephrosis, but
Table 42.1  Hydronephrosis grading on ultrasound imaging
APD at >20 weeks gestation/
SFU grade Patterns of renal sinus splitting Grade calyceal dilation (13)
SFU 0 No splitting n/a
42  Vesicoureteral Reflux

SFU 1 Urine in pelvis barely splits 1 1 cm Normal calyces

sinus

SFU 2 Urine fills intrarenal pelvis or 2 1–1.5 cm calyces are normal

urine fills extrarenal pelvis and
major calyces dilated

(continued)
535
Table 42.1 (continued)
536

APD at >20 weeks gestation/

SFU grade Patterns of renal sinus splitting Grade calyceal dilation (13)
SFU 3 SFU grade 2 + minor calyces 3 >1.5 cm slight caliectasis
uniformly dilated and
parenchyma preserved

SFU 4 SFU grade3 + parenchyma 4 >1.5 cm moderate caliectasis

thinning

5 >1.5 cm with severe caliectasis

and thinning of the renal cortex
<2 mm thick

Table 42.1 [refers to 23, 24]—SFU hydronephrosis grading

SFU Society for Fetal Urology, APD anterior-posterior diameter
M. C. Y. Wong and G. Mattioli
42  Vesicoureteral Reflux 537

should be mandatory on those with bilateral 42.3.2 Siblings and/or Offspring

significant hydronephrosis associated with
­ of Reflux Patients
distended bladder and increased renal echo-
­
genicity as the risk of bladder outlet obstruction The screening of siblings and offspring of patients
(e.g. in case of PUVs) is higher with a more with VUR is very controversial. Siblings of
severe disease process [26]. The initial serum patients with VUR are at greater risk of having
creatinine reflects maternal renal function, but it reflux compared to the general population. It
could be useful as baseline value. Serum creati- seems that the incidence of sibling VUR is maxi-
nine for a term newborn should be 0.4 mg/dL by mal in patients who are younger than 3 years old.
day 7 of life [26]. In symptomatic siblings younger than 3  years
Imaging includes postnatal renal and bladder old, reflux is usually high grade and associated
US, voiding cystourethrogram (VCUG) and with a higher incidence of renal scarring [29].
diuretic renal scintigraphy [21, 27]. If PUVs are The screening is recommended in siblings
suspected, the postnatal US and VCUG should be younger than 3 years old of index patients with
performed immediately as the risk of renal insuf- grades III–V VUR [29]. In older asymptomatic
ficiency is high [26]. In the presence of PUVs, the siblings of index patients, the incidence is very
VCUG will demonstrate a dilated posterior ure- low, and the observation alone is the preferred
thra and trabeculated bladder, often vesicoure- option [30]. Other authors suggest the necessity
teral reflux, and the valve leaflets themselves of screening all siblings of index patients with
could be detected [4, 15]. It is important to have a VUR as the risk of nephropathy and renal scar-
voiding view of the urethra without the catheter ring is present also in asymptomatic older sib-
in order to make a complete evaluation of the ure- lings [31].
thra and to document all cases of valves [4, 15].
Current SFU guidelines suggest that a prena-
tal hydronephrosis diagnosed in the second tri- 42.3.3 Children with Febrile Urinary
mester that resolves on repeat ultrasound in the Tract Infections/
third trimester does not require postnatal evalua- Pyelonephritis
tion, while it is required in any cases of prenatal
hydronephrosis in the third trimester [28]. UTIs are the most common bacterial infections in
The postnatal US ideally should be per- young children with an incidence of renal scar-
formed between 5 and 30 days, as performing it ring of 15%. Children with VUR are significantly
in the first 2 days of life may underestimate the more likely to develop pyelonephritis and renal
degree of hydronephrosis due to the newborn’s scarring compared with children without VUR
oliguria [1, 26]. It is commonly recommended [32]. Infections caused by Escherichia coli are
that a follow-­up ultrasound after 1  month is the most common, although, in the first year of
necessary to confirm resolution. In infants with life, Klebsiella pneumoniae, Enterobacter spp.,
two normal successive scans, VUR is a rare Enterococcus spp. and Pseudomonas spp. are
entity, and, if present, it is likely to be low grade more frequent than later in life [33].
[1, 16, 27]. Signs and symptoms of UTIs are usually non-
US cortical abnormalities (as cortical thinning specific, especially in newborns. In young chil-
or increased echogenicity) are more common in dren fever may be the only symptom of UTIs. In
high-grade hydronephrosis and warrant the use newborns UTIs may manifest themselves as sep-
of VCUG for detecting VUR and/or PUVs [1]. sis with nonspecific signs and symptoms as poor
VCUG for VUR evaluation is recommended also weight gain, appetite loss, anorexia, vomiting,
in patients with bilateral high-grade hydroure- poor sucking, irritability, lethargy, convulsions
teronephrosis, duplex kidneys with hydronephro- and hypothermia [34]. In older children, lower
sis, ureterocele and abnormal bladders, because urinary tract symptoms include dysuria, fre-
the likelihood of VUR is much higher. quency, urgency, malodorous urine, incontinence,
538 M. C. Y. Wong and G. Mattioli

haematuria and suprapubic pain for the upper uri- ing acute pyelonephritis to allow acute reversible
nary tract, fever and flank pain [34]. lesions to resolve in order to detect definitive
The physical examination should be complete, renal scarring [35].
covering nutritional aspects, growth and psycho-
motor development. Laboratory tests include
C-reactive protein, blood cell counts and renal 42.4 Imaging
function, and, in severe cases, blood cultures
should also be taken [34]. Diagnosing UTIs The aim of the diagnostic work-up should be to
requires appropriate collection of uncontami- evaluate the overall health and development of
nated urine sample for uranalysis and urine cul- the child, the presence of UTIs, renal status, the
ture. It is recommended to collect urine in a clean presence and grading of VUR and the presence of
manner in children who are toilet-trained, while low urinary tract obstruction. A basic diagnostic
in infants and younger children, urine should be work-up comprises a detailed medical history
obtained by urinary catheterisation or suprapubic (including family history), physical examination
aspiration [35]. Urine culture remains the refer- including blood pressure measurement, urinaly-
ence standard for diagnosing UTIs, even if the sis (assessing proteinuria), urine culture and
results are not immediate [35]. Significant UTIs serum creatinine in patients with bilateral renal
are characterised by more than 105  CFU/ml of parenchymal abnormalities [1]. Currently there is
voided urine [34]. no consensus regarding the best imaging
In patients with UTIs, imaging techniques are approach after the first episode of febrile UTI. In
very important. The most effective diagnostic this context, Williams et al. suggest a simple and
strategy for children with UTI has been debated direct approach: (1) renal and bladder US in all
for several years, but no consensus has yet been children and (2) VCUG and/or DMSA for chil-
reached. Renal US is the first-line imaging exam dren with abnormal renal tract sonography.
if a UTI is suspected. It is useful for detecting
renal abscess, hydronephrosis, congenital abnor-
malities and sometimes stones, but it has a lower 42.4.1 Renal and Bladder Ultrasound
sensitivity for diagnosing pyelonephritis than (US)
dimercaptosuccinic acid renal scan—DMSA
[35]. Renal and bladder US is a non-invasive tool and
Two possible imaging strategies have been provides reliable information regarding bladder
proposed for the diagnosis of VUR in patients wall, kidney structure, size, parenchymal thick-
with UTI: the bottom-up method (VCUG and, if ness and collecting system dilation [1]. US is
positive, a DMSA scan) or the top-down method considered the first-line imaging exam in paedi-
(DMSA scan and, if positive, VCUG) [34, 36, atric population because of the lack of radiation,
37]. The American Academy of Pediatrics guide- low cost and easy access [26]. A good hydration
line recommends that VCUG should not be per- of the child should be required during the US,
formed routinely after the first febrile UTI [38]. and thus he is allowed to eat and drink normally
The EAU/ESPU guideline recommends that, for prior to this study [26]. As said, in patients with
infants under 1  year of age, VUR should be prenatal hydronephrosis, the postnatal US ideally
excluded by VCUG and/or DMSA scan [1]. A should be performed between 5 and 30 days, as in
VCUG is usually delayed for 2–4  weeks after the first 2 days of life, the neonatal oliguria may
successful UTI treatment to assess the presence lead to underestimate the degree of hydronephro-
of VUR and/or PUVs. Grade III, or higher, is sig- sis [1, 26], while when PUVs are suspected, the
nificantly associated with a higher risk of renal US should be performed immediately as the risk
cortical damage, and a DMSA scan should be of renal insufficiency is higher [26]. The follow-
considered to assess for renal scarring [33]. ing features must be carefully evaluated: renal
Usually a delay of 4–6 months is needed follow- parenchyma and size, degree of hydronephrosis,
42  Vesicoureteral Reflux 539

presence of associated ureteral dilation, dupli-

cated collecting systems, ectopic ureters or ure-
teroceles and bladder anatomy [1, 16].

42.4.2 Voiding Cystourethrogram

(VCUG)

VCUG is required to evaluate the anatomy and

capacity of the bladder, bladder neck and urethra
and to detect VUR (Figs. 42.1 and 42.2) [26]. In
the international scientific panorama, no agree-
ment on performing VCUG routinely has been
achieved. In fact, on the one hand, VCUG is con-
sidered the gold standard as it better characterises
VUR and permits evaluation of the urethra and
bladder [2]; on the other hand, an inappropriate
number of negative VCUGs and radiation expo-
sure could be avoided [39]. Lee et al. suggest this
Fig. 42.2  CUM image of a newborn of 3  days of age
with PUVs and consequent bilateral reflux

radiologic exam should be required only if the

US has one of the following three findings: pres-
ence of hydroureter, renal dysmorphia or dupli-
cation [39]. In 1985, the International Reflux
Study Committee introduced a uniform system
for the classification of VUR. It is based upon the
extent of filling and dilation by VUR of the ure-
ter, the renal pelvis and the calyces [40]
(Table 42.2):

42.4.3 Renal Cortical Scintigraphy

(Dimercaptosuccinic Acid
(DMSA) Renal Scan)

Renal cortical scintigraphy with DMSA is the

gold standard for diagnosing renal scars and
pyelonephritis [2]. DMSA is the best nuclear
agent for visualising the cortical tissue and for
evaluating the differential function between the
kidneys. In fact, DMSA is taken up by proximal
renal tubular cells and in areas of acute inflam-
mation or scarring; DMSA uptake is poor and
Fig. 42.1  CUM image of a bilateral reflux in a 2-year-old appears as cold spots. DMSA is important to
girl with recurrent UTIs and reflux nephropathy detect and monitor renal scarring [1, 41].
540 M. C. Y. Wong and G. Mattioli

Table 42.2  Grading system for VUR on VCUG, according to the International Reflux Study Committee [refer to 1, 36]

Grade I Reflux does not reach the renal pelvis; varying degrees of ureteral dilatation
Grade II Reflux reaches the renal pelvis; no dilatation of the collecting system; normal fornices
Grade III Mild or moderate dilatation of the ureter, with or without kinking; moderate dilatation of the
collecting system; normal or minimally deformed fornices
Grade IV Moderate dilatation of the ureter with or without kinking; moderate dilatation of the collecting
system; blunt fornices, but impressions of the papillae still visible
Grade V Gross dilatation and kinking of the ureter, marked dilatation of the collecting system; papillary
impressions no longer visible; intraparenchymal reflux

In 2004, Hansson et  al. introduced the top-­ • First diagnosis in females.
down approach, which consists of performing a • VUR monitoring both during antibiotic pro-
DMSA scintigraphy in all patients with the first phylaxis and after endoscopic treatment and/
UTI and later performing VCUG only in those or vesicoureteral reimplantation.
patients with defects on DMSA scintigraphy [42]. • Stenotic megaureters and/or ureteroceles
Following this approach, a great number of unnec- already diagnosed and treated or not treated
essary VCUGs are avoided and less than 0.05% of by endoscopy or transvesical surgery.
children with damaged kidney is missed [42]. • Diagnosis of VUR in transplanted kidneys
[46, 47].

42.4.4 Echo-Enhanced
Cystosonography (CSG) 42.5 Treatment

Echo-enhanced CSG has been proposed as an There are two approaches for VUR therapeutic
alternative exam to VCUG.  It is a safe imaging management [1]:
tool, which allows the detection of VUR without
the exposition to ionising radiation. Excellent 1. Conservative approach
results have been described with the use of US 2. Surgical approach
echo-enhancement agents made of galactose sus-
pension as SH U 508A in paediatric patients [43–
47]. CSG has a diagnostic accuracy superior to 42.5.1 Conservative Approach
90%, and it seems that CSG may also help to
evaluate disease in patients in whom there is a The aim of the conservative approach is to pre-
high suspicion for VUR but a negative VCUG vent febrile UTI and scar formation, considering
image, because it can be repeated without addi- that approximately 20% of those children who
tional radiation exposure [47]. CSG can be an experience one infection will have a repeat epi-
alternative to VCUG under the following sode [1, 48]. The conservative option is based on
conditions: the knowledge that VUR can be resolved sponta-
42  Vesicoureteral Reflux 541

neously, especially in young patients with low 42.5.2.1 Primary VUR Surgical
grade; and it includes watchful waiting, antibiotic Treatment
prophylaxis, bladder rehabilitation and bowel Surgical treatment is usually reserved for patients
management [49]. with high-grade VUR, recurrent UTI despite
In scientific literature, the use of antibiotic antibiotic prophylaxis and noncompliance with
prophylaxis has always been very controversial prophylactic antibiotics [58]. Surgical treatment
because of the lack of properly randomised and can be carried out by endoscopic injection of
controlled studies. For a long time, evidence bulking agents or ureteral reimplantation.
regarding the efficacy of prophylactic therapy to
prevent recurrences after the first episode of UTI Endoscopic VUR Treatment
has been lacking for the infant population [48]. Since its first clinical application in VUR in
Several studies have prospectively observed 1984 by O’Donnell and Puri [59], endoscopic
children with reflux on and off prophylaxis and treatment has gained great popularity among
found similar rates of infection between the paediatric urologists, particularly after dextra-
groups [50–54]. In 2014 the Randomized nomer/hyaluronic acid (Dx/HA) copolymer
Intervention for Children with Vesicoureteral approval by the US Food and Drug
Reflux (RIVUR) trial was published. It is a ran- Administration (FDA) in 2001. Over the years,
domised, double-­blind, placebo-controlled trial a number of different tissue-­augmenting sub-
of prophylaxis with trimethoprim-sulfamethoxa- stances have been evaluated in clinical practice:
zole in children with VUR that was diagnosed polytetrafluoroethylene (Teflon), bovine colla-
after a first or second febrile or symptomatic uri- gen, polydimethylsiloxane (Macroplastique),
nary tract infection [55]. According to this study, autologous chondrocytes, synthetic calcium
antibiotic prophylaxis reduces the risk of recur- hydroxyapatite, Dx/HA copolymer (Deflux) and
rences by 50% compared to placebo. Moreover, polyacrylate-polyalcohol copolymer (Vantris)
it seems that children with bladder and bowel [59–67]. Using cystoscopy, bulking agents are
dysfunction at baseline and children whose first injected beneath the intramural part of the ureter
infection is febrile derive particular benefit from in a submucosal location, elevating the ureteral
prophylaxis. orifice and the distal ureter so that competence
Another controversial aspect is the occurrence is increased. The lumen is consequently nar-
of renal scarring in children with and without rowed, preventing urine reflux into the ureter,
prophylaxis. It seems that the scar occurrence while still allowing the urine’s antegrade flow
does not differ significantly between the two [68]. Two possible techniques have been
groups [55]. described: subureteral transurethral injection
Finally, several studies have shown VUR (STING) and hydrodistension implantation
resolution after treatment for bladder and technique (HIT). STING technique was first
bowel dysfunction (BBD), which underlines introduced by Matouschek in 1981 [69] and
the important correlation between the treat- subsequently popularised by O’Donnell and
ment of BBD and higher success rates of surgi- Puri in 1984 [59]. STING consists of inserting
cal VUR treatments, as well as medical therapy, the needle 2–3 mm below the ureteric orifice at
biofeedback and behavioural treatment 6-o’clock position and advancing it for another
[56, 57]. 3  mm (Fig.  42.3). The intention is to create a
‘crescent-shaped’ ureteric orifice [69, 70]. HIT
technique was first described by Kirsch in 2004
42.5.2 Surgical Approach [71]. In this procedure, the lumen of the distal
ureter is distended by hydrostatic pressure, and
Surgical approach should be distinguished the bulking agent is injected 4 mm into the sub-
between primary VUR and secondary VUR treat- mucosa of the mid/distal ureteral tunnel at the
ment (VUP treatment). 6-o’clock position (Fig.  42.3). The aim is to
542 M. C. Y. Wong and G. Mattioli

Fig. 42.3 STING
technique on the left and
HIT technique on the
right (from G. Lackgren
and A.J. Kirsch (2010).
Surgery illustrated
Surgical atlas:
endoscopic treatment of
VUR [72])

convert the ureteric orifice into a volcano- stance, which may lead to the better stability of
shaped mound upon completion of the injection the injectable material and avoids VUR recur-
[70, 71]. It seems that HIT is superior to STING rence, also after 3 years of follow-up [76–78].
technique for resolution of VUR after Dx/Ha Complications after the endoscopic procedure
injection [70]. are infrequent and relate mainly to the obstruc-
According to a meta-analysis conducted in tion of ureterovesical junction and the develop-
2010 [73], within 5527 patients and 8101 renal ment of a new contralateral VUR after treatment
units, VUR resolution after one endoscopic treat- of unilateral VUR [78].
ment with Dx/HA is 78.5% for grades I and II Endoscopic approach is a safe procedure with
reflux, 72% for grade III, 63% for grade IV and low risk of complications, and it is currently the
51% for grade V.  If the first injection is method of choice among most urologists and par-
­unsuccessful, the second treatment has a success ents for children over the age of 1 year [58, 79].
rate of 68% and the third treatment 34%. The
overall success rate with one or more Dx/HA Ureteral Reimplantation
injections is 85%. The success rate is correlated Various intravesical and extravesical techniques
to the preoperative VUR grade, and it is signifi- have been described for the surgical correction of
cantly lower for duplicated (50%) versus single VUR. They are all based upon the basic principle
(73%) systems and neuropathic (62%) versus of lengthening the intramural part of the ureter by
normal (74%) bladders [73]. submucosal implantation of the ureter to create a
Some studies have shown that, after endo- 4–5:1 ratio of submucosal tunnel length to ure-
scopic Dx/HA injection, there is a high recur- teral width. The most widely used technique is
rence rate which may rise as high as 20% in the intravesical Cohen cross-trigonal reimplanta-
2  years [74, 75]. These findings have led to tion [80]. The main concern with this procedure
research for new substances with a higher long-­ is the difficulty of accessing the ureters endo-
term efficacy, and, for this reason, polyacrylate-­ scopically if needed when the child is older [1].
polyalcohol copolymer has been introduced. It is Success rate currently ranges between 95% and
a non-biodegradable tissue-augmenting sub- 98%. Other reimplantation techniques which
42  Vesicoureteral Reflux 543

have been described are Politano-Leadbetter BJU International, 94: 679–698. doi:https://
suprahiatal reimplantation [81], Glenn-Anderson d o i . o rg / 1 0 . 1 1 1 1 / j . 1 4 6 4 - 4 1 0 X . 2 0 0 4 .
infrahiatal reimplantation [82] and Lich-Gregoir 05083.x) [88]:
extravesical reimplantation [83]. VUR surgical
treatment has been described also with laparo-
scopic and robotic approaches. Lakshmanan
et al. were the first to describe laparoscopic extra-
vesical reimplantation in humans [84]. A novel
minimally invasive cross-trigonal ureteral reim-
plantation technique under pneumovesicum was
reported by Yeung in 2005, and it is now wide-
spread with a high success rate (92–94%)
[85–87].

Cohen Reimplantation
Cohen described the intravesical cross-trigo-
nal reimplantation in 1975 [80]. The proce-
dure is illustrated in the following figures
(from Mure, P.-Y. and Mouriquand, P.  D.E.
(2004), Surgical Atlas The Cohen procedure.

1. A transverse suprapubic incision is made 

2 cm above the pubic symphysis.
544 M. C. Y. Wong and G. Mattioli

2. The rectus and the bladder are opened verti- 3. Two or three stay sutures are placed on each
cally in the midline. side to expose the bladder. To expose the tri-
gone, one or several swabs are put inside the
bladder and retracted upwards. A 3/0 or 4/0
absorbable suture is placed at the lowest
point of the vesicostomy, to prevent the inci-
sion downwards into the bladder neck and
the urethra. A feeding tube (usually 4F) is
inserted into each ureter.
42  Vesicoureteral Reflux 545

4. A stay suture is placed around each ureteric 5. It is essential to enter the correct plane
orifice and tied over the feeding tube, the between the bladder and the transparietal
ureteric orifice is circumcised with diathermy ureter, commencing below the orifice, using
and the distal 2  cm of ureter can be Reynolds scissors. Muscle fibres are grasped
mobilized. with fine forceps, coagulated and divided.
The fibres should be coagulated some
­distance from the ureter, to avoid damaging
its blood supply.
546 M. C. Y. Wong and G. Mattioli

6. The dissection continues progressively, cir-

cumferentially until the ureter is completely
freed.

7. The submucosal tunnel is then formed; it is ­ idline of the posterior surface of the blad-
m
usually a horizontal tunnel, crossing the der, just above the trigone.

42  Vesicoureteral Reflux 547

8. The length of the submucosal tunnel should

be at least five times the ureteric diameter
(Paquin’s rule) [89]. If this cannot be fulfilled,
modelling of the ureter should be considered
and there are two possibilities. On the left, the
figure describes the Hendren’s technique in
which the calibre of the ureter is reduced by
excising a strip of ureter [90]. On the right, the
figure describes the Kalicinski’s technique, in
which the calibre of the ureter is reduced by
infolding the ureter [91].
548 M. C. Y. Wong and G. Mattioli

9. The site of the new ureteric orifice is selected tunnel should be wide enough to allow easy
and the bladder mucosa lifted from the insertion of the ureter, with no constriction.
underlying bladder muscles with a pair of A similar procedure can be used for the
Reynolds scissors, starting either from the opposite ureter in case of bilateral
hiatus or from the new ureteric orifice. The reimplantation.


42  Vesicoureteral Reflux 549

10. The 5/0 absorbable suture anchors the ureter

to the bladder muscles and the
­ureterovesicostomy is completed with inter-
rupted 6/0 absorbable sutures.

12. The bladder is closed with a 3/0 or 4/0 suture

(interrupted or continuous). The prevesical
and subcutaneous spaces are drained by a
suction drain. The abdominal wall, the subcu-
taneous tissues and the skin are then closed.

42.5.2.2 Secondary VUR Surgical

Treatment
The treatment of secondary VUR consists in
relieving the obstruction and pressure on the uri-
nary tract, with care to maintain normal bladder
and renal function for as long as possible [4]. The
surgical approach comprises also foetal interven-
tion which should be proposed to parents of foe-
11. For some surgeons, an infant feeding tube or tuses with oligohydramnios after 18  weeks’
JJ stent is inserted into the reimplanted ureter gestation and severe bilateral hydronephrosis, but
and exteriorised through the bladder wall, with ‘normal renal function’ [92]. It is important
the rectus muscle and the skin, using the to underline that amniotic fluid is necessary for
punch of a suprapubic catheter. The feeding normal lung development, and its absence may
tube is left in position for 2  days or for lead to pulmonary hypoplasia, causing a life-­
10  days if the ureter has been remodelled. threatening problem [1]. The main technique uti-
There is no consensus on the efficacy of lised for foetal intervention is the vesicoamniotic
drainage of the reimplanted ureter, and some shunting, whereby a double pigtail stent is intro-
surgeons do not leave any drainage. The duced percutaneously via a trocar, under ultra-
bladder is drained either by a transurethral sound guidance and maternal local anaesthetic.
catheter for 5  days or by a suprapubic An alternative is foetal cystoscopy, whereby a
catheter. trocar is placed inside the foetal bladder under
550 M. C. Y. Wong and G. Mattioli

ultrasound guidance and the foetoscope is nally defined by Young in 1919 but was later
advanced into the foetal bladder in an antegrade determined to be an overclassification [94, 95].
fashion and valves visualised and ablated [13]. Type 1 PUVs are descripted as a valvelike lesion
After birth, a catheter drainage of the bladder oblique to the urethral axis, the most important
is inserted, with close monitoring of serum elec- finding of which is a connection of the lesion to
trolytes and renal function, and antibiotics the verumontanum at the 5 and 7 o’clock posi-
administration to prevent UTIs [4]. Primary valve tions with the formation of posterolateral folds
ablation is considered the treatment of choice for (Fig.  42.2). Type 3 PUVs are described as a
PUVs, while controversy exists regarding the membrane or diaphragm with a hole present in its
vesical or supravesical diversion and delayed centre (Fig. 42.4).
valve ablation [93]. Actually, at the moment, it Small paediatric cystoscopes and resecto-
seems that there are no significant differences in scopes are nowadays available either to incise or
the major outcomes between those children to resect the valves at the 5, 7 or 12 o’clock posi-
treated by initial vesicostomy and those who tion, or at all three positions, depending on the
have undergone primary fulguration [93]. surgeon’s preference [1]. Valve ablation can be
performed both with cold knife ablation and dia-
Primary Valve Ablation thermy hook, even if it seems that the first one
Nowadays, after catheter drainage, if hydrone- has lower rate of urethral stricture than the latter
phrosis and creatinine improve, the best practice one. After valve ablation two complications can
guidelines suggest planning endoscopic valve occur: urethral stricture and valve residual [96].
ablation when the child is medically stable [4]. After 3 months a VCUG or a second cystoscopy
Cystoscopy is performed, and after filling the is performed in order to demonstrate the effec-
bladder with saline, the suprapubic region is tiveness of the treatment [1].
compressed with Credé’s manoeuvre to fully
dilate and visualise the posterior urethra. There Vesicostomy
are two main types of PUVs detected during the A temporary vesicostomy is considered in new-
urethroscopy: types 1 and 3. Type 2 was origi- born too small (under 2000  g) and in those

Fig. 42.4  On the left, endoscopic findings of type 1 treatment for posterior urethral valve as an etiology for
VUPs and on the right endoscopic findings of type 3 vesicoureteral reflux or urge incontinence in children.
VUPs (From Nakai H et  al. Aggressive diagnosis and Investig Clin Urol. 2017 June;58(Suppl 1): S46–S53) [95]
42  Vesicoureteral Reflux 551

patients with worsening of hydronephrosis and 7. Hellström A, Hanson E, Hansson S, Hjälmås K, Jodal
U. Association between urinary symptoms at 7 years
creatinine despite the bladder catheter drainage old and previous urinary tract infection. Arch Dis
[1, 4]. Vesicostomy is a surgical procedure which Child. 1991;66(2):232–4.
protects the upper urinary tract, decreases hydro- 8. Jakobsson B, Esbjörner E, Hansson S. Minimum inci-
nephrosis and improves kidney function in more dence and diagnostic rate of first urinary tract infec-
tion. Pediatrics. 1999;104(2 Pt 1):222–6.
than 90% of patients [97]. In literature, there has 9. Brandström P, Hansson S. Long-term, low-dose pro-
been a long debate regarding the bladder function phylaxis against urinary tract infections in young chil-
after vesicostomy. Some authors concern that dren. Pediatr Nephrol. 2015;30(3):425–32.
vesicostomy lead to reduced bladder compliance 10. Peters C, Rushton HG.  Vesicoureteral reflux associ-
ate renal damage: congenital reflux nephropathy and
and capacity, but nowadays no valid data are acquired renal scarring. J Urol. 2010;184(1):265–73.
available [98, 99]. Finally, it seems that vesicos- 11. Estrada CR Jr, Passerotti CC, Graham DA, Peters CA,
tomy is more advantageous than bilateral loop Bauer SB, Diamond DA, Cilento BG Jr, Borer JG,
cutaneous ureterostomy because it enables free Cendron M, Nelson CP, Lee RS, Zhou J, Retik AB,
Nguyen HT. Nomograms for predicting annal resolu-
drainage of urine and avoids a completely defunc- tion rate of primary vesicoureteral reflux: results from
tionalised bladder [98]. 2,462 children. J Urol. 2009;182(4):1535–41.
12. Heikkila J, et al. Long-term risk of end stage renal dis-
High Urinary Tract Diversion ease in patients with posterior urethral valves. J Urol.
2011;186(6):2392–6.
High urinary tract diversion comprises high loop 13. Farrugia MK.  Fetal bladder outlet obstruction:

ureterostomy, ring ureterostomy, end ureteros- Embryopathology, in utero intervention and outcome.
tomy or pyelostomy. Diversion may be suitable if J Pediatr Urol. 2016;12(5):296–303.
there are recurrent infections of the upper tract, 14. Yohannes P, Hanna M.  Current trends in the man-
agement of posterior urethral valves in the pediatric
no improvement in renal function and/or an population. Urology. 2002;60(6):947–53.
increase in upper tract dilatation, despite ade- 15. Lissauer D, Morris RK, Kilby MD.  Fetal lower uri-
quate bladder drainage. Nowadays this surgical nary tract obstruction. Semin Fetal Neonatal Med.
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Liu DB, Armstrong WR 3rd, Maizels
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B, Campos A, Young L.  Clinical significance of E.  Treatment of vesicoureteral reflux by endoscopic
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 Ureterocele
43
Pierluigi Lelli Chiesa, Dacia Di Renzo,
and Giuseppe Lauriti

43.1 Definition Chwalla [1] theorized that a delay in rupture

and Demographics in Chwalla’s membrane, which separates the
Wolffian duct from the urogenital sinus, would
Ureterocele (UC) is a cystic dilatation of the ter- result in stenosis of the orifice and in aneurismal-­
minal, intravesical portion of the ureter. type dilatation of the distal ureteral segment. This
The incidence of UC is not well established. theory of obstruction fits well with UC having a
Different autopsy studies indicate a wide occur- stenotic orifice, actually the majority, but does
rence rate of 1 in 500 to 4000 children. UC are not adequately explain the embryology of those
3–7 times more common in females than males with normal or patulous orifices.
and more frequent in Caucasians than Blacks. Tanagho [2] postulated that the distal ureteral
There is a slight left-sided predominance, and lumen is delayed in formation and, therefore,
bilateral UC occurs in approximately 10% of results in ureteral expansion as result of hydro-
cases. static pressure.
UC can vary in size and location, while various Additionally, Stephens [3, 4] proposed an
anatomical features may be associated with UC, intrinsic muscular defect in the wall of the ureter
including the presence of duplication anomalies, which results in dilatation of the terminal portion
vesicoureteral reflux (VUR) into the ipsilateral and UC formation. Examining the musculature of
lower pole ureter or contralateral renal unit, and the intravesical portion of ectopic ureters associ-
presence of a cystic dysplastic moiety pertinent ated with UC, deficiency of the terminal muscu-
to the UC (see Classification paragraph). lature has been observed, compared with ectopic
ureters without UC.

43.2 Embryology
43.3 Classification
There are several theories that have been pos-
tulated to explain UC formation, with lack of a Traditionally UC are classified according to loca-
singular explanation that fits the variability found tion of ureteral orifice, as described by Ericsson
in UC. in 1954 [5]:

P. Lelli Chiesa (*) · D. Di Renzo · G. Lauriti –– Simple if the UC is entirely contained within
Department of Pediatric Surgery, “Spirito Santo” the bladder.
Hospital, Pescara, and “G. d’Annunzio” University, –– Ectopic if the UC extends into the bladder
Chieti-Pescara, Italy
e-mail: [email protected] neck or posterior urethra.

© Springer Nature Switzerland AG 2019 555

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_43
556 P. Lelli Chiesa et al.

Stephens [3, 4] has provided a more patho- duplicated systems. The contralateral upper tract
physiologic classification, dividing UC into four of a duplicated system with UC is likewise dupli-
categories: cated in 30–40% of cases. Ectopic UC are mostly
associated with the upper pole ureter of a duplex
–– Stenotic UC corresponds to the simple UC of system but also could be present in a single sys-
Ericsson’s classification; it is entirely con- tem. Intravesical UC are usually associated with
tained into the bladder and has a small orifice single systems, but, rarely, they may also be per-
that can vary in size and, therefore, in the tinent to the upper moiety of a duplicated system,
degree of distension of the UC itself. especially in males.
–– Sphincteric UC is an ectopic UC in which the
orifice is located within the internal sphincter
mechanism (bladder neck or proximal ure- 43.4 Presentation
thra); the orifice can be normal or large in size
with relative obstruction occurring, except In the last decades, the widespread use of prenatal
during time of voiding with relaxation of the ultrasound (US) has significantly modified mode
internal sphincter mechanism. of presentation and patient age at time of diagno-
–– Sphincterostenotic UC has a orifice located sis. Currently UC is diagnosed at neonatal evalua-
within the sphincter mechanism and, in addi- tion of prenatally detected hydronephrosis in 75%
tion, the orifice is stenotic; as a result UC does of cases. Therefore age at presentation is within
not empty during voiding and hence tends to the first week of life, with less than 25% present-
be large and tense and may act as a ball valve ing later, after urinary tract infection. Most often
into the bladder outlet and cause obstruction. in the past, rarely today, sepsis, hematuria, urinary
–– Cecoureterocele has an orifice located within incontinence, and/or flank pain can be also pres-
the bladder; however, a “cecum” or a tongue ent at presentation. A palpable mass may also be
of UC extends submucosally into the urethra. the first sign of UC, resulting from an obstructed
dilated upper pole (obstructive UC with stenotic
The best classification to date is based on orifice) or distended, obstructed bladder.
the report of the Committee on Terminology, Bladder outlet obstruction (BOO) can be
Nomenclature and Classification of the Urology caused by a tense UC which acts as a ball valve
Section of the American Academy of Pediatrics. into the bladder neck or by a cecoureterocele
It subdivides UC based on the number of ureters which elevates the floor of the bladder neck sub-
that drain the kidney pertinent to the UC, the mucosally or a distal mucosal lip which blocks
location and the extent of UC, and the additional the BOO. Because most UC become compressed
anatomic distortions of the UC: upon voiding, obstruction usually does not occur.
The most common cause of urethral obstruction
–– Duplex system UC is pertinent to the upper in the little girl is urethral prolapse of a UC, the
pole of a completely duplicated collecting so-called dumbbell UC, presenting as perineal
system. mass (Figs. 43.1 and 43.2).
–– Single system UC is pertinent to a single ureter
draining the kidney.
–– Intravesical if the UC and its orifice are 43.5 Diagnosis
located entirely within the bladder.
–– Ectopic if the UC and its orifice extend beyond Antenatal ultrasound, performed after the 16th
the trigone to the bladder neck or outside of gestational week, is able to detect fetal hydrone-
the bladder to involve the urethra. phrosis, often associated with UC (Fig.  43.3a);
after the 30th week of pregnancy, the UC can be
Ectopic UC constitutes 60–70% of UC in occasionally demonstrated within the fetal blad-
pediatric age, 70–80% being associated with der as well (Fig. 43.3b).
43 Ureterocele 557

However, in the majority of cases, definitive into a dilated ureter in the bony pelvis and into
diagnosis can be achieved only postnatally. upper pole hydroureteronephrosis, if duplication
The goals of diagnosis are (1) to identify the is present. Hydronephrosis, thickness, and echo-
ureterocele, define the side involved, and evalu- genicity of renal parenchyma can be also evalu-
ate the status of both ipsilateral and contralateral ated (Fig. 43.4b).
kidneys and the condition of the bladder and (2) After US, voiding cystourethrogram is an
to detect the presence of VUR and of contralat- important part of the evaluation of patients with
eral malformations. UC, given its frequent association with reflux.
The diagnostic workup relies on the use of The ipsilateral lower pole system of a dupli-
US, voiding cystourethrogram (VCUG), nuclear cation with UC is refluent in 40–50% of cases
scan, and cystoscopy, if required. In the past (Fig. 43.5a). The contralateral system is affected
intravenous pyelogram (IVP) was an important by reflux in approximately 15–25% of cases as
diagnostic tool to better study urinary tract anat- well. VCUG provides information also regard-
omy, nowadays almost completely superseded by ing the quality of detrusor backing of the UC; in
MR urography. fact with poor detrusor backing, a diverticulum-
Postnatal US, done to confirm a prenatal like effect is seen. In 15% of cases, reflux can be
suspicion or because of symptoms or as routine observed into the UC, most often with cecoure-
screening, reveals a well-defined cystic intra- teroceles or those with a patulous orifice located
vesical mass (Fig.  43.4a). This can be followed in the bladder neck. Single system intravesical
UC are less likely associated with refluent units
(Fig. 43.5b).
Renal scintigraphy should be used to evaluate
renal function (especially of the upper pole moi-
ety if a duplex system is suspected) and even-
tual degree of obstruction and to detect renal
scarring (Fig.  43.6). Technetium 99m (99mTc)
diethylenetriamine penta-acetic acid (DTPA)
and mercaptoacetyltriglycine (MAG3) scans
provide reasonable assessments of function and
obstruction. Since 99mTc dimercaptosuccinic
acid (DMSA) scans result in renal tubular label-
ing and are unaffected by obstruction, they are
more sensitive to low levels of renal function
Fig. 43.1  UC prolapsing through urethra, presenting as and are sometimes helpful in detecting occult
perineal mass duplex anomalies and small kidneys associated

a b c

Fig. 43.2  Dumbbell UC: US images of intravesical (a), urethral (b), and perineal (c) portions (Photos are courtesy of
Dr. A.A. Caldamone)
558 P. Lelli Chiesa et al.

a b

Fig. 43.3  Prenatal US showing bilateral hydronephrosis (a) and a UC (white arrow) within the distended bladder (b)

a b

Fig. 43.4  Neonatal US showing a big UC inside the bladder (a) and hydronephrosis of upper pole (b)

with ureteral anomalies that are not identified by cine imaging has made this examination obsolete
other techniques [6]. in most cases, although when the anatomy is con-
The upper pole of a duplex kidney or a solitary fused, it may still play a role. Anatomy of upper
kidney is considered nonfunctioning when its and lower tract and renal functionality can be
contribution to the overall renal function is less detected. When the associated upper tract paren-
than 10%. Obstruction is considered in cases of chyma functions adequately, the presence or the
severe hydroureteronephrosis that suggests poor absence of a duplication anomaly can be easily
drainage of the upper pole or kidney. To assess visualized and the typical “cobra head” defor-
upper pole/kidney obstruction, a diuretic renog- mity in the bladder can be observed, resulting
raphy with Furosemide is usually performed. from opacified urine surrounded by a radiolucent
Intravenous pyelogram was the most impor- halo representing the UC wall (Fig. 43.7).
tant diagnostic step in the past. Nowadays the Due to the fact that the most of associ-
progress of ultrasonography and of nuclear medi- ated upper pole segments are dysplastic and,
43 Ureterocele 559

a b

Fig. 43.5  VCUG showing grade 5 reflux into the lower system and a two-lobes UC inside the bladder (a); VCUG
showing absence of reflux and intravesical UC seen as a filling defect (b)

a b

Fig. 43.6  MAG3 scan showing functioning single system kidneys (a) and nonfunctioning upper pole in a right dupli-
cated system (b)

t­ herefore, poorly functioning at best, radiological are visible. The opacified collecting system of
findings are often indirect. If the function of the the affected kidney usually has too few calyces
pertinent parenchyma is not adequate to opacify and lacks an upper pole infundibulum. When
the collecting system, the effects of the hydro- the upper pole moiety is hydronephrotic, it will
nephrosis on the associated lower pole structures tend to push the lower pole moiety laterally and
560 P. Lelli Chiesa et al.

i­nferiorly producing the classic “drooping lily” and cause distal lower pole ureter to appear tortu-
effect. A dilated upper pole hydroureter may ous as it becomes more closely intertwined with
force the lower pole pelvis and ureter laterally the dilated upper pole ureter. As the bladder fills
with contrast material, a negative shadow will be
created by the UC filled with unopacified urine,
in the earlier films.
Cystoscopy is an important diagnostic tool
to confirm or define UC location (Fig. 43.8) and
kind of system; it is fundamental before per-
forming endoscopic treatments (transurethral
incision or puncture of UC as well as endoscopic
correction of eventually associated reflux). The
bladder should be examined both when full and
when completely empty because compressible
UC may not be evident in a full bladder or may
appear as a bladder diverticulum. On the con-
trary, the dilated distal end of an ectopic ureter
or megaureter may elevate the trigone, creat-
ing the cystoscopic appearance of a so-called
pseudo-ureterocele.

43.6 Management: Introduction

Multiple treatment strategies are available for

pediatric UCs; consensus on the best initial
approach is lacking; therefore the treatment
of this uropathy remains a matter of debate.
Historically, aggressive treatments were the rule
to prevent renal damage secondary to infections
Fig. 43.7  IVP in bilateral duplex system associated with
and obstruction. However, treatment objectives
small bilateral intravesical ureteroceles

a b

Fig. 43.8  Cystoscopic picture of intravesical (a) and ectopic UC (b) (Photos are courtesy of Dr. A.A. Caldamone)
43 Ureterocele 561

and timing have changed through years and since optimal management of UCs remains controver-
the advent of prenatal diagnosis, which modi- sial and begins with the same algorithm used in
fied natural history of this malformation. Current all patients, namely, evaluation of the history,
treatment strategies tend toward a more conser- physical examination, imaging, and discussion
vative approach, because it appears the same with the family [15].
functional results can be achieved [7]. Over the past 40  years, the management of
The goals of treatment are: ectopic ureteroceles has significantly changed.
Initially, it was thought that upper pole par-
–– Prompt decompression of obstructed urinary tial nephrectomy alone was optimal, or, in rare
tracts with infection. cases, nephrectomy if the entire kidney was
–– Elimination of any potential source of essentially nonfunctioning. Over time many of
infection. these patients required further surgery, leading
–– Relief of significant obstruction of the upper to the adoption of a single-stage upper pole par-
tract and/or the BOO. tial nephrectomy, total ureterectomy of the upper
–– Elimination of clinically significant reflux. pole ureter, ureterocelectomy or marsupializa-
–– Preservation of renal function (including func- tion, and unilateral or bilateral ureteroneocystos-
tional moiety of a duplex system). tomy based on the involvement of each ureter in
–– Restoration and maintenance of continence. the ureterocele [16].
–– Prevention and treatment of any bladder wall In recent years, conservative management
deficiency (diverticula, poor detrusor of asymptomatic patients without obstruction
backing). has shown that these patients remain free of
–– Minimization of the number of surgical proce- ­symptoms, hydronephrosis tends to resolve as
dures and surgical morbidity [8, 9]. ureterocele collapses, and vesicoureteral reflux
tends to disappear spontaneously. Transurethral
However, the means of accomplishing these puncture (TUP) has become a popular, safe,
objectives still remain a significant challenge in and minimally invasive procedure. However,
modern pediatric urology. Practice patterns are concern exists regarding new-onset reflux after
widely variable, and no randomized controlled puncture and the frequent need for subsequent
trials exist to guide management decisions [10, interventions. Although more invasive proce-
11]. Moreover to compare methods is difficult dures such as upper pole partial nephrectomy
because each patient can have a different clini- or reimplantation are safe and associated with a
cal history, so no single method of treatment low percentage of complications, they may not
suffices for all cases and management needs to always be necessary (Fig. 43.9) [7].
be individualized [12]. The selection of a treat- The first point to be decided is whether
ment modality, including nonoperative manage- patients really need intervention or can be man-
ment, endoscopic ureterocele decompression, aged conservatively. Indeed, the present aim is
upper pole nephrectomy, high or low uretero- to achieve goals of treatment and avoid com-
ureterostomy, and excision of the ureterocele plications, with the fewest possible interven-
with ureteral reimplant, can therefore only be tions. In fact, doubts have recently arisen as to
based on the balance between potential risks whether early diagnosis, often prenatal, leads
inherent to the condition and the summation of to unnecessary interventions [7]. Current trends
published results for a multitude of therapeutic are away from single-stage open reconstruc-
alternatives [13, 14]. Also surgeon’s prefer- tion (heminephrectomy, ureterocele excision,
ence weights on the choice, even if each sur- bladder base/neck reconstruction, and ureteral
geon should be skilled in multiple approaches. reimplantation) and oriented toward conser-
Ultimately, the decision to treat (and when to vative management and minimally invasive
treat) is difficult as every patient is unique: the approaches [9].
562 P. Lelli Chiesa et al.

Fig. 43.9 Initial Obstruction

therapeutic protocol. TUP Symptoms (mainly UTI)
transurethral puncture, yes no
UPPN upper pole partial
nephrectomy, UTI urinary
tract infection (from Operative Non-operative
Gander R et al.) [7] management management

Functioning upper pole

or kidney?

yes no

TUP UPPN or
Nephrectomy with
failed aspiration of the
ureterocele
Reimplantation and
ureterocele excision

43.7 Nonoperative Management decompression. Reflux into the ipsilateral renal

unit and into both the ipsilateral and contralat-
Under specific circumstances, UCs themselves eral renal units resolved. A third patient with
require no surgical therapy. Because the major- ipsilateral reflux did not undergo follow-up cys-
ity of UCs are detected antenatally and patients tography, as she was clinically well; thus, it was
are often asymptomatic at birth, the lack of a sig- assumed that the reflux resolved. During a mean
nificant urinary tract obstruction could prompt follow-up of 36  months, only one child had a
consideration of nonoperative management UTI.
(Table 43.1) [14]. Han et  al. [19] reported 13 cases initially
Shankar et al. [17] reported 14 of 52 patients managed conservatively. In contrast to Shankar
with UC who were managed conservatively. et al., they stated that functioning upper pole was
Their selection criteria for nonoperative manage- not a criterion for surgical intervention; those
ment were nonfunctioning upper pole moieties, patients were evaluated with MAG3 to determine
nonobstructed lower poles, absent or low-grade adequate drainage. If high-grade obstruction was
VUR to the lower pole, and no BOO.  Patients present, patients were managed surgically.
with upper pole function >10% were considered Gander et  al. [7] agree with Han et  al. that
for surgical intervention. After a median follow- patients with a functioning upper pole who are
up of 8  years, no patient underwent surgery or managed conservatively should be carefully
had a UTI.  The authors estimate that a further evaluated for obstruction. Based on their results
seven patients—or a total of 27% from the origi- and the previously studies, they suggest that
nal cohort of 52—might have also been managed asymptomatic patients without obstruction can
expectantly. be safely managed conservatively and followed
Coplen and Austen [18] reported on a cohort up with US. Special attention should be paid to
of eight children with UCs associated with cystic patients with a functioning upper pole to detect
dysplastic moieties, four cases with single sys- obstruction during follow-up; mercaptoacetyltri-
tems and four with duplex systems, who under- glycine is probably the best tool for this purpose.
went no surgical management. In all children, the Also Direnna and Leonard’s [20] study sup-
cystic dysplastic moiety involuted resulting in ports a nonoperative course in selected patients.
 43 Ureterocele

Table 43.1  Review of nonoperative management of ureteroceles (from Pohl HG) [14]
Indications for Hydronephrosis
Presentation nonoperative Antibiotic No. undergoing No. resolution/MCDK
Reference (n) management prophylaxis Follow-up surgery UTI VUR resolution (n) involution
Shankar et al. Prenatal <10% function lower Yes Median, 8 years 0 0 Resolution in 6/14
[17] (14) pole (range,
Nonobstructed lower 1.6–128 years)
pole
Lower pole VUR ≤3
No bladder outlet
obstruction
Coplen and Prenatal (8) Multicystic dysplasia – Mean, 3 years (range 0 1 Involution of MCD in
Austin [18] 1.2–4.5 years) 8/8
Han et al. Prenatal Nonobstructed upper Yes Median, 3.42 years Progressive 3 Ipsilateral lower pole Involution of dysplastic
[19] (10) pole (range, 1–8 years) obstruction (1) VUR grade III (2) unit (3)
UTI (3) Multicystic dysplasia UTI (3) Ipsilateral lower pole Resolution of hydro (6)
VUR, grade IV (3)
Direnna and Duplex (6) Lower pole VUR ≤3 Yes Median, 5 years 0 0 Ipsilateral lower pole Resolution of hydro (6)
Leonard [20] Single (4) Nonobstructed lower (range 1–11 years) VUR, grade ≤ III (4) VUR resolved (2)
pole
No bladder obstruction
UTI urinary tract infection, VUR vesicoureteral reflux
563
564 P. Lelli Chiesa et al.

The authors admit that this cohort represents a Indeed endoscopic UC decompression is
minority of the patients diagnosed prenatally a widely used, minimally invasive method of
with UC but underscores the importance of achieving timely UC decompression and decreas-
individualizing the management of prenatally ing the risk of UTI while avoiding, or at least
detected UCs. postponing, extensive trigonal surgery in infants
In summary these studies suggest that a sub- [9]. Moreover it is a relative simple and quick
group of patients presenting with nonobstruc- procedure, which can be performed as one-­day
tive noninfected ureteroceles, especially but not surgery (Fig. 43.10).
exclusively in presence of a nonfunctioning dys- Endoscopic puncture represents the treatment
plastic moiety, rarely require surgery, even if low- of choice in several clinical scenarios, both in the
grade reflux is present. In conclusion, according urgency and in the elective setting.
to new trends proposed in the literature, the most For patients with UC presenting at birth
successful therapeutic approach to prenatally with systemic infection and azotemia, or high-
diagnosed ureteroceles without symptoms or grade obstruction, or prolapse of the ureterocele
signs of obstruction appears to be nonsurgical. through the urethra with BOO, endoscopic inci-
However, any patient being managed conserva- sion is the initial therapeutic approach of choice.
tively should be followed, and the development This permits immediate decompression of the
of BOO, symptomatic UTI, or significant wors- renal system and faster resolution of sepsis and,
ening of upper tract obstruction should prompt in a part of cases, can be the only treatment
consideration of operative intervention [9]. We necessary.
underline, however, that this subset of cases are In the elective setting, essential preopera-
only a small percentage. tive considerations include UC type and posi-
tion, upper tract anatomy and function, and
presence of associated ipsilateral and/or con-
43.8 Surgical Management tralateral VUR.  In the past, management has
been based primarily on UC position, with
It is currently beyond any doubt that patients with endoscopic intervention preferred for intravesi-
significant obstruction or symptoms require sur- cal UCs and upper tract approach or complete
gical intervention. reconstruction used for ectopic, duplex system
UCs. Reoperation rates have often been used as
a primary outcome measure to evaluate the suc-
43.8.1  TUP cess of TUP. Indeed endoscopic puncture offers
the greatest potential as a definitive treatment of
Although a fraction of patients with minor uri- patients with intravesical single-system uretero-
nary tract obstruction may present as older celes. Successful decompression without reflux
children, the vast majority today in developed may be achieved in 70–80% of such cases [10,
countries are diagnosed on prenatal ultrasound, 23]. Nonetheless, several investigators broad-
making early treatment in the neonatal period the ened the use of endoscopic puncture to include
new standard. In addition to changes in patterns ectopic UCs [13, 23–26], whereas others com-
of diagnosis, improvements in pediatric anes- bined endoscopic puncture with ureteral bulking
thesia and endoscopic technology and technique agent injection in the setting of associated high-
have resulted in an increasing shift of the timing grade reflux [27].
of intervention toward younger ages [21]. Thus, TUP represents an effective short-term correc-
patients requiring UC surgery are younger, and tion of upper pole obstruction but may not repre-
younger patients are better able to tolerate an sent definitive therapy in most cases of ectopic
endoscopic approach than more complex surgi- UC ([26, 28, 29] [23, 24]). Many children require
cal techniques [22]. repeat puncture for adequate decompression or,
43 Ureterocele 565

a b

c d

Fig. 43.10  TUI of intravesical UC (a) and its decompression after puncture (b). Another case of intravesical UC just
punctured (c) and decompressed (d) (Photos are courtesy of Dr. A.A. Caldamone)

more commonly, subsequent reconstructive sur- involved by the UC, and, in case of subsequent
gery for persistent obstruction, recurrent infec- bladder surgery, reduces the need for ureteral
tion, or persistent or de novo reflux. Furthermore, tapering [8].
incision or puncture may increase the likelihood Although much of the discussion surrounding
of future surgery in patients with no preoperative the management of UCs focuses on the decom-
reflux, perhaps because of procedure-related de pression of the upper urinary tract or upper pole
novo reflux, although this remains unclear [24, moiety, management of any VUR into the ipsi-
27]. In light of these concerns, an upper tract lateral lower pole or contralateral renal unit must
approach has traditionally been used for ectopic also be considered. Also, VUR that is created
UCs [9]. However, [13] showed no difference by endoscopic decompression of the UC has the
in outcomes regarding UC location, leading the potential to further complicate management [14].
authors to suggest that differentiating between In effect, there is still concern about new onset or
orthotopic and ectopic UCs is clinically use- worsening of reflux after primary puncture. Some
less. Anyway, even in cases needing secondary evidence suggests that endoscopic puncture may
surgery, TUP obviates obstruction, allows a bet- be used irrespective of the presence of reflux and
ter functional evaluation of the kidney or pole that minimally invasive techniques may be used
566 P. Lelli Chiesa et al.

to treat children with VUR either inherent to a often used until postoperative imaging is com-
duplex system or resulting from previous endo- pleted to assess for VUR [9].
scopic puncture [9]. However, VUR after punc-
ture can be also managed conservatively because
it tends to disappear. If treatment is required due 43.8.2  Technique
to symptomatic VUR, endoscopic injection could
be a first option [7]. Several cystoscopic devices and techniques have
Adorisio and colleagues [30] applied TUP in been used to decompress the UC and the urinary
46 consecutive cases irrespective of the presence tract accordingly.
of reflux. Among 14 patients who had prepunc- In recent years, endoscopic puncture has sup-
ture VUR, 10 had spontaneous resolution in fol- planted incision as the preferred technique [10,
low-up, and the remaining 4 were corrected with 11]. Several different methods of endoscopic
endoscopic injection. Five of 46 patients devel- decompression exist, such as electrocoagulation,
oped de novo reflux into the ipsilateral upper pole Collins knife incision, and, most recently, laser
moiety. Two of these experienced spontaneous incision.
resolution, whereas two underwent endoscopic Endoscopic puncture is typically performed
correction. with an 8-Fr or 10-Fr endoscope and flexible
Regarding endoscopic puncture in the setting 3-Fr monopolar wire electrode (Bugbee-type
of poor or absent UC moiety function, the risk endoscopic electrode). The cutting current
of subsequent morbidity (e.g., UTI, urolithiasis, should be set high enough to ensure a clean
hypertension, malignancy) conferred by leaving puncture. The bladder should be incompletely
a nonfunctioning UC-associated moiety in vivo is filled to achieve maximal UC distension for
not well understood [9]. For symptomatic patients puncture. Intravesical UCs should be punc-
with a nonfunctioning or a minimally function- tured with a single shot, close to the base, in
ing upper pole (considered if upper pole function a declivous position, allowing collapsed tissue
contributes <10% to total renal function), UPPN and some intravesical ureter to establish an anti-
has always been considered a definitive and safe reflux valve. Incising distally on the UC, close
option. However, even if associated with good to the bladder floor, should prevent postopera-
results, it may not always be necessary. The cys- tive reflux [8, 9]. For ectopic UC, a single punc-
tic dysplastic upper pole tends to involute, and no ture of the intravesical portion of the UC can be
higher incidence of infections or complications made just proximal to the bladder neck [9]. In
has more recently been observed. Thus, the ques- the past a further incision at the urethral level
tion arises as to whether UPPN is really necessary was considered to be necessary to remove any
in these patients [7]. Chertin and colleagues [31, potential flap that might obstruct the bladder
32] examined the long-term morbidity associated outlet. Afterwards no adverse effects have been
with a nonfunctioning or poorly functioning moi- reported by leaving the intraurethral extension
ety left in situ after endoscopic puncture. Their of the UC intact, if a good decompression of the
data support the fact that conservative approach intravesical portion was obtained [8].
may not contribute to additional morbidity or
subsequent need of heminephrectomy.
Postoperative care and follow-up after TUP is 43.8.3  Laser
highly individualized. Hospitalization with intra-
venous antibiotics and monitoring may be neces- The use of laser during cystoscopic procedures
sary after acute decompression in the setting of in pediatric patients was first described to ablate
systemic infection. In the elective setting, it is posterior urethral valves (PUV) by Ehrlich in
frequently an outpatient procedure. 1987 [33] using neodymium-­doped: yttrium alu-
Postoperative imaging should include US and minum garnet (Nd:YAG) laser. He reported his
VCUG at 4–6 weeks. Prophylactic antibiotics are experience in a small cohort of six boys (age
43 Ureterocele 567

7–20  months), performing the procedure in an guration, urethral stricture, and incontinence in
antegrade manner through cutaneous vesicos- those children treated with laser ablation. Despite
tomy. Since that time, it has been utilized only this encouraging evidence, the mean age for this
sporadically and only to treat PUV, with infre- study was 24 months (range 3–60 months) with
quent case series. In 2000, Bhatnagar et  al. no neonates [21, 37].
[34] reported on a cohort of 23 older boys (age Indeed, the literature contains only few reports
3  months–9  years) with PUV, still using the of laser ablation in neonates (defined as <28 days
Nd:YAG laser. old) for either urethral valves or ureterocele. The
The first to use laser technique to decompress first report was in [38] by Biewald and Schier,
UC in pediatric patients was Marr in 2002 [22]. who treated with Nd:YAG laser 13 patients with
He treated 14 patients, using either potassium PUV. The first authors to treat newborn for UC
titanyl phosphate or holmium:yttrium aluminum were Jankowski and Palmer in 2006 [35]. They
garnet (Ho:YAG) laser, reporting a 100% decom- treated four patients with five UC, with Ho:YAG
pression rate. The laser decompressed thick and laser. Two patients had ectopic UCs, both of
thin ureteroceles, and no endoscopic retreatment which were associated with a duplicated col-
was necessary. Marr was also the first to use lecting system. One patient had an intravesical
Ho:YAG laser in pediatric patients [22]. UC, and one had bilateral intravesical UCs that
The Ho:YAG laser has been the newest were punctured simultaneously. Four of the five
technologic advance in the endoscopic treat- UCs (80%) were adequately decompressed after
ment of ureteroceles in children [35]. The one attempt as determined by the postoperative
Ho:YAG laser is a solid-state, pulsed laser that US and VCUG findings. One patient required
emits light at 2100 nm. It combines the quali- a second puncture of the UC at 46  days of age
ties of the carbon dioxide and Nd:YAG lasers because of incomplete decompression. None of
providing both tissue cutting and coagulation the patients experienced intraoperative or post-
in a single device. Since the holmium wave- operative complications from transurethral laser
length can be transmitted down optical fibers, puncture of the UC, including bladder perfora-
it is especially suited for endoscopic surgery. tion, bladder neck or urinary sphincter injury, or
Tissue ablation occurs superficially, provid- urinary tract infection. None of the four patients
ing for precise incision with a thermal injury developed new VUR after laser puncture. Both
zone ranging from 0.5 to 1.0 mm. This level of patients with intravesical UCs did not demon-
coagulation is sufficient for adequate hemosta- strate preoperative or postoperative VUR.  One
sis [36]. Ho:YAG laser in contrast to Nd:YAG of the two patients with an ectopic UC demon-
laser has the advantages of greater precision, strated VUR before and after UC treatment; the
shallower penetration, less variability between other child never demonstrated VUR. In a more
different tissues, and less potential for thermal recent series by Pagano [21], Ho:YAG laser was
tissue injury [21]. used to treat eight newborn with UC and nine
The first author to report an extensive use of with urethral valves. Among patients with UCs,
Ho:YAG laser and comparing it to electrofulgu- all demonstrated partial or complete decompres-
ration was Mandal in 2013 [37], even if he did sion of the UC and improvement in hydrouretero-
not treat UC cases. His is the largest pediatric nephrosis at 3 months. No patient had change in
series to date reporting laser treatment of PUV VUR (either new-onset, worsening, or resolu-
in a cohort of 40 boys (mean age 24  months), tion) postoperatively; however, three patients had
comparing these patients in a nonrandomized persistent VUR that ultimately required ureteral
retrospective manner to 40 boys who under- reimplantation, all of which were into lower pole
went electrofulguration. They noted significantly moieties of duplicated systems. The relatively
shorter operative times and higher rates of spon- small sample size limits drawing wider conclu-
taneous voiding after catheter removal, as well as sions for general adoption in the pediatric uro-
nonsignificant trends toward lower rates of reful- logic community, yet to our knowledge this is the
568 P. Lelli Chiesa et al.

largest series to date on the use of Ho:YAG laser An additional, more theoretical, benefit is that
in the neonatal population. the energy supplied by the laser vaporizes the
The use of laser fibers in the neonate has treated tissue rather than just simply cauterizing,
several advantages compared with other more-­ incising, or puncturing the tissue as performed
established modalities. with electrocautery, stylet, and cold knife inci-
One advantage is that the laser fibers are sion, respectively. This may allow for the small
smaller, which is advantageous in the smaller incision made by the laser not to reseal compared
anatomy of the neonate [35]. From a techno- with the other conventional techniques [35]. The
logical standpoint, improvements in cystoscopic probability of the incision resealing is less than
and optic technology have allowed for the con- puncture, conventional incision, or electrocau-
struction of smaller cystoscopes over time while tery [22].
maintaining excellent visualization. The laser One known potential risk of transurethral
fiber lends itself well to these small cystoscopes decompression of a UC is iatrogenic VUR.
as the small caliber fibers can fit well through Previous studies have reported rates of iatrogenic
the working channels of the instruments and still reflux ranging from 18 to 27%, with t­raditional
allow for some irrigation flow [21]. In Pagano’s techniques. The precision and small hole afforded
[21] series small laser fiber (200 μm) were used by laser puncture may decrease the incidence
to decompress UC in newborns and, as reported, of iatrogenic reflux [35]. However, additional
that allowed a more accurate puncture while still procedures must be performed to confirm this
allowing for discrete tissue destruction by vapor- hypothesis.
ization. Although small Bugbee electrodes can
still be used with small neonatal cystoscopes, in
Pagano et al. experience, laser fiber offers greater 43.9 Fetal Intervention
precision and control [21]. On the other side,
Jankowski and Palmer used a larger fiber (365 or Fetal lower urinary tract obstruction (LUTO) is a
550 μm) except in one case (200 μm). The only rare and complex disease entity that carries with
one failed attempt at decompression occurred it a high degree of neonatal mortality and long-­
using the smaller laser fiber, which was then term morbidity. With the advent of fetal US in
successfully decompressed with a 550 μm fiber. the early 1970s, fetal intervention—initially vesi-
As the size of the laser fiber has a direct correla- cocentesis, later vesicoamniotic shunting (VAS),
tion with the puncture size of the UC, this may and more recently fetal cystoscopy—has been
explain why retreatment was required in the only proposed to reduce mortality and limit or reverse
patient treated with the smaller fiber [35]. renal injury for these patients. However, the ben-
Another benefit is that the laser fiber does not efits of fetal intervention remain controversial.
have the thermal effect beyond the point of inci- Outcome data in studies of fetal intervention in
sion site compared with the Bugbee electrode. LUTO are often confounded by small samples
This allows for precise puncture of the UC, and, sizes, limited follow-up data, and variations in
if necessary, multiple, small punctures can be criteria for intervention [39].
made rather than one comparably large puncture One of the major challenges in understanding
with the Bugbee electrode [35]. Laser energy not the role of fetal intervention in the management
only maintains the advantages of good hemo- of LUTO is the heterogeneity of urinary tract and
stasis comparable to coagulation electrosurgery renal pathology in LUTO itself. While PUV is
but also has the advantage of less thermal tissue the predominant etiologic mechanism of LUTO,
damage and earlier re-epithelialization of tissue. other processes, including urethral atresia, ure-
These advantages have lent themselves to the thral stenosis, obstructing UCs, and prune belly
adoption of the laser elsewhere in urologic prac- syndrome, are reported with some frequency.
tice, including as a common modality for treat- The severity of obstruction is also highly variable
ment of urethral and ureteral strictures [21]. and dependent on the underlying mechanism of
43 Ureterocele 569

obstruction. Added to the complexity of LUTO some cases required serial VAS placement. For
are also variations in renal pathology. Animal those patients who at the time of evaluation had
and human data strongly support the hypothesis evidence of severe LUTO with established renal
that the developing kidney is uniquely suscep- disease (Stage 3), fetal intervention was individu-
tible to injury from obstruction of urinary flow. alized and often based on bladder capacity and
Thus, variability in the degree of obstruction and bladder refilling after vesicocentesis [39, 41].
the gestational age at the onset of obstructed uri- Once the decision to intervene has been
nary flow are likely to have a direct impact on the made, the next question is: “how?” Fetal vesi-
severity of renal damage. The resulting second- costomy achieves the task but is now out of date
ary renal dysplasia or cystic dysplasia can occur [42]. Vesicoamniotic shunting (VAS) could
unilaterally or bilaterally and is often undetect- work, but there is still a high incidence of dis-
able until later in gestation. Other primary renal lodgement, and shunt technology has not been
developmental anomalies, such as renal hypopla- updated for the last 20–25 years. In utero fetal
sia or glomerulocystic disease, are reported fre- cystoscopy is emerging as a new and exciting
quently in LUTO [39, 40]. modality but is clearly technically challenging.
In an attempt to better define subsets of Most of current experience is with valve abla-
patients that would benefit from fetal interven- tion of PUV, which can often be difficult in the
tion, a LUTO classification system was devel- newborn, especially in the premature, growth-
oped at the Texas Children’s Fetal Center in 2012 restricted babies, let alone in even smaller
that incorporated (1) fetal urinary biomarkers of fetuses. In addition, valve ablation is not always
renal injury, (2) amniotic fluid levels as a surro- adequate to decompress the urinary tract, result-
gate for the severity of obstruction, and (3) imag- ing in persistently dilated upper tracts and dete-
ing studies to identify signs of renal dysplastic or riorating renal function. The in utero setting of
cystic changes (Table 43.2) [41]. a desperately compromised fetus with severe
For patients with low risk of either renal dis- obstruction and a limited window of time com-
ease or pulmonary hypoplasia (Stage 1), inter- pound this difficulty [39].
vention was not recommended. Patients with Normally UC are unilateral and may cause
signs of severe LUTO felt to be at high risk for only ureteral obstruction. However, although
either progressive renal injury or pulmonary uncommon, a large, bulging, or prolapsing UC
hypoplasia, but without evidence of severe pre-­ may cause BOO [43]. Usually, when fetal BOO
existing renal damage (Stage 2), underwent VAS; from UCs is diagnosed, the fetus is monitored in

Table 43.2  Proposed classification of fetal lower urinary tract obstruction (LUTO) according to severity (from
Ruano R et al.) [41]
Stage II (severe LUTO, with prenatal Stage III (severe LUTO, with prenatal
Stage I (mild findings suggestive of preserved fetal findings suggestive of fetal abnormal renal
LUTO) renal function) function)
Amount of Normal Oligohydramnios or anhydramnios Oligohydramnios, but usually
amniotic fluid anhydramnios
Echogenicity of Normal Hyperechogenic Hyperechogenic
fetal kidneys
Renal cortical Absent Absent Can be present
cysts
Renal dysplasia Absent Absent Can be present
Fetal urinary Favorable Favorable within three consecutive Not favorable after three consecutive
biochemistry evaluations evaluations
Fetal Not Indicated to prevent pulmonary May be indicated to prevent pulmonary
intervention indicated hypoplasia and severe renal hypoplasia but not postnatal renal
impairment impairment; further studies are necessary
The disease can progress from Stage I to Stage II and then to Stage III during pregnancy
570 P. Lelli Chiesa et al.

utero, and then at birth an endoscopic incision of b­ ladder-outlet obstruction and oligohydramnios
the UC may be done. Fetal intervention should are present.
be considered in the presence of severe BOO, The second experience with fetal endos-
which may result in bilateral renal damage, oli- copy was that of Montebruno in 2015 [47], who
gohydramnios, pulmonary hypoplasia, and neo- reported the successful use of fetoscopy to treat a
natal death. Indications are sonographic findings case of prolapsed UC in a 26-week female fetus,
suggestive of progressive obstruction such as causing intermittent BOO and oligohydramnios.
increasing bilateral hydronephrosis, hyperecho- In this clinical case, however, the UC was pro-
genic kidneys, and significant reduction of amni- lapsed through the external urethral outlet pro-
otic fluid volume [44, 45]. truding from the vulva; therefore, there was no
In 2001 Quintero [45] wrote that prenatal need to access the fetal bladder. Under maternal
treatment of bladder-outlet obstructing fetal UC local anesthesia and sedation, and fetal intra-
constituted an important landmark in minimally muscular analgesia and immobilization, a 3 mm
invasive fetal therapy, expanding the applications trocar was percutaneously introduced into the
of this approach for the in utero correction of amniotic cavity. By direct vision, the UC emerg-
birth defects. Anyway, the value and limitations ing between major labia of the vulva was identi-
of that novel prenatal intervention were yet to be fied and perforated under combined endoscopic
proved. and US control, by gently touching with a diode
As for PUV, treatment options include repeated laser fiber at power settings of 10  W, with suc-
amnioinfusions, placement of a vesicoamniotic cessful and persistent decompression of the UC
shunt, ultrasound-guided percutaneous needle and progressive reduction of the upper tract dila-
incision, or, more recently, fetal cystoscopic laser tation. Amniotic fluid remained normal through-
incision [43, 46]. It is obvious that, compared to out the whole pregnancy.
percutaneous needle puncture, endoscopic visu- In 2016 [44] Persico et  al. reported two
alization of the UC has the major advantage of additional cases of fetal UC treated by cysto-
allowing precise selection of the size and site of scopic laser decompression. In the first case,
the UC puncture and to protect the bladder wall a standard 3.3  mm uterine entry was used.
from damage [44]. The ureterocele was incised under endoscopic
The first to report fetal cystoscopic laser inci- vision using a 400  μm diameter diode laser
sion of UC was Quintero in 2001 [45]. Under fiber, with a power output of 10–15 W, with UC
general anesthesia the bladder of the fetus was decompression and subsequent improvement
accessed percutaneously under ultrasound guid- in hydronephrosis and restoration of normal
ance with a 3.5  mm trocar. Fetal cystoscopy amniotic fluid volume. For the second case, a
showed a cecoureterocele extending from the new approach was adopted using an all-seeing-
right side of the bladder floor (bladder neck) needle 1.6 mm endoscope. A 200 μm diameter
to the urethra. The UC was incised without Ho:YAG laser fiber, with a power output of
complications with a Nd:YAG laser (Surgical 10–15  W, was used to incise the UC, achiev-
Laser Technologies, Montgomeryville, PA, ing decompression of the UC, improvement
USA) using a 400 μm contact fiber both at the in hydronephrosis, and restoration of normal
level of the urethra and bladder, with immedi- amniotic fluid volume.
ate decompression of the lesion. As a result of The experience from Persico et  al. suggests
the treatment, amniotic fluid volume increased, that effective fetal cystoscopic laser treatment
pregnancy proceeded until term, left kidney of an UC under direct vision can be carried out
function was preserved, and pulmonary hypo- using an instrument with a much smaller diameter
plasia from oligohydramnios was avoided. (1.6  mm) than the standard 3.3  mm fetoscopic
Unfortunately, right kidney function could not access, and this approach provided an equally
be preserved. Earlier intervention in future good endoscopic view while retaining the ability
cases may be warranted but only in cases where to use a laser fiber. Up to date there are no previ-
43 Ureterocele 571

ous reports on its use for the intrauterine treatment bladder-­outlet injury, and risks to leave hypo-
of fetal UC. The diameter of the instrument used functioning or dysplastic renal segments.
for intra-amniotic access is particularly important In the past there was general agreement that
in fetal surgery because it has been shown to be this form of procedure carries an increased risk
directly related to the risk of premature rupture of of voiding dysfunction, although several authors
membranes, a common complication of intrauter- have shown that voiding dysfunction is part of
ine procedures. The minimally invasive technique the disease in many patients, even when the
described in this report, using a fine needle which patient is not operated on. However, with recent
allows for good endoscopic views and provides a standards of care at present, some authors advise
working channel for a laser fiber, has many poten- this approach which could be performed safely
tials for wider application in the field of prenatal at any age without consequences for bladder
intervention [44]. function, even if its role for the prevention of
urinary incontinence is questionable up to now
[13, 48, 49].
43.10 Lower Tract Approaches Ureteral reimplantation via Cohen’s method
is highly successful to stop reflux. Nonetheless,
Lower tract approaches to pyeloureteral duplex while the procedure still represents the most
system anomalies have traditionally included effective and consistent approach for achieving
total reconstruction and superior moiety (SM) single-stage cure of VUR, it is not 100% effective
salvage procedures, such as ipsilateral uretero- [49–51]. Beganovic et al. [52] reported persistent
ureterostomy (IUU) and ureteropyelostomy. VUR in 13% of cases and a secondary surgery
rate of 36% during long-term follow-up of 53
patients. Therefore, total reconstruction should
43.10.1  Total Reconstruction be limited to cases of preoperative multiple or
(Fig. 43.11) high-grade VUR [49, 50, 53].
Few attempts have been made to simplify
During previous years, total reconstruction was this surgical procedure. On the one hand, Gran
infrequently recommended in infants because et  al. [54] proposed avoiding the upper tract
of the risk of damaging the bladder. Concerns approach and also reimplanting the ureter of the
about lower urinary tract reconstruction include nonfunctioning pole; none of their 16 patients
­persistent reflux or obstruction from reimplan- developed any problems during an average fol-
tation procedure, urinary incontinence from low-up of 5 years. This result was confirmed by

Fig. 43.11  UC excision and reimplant in duplex system intravesical UC

572 P. Lelli Chiesa et al.

Wang et  al. [55]. On the other hand, IUU has ity [9, 61, 62]. Furthermore, the application of
been reported as a viable option, even in cases laparoscopic and robot-assisted techniques for
in which there is a marked discrepancy in diam- IUU has caused renewed interest in the applica-
eter between the donor and recipient ureter [56, tion of UU in the management of ectopic duplex
57]. Finally, others have suggested avoiding ureters. UU offers a theoretical advantage over
UC excision and bladder neck reconstruction heminephrectomy by preserving any function-
and, instead, performing the whole procedure ing upper pole renal parenchyma and avoiding
via an extravesical approach [10, 58]. potential morbidity from renal surgery, includ-
Furthermore, one of the demanding points ing damage to the more viable lower pole moi-
of reconstruction is reported to be the removal ety. Hence, minimally invasive IUU can be an
of the posterior mucosal wall inside the distal excellent option in carefully selected patients.
ureterocele and the repair of thinned-out poste- Though, Vates et al. [60] argue for judicious use
rior bladder wall, in order to provide adequate in the setting of absent SM function, high-grade
muscular backing. The complete mobilization recipient ureteral VUR, and massively dilated
of the distal lip of ureterocele is in some cases donor ureter.
difficult because it extends deep in the urethra Conventional laparoscopic IUU is feasible
and removal of the mucosa brings risks to injure and has been described [63, 64]. However,
sphincter mechanisms or even create urethrovag- the delicate intracorporeal suturing and fine
inal fistulas in female patients. In these instances ­reconstructive techniques necessary for the repair
Shimada et  al. [59] suggested to cut the distal with current conventional laparoscopic instru-
edge of the UC in order not to leave valvular ments remain challenging for other than expert
structure and fulgulate posterior mucosal epithe- laparoscopic surgeons [65]. Therefore, overall
lium instead of complete removal of the mucosal clinical experience with minimally invasive IUU
layer. remains limited, and published data describing
outcomes and complications are sparse. Most
investigators reserve IUU for children without
43.10.2  Superior Moiety Salvage IM VUR in order to avoid introducing reflux into
Procedures a functioning but anatomically abnormal upper
pole moiety [62, 63, 66]. However, a few cen-
Some investigators have shown that SM salvage ters have begun using IUU for the management
procedure (IUU, ureteropyelostomy) recov- of duplex anomalies irrespective of the degree
ers only a modest percentile of overall renal of ureteral dilatation, SM functionality, or pres-
function and may contribute to overall surgi- ence of ipsilateral reflux [57, 67]. Reimplantation
cal morbidity in some patients. Vates and col- of a refluxing lower pole ureter along with con-
leagues [60] reported that an average decrease comitant IUU is also a successful technique on
in overall renal function among the 31 patients the whole, although persistent VUR may be seen
who underwent partial nephrectomy was only [56, 57].
2.25%. Several case series report successful robotic-­
When obstruction of the upper pole moiety is assisted IUU procedures: the advantages of
the only feature encountered with duplex system robotic approach include superior exposure and
UCs, anastomosis between the upper and lower visualization, tremor filtration, motion scaling,
pole ureters is an appealing approach, particu- and wrist-like instrumentation with a highly
larly, as poorly or nonfunctioning upper poles magnified three-dimensional image, which may
do not require removal [14]. Therefore, IUU convey a potentially decreased risk of compli-
is an increasingly used alternative for children cations while improving cosmesis with smaller
with pyeloureteral duplication in whom the port incisions [61, 68–70]. Moreover, given the
obstructed moiety has significant functional- technical difficulties associated with conven-
43 Ureterocele 573

tional laparoscopic suturing, robotic-assisted 43.11 Upper Tract Approaches

surgery may reduce the learning curve and
increase the prevalence of performing minimally Upper tract approaches to pyeloureteral duplex
invasive surgery for IUU on infants and children system anomalies have traditionally included
with ectopic ureters [71]. These features increase pyelopyelostomy, ureteropyelostomy, and SM
surgeon dexterity by almost 50% in comparison heminephrectomy. The first two are seldom used
to conventional laparoscopic surgery and have because they seem to offer no advantage com-
been shown to decrease skills-based errors by pared with SM heminephrectomy and may por-
93% [72]. This is particularly important in com- tend a higher morbidity [9, 60].
plex procedures like IUUs that require precise
suturing to establish a watertight anastomosis.
Furthermore, in studies comparing robotic- 43.11.1  Heminephrectomy
assisted to open pediatric IUUs, pyeloplasties, with Partial Ureterectomy
and extravesical reimplantations, patients in the
robotic group presented comparable operative Heminephrectomy is traditionally considered a
times, estimated blood loss, and complication more definitive surgery compared to IUU, and
rates with slightly shorter lengths of hospital it is appropriate for children with ectopic duplex
stay and higher rates of improved hydronephro- system UC without VUR and is definitive in 85%
sis or drainage during initial follow-up imaging of such cases [26, 28, 79]. Heminephrectomy has
[73–75]. However, the use of robotic-assisted been referred to as the “simple” approach, favor-
procedures in the pediatric population was ini- ing excision of a poorly functioning upper pole
tially limited due to concerns regarding operat- moiety over lower tract reconstruction with IUU
ing the robot in smaller working spaces. Only (Fig. 43.12).
few reports currently exist analyzing the use As reported by Michaud [80], it offers theo-
of robotic-assisted procedures exclusively in retical advantages over UU by avoiding dis-
infants [76–78]. Nevertheless, as it has increas- tal ureteral dissection and potential pathology
ingly been demonstrated to be feasible and safe, associated with leaving the upper pole moiety
the role of robotic surgery in the pediatric popu- including hypertension from renal dysplasia and
lation has expanded. pyelonephritis. However, concerns with the use

a b

Fig. 43.12  Heminephrectomy with partial ureterectomy: isolation of proximal dilated ureter (a) and removed displas-
tyc upper pole, dilated pelvis, and ureter (b)
574 P. Lelli Chiesa et al.

of heminephrectomy include loss of renal func- avoiding to leave a refluxing ureteral stump [96,
tion from damage to the lower pole moiety, con- 97]. Moreover, in retroperitoneal laparoscopic
tinued or new-onset lower pole VUR, and the heminephrectomy one significant risk factor
need for reoperation on the distal ureter. leading to the possibility of conversion is the age
Several studies have shown the utility of of the child; the risk is greater in the younger age
heminephrectomy, especially in children with group, especially in the first 6 months of life [84,
absent SM function and absence of preoperative 86, 98]. Hence, the spatial limitations of the nar-
­ipsilateral VUR.  Potential suboptimal outcomes row retroperitoneal working space in children
include ipsilateral hemi pole functional loss, UTI younger than 12  months and the difficulty of
caused by persistent VUR, de novo VUR, and removing the entire ureter near the bladder dome
need for additional surgery. However, only few lead some authors to recommend the retroperito-
long-term data exist with respect to long-term neal approach in patients older than 12  months
functional renal outcomes after minimally inva- who need an upper or lower pole heminephrec-
sive SM heminephrectomy. tomy with partial ureterectomy [97]. However,
Laparoscopic retroperitoneal [81–86], laparo- retroperitoneal laparoscopic heminephrectomy
scopic intraperitoneal [31, 32, 55, 87–90], robotic allows direct access to and excellent exposure of
retroperitoneal [91], and robotic intraperitoneal the kidney and its pedicle as well as minimal in
[92, 93] approaches have been described with situ mobilization of the kidney and surrounding
respect to heminephrectomy. There are several structures. Moreover, this technique decreases
advantages offered by these approaches com- the risk of intraperitoneal organ injury and
pared with open surgery. First, the innocent pole ­postoperative adhesions, which is of paramount
is not directly manipulated as it is often in open importance for the future of our pediatric popula-
surgery, which requires mobilization of the kid- tion [99].
ney from surrounding structures and downward The robotic intraperitoneal technique is pre-
traction for exposure. Such maneuvers risk tor- ferred by some authors [9, 93], in part because
sion of the renal pedicle and consequent injury or of the superior three-dimensional visualiza-
thrombosis of innocent pole vasculature [85, 94]. tion and magnification afforded by the robot,
In contrast, a laparoscopic approach is performed in part because of the articulating instrument
with the kidney in situ with minimal traction that allows for the use of only two small robotic
on the pedicle [82]. This approach may reduce working ports in most cases, in part because
the risk of remnant pole vasospasm or vascular this procedure seems to be associated with low
injury [70]. Furthermore, minimally invasive complication rates [92]. Moreover, robotic tech-
approaches offer a shorter hospital stay and an nology allows more accurate distinction of the
improved cosmesis with comparable operative vascular and anatomic plane between upper and
duration [95]. lower poles of the duplex system, as well as an
Transperitoneal and retroperitoneal laparo- improved ability to preserve innocent pole vas-
scopic heminephrectomy are comparable with culature, parenchyma, and ureter. Specifically,
respect to operative duration, hospital stay, and Malik and colleagues [100] reported that robotic
analgesic requirements, and both are superior to intraperitoneal technique allows easy and effi-
open surgery in these respects [31, 32, 83, 93]. cient identification of the ureters. Therefore, the
Laparoscopic intraperitoneal heminephrectomy authors do not require the placement of a retro-
seems to be a faster, safer, and easier procedure grade ureteral catheter preoperatively, avoiding
to perform in children compared to laparoscopic additional instrumentation.
retroperitoneal approach due to a larger opera- However, heminephrectomy does not fre-
tive chamber available, a good overall exposure quently represent a curative intervention for
of the anatomy of the kidney, and its vascular- children with duplex system anomalies and
ization and the possibility to remove the entire VUR.  Husmann and colleagues [26, 28] found
ureter near the bladder dome in refluxing systems that in children with ectopic ureterocele in whom
43 Ureterocele 575

preoperative VCUG shows reflux, both endo- 10. Merguerian PA, Taenzer A, Knoerlein K, et  al.

Variation in management of duplex system intravesi-
scopic incision and heminephrectomy are defini- cal ureteroceles: a survey of pediatric urologists. J
tive in only 16% of cases. Several studies have Urol. 2010;184:1625.
shown a prevalence of de novo ipsilateral lower 11. Merguerian PA, Byun E, Chang B.  Lower urinary
pole or contralateral reflux of 40–50% after upper tract reconstruction for duplicated renal units with
ureterocele. Is excision of the ureterocele with recon-
tract surgery [19, 26, 28, 101]. struction of the bladder base necessary? J Urol.
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tomy alone when compared to the three other ing challenge in infancy and childhood. BJU Int.
2002;90:777–83.
surgical approaches (lower tract reconstruc- 13. Castagnetti M, El-Ghoneimi A.  Management of

tion LTR, simultaneous upper and lower tract duplex system ureteroceles in neonates and infants.
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Although heminephrectomy was a definitive pro- 14. Pohl HG.  Recent advances in the management of

ureteroceles in infants and children: why less may be
cedure in some patients without reflux at presen- more. Curr Opin Urol. 2011;21:322–7.
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17. Shankar KR, Vishwanath N, Rickwood AM. Outcome
Acknowledgments Authors would like to thank Dr. of patients with prenatally detected duplex system
Anthony A. Caldamone – Professor in Surgery (Urology) ureterocele; natural history of those managed expec-
and Pediatrics at Brown University, Providence RI, U.S. tantly. J Urol. 2001;165:1226–8.
– for providing iconography (Figs. 43.2, 43.8, and 43.10). 18. Coplen DE, Austin PF.  Outcome analysis of prena-
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laparoscopic heminephrectomy in duplex kidney in
 Posterior Urethral Valves: Fetal
and Neonatal Aspects 44
Lisieux Eyer de Jesus and João Luiz Pippi-Salle

Posterior urethral valves (PUV) are the most 44.1 PUV: Definition
common form of urethral obstruction. The dis- and Physiopathology
ease occurs in 1:5000–1:8000 live male neonates
[1]. PUV are a significant cause of perinatal mor- PUV are mucosal leaflets that determine partial
tality and one of the most common causes of kid- obstruction on the proximal (posterior) urethra.
ney failure in infancy and childhood (a third of Their embryological origin is controversial.
the patients suffering from PUV progress to ter- PUV were classified by Young [3] into three
minal kidney failure during life, and PUV consti- types (Fig. 44.1):
tute 15% of children undergoing renal
transplantation). Grade 5 kidney failure is rare 1. Type I, the most common (approximately

(7:1,000,000 neonates), but is determined almost 95%): A membranous incomplete leaflet in a
exclusively by PUV/fetal urethral obstruction caudal and anterior direction, shaped as a
and bilateral renal hypoplasia/dysplasia. Survival crescent moon, with the concavity facing the
of such neonates in dialysis is possible in modern verumontanum, where from it originates.
referral centers: around 80% survive till pre- 2. Type II, nowadays considered clinically insig-
school age [2], but at the cost of a very high mor- nificant: The bicuspid valves assume a
bidity and the need for renal transplantation in cephalic direction from the verumontanum to
young children. the bladder neck.
The purpose in this chapter is to explore the 3. Type III (approximately 5%): A membra-
aspects of PUV during fetal life and infancy, nous concentric perforated diaphragm
especially in what concerns diagnostic and thera- located in the posterior urethra, near to the
peutic interventions on the disease. verumontanum.

Recently a unifying concept was proposed by

Dewan and Goh [4], suggesting that PUV are in
fact a unique disease, caused by a congenital
L. E. de Jesus obstructing posterior urethral membrane
Pediatric Surgery and Urology Department, Antonio (COPUM) that originates from the caudalmost
Pedro University Hospital, Rio de Janeiro, Brazil
end of the Wolffian duct when the duct fuses with
Servidores do Estado Federal Hospital, the developing cloaca (4th gestational week). The
Rio de Janeiro, Brazil
persistent membrane obliterates in a variable
J. L. Pippi-Salle (*) fashion, determining various degrees of obstruc-
Division Chief of Urology Sidra Medical and
Research Center, Doha, Qatar tion, affecting the development of the kidneys,

© Springer Nature Switzerland AG 2019 579

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_44
580 L. E. de Jesus and J. L. Pippi-Salle

Type 1 Type 2 Type 3

Fig. 44.1  Posterior urethral valves, types (schematic). Superior line: anatomical view, coronal cut. Inferior line: endo-
scopic view (valves in yellow). Verumontanum: blue circles

ureters, and bladder. For these authors COPUM namely, uni- or bilateral dysplasia. The distal
should be differentiated from Cobb’s collar, a tubules are the most affected, resulting in a lim-
transverse partial obstruction located near the ited concentrating capacity and a
external urethral sphincter. pseudoaldosteronism-­ like polyuric syndrome
Fetal response to urethral obstruction is char- that persist temporarily or permanently after
acterized by hyperplasia and hypertrophy of the relieving the obstruction (post-obstructive
muscular bladder wall. The functional and ana- diuresis).
tomical reactive modifications of the detrusor, As fetal urine is the main component of the
together with increased deposition of specific amniotic fluid, severe urethral obstruction dur-
collagen types, determine progressive thicken- ing fetal life may determine oligohydramnios
ing, muscular hyperactivity, and loss of bladder from the second trimester of pregnancy. The
compliance. Early in gestation, the bladder pres- severity of oligohydramnios has prognostic and
ents as an enlarged fluid-filled structure (mega- therapeutic implications and has to be moni-
cystis) and evolves to a thickened, low-capacity, tored during pregnancy in fetuses with images
low-compliance, pseudodiverticular organ. suggestive of PUV.  The decreased amount of
Bladder emptying occurs at expense of high amniotic fluid causes secondary pulmonary
pressures from fetal life. Back pressure deter- hypoplasia, as the normal development of the
mines hydroureteronephrosis, frequently associ- lungs depends on the aspiration of amniotic
ated with parenchymal atrophy. Either fluid. Oligohydramnios may also cause mor-
vesicoureteral reflux or functional obstruction of phological abnormalities, especially clubfeet
the terminal ureters can occur secondarily to high and, in severe cases, face deformities (Potter’s
bladder pressures, detrusor hypertrophy, and low face). Severe cases of PUV can lead to prenatal
bladder compliance. fetal death. Figure  44.2 illustrated many fea-
The ongoing obstruction in the developing tures of dysmorphic urinary tract associated
kidneys can determine structural abnormalities, with PUV.
44  Posterior Urethral Valves: Fetal and Neonatal Aspects 581

<1% of the gestations, and most persistent

cases are due to PUV (Fig. 44.3). The differ-
ential diagnosis of fetal megacystis is between
obstructive problems (mainly PUV), transi-
tory maturational phenomena and a compo-
nent in syndromic fetuses. A dedicated
ultrasonographist should be attentive for the
fact that, from the second trimester, failure of
bladder emptying for 45 min suggests obstruc-
tion [1].
4. Thickened bladder/megacystis.
5. Bilateral hydroureteronephrosis is typical, but
approximately 15% of the fetuses present uni-
lateral dilatation.
6. Renal dysplasia (hyperechogenic kidneys,

multiple cortical cysts, loss of corticomedul-
lary differentiation).
Fig. 44.2  Autopsy of a fetus with severe PUV (bilateral
renal dysplasia, hydroureteronephrosis, thickened detru-
7. Dilatation of the posterior urethra (keyhole
sor, and dilated posterior urethra) sign), which is detectable in half the cases of
PUV, but presents low specificity (may be
detected in 1/3 of non-PUV lower urinary tract
obstruction (LUTO) cases [1])—Fig. 44.4.
44.2 PUV: Prenatal Aspects
Fetal MRI may also document the same find-
Prenatal ultrasonography is now routine, with at ings (Fig. 44.5). The main differential diagnoses
least three evaluations in the first, second, and are prune belly syndrome, other urethral obstruc-
third trimesters. PUV is commonly diagnosed tions of the posterior urethra (stenosis and atre-
from the 16th gestational week, after formation sia), urethral anterior valves, syringocele or
of the kidneys and predominance of urine as the diverticula, obstructive prolapsing ureteroceles,
foremost component of the amniotic fluid, congenital megalourethra, severe vesicoureteral
although some signs may be seen earlier, espe- reflux associated with detrusor-sphincter dyssyn-
cially in severe cases. ergia [7], and megacystis-megaureter-microcolon
The disease is normally perceived during the associations.
second trimester, from a constellation of symp- As mentioned before the pregnancy needs to
toms (male gender, bilateral hydroureteronephro- be closely monitored in any fetus suspected of
sis, megacystis, dilated posterior urethra, and PUV, in order to detect the two main fetal com-
oligohydramnios). The main ultrasound signals plications of the disease:
to suggest PUV are:
1. Oligohydramnios (that suggests secondary

1 . Male fetus (PUV is exclusive of males). kidney damage and dysplasia and is directly
2. Oligohydramnios, which is also a poor prog- related to lung hypoplasia and fetal respira-
nostic sign. tory insufficiency). Oligohydramnios is the
3. Megacystis (defined as ≥7  mm longitudinal trigger to consider intrauterine therapy for
bladder diameter in the first trimester and fetal PUV cases.
bladder longitudinal diameter  ≥gestational 2. Fetal ascites or perinephric urinoma, normally
age (weeks) + 12 mm in the second and third secondary to the rupture of a renal calix sec-
trimesters [5]). Early diagnosis suggests a ondary to back pressure. Bladder rupture is
worse prognosis [6]. Megacystis is present in exceedingly rare.
582 L. E. de Jesus and J. L. Pippi-Salle

Fig. 44.3  Ultrasound of

17-week fetus with
megacystis caused by
PUV (K kidney,
B bladder)

Fig. 44.4  Ultrasound in a fetus with megacystis and key-

hole sign in a bladder with thickened detrusor

Future renal prognosis is mainly determined

by signs of kidney dysplasia, especially hyper-
echogenicity, cortical cysts, and loss of cortico-
medullary differentiation [8, 9] (Fig. 44.6). Total
Fig. 44.5  Fetal MRI, posterior urethral valves, showing
parenchymal area/cortical volume before decom- megacystis and posterior urethral dilatation
pression has also been suggested as a prognostic
marker, but no prenatal nomograms are available
till now [8, 10, 11]. Lower urinary TGF-β1, nary/amniotic peptide profile is also being
TNF-­α, and microalbumin suggest better prog- researched in search of prognostic markers for
nosis, as well as progressive lowering of these fetal urinary obstruction [14].
markers after decompression [12]. Recently There is also some evidence that antenatal
some authors have suggested that certain genetic detection of PUV allows a better prognosis
markers (copy number variants) may also affect [15], possibly to planned delivery in better
kidney prognosis in PUV cases [13]. Fetal uri- equipped centers, where the neonates may
44  Posterior Urethral Valves: Fetal and Neonatal Aspects 583

Fig. 44.6 Postnatal
ultrasound of baby with
PUV (hyperechogenic
kidney and cortical
cysts)

receive expert nephrological care, including pulmonary insufficiency, but less so to avoid kid-
dialysis as needed. Also, there is a clear bias in ney failure.
the literature as unfavorable cases are randomly The pertinent literature reporting prenatal
born in underdeveloped countries, while in interventions suffers from several biases, namely,
developed ones, fetal diagnosis of severe dis- analysis of small populations, high taxes of vol-
ease leads to abortions, therefore selecting untary termination (including after prenatal treat-
favorable cases. ment), and different criteria for fetal selection.
Fetal intervention to treat PUV may be Recent research comparing nonintervention, VAS
done by: and ITVLA, in severe LUTO cases suggests that:

1. Repeated vesicocentesis. (a) The probability of perinatal survival increases

2. Vesicoamniotic shunting (VAS). in the intervention groups, possibly due to
3. Intrauterine antegrade transvesical laser valve better postnatal pulmonary function.
ablation (ITVLA). (b) Renal function tends to be better in the first
4. Amnioinfusion (indicated in late pregnancy to semester of life only in the ITVLA group
avoid premature births in cases of severe late [16].
oligohydramnios).
5. Intraperitoneal shunting as a treatment for
Prenatal intervention should not be offered to
severe fetal ascites (uncommon). fetuses affected by irreversible fetal kidney
­failure, as suggested by ultrasound and analysis
VAS or ITVLA may be considered only in of fetal urine, obtained by transabdominal trans-
singleton pregnancies with early, severe, or pro- uterine puncture of the fetal bladder. Table 44.1
gressive oligohydramnios in genetically normal describes the most common markers to evaluate
fetuses unaffected by other severe malforma- fetal kidney viability (Table 44.1) [1].
tions. A careful discussion with the parents is VAS and ITLVA are better indicated for a sec-
needed. Maternal risks are to be considered. In ond trimester fetus with oligohydramnios and
addition these interventions offer no guarantee of favorable urinary markers. Both VAS and ITVLA
recovery of renal function for the future baby. offer better perinatal survivals (mostly as a con-
Fetal therapy for PUV does succeed to prevent sequence of avoiding respiratory insufficiency
584 L. E. de Jesus and J. L. Pippi-Salle

Table 44.1  Fetal urine markers obtained by repeated

bladder aspirations
Fetal urinary prognostic marker Favorable values
Sodium <100 mEq/L
Chloride <90 mEq/L
Calcium <8 mg/dL
Osmolality <200 mOsm/L
Protein <20 mg/dL
β2-Microglobulin <6 mg/L

secondary to PUV) and, probably, lower rates of

postnatal kidney failure, considering that the
fetuses selected for the procedures are among the
Fig. 44.7  Bladder prolapse in a shunted baby with PUV
PUV cases with viable renal function. Even so,
both methods have been unable to eliminate the
risk of future kidney failure, possibly because inal and uterine walls and the fetal abdominal and
fetal intervention is done after the embryological bladder walls. Once inside the bladder wall, the
period of embryological kidney formation, there- endoscope is then used to antegradely ablate the
fore does not prevent renal dysplasia. urethral valve with laser. Prospective series of
VAS was the first successful fetal treatment ITVLA are still rare, but the results suggest fetal
for PUV. A double pigtail catheter is transabdom- survival higher than 50%, elimination of pulmo-
inally inserted into the fetal bladder, communi- nary hypoplasia, normalization of amniotic fluid
cating the organ with the amniotic cavity. The and bladder anatomy, and postnatal adequate kid-
procedure is minimally invasive and may be done ney function in approximately ¾ of the patients
under local anesthesia. An ultrasound-guided [17–19]. Obstetric problems with ITVLA are the
Seldinger-like puncture method is used. The same as with VAS. The procedure does not have
mother’s abdominal and uterine walls and the the risks of catheter migration/dislodgement,
fetal abdominal and bladder walls are punctured. obstruction, extra-­anatomical positioning, and iat-
A guidewire is inserted. A double-coil catheter is rogenic gastroschisis. Theoretically ITVLA is
inserted over the guidewire. One extremity of the also advantageous to provide a more physiologi-
catheter is located inside the fetal bladder. The cal development of the cycling bladder. Serious
other end extrudes through the fetal abdominal urological complications (urethral fistulae and
wall into the amniotic cavity. The risks to the stenoses) have been reported [19].
mother are relatively small, including premature
membrane rupture, premature labor, and chorio-
amniotic infection. The main risks for the fetus 44.3 Postnatal Management
are dislocation of the catheter (spontaneous,
driven by fetal growth or pulled by the fetus), Most cases of PUV are antenatally diagnosed and
bladder prolapse, and iatrogenic gastroschisis have bilateral hydroureteronephrosis associated
(Fig. 44.7). with a thickened detrusor on postnatal ultra-
The limited success, the complications with sound. In cases with oligohydramnios and renal
VAS and the proper nature of the method (pallia- and/or pulmonary hypoplasia/insufficiency,
tive shunting that excludes fetal bladder cycling) Potter facies features may be present. Male
and the recent technological progress gave rise to babies with an antenatal diagnosis of LUTO
ITVLA, a newer proposal to treat fetal PUV.  In should be delivered in hospitals with neonatal
this case maternal and fetal anesthesia are needed. intensive care unit (NICU) and specialized
The fetal bladder is accessed through an endo- nephro-urological ­ pediatric care available.
scope that perforates serially the mother’s abdom- Pulmonary insufficiency may associate with the
44  Posterior Urethral Valves: Fetal and Neonatal Aspects 585

Fig. 44.8  Perinatal ultrasound (left, hyperechogenic dysplastic kidney; right, thick bladder and bilateral ureteral
dilatation)

need for ventilators and ­prematurity is common. any male babies presenting with UTI/urinary
Respiratory insufficiency is usually seen after sepsis should be investigated with ultrasound,
pregnancies complicated by severe oligohydram- and if hydroureteronephrosis and a thickened
nios without fetal intervention. Pneumothorax bladder is present, diagnosis of PUV should be
may result from the attempts to ventilate such entertained. The following management is
babies. warranted:
In patients without prenatal diagnosis, the
most common presentation of the disease is peri- 1. The children must be submitted to a confirma-
natal sepsis secondary to urinary tract infection tory ultrasound examination as soon as possi-
(UTI). Of note, neonates with UTI do not present ble after birth (Fig. 44.8).
with typical signs as seen in older children. The 2. Any male babies suspected of having PUV
baby may present with sepsis, failure to thrive must be catheterized as soon as possible after
and refusal to feed, all of them nonspecific signs birth. Catheters without balloons are prefera-
of UTI. ble, as the balloon irritates the trigone and
Urinary retention, abnormal flow and voiding those catheters show worse drainage as com-
problems are always present in neonates with pared to non-ballonated catheters with the
PUV.  One should not discard this diagnosis same diameter. Catheterization may be diffi-
because the baby seems to void adequately, cult: The catheter may curl and stop at the
although usually with weak stream and high dilated posterior urethra. In this case Coudé
post-­voiding residuals [20]. catheters may be of help. An open-ended cath-
The physical examination of the baby may be eter can also be inserted passing over a glide-
unremarkable. The dilated kidneys may be pal- wire (Seldinger-like technique). Some authors
pable, as well as the bladder. Even an empty blad- have suggested the usage of double-J catheters
der may be palpated, because of the thickened [21], but they need to be inserted over a guide-
bladder wall. Some babies present problems that wire, which may be difficult without sedating
are secondary to oligohydramnios (Potter facies, the child and without using an endoscope.
clubfeet) or to fetal intervention. Associated mal- Most term neonates can be catheterized with a
formations are uncommon. 5–6 Fr tubes. Prematures and small-for-age
Any male neonate presenting with bilateral babies may need smaller catheters.
hydroureteronephrosis is suspect of PUV. Also, Cystostomies are not indicated, except in
586 L. E. de Jesus and J. L. Pippi-Salle

exceptional circumstances, when no other and no exposure to radiation. However, there

way to catheterize is possible. are disadvantages such as the need for exper-
3. After drainage post-obstructive diuresis may tise and clear demonstration of the urethral
occur, requiring careful replacement and elec- and bladder anatomy [23]. Transperineal
trolyte monitoring. Nephrological consulta- ultrasound is the only image exam capable to
tion is advised to manage such patients. visualize the PUV per se (Fig. 44.10).
4. The creatinine serum values after catheteriza-
tion must be serially followed. One should
remember that the baby’s creatinine reflects 44.3.1 Treatment
partially the mother’s values in the first days
of life. As a rule, during the first week, creati- 44.3.1.1 Valve Ablation
nine values are relatively higher than the nor- The treatment of PUV involves endoscopic valve
mal and decrease gradually to the normal ablation with cold knife (preferable) (Fig. 44.11),
childhood values. Only after the first week electrocoagulation with bugbee or hook elec-
serum creatinine reflects exclusively the kid- trodes and laser fulguration [24, 25]. The valves
ney function of the child. Two important con- should be ablated at 12–5–7 o’clock positions.
cepts to retain are (a) creatinine nadir, defined Warm irrigation fluid should be used in order to
as the lowest measured serum creatinine and avoid hypothermia in babies. Forceful ablation of
(b) velocity to reach creatinine nadir. the valves with a Whitaker hook (insulated cro-
Generally speaking, the faster the child chet needle) or Fogarty balloon catheter may be
reaches the creatinine nadir, the better the used if appropriate endoscopic equipment is not
prognosis. For many authors, a nadir available or if the patient presents a high risk for
>0.85  mg/dL (>75  μmol/L) during the first anesthesia, as this procedure may be done at the
year of life signals bad prognosis for the renal NICU with local transurethral anesthesia [26].
function in the future [22]. Circumcision should be done concurrent to abla-
5. As mentioned above the metabolic conditions tion, as the procedure minimizes the occurrence
of the child are also to be monitored, espe- of postoperative UTIs [1]. Most authors suggest
cially diuresis, as post-obstructive diuresis doing a voiding cystourethrogram post ablation
can occur. The child may present severe poly- but often postpone it if the baby is voiding well,
uria that may attain >4 mL/kg/h. Venous gas- the hydronephrosis decreases, and creatinine is
ometries and evaluation/treatment of acidosis stable.
are needed, as well as serum electrolyte evalu-
ation. There is a risk of dehydration in the 44.3.1.2 Urinary Diversion
absence of compensatory intake. Severe cases Vesicostomy should be used whenever valve
of PUV typically present dysfunction of the ablation is impracticable due to lack of adequate
distal nephron and may show pseudohypoal- instrumentation or in very small babies (prema-
dosteronism (metabolic acidosis, hyponatre- tures) with a small caliber urethra. One should
mia, and hyperkalemia). not hesitate to do this procedure in such cases as
6. The gold-standard exam to diagnose PUV is forceful instrumentation of a small urethra can
the voiding cystourethrogram (VCUG) that traumatize it and cause strictures, a challenging
should be performed immediately after stabi- problem in infants. Although considered a simple
lizing the baby (Figs. 44.9 a–c). The exam not procedure, vesicostomies are prone to stenosis if
only demonstrates the valves but also diagno- not done properly. The opening at the bladder
ses bladder problems and secondary vesico- dome should be wide as the thickened detrusor
ureteral reflux. Transperineal ultrasound was precludes prolapse.
recently reported as a good investigation alter-
native, with the advantages of being feasible 44.3.1.3 High Diversion
without removing the baby from the NICU, The indication of high diversions (high ureter-
being painless and posing no risks of infection ostomies and pyelostomies) is controversial
44  Posterior Urethral Valves: Fetal and Neonatal Aspects 587

b c

Fig. 44.9 (a) PUV – dilated posterior urethra (larger than thra and no vesicoureteral reflux. (c) PUV and left vesico-
the bladder!) and bilateral vesicoureteral reflux. (b) ureteral reflux associated with dysplastic kidney
Trabeculated bladder and typical dilation of posterior ure-

although, in our opinion, they are beneficial in renal function. They have been classically used
some cases. Patients in significant renal failure in those patients that do not recover kidney
may benefit from cutaneous ureterostomies, and function after an adequate period of decompres-
they prevent UTI and further deterioration of sion, those with persistent severe dilatation after
588 L. E. de Jesus and J. L. Pippi-Salle

urethra

VALVE

Posterior
urethra

Fig. 44.10  Transperineal ultrasound, demonstrating pos-

terior urethral valves

decompression, or children presenting untreat-

able urinary sepsis after antibioticotherapy and
bladder decompression. In addition there is evi-
dence that, although it does not prevent progres-
sion of renal failure, this occurs more slowly,
postponing the need for dialysis or transplant to Fig. 44.11  Neonatal resectoscope and hook cold knife:
a later stage in life [27]. High diversions imply Preferred way to ablate PUV
building stomas that may be difficult to deal
with, as they are too high to be protected by dia-
pers and do not adapt well to urinary bags. Despite the various controversies and disad-
Besides, they may be socially stigmatizing. In vantages of high diversions, some patients, espe-
addition, future surgical undiversion can be cially those presenting severe renal damage
challenging, in order to avoid kinking or devas- which would be candidates to kidney transplanta-
cularization of the ureter. Other authors believe tion during infancy or children living in countries
that patients that do not respond to catheteriza- without transplant availability, need special con-
tion and/or vesicostomies have irreversible kid- siderations. For those children high urinary diver-
ney damage that will not improve by high sion seems to prolong life of the native kidneys
diversions. Occasionally the persistent dilata- and to postpone the need for transplantation [27].
tion of the high tract may occur due to “pinch- After successful valve ablation, urodynamic
ing” of the distal ureter by the thickened bladder problems are expected. Secondary hyper-
detrusor. Initial treatment with anticholinergics active low-compliant low-capacity bladders are
is warranted in such cases, but if unsuccessful typical of young children presenting with
we should not hesitate to perform a high diver- PUV.  Polyuria complicates the clinical scenario.
sion. Some authors suggest the use of Sober Y Bladder hyperactivity may be treated with oral
ureterostomy (Fig.  44.12) to avoid bladder anticholinergics, and some groups have demon-
defunctionalization, but this procedure is more strated that systematic treatment from neonatal
demanding (same as pyeloplasty) which can be age is advantageous [28]. One should resist temp-
problematic in an unstable uremic patient, the tation to augment PUV bladders as most will even-
usual candidates for such intervention. tually self-augment themselves due to progressive
44  Posterior Urethral Valves: Fetal and Neonatal Aspects 589

Fig. 44.12 
Diagrammatic URINE
representation of high
diversions PYELOSTOMY

PELVIS

URETER
“LOOP”
URINE URETEROSTOMY

“Y” (SOBER)
URETEROSTOMY

URINE

detrusor failure that usually occurs late in child- functional exclusion is not a reason for ablative
hood or puberty. surgery.
Bladder neck hypertrophy is also common and Kidney failure presents in approximately 30%
may be treated with alpha-blockers. Bladder neck of PUV patients. Terminal kidneys distribute
incision may be proposed. In this case the risk of among age groups, typically neonates (cases pre-
iatrogenic incontinence is difficult to evaluate, as senting severe antenatal oligohydramnios), tod-
wetting is quite common in those children, due to dlers (surviving neonatal period, especially after
bladder dysfunction and polyuria. multiple UTI episodes), school-aged children
Vesicoureteral reflux is present in 30–50% of (typically 7–8 years old), and young adults, soon
PUV cases and resolves in most patients after after puberty and postpubertal growth.
treatment of the urethral obstruction and urody-
namic bladder problems. A special group are the
patients presenting the so-called VURD syn-
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 Hydrometrocolpos
45
Devendra K. Gupta, Shilpa Sharma,
and Kashish Khanna

the uterus and vagina by fluid other than blood or

45.1 Introduction
pus [1–4]. Vagina distends much more than the
uterus. The accumulation of blood or pus in both
Hydrometrocolpos (HMC) is a rare genitourinary
the vagina and the uterus is called hematometro-
condition found in females in which the uterus
colpos or pyometrocolpos, respectively.
and vagina are grossly distended by retained vag-
Sometimes, only the vagina gets distended, and
inal secretions or urine. It is caused by excessive
the uterus is not distended by fluid, blood, or pus;
vaginal secretions and distal vaginal obstruction
it is then called hydrocolpos, hematocolpos, or
[1, 2]. The condition can be recognized early dur-
pyocolpos, respectively.
ing the antenatal period with prenatal ultrasound
(USG) and fetal magnetic resonance imaging
(MRI). The reported incidence has increased to
1/16,000 live births with the growing use of these 45.3 Embryopathogenesis
antenatal investigative modalities.
HMC presents at the two peaks of age in chil- During the second month of fetal life, the
dren, initially during the neonatal period, when there Mullerian ducts develop as tubular invaginations
is a high vaginal secretion under the influence of parallel to mesonephric ducts [5]. The caudal
high maternal hormones, and then at early puberty ends form the uterus and vagina and fuse in the
with production of estrogenic hormones. The distal midline to meet the urogenital sinus (UGS). The
vaginal obstruction is mostly due to imperforate distal portion of the fused Mullerian ducts is tem-
hymen, followed by the presence of a transverse porarily occluded completely by a solid cord of
vaginal septum, and less commonly due to the vagi- cells, the Mullerian tubercle, the caudal end of
nal atresia of the distal two third of the vagina [3, 4]. which becomes the hymen [6].
Failure of degeneration of the epithelial
cord in the Mullerian tubercle results in imper-
45.2 Definition forate hymen. Persistence of a portion of the
solid cord of cells in the fused Mullerian ducts
The word Hydrometrocolpos is derived from the above the hymen results in vaginal atresia.
Greek terms hydro which means water (fluid); Transverse septum of the vagina results from
metro, tubular structure (uterus); and colpos, incomplete coalescence of vacuoles that
vagina. Hydrometrocolpos refers to distension of develop as the epithelial cord begins to degen-
erate [1, 2, 4].
D. K. Gupta (*) · S. Sharma · K. Khanna The retained fluid in HMC is usually serous
Department of Pediatric Surgery, All India Institute of
Medical Sciences, New Delhi, India or mucoid with large numbers of desquamated

© Springer Nature Switzerland AG 2019 591

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_45
592 D. K. Gupta et al.

epithelial cells and leukocytes. Secondary infec- 45.6 Clinical Presentation

tion of the vaginal fluid, usually with colonic
organisms, is not uncommon and is a real risk to Neonatal/early presentation: About 80% of the
life [4]. HMC is classified into two types on the cases present in the first 3  months of life. The
basis of its contents: typical presentation in a neonate is abdominal
distension of the lower abdomen along with a
• Secretory: mucoid viscid material secreted by palpable lower midline mass usually as a surgical
cervical uterine glands. emergency. Occasionally, the newborn baby girl
• Urinary: urine is collected in the vagina due may also present with a bulging hymen and an
to a valvular flow of urine to vagina. absence of vaginal orifice [1–3, 9].
The baby is usually sick due to the gross dis-
It is expected that both the estrogenic stimula- tension and associated sepsis due to purulent
tion and the vaginal obstruction must coexist material as content of the HMC.  The upper
before HMC develops. If the fetal reproductive vagina usually takes the brunt and becomes enor-
tract is sufficiently stimulated by maternal hor- mously dilated with the contents. The less disten-
mones, a newborn infant having the vaginal sible and thick muscular uterus is involved to a
obstruction will develop HMC. If there is lower lesser degree, but it is always larger than the nor-
level of maternal hormones, the obstruction mal size. The mass may extend up to the costal
though present may remain unnoticed until margin and may cause life-threatening respira-
puberty. It is probably due to this reason that in tory distress.
most patients, HMC though congenital in origin The mass is so large that it may cause obstruc-
is not symptomatically manifested until hemato- tive or compressive features on the surrounding
colpos is superimposed at the time of the men- structures in the pelvis, leading to urinary reten-
arche [2]. tion and constipation [10]. The presence of the
distended vagina may kink the urethra and com-
press it causing acute urinary retention.
45.4 Antenatal Diagnosis Compression of the ureters at the pelvic brim
results in hydronephrosis and hydroureter.
Antenatal diagnosis of HMC may be associated Compression of the great vessels like inferior
with oligohydramnios. It may initially be mis- vena cava and iliac vessels causes cyanosis,
diagnosed as a large bladder [7]. USG shows a edema, and ecchymosis of the perineum, lower
large retrovesical septate hypoechogenic mass extremities, and abdominal wall. The rectum is
in the fetal abdomen. Fetal MRI helps in usually not affected. However, rarely, constipa-
detailed assessment of fetal urogenital anoma- tion may result after HMC.
lies [8]. Postaxial polydactyly in the fetus asso- On perineal examination, a bulging hymenal
ciated with a retrovesical cystic structure membrane may be seen. This may be due to
provides a great suspicion of HMC-associated imperforate hymen or a bulging transverse vagi-
syndromes. nal septum. Per rectal examination (if feasible)
will reveal a pelvic mass felt anteriorly. In high
vaginal atresia or UGS, two perineal openings
45.5 Classification will be seen. A single perineal opening points
toward common cloaca with HMC.
Hydrometrocolpos has been classified into five In vaginal atresia, the location where the vagi-
types on the basis of the type and level of obstruc- nal orifice should be located may be retracted
tion [1–3]. Two third of the cases are associated upward into the pelvis due to the enlarging upper
with imperforate hymen or type I HMC. Table 45.1 vagina escaping from the small pelvis into the
summarizes the classification of HMC. more capacious abdominal cavity [1, 2].
45 Hydrometrocolpos 593

Table 45.1  Classification of types of hydrometrocolpos

Type Description Subtype
I Low hymenal Imperforate
obstruction hymen

II Midplane A—Without
transverse communication
membrane or B—With a small
septum orifice as
communication
A  B 
III High A—Without any
obstruction perineal swelling
with distal B—With perineal
vaginal swelling
atresia

IV Vaginal
atresia with
persistence
of the
urogenital
sinus

V Vaginal
atresia with
cloacal
anomaly
594 D. K. Gupta et al.

Infection of the dilated tract with collection of Table 45.2  Hydrometrocolpos and associated anomalies
and syndromes
fluid is the real risk and cause of high morbidity
and mortality in such babies. Most newborns with Congenital anomalies
HMC would present with an infected system, sep- I Genitourinary Bicornuate uterus, double
system vagina, duplication of uterus
ticemia, respiratory distress, and fever. The and vagina, bifid clitoris,
infected fluid needs to be drained out urgently to congenital urethral membrane,
improve the general condition and save the baby. double ureter, ureteral stenosis,
Late presentation: At puberty, the girl may urethral atresia, renal agenesis,
ambiguous genitalia
present with amenorrhea, cyclical abdominal II Gastrointestinal Anorectal malformation,
pain, and an abdominal mass secondary to hema- esophageal atresia and
tocolpos as a result of onset of menarche or tracheoesophageal fistula,
HMC.  On rare occasions, there may be leukor- duodenal atresia,
paraesophageal hiatal hernia,
rhea through a pinpoint opening in the hymen. and congenital aganglionosis
Adults may present with inability to consummate III Cardiac Congenital heart disease (CHD)
and infertility. IV Vertebral Vertebral segmentation
anomalies
Syndromes
45.7 Associated Anomalies I McKusick-­ Vaginal atresia, HMC,
Kaufman postaxial polydactyly, hydrops
and Syndromes syndrome fetalis hexadactyly, congenital
cardiac anomalies [11, 12]
About 50% of newborns with HMC are stillbirth II Bardet-Biedl The same as MKS with retinal
[1]. This may probably be due to the other asso- syndrome dystrophy or retinitis
ciated anomalies and disorders. The most com- pigmentosa, obesity,
nephropathy, mental
mon and serious are genitourinary anomalies. disturbance
HMC may present as a part of other disorders III Ellis-van Chondrodystrophy with
(Table 45.2). Creveld polydactyly
The phenotypic overlap of BBS and MKS, syndrome
both autosomal recessive syndromes, including IV Langer-Giedion Multiple exostoses, learning
syndrome difficulties, short stature,
HMC and postaxial polydactyly in the neonatal unique facial features, small
stage may cause confusion for appropriate diag- head, and skeletal
nosis. Re-evaluation at a later age for mental abnormalities
retardation, obesity, and retinitis pigmentosa
leads to the diagnosis of BBS.  Also, uterine,
ovarian, fallopian tube, and renal anomalies are 45.8 Investigations
more common in BBS than in MKS. By contrast,
upper reproductive tract anomalies are not seen Apart from routine blood and urine tests, investi-
with MKS. gations to confirm the diagnosis and the type of
HMC may present as a part of VACTERL anomaly and also to plan the management are
association or may also present as a chromo- done and include:
somal disorder. Interstitial deletion of chromo-
some 8q21.11-q24.13 was reported to be 1. X-ray—on plain X-ray of the abdomen, a
associated with trichorhinophalangeal syndrome mass may be seen in the lower abdomen and
type II (Langer-Giedion syndrome) [13]. pelvis displacing the small intestinal loops
HMC may rarely be associated with Mullerian into the epigastrium. Neonatal peritoneal cal-
dysgenesis syndrome, staphyloma of the eye, cifications along with the ascites may be seen
severe hydrops, vertebral segmentation anoma- in HMC secondary to imperforate hymen,
lies, lung hypoplasia, corpus callosum hypopla- without the evidence of gastrointestinal tract
sia, and single umbilical artery [14]. obstruction [15].
45 Hydrometrocolpos 595

a b

Fig. 45.1 (a) A 6-month-old girl with huge abdominal of bifid hydrometrocolpos with obstruction due to distal
lump and no vaginal orifice in the perineum (hydrometro- vaginal atresia
colpos due to distal vaginal atresia). (b) MRI suggestive

2. Skeletal X-rays and digital skiagram may be 45.9 Management

done to identify vertebral and limb
anomalies. The treatment of HMC is surgical. However,
3. USG—to identify dilated vagina and upper medical management is required to treat the
urinary tract anomalies. A trans-perineal infection, build up the baby, and make her fit for
USG can help measure a caudally placed surgery. The type of procedure and the timing of
obstructive vaginal septum. USG after blad- surgical intervention will depend upon the sever-
der drainage may help in the diagnosis of ity of the condition, the type of anomaly, and the
HMC [16, 17]. age at presentation.
4. Retrograde genitourethrogram (RGU), Early neonatal surgery is indicated when a
micturating cystourethrogram (MCU), and grossly distended HMC presents with a bulging
dye study—to identify the urogenital sinus hymen. It is often associated with complications
and its communication with vagina. like abdominal mass, urinary obstruction, consti-
5. Endoscopy—to delineate the anatomy and pation, sepsis, dehydration, and even respiratory
the length of common channel (C.C) in cases distress. Laparotomy is indicated in patients with
of cloaca and UGS. high vaginal obstruction and for the treatment of
6. Intravenous urography, CT scan, and abdominal complications or the associated anom-
MRI—to delineate anatomy while planning alies. Temporary decompression by needle aspi-
corrective surgery (Fig. 45.1). ration or an abdominal tube or a flap vaginostomy
7. Echocardiogram—to rule out cardiac may be required to drain the infected material
anomalies. from the vagina. Early drainage in neonates facil-
8. Renogram studies—renal function studies to itates drainage of the infected material and thus
rule out associated renal abnormalities. reduction of the chances of sepsis.
596 D. K. Gupta et al.

Table 45.3  Management algorithm for hydrometrocolpos

Type I Type II Type III Type IV Type V
Diagnosis Imperforate Transverse vaginal Vaginal atresia Urogenital Cloaca
hymen septum sinus
Initial Vaginostomy (indwelling catheter/flap)
procedure
Subtypes A—Low/ B—With Agenesis of lower UGS/cloaca
bulging a small vagina Common Common channel
orifice channel length length >2.5 cm
<2.5 cm
Treatment Hymenectomy Cruciate incision/ Abdominoperineal TUM or PSARVUP +
options or excision and repair, pull-through of PSARVUP vaginal
hymenotomy with post-op dilatation vagina replacement
UGS urogenital sinus, TUM total urogenital mobilization, PSARVUP Posterior sagittal anorecto-vagino-urethroplasty

Surgery in the prepubertal age is done to allow drain the dirty infected fluid, followed by a defin-
natural passage for menstrual flow and create a itive repair later on, is the preferred option.
passage for sexual activity and for psychosocial Various surgical options are:
reasons.
Preoperative resuscitation—The newborn 1. Drainage procedures.
should be nursed in head-up position and resusci- a. Hymenotomy/hymenectomy
tated with oxygen, IV fluids, IV antibiotics, incu- b. Vaginostomy (perineal/abdominal)
bator care, nasogastric tube decompression, a 2. Abdominoperineal repair of vagina
Foley’s catheterization of urinary bladder, and 3. Total urogenital mobilization (TUM)
the rectal syringing (in cases associated with con- 4. Vaginal pull-through with posterior sagittal

stipation). In the presence of a huge distended anorecto-vagino-urethroplasty (PSARVUP)
HMC in a sick neonate, a preliminary drainage 5. Vaginal replacement
by puncturing the vagina under USG guidance
may be done for 24–48 h prior to corrective sur- Drainage procedures—In type I/II, drainage
gery [18]. Alternatively, the hymen or the vaginal procedures are the definitive treatment. In all
septum (type I and II anomaly) can be incised other types/in pyometra, drainage of the retained/
under the USG guidance or even under vision in infected material is the first stage in treatment.
experienced hands. An USG-guided bilateral Hymenotomy/ hymenectomy—A bulging
tube nephrostomy helps in quick relief from membrane in an infant with imperforate hymen or
obstructive uropathy in sick neonates. transverse septum of the vagina may be incised
The following algorithm simplifies the man- without anesthesia. However, excision is prefera-
agement of this complex condition (Table 45.3). ble if the hymen is thickened or the patient is an
adolescent. Hymenotomy may resolve the acute
renal failure caused due to obstruction by
45.10 Surgical Options HMC. The patency of the opening is maintained
by the initial use of a drain followed by repeated
First requirement is the early drainage of the fluid dilatations [1].
from the closed cavity. The management is sim- Steps of hymenectomy with illustrations are
ple with low type I and II anomalies. In these given in Fig. 45.2.
cases, drainage procedures alone may be cura- A contrast study may be performed to delin-
tive. At the most, some of the patients may require eate the internal anatomy. The vagina is drained
postoperative dilatation for a few months. for about 2–3  weeks. This is a simple, bedside
However, the patients with type III, IV, and V procedure which can be performed in the inten-
HMC anomalies are usually obstructed and often sive care unit if the baby is sick. The depth can be
infected. Thus, an initial drainage procedure to pre-assessed by needle puncture and USG. It can
45 Hydrometrocolpos 597

a b c

d e

Fig. 45.2  Steps of hymenectomy (to be redrawn)

also be performed under GA in the operation the- • Abdominal vaginostomy (Fig.  45.4) may
ater. Antibiotics should be given for 5–7 days. either be in the form of an indwelling cathe-
Vaginostomy—It serves as a temporizing ter or a tube:
drainage procedure for cases with infected fluid, –– An indwelling catheter has certain disad-
usually as the first stage of treatment for type III, vantages like infection; encrustation and
IV, and V HMC-infected cases. also the need to keep the tube in situ,
requiring frequent catheter changing; and
• Perineal vaginostomy [1] (Fig. 45.3) is done an inconvenience to the child.
through the perineal route in type II: –– Alternately, a U-shaped flap of the vagina
(a) When a low transverse vaginal septum is is made into a shape of a tube that pro-
present (between the lower one third and vides drainage through the natural tract
upper two third of the vagina) and is seen and is fixed to the abdominal wall and the
as a bulge at the perineum. skin. A tubed or the flap vaginostomy
(b) In some patients, a pinpoint vaginal ori- avoids the long-term use of any indwell-
fice may be visible that may be surgi- ing catheter and at the same time provides
cally enlarged and oversewn with the an effective drainage. It also provides an
placement of a catheter for about easy access for performing the dye studies
2  weeks, in the vagina for establishing to outline the anatomy before doing a
the drainage. definitive surgery [1].
598 D. K. Gupta et al.

a b c

Fig. 45.3  Perineal vaginostomy in a girl with hydrometrocolpos due to transverse vaginal septum

a b c

Fig. 45.4  Abdominal tube vaginostomy in a girl presenting with infected hydrometrocolpos with urogenital sinus,
causing urinary obstruction and septicemia

45.10.1 Abdominoperineal Repair perineum by an abdominoperineal combined

of Vagina [1, 2] vaginal pull-­through. The normal upper vagina
is pulled down and is sewn with the perineum in
In a few cases of type II (transverse vaginal place. If required, a Barrow’s skin pedicle flap
septum) and most type III (atresia of lower can be added to reach the vaginal wall, falling
vagina), following initial vaginostomy and short by about 1–1.5  cm. A Silastic catheter
drainage, the vagina is exteriorized onto the drains the vagina from below, and another
45 Hydrometrocolpos 599

c­ atheter drains the HMC from above (kept for a the vaginal wall is very much thick and also
week). adherent with the pelvic structures; thus it is
For type III–V HMC (atresia of the lower two almost impossible to achieve length and bring it
third of the vagina, UGS or common cloaca), an to the perineum by using the posterior sagittal
abdominal route is preferred for doing the vagi- route. Thus, there is a need for vaginal
nostomy. In type V HMC associated with cloacal substitution.
anomaly, an additional right transverse colos- Bowel vaginoplasty is done for cases with lon-
tomy is also required during the first stage of ger common channel more than 2.5 cm. A loop of
surgery. sigmoid colon or an ileum is used for vaginal
reconstruction in patients with a narrow distal
vagina, or if the vagina has retracted following its
45.10.2 Total Urogenital repair, flaps of perineal skin may be used to con-
Mobilization (TUM) [1, 2] tribute to the distal vaginal segment. A Barrow’s
skin flap is the most commonly used procedure.
In type IV, if the common channel of the UGS is An inverted “Y” incision is given with the vertical
found to be less than 2.5 cm long on endoscopy limb of Y going inside the vaginal introitus for a
and the dye study, a disconnection of the vagina cm or so in the posterior midline wall. The
and the urethra may be done by posterior sagittal V-shaped perineal skin with an intact blood sup-
anorectoplasty (PSARP) route. The vagina may ply is created and mobilized sufficiently. It is then
be exteriorized onto the perineum, while the UGS advanced in the vagina and sutured to the margins
can be made to function as the main urethra. of the incision edges in the introitus.
However, the authors have most of the time found Many surgeons have used free skin graft over
it difficult to mobilize the dilated vagina and a vaginal mold, a cylinder of a prosthetic patch
bring it down if there had been a history of (Silastic or Gore-Tex), or the buccal mucosa graft
infected HMC. with a mesh to form the neo-vagina. Retractions
UGS can also be mobilized by total urogenital and graft contraction are common with these pro-
mobilization (TUM) to bring the urethra and the cedures. Surgical expertise and experience with a
vagina both on to the perineum. If the vaginal large number of cases are a requisite to undertake
introitus is narrow, it can be widened by placing these surgeries. It has been seen that the vagino-
a Barrow’s skin pedicled flap in its posterior wall. plasty with flaps is prone to shrinkage and needs
repeated dilatations. The results are more
­favorable when performed at puberty at the time
45.10.3 Vaginal Replacement of menarche or just before marriage.
and Posterior In patients with cloacal abnormality with dupli-
Sagittal Anorecto– cation of vagina and HMC, a vaginal switch proce-
Vagino–Urethroplasty dure is also an option for vaginal reconstruction.
(PSARVUP) [1, 2]

In patients with UGS with the common channel 45.11 Results and Follow-Up
length more than 2.5  cm and in patients with
HMC with cloacal malformation, a vaginal Regular follow-up visits to look for complica-
replacement would be required. First by PSARP tions like vaginal infection, retraction, tube dis-
route, the rectum can be bisected or lifted off lodgement, neo-vaginal stenosis, mucosal
from its bed to approach the vagina direct from prolapse, and perineal excoriation are important.
behind (PSARVUP). The fistulous communica- Vaginal dilatations may be required till marriage,
tion of the UGS, between the urethra and the though frequency may decrease. Girls may come
vagina, is divided and suture repaired, and the with menstrual irregularity, endometriosis, and
vagina is freed. In cases with infected HMC, infertility.
600 D. K. Gupta et al.

References 10. Vitale V, Cigliano B, Vallone G.  Imperforate hymen

causing congenital hydrometrocolpos. J Ultrasound.
2013;16:37–9.
1. Gupta DK, Shilpa S.  Hydrometrocolpos. In: Puri
11.
Tilahun B, Woldegebriel F, Wolde Z, Tadele
P, Hoellworth M, editors. Pediatric surgery—diag-
H.  Hydrometrocolpos presenting as a huge abdomi-
nosis and management. Berlin: Springer; 2009.
nal swelling and obstructive uropathy in a 4 day old
p. 957–66.
newborn: a diagnostic challenge. Ethiop J Health Sci.
2. Gupta DK. Hydrometrocolpos, in Edition. Ed. Prem
2016;26:89–91.
Puri published by Newborn surgery 2nd CRC Press,
12.
Rohatgi M, Gupta DK, Luthra M.  Neonatal
New York 2003. 875–882.
Hydrometrocolpos associated with McKusick
3. Gupta DK, Lal A. Hydrometrocolpos in the newborn.
Kaufman Syndrome. Indian J Pediatr. 1989;
In: Gupta DK, editor. Textbook of neonatal surgery.
56:438–41.
Delhi: Modern Publishers; 2000. p. 518–20.
13.
McLoughlin TG, Shanklin DR.  Pathology of
4. Spencer R, Levy DM. Hydrometrocolpos. Ann Surg.
Laurence-Moon-Bardet-Biedl syndrome. J Pathol
1962;155:558–71.
Bacteriol. 1967;93:65–79.
5. Koff AK.  Development of the vagina in the human
14. Martin H, Reed MD, Griscome T. Hydrometrocolpos
fetus. In: Contributions to embryology No. 140,
in infancy. Am J Roentgenol. 1973;118:1–13.
Carnegie Institute of Washington 1933;24:61.
15. Hu M, Methratta S. An unusual case of neonatal peri-
6. Patten BM.  Human embryology. Philadelphia: The
toneal calcifications associated with hydrometrocol-
Blakiston Company; 1946.
pos. Pediatr Radiol. 2001;31:742–4.
7. Hassan M, Saba E.  Prenatal ultrasonographic diag-
16. Cramer B, Green J, Harnett J, et al. Sonographic and
nosis of hydrometrocolpos. J Med Ultrasound.
urographic correlation in Bardet-Biedl syndrome (for-
2010;18(2):81–4.
merly Laurence-Moon-Biedl syndrome). Urol Radiol.
8. McKusick V, Bauer BL, Koop CE, Scott
1988;10:176–80.
RB. Hydrometrocolpos as a simply inherited malfor-
17. Banerjee AK, Clarke O, MacDonald LM. Sonographic
mation. JAMA. 1964;189:813–6.
detection of neonatal hydrometrocolpos. Br J Radiol.
9. Hayashi S, Sago H, Kashima K, Kitano Y, Kuroda T,
1992;65(771):268.
Honna T, et al. Prenatal diagnosis of fetal hydrome-
18. Rohatgi M, Luthra M, Gupta DK, Bhargava S.  An
trocolpos secondary to a cloacal anomaly by mag-
unusual presentation of neonatal hydrometrocolpos
netic resonance imaging. Ultrasound Obstet Gynecol.
with review of pathogenesis and management. Pediatr
2005;26:577–9.
Surg Int. 1987;2:372–6.
 Different Sexual
Development (DSD) 46
Maria Marcela Bailez

46.1 Introduction participation in decision-making is encouraged;

and (5) patient and family concerns should be
Nearly 1 in 4500 infants is born with abnormali- respected and addressed in strict confidence.
ties of the external genitalia. Contemporary management sees DSD deci-
Detection of the abnormality is usually sion-making as multifaceted, involving many
immediate at birth and is followed by a cascade different factors (none to the exclusion of the oth-
of events beginning with disclosure of genital ers), including etiology, fertility, and most likely
anomaly to the expectant parents followed by the gender outcome [3].
time-consuming diagnostic evaluations.
Patients with ambiguous genitalia mostly
present in the newborn period requiring a mul- 46.2 Presentation and Diagnosis
tidisciplinary team which involves a pediatric
surgeon/urologist to assign the sex of rearing as External genitalia exam includes the gonadal
soon as possible after a thorough genetic, ana- palpation and perineal exam; both are the key to
tomic, functional, and socioeconomic workup. choose the sequence of diagnostic procedures to
DSD is defined as congenital conditions reach an etiologic diagnosis.
in which development of the chromosomal, It is important to visualize both faces of the
gonadal, or anatomical sex is atypical [1, 2]. phallus, looking for the urethral orifice, defining
According to the Consensus Statement on its localization and aspect. Inguinal and perineal
Management of Intersex Disorders, optimal clin- palpation looking for gonads is the other diag-
ical management of individuals with DSD should nostic key.
comprise the following: (1) gender assignment Each patient needs to be considered in an indi-
must be avoided before expert evaluation in new- vidual basis.
borns; (2) evaluation and long-term management Traditionally DSD patients were classified
must be performed at a center with an experienced into three groups based on gonadal structure:
multidisciplinary team; (3) all individuals should
receive a gender assignment; (4) open communi- • Presence of two well-defined ovaries with
cation with patients and families is essential, and ambiguous or male external genitalia (female
pseudohermaphroditism; now called overvir-
ilized XX female). These patients have a 46
M. M. Bailez (*) XX karyotype, and virilization of the external
Department of Pediatric Surgery, Garrahan’s genitalia results from exposure to high level of
Children’s Hospital, University of Buenos Aires,
Buenos Aires, Argentina androgens in utero, while they have female

© Springer Nature Switzerland AG 2019 601

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_46
602 M. M. Bailez

internal genitalia. Congenital adrenal tissues present sensitivity for the virilizing
­hyperplasia (CAH) is the most common dis- effect of androgens.
ease in this group and accounts for 50–80% of Molecular biology techniques are more sen-
all the cases of ambiguity, depending on the sitive and specific tests for assessment of the
population analyzed. The most common enzy- tissue sensibility to androgens but not always
matic defect is 21-hydroxylase deficiency. available.
The incidence of 21-hydroxylase deficiency is Histology is only required for diagnosis in
1  in 15,000–40,000 newborns. Other defects patients with abnormal gonads (G3).
are 11-hidroxylase (hypertension) and 3-b-ol-­ Except for gonadal biopsy or resection, no
dehydrogenase or aromatase. other surgery is performed in the neonatal period.
• Presence of two well-defined testicles with Most of the reconstructive procedures, although
ambiguous or female external genitalia (male done early, are not recommended after the first
pseudohermaphroditism; now called undervir- month of life.
ilized XY male). These patients have a 46 XY Evolution of practice in the last years tends to
karyotype, and ambiguity of the external geni- postpone surgery. Sex assignment does not mean
talia results from a failure of the masculiniza- inevitable surgical intervention. Each case needs
tion androgenic action of the male fetus. This to be considered in its own terms. Preservation
can be due to a failure in androgenic synthesis of tissue, particularly gonadal tissue, and main-
or in the biological response. This group tenance of the integrity of the body as whole are
includes rare defects of the biosynthesis of aspects to care and receive higher priority.
testosterone, defect of the 5-alpha reductase The role of surgery consists in (1) gonadal
(enzyme that converts testosterone in dihy- treatment, (2) feminizing genitoplasty, and (3)
drotestosterone) and partial androgen insensi- urethral/penile reconstruction in the underviril-
tivity syndrome (partial defect of androgenic ized child.
receptors). It is important to recognize that
patients with a 46 XY karyotype and dysge-
netic testicles are sometimes included in this 46.3 Role of the Surgeon
group in the literature.
• Presence of incomplete differentiated gonads The surgeon plays an important initial role in
or coexisting ovarian and testicular tissue with the interdisciplinary group that an institution is
ambiguous or female external genitalia. This obliged to have to take care of these complex
is a heterogeneous group with one common patients. He not only needs to take care of the
factor which is a structural defect in gonadal best operative techniques for better functional
differentiation with or without a chromosome results but also manages the proper information
alteration. Patients with mixed gonadal dys- (after conscious discussion of the group) to be
genesis, testicular dysgenesis, and true her- given to parents and family. The use of improper
maphroditism (now called ovotesticular words and misinformation may result in irrevers-
disorder of sex development) are included in ible sequela. In our opinion, the surgeon has to be
this group. very well informed and participate actively in the
preoperative workup before taking contact with
The possibility of the ambiguous genita- the family.
lia to virilize can be estimated after an hCG
test or an appropriate stimulation trial with
testosterone or topical DHT. This can be esti- 46.4 Gonadal Treatment
mated by demonstrating the increment of the
penile dimensions or indirectly by the dosage Gonadal histology (biopsy or gonadectomy) is
of androgen-sensitive circulating substances required in selected DSD patients with abnormal
(SHBG). Its values are reduced if the patient gonadal development like gonadal dysgenesis.
46  Different Sexual Development (DSD) 603

Fig. 46.2  Intraoperative view of ovotestis

Fig. 46.1  Scheme of gonadal biopsy

The existence of a Y chromosome is associ-

ated with a higher risk of developing germ cell
tumors as gonadoblastoma.
Gonadal biopsies must be taken along the
longitudinal axis of the gonad as both ovarian
and testicular tissues may be found at the polar
ends of the gonad (Fig.  46.1). Patients with
Ovotesticular dysgenesis may have an ovary (O)
and testicle (T), bilateral ovotestes (OT), and an
O and OT (Fig. 46.2).
Surgical management in DSD should also Fig. 46.3  Intraoperative view of streak gonad
consider options that will facilitate the chances
of fertility. Ovarian component of ovotestes may the scrotum of patients with male sex assignment
be separated and the testicular tissue removed, because this gonad is functional.
using zoom lens, although it must be kept in The highest tumor risk is found in TSPY
mind that these gonads need to be followed (testis-­specific protein Y-encoded)-positive
closely. gonadal dysgenesis and partial androgen insen-
If a streak gonad is recognized like in most sitivity (PAIS) with intra-abdominal gonads,
patients with 45 /0 46 XY gonadal dysgenesis, it whereas the lowest risk (5%) is found in ovotestis
is removed without prior biopsy together with the and complete androgen insensitivity (CAIS).
surrounding peritoneum and the ipsilateral gona- To analyze the spectrum of gonads of the DSD
duct (Fig. 46.3). This gonad has to be removed, patients that we treated and assess the incidence
avoiding previous biopsy, as it has 25–50% of germ cell tumors, we conducted a prospective
chances to develop a gonadoblastoma and/or and observational study of DSD patients who
dysgerminoma and as there is the possibility of underwent gonadal surgery. Age, sex assigned,
an in situ tumor at the time of the procedure. It scale of external masculinization (EMS), karyo-
is usually associated with an intra-­abdominal or type, molecular analysis, surgical approach, and
inguinal dysgenetic testicle, which is removed pathology of the gonads were analyzed.
at the same time in patients with female sex Patients were divided into three groups: chro-
assignment. Although there is the same risk of mosomal dysgenesis (G1), 46 XX gonadal dys-
malignancy in the contralateral gonad (dysge- genesis (G2), and 46 XY gonadal dysgenesis
netic testicle), it may biopsied and preserved in (G3) (Table 46.1).
604 M. M. Bailez

Table 46.1  Classification of DSD analyzed

Chromosomal DSD 46,XY DSD 46,XX DSD
45,X and variants (Turner) Gonadal disorders Disorders of gonadal development
47,XXY and variants Partial/complete dysgenesis
(Klinefelter)
  • Gonadal dysgenesis
45,X/46,XY (mosaicisms) DSD ovotesticular   • Ovotesticular DSD
46,XX/46,XY (chimera) Testicular regression   • Testicular DSD
Androgen biosynthesis or action Excess of extragonadal androgens
disorders
  • Mutation of AR (androgen receptor) Congenital adrenal hyperplasia
(21OHD)
Others
  • Malformations   • Other enzymatic deficits
  • Hypogonadotropic hypogonadism   • Maternal androgens
Others
  • Malformations

Fig. 46.4  Summary of results

More than half of the gonads were intra-­ in 87.5% of them. Male sex was assigned in 19,
abdominal and were treated laparoscopically with a mean of 7.26 EMS (1–10). Histological
using 3 or 5 mm instruments. All streak gonads analysis of 89 gonads was completed identify-
were removed, avoiding previous biopsy. We ing 52 streak gonads, 32 dysgenetic testes, and
always waited for the result of biopsy before 5 ovotestes. Six germ cells tumors (GCT) were
removing any other gonad than a classical found in four patients.
streak.
In total 94 patients with a mean age of
56.42  months (range, 2–216) were analyzed 46.4.2 G2
(Fig. 46.4).
Fifteen patients with a mean age of 27.6 months
(2–180) were included in G2. Male gender was
46.4.1 G1 assigned to six with a mean EMS of 6.82 (range,
4–8.5). Twenty-nine gonads were analyzed:
Forty-eight patients (19 with a Turner syndrome) 10 ovotestes, 15 dysgenetic testes, and 4 ova-
with a mean age of 105  months (2–216) were ries. Bilateral gonadoblastoma was found in a
included in G1. The karyotype was 45 X0/46 XY 6-month-old patient with bilateral ovotestes.
46  Different Sexual Development (DSD) 605

46.4.3 G3 p­ revious sex assignment. There is an advantage of

a laparoscopic approach in these patients requir-
Mean age of the 31 patients in G3 was 69.71 months ing secondary pelvic exploration, especially
(5–192). Five of them had an SF-1 NR5A muta- because many of them are potentially fertile.
tion, 6 a WT1, and 6 a complete and 3 a partial An additional role of laparoscopy is excision of
androgen insensitivity syndrome. A new mutation Mullerian structures, prostatic utricle, and orchi-
in the SRY (p.MET64VAL) gene was identified in dopexy in patients raised as males. In patients
two sisters. Male gender was assigned in ten with with a symptomatic utriculus, removal is best per-
a mean EMS of 4.52 (range, 1–10). Fifty-nine formed laparoscopically to increase the chance of
gonads were analyzed, i­dentifying 41 dysgenetic preserving continuity of the vas deferens.
testes, 10 streak gonads and 8 testes. Eight GCT An inguinal approach may be indicated in
were found in five patients (16%) (seven in streak patients with palpable gonads. We still prefer a lap-
gonads and one in a dysgenetic testicle). aroscopic approach in most of them as it enables
We concluded that DSD patients with not only better visualization of potential Mullerian
gonadal dysgenesis have a wide variability. structures but also allows for treatment of a patent
The incidence of gonadoblastoma is not negli- peritoneal sac, when removing the gonads, with
gible in patients 46 XY and even feasible in 46 better cosmetic results. In addition, most of these
XX.  The incidence of GCT was 8.3, 6.6, and patients have asymmetric gonads with one of them
16% in G1, 2, and 3, respectively (Fig.  46.4). being intra-abdominal. We reserve the inguinal
Early histological analysis and monitoring of approach for XY patients with symmetric palpable
these patients are mandatory. To our knowledge, gonads introducing the telescope through the asso-
this is the first report of bilateral gonadoblas- ciated hernia sac in order to rule out the presence
toma in ovotestes at a very early age. of Mullerian structures.
Although we used to schedule simultaneous Nowadays the resection of testicles in CAIS
gonadal and genitalia procedures with good results patients is postponed after spontaneous breast
encouraged by the laparoscopic better visualiza- development that occurs because of the periph-
tion and quicker access to intraperitoneal, actually eral conversion of androgens to estrogens in
we prefer to avoid resection of any gonad except a puberty.
classical streak before having definitive histology
and postpone genitalia surgical procedures.
Sex may be assigned prior to laparoscopy in References
patients with 45 XO/46 XY gonadal dysgenesis.
This is based on a functional and psychoso- 1. Lee PA, Houk CP, Faisal Ahmed S, IA Hughes, in
collaboration with the participants in the International
cial basis in combination with the results of the Consensus Conference on Intersex organized by the
karyotyping, HCG testing, and interview of the Lawson Wilkins Pediatric Endocrine Society and
parents. the European Society for Pediatric Endocrinology
We have never found functional ovarian tissue Department of Pediatrics, Penn State College
of Medicine, Hershey: Consensus Statement on
in these patients. Management of Intersex Disorders. Pediatrics.
Patients with ovotesticular dysgenesis do not 2006;118: 488–500.
have such a classical pattern, and definitive his- 2. Grumbach MM, Hughes IA, Conte FA. Disorders of
tology is often necessary for sex assignment. sex differentiation In: Larsen PR, Kronenberg HM,
Melmed S, Polonsky KS, editors. Williams textbook
Although the most common karyotype is 46 of endocrinology. 10th ed. Heidelberg: Saunders;
XX and the most common gonadal combination 2003. p. 842–1002.
ovary/ovotestes, each case is unique and should 3. Lee PA, Nordenström A, Houk CP, Faisal Ahmed
be treated on an individual basis. Sometimes the S, Auchus R, Baratz A, Baratz Dalke K, Liao L-M,
Lin-Su K, Looijenga 3rd LHJ, Mazur T, Meyer-­
macroscopic aspect of the gonad and gonaduct Bahlburg HFL, Mouriquand P, Quigley CA, Sandberg
as well as the result of a frozen section biopsy DE, Vilain E, Witchel S, and the Global DSD Update
strongly favors gonadectomy in patients with Consortium.
 Congenital Anomalies
of the External Male Genitalia 47
Francesco Di Lorenzo, Neil Di Salvo,
and Mario Lima

This chapter is aimed at describing the main con- In the first trimester, these cells are induced by
genital disorders of the external male genitalia placental human chorionic gonadotropin (HCG).
(penis, scrotum, and testis) in order to enable After the first trimester, during the rest of ges-
the reader a prompt recognition of such malfor- tation, fetal testosterone secretion is maintained
mations in newborns. The latter is fundamental by activation of the fetal pituitary gland through
when formulating potential surgical planning production of the luteinizing hormone (LH). The
which is almost never carried out in the neona- hypothalamus-pituitary gland-testis axis goes on
tal period. Recognizing and then planning the until the first 4 months of life. Throughout all this
correction will surely allay parental anxiety. period, both antenatally and postnatally, exter-
Description of the corrective surgical techniques nal genitalia continue to grow. Second reactiva-
goes beyond the purposes of this chapter. We will tion of the abovementioned axis during puberty
therefore tackle the anatomic description, etiol- will again promote penile, scrotal, and testicular
ogy, initial evaluation, and timing of treatment growth and transformation.
of these anomalies. As for all congenital anoma- The undifferentiated primitive fetal structures
lies, a good basic knowledge of the embryologic from which external genitalia arise are essen-
development of the male genitalia is necessary tially three: the genital tubercle, the genital folds,
in identifying and understanding their etiology. and the labioscrotal folds. The first becomes the
The presence of the Y-chromosome, more pre- penile glans in males and the clitoris in females;
cisely its “sexual-specific” region, that is to say the urogenital folds will progressively close in a
the sex-determining region (SRY) which consists cranio-caudal direction thus becoming the penile
in a single couple of genes, is essential in starting shaft with the proximal urethra in the inside; and
the transformation of the undifferentiated gonad finally the labioscrotal folds will differentiate
into the testis. into the scrotum and the labia majora in males
The biochemical stimulus for differentia- and females, respectively.
tion of the external genitalia, which takes place From this brief description, it is easy to under-
between the 9th and 14th week of gestation, is stand that a good function of the fetal hypothala-
given by testosterone that is produced by the mus, pituitary gland, and Leydig cells with a
Leydig cells of fetal testis tissue. subsequent appropriated timing of activation is
fundamental.
F. Di Lorenzo (*) · N. Di Salvo · M. Lima
Department of Pediatric Surgery, S.Orsola Hospital,
Bologna University, Bologna, Italy
e-mail: [email protected];
[email protected]

© Springer Nature Switzerland AG 2019 607

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_47
608 F. Di Lorenzo et al.

47.1 Penile Agenesis (Aphallia) In more than half of cases, penile agenesis
is associated with other malformations: geni-
The absence of the penis, in male individuals tourinary (54%) such as urethral valves or atre-
with normal scrotum and testicles, a perineal sia, cryptorchidism, vesicoureteral reflux, cystic
(anorectal) urethral meatus, without chromoso- renal dysplasia, and horseshoe kidneys; digestive
mic and endocrine anomalies, is one of the most such as esophageal and duodenal atresia, ano-
rare, serious malformations of the genitourinary rectal malformation, and Hirschsprung disease;
tract. This pathology affects 1 every 1–3 million scheletric (phocomelia and vertebral anomalies);
of live newborns with only a few cases reported and cardiovascular.
in literature. It is an atypical expression of cau- On a prognostic level, the more proximal
dal regression and embryonically the result of the meatus in relation to the anus, worse are the
a missed formation of the genital tubercle and associated malformations and therefore higher
folds, which is an initial and fundamental step in morbidity and mortality. For instance, in cases
the development of the penis (Fig. 47.1). of very short urethras, the bladder neck struc-
Based on the localization of the urethral tures often may be lacking or even totally miss-
meatus in relation to the anal sphincter, we can ing, thus resulting in continence dysfunctions.
distinguish the following types (Fig.47.2): On a clinical level, the patient affected by true
penile agenesis presents a regular chromosomic
–– Post-sphincteric (urethra-anal fistula) 60% pattern and normal scrotum and testis whose
–– Pre-sphincteric (prostatic-rectal fistula) 22% endocrine function is conserved. A frequent
–– Urethral atresia (vesico-rectal fistula) 12% finding is the presence of a cutaneous appendix
near the anus.
In the remaining cases, the urethra ends ante- In most cases diagnosis is easy and obvi-
riorly to the scrotum or even above the pubic ous; nevertheless a buried penis, an intrauterine
symphysis. amputation of the penis, and a severe posterior
hypospadias are sometimes confused with this
a pathology.
In the past, all children affected by aphallia
were gender-reassigned; this viewpoint was due
to the difficulty of surgical reconstruction of a
functional penis and urethra. The routine standard
approach was to remove the male gonads and cre-
ate a functional female genital and urinary tract.
Reconstruction was accomplished by creation of
a neovagina using a colonic segment. Recently
several doubts have arisen about this approach,
because of the increasing awareness of testoster-
b one imprinting on the brain which leads to sig-
nificant psychosocial issues as the child matures.
Therefore the choice of not gender reassigning
the child is nowadays considered an option. In
these cases early reconstruction of the lower
urinary tract and penis should be carried out. In
both cases though, long ­term counselling involv-
ing a multidisciplinary team including behavioral
medicine specialists, endocrinologists, psycholo-
gists, urologists, and social workers should be
provided.
Fig. 47.1 (a, b) Patient affected from penile agenesis
47  Congenital Anomalies of the External Male Genitalia 609

a b

Fig. 47.2 (a) post-sphincteric penile agenesis (urethra-anal fistula); (b) pre-sphincteric penile agenesis (prostatic-­
rectal fistula); (c) urethral atresia (vesico-rectal fistula)

47.2 Micropenis The majority of patients affected by micrope-

nis are able to produce LH, follicle-stimulating
Micropenis is defined as a morphologically nor- hormone (FSH), and testosterone after exogenous
mal penis whose length is 2.5 standard deviations stimulation with gonadotropin-releasing hor-
(SD) inferior than the reference for age with tes- mone (GnRH), demonstrating full functionality
tis present in the scrotal sac, thus eliminating any of the pituitary gland and the testis. Furthermore,
doubt of genital ambiguity. A low stimulation by these patients’ penis respond to both topical and
androgens is the cause of a poor development of systemic administration of testosterone. It is evi-
the penis. On the etiopathogenetic basis, there dent from this that the problem is localized in the
are basically two conditions that can lead to such hypothalamus. Nevertheless, since a central lesion
conditions: may be associated with multiple hormonal defects
that could determine disastrous effects, a pediatric
–– Functional anomaly of the hypothalamus-­ endocrinologist should be consulted as soon as a
pituitary gland axis with subsequent insuffi- diagnosis of micropenis has been formulated. He
cient induction of Leydig cells with low or she will carry out anterior pituitary and endo-
production of testosterone. crine testicular function testing. In cases in where
–– Peripheric insensibility to testosterone. testicular failure is diagnosed and the testis can-
610 F. Di Lorenzo et al.

not be palpated (ambigous genitalia), laparoscopy early division of the pubic tubercle beginning
should be carried out to determine the presence or from the fifth week of gestation, even though
nonpresence of testicular tissue in the abdomen. an incomplete fusion of the genital tubercle has
Systemic medical therapy must be given early been suggested. Clinically it can appear in differ-
in the first year of life in order to accomplish sat- ent forms from a simple duplication of the penis
isfying results even though timing of hormonal glans up to a complete duplication of the entire
stimulation with testosterone is controversial. penis, associated with a urethro-vesical dupli-
Alternatively, a 3% testosterone cream can be cation (Fig.  47.3). In the complex “exstrophy-­
used topically; however, absorption is variable epispadias,” there is an apparent diphallia.
and posology has not yet been precisely defined. Nevertheless it is more appropriate to refer to
these cases as “bifid penis” since two corporal
bodies are well distinguishable and separated
47.3 Buried/Hidden Penis with their own hemi-glans.
The treatment of this form is always preceded
Congenital buried penis in children is a rela- by a precise preoperative evaluation of the geni-
tively rare and poorly known pathology. It can be tourinary tract. The principles that surgeons must
defined as a congenital deficiency of penile shaft follow when choosing which penis to save are
skin often associated with a tight foreskin (phimo- based on the morphology and erectile function of
sis), resulting sometimes in the urine dilating the both the units.
preputial “reservoir,” still called preputial bladder.
Congenital buried penis is a separate entity from
the acquired one even in children, as it happens
after early circumcision. Some authors refer to
this condition as trapped penis. This condition can
create such an important psychological involve-
ment both in the parents and the pediatric patient.
Functional problems can arise since it can be
responsible for recurrent urinary tract infections
and balanitis or dysuria. Surgical correction is dif-
ficult with sometimes disappointing results.
Urination issues, recurrent infections, or a
strong demand from the parents and patient seem
to be the major surgical indication for correction of
this pathology, certainly after the child has started
to walk and has lost most of the prepubic fat pad
even though this surgery can be performed safely
in children from 3 months of age. It is reasonable
to treat this pathology as the majority of penile
pathologies in children, between the 12th and 24th
month of life, before the school starting age.

47.4 Duplication of the Penis

(Diphallia) and Bifid Penis

Duplication of the penis or diphallia represents

another rare malformation (1 every five million Fig. 47.3  Complete duplication of the penis with con-
live births). The most plausible hypothesis is an sensual urethra-vesical duplication
47  Congenital Anomalies of the External Male Genitalia 611

47.5 Scrotal Agenesis associated with posterior hypospadias and other

congenital anomalies especially of the urinary
Congenital scrotal agenesis (CSA) is an extremely tract but also of the digestive and cardiovascular
rare congenital anomaly (Fig. 47.4). It is associated system, sometimes extremely serious and incom-
with a male karyotype. Bilateral testes are present patible with life. From a clinical standpoint,
in a cryptorchid or ectopic position, and external penoscrotal transposition can present in the com-
androgen-dependent structures, including the penis, plete or minor form (as bifid scrotum) in which
are normal. A possible explanation for this condi- the urethra is not constantly involved.
tion is an arrest in primary scrotal development: the Surgical correction consists in mobilizing the
most likely explanation for CSA is a failure of the two hemisacs with rotation and advancement
labioscrotal fold to develop at all. Physical exami- flaps and repositioning them below the penis, or,
nation should attempt identification of the pres- alternatively, a tunneling of the penis can be per-
ence and location of the testes and diagnose other formed on the central line. Generally it is advis-
congenital anomalies including facial anomalies, able to procrastinate an eventual urethroplasty
developmental delay and cognitive impairment, after scrotal correction.
nystagmus, clinodactyly, cardiac septal defects,
anterior displaced anus, and clubfoot. Surgical con-
struction of the scrotum may be attempted by vari- 47.7 Bifid Scrotum
ous techniques. In infants with scrotal agenesis, it is
important that the child not be circumcised because It is due to a missed fusion of the genital folds
the prepuce is invaluable for scrotal reconstruction. along the scrotal septum. It is often associ-
ated with severe forms of hypospadias (scrotal
and perineal ones) and ambiguous genitalia.
47.6 Penoscrotal Transposition It rarely presents as an isolated malforma-
tion. Surgical correction is obtained by rotat-
In the penoscrotal transposition, the base of the ing below in the missing septum an anterior
penis is located below the higher insertion of skin flap and suturing it with the two hemisacs
the two scrotal hemisacs (Fig.  47.5). It is often (Fig. 47.6).

a b

Fig. 47.4 (a, b) A patient with scrotal agenesis

612 F. Di Lorenzo et al.

a 47.8 Ectopic Scrotum

The anomaly can be uni- or bilateral, complete

or incomplete. The ectopic scrotum can be
seen in many areas, starting from the inguinal
canal up to the buttock, medially to the infe-
rior limb.
Embryonically it is believed that ectopic
scrotum develops due to a defect in the guber-
nacular development. Also an anomalous
migration or division of the labioscrotal folds
has been advocated. Careful physical exami-
b nation to localize the testes and upper urinary
tract imaging with ultrasounds, in order to diag-
nose a likely associated urinary malformation,
is recommended.
The testis in the hemisac can be normal or
atrophic. In the latter case, it will have to be
removed at time of surgical correction. The exact
timing of surgery is usually between 6 months
and 3 years, basically determined by the associ-
ation with undescended testis and therefore the
necessity to perform an orchiopexy.
Fig. 47.5 (a, b) Penoscrotal transposition. The patient
also presented a posterior hypospadias
References
1. Dòmini R, De Castro R. Chirurgia delle malformazi-
oni urinarie e genitali. Padova: Piccin Editore;
1998.
2. Gearhart JG, Rink RC, PDE M.  Pediatric urology.
Philadelphia: Saunders Elseviers; 2010.
3. Janoff DM, Skoog SJ.  Congenital scrotal agenesis:
description of a rare anomaly and management strate-
gies. J Urol. 2005;173:589–91.
4. Lima M, Manzoni G, editors. Pediatric urology: con-
temporary strategies from fetal life to adolescence.
Milan: Springer; 2015.

Fig. 47.6  Patient affected from bifid scrotum. In this par-

ticular case, he also presented steno-atresia of the urethra
and a high anorectal malformation (pouch colon)
 Part IX
Nervous System
 Surgical Treatment of Central
Nervous System Malformations 48
Mirko Scagnet, Federico Mussa, Flavio Giordano,
Regina Mura, Elena Arcovio, Massimiliano Sanzo,
Pier Arturo Donati, Barbara Spacca,
Manuela Grandoni, Giuseppe Oliveri,
and Lorenzo Genitori

48.1 Introduction has radically changed the approach to the lesions

of the skull base; with a transnasal endoscopic
The surgical treatment of CNS malformations is a approach, you can reach every skull base.
big challenge for neurosurgeons. The developing Authors of this chapter intend to describe
technologies, from the new radiological imaging the current state of art in the surgical manage-
techniques as well the surgical armamentarium, ment of CNS malformations basing on their
and the improving of knowledge of such dis- experience and reviewing the pertinent literature
eases, have dramatically changed the opportunity (Table 48.1).
to treat the different malformations with best
results and quality of life for patients and family.
The neuroendoscopy, for example, has radi- 48.2 Hydrocephalus and CSF-­
cally changed the surgical approach to many Related Disturbances:
CSF-related diseases, giving, in some cases, Etiology and Management
the opportunity to treat the hydrocephalus in
a minimally invasive and more physiological 48.2.1  Hydrocephalus
way. The new biomaterials such as resorbable from Aqueductal Stenosis
plate and screws have changed the possibil-
ity for the surgical management of craniofacial Cerebrospinal fluid, (CSF) flows from the two
disease. Endoscopic endonasal approach (EEA) paired and symmetrical lateral ventricles to the
third ventricle, unpaired and situated on the mid-
line, through the foramina of Monro, and then to
the fourth ventricle. The narrow channel which
connects the third and fourth ventricles is the
aqueduct of Sylvius.
M. Scagnet · F. Mussa · F. Giordano · R. Mura Aqueductal stenosis is the most common
E. Arcovio · M. Sanzo · P. A. Donati · B. Spacca cause of congenital hydrocephalus, but a stenosis
M. Grandoni · L. Genitori (*) can be present in the neonatal period or even later
Department of Neurosurgery, Ospedale Pediatrico
in the adolescence. The male/female ratio is 2:1.
Meyer, Firenze, Italy
e-mail: [email protected]; [email protected] Aqueductal stenosis can be congenital or
acquired and is present in about 50% of patients
G. Oliveri
Department of Neurosurgery, Policlinico Le Scotte, with congenital hydrocephalus and in 15–20% of
Siena, Italy patients with hydrocephalus.

© Springer Nature Switzerland AG 2019 615

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_48
616 M. Scagnet et al.

Table 48.1  Surgical procedures for CNS malformations in children 1996–2016

Procedure N %
Neuroendoscopy 1444 25.15
Shunting procedures 2086 36.2
Craniofacial repair for craniosynostosis 1415 24.6
Excision of encephalocele 83 1.4
Posterior fossa decompression for Chiari type I anomaly 434 7.5
Surgery for dysraphic state 293 5.1
Fetal surgery 3 0.05

48.2.1.1 Embryology For this reason it is clear why a severe stenosis

The aqueduct of Sylvius develops about the 6th results in increased intracranial pressure, (ICP)
week of gestation. Embryologically, the brain and it explains why a change of the shape of the
starts out as a tubular structure. As the brain aqueductal lumen, which produces a mild ste-
grows, the inner tube remains as a series of inter- nosis, may result in an important flow alteration
connected cavities termed as ventricles. with subsequent further damage of the lumen
The ventricular system closes in Stage 12 and the establishment of a pathological pressure
(26–30 days of gestational age) at the end of neu- gradient between the supra- and the infratentorial
rulation; in Stage 15 (35–38 days of gestational compartments.
age), the evaginations of the cerebral hemi-
spheres develop with enlargement of the lateral 48.2.1.3 Classification
ventricles, the third ventricle, and the foramen of From the anatomical standpoint, the aqueductal
Monro. stenosis can be defined as intrinsic (primary) or
During Stage 20 (51–53  days of gestational extrinsic (secondary). There are multiple causes
age), the choroid plexuses develop a secretory of obstruction, but their morphological differen-
epithelium; the leptomeninx is beginning to form tiation is often impossible.
a potential subarachnoid space, and the roof of The possible etiologies are:
the fourth ventricle perforates. Due to the growth
of contiguous structures (mesencephalon, cor- • DEVELOPMENTAL: forking, narrowing,
pora quadrigemina, and crura cerebri) in this transverse septum.
period, the aqueduct of Sylvius narrows. • GENETIC: Bickers and Adams syndrome, an
X-linked recessive chromosomal anomaly,
48.2.1.2 Anatomy accounts for approximately 7% of male hydro-
The aqueduct is a narrow irregular channel situ- cephalus. It is characterized by stenosis of
ated in the dorsal midbrain between the posterior aqueduct, mental retardation, adducted
commissura and the lamina tecti posteriorly and thumbs, and spastic paraparesis. As for all
oculomotor, trochlear nuclei, medial longitudinal X-linked recessive diseases, only males are
fasciculus, and red nuclei anteriorly. affected, but the disease is transmitted through
Its lumen ranges normally from 0.2 to 1.8 mm the females of the family. In addition to the
and its length averages 11  mm. This explains X-linked inheritance, an autosomal recessive
why it is considered the critical point of the CSF pattern has been identified in families in which
pathway. both sexes are affected. Hydrocephalus may
In his experimental studies, Jacobson noticed also be present in a number of major and
that the laminar flow of CSF through the aque- minor chromosomal aberrations affecting
duct is very important and it is secured by its par- chromosomes 8, 9, 13, 15, 18, or 21.
ticular shape. Therefore a change of its shape will • MALFORMATIVE: cysts of the posterior
alter the flow rate and the flow pattern. fossa and of the tentorial incisural, spina
48  Surgical Treatment of Central Nervous System Malformations 617

bifida, or hydranencephaly where aqueductal The prenatal detection of fetal hydrocepha-

stenosis is primary or secondary in origin. lus has traditionally relied on sonographic
• CHEMICAL: trypan blue, salicilyte, cupri- measurements of ventricles. The most useful
zone, if taken by the mother during pregnancy, measurement is the transverse atrial width,
­vitamin B and folic acid deficiency in early ges- which is normally between 4 and 8  mm with
tation and vitamin A deficiency in newborn. an upper limit of normal at 10 mm. The utility
• INFECTIOUS: aqueductal gliosis due to bac- of the measurement is based on the fact that the
terial or viral intrauterine or postnatal infec- atria are easily identified, and the measurement
tions (50%) (toxoplasmosis, CMV, syphilis, is nearly constant between 15 and 35 weeks of
rheo-, paramyxo-, arboviruses, influenza). gestation. Prenatal sonographic data include
• VASCULAR: vein of Galen aneurysms, intra- also the biparietal diameter, size of the third
cranial hemorrhages in premature and new- ventricle, the ratio between laterals and third
born as well as in adults. ventricle, and thickness of the frontoparietal
• NEOPLASTIC: (extremely rare) posterior cortical mantle.
fossa, brain stem, and pineal region tumors. The finding of fetal ventriculomegaly requires
• and sometimes cryptogenetic. a prompt evaluation that begins with a concerted
• DEVELOPMENTAL STENOSIS: Develop­ effort to rule out additional anomalies.
mental stenosis represents the 10% of the eti- For those patients diagnosed before the legal
ology of hydrocephalus in newborn. Incidence limit of abortion, there is urgency to complete the
rate is 0.5–1 on 1000 births. work-up to allow an informed parental decision.
The maternal gestational history is reviewed for
• Aqueductal agenesia (complete or partial) in previous outcomes, early drug exposures, and
which small ependymal nests represent the unexpected illnesses, and the family history is
consequence of an abnormal infolding of the reviewed for X-linked hydrocephalus and neural
neural plate. It is very rare. tube malformations.
• Aqueductal forking in which the aqueduct is Ultrasound evaluations alone can miss impor-
splitted in two or more irregular channels that tant anomalies, which will affect the outcome, so
can be blind, independent, or communicate ultrafast fetal MRI has been developed as a more
with each other. anatomically precise modality for prenatal neuro-
• Aqueductal occlusion due to the formation of imaging. There is no apparent risk to the mother
an ependymary septum at its lower tract. or fetus from the radiofrequency pulses or the
• Aqueductal stenosis where a gliotic prolifer- magnetic field. Therefore, ideally, an MRI scan is
ation, which develops in areas of the aqueduct obtained and interpreted by an experienced pedi-
without ependymal lining “denuded areas,” atric neuroradiologist to rule out any additional
narrows its lumen. CNS anomalies.
Amniocentesis is performed for viral cultures,
48.2.1.4 Diagnosis chromosomal analysis, and alpha-fetoprotein
Prenatal sonograms, in utero MRI, postnatal cra- levels.
nial ultrasound, and head CT and MR represent
the diagnostic tools to detect aqueductal stenosis. Postnatal Diagnosis
On CT scan, blockage at the aqueduct is assumed
Fetal Diagnosis when the lateral and third ventricles are enlarged
The early antenatal diagnosis still remains as a proximal to the obstruction, and the fourth ven-
diagnostic challenge, since the diagnosis of ven- tricle is relatively small.
triculomegaly or hydrocephalus may not become An MRI examination, in T1 and T2 sequences,
apparent until 18 weeks of gestation. Aqueductal with 3-mm-thick, contiguous midline sagittal
stenosis is usually diagnosed in the second or sections, will reveal the presence of an aqueduc-
third trimester of pregnancy. tal stenosis and its etiology.
618 M. Scagnet et al.

At aqueductal level, the “flow void” signal 48.3 Arachnoid Cyst

produced by CSF flow pulsations, in T2 images,
appears hypointense in comparison with v­ entricular Arachnoid cysts are collections of CSF in the
CSF. This is considered the most important radio- subarachnoid space. They are relatively closed
logical sign of aqueduct patency. spaces with a very poor fluid circulation inside
It is important to notice that in aqueductal them and throughout the entire subarachnoid
shape modifications, the increase of flow velocity space.
may result in a void signal with a false diagnosis The anatomy of the subarachnoid space and
of aqueductal patency on MRI examination. cisterns, described first by Vesalius in 1555, had a
Another and more reliable method to study the thorough description by Yasargil (Microsurgical
CSF pathways is the cardiac-gated cine MRI. anatomy of basal cisterns,1984, Georg Thieme
Verlag Vol I).
48.2.1.5 Prognosis Many of the subarachnoid cisterns can be
The prenatal detection of hydrocephalus has considered anatomically distinct compartments.
facilitated obstetric care but presents a source of After normal development, there is a continu-
uncertainty for the family and a challenge for the ous exchange of CSF from one compartment to
team counseling parents regarding their fetus. another, via trabeculated porous of various sizes.
It is clear that fetal ventriculomegaly with These apertures and communications may
associated abnormalities have a poor outcome. In become plugged and partially or totally obliter-
cases of ventriculomegaly associated with infec- ated by various mechanisms (infection, hemor-
tions, chromosomal abnormalities and severe rhage, etc.).
CNS and extracranial abnormalities, the poor Various cystic lesions may be observed in
prognosis may influence the family’s decision to different regions of the intracranial and spinal
continue the pregnancy. The outcome of isolated spaces.
fetal hydrocephalus, however, is variable.
Published studies of neonates with aqueductal
stenosis have noted variable outcomes, with nor- 48.3.1  Sylvian Cyst
mal development seen in 24–86% of cases. The
prognosis of aqueductal stenosis depends on the They are cavities located in the temporal region.
following: the extent of venticulomegaly, how They may assume huge proportion, and they may
early during gestation it becomes evident, and extend as far as a whole hemisphere. We describe
its progression with time. However, it is not pos- three forms (Galassi et al. Surg Neurol 17:363–9,
sible to predict in an affordable way if the baby 1982).
will be mentally handicapped or not and, if yes,
to which extent. Fetuses with aqueductal stenosis 1. Internal cyst (mesial to the temporal lobe). It
have a good survival rate, because they usually is a small, biconvex cyst, located in the ante-
do not have associated abnormalities. Males with rior temporal tip. Classically no mass effect is
X-linked hydrocephalus generally have a less present.
favorable prognosis. 2. Internal and external to the temporal lobe.

Prenatal factors such as progression, degree They usually involve the proximal and inter-
of cortical mantle thinning to less than 1.5 cm, mediate segments of sylvian fissure. There
and in utero duration of greater than 4  weeks may be a mass effect on ventricular structures
contribute to a worse prognosis. On the other and/or cranial nerves.
hand, those with mild isolated ventriculo- 3. Huge almost hemispheric cyst. They involve
megaly of less than 12  mm have an excellent the entire sylvian fissure with normally
prognosis. marked shift of the midline structures.
48  Surgical Treatment of Central Nervous System Malformations 619

Surgical indication depends on signs of raised 48.3.4  Interhemispheric Cyst

Intracranial pressure (ICP) and/or compression
of cranial nerves. In case of huge volume, the They are complex malformations involving the
surgical treatment must be considered. brain, corpus callosum, and commissures.
If seizures are the only sign the surgical indi- They may be associated with hydrocephalus.
cation is controversial. In the neonatal period, the signs of raised ICP are
Marsupialization of the cyst with the cisternal frequently observed.
space is the recommended procedure. Surgical indication depends on hydrocepha-
In some cases, especially in very young babies, lus. Temporary CSF diversion by shunting of the
a temporary shunting procedure may be effective. cyst is the best tool.
Marsupialization can be done by microsurgi- Secondary the shunt may be removed after the
cal technique and by neuroendoscopy (see chap- endoscopic marsupialization of the cyst into the
ter on Neuroendoscopy). ventricle.

48.3.2  Suprasellar Cyst 48.3.5  Septum Pellucidum, Velum

Interpositum,
They are cavities located in the suprasellar space. and Quadrigeminal Cyst
They may be arachnoid cysts or a neuroepithelial
cysts realizing a true hamartoma. Rarely these cysts have mass effect and disturb
Signs are related to hydrocephalus or endo- the CSF circulation.
crine dysfunctions like precocious puberty. Surgical indication is quite rare.
In older children or adults, signs of increased Quadrigeminal cyst may disturb CSF circula-
ICP may be difficult to identify. For example, tion in the aqueduct causing mild hydrocephalus.
seizures, lipotimia, or episode of raised arterial Endoscopic approach with third ventriculostomy
blood pressure may mask a real state of IIC. resolves the hydrocephalus without approaching
Surgery is mandatory in almost all cases of the cyst. In some cases, endoscopic marsupializa-
suprasellar cyst. tion of the cyst via the ventricle is feasible.
Today the gold standard is the endoscopic
approach with marsupialization of the cyst into
ventricles and cisterns. 48.3.6  Posterior Fossa Cyst

The Dandy–Walker complex must be excluded

48.3.3  Convexity Cyst from the arachnoid cyst of the posterior fossa.
The so-called Dandy–Walker variant must
They are mild volume cavities on the surface of also be excluded.
the brain mainly located on the outer surface of The Blake’s pouch is a retrocerebellar cystic
the parietal lobe, rarely on the mesial one. evagination of the posterior tela choroidea, with-
Signs are related to local mass effect on cere- out agenesis of the cerebellar vermis.
bral gyri and sulci. Rarely the posterior fossa cysts are
Seizures are frequent. Focal headache is symptomatic.
described. Even very huge retrocerebellar cyst rarely dis-
Surgical indication is controversial and based turbs the CSF dynamics.
on the volume of the cyst and the frequency of In some cases, overcrowding the posterior
the seizures. fossa, a supracerebellar cyst may induce the her-
Microsurgical marsupialization with sub- niation of the cerebellar tonsils, becoming symp-
arachnoid space is the technique of choice. tomatic. In like manner, a retrocerebellar cyst or
620 M. Scagnet et al.

a Blake’s pouch may push down and occlude the hypothalamic hamartoma (HH), and is currently
cisterna magna and become symptomatic. used in rare subtypes of hydrocephalus.
In these cases an osseous anomaly with a In pediatric age, the high incidence of hydro-
reduced volume of the posterior fossa explains cephalus, isolated or associated with almost
the presence of the symptoms. all the cerebral lesions, makes neuroendos-
Microsurgical marsupialization (supracer- copy a valid and suitable tool for multimodal
ebellar or cerebellopontine angle cyst) and endo- treatment.
scopic approach (retrocerebellar) are the best First of all endoscopic third ventriculostomy
techniques to resolve these problems. (ETV) is today recognized as the gold standard
treatment of obstructive hydrocephalus, both in
children and infants, with an overall success rate
48.3.7  Spinal Cyst in a range of 65–85% in many published series,
depending on the institution, patients’ age, defi-
Arachnoid cysts may be located into the spinal nition of failure, origin of hydrocephalus, indica-
canal at various levels. tion, and follow-up period.
Their volume is small, but they might grow Obstructive hydrocephalus due to aqueductal
with a mass effect on the spinal cord and/or root stenosis in children older than 1 year is charac-
and become symptomatic in a short period. terized by 98% of patients shunt-free after ETV.
Scoliosis may be a revealing sign. ETV remains as a controversial hydrocephalus
There can be true arachnoid cysts, but a treatment option with high failure rates in pediat-
connective basal membrane is often found at ric patients with a history of myelomeningocele
histological exam realizing the so-called lepto- (MMC). In some cases ETV can be performed
meningeal cyst. with success rate of almost 50%. The proce-
Direct microsurgical approach by laminotomy dure should be delayed until the patient com-
and marsupialization of the cyst is mandatory if pletes 1 month of age. At Saint Louis Fetal Care
neurological signs are present. Institute, overall ETV success rate was 11/24
(45.8%) in patients who underwent fetal MMC
repair. Young age (less than 6  months) and late
48.4 Management gestational age (GA) at time of fetal MMC repair
of Hydrocephalus and CSF-­ (after 23  weeks GA) were predictors for ETV
Related Disturbances failure [1]. In patients more than 6 months of age
after shunt failure has been shown to have a good
48.4.1  Neuroendoscopy long-term success (approximately 80%) [2].
ETV in Dandy–Walker malformation can be an
Neuroendoscopy appeared at the beginning of effective means to achieve reduction in hydroceph-
the last century and started modifying general alus and is a recommended line of treatment [3].
neurosurgery during the last 20 years, thanks to Hydrocephalus in Chiari 1 malformation is a
technological progress of optical fibers. Besides known entity with a complex etiology which is a
radically changing the neurosurgical treatment of matter of great debate. However the use of ETV
hydrocephalus, nowadays neuroendoscopy is an in Chiari 1 malformation is spreading mainly
alternative and effective treatment for other intra- because it causes reduced hampering of the
cerebral and periventricular lesions located in the physiological pathways of CSF flow and absorp-
third and the lateral ventricles, such as arachnoid tion [4].
and colloids cysts. ETV may be considered the first treatment of
Furthermore neuroendoscopy allows biopsy choice for the forms of hydrocephalus that are mul-
and sometimes removal of intra- and paraventric- tifactorial and associated with complex craniosyn-
ular tumors, including vascular malformation and ostosis. Hydrocephalus should be managed before
48  Surgical Treatment of Central Nervous System Malformations 621

cranioplasty and offers less risks of skull growth 48.4.1.1 The Endoscope
impairment and infections than shunt, but its Techniques for intraventricular catheter place-
long-term success rate is reported to be 60%. So, ment may be ameliorated with pediatric
a close clinical monitoring is mandatory because neuroendoscopy.
of the high failure rate of ETV in these patients The 9.5 Fr rigid neuroendoscope produced
[5, 6]. by Storz™ is very useful and versatile in
The role of ETV in tumoral hydrocephalus pediatric neurosurgery. Despite very small
is primary: in literature series, ETV was found dimension of external diameter and thanks
to have a success rate of 70–90% and has been to a particular optical smallness, this instru-
recommended as the ideal treatment for hydro- ment is equipped with a 3 Fr operative channel
cephalus in such cases [7]. Posterior fossa tumors like that of bigger endoscopes. So it is pos-
with hydrocephalus must be treated first by ETV, sible to make the same operations as with the
followed by direct approach to the tumor few larger endoscopes. The penetration of cortical
days later. In our series the ETV success rate in surface is smaller and less traumatic. During
posterior fossa surgery is 78.5%. the ventricular tapping, the risk of injuries of
ETV for pineal region tumors is regarded as ependymal vein is lower.
the primary line of intervention with the advan- Moreover in particular surgical situation like
tage of not only relieving hydrocephalus but also narrow foramen of Monro or rigid and small ven-
providing window for biopsy and CSF analysis tricles, this instrument avoid injuries to the neigh-
and to inspect for tumor seedlings and dissemina- boring structures. In the third ventricle, in case of
tion if any [8]. huge massa intermedia, the targeting of the stoma
In infants the number of CSF shunting proce- is easier, and the penetration of the interpeduncu-
dures is being reduced by neuroendoscopy. lar cistern is possible too.
Posthemorrhagic hydrocephalus in preterm
newborns can be treated too by neuroendoscopy 48.4.1.2 Third
instead of traditional techniques. Ventriculocisternostomy
Indeed, in all cases of obstructive hydro- It is a standardized technique to open the third
cephalus (obstruction of the outlets of fourth ventricle floor to make it communicate with basal
ventricle, cysts, Chiari malformation, complex cisterns in order to divert the CSF circulation from
craniosynostosis), ETV may be considered the aqueduct and fourth ventricle. It is utilized
the first-choice treatment [5]. In case of shunt for obstructive hydrocephalus due to aqueduc-
failure, ETV can be proposed instead of ven- tal stenosis on a malformative basis (aqueductal
triculoperitoneal shunt revision, achieving 82% atresia, arachnoid cysts of lamina quadrigemina)
success rate of children shunt-free [9]. A signifi- and tumoral (posterior fossa, pineal or brainstem
cant improvement in our understanding has been tumor, tectal hamartoma) and also in the presence
contributed by the preliminary results published of aqueductal flow disturbance due to hemor-
by The International Infant Hydrocephalus rhages or infections.
Study Group; this prospective, multicenter com- The surgical technique is standardized in all
parison of ETV, and shunt success in infants cases. We used a Storz™ rigid neuroendoscope
(<24  months old) suggest that shunting has a of 9.5 French, a Fogarty balloon catheter with
superior success rate as compared to ETV (66% an outer diameter of 3.2 mm and 30° angulated
vs. 88% at age of 6 months), slightly higher than optic. The camera was oriented with the opera-
would have been predicted by the ETV Success tive sheet. Under general anesthesia, the patients
Score (57%). were positioned supine with the head slightly
Even in shunted children with slit ventricle flexed, and a pre-coronal 5  mm burr hole was
syndrome, ETV may be considered an alternative made. In infants, the access was performed at the
choice [10]. lateral margin of the anterior fontanel.
622 M. Scagnet et al.

After opening the dura and the arachnoidal a

surface, the endoscope was inserted “freehand”
without a stilet under direct view control. The
presence of mandrin passed inside the operative
channel and prevented the passage of small brain
particles into the endoscope during the introduc-
tion. After the lateral ventricle was reached, the
foramen of Monro was identified following the
choroid plexus, at the confluence with the venous
angle formed by anastomosis of the anterior septal
vein and the thalamostriatal vein. The endoscope
crossed the Monro to reach the third ventricle.
The fenestration was performed in the triangle
between the tuber cinereum anteriorly and the
mammillary bodies posteriorly, as close as pos-
sible to the dorsum sellae to avoid injury to the
b
basilar artery complex (Fig.  48.1). The opening
in the floor of the third ventricle was made with a
1 mm coagulator fiber followed by the insertion of
a 2 French Fogarty balloon catheter inflated with
0.2  cc of saline solution in the cistern and then
withdrawn into the third ventricle (Fig. 48.2). No
forceps or blunt technique was used. After the
perforation of the floor of the third ventricle, the
neuroendoscope was always introduced through
the stoma into the interpeduncular cisternal space
to open the two layers of the Liliequist membrane
to reach the prepontine cistern, after the identifi-

Fig. 48.2  Endoscopic view. (a) Opening of the floor by

coagulator. (b) The balloon of the Fogarty catheter is
inflated through the stoma

cation of basilar artery. The endoscope was then

retracted (Fig.  48.3). Irrigation was carried out
carefully and manually if necessary; no continu-
ous irrigation was used. The whole procedure was
always carried out in a “freehand” fashion and
took an average time of 30 min.

48.4.1.3 Septostomy
Septostomy consists in opening the septum pel-
lucidum (Fig. 48.4) in case of monoventricular or
biventricular hydrocephalus. It is also applied to
Fig. 48.1  Endoscopic view of the floor of the third ven-
tricle. the tuber cinereum and mammillary bodies are open pathologic septa inside ventricles in multicys-
visible tic hydrocephalus [11]. Multistep neuroendoscopic
48  Surgical Treatment of Central Nervous System Malformations 623

b
Fig. 48.3  Endoscopic view: the stoma is open between
the third ventricle and the interpeduncolar cistern

treatment of multiloculated hydrocephalus

reduces the number of intracranial shunts.
To perform the septostomy, a lateral pre-­
coronal hole is performed to achieve perpendicu-
lar and not parallel access to the septum.

48.4.1.4 Arachnoid Cysts

Marsupialization
The technique aims to open the wall of the cyst
inside the CSF cisterns and/or ventricular cavi-
ties: for example, a temporo-sylvian cyst can be
put in communication with optic, internal carotid Fig. 48.4  Endoscopic view. (a) The Fogarty ballon is
artery and perimesencephalic cistern (Fig. 48.5). pushed through the septum pellucidum. (b) Opening
A suprasellar cyst may be fenestrated into the between the two lateral ventricles
interpeduncular cistern, while an interhemi-
spheric cyst is opened into the ventricular cavi-
ties [11]. Posterior fossa cyst (retrocerebellar, The best surgical management of sylvian
pontocerebellar angle, supracerebellar) may be arachnoid cysts has been discussed and is still
fenestrated into the cisterna magna or into the controversial. The microsurgical approach
pontocerebellar cisterns and perimedullary cis- results in 88% success rate, while the endo-
ternal spaces. scopic technique in 70%. In our experience,
Among reviewed quadrigeminal cistern cysts 40 patients have been operated with endo-
treated by endoscopic fenestration, complete or scopic fenestration for middle fossa arachnoid
partial clinical remission was achieved on average cysts: in 92.5% there was a satisfactory clinical
in 88.5% [12–14]; for suprasellar cysts is 89.7% outcome, and in 72.5% patients the cyst was
and for posterior cranial fossa 83.3%, similar to reduced in size or completely disappeared.
the results of craniotomy and cyst shunting, 86% Endoscopic fenestration failure occurred in
and 90%, respectively [15–19]. 10% of patients (n  =  4), necessitating repeat
624 M. Scagnet et al.

a b

Fig. 48.5  MRI Axial view. (a) Huge arachnid cyst in the scopic approach). Note the almost complete disappear-
temporo-sylvian region with compression of the midline ance of the cyst
structures. (b) MRI Axial view: Post operative (endo-

surgical treatment, one with cystoperitoneal

shunting and three with a redo-endoscopic pro-
cedure [20].
Arachnoid cysts of the cortical and interhemi-
spheric regions are best treated by craniotomy
with direct cyst fenestration.
In case of endoscopic surgery failure, redo-­
endoscopy and direct microsurgical opening of
the cyst through craniotomy are to be considered
the first instance; cystoperitoneal shunting today
represents last-choice surgery.

48.4.1.5 Placement of Catheters

In the presence of virtual ventricles or ventricles
with multiple septations, neuroendoscopy enables
a catheter to be placed in the selected place, also
allowing its connection with an Ommaya reser- Fig. 48.6  Endoscopic view of Hypothalamic hamartoma
voir for CSF tapping and/or drug delivering [11]. (*). Tuber cinereum (Tc), infundibular recess (Inf.)

48.4.1.6 Computer-Assisted 48.4.1.7 Functional Neurosurgery

Neuroendoscopy Neuroendoscopy can be utilized in epilepsy
Neuroendoscopy can be utilized together with surgery for the deafferentation of hypothalamic
neuronavigator for procedures in small or virtual hamartoma (HH) (Fig. 48.6). HHs are rare, non-
CSF pathways as well as for treating deep cystic neoplastic, congenital malformations arising
lesions. from the inferior hypothalamus and associated
48  Surgical Treatment of Central Nervous System Malformations 625

with gelastic and dacrystic seizures, precocious Flushing is accomplished simply by pressing on
puberty, and cognitive problems. Recent reports the skin overlying the flushing chamber.
indicate that endoscopic disconnection of HHs Assuming that “the best shunt is no shunt,”
seems to be safer and more effective than other none of the innumerable multicentric trials have
modalities [21, 22]. In most cases, navigation showed that any shunting system is more effec-
assistance is recommended because lateral and tive than another.
third ventricles are normal sizes in these patients. At the moment at least 127 different designs
are available but most of these are only clones.

48.5 Shunting Procedures

48.5.1  CSF Shunt Valves
The evacuation of superficial intracranial fluid in
hydrocephalic children was first described in detail 48.5.1.1 D  ifferential Pressure Pre-­
in the tenth century by Abu Al-KassimKhalaf Ibn settled Valves
Abbas Al Zaharawi (936–1013) said Abulcassis These valves are subdivided in four broad catego-
in Al-Andalous. ries: slit valves, miter valves, diaphragm valves, and
In 1893 the first permanent ventriculo-­ ball-in-cone valves. These systems have pre-defined
subarachnoid-­subgaleal shunt was described by operating pressures with three or five performance
Mikulicz, who proposed a simultaneous ven- levels that vary from very low to high. Differential
triculostomy and drainage into extrathecal low-­ ­pressure valves open when the intraventricular pres-
pressure compartment. sure rise above the precalibrated opening pressure,
Between 1898 and 1925, lumboperitoneal and allowing CSF outflow, and close when the pres-
ventriculoperitoneal, ventriculovenous, ventriculo- sure falls below the closing pressure of the valve.
pleural, and ventriculoureteral shunts were invented, The limitation of standard differential valves is that
but, in most cases, these systems had a high failure the flow increases when the pressure differential
rate due to insufficient implant materials. increases (i.e., orthostatic pressure in standing posi-
Artificial CSF valves were proposed in 1948 tion) leading to overdrainage complications.
by Ingrham, by Bush at MIT in 1949  in collabo-
ration with Matson, and by Nulsen and Spitz in 48.5.1.2 Anti-siphoning Devices
Philadelphia. During the 1950s, the Spitz–Holter These devices have been developed by Portnoy
shunt was developed leading to a tremendous impact et  al. in 1973, in the attempt to counteract the
on neurosurgical procedures for hydrocephalus. complication of overdrainage. The device is
After the first generation of simple differential implanted below the valve and is responsive to
pressure valves, which are unable to drain physi- atmospheric pressure transmitted through the
ologically in all body positions, a second genera- skin, in fact, thanks to a small diaphragm that
tion of adjustable, autoregulating, anti-siphoning, reduces CSF flow when the pressure inside the
and gravitational valves was developed. shunt falls below the atmospheric pressure. The
Many shunt systems also have a flexible flush- problem is that if it becomes incased by scar tis-
ing chamber (reservoir) which may be housed sue, it is unable to sense atmospheric pressure.
within the same unit as the valve or may be a
separate unit along the shunt, depending on the 48.5.1.3 Programmable Valves
design of the shunt system. This chamber serves These valves have an adjustable ball-spring mech-
several important purposes. It permits to obtain anism and operate as a differential device with
samples of CSF from the shunt with a needle and the advantage that it is possible to modify the
syringe and to inject the chamber for testing shunt operating pressure of the valve once it has been
function and for medical treatment. The chamber implanted by means of an external device with a
also allows the shunt to be “flushed” or pumped. magnet placed on the skin.
626 M. Scagnet et al.

Some authors have not reported a higher effi- subcutaneous space and placed in the perito-
cacy and safety rate of these devices compared to neum. The advantages and disadvantages are as
precalibrated valves. Other Authors believe that follows:
this type of shunt is superior because “..one can- Advantages:
not know in advance which case will turn out to
be complicated…”. 1 . Less morbidity from shunt infections.
2. The possibility of placing a length of distal
48.5.1.4 Flow-Regulating Valves tubing to accommodate the patient’s distal
In these valves CSF flow through the device var- growth.
ies in correlation to the variation of CSF pressure.
In attempt to keep the CSF flow rate constant, the Disadvantage:
mechanism resistance increases as the pressure
gradient increases. 1. Peritoneal adhesions or infections.
In conclusion none of the described types
of valve appears to be best for the initial treat- The risk of seizures, which appears higher
ment of pediatric hydrocephalus. with frontal positioning, has been reported to
be 5.5% in the first year after placement of a
ventricular catheter. The risk rate dropped to
­
48.5.2  Shunt Surgery Techniques 1.1% after 3 years.

Especially in children the ventriculoperitoneal 48.5.2.3 Procedure

route is preferred to the ventriculoatrial route Shampoo the night before the procedure is rec-
because it is easier to place and is followed by ommended; before surgery an antiseptic iodine
less morbidity. solution is used. It is not proven that hair shaving
Many studies have been carried out to evaluate reduces contamination, so we do not shave the hair.
the possibility of prevention and reversibility of Under general anesthesia, the patient is posi-
pathological changes in hydrocephalic brain after tioned supine with the head rotated on the oppo-
shunting. site side of the planned implantation. The neck is
In experimental models it has been demon- extended and lifted with a rolled drape positioned
strated that, after early shunting, many damages underneath, to obtain a straight and flat line
to the gray (reduction of neuron size, disorien- between head and abdomen in order to facilitate
tation, dendritic deterioration) and white matter the subcutaneous passage.
(periventricular edema, axonal damage, demy- The site of the cranial and abdominal inci-
elinization, gliosis) and brain metabolism can sion should be selected and marked before
partially recover. draping. After an accurate skin preparation
(5 min) with iodine solution, the patient must
48.5.2.1 External Ventricular be entirely covered by drapes with the exclu-
Drainage sion of a small skin corridor between the head
A short-term CSF shunt device may be needed and the abdomen. An adhesive plastic sterile
for hydrocephalus following intraventricular drape is then placed over the exposed skin to
hemorrhage, bacterial infection, or after brain avoid contact with the skin surface. Skin inci-
tumor surgery with a high risk of postoperative sions must be adequate and the cranial incision
hydrocephalus. should not overlie the valve.
Ventricular catheter can be inserted in the lat-
48.5.2.2 Ventriculoperitoneal Shunt eral ventricle via the frontal or the occipital horn;
This is the most popular shunting procedure. which burr hole location is advisable is contro-
The ventricular catheter is placed through an versial. Some authors reported that “…shunts
occipital or frontal burr hole and connected to inserted via the frontal region functioned signifi-
the valve. The distal catheter is tunneled in the cantly longer than parietally inserted shunts”.
48  Surgical Treatment of Central Nervous System Malformations 627

Frontal burr hole must be placed 2.5–3 cm. catheter is introduced into the transverse facial
from the midline, on the midpupillary line, and or jugular vein, and the amount of distal tubing
1 cm. anteriorly to the coronal suture, parieto-­ is standard and cannot be adapted to the child’s
occipital burr hole at about 7  cm. from the growth.
inion. Burr hole size must be adequate to the
implanted device and can be carried out with a 48.5.2.5 Procedure
twist drill. It is advisable to prepare a fluoroscopic control
The peritoneal cavity is approached with a in the operating theater. Patient position, skin
minilaparotomy and a trocar or endoscopically. preparation, and cranial procedure are identical
We prefer a small laparotomy, and the abdominal to ventriculoperitoneal shunting procedure.
incision is carried out transversally in the para- Drapes are used to cover the patient except
umbilical region. Tunnelization should be carried for the part of the skin included between the
out between the two skin incisions starting from burr hole and the sternal notch. An oblique skin
the abdominal incision especially if the implant incision is carried out on the neck at half way
of a pre-assembled system has been planned. between the mastoid and the sternal notch. When
The tunneling instrument must be passed not the platysma muscle has been divided, it is pos-
too deeply or too superficially in order to avoid, sible to identify the posterior border of the ster-
respectively, chest or posterior fossa injuries and nocleidomastoid (SCM) muscle and the external
skin lacerations. jugular vein. Proceeding with deep dissection
After the tube and reservoir are in place, the underneath the SCM muscle, it is possible to
dural opening is carried out with low-power identify the internal jugular vein and the com-
monopolar applied to a small brain needle; it mon facial vein; they both lie just lateral to the
should have the same diameter of ventricular carotid artery. Once the facial vein is isolated
catheter to avoid CSF leakage, and the pia is cau- and hemostatic lace and silk ties are positioned,
terized with bipolar forceps. a phlebotomy is carried out on it, and the cath-
The catheter trajectory is determined eter is passed, under fluoroscopic control, into
according to external landmarks. From a the jugular vein until its tip is placed in the right
frontal approach, catheter is inserted perpen- atrium, just above the tricuspid valve. Once
dicularly to the skull, aiming the posterior atrial catheter is well positioned, it is trimmed to
projection of the medial epicanthus. From an the appropriate length and definitively connected
occipital burr hole, the target will be the mid- to the valve.
point of the forehead.
Introducing the proximal catheter, it is possi-
ble to feel the ventricular cavity entry as a “pop” 48.5.3  Shunt Complications
when the ependyma is breached, with a concomi-
tant gush of CSF. CSF shunting represents the neurosurgical pro-
A right-angled guide allows catheter bending cedure with the highest failure rate. Most com-
and stabilization before attaching it to the valve. plications that require revision of the shunt occur
Once CSF is flowing out of the tip of the distal within 6 months to 1 year after surgery.
catheter, it is time to insert it into the peritoneal The main causes of shunt dysfunction are:
cavity.
Soft tissue should be closed in two layers with • Obstruction
careful apposition of the edges. • Infections
• Mechanical problems (migration, disconnec-
48.5.2.4 Ventriculoatrial Shunt tion, malpositioning)
This is a less commonly used procedure for the • Other complications
high risk of infection (sepsy, pulmonary embolus,
cor pulmonale, nephritis, and death). The shunt Obstruction can occur in any of the compo-
procedure is more demanding because the distal nents of the shunt device. The ventricular catheter
628 M. Scagnet et al.

may be obstructed by choroid plexus tissue or by that’s why an experienced neurosurgeon should
ventricular wall. Blood cells, bacteria proteins, perform the procedure.
and other tissue debris may also block the ven- In order to reduce the risk of contamination, a
tricular catheter and/or valve. Moreover, the tip surgical team should consist of the surgeon, the
of the peritoneal catheter may be obstructed by assistant, the anesthesiologist, and the circulating
loops, fat abdominal tissue, and other abdominal nurse only.
pathologies. Care must be taken to the selection of the
Shunt infection is usually caused by a shunt, and the sterile package of the device
child’s own bacterial organisms. The most fre- should be open at the very last moment, immedi-
quent organism is Staphylococcus epidermidis ately before the implantation. Testing the valve,
which is normally present on the surface of a when not necessary, is not advisable.
child’s skin, in sweat glands, and in hair fol- Prophylactic intravenous antibiotic, a cepha-
licles deep in the skin. These infections are losporin of second generation, should be admin-
most likely to occur 1 month after surgery and istered 30 min before the skin incision.
sometimes up to 6 months after the placement To minimize contact with patient skin while
of a shunt [23]. passing the distal catheter, only two skin incisions
Mechanical and other complications are should be performed. A meticulous h­emostasis
described too. Shunts are very long-lasting and utilization of intraoperative antibiotic wash-
system, although their hardware may become ing is important to prevent bacterial growth. Skin
disengaged as a result of the child’s growth, incision should not overlie the valve, so a careful
with migration into the body cavities where siting of the valve case and a good quality of soft
they were originally placed. The valve itself tissue closure preferably in multiple layers are
rarely breaks down because of mechanical mandatory.
malfunction even if the shunting device may
over- or hypodrain CSF. The overdrainage 48.5.3.3 Postoperative Period
may result in slit ventricle syndrome and/or Care must be taken in head positioning in order
subdural hepatoma: in these patients cranial to avoid pressure on the valve especially in pre-
vault expansion and/or subtemporal decom- matures and newborns. During the period in hos-
pression may be needed to achieve ventricular pital, which lengths approximately 4 days for the
re-expansion. first shunt procedure and 2 days for a shunt revi-
sion, patients shampoo twice [23].
48.5.3.1 Preoperative Period
Patient should be assessed taking into consider-
ation general medical conditions and the pres- 48.6 Craniofacial Repair
ence of eventual skin problems. Hair shaving is for Craniofacial
not advised and skin should be prepared with Dysmorphism
povidone iodine washing.
Surgical treatment of craniosynostosis aims to
48.5.3.2 Shunt Procedure correct the deviated calvarial shape, to stop the
Shunt procedures should be scheduled early in compensatory growth, and to modify its effects
the morning, before other operations. Newborns by normalizing the physiological functions. This
and infants have the precedence on older chil- can be achieved, but not always completely, by
dren, and no more than four shunt procedures the “dynamization” of the restricted skull growth
should be performed in a day. The optimal length and the redirection of the abnormally oriented
of a shunt procedure is comprised in 20–40 min; growth vectors.
48  Surgical Treatment of Central Nervous System Malformations 629

In some craniosynostosis (scaphocephaly) Successively, when complete growth is

only affecting the cranial vault, a simple and wide achieved, treatment can be completed with rhino-
suturectomy allows a passive reshaping, espe- plasty and canthopexy procedures.
cially in the first 2  months of life, utilizing the
released directional vectors of growth with the
final result of a good cranial expansion and cos- 48.6.1  Preoperative Assessment
metic correction.
In other craniosynostosis involving the vault Early surgical correction is extremely important
and the skull base simultaneously (e.g., brachy- to achieve best functional and cosmetic result: the
cephalies, trigonocephalies, and most plagio- chance of an optimal aesthetic result decreases
cephalies), active reshaping is required by with child age, especially after 12  months.
bringing vault regions into the desired position Unfortunately, toddlers in first months of life are
and remodeling shape, orientation, and angles of characterized by “triple precariousness” (large
the orbital bar. needs, insufficient supplies, inadequate con-
The best time for this kind of correction is trol mechanisms) making necessary and accu-
between the fourth and the sixth month of life. rate clinical examination to detect concomitant
On the other hand, the management of com- pathologies (e.g., cardiopulmonary system, coag-
plex craniofacial malformations (e.g., Crouzon, ulopathies, etc.) and reduce anesthesiological and
Apart, and Pfeiffer syndromes and cloverleaf surgical risks.
skull syndrome) is characterized by a multistep
surgery. Initial anterior skull and orbital ridge
remodeling with expansion and volumetric
increase of the anterior cranial fossa aims to 48.6.2  Surgical Procedures
resolve the intracranial hypertension, manage
breathing and feeding problems, and safeguard 48.6.2.1 Craniectomy
brain growth and visual function. Posterior and Suturectomy
skull expansion is sometimes needed when This technique is only applied in infants in the
the occipital regions appear extremely flat; if first months of life which cranial deformities
Chiari type 1 anomaly coexist, occipital fora- restricted to the vault (scaphocephaly). Goal of
men and occipital former opening may be com- surgery is releasing the directional growth vec-
bined [24]. tors in correspondence of the prematurely fused
The second step is addressed to midfa- suture in order to allow a harmonic expansion of
cial advancement, which is performed later, the brain.
around the fourth year of life. In cases of Vertex craniectomies, associated to strip cra-
severe midfacial retrusion, causing psycholog- niotomies along coronal and lambdoid sutures,
ical problems in preschool age, early maxil- must be preferred to small suturectomies to avoid
lary distraction can be performed by means of precocious reossification. The bony defects will
mechanical devices that provide a progressive close by the end of the first year when the infant
advancement and correction of the facial dys- learns to walk.
morphism and subsequent enlargement of the The advantage of this technique is represented
nasal airway. by the possibility of a more precocious correction
This procedure is sometimes definitive or can and a smaller skin incision (linear or “S-shaped”
prepare the child for subsequent programmed tra- vertex incision) with reduced blood loss; the dis-
ditional midfacial advancement using the Le Fort advantages are represented by a delayed cosmetic
III technique. result.
630 M. Scagnet et al.

Posterior plagiocephaly is the less common which accomplishes a satisfactory and imme-
kind of craniosynostosis, and a differential diag- diate active remodeling of the cranial vault
nosis from the more frequent positional plagio- (Fig. 48.7).
cephaly is often required. Posterior positional
plagiocephaly responds to “position therapy” 48.6.2.3 Fronto-orbital Advancement
or is solved by the use of external orthoses that and Remodeling
mold the cranium. This technique first described by Tessier and suc-
Surgical treatment is reserved only to true cessively modified by Marchac is used in vari-
lambdoid premature synostosis which consists in ous fashions for trigonocephaly, plagiocephaly
a vault reshapening by performing “fan or radial (Fig.  48.8), brachycephaly, and oxycephaly, to
osteotomies.” expand anterior cranial fossa and remodel frontal
bone and orbital bar.
48.6.2.2 Cranial Vault Remodeling The procedure is characterized by a bicoronal
When an immediate cosmetic result is required skin incision, anterior lift of the scalp flap until
for scaphocephaly, more invasive procedures are the orbital rims, elevation of the pericranium, and
employed. detachment of the temporalis muscle and of the
Many authors recommend the Marchac and periosteum until the upper part of the orbital cav-
Renier multisegment technique which allows ities and frontozygomatic process are exposed. A
good cranial reshaping and volume expansion. bifrontal bone flap, included between the coronal
In these cases, in scaphocephalies, we prefer sutures and a horizontal line about 2.5 cm above
the “pi procedure” described by Jane in 1986 the orbital rims, is then outlined and removed.

a b

Fig. 48.7  Scaphocefaly (a) Preoperative view from above. (b) Postoperative appearence after cranial vault remodelling
(from above)
48  Surgical Treatment of Central Nervous System Malformations 631

a b

Fig. 48.8  Right anterior plagiocephaly. (a) Preoperative view. Note the facial scoliosis. (b) Postoperative (at 3 years).
Note the symmetry of the craniofacial skull

The fronto-orbital bandeau is removed en bloc, 48.7 N

 ew Minimally Invasive
avoiding to open the periorbital capsule, perform- Surgical Techniques
ing multiple osteotomies carried out along the for the Treatment
orbital roofs, the frontozygomatic sutures, the of Craniosynostosis
lesser sphenoid wing, medially above the frontona-
sal suture, and along the temporal bone with piezo- In 1890, Lannelongue published the first correc-
surgery or a chisel. At this point care is taken to tive action of a craniostenosis (scaphocephaly).
detect dural lacerations and eventually repair them. From that first surgery, many other surgical tech-
The orbital bar is then bent by grooving the niques have occurred.
inner table or with a bender instrument, reshaped, Thanks to an increase in knowledge about the
and repositioned with the new orientation and etiology of these diseases, we have gone from
angle. A good stability especially in brachyceph- a minimal technique, how can it be considered
aly (Fig.  48.9) may be achieved with the use of mere suturectomy, to a highly qualified remodel-
bioresorbable lactic acid polymer plates. After its ing surgery breaks through the cranial vault [25].
recontouring, the frontal bone is repositioned and Furthermore, in the recent developments on
ensured to the orbital bar or leaving it free to “float” the pathogenesis and non-marginal help brought
on the frontal lobes. The temporal bone defect is by new neuroimaging techniques (TC, TC-3D,
filled advancing and rotating anteriorly the tempo- and MRI), over the past decade, there has been
ralis muscle. The bone surface is then covered by a new turnaround returning to prefer a minimally
pericranium and the scalp is closed in layers. invasive technique [26]. The aim is to obtain the
Treatment of plagiocephaly can also be same result by reducing the morbidity.
performed by advancing and remodeling the This reaches its peak in spring-mediated sur-
orbital bar only on the affected side. gery, in which a simple removal of stitches bind-
632 M. Scagnet et al.

a b

Fig. 48.9  Brachycefphaly. (a) Preoperative view. (b) Postoperative view after fronts-orbital advancement with biore-
sorbable plates and screw

ing the dynamic Expander placement in time of tuated: 505 only suturectomy (27 with endo-
a few months will reshape the skull helping us to scopic technique), 30 suturectomy  +  metal
achieve the desired result. springs, and 355 suturectomy  +  absorbable
Since 2007 was introduced at our neurosur- springs. The range of craniosynostosis treated
gery division the use of dynamic metal expand- with suturectomy + absorbable springs includes
ers (technique introduced in 1997 by Dr. Claus (Fig. 48.10):
Lauritzen, Sweden) to allow more and more
minimally invasive interventions. This new tech- • Scaphocephaly 19
nique involves excision of the pathological suture • Plagiocephaly 156
and the subsequent suture placement of dynamic • Trigonocephaly 70
metal expanders. The weak point of this type of • Brachycephaly 38
surgery is that such expansion should be removed • Pachycephaly 9
to achieve results; therefore the small patient • Multicultural craniosynostosis 51
should be submitted for a second surgery under • Crouzon syndrome 7
general anesthesia [27]. • Pfeiffer syndrome 2
To avoid this, the dynamic Expander 2009 was • Saethre–Chotzen syndrome 1
introduced built with absorbable material (poly- • Clover leaf shape of skull
lactic acid and polyglycolic). Estimated time to
complete resorption is 18 months. The mean hospitalization time was 5.8  days
In total, from January 2009 to March 2017, (range 2–12). The surgical timing was 53′ for
890 patients have been operated with this mini-­ placement (range 35′–13′).
invasive technique. 497 patients were males As we highlighted the complications, only dis-
and 393 were females. The age of the patients placement of three different patients with metallic
range from 1 to 31 months. The mean age was springs comes to three different diseases: Pfeiffer
9.1 months. The following surgeries were effec- syndrome, pachycephaly, and anterior plagio-
48  Surgical Treatment of Central Nervous System Malformations 633

scaphocephaly plagiocephaly trigonocephaly

brachicephaly brachicephaly pachicephaly
mult. craniosinostosys Crouzon pfeiffer
saethre-chozen Kleeblattshádel

2%
14%
2% 1%
6% 0%
5%
1%

19%

8%
43%

Fig. 48.10  Boy, 6 months at surgery. Clinical outcome on the right photo at 18th month. Minimally invasive technique
with absorbable systems

cephaly. The pitfall of procedures was identified • Good (13.4%): cosmetic results acceptable to
and consists in positioning the metal spring hook the majority but less than ideal decreed, gener-
on the closure sick. ally secondary to a slight asymmetric.
Highlighted benefits compared to the tradi- • Insufficient (5.7%): presence of an asymme-
tional technique are a reduction in blood loss try evident or a cranial shape/size not
(from 190 to 20  cc) resulting in reduced need acceptable.
for intraoperative blood transfusion, add to that
a less postoperative analgesia and the reduction In conclusion, the spring-assisted surgery
in days of hospitalization with lower costs for offers in selected cases an excellent expansion of
individual patient. selected areas of the skull, allowing you to expand
The aesthetic and functional results were then at the same time to different areas of the skull.
evaluated by a team formed by the surgeon and In the simplest of craniosynostosis is recom-
family. These can be clustered as the following: mended the use of minimally invasive surgery
with absorbable spring, while in more complex
• Excellent (80%): craniofacial symmetry, nor- cases of absorbable spring, it is recommended
malization of skull shape and size, and aes- a minimally invasive surgery in more steps
thetic results that are pleasing to the team. (Figs. 48.10, 48.11, 48.12, and 48.13).
634 M. Scagnet et al.

a b

Fig. 48.11  Craniosynostosis treated with suturectomy + absorbable springs

a b

Fig. 48.12  Right plagiocephaly. Minimally invasive technique with suturectomy and placement of metallic dynamic
Expander
48  Surgical Treatment of Central Nervous System Malformations 635

a b

Fig. 48.13  Girl, 6 months at surgery. Clinical outcome with minimally invasive technique at 18th month

48.8 Excision of Cephaloceles enon creates a “fifth” ventricle which raises the
risk of postoperative hydrocephalus. The hydro-
48.8.1  Intrateutoria Cephaloceles cephalus is more common in meningoencepha-
loceles than in meningocele being due to the loss
First question is deciding whether to treat or of supplementary space of CSF accumulation
not a newborn with encephalocele. As a mat- and to coexistent subclinical infections. In case
ter of fact, all meningoceles should be closed of progressive hydrocephalus, a CSF ventricu-
because they do not usually contain brain struc- loperitoneal shunt is to be placed. Furthermore,
tures. On the other side, in case of large menin- in case of CSF collection under the wound, the
goencephaloceles with large amount of cerebral CSF diversion allows an easier and faster wound
structures (sometimes exceeding the entire vol- healing. In case of hydrocephalus associated
ume of normal brain) and associated malforma- with CSF infections, the treatment is external
tions, the surgical indication must be discussed ventricular drainage.
with parents because of their poor prognosis.
Prognostic factors to be considered are size of the
encephalocele, the amount of vital brain tissue, 48.8.2  Cranial Vault Cephaloceles
microcephaly, and hydrocephalus associated. In
these forms, the neurological outcome is usually Goal of surgery is cosmetic without trying to
dismal because of higher incidence of hydroceph- remove all the intracranial portion of the content.
alus and other brain malformations. Goals of sur- Skin incision is tailored to the site and exten-
gery are removing the sac with dysplastic tissue, sion of the sac; the cranial defect is repaired with
preserving functional nerve structures, and clos- autologous bone.
ing the malformation with not-dysplastic skin.
In the early postoperative period, seizures,
CSF collections, hydrocephalus, and infection 48.8.3  Fronto-ethmoidal or Sincipital
may occur. Seizures are due to the presence of Encephaloceles
dysplastic and epileptogenic brain structures.
It is usual to observe a CSF accumulation into The encephalocele is to be removed with its
the site of surgery. This “dead space” is to be whole content by a subfrontal extradural route via
avoided by compressive dressing: this phenom- an anterior bifrontal bone flap. The craniotomy­is
636 M. Scagnet et al.

made just above the anterior cranial fossa floor nasal-transsphenoidal approach uses the well-
sometimes including a fronto-­orbital osteotomy known technique of pituitary surgery to gain
to dissect better the sac in a single-step procedure. access to the sphenoid bone; this latest surgical
After sac excision and watertight dural closure technique is highly innovative and allows you
with nonadsorbable suture, a cranial base plasty to reach all parts of the skull base. In all these
with peduncolarized autologous periosteum flap techniques, the common principle is not trying
is realized to seal the bony defect. A CSF leak- to put the whole sac inside the cranium but only
age (rhinorrhea and/or CSF “tears”) may occur to reduce the extent to which it stretches into the
with risk of meningitis avoidable by an external nasal cavity and epipharynx to stop traction on
lumbar drainage. vital structures. Closure and reinforcing of the
sac is made by application of multiple layers
of oxidized cellulose and fibrin glue; the bone
48.8.4  Basal Encephaloceles defect can be closed by autologous bone pow-
der, nasal septum cartilage, autologous bone of
The surgical management of transsphenoidal, nasal turbinates, and sometimes other heterolo-
intrasphenoidal, and transethmoidal cephalo- gous ossification inducers. Reparation may be
celes is still controversial because of high mor- made through an endoscopic nasal approach,
bidity, permanent impairment, and mortality as described in an increasing number of cases
especially in neonatal period and infancy. The reported in literature.
goal of surgery is the reduction of the prolapsed
sac to lessen the traction on the vital struc-
tures, preserving their function, and obtaining 48.8.5  Other Forms of Cranial
a watertight dural closure with reparation of the Dysraphism: Atretic
bone defect. Encephaloceles
The most important question still remaining
is the route of the surgery transcranial versus A horizontal skin incision in a rhomboidal
extracranial. As described by many authors, the fashion is made around the sac. The dysplas-
transcranial transbasal route via a bifrontal bone tic skin is removed with the nonvital inner
flap is followed by higher mortality and morbid- tissue. The intracranial portion, if present,
ity especially in younger patients. On the other must be left in place. The cranial defect is
hand, since these lesions progressively enlarge, it closed by tubularizing the periosteum which
is best to operate early in order to prevent further is then covered by autologous bony pow-
damage to the herniated brain tissue, preserve der. The skin is closed with nonadsorbable
vision, and avoid progressive respiratory dis- sutures.
tress. Sometimes, urgent repair may be needed
in patients with CSF leaks or hemorrhage after
inadvertent removal of a cephalocele mimicking 48.8.6  Congenital Defects
a nasal polyp. of the Scalp (Aplasia Cutis
So, nowadays the extracranial approach is Congenita)
preferred even in infancy, especially in case
­
of p­rogressive and life-threatening symp- Smaller lesions can be treated conservatively,
toms. Different approaches may be per- waiting for spontaneous healing and epitheli-
formed: transpalatal, transnasal-­ transmaxillary, alization. Larger lesions must be repaired using
transnasal-­ transsphenoidal, or combined rotational skin flaps, sometimes prepared in
approaches. In the transpalatal approach, the sac advance by implanting skin expanders. In cases
can be easily viewed and dissected by parame- of massive agenesis of the scalp, desiccation and
dian splitting of the uvula and soft palate and injury of the brain must be avoided by keeping
partial osteotomy of the hard palate. The trans- the lesion moist.
48  Surgical Treatment of Central Nervous System Malformations 637

48.9 Chiari Type I Anomaly reduced length of the clivus, and retroflexion of
the odontoid [34].
48.9.1  Surgical Pathology A variety of other clinical conditions and syn-
dromes have been associated. The most common
The “Chiari anomaly” is defined by herniation of associated condition are neurofibromatosis type 1
the cerebellar tonsils and medial part of the inferior [35, 36] and growth hormone deficiency [35, 36].
lobes of the cerebellum below the plane of foramen The best method to identify the typical
magnum in different degrees. aspects of Chiari’s malformation and associated
Currently, Chiari type I anomaly is character- abnormalities, including syrinx, hydrocepha-
ized by a caudal descent of the cerebral tonsil lus, and craniovertebral anomalies, is definitely
more than 5 mm under the foramen [28]. the MRI.  CSF dynamic studies at the foramen
Besides the tonsil herniation, Chiari I land- magnum are now routinely used to determine
marks are cisterna magna obliteration and the severity of CSF flow disturbance. The degree
reduced or absent CSF flow at the cervicomedul- of CSF flow disturbance has been shown to cor-
lary junction [29]. relate with severity and development of clinical
The physiopathological basis of onset of symptoms.
clinical symptoms in Chiari type I patients is Syringomyelia or hydromyelia corresponds
the development of an abnormal pressure gradi- to the progressive cavitation of the spine and is
ent between the cranial and spinal compartment associated to Chiari I in 30–76% of cases.
at the foramen magnum level [30]. Hence, an The most common location is the lower cervi-
intermittent vector of force develops at this level cal spinal cord, followed by the cervicothoracic
leading to the progressive downward movement junction and the upper thoracic region. Holocord
of developing tissue through the foramen mag- syringomyelia is about 20% of the cases, and
num. If this progressive phenomenon occurs after syringobulbia varies from 1 to 17% [37]. In our
complete development of cerebellar tonsils, the experience, syringomyelia is present in 36% of
pressure gradient causes tonsillar herniations and cases, in particular: syringobulbia, 4%; cervical,
starts spine cavitation that is syringomyelia for- 35%; dorsal, 15%; cervical dorsal, 27%; lumbo-
mation [31]. sacral, 2%; and holocord, 17%.
Though several hypotheses have been pro- A side effect of syringomyelia is scoliosis
posed to explain its pathogenesis, there is not a that is found in 25–50% of subjects present-
single pathogenetic theory. The most accepted ing Chiari I anomaly before skeletal maturity
theory considers this malformation as the result [38]. The physiopathological explanation of
of a mesodermal defect with consequent under- spine cavitation associated with Chiari relies
sized posterior cranial fossa and overcrowding of to the abnormal gradient of CSF pressure at
the neural structures. the foramen magnum level. The syrinx forma-
Indeed, several morphometric studies have tion seems to be the result of obstruction of CSF
shown that patients with Chiari malformation flow at the foramen magnum that increases the
have a posterior fossa volume smaller than systolic pulse wave in the spinal subarachnoid
normal [32]. space drawing CSF into the spinal central canal
In Chiari I patients, the volume of posterior through anatomically continuous perivascular
fossa is 23% smaller, and other posterior cranial and interstitial spaces [39].
fossa malformations are described in about 76% As in our experience, in 10% of cases of
of patients [33]: occipital dysplasia, platybasia, Chiari I anomaly, hydrocephalus is associated
occipitalization of the atlas, fusion of cervical [34]. Hydrocephalus is not communicating and
vertebrae, Klippel–Feil syndrome (i.e., com- seems to be due to stenosis of the fourth ventri-
plete fusion and ossification of cervical spine), cle outlets (foramen of Magendie and foramens
basilar invagination, reduced length of the of Luschka). Its consequences are increased
supraocciput, increased slope of the tentorium, by compression of cisterna magna by prolapse
638 M. Scagnet et al.

of the tonsils. The mechanism that associates postoperative neck pain. Then, a suboccipital cra-
Chiari I with this type of hydrocephalus is dou- niectomy is made.
ble. The presence of hydrocephalus exaggerates The size of the craniectomy varies from
the Chiari phenomenon of cerebellar tonsil her- 2 × 2 cm to 3.5 × 3.5 cm.
niation because of the presence of an enlarged A posterior C1 laminectomy is made of about
fourth ventricle. On the other side, the tonsil 2.5 cm. It is not necessary to extend laterally the
herniation itself may be a concause in narrowing craniectomy to reduce the surgical risk. A dense,
a substenotic Magendie foramen leading to the fibrous, and constrictive band covers the atlo-­
­precipitation of hydrocephalus. In 9% of patients occipital membrane causing intradural compres-
with Chiari I, hydrocephalus and syringomyelia sion and arachnoid adhesion.
coexist [40]. Several techniques that have been advocated
for posterior fossa decompression includes bone
decompression only, removal of the atlo-occip-
48.9.2  Posterior Fossa ital membrane with the outer dura layer [44],
Decompression for Chiari intradural extra-arachnoid durotomy with and
Type I Anomaly without duraplasty, intra-arachnoid lysis of the
scarring and adhesions around the herniated ton-
In 1988 the American Association of Neurological sil [29], coagulation of herniated cerebellar ton-
Surgeons (AANS) had declared that in Chiari sils respecting the integrity of pia and arachnoid
I patients, the posterior fossa decompression is [45], resection of cerebellar tonsils with subpial
always mandatory in the presence of signs of approach in case of very high gliotic tonsils not
brainstem dysfunction, questionable in case of reduced by simple coagulation [46], as well as
mild symptoms and headache, and not recom- opening the foramen of Magendie and obex plug-
mended in case of asymptomatic patients [41]. ging and section of filum terminale [47].
Today there is a general agreement to treat Chiari The treatment of Chiari malformation type 1
I characterized by cerebellar tonsil prolapse of at with posterior fossa decompression without or
least 5  mm down to the foramen magnum with with duraplasty is controversial.
appropriate symptoms. In borderline cases (pro- Surgical morbidity may occur in form of ver-
lapse of 0–5  mm), surgical indication must be tebral artery damage, acute hydrocephalus, cer-
evaluated according to each individual clinical ebellar ptosis, pseudomeningocele, CSF leakage,
context. In the presence of syringomyelia, sur- subdural collections, cervical instability, and
gery is mandatory even in the presence of limited acute life-threatening sign of brainstem dysfunc-
tonsil descent to avoid further enlargement and tion [42].
clinical deterioration [42]. Goal of surgery is to Indeed, the intradural techniques are associ-
restore normal CSF flow thus reestablishing a ated with increased risk of complications between
pressure balance between intracranial and intra- 15 and 25% [48] including wound infection, CSF
spinal subarachnoidal spaces by decompressing leak, pseudomeningocele, meningitis, and com-
the inferior cerebellum and cervicomedullary plication associated with dural graft. Posterior
region at the level of foramen magnum [43]. fossa decompression with extradural lysis of the
Patients are placed in a prone position with sclerotic band and opening of the outer dural
slight flexion of the neck to allow for visual- layer offers a minimally invasive decompres-
ization of the occipital bone. A midline vertical sion technique with lower risk of complications
incision is made from just inferior to the inion between 2 and 6% [48].
to the C3 level. Myofascial dissection is carried A number of modern series published by
out along the median raphe. Special care must authors like Zerah [49] and Genitori [50] have
be given in avoiding muscle dissection from C2 stressed the good results of this technique which
level (semispinalis cervicis and multifidus mus- is not followed by the frequent complications
cle) to prevent cervical instability and to reduce and is characterized by shorter hospitalization as
48  Surgical Treatment of Central Nervous System Malformations 639

a b

Fig. 48.14  Minimally invasive technology with suturectomy and positioning dynamic Expander reabsorbable mate-
rial. Left, plagiocephaly

compared with surgical morbidity after surgery with duroplastic is vitiated by a higher rate of
characterized by dural opening; surgical out- complications, until 40%.
comes are good both in reducing syringomyelia Milhorat and Bolognese [51] have proposed
and in improving its secondary effects like scoli- an intraoperative control by intraoperative color
osis (Fig. 48.14). Anyway, in case of clinical and/ Doppler ultrasonography (CDU) to tailor the
or radiological Chiari I r­ecurrence or enlarge- extension posterior fossa bony decompression
ment of syringomyelic cavities, the dural expan- and C1 laminectomy and the need of additional
sion must be considered [50]. steps like duraplasty and shrinkage or resection
Several neurosurgeons have adopted this of the cerebellar tonsils. In first surgical steps,
technique with the caveat that there might be an CDU allows to distinguish better all the poste-
increased risk of reoperation (12.6% vs. 2.1%). rior fossa structures including aberrant vascular
In our study of 434 patients (from 2000 to anatomy, asymmetrical herniations, and neural
2015), the complication rate occurred using a displacement; this reduces the surgical risk of
minimally decompression technique is 1.9% and error especially in patients undergoing reopera-
using intradural technique is 33%. Furthermore, tion with a lot of meningo-cerebral scarring [51].
in our experience, it has emerged that the rate of At the end of posterior fossa decompression,
reoperation after extradural technique is 6.5%. CDU serves to control if the CSF circulation and
The aim of surgery is clinical improvement pulsatility are restored by measuring CSF flow
and ranges between 61.5 and 93% based on the velocities and viewing CSF flow directions. The
study being studied. optimal CSF flow to obtain has a peak velocity of
According to some studies, the most appropri- 3–5  cm/s, bidirectional movement, and a wave-
ate therapeutic option is posterior decompression form exhibiting arterial, venous, and respiratory
with dural plastics as it results in a better clinical variations [51].
outcome. In a recent study, Aaron et al. observed signifi-
In fact, the improvement of syringomyelia, cant CSF flow changes when simply positioning the
reported after posterior fossa decompression patient for surgery, using intraoperative MRI [52].
with dural plastic, arrives at 91.5% in contrast to In the past, in the presence of syringomyelia-­
the technique without dural opening that reaches hydromyelia, some authors have proposed to
65.7%, although the decompression associated put a shunt between the fourth ventricle and the
640 M. Scagnet et al.

subarachnoidal spaces [53], while others prefer At birth a number of precautions have to be
to make a syringostomy by myelotomy [54]. taken to avoid hypothermia, hypovolemia, and
Syringo-subarachnoid shunting by a little cath- hypoglycemia. A complete diagnostic work-up
eter has been also suggested even if spinal cord must be performed to evaluate the neurological
injury after insertion of catheter in the spinal status of the newborn and the associated prob-
cavity is described [55]. A syringo-peritoneal or lems (brain malformation, hydrocephalus, uro-
pleural shunt has been advocated because of the logical and orthopedic impairments).
higher differential pressure compared with the Surgery must be performed within the first
subarachnoidal space [56]. The catheter used is 48 h to avoid septic meningitis, sepsis, and sec-
“K” or “T” shaped and 2  mm large. The surgi- ondary injury to the placode requiring repair. Any
cal technique consists in anchoring the catheter delay after 72 h increases this risk to 37% com-
to the dura and putting its end in the planned cav- pared to 7% in case of early closure. Neonatal
ity. The insertion of valve device to regulate CSF meningitis is a serious complication because it
draining must be evaluated even if it is not usu- impairs intellectual development.
ally utilized [43]. The techniques of tunnelization The neonate is positioned prone with all pres-
of the distal end of the catheter are the same as sure points on smooth pads in a Trendelenburg
described for hydrocephalus shunting surgery. position to reduce CSF leaking; warming tables
Some technical reports describe the possibility are utilized. Tracheal intubation should be car-
to treat Chiari anomaly by tapping the syringo- ried out in a donut position if possible to reduce
myelia cavity by a percutaneous aspiration after the trauma to the sac. Usual antiseptic drugs (i.e.,
failure of previous treatment [57]. povidone iodine must be avoided).
As regards the associated hydrocephalus, Goals of surgery are (1) identification of all
most authors agree that it is the result of impaired anatomical planes according to the well-known
CSF circulation within the posterior fossa at the embryological physiopathology, (2) reconstruc-
level of the outlets of the fourth ventricle, syl- tion of the placode, (3) closure of meningeal cov-
vian aqueduct or arachnoid cisterns. The cur- erings, and (4) closure of the fascia and skin.
rent trend is to treat the hydrocephalus first and The first step is an incision at the meningo-­
then follow the clinical evolution [58]. Posterior epithelial junction and dissection of the neural
fossa surgery is to be considered in case of onset placode under the control of operative micro-
of Chiari symptoms even if hydrocephalus is scope. Arachnoidal adhesions between the plac-
solved. The first-choice surgery is endoscopic ode and underlying dura are lysed. Any other
third ventriculostomy [5]. In our experience, all associated abnormalities are to be identified and
patients showed a rapid resolution of the symp- eventually removed (i.e., dermoids, lipomas,
toms related to increased intracranial pressure. neuroenteric cysts, etc.). All residual epidermal
and dermal elements must be removed to avoid
the future formation of a dermoid or lipoma. At
48.10 Closure this stage, the placode is tubulized with nonad-
of Myelomeningocele (Spina sorbable suture (Nylon 5/0), and the recurrent
Bifida Aperta) spinal roots must be respected. The meningeal
layer is then dissected as far as possible to cover
Delivery by cesarean section is suggested to the new spinal cord, aiming to maintain it sub-
diminish local trauma to the malformation and merged in CSF in order to avoid secondary teth-
prevent the contact of amniotic fluid with the ering. Sometimes a duraplasty is created with
myelomeningocele sac especially if it is ruptured: an autologous flap (periosteum, fascia lata) or
the amniotic fluid is toxic for the neural tissue, more frequently with artificial biocompatible
and cases of aseptic ventriculitis are described. material like PTFE (polytetrafluoroethylene).
The malformation must be protected and kept In a case with a huge kyphosis, kyphectomy is
moist using tulle gras. necessary during the first surgery to enable easy
48  Surgical Treatment of Central Nervous System Malformations 641

closure of the defect. At the end of the proce- 48.11 Spinal Detethering
dure, a myofascial layer is prepared to cover the Technique
dura, and the exceeding and dysplastic skin is
excised before final closure is made with nonad- 48.11.1  Lipomas
sorbable sutures (Nylon 3/0). A releasing inci-
sion in the fascia laterally away from the defect • Lipoma of the filum terminale: surgical
may be useful to obtain a tension-free closure. approach starts by a skin incision in the mid-
In case of large defect, the lumbosacral muscu- line; the subcutaneous is incised with Bovie
lature is useful to create flaps to cover the mal- until the fascia is exposed. Then, paravertebral
formations even if rotational flaps do not often muscles are dissected off the laminae, and a
function because of ischemia. Deep dissection 1–2 level laminotomy is performed. The use
of latissimus dorsi may be dangerous because of of the surgical microscope is necessary to per-
the risk of damage to retroperitoneal and pulmo- form the next surgical step. The dura is opened
nary structures. in a craniocaudal fashion and suspended. The
In the early postoperative period, the new- Trendelenburg position of the table allow, at
born must be strictly monitored. The recom- this point, to evitate loss of CSF and to keep
mended position is Trendelenburg prone or the surgical field clear of CSF. The filum lipo-
lateral protecting the wound from urine and matosus is identified, coagulated, and sec-
fecal contamination. Periodical measurement tioned using the microscissors. Normally after
of the cranial circumference and ultrasound this step, there is a remarkable ascension of
tomography are performed to rule out the the proximal end of the filum. The dura is
hydrocephalus. Ventriculoperitoneal shunt- closed with a 5/0 Prolene running suture.
ing is mandatory at first sign of hydrocephalus Fibrin glue and oxidized cellulose are posi-
and/or in case of CSF leakage from the wound tioned on the dura. The laminae are reposi-
and/or brainstem dysfunction related to Chiari tioned with care to set it in the normal position
II.  Endoscopic third ventriculostomy (ETV) and sutured with Vycril 2/0. The fascia is
achieves good results in secondary treatment closed. Subcutaneous tissue and skin are
of hydrocephalus in such children with shunt closed with resorbable suture.
dysfunction. • Usami et  al. [59] described a series of 174
Surgery for Chiari type II anomaly should be patients treated for lipoma of filum terminale.
considered if at least one of the four Griebel’s They found an improvement of symptoms in
criteria is present: (1) continuous stridor with 50% of patients at 2.1-year follow-up period;
respiratory difficulty, (2) recurrent ab ingestis one of 85 asymptomatic patients deteriorated
pneumoniae, (3) bradycardia or apnea, and (4) (urological deficit). Nine patients presented
cyanosis. The surgical technique involves wide complications after surgery, eight transient
dissection of the foramen magnum along with and one permanent.
posterior C1 laminectomy; a large duraplasty is • In the period between 1994 and 2015, we
then constructed using a­utologous or artificial treated 115 patients with lipoma of filum ter-
material. However, this procedure is justified minale, 52 were female and 64 male, mean age
only if the hydrocephalus is well treated; in fact at surgery was 2.5  years. Thirty-five (30.4%)
Chiari II may decompensate because of shunt had skin stigmas and in 24 (20.8%) lipoma of
dysfunction [55]. the filum terminale was associated with ano-
Surgical mortality is near zero, while postop- rectal malformation. Symptoms at diagnosis
erative complications may be serious. The most were present in 52 patients (45.2%). Two
frequent is wound dehiscence with CSF leak, patients underwent first to section of filum ter-
followed by local infection (1–1.5%), neonatal minale externum with no improvement and
sepsis, and all the other complications connected then to filum terminale sectioning. Symptoms
with shunt and posterior fossa surgery. improved in ten patients (19.2%), any clinical
642 M. Scagnet et al.

deterioration related to surgery presented. All performed above the lesion entry zone in the
patients were positioned in Trendelenburg for dura if it is present. The use of the surgical
3  days and then progressively mobilized to microscope is necessary to perform the next
avoid the risk of CSF leakage. In our series surgical step. The dura is opened in a cranio-
four patients presented CSF leakage treated in caudal fashion and suspended. The untether-
three cases conservatively with bed rest and ing is achieved by dividing the lipoma below
compressive medication. Surgical treatment of the transitional zone which is identified
filum terminale lipoma is a safe procedure with between the conus and lipoma to avoid neural
low rate of complications. elements. Often, after division of the lipoma,
• Caudal lipoma (Fig. 48.15): surgical approach the cord shows a remarkable degree of retrac-
starts by a skin incision in the midline. The tion. The dura is closed with a Gore-Tex patch
fascia is exposed. The paravertebral muscles using a 5/0 Gore-Tex running suture to avoid
are dissected off the laminas with very careful retethering the scar and the dural elements.
dissection in the zone of the schisis to not pen- The laminae are repositioned carefully in the
etrate the dura. A two-level laminotomy is normal position.

Fig. 48.15 MRI
a b
(sagittal view).
Dysraphic state. (a)
Caudal lipoma,
preoperative view. (b)
Postoperative view. Note
the detethering of the
spinal cord
48  Surgical Treatment of Central Nervous System Malformations 643

• We treated 18 patients with caudal lipoma, 10 can be dissected and debulked using a CO–
males and 8 females, mean age of 10  years. laser or ultrasonic aspirator (CUSA) (MzLone
Eight patients presented skin stigmas; in four 1986). It is not necessary to attempt to debulk
lipoma was associated with anorectal malfor- the lipoma into the spinal cord since it doesn’t
mations. Urological or motor deficits or both increase in size. Careful dissection must be
were present in 14 patients at diagnosis time taken at the interface between lipoma and the
(77.7%). At last follow-up, none of asymp- spinal cord. The filum can be divided after his
tomatic patients presented deficits; four of identification. The detethering, in this case, is
symptomatic patients showed clinical from the superficial planes. Nerve roots are
improvement (28.5%), eight an invariated horizontalized and cannot be liberated from
clinical status (57.1%), and two worsened. the lateral surface of the lipoma.
• Lipomyelomeningocele (Fig. 48.16): The ini- • Pang et al. [60, 61] advocated a total or near-­
tial surgical approach is the same than the total resection for lipomas with reconstruction
other types. At the level of the dura, it may be of placode to ensure a better long-term out-
important to recognize the “normal dura” come. He described a clinical deterioration in
from the capsule of the lipoma. The lipoma 4.1% cases and a low complication rate (0.7%

Fig. 48.16 MRI
a b
(sagittal view)
Dysraphic state. (a)
Lipomyelomeningocele,
preoperative view. (b)
Postoperative view. The
lipoma has not been
completely removed, but
the spinal cord is
detethered
644 M. Scagnet et al.

CSF leakage and 1.1% wound complications).

In 2010 they compared two groups who under-
went, respectively, total or partial resection
and found that in short-term follow-up, results
were similar: in asymptomatic patients 98%
of first group and 94% in the second didn’t
develop neurological impairment. In symp-
tomatic patients 94% of total resections were
improved or stable versus 95% of partial
group. The progression-free survival described
for total resection was 82.8% at 16 years and
34.6% for partial resection at 10 years.
• In our institution underwent surgical treatment
96 patients underwent surgical treatment with
lipomyelomeningocele, 62 females and 34
males, with median age of 4 years. Of these 74
were classified as transitional and 22 as dorsal
lipomas. In 77 patients were present skin anom-
alies as subcutaneous lipoma or other skin stig-
mas. Neurological impairment was present in
19 patients (14  in transitional and 5  in dorsal
lipomas) and urological deficits were in 31
patients (24  in transitional lipomas and 7  in
dorsal). In six cases dysraphism was associated Fig. 48.17  MRI (coronal view). Dysraphic state: dyaste-
with anorectal malformations. All patients matomyelia. Note the split cord malformation
except one underwent a partial resection of
lipoma. At last follow-up, 19 patients presented be removed taking care of tight adhesions
an improvement of clinical status (17 in transi- between the cord and dura. The skin incision
tional group and 2  in dorsal group). Two is in the midline extending above and below
patients showed urological deficits without any the lesion. The laminae are dissected off the
radiological sign of retethering. The patient paravertebral muscles starting where the spi-
who underwent a gross total removal of lipoma nous processes are normal. A minimal lami-
worsened; three patients needed a reoperation nectomy is begun in a normal area to avoid the
for retethering after 4 and 6 years after first sur- risk of a kyphoscoliosis. The bony spur is then
gical treatment. Complications were repre- progressively exposed and removed after a
sented by CSF leakage in nine cases, treated subperiostal dissection of the septum avoiding
conservatively in all by two cases, and local lateral movements which can injure the adja-
wound dehiscence and infection in seven cases. cent hemicords. The two dural sacs are pro-
gressively exposed, and the dura is opened by
an incision encircling the dural cleft and
48.11.2  Adhesions, Bands, Thick extended toward each extremity. The
Filum, and Diastematomyelia ­adhesions between the medial aspect of the
hemicord and the dural sleeves must be pro-
• Diastematomyelia (Fig.  48.17): the surgical gressively severed. The closure of the dura is
approach is planned on the base of the radio- performed with a duroplasty in Gore-Tex
logical evaluation. The aim of surgery is the patch. In the type II SCM, the procedure is
untethering of the spinal cord, and the tech- more simple. The dural tube is single, and the
nique varies with the two types of SCM.  In two hemicords with the median septum may
type I SCM, the osteocartilagineous spur must have three different positions: the first type in
48  Surgical Treatment of Central Nervous System Malformations 645

which a complete fibrous septum transfixes made during pregnancy, were symptomatic.
the hemicords and is fixed on the ventral and Four patients presented skin stigmas. In five
dorsal surfaces of the dura, the second type in cases was detected by MRI another spinal cord
which the septum is only ventral fixing the lesion (one caudal lipoma, one dermal sinus,
ventromedial aspect of the hemicords to the one meningocele manqué, two lipomas of filum
dura, and the third type where the septum fix- terminale). In two patients the surgical proce-
ing the dorsal aspect of the hemicords (Pang, dure was as described above; in one patient the
Neurosurgery 3:451–500, 1992). caudal lipoma was debulked, and in six cases
• The aim of surgery is to sever the adhesions only the section of filum terminale was per-
and remove the septum opening the dura. In formed. At last follow-up, patient showed a
the case of ventral septum, the hemicord must worsening of preoperative clinical status, and
be gently rotated to allow the severing from none required any other surgical procedure.
the septum itself. The dura in all cases is
closed performing a dural patch in Gore-Tex.
• Patients with diastematomyelia should be 48.11.3  Dermal Sinus (Fig. 48.18)
investigated for other spinal cord and vertebral
anomalies. Filum terminale anomalies could For the dermal sinus tract, the skin is incised
not be detected by MRI as described by Selcuki around the skin opening. The tract itself is dis-
et al. [62, 63], and failure of untethering proce- sected free of the underlined subcutaneous tis-
dure could be related to a tight filum terminale sues, down to the point where it pierces and
which wasn’t cut at first procedure [64]. penetrates the underlying muscular fascia. Every
• We treated nine patients with diastematomyelia, attempt is made to preserve the tract as the lami-
seven females and two males, with mean age of notomy is made one or to level above and below
3 years. All but one, in whom the diagnosis was the tract as it enters the dura. Then the dura is

a b

Fig. 48.18  Dysraphic state. (a) MRI (sagittal view). Dermal sinus and tract. (b) For full color version, see color plate
section. Intraoperative view. Note the stalk fixing the spinal cord
646 M. Scagnet et al.

a b

Fig. 48.19  MRI (sagittal view). Dysraphic state. (a) Neuroenteric cyst. (b) postoperative appearance with removal of
the cyst by an anterior approach

opened in the cranial and caudal direction, and in 1 case with a split cord malformation. At last
two incisions are made around the stock as it follow-up, 50 patients had a stable clinical status
penetrates the dura. At this point, the stock is and 4 improved. One patient who underwent a
sectioned and removed. Associated lesions such gross total removal of transitional lipoma showed
as dermoids and lipomas should be removed a clinical deterioration (Fig. 48.19).
with magnification under operative microscope.
Radmanesh et  al. [65] described 35 cases
of dermal sinus which operated and concluded 48.12 Fetal Surgery
that early diagnosis and complete resection of
sinus is crucial to avoid development of clinical Fetal surgery represents a multidisciplinary
deficits. approach to some CNS malformations and
We treated 55 patients with spinal dermal tumors diagnosed in utero [66]. Nowadays,
sinus, 31 females and 24 males, with mean age of these new techniques deal essentially with pre-
4 years. Four were previously operated in other natal hydrocephalus and m­ yelomeningocele [67]
institutions. In 43 cases skin anomalies were and are feasible, thanks to a full collaboration
present; 14 patients presented neurological and/ between obstetric surgeon, anesthesiologist, and
or urological impairment (25%). In six patients neurosurgeon [68]. Prenatal imaging by fetal
were present signs of infection at the time of magnetic resonance imaging (MRI) is mandatory
diagnosis. In 5 cases dermal sinus was associated to gain a complete and precise evaluation of mal-
with fatty filum, in 18 cases with a lipoma, and formations [69].
48  Surgical Treatment of Central Nervous System Malformations 647

48.12.1  Prenatal Hydrocephalus by periodical ultrasound tomography; infec-

tions and genetic anomalies must be ruled out by
The incidence of true fetal hydrocephalus ranges amniocentesis. Indeed, fetuses harboring hydro-
from 1 to 4:1000 births [70]. In 70% of cases, cephalus linked to another CNS malformation
other CNS anomalies are associated (holopros- (e.g., Dandy–Walker complex, X-linked hydro-
encephaly, Dandy–Walker complex, spina bifida, cephalus, etc.) do not show improved intellectual
corpus callosum agenesia, etc.), and in 7–15% outcome after fetal surgery [71]. In the case of
of fetuses systemic malformations coexist [10]. polymalfomation hydrocephalus, the termination
In 3–10% of cases, different cromosomopathies of pregnancy should be suggested to the family.
have been screened, involving chromosomes 1, If the hydrocephalus is stable or resolving, the
6, 9, 13, 18, 21, 22, or X. child is delivered at term and then treated [71].
Fetal hydrocephalus may be due to ventricular In the past, repeated cephalocentesis was per-
obstruction (congenital tumors, intraventricular formed to obtain temporary control until deliv-
hemorrhage), CNS maldevelopment, or acquired ery was possible [75] even if this technique
intrauterine damage (infections, hemorrhages) involved a higher risk of fetus infection, hemor-
[71]. The most frequent cause of isolated fetal rhage, and porencephaly [70]. Today, fetal CSF
hydrocephalus is aqueductal stenosis [70]. shunting surgery is preferred, aiming to obtain a
In his “Perspective Classification of temporary relief from intracranial pressure while
Congenital Hydrocephalus (PCCH),” Oi divided waiting for the earliest possible delivery for
prenatal hydrocephalus into four phases accord- definitive treatment in better general conditions
ing to the gestational age of diagnosis [69]. Phase [71]. Ventriculo-amniotic shunts were proposed
II (22–31  weeks) corresponds to the the period by Clewell et  al. [76]. This shunting technique
of “intrauterine preservation”; during this phase is hindered by a high incidence of complica-
if the hydrocephalus becomes progressive, the tions such as catheter obstruction, migration of
damage to CNS may be irreversible after birth. the device into the amniotic cavity, and infection
Between 22 and 31  weeks of gestational age, [70]. Furthermore, fetal hydrocephalus is high
the fetal lungs are not developed enough, requir- pressure but surrounded by a higher intrauterine
ing preservation in the uterus, and it is obvi- pressure, which impedes its correct functioning
ous that the earlier the onset of hydrocephalus, [77]. On this pathological basis, Oi has proposed
the greater the damage to the developing CNS; the use of a fetal ventricular-maternal peritoneal
hence, the earlier the treatment, the better the shunt [78]. Bruner has introduced a new type
results from both motor and cognitive points of of ventriculo-amniotic shunting to improve the
view [72]. Thus phase II hydrocephalus is ame- fixation [79]. As a rule, these requirements for
nable to prenatal surgical treatment [73]. Surgery such shunts include a safe and simple insertion
is suggested only in case of hydrocephalus not technique, valid scalp fixation, and a one-way
associated with other systemic and/or brain valve to prevent intraventricular reflux of amni-
malformations because surgical and patient out- otic fluid (Von Kochet al., 2003). As suggested
comes are better [70]. According to the guide- by Cavalheiro et  al. [70], endoscopic third ven-
lines of the International Fetal Surgery Registry triculostomy may be considered in case of hydro-
[74], the ideal candidate to be submitted to fetal cephalus due to pure aqueductal stenosis.
surgery should have an isolated hydrocephalus
from non-­ X-­linked aqueductal stenosis diag-
nosed before 28  weeks of gestation and before 48.12.2  Myelomeningocele
the cortical mantle thickness is less than 1.5 cm;
the hydrocephalus must be moderate to severe Much clinical and experimental evidence shows
and not associated to other fetal brain anomalies neurological deterioration in the affected fetus
on MRI; its progression has been documented during pregnancy according to the “two-hit”
648 M. Scagnet et al.

hypothesis, the first hit being the embryologi- amniotic leakage, uterine dehiscence, placental
cal spinal cord malformation [80]. Some reports abruption, preterm delivery, and one death were
have documented normal movement of the lower observed. Furthermore, this technique was only
extremity in fetuses with spina bifida aperta palliative and not curative, as the skin graft was
before 17–20  weeks, followed by a fairly com- short-lived [86].
plete paralysis in late gestation [81]. This deterio- Accordingly, the technique of open intrauter-
ration seems to be due to the exposure of nervous ine repair was developed, on the basis of experi-
tissue to meconium and amniotic fluid [82] and mental models suggesting that most secondary
to direct trauma of the placode from the uterine damage takes place during the third trimester of
wall during fetal movements [83]. The amniotic pregnancy [89]. The mother underwent cesarean
fluid becomes more hypotonic thus more toxic as section under general plus epidural anesthesia at
fetal urine output increases after kidney matura- 28–30 weeks of gestation; this anesthetic combi-
tion which takes place after 22  weeks of gesta- nation seems to reduce the incidence of unwanted
tion [84]. Furthermore, there is evidence that the uterine contractions and allows sedation of the
Chiari type II anomaly is also acquired as a result fetus too [90]. After the uterus is exteriorized
of the continuous CSF leakage from the placode, through a Pfannenstiel incision and the fetus and
which leads to progressive hindbrain prolapse placenta are localized by ultrasound scan, the
[85]. These findings constitute the physiopatho- Tulipan-Bruner trocar is inserted into the uterus
logical background for myelomeningocele repair [87, 88] to tap most of amniotic fluid which is
in utero [80]. conserved in warm syringes. A 5  cm incision
From 1997 to 2003 more than 200 fetal sur- is made in the uterus and the fetus positioned
gical procedures were performed and results with the placode in the middle of hysterotomy.
showed clinical improvement for the fetus but an The myelomeningocele is then closed using the
increased risk for the mother in term of preterm standard neurosurgical technique with nonre-
labor and uterine dehiscence and an increased sorbable Nylon 7/0 sutures for the placode tubu-
risk of death or preterm birth for fetus [67]. lization and Nylon 5/0 for the skin [90]. During
The first cases were treated by an endoscopic the whole procedure, the fetal heartbeat is moni-
technique pioneered by Copeland et  al. [86]. tored by ultrasound and continuous electronic
This was performed between 22 and 24  weeks fetal monitoring. The uterus is closed in layers
of gestation using a 4 mm rigid endoscope. First, with adsorbable sutures, and the amniotic fluid is
the mother underwent laparotomy under gen- replaced, sometimes with saline solution until its
eral and epidural anesthesia, with exposure of turgor becomes similar to the preoperative state,
the gravid uterus. Then, three endoscopic ports in order to reduce the risk of uterine contrac-
were inserted into the maternal uterus (one for tions [90]. The wall of the abdomen is closed in
the endoscope and two operative channels for a standard fashion, and the fetus continues to be
instruments). Because of its turbidity, amniotic monitored. The mother is administered tocolytic
fluid was tapped until the fetus was completely agents (indomethacin, terbutaline). In the postop-
exposed, and the fluid was replaced by carbon erative period, both the mother and the fetus are
dioxide to maintain ambient intrauterine pres- periodically monitored until delivery by cesarean
sure. After positioning of the fetus, the placode section, which is usually planned at 34–35 weeks
was covered with a maternal split-thickness of gestation; delivery is anticipated only in case
skin graft because it was not possible to use a of uncontrolled amniotic leak or premature con-
standard skin suture. All the reconstruction was tractions, trying to balance, in all cases, the risk
sealed by oxidized cellulose and fibrin glue [87, of dehiscence of the hysterotomy and iatrogenic
88]. The surgical results were not satisfactory fetal immaturity [90]. In the series of 50 cases
because fetal morbidity and mortality and mater- operated on by Tulipan and co-workers, surgical
nal morbidity were high: in the four cases treated morbidity was low and included uterine contrac-
by Tulipan and Bruner [87, 88], amnionitis, tions, placental abruption, and amniotic leakage;
48  Surgical Treatment of Central Nervous System Malformations 649

uterine dehiscence with prolapse of the fetus vious hysterectomy). MOMS trial included 183
into the peritoneal cavity was the most serious. women and was stopped earlier than planned for
In only one case did premature delivery occur. the evidence of better outcome for the infants who
Surgical mortality in utero involved only one underwent fetal repair before 26 weeks of gesta-
fetus [90] even if, in other series, there is a peri- tion. Ventricular shunt placement was less in pre-
natal mortality of about 6% due to the extreme natal group than in postnatal (40% vs. 82%) at
prematurity [91]. 12 months and these infants had a better motor and
Unwanted side effects of tocolytic therapy are mental outcome at 30 months of age. An improve-
possible in the mother, such as tachycardia, fever, ment was present also in hindbrain herniation by
dyspnea, and pulmonary edema [90]. The newborn 12 months and ambulation by 30 months.
may show local dehiscence at the site of placode Tulipan et al. [99] update the 1 year outcomes
repair, which is usually managed conservatively [90]. for the complete trial and confirmed the benefit of
The most encouraging surgical results are the prenatal surgery regard to shunting (44% shunt-
lower incidence of Chiari II and of hydrocepha- ing in prenatal group versus 84% in postnatal
lus [90]. Chiari type II anomaly after fetal surgery group). They identified in the ventricular size a
accounts for only 16% rather than the described preoperative predictor of shunt-dependent hydro-
incidence of 95% [92–94]. Other studies have cephalus: there were no benefits related to shunt-
shown that hindbrain prolapse is reversed rather ing in fetuses whose ventricles were 15  mm or
than prevented by fetal surgery: postoperative larger at screening.
fetal MRI at 3 weeks have well documented the In the last years endoscopic third ventriculos-
ascent of these structures [95]. tomy (ETV) as alternative to shunt has been pro-
Resolution of Chiari II anomaly reduces the posed even in patients who underwent fetal surgical
incidence of hydrocephalus to 42.7 from 90% repair. Elbabaa et al. [1] described a series of 60 fetal
[67] thanks to restoration of CSF pathway at the myelomengocele repairs and analyze factors related
level of the fourth ventricle outlets [96]. to failure of ETV.  Successful procedures were
Despite a number of experimental and clinical related to ventricular size less than 4 mm in utero
studies to the contrary [80], Tulipan’s series did and ventricular size after surgical repair less than
not show any neurological improvement, as the 15 mm, while failure was related to age less than 6
neonates showed neurological impairment exactly months and repair after 25 week of gestational age.
corresponding to the level of the defect [90]. Brock et  al. [15] evaluated the urologic out-
In some cases, a secondary, late tethering of come in 56 patients who underwent prenatal
the spinal cord has been described because of surgery and 59 treated postnatal by 30 months
epidermoid inclusion cysts, which required fur- of age. They didn’t find a significant difference
ther treatment [97]. between the two groups (38% rates of clean inter-
A multicenter randomized controlled trial, mittent catheterization in prenatal group vs. 51%
the Management of Myelomeningocele Study in postnatal group). However they found less
(MOMS), was conducted from 2003 to 2010 by bladder trabeculation and reduction of an open
three different institutions (Children’s Hospital bladder neck which significance is unclear.
of Philadelphia, Vanderbilt Medical University,
UCLA) [98]. The selection criteria were the fol-
lowing: singleton pregnancy, evidence of hindbrain
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 Central Nervous System
Congenital Tumors 49
Barbara Spacca, Iacopo Sardi,
Annamaria Buccoliero, Regina Mura, Milena Guidi,
Chiara Caporalini, Flavio Giordano,
Leonardo Bussolin, Massimiliano Sanzo,
and Lorenzo Genitori

49.1 Introduction them, we refer to the Central Brain Tumor

Registry of the United States (CBTRUS), to the
Central nervous system (CNS) tumors are the International Association of Cancer Registries
most common solid tumors in childhood [1]. (IARC—www.iacr.com.fr), and to the data
After the age of 15 years, their incidence in the obtained through the AIEOP (Associazione
general population gradually decreases, and they Italiana Ematologia Oncologia Pediatrica—
are one of the less common types of tumors in the Italian Association for Pediatric Hematology and
elderly [1]. Oncology). Those data, especially if collected
A thorough analysis of the epidemiology of from different countries, are difficult to analyze,
CNS tumors reveals that the age differences are and the difficulties increase if we try to assess
not only with regard to the absolute number, and data about a specific group of CNS tumors in
therefore their incidence, but there also are childhood compared with congenital ones. This
important implications for histology and overall is because of their rarity and their definition
survival [1]. In children, pilocytic astrocytomas, itself. Congenital CNS tumors were first consid-
germ cell tumors, and embryonal tumors are ered as tumors diagnosed during the first 60 days
much more common than in adulthood, whereas of life of a child [2, 3]. Later, congenital tumors
exactly the opposite is true as far as pituitary ade- were defined as definitely congenital if already
nomas, meningiomas, and spinal and cranial evident at birth; probably congenital if the diag-
nerves tumors are concerned [1]. nosis was made within the first week of life; and
Those kinds of observations and more are pos- possibly congenital if the diagnosis was made
sible, thanks to international and national regis- within the first 4 weeks of life [4]. However, later
tries, which collect huge amounts of data. Among in the medical literature, congenital tumors of the

A. Buccoliero · C. Caporalini
B. Spacca (*) · R. Mura · F. Giordano · M. Sanzo · Pathology, “Anna Meyer” Children’s Hospital,
L. Genitori Florence, Italy
Neurosurgery, “Anna Meyer” Children’s Hospital, e-mail: [email protected]; chiara.
Florence, Italy [email protected]
e-mail: [email protected]; regina.mura@
meyer.it; [email protected]; massimiliano. L. Bussolin
[email protected]; [email protected] Neuroanesthesiology, “Anna Meyer” Children’s
Hospital, Florence, Italy
I. Sardi · M. Guidi e-mail: [email protected]
Neuro-Oncology, “Anna Meyer” Children’s Hospital,
Florence, Italy
e-mail: [email protected]

© Springer Nature Switzerland AG 2019 653

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_49
654 B. Spacca et al.

CNS were extended again and were considered in Honduras, but it can then go up as high as 35.5
as tumors diagnosed in infants younger than cases in Chile. Important differences can also be
2 months of age [5], and in different series and observed in national registries where data are col-
many case reports, tumors diagnosed up to the lected distinguishing between different areas, or
first 2  years of life are discussed together with different population races, or different time
congenital tumors [6–8]. This is because the frames. New Zealand has an overall annual inci-
diagnosis, the clinical presentation, the problems dence of 22.9 cases, but if only the data on Maori
in managing these patients, the surgical compli- populations are taken into account, the same
cations, and the limitations in oncological treat- value drops to 6.2 new cases for one million chil-
ments are similar. Moreover, we have to consider dren younger than 1  year of age every year. In
that the neurons and white matter are not com- France, in the regions of Loire-Atlantique and
pletely mature in infants. Therefore, the clinical Vendée, the incidence expressed as before is 14.7
presentation of a brain tumor can be delayed new cases every year, whereas in the Gironde, it
because infants are not able to complain or to rises to 73 new cases/year. In Italy, in the region
present specific neurological signs and/or symp- of Piedmont, between 1990 and 1999, 6 new
toms and the diagnosis is frequently reached only cases as an absolute number were diagnosed,
when increased intracranial symptoms appear, whereas in the same region, there were 23
often associated with huge tumors whose growth between 2000 and 2011. In Europe, the median
period is unknown. value is considered to be between 30 and 40 new
It is evident that a definition of congenital cases a year, but in Norway this value is 79.4
CNS tumors is complex and it is even more com- cases vs 11.8 cases in Malta.
plex if we consider that certain types of tumors, Those data taken together are not enough to
such as teratomas or craniopharyngiomas, are draw conclusions, but it is possible to speculate
definitely considered as having their origin in the that there might be multiple protective and risk
uterus, but their diagnosis, especially for cranio- factors as far as the risk of developing a congeni-
pharyngiomas, is only rarely obtained in the peri- tal CNS tumor is concerned. It appears evident
natal period [9]. that those factors can be genetical, environmen-
The incidence of congenital CNS tumors is tal, and racial.
difficult to define. If we strictly stay with the defi-
nition of congenital CNS tumors as those diag-
nosed within the first 4  weeks after birth, a 49.2 Risk Factors
reasonable evaluation is probably 0.5–1.5% of all
CNS tumors in children [2, 5, 10–15]. If we look The etiology of CNS tumors is still largely
at data from the cancer registries, we cannot unknown. Many genetic syndromes are associ-
obtain data referred only to this small group, but ated with the risk of development of CNS tumors.
we can observe that the incidence of CNS tumors It is grossly estimated that about 5% of these
tends to increase after 1 year of age and then it tumors diagnosed in childhood are related to
reduces after the teenage (www.iacr.com.fr) [1]. known genetic syndromes [16]. Among them, we
The data from the IACR (www.iacr.com.fr) can recognize different diseases, first of all the
demonstrate that the incidence of CNS tumors in so-called neurophakomatoses.
children younger than 1  year of age in Western The tuberous sclerosis complex (TCS) is a
countries (the United States and Europe) is dominantly inherited disorder that consists in the
around 30–40 cases every million children mutation of either TCS1 or TCS2 with conse-
younger than 1 year of age every year. But if we quent abnormal differentiation and proliferation
analyze the same data from the same registries of cells, especially in the brain, skin, kidneys, and
for different countries and continents, the results heart due to an abnormal function of the proteins
can be very different. In South America, for hamartin and tuberin. Up to 14% of patients in
example, the incidence can be as low as 1.8 cases childhood develop subependymal giant cell
49  Central Nervous System Congenital Tumors 655

astrocytomas (SEGAs), which grow typically in In addition to genetic syndromes known to be

the anterior portion of the lateral ventricles and associated with the risk of developing CNS
can produce an obstruction to cerebrospinal fluid tumors, many studies were set up to try to under-
(CSF) flow with consequent hydrocephalus and stand if exposure to specific factors increases the
increased intracranial pressure (Fig. 49.1) [17]. risk of developing CNS tumors and if genetic
Neurofibromatosis (NF) type 1 and type 2 are mutations not included in known genetic syn-
dominantly inherited disorders due to mutation on dromes can play a role in the same direction.
chromosomes 17q11.2 and 22q11.2 respectively. When it comes to analyzing this type of parame-
Patients affected by NF1 are at a higher risk, in up ter in patients affected by a congenital tumor, the
to 15% of the cases [18], of developing tumoral studies focus on the exposure within a relatively
diseases arising from astrocytes and presenting as short time span, which starts the conception and
pilocytic astrocytomas, especially along the optic ends with the diagnosis of the tumor in the off-
pathway or in the brainstem. Plexiform neurofi- spring. Nevertheless, such an analysis is compli-
bromas are less common in childhood. cated, most are retrospective studies, and are
Even rarer in pediatric patients is Von Hippel- based on interviews. Therefore, they are affected
Lindau disease, a dominantly inherited disease by many biases.
associated with the risk of developing hemangio- Studies on possible genetic mutation, outside
blastomas. The most common location is cerebel- known genetic syndromes, developed during
lar, but they can develop along the axis, and it is not pregnancy or shortly after, have their roots in
uncommon to have multiple lesions [19]. known cancer risk factors that induce DNA
Many other genetic syndromes are associated changes and that can produce an alteration in the
with a higher risk of developing CNS tumors. We normal fetal development if the mother is exposed
report them in Table 49.1. to them, resulting in the so-called congenital

Fig. 49.1  F.B., 5 months old, boy, TSC2 mutation. This ventricle, and one, less common, in the occipital horn of
patient presents two subependymal giant cell astrocyto- the right lateral ventricle
mas (SEGAs), one in the anterior part of the right lateral
Table 49.1  The most common known genetic syndromes associated with CNS tumors
656

Syndrome Gene Chromosome Nervous system Skin Other tissues

Neurofibromatosis NF-1 17q11 Neurofibroma, malignant peripheral nerve Cafè-au-lait spots, Iris hamartomas, osseous lesion,
type 1 sheath tumor, optic nerve glioma, axillary freckling pheochromocytoma, leukemia
astrocytoma
Neurofibromatosis NF-2 22q12 Bilateral vestibular schwannoma, – Poster lens opacities, retinal hamartoma
type 2 peripheral schwannoma, meningiomas,
meningioangiomatosis, spinal
ependymoma, astrocytoma, glial
hamartias, cerebral calcification
Von Hippel-Lindau VHL 3p25 Hemangioblastoma – Retinal hemangioblastoma, renal cell
carcinoma, pheochromocytoma, visceral
cystic
Tuberous sclerosis TSC1 9p34 Subependymal giant cell astrocytoma, Cutaneous angiofibroma Cardiac rhabdomyoma, adenomatous
complex TSC2 16p13 cortical dysplasia (“adenoma sebaceum”), polyps of the duodenum and the small
peau chagrin, subungual intestine, cyst of the lung and kidney,
fibroma lymphangioleiomyomatosis, renal
angiomyolipoma
Li-Fraumeni TP53 17p13 Astrocytomas, primitive neuroectodermal – Breast carcinoma, bone and soft-tissue
tumors sarcoma, adrenocortical carcinoma,
leukemia
Cowden PTEN 10q23 Dysplastic gangliocytoma of the Multiple trichilemmoma, Hamartomatous polyps of the colon,
cerebellum (Lhermitte-Duclos), fibroma thyroid neoplasms, breast carcinoma
megalencephaly
Turcot APC 5q21 Medulloblastoma Cafè-au-lait spots Colorectal polyps
hMLH1 3p21 Glioblastoma Colorectal polyps
hPSM2 7p22
Nevoid basal cell PTCH 9q31 Medulloblastoma Multiple basal cell Jaw cysts, ovarian fibroma, skeletal
carcinoma syndrome carcinomas, palmar and abnormalities
(Gorlin) plantar pits
Rhabdoid tumor INI1 22q11.2 Atypical teratoid/rhabdoid tumor – Renal and extrarenal malignant rhabdoid
predisposition tumors
syndrome
B. Spacca et al.
49  Central Nervous System Congenital Tumors 657

anomalies. The strength of this observation is brain tumor to the child [29, 30], but again differ-
increased by a number of studies reporting that ent studies report that there is no particular asso-
children with tumors are at a higher risk of having ciation [30–32]. The Parental exposure to electric
associated congenital malformations compared and magnetic fields during the perinatal period
with the general pediatric population not affected has been considered as a possible risk for brain
by tumors and compared with their siblings [20, tumors in the offspring [33], but it is still a con-
21]. It is feasible to admit that a factor that exerts troversial issue and under investigation.
a teratogenic effect if active during pregnancy A similar conclusion can be reached for paren-
might induce genetic mutations responsible for tal occupational exposure or for the exposure to
malformations or tumors, or even both in the different possible environmental factors [34–37].
same patient. According to Mann, the excessive On the other hand, when it comes to consider-
number of malformations found in children with ing protective factors for CNS tumors, a protec-
cancer may indicate that in up to 1 in 20 cases, tive effect has been associated with the intake of
one or more antenatal events may lead to malfor- vegetables, fruit, folate, and vitamin C in early
mation and to a tumor [20]. pregnancy with regard to the risk of PNET in the
It is commonly accepted that exposure to ion- offspring [32].
izing radiation can cause tumors, including CNS
tumors and congenital CNS tumors if the expo-
sure happens during fetal life [22, 23]. It is esti- 49.3 Clinical Considerations
mated that if embryos or fetuses are exposed to a
dose of ionizing radiation of 0.2 Gy, the risk for Even if the patients included are not only chil-
malformation doubles, as has been extrapolated dren younger than 2 months but also those up to
from studies on rodents [23], even if a dose of as 12  months, congenital CNS tumors have some
little as 10 mSv (equivalent to 1 cGy = 0.01 Gy) peculiarities that increase their aggressivity,
to the fetus can increase the risk of childhood although they may be benign from the histologi-
cancer [24]. The general risk for a child exposed cal point of view. Their diagnosis and treatment
during his development in the uterus to ionizing can therefore be quite difficult.
radiation is estimated to be 0.06% for every cGy A first consideration is that when it comes to
of radiation [25]. Studies on the Japanese popula- CNS tumors, and not only congenital CNS
tion exposed to that factor reveal that exposure in tumors, the term “benign” is relative, because it is
the uterus to ionizing radiation seems to increase not always possible to resect them completely
the risk of developing solid tumors more than if depending on their location. Moreover, in the
the exposure happens to an already born child, specific case of the young patients we are talking
who instead is at a higher risk of developing about, there are many problems that make this
blood cancer [24]. state more complex.
Various substances and general conditions The clinical presentation and diagnosis of
have been studied as possible causes of solid congenital CNS tumors happen frequently
tumors in children born from exposed parents. because of signs and symptoms of increased
High birth weight (>4 kg) was analyzed as a pos- intracranial pressure [2, 6, 7] instead of neuro-
sible factor associated with the risk of CNS can- logical signs and/or symptoms. The reason is
cer in children, but results are not the same in probably related to at least two mechanisms that
different studies, as some authors report an grant to infants the ability to offset the growth of
increase in the risk, especially for astrocytomas the tumor without clinical evidence of it. The first
and embryonal tumors [26, 27], whereas other is the incomplete maturity of neurons and white
studies report that it is not [28]. matter in infants and toddlers [8, 38]. As a conse-
A high level of nitrite intake by the mother quence, it may be that a tumor growing when the
during pregnancy with the diet (cured meat, specialized activity of groups of neurons is not
water) has been associated with a higher risk of yet defined might result in a reorganization of the
658 B. Spacca et al.

activities controlled by those groups of neurons As observed before, the plasticity of the skull
themselves without evident neurological on the one hand and the neuronal plasticity and
sequelae. Specific neurological signs/symptoms immaturity on the other result in the ability of
do not appear until the mass reaches a volume infants to offset the growth of the tumor for much
that produces a significant neuronal loss. The longer than older children and adults. The conse-
second mechanism is related to the plasticity of quences are not only related to a “late” diagnosis
the skull and to its opened sutures and fonta- but open to more possible considerations. It is not
nelles. The skull can grow and deform to accept rare that the tumor at diagnosis has already
the growing tumor (Fig. 49.2). reached considerable dimensions. They are often
The most common clinical presentation classified as giant tumors, or they involve more
according to the literature is intracranial hyper- than one lobe at diagnosis (Figs. 49.3, 49.4). Asai
tension, such as macrocrania, bulging fontanelle, et al. [39] reported in their series a mean diameter
irritability, and failure to thrive, which account of tumors at diagnosis of 4.6 cm. Buetow et al.
for 42–65% of the reasons to seek for medical [2] described that 18 cases out of 45 congenital
advice and consequent diagnosis [6, 21, 38]. Far tumors at diagnosis had a volume of more than
less common are seizures, cranial nerve palsy, one third of the whole cerebral volume. A direct
and focal neurology [6, 7, 21, 38]. In our series of consequence is that such huge tumors cannot
94 patients with a CNS tumor younger than always be completely surgically resected and that
1 year at diagnosis retrospectively reviewed, the at presentation the patient can have a sudden
clinical presentation was available for 86 patients, deterioration of their clinical general and neuro-
and it resulted in 43 cases (50%) presenting with logical status. A certain number of patients are
signs and/or symptoms related to intracranial admitted with a compromised Glasgow Coma
hypertension. Scale. In the series by Oi et al. [21], 66 patients

Fig. 49.2 N.R., 8  months old, girl, choroid plexus

carcinoma. The tumor grew from the lateral ventricle and Fig. 49.3  L.L., 1-month-old girl, presenting with macro-
completely altered the normal brain. During its growth crania and increasing head circumference
the tumor induced macrocrania and deformed and thinned
the skull
49  Central Nervous System Congenital Tumors 659

(21.5%) presented with disturbed consciousness; supratentorial tumors more frequently than
in the series by Di Rocco et al. [38], impairment infratentorial. A supratentorial location is
of consciousness was reported for 4% of the observed in 60–70% of the cases [2, 7, 21, 38]. In
patients; in the series by Buetow et al. [2], 1 our series, 56 patients (59.5%) out of 94 had a
patient out of 45 was lethargic at presentation; supratentorial tumor.
Lang et al. [7] described 1 patient out of 16 as Hydrocephalus is a frequent problem in these
being lethargic at presentation. In our series, 7 patients, both at diagnosis and later on during
patients (8.2%) out of 86 presented with a dete- their management. It is commonly related to the
rioration in the level of consciousness. obstruction of the CFS flow produced by the
Another consideration is that as a consequence tumor and can be complicated by cystic compo-
of skull plasticity and neural immaturity/plastic- nents (Figs. 49.5, 49.6, and 49.7). Many patients
ity, tumors could develop during the first weeks require more surgical procedures dedicated to
of life but become clinically evident only later. the treatment of the hydrocephalus. Buetow et al.
This observation challenges the rigid definition describe 21 patients out of 45 at diagnosis had
of Solitaire and Krigman [4], which takes into already presented with hydrocephalus [2]. In
consideration only congenital tumors diagnosed our series, hydrocephalus was already present at
within the first 4 weeks of life. diagnosis in 21 patients (24.4%) out of 86, and
The location of CNS tumors in children in 39 patients (41.4%) out of 94, the first surgi-
younger than 12  months differs significantly cal treatment offered consisted of a diversion
when compared with the general epidemiology procedure on CSF or in the cystic components
of brain tumors in children. These patients have of the tumor.
The increased use of ultrasound and MRI dur-
ing pregnancy has of course given rise to a num-
ber of cases of CNS tumors diagnosed during
fetal life [9, 14, 40–45]. Most of the reports dis-
cuss lesions observed late during pregnancy [9,
41, 43, 44]. In our series, 3 patients (3.5%) out of
86 received a diagnosis in utero (Fig. 49.8). Many
reports describe diagnosis in utero for teratoma
[40, 44]. It is less common a diagnosis in utero
than for other histologies, such as the craniopha-
ryngioma described by Kageji et al. [9]. In our
series, the three cases diagnosed using fetal scans
were PNET in two cases and glioneuronal tumor
in one.
The increased use of fetal ultrasound can other-
wise increase the discussion on how and when
congenital tumors develop. In our series, we
observed a case of a 2-month-old girl admitted for
macrocrania who had undergone serial fetal ultra-
sound before birth because the mother was fol-
lowed up at the high-risk pregnancy service owing
to a previous miscarriage related to a confirmed
genetical disease. The last fetal ultrasound was
performed 10  days before birth, and the report
described all the normal brain fetal morphology
Fig. 49.4  D.P.C., 1-month-old boy, presenting to the
emergency department because of a reduced level of with no evidence of any abnormalities: normal
consciousness midline structures, normal brain sonography, and
660 B. Spacca et al.

Figs. 49.5 and

49.6  a, b E.A.,
7-month-old boy,
presenting with
macrocrania and Russell
syndrome. On MRI at
diagnosis he had an optic
chiasmatic tumor with
hydrocephalus and
multiple spinal
metastases. Histology:
high-grade glioma

a b

normal anthropometric parameters. The patient presented the lesion shown in Fig. 49.9. She under-
was admitted as an emergency and sent by the went an emergency procedure of CSF diversion
pediatrician because of macrocrania (increased but had a respiratory arrest 6 h after admission into
head c­ircumference of 6  cm in 1  month) and a hospital. The histology obtained by a biopsy
bulging fontanelle. On admission, the patient revealed a glioblastoma multiforme.
49  Central Nervous System Congenital Tumors 661

a b

Fig. 49.7  G.F., 2-month-old boy, presenting with macrocrania. CT at presentation discovered a giant supratentorial
tumor with solid and cystic components and associated hydrocephalus. Histology: immature teratoma

a b

c d

Fig. 49.8 (a, b) M.F.G., ultrasound at 35  weeks’ Roberto Biagiotti for the ultrasound images). (c) Fetal
gestation revealed a huge posterior fossa tumor with MRI. (d) MRI at birth. Histology: primitive neuroectoder-
associated obstructive hydrocephalus (we thank Dr. mal tumor
662 B. Spacca et al.

Fig. 49.10  Immature teratoma. Mature (choroid plexus

is appreciable on the left) and immature (neural tube-like
structures are appreciable on the right) tissues, hematoxy-
Fig. 49.9  A.T., 2-month-old baby girl. Histology: glio-
lin and eosin (H&E), original magnification ×20
blastoma multiforme; Mib-1: 85%

49.4.1 Teratoma
49.4 Histology
Teratoma is the most common congenital CNS
The first congenital intracranial tumor was tumor. It typically occurs along the midline of the
reported by Holt in 1917, who described a gliosar- body from the coccyx, which is the most com-
coma in a 2-week-old infant [46]. Successive mon site, to the pineal gland. The head and neck
reports demonstrated that there is a large variety are the second most frequent sites. Intracranial
of histopathological types of congenital brain lesions typically arise in the pineal region.
tumors. The proportion of each histotype varies Teratomas are germ cell tumors composed of tis-
among different series. Indeed, the literature sur- sues derived from the three germ cell layers
rounding this population is mostly composed of (ectoderm, endoderm, and mesoderm).
case reports or small case series, and only a few Ectodermal components, especially neural tissue,
recent papers provided a literature review. are the dominant feature of fetal cases [49].
Larouche et al. published a literature review draw- Teratomas are histologically classified as mature
ing many series together, including more than or immature. Mature teratomas consist exclu-
1200 patients, and confirmed the marked histo- sively of fully differentiated tissues, i.e., skin and
logical heterogeneity [47]. skin appendage, adipose tissue, neural tissue,
The histotypes encountered during the intra- muscle, cartilage, bone, or glands; whereas
uterine life and within the first year of age are immature teratomas also contain incompletely
remarkably different from those occurring in differentiated components similar to fetal tissues.
older children and adults. Teratoma is the most Frequently, immature components are primitive
common perinatal congenital brain tumor, rep- neuroectodermal structures resembling the neu-
resenting about 30% of all CNS tumors detected ral tube (Fig. 49.10) [50].
during the fetal and neonatal periods [48].
Other tumor subtypes are astrocytomas (low-
grade astrocytoma and high-grade astrocy- 49.4.2 Astrocytomas
toma), embryonal tumors, and choroid plexus
tumors. Less common histologies include glio- Astrocytomas follow teratomas in frequency,
neuronal tumors, craniopharyngiomas, and accounting for 20–45% of all congenital brain
ependymomas [49]. tumors [51]. They can present various degrees of
49  Central Nervous System Congenital Tumors 663

infants and young children, arises in the

hypothalamic/chiasmatic region, and has a less
favorable prognosis [55]. Nevertheless, a number
of subsequent studies provided evidence that
these tumors may occur later in life, in regions
other than the hypothalamic/chiasmatic area, and
have a benign behavior [56].
A few cases of SEGAs have been reported in
the perinatal period either as sporadic tumors or
associated with the tuberous sclerosis complex
(TSC) [57, 58]. SEGAs are benign, slowly grow-
ing tumors typically arising in the wall of the lat-
eral ventricles. The histogenesis of SEGA is
Fig. 49.11  Pilocytic astrocytomas. Small bipolar cells
and Rosenthal fibers (elongated eosinophilic structures), controversial. Older studies suggested an astro-
H&E, original magnification ×20 cytic nature, whereas a number of recent reports
demonstrated a mixed glioneuronal nature.
Indeed, SEGAs consist of three types of cells,
differentiation and can range from low-grade which can be present in different proportions:
tumors to high-grade tumors. small/spindle cells, gemistocytic-­like cells, and
Low-grade gliomas are mostly represented by ganglion-like cells (Fig. 49.12). These three types
pilocytic astrocytomas and less frequently by of cells may show at an immunohistochemical
SEGAs, both grade I tumors according to the and ultrastructural level glial and/or neuronal fea-
World Health Organization (WHO) [50]. tures (Fig.  49.12) [59]. Nuclear pleomorphism
Commonly, they are well circumscribed and have and increased mitotic activity may be observed in
only a narrow margin of infiltration into the sur- some rare cases [50].
rounding tissues. High-grade astrocytomas, anaplastic astrocy-
Pilocytic astrocytomas may be sporadic or tomas, and glioblastomas are more common in
occur in patients carrying the NF1 mutation. the fetus and in neonates than in older children
Most pilocytic astrocytomas in NF1 are localized [51]. Anaplastic astrocytomas are WHO grade III
within the optic pathway, and a bilateral growth diffusely infiltrating lesions with nuclear atypia,
is characteristic [52]. Pilocytic astrocytomas increased cellularity, and greater proliferative
often have a microscopically biphasic pattern, activity. In the current WHO classification of
with compact areas composed of small bipolar CNS tumors, anaplastic astrocytomas are further
and stellate-shaped cells and loose-textured areas subdivided according to the presence or absence
composed of multipolar cells with microcysts. of isocytrate dehydrogenase (IDH) 1 or 2 gene
Rosenthal fibers and eosinophilic granular bodies mutation: anaplastic astrocytoma IDH-mutant
are commonly observed, particularly in compact (better prognosis) and anaplastic astrocytoma
areas (Fig.  49.11). Mitoses are uncommon, but IDH-wildtype (poorer prognosis) [50]. Pediatric
sometimes pilocytic astrocytomas in early child- astrocytomas, either low grade or high grade, in
hood may exhibit morphologically aggressive most cases, do not harbor these mutations [60].
features and be misdiagnosed as high-grade However, to the best of our knowledge, no pub-
tumors [53, 54]. lished information about the IDH gene mutations
A variant of pilocytic astrocytoma named in congenital ­anaplastic astrocytoma have been
pilomyxoid astrocytoma has been described. Its reported in the English medical literature to date.
most typical morphological characteristic is an Glioblastomas (WHO grade IV tumors) rep-
angiocentric astrocytic proliferation embedded in resent about half of all perinatal astrocytomas
a myxoid background. The first reports indicated in Isaacs’ series [45]. They are microscopi-
that pilomyxoid astrocytomas typically affect cally characterized by hypercellularity, marked
664 B. Spacca et al.

a b

Fig. 49.12  Subependymal giant cell astrocytoma. (a) like cells, H&E, original magnification ×20. (b) Ganglion-
Subependymal proliferation (the thin ependymal lining is like cells as demonstrated by immunohistochemistry,
appreciable on the right) of predominant gemistocytic- neurofilaments, original magnification ×60

49.4.3 Choroid Plexus Tumors

Choroid plexus tumors comprise papillomas

(WHO grade I), atypical papillomas (WHO grade
II), and carcinomas (WHO grade III) [50]. They
originate from the choroid plexus epithelium and
consequently are mostly located within the ven-
tricular system, in particular, the lateral ventri-
cles, where the normal choroid plexus is. Choroid
plexus tumors occur sporadically or in rare cases
in association with familiar syndromes, in par-
ticular, the Aicardi and Li-Fraumeni syndromes
Fig. 49.13  Glioblastoma. Hypercellularity and pleomor- [50]. Choroid plexus papillomas account for
phism. H&E, original magnification ×20 2–4% of all brain tumors that occur in children
aged <15 years and for 10–20% of those occur-
pleomorphism, intense mitotic activity, micro- ring in the first year of life [62]. Those tumors are
vascular proliferation, and palisading necrosis benign and histologically characterized by a pap-
[50] (Fig.  49.13). Fetal and neonatal glioblas- illary pattern of growth in a single layer of uni-
tomas are genetically different from their adult form cuboidal-columnar epithelial cells with
counterparts and show a low frequency of known round-­oval basally situated nuclei. The mitotic
genetic defects [61]. activity is absent or very low. Atypical choroid
A new entity of astrocytic tumors called dif- plexus papillomas are a rare and newly intro-
fuse midline glioma H3 K27M-mutant was intro- duced entity, with intermediate characteristics
duced in the latest edition of the WHO between papillomas and carcinomas. Their domi-
classification [50]. Diffuse midline glioma H3 nant microscopic characteristic is increased
K27M-mutant is an infiltrative midline high- mitotic activity (Fig. 49.14), and from a clinical
grade (WHO IV) brain tumor that predominates point of view, they carry a higher risk of recur-
in children. This kind of tumor has a poor prog- rence. However, there is evidence that a high
nosis despite current therapies (2-year survival mitotic count has much prognostic value in adults
rate of <10%) [50]. To the best of our knowledge, and children older than 3 years of age, but not in
no congenital cases have been yet described in younger children [63]. Choroid plexus carcino-
the English-language medical literature. mas are frankly malignant epithelial neoplasms,
49  Central Nervous System Congenital Tumors 665

Fig. 49.14  Atypical choroid plexus papilloma. Columnar Fig. 49.15  Medulloblastoma. Small round undifferenti-
and mitotically active neoplastic cells with a papillary ated cells, in many areas organized in rosettes (Homer
architecture, H&E, original magnification ×40 Wright rosettes consisting of a halo of tumor cells sur-
rounding a central region containing neuropil), H&E,
original magnification ×20
with frequent mitoses, increased cellular density,
nuclear pleomorphism, and necrotic areas. defined entities designated as “CNS neuroblas-
Lesions with these morphological features toma with FOXR2 activation (CNS NB-FOXR2),”
account for 14% of tumors occurring in the first “CNS Ewing sarcoma family tumor with CIC
year of life [50, 62]. alteration (CNS EFT-CIC),” “CNS high-grade
neuroepithelial tumor with MN1 alteration (CNS
HGNET-MN1),” and “CNS high-grade neuroepi-
49.4.4 Embryonal Tumors thelial tumor with BCOR alteration (CNS
HGNET-BCOR)” [65].
Embryonal tumors are highly malignant [50]. As Medulloblastoma is the most common CNS
a group, in most series, they follow teratomas, embryonal tumor. Although it constitutes approx-
astrocytomas, and choroid plexus tumors in terms imately 25% of CNS tumors in children, the con-
of frequency in the perinatal age [13, 64]. The genital form is rare [66]. Microscopically,
WHO classifies embryonal tumors as medullo- medulloblastomas are cerebellar tumors com-
blastoma, embryonal tumor with multilayered posed of small round undifferentiated cells with
rosettes C19MC-altered, medulloepithelioma, mild to moderate nuclear pleomorphism and a
CNS neuroblastoma and ganglioneuroblastoma, high mitotic count (Fig. 49.15). Of the four histo-
embryonal tumor not otherwise specified, and logical variants of medulloblastoma (classic, des-
atypical teratoid/rhabdoid tumor [50]. In the cur- moplastic/nodular, extensive nodularity, and
rent WHO classification of CNS tumors, CNS large cell/anaplastic), medulloblastoma with
primitive neuroectodermal tumor (PNET) and extensive nodularity is, by far, the most common
supratentorial PNET have been removed from type in children younger than 2 years [67]. The
the diagnostic lexicon [50]. Indeed, Sturm et al. recognition of this entity is important, as the out-
recently conducted integrated genomic analyses come can be excellent [68]. In the last WHO clas-
of 323 CNS-PNET patients and demonstrated sification, medulloblastomas are classified not
that among the tumors diagnosed as PNET, there only according to their histopathological features
is a proportion of tumors displaying molecular but also to their molecular characteristics [50].
profiles indistinguishable from those of various The molecular classification distinguishes four
other well-defined CNS tumor entities and principal groups: WNT-activated MB (10%),
another proportion of tumors with peculiar SHH-activated MB (30%), group 3  MB (20%),
molecular characteristics. These observations and group 4  MB (40%), both non-WNT/non-­
suggest the existence of four new genetically SHH [50].
666 B. Spacca et al.

Atypical teratoid/rhabdoid tumors were first (Fig.  49.17) [50] . The age at presentation can
described in 1987 by Lefkowitz et al. [69]. They range from 2  months to 70  years. Diagnosis in
constitute 1–2% of all pediatric brain tumors, are newborns is rare, with only few cases reported in
highly aggressive, and are usually present in the literature [70, 71]. Most are localized in the
children younger than 2 years and may be con- temporal lobe (70%) but every site of CNS can be
genital. Atypical teratoid/rhabdoid tumors are involved. The most common genetic alteration in
embryonal tumors composed of poorly differen- these tumors is BRAF V600E mutation, occur-
tiated elements, frequently including rhabdoid ring in about 20–60% of investigated cases [50].
cells, which are immature, large tumor cells with
vesicular nuclei, prominent nucleoli, moderate 49.4.5.2 Desmoplastic Infantile
amounts of cytoplasm, and pale intracytoplasmic Astrocytomas/Gangliogliomas
rhabdoid inclusions (Fig.  49.16). Mutations of Desmoplastic infantile astrocytomas/gangliogli-
the SMARCB1 gene (or rarely the SMARCA4 omas (DIAs/DIGs) are benign neoplasms
gene), resulting in loss of expression of the INI1 (WHO I) [50] and are almost exclusively found
protein, are the hallmark of this tumor [50]. in infants [72, 73]. Their incidence can only be
Constitutional SMARCB1 mutations define the estimated from institutional series, and it ranges
rhabdoid predisposition syndrome where from 0.3 to 15.8% [73, 74]. Macroscopically, the
affected patients are predisposed to renal and appearance of these tumors is that of a massive,
extrarenal rhabdoid tumors and exceptionally to supratentorial, cystic lesion with a solid mural
a variety of CNS tumors, including choroid nodule. Multi-lobar involvement is common.
plexus carcinomas, PNETs, and a subset of Histologically, they are composed of a prominent
medulloblastomas [50]. collagenous stroma with a neuroepithelial popu-
lation restricted to neoplastic astrocytes (DIAs)
or to astrocytes together with a variable mature
49.4.5 Glioneuronal Tumors neuronal component (DIGs) [50].

49.4.5.1 Ganglioglioma 49.4.5.3 Craniopharyngiomas

Gangliogliomas are rare, well-­differentiated, and Craniopharyngiomas constitute 5–11% of all
commonly low-grade (WHO I) glioneuronal intracranial tumors in children, but they seldom
tumors composed of neoplastic glial cells in occur in the perinatal period. Overall, cranio-
combination with dysplastic ganglion cells pharyngiomas account for 5.6% of all tumors

Fig. 49.16 Atypical teratoid/rhabdoid tumors.  Large

tumor cells with prominent nucleoli and high mitotic Fig. 49.17  Ganglioglioma. Neoplastic elongated glial
activity (a mitosis is appreciable in the center of the fig- cells in combination with neoplastic ganglion cells and
ure), H&E, original magnification ×60 lymphocytes, H&E, original magnification ×20
49  Central Nervous System Congenital Tumors 667

diagnosed in the fetal and neonatal periods [49]. 49.4.6 Ependymal Tumors
They are benign epithelial tumors (WHO I) of
the sellar region, presumably derived from the Ependymomas are included among rare congeni-
embryonic remnants of Rathke’s pouch epithe- tal brain tumors. Congenital ependymomas may
lium [50]. There are two clinicopathological either present in the fetus or manifest in the neo-
variants of craniopharyngioma with distinct natal period, but are more common during the
genotypes and phenotypes [50]. first year of life [75–77]. Ependymomas are cir-
Adamantinomatous craniopharyngiomas show cumscribed WHO grade II or III gliomas com-
CTNNB1 mutations and aberrant nuclear posed of monomorphic small cells, in a fibrillary
expression of beta-catenin in about 95% of matrix, arranged in ependymal rosettes (true) and
cases. Papillary craniopharyngiomas occur pseudorosettes with perivascular enucleate zones.
almost exclusively in adults and harbor Pseudorosettes can be found in almost all epen-
BRAFV600E mutations in 80–95% of cases. dymomas, whereas ependymal rosettes are pres-
Adamantinomatous craniopharyngioma is char- ent in only a few cases [50].
acteristically solid and cystic and composed of
well-differentiated epithelium with basal pala-
sading organized in cords, lobules, and nodular 49.4.7 Differential Diagnosis
whorls. Anucleate nests of squamous ghost
cells, keratin pearls, microcystic areas, calcifi- Besides the tumors, other congenital conditions
cations, and lymphocytic and giant cell infil- can mimic the clinical presentation of tumors.
trates are also typical. Piloid gliosis with Tumor-­ like masses are not uncommon and
Rosenthal fibers is commonly observed in the should be included in the differential diagnosis
surrounding brain (Fig. 49.18). Papillary cranio- of congenital brain tumors. The lesions most
pharyngioma affects adults almost exclusively, commonly found are spontaneous intracranial
is rarely cystic, and is mostly localized in the hemorrhage and congenital malformation, in
area of the third ventricle. Histologically, it is particular, giant subcortical heterotopia.
characterized by fibrovascular cores lined with Intracranial hemorrhage can occur in the pres-
squamous epithelium [50]. ence of coagulation factor deficiency or vascular
malformations [78, 79]. Giant subcortical het-
erotopia is part of the so-­called neuronal migra-
tion disorder, and it presents as a mass-like
nodular conglomerate of dysplastic grey matter
that may replace a cerebral lobe or even the
greater part of a hemisphere [80].

49.5 Treatment

The treatment for congenital brain tumors does

not substantially differ in terms of the basic prin-
ciples from the treatment for brain tumors in
older patients, as it consists of surgical and medi-
cal treatment. Having said that, it is actually so
different compared with the treatment of older
children with brain tumors that it is mandatory to
consider them separately.
Fig. 49.18  Craniopharyngioma. Well-differentiated epi-
thelium (bottom left, top right), stellate cells, and squa- Younger children have specific requirements.
mous ghost (top left), H&E, original magnification ×20 There are fewer weapons that can be used than in
668 B. Spacca et al.

older children and adults, because of the detri- heated coat and mattress during the surgical
mental effect that chemotherapy and radiother- procedure.
apy can have on their development. As a general When it comes to positioning, it is important
rule, it is advisable not to use radiotherapy in again to consider that the head is small, but at the
children younger than 3  years of age [81]. The same time, in infants and younger children, it
first consequence is evidently to refer to the sur- constitutes up to two thirds of the body. In infants,
gical treatment: a complete surgical resection is it is advisable to avoid some positions, such as
the best chance of survival, but it is often difficult the sitting position. Correct positioning of the
to obtain. Tumors are frequently huge in dimen- head is extremely important, as it allows many
sion, and an aggressive surgical approach may possible complications to be reduced during the
not be possible, as it cannot always be tolerated surgical procedure. It is critical, while chasing
by young children. the “perfect” position, to try to obtain one that
In addition, as observed in the previous para- allows prevention of cerebral collapse. Cerebral
graphs, there is a significant number of different collapse is a complication that can follow almost
histologies in a relatively small number of series every resective surgery on the brain of very young
and cases reported in the medical literature. The babies. The positioning of the head is a challeng-
result is of course that the treatment of these ing and complex moment that requires close
patients is a challenge. cooperation between surgeon and anesthesist to
consider and to help to prevent possible compli-
cations during surgery. A horseshoe head holder
49.5.1 Surgical Treatment is generally preferred to a pin head holder, owing
to the thin skull of infants and the associated risk
49.5.1.1 Anesthesia and Surgical of fractures of the skull itself with pins. Once the
Position head is positioned to try to optimize the needs of
The first elements to be considered when it surgeon and anesthesist, it is important to place
comes to surgery are the anesthesia and the adequate anti-decubitus material at points of
position of the head. Children younger than increased body pressure to reduce the risk of
1 year of age have a significant disproportion in pressure sores as the skin of infants is extremely
terms of dimension between the head and the delicate.
body; they present a small amount of blood,
which is estimated around 60–80 mL per kg of 49.5.1.2 Risk of Bleeding
body weight, and have an immature immuno- It is mandatory to start surgery only if there is an
logical and endocrine system to cope with the adequate volume of blood, platelets, and plasma
surgical stress. for transfusion available in the operating room.
The body temperature of small children tends Young children with brain tumors are frequently
to decrease during surgery. During anesthesia, in a situation of increased intracranial pressure,
the metabolic activity of the body is reduced, which can be associated with a higher risk of
and the body temperature is lower. At the same bleeding, even during the very first steps of sur-
time, in children, the size of the head compared gery, when the surgeon deals with skin and bone.
with the overall dimension of the body is larger For this reason, if the CSF dynamic is perturbated
than in adults and produces a significant loss of on admission, the first line of treatment has to be
temperature. To start with, it is advisable to CSF diversion (ventriculoperitoneal shunt or
operate on infants and very young children in external ventricular drainage) or neuroendoscopy.
operating rooms where it is possible to increase These “minor” surgical procedures allow a rebal-
the temperature of the room, to use a preheated ancing of the intracranial pressure and help to
solution for IV infusion, and to use a disposable reduce the pressure and distortion on the normal
49  Central Nervous System Congenital Tumors 669

brain parenchyma improving life functions and 49.5.1.3 Cerebral Collapse

with them the general and neurological condition We underlined before that congenital cerebral
of the patient. The same considerations are advis- tumors may have a huge volume, especially if
able if the tumor presents with a significant cystic compared with the volume of the normal brain.
component. When a procedure can reduce the As a consequence, during and after radical resec-
dimensions of the cyst and the intracranial pres- tion, the residual normal brain collapses. This
sure, it is advisable again to operate first on the fact may cause neurological deficit even in
cystic component and, eventually, if still advis- remote areas. The main reason for neurological
able according to the results of cytology/histology problems depends on the abnormal angle that is
and to the general and neurological condition of acquired by neural fibers and tracts following the
the patient, to carry out a resective surgery on the line of brain collapse. For this reason, it is man-
rest of the tumor. If these features (intracranial datory to allow a progressive recovery of the nor-
pressure, distortion, and compression of the brain mal shape of the brain during the resective
parenchyma) are addressed before the resective procedure, first of all with an adequate support of
surgery, the expected results will be first a reduc- IV fluid and then with specific maneuvers. It is
tion of the bleeding and second, but no less impor- possible to use transiently various devices that
tant, a more physiological anatomy. are useful to replace the volume loss left where
A minor loss of blood in infants can produce a the tumor was. Instruments such as Fogarty bal-
significant change in the main parameters. It is loons or Foley catheters can be passed through
very important that the surgeon reduces the blood the cerebral cortex into the cavity obtained after
loss as much as possible and that the anesthetist the resection of the tumor and kept inflated dur-
allows an adequate and immediate replacement ing the time necessary for the brain to expand as
of fluids and blood from the very start of the sur- much as possible (Fig. 49.19).
gery. The tumors are often massive and, espe- After surgery, particular care must be taken to
cially when malignant, have a rich vessel texture try to keep the position of the head as neutral as
with a consequent high risk of bleeding. The pre- possible, to attempt to reduce the passive motion
vious recommendations are even stronger for of the brain into the head.
proceeding with the surgery. If during the resec-
tive craniotomy the bleeding is too much and/or 49.5.1.4 Instrumentation
the vital functions are too stressed, it is very The standard equipment of neurosurgical oper-
important to stop the resection immediately and ating rooms must of course be warranted,
to pursue good hemostasis, replenishing the vol- starting with the operative microscope. A neuro-
ume of the cavity left from the tumor removed by navigation system can be useful, but it needs to
using hemostatic material, and if the resection is be a magnetic one, as a nonrigid fixation is gen-
not considered adequate, reschedule the surgery erally preferred. It is important from this point
after a few days when the general condition of the of view to consider that, as mentioned above,
patient has improved. A multistep surgery when there can be significant shifting of the brain
dealing with large brain tumors in very young structures during and after the resection of the
children does often warrant better results in terms tumor, especially if it is large and, consequently,
of both final tumor resection and morbidity/ this reduces the appropriateness of the
mortality. neuronavigation.
In our series of 94 congenital tumors operated The use of intraoperative ultrasound can be of
on, there was one infant who weighed 2.5 kg and use to reduce this loss of accuracy.
who died during surgery because of bleeding that The use of intraoperative monitoring in infants
could not be controlled. The histology revealed is not as useful as it can be in older children. There
glioblastoma multiforme. are at least two reasons for this. The first is that, as
670 B. Spacca et al.

a b

c d

Fig. 49.19  J.B, 2-month-old girl. Presenting with a bulg- structures. (c) MRI 2 years after surgery. According to the
ing fontanelle and a reduced level of consciousness. (a) WHO classification at the time of surgery, the tumor was
MRI at presentation. (b) MRI after gross total surgical diagnosed as a PNET. (d) Intraoperative images of the
resection. The cerebral collapse is evident with a promi- progressive reduction of cerebral collapse with the use of
nent subdural collection and a distortion of the midline a Fogarty balloon

said before, in very young children, the maturity not be reliable. The second reason is that some-
of the neurons and white matter is not complete. times in infants, the tumor is so huge in dimension
As a consequence, intraoperative monitoring may that it completely deforms the architecture and
49  Central Nervous System Congenital Tumors 671

anatomy of the brain, thus also rendering intraop- most common neonatal brain tumor in several
erative monitoring unreliable. major studies [87, 88]. Teratomas arise from sev-
eral locations within the CNS, the pineal, the
hypothalamic area, the suprasellar region, and
49.5.2 Medical Treatment the cerebral hemispheres, and they could erode
through the skull and extend into the orbit, oral
The most commonly encountered pathological cavity, or into the neck. Intracranial teratomas are
conditions include teratomas, low- and high- typically large cystic tumors with solid areas
grade astrocytomas, craniopharyngiomas, and replacing much of the brain [89]. The prognosis
choroid plexus and embryonal tumors. Less com- worsens with increasing tumor size and decreas-
monly encountered diseases include ependymo- ing gestational age at diagnosis. They have one of
mas, germinomas, malignant schwannomas, and the lowest survival rates for all patients with peri-
malignant meningiomas [82, 83]. natal brain tumors, which could be attributed to
Beyond the histological type, congenital CNS the presence of advanced disease at the time of
tumors have a dismal prognosis because of age diagnosis [51]. Research into markers such as
and the need for neurosurgical support and a beta-human chorionic gonadotropin (β-HCG)
newborn intensive care unit. Some malignant his- and alpha-fetoprotein (α-FP) in addition to imag-
totypes start out as large-scale injuries not diag- ing could help to reach a more certain preopera-
nosed in the fetal age. For all these reasons and tive diagnosis, especially for immature/mature
the poor prognosis, many pediatric oncology cen- teratomas and germinomas. Generally, children
ters prefer not to treat them. with high levels of β-HCG or α-FP and proven
Being rare diseases, the therapeutic approaches tumor are considered to suffer from a malignant
are not standardized, owing to the lack of a clear disease [90].
understanding of the role of genetic patterns and Craniopharyngiomas are the most common
support therapy management in infants with con- tumors in the parasellar region in childhood, but
genital CNS tumors. Therefore, there is still no they seldom occur in the perinatal period [91].
consolidated treatment through an international They are considered benign tumors, but when
consensus for the therapy of congenital malig- occurring in fetuses and neonates they generally
nant brain tumors. have a poor prognosis [50, 92]. Surgery is the
The prognostic factors are residual disease main treatment for these tumors, also because
after surgery, histology, and the presence of postoperative therapy could cause several side
metastasis. effects in these patients [93].
In children under 12  months, the treatment Astrocytomas follow teratomas in frequency,
includes surgery and adjuvant chemotherapy to accounting for 18–47% of all congenital lesions,
avoid or to defer radiation therapy. As is well and they present with various degrees of differen-
known, the predisposition of the young brain to tiation, from benign to malignant tumors [51].
radiotherapy-induced cognitive deficits and leu- Fetal astrocytomas differ from those in the
koencephalopathy, which increases for a long pediatric population in terms of their gross and
time after radiotherapy, has set age limitations on histological features, site of origin, and clinical
the use of radiotherapy in infants. However, the manifestations; in particular, cerebellar pilocytic
ideal approach for very young children remains astrocytoma is notably absent in the fetal group.
postoperative chemotherapy alone, which can Congenital astrocytomas are generally solid
lead to a good outcome in half the cases [84–86]. masses involving the cerebral hemispheres, thal-
Teratomas and craniopharyngiomas only amus, or optic nerve [49].
require a surgical approach, with the aim of Furthermore, there is a high association
obtaining a complete resection of the disease. between optic pathway pilocytic astrocytomas
Teratomas are not only the main intracranial (grade I) and neurofibromatosis type 1 (NF-1),
germ cell congenital brain tumor, but is also the approaching 50% in some series [94]. There is no
672 B. Spacca et al.

correlation between the extent of surgical resec- previously mentioned, PNETs have been
tion, the presence of residual tumor, irradiation, removed from the current WHO classification
and the length of survival or degree of residual of CNS tumors [50]. Tumors in the past diag-
disability in congenital optic pathway gliomas. nosed as CNS-PNETs occurred primarily in the
Optic pathways astrocytomas are considered pediatric age group and were characterized by
benign in nature, because their natural history the capacity for differentiation along neuronal,
can evolve with long periods of dormancy and astrocytic, muscular ependymal, and melanotic
they can occasionally present spontaneous cell lines [51]. One-fourth of all tumors diag-
regression; therefore, their treatment should be as nosed as cerebral PNETs occurred before
conservative as possible. Radiotherapy is not rec- 2  years of age and were highly aggressive,
ommended, especially in patients with NF-1 metastasizing widely throughout the CSF path-
because of the high risk of a second malignant ways and invading the meninges of the brain
neoplasm [94]. Interestingly, patients with a and spinal cord [83].
tuberous sclerosis complex develop low-grade Medulloblastoma follows teratomas, and
astrocytomas (subependymal giant cell astrocy- astrocytomas, and choroid plexus tumors in inci-
tomas) in the perinatal period [57]. dence in several perinatal series [51]. At diagno-
Anaplastic astrocytomas (WHO grade III) sis, these tumors could have metastatic lesions as
may occur in the fetus and newborn. Children the initial manifestation, which is unusual for a
with anaplastic astrocytomas have a better out- brain tumor in this age group [97]. Congenital
come than those with glioblastoma, with long-­ anomalies in patients with medulloblastoma have
term survivors reported. One-third of all been described (e.g., imperforate anus, omphalo-
astrocytomas are glioblastomas multiforme cele, myelomeningocele, cleft palate, cerebellar
(WHO grade IV). In infants, they often arise agenesis, dural arteriovenous malformations, and
from the cerebral hemisphere and basal nuclei. acrania) [51].
Glioblastomas involve a high risk of bleeding Patients with Gorlin syndrome are at an
and infection. Bleeding (within the tumor) may increased risk of medulloblastoma, with an inci-
be the initial imaging finding in the perinatal dence of 1–2% [98]. Furthermore, there is a sig-
period [95]. nificant association between medulloblastoma
The overall survival rate for newborns with and rhabdoid tumor of the kidney [99]. The loss
astrocytoma remains discouraging. The meta-­ of portions of chromosome 17p has been
analysis of Isaacs reported that overall, only one described in medulloblastoma patients [100].
third (16 out of 47) of the patients survived and Medulloblastomas originate from the vermis
six (13%) were stillborn. Infants diagnosed with of the cerebellum and grow into the fourth ven-
low-grade astrocytomas showed a higher rate of tricle and adjacent cerebellar hemispheres.
survival (37%) vs infants with high-grade astro- Subsequently, obstructive hydrocephalus and
cytoma (anaplastic astrocytoma or glioblastoma leptomeningeal seeding occur along the cere-
multiforme; 14%). Only 2 out of 15 (13%) brospinal axis [51]. The tumor enters the blood-
patients with glioblastoma survived [96]. The stream and metastasizes in the CSF and seldom
low survival could be recognized in a chemother- to organs outside the CNS, primarily to the
apy regimen with limited success in infants less liver, lungs, and bone marrow, and sometimes to
than 3 months of age [65] and in the impossibility the lymph nodes [97, 101]. The treatment of
of using radiation treatment on immature brains infants with medulloblastoma is problematical
because of its injurious effects on growth and because irradiation of the infant brain carries a
development of the brain and skeleton [51]. high risk of intellectual, skeletal, and endocrine
The term PNET is applied to a group of sequelae [102].
small-­cell malignant tumors of the central and The prognosis for newborns with medullo-
peripheral nervous systems and soft tissues. As blastoma in general remains discouraging.
49  Central Nervous System Congenital Tumors 673

Infants clearly have a worse prognosis than older Generally, both European and American clini-
children, although the outcome appears to be
­ cal studies demonstrated the efficacy of high-­
improved by chemotherapy [103]. Isaacs reported dose chemotherapy (HDCT) and autologous
that only 1 out of 19 neonates with medulloblas- stem cell rescue (ASCR) for most malignant
toma was alive after adjuvant treatment [51]. The brain tumors in very young patients.
highly malignant AT/RT is similar biologically During the last decades, therapeutic
and histologically to the rhabdoid tumors present approaches have been varied with different sur-
in the kidney, soft tissues, and other sites [104, vival rates. The report of the Children’s Memorial
105]. The major site of origin of these aggressive Hospital of Chicago, on 341 infants treated dur-
tumors is the posterior fossa, particularly the cer- ing the period 1967 to 1980, showed that only 18
ebellum, but the cerebral hemispheres and the patients (malignant glioma or medulloblastoma)
brainstem are other primary sites [106]. AT/RT is underwent radiotherapy. Any children treated
associated with the monosomy 22 [107]. AT/RT with a combination of nitrosoureas and vincris-
has been often misdiagnosed as PNET or medul- tine did not achieve remission of the disease. The
loblastoma because 70% of AT/RTs sometimes survival rates at 1, 3, and 5 years were confirmed
contain histological characteristics indistinguish- to be 46%, 30%, and 22% respectively. They con-
able from classic PNET/medulloblastoma [108]. cluded that postoperative radiation therapy was
Nonetheless, differentiation between these two recommended for malignant tumors with evi-
entities is important because AT/RT has a dismal dence of disease. However, caution was expressed
prognosis and requires radical and aggressive concerning the use of whole-brain and spinal
treatment with surgery and adjuvant therapies cord irradiation in infants aged less than
such as radiotherapy and high-dose chemother- 12 months [113]. They obtained better results in
apy with autologous bone marrow transplant terms of overall survival, given the use of radio-
[109]. therapy (more than 5000 rads of the whole brain).
Choroid plexus carcinomas are diagnosed in Jooma et al. reported a large series of 100 infants
the first year of life in about one-third of the with intracranial tumors symptomatic during the
cases [110]. Most choroid plexus carcinomas first year of life that were treated with chemo-
occur in the lateral ventricles. They can dissemi- therapy and 39 patients were treated with radio-
nate throughout the cerebrospinal subarachnoid therapy. The cumulative average survival was
space. This feature may already be present at 27 months, which increased to 37 months after a
diagnosis, and, in any case, when present, it good resection. The operative mortality was 30%.
worsens the prognosis [111]. Choroid plexus The irradiated patients had a 5-year survival rate
tumors have one of the best survival rates of all of 43%. The morbidity was highly irrespective of
congenital brain tumors (73% survival rate of the radiotherapy; however, 60% of patients who sur-
33 patients) [51]. vived 12  months showed a moderate or severe
The main treatment remains a total surgical disability [75].
resection [112], but currently the use of chemo- Some therapeutic approaches are evaluable
therapy in patients with this malignancy has through single reports of congenital malignant
produced some encouraging results, achieving gliomas. A 2-month-old infant diagnosed with a
a better outcome than in older children and gliosarcoma underwent a subtotal resection and
adults [51]. monthly chemotherapy (including vincristine,
Despite the remarkable mortality of congeni- carmustine, procarbazine, cytosine arabinoside,
tal brain tumors, each center does not refer to cisplatin, and cytoxan) without tumor progres-
specific guidelines that can help in the treatment sion at 11 months of follow-up [114]. Two cases
of these cancers. Moreover, there are currently no of congenital glioblastomas were subjected to
differentiated protocols for each histological partial removal. One patient was subjected to che-
subtype. motherapy after surgery consisting of etoposide,
674 B. Spacca et al.

vincristine, cisplatin, and cyclophosphamide. The included methotrexate 250  mg/kg plus vincris-
patient completed chemotherapy and was alive tine 0.04 mg/kg, etoposide 80 mg/kg, cyclophos-
with minimal neurological deficits and no evi- phamide 135 mg/kg plus vincristine 0.04 mg/kg,
dence of disease. Interestingly, the second patient and carboplatin 25 mg/kg. Peripheral blood stem
omitted adjuvant chemotherapy for r­ eligious rea- cells have to be collected for rescue therapy.
sons. Currently, the child is alive with minimal Intensification and consolidation phases include
neurological deficit and no evidence of his malig- two high-dose chemotherapy regimens: thiotepa
nancy 2 years after surgery [86]. A patient with at myeloablative doses (10 mg/kg/day for 3 days)
glioblastoma multiforme underwent surgery and followed by ASCR.  The second conditioning
adjuvant chemotherapy according to the regimen also includes carboplatin (16 mg/kg/day
Children’s Cancer Group (CCG) 9921 protocol, for 2 days) with thiotepa [118, 119].
consisting of carboplatin, etoposide, ifosfamide, Tumors such as AT/RT and choroid plexus
and vincristine. The patient was alive at 23 months carcinoma could receive intrathecal chemother-
of age [115]. A girl with congenital glioblastoma apy with methotrexate coupled with systemic
was approached with surgery, adjuvant chemo- chemotherapy [119].
therapy, and radiation therapy. The MRI scan, After the induction phase (four cycles of che-
3 years after her surgery, showed no evidence of motherapy and before HDCT plus ASCR), brain
tumor recurrence [116]. Eventually, a child with a and spine MRI are performed to evaluate the
congenital malignant meningioma treated with presence of macroscopic solid or leptomeningeal
surgery and chemotherapy according to the CCG metastasis. Bone marrow examination and cere-
protocol for children aged less than 3 years with brospinal fluid (CSF) cytology are part of the ini-
malignant brain tumors (CCG 9921, Regimen A: tial evaluation looking for metastatic disease
cisplatin, etoposide, vincristine, and cyclophos- made before beginning the therapy. It is required
phamide) was alive with no evidence of disease for most embryonal tumors such as medulloblas-
on MRI at 14 months of age [116, 117]. tomas and AT/RT [84–86, 120].
Di Rocco and coworkers reported a meta-­ In conclusion, chemotherapy remains a much
analysis on a multicenter international series of accepted and well-tolerated adjuvant therapy for
886 children with brain tumor treated during the this age group. It has been proven beneficial as an
first year of life. Radiotherapy was administered adjuvant therapy in many tumors once the mass is
in only 129 cases, and 119 infants were subjected resected incompletely or in cases with malignant
to chemotherapy (without specifying the type of pathology in spite of complete resection. Only
therapy). 53.4% of these patients were still alive patients with malignant unresectable CNS tumors
(473 out of 886). They demonstrated that around or poor responders to chemotherapy could be
half of patients with congenital brain tumors can subjected to radiotherapy or neoadjuvant chemo-
survive with few side effects associated with che- therapy [121].
motherapy and infants receiving whole-brain It is noteworthy from clinical observations and
radiation tended to have greater deficits in the experimental in vivo data that the immature brain
long term [38]. is much more susceptible to radiation. An intel-
A study described a statistical analysis of 307 lectual or growth retardation, delayed hypopitu-
infantile brain tumors collected from different itarism, occlusive neurovascular complications,
countries. 51.1% of the patients were subjected and risks of a second malignant neoplasm in the
only to surgery treatment. A total of 110 infants treatment field have been reported [122].
received radiotherapy and only 37 received che- Actually, to avoid these intolerable side effects
motherapy. The 3-year overall survival was only for pediatric patients, proton therapy probably
35.5% and 26.1% after 5 years [21]. offers the greatest margin of benefit [123].
The Italian experience for children younger Several small series on proton treatment for low-­
than 3  years, independently of tumor histology, grade gliomas, sarcomas, or other pediatric
proposes four courses in the induction phase that tumors are available, all reporting excellent
49  Central Nervous System Congenital Tumors 675

tolerability and comparable outcomes with ted for spine tumors. Among them, 25 (30.1%)
photons [124]. were properly defined as congenital (diagnosed
Our knowledge of congenital brain tumors is before 2  months of age); 58 (69.9%) were
still limited, and a standard, effective, and between 2 and 12  months of age at diagnosis.
well-­
­ accepted treatment protocol for optimal Thirteen patients were excluded because of a
management of neonatal brain tumors is yet to be lack of data (1 in the group of patients younger
defined. than 2 months, 12 in the group of patients older
The goals to be achieved are an improvement than 2  months). When considered all together,
of management and prognosis of these cancers the 70 patients consisted of 47 boys vs 23 girls
through a better knowledge of the clinical behav- (M/F 2:1) and presented a supratentorial tumor
ior and genetic characteristics. in 52 cases (74.2%). An intraventricular tumor
Some epidemiological studies of congenital was observed in 15 of them (21.4%; 3  in the
brain tumors have documented several causes. group of patients younger than 2  months and
However, the search for causative factors for 12 in the group of patients older than 2 months
developing brain tumors continues. Certainly, the at diagnosis).
associations between primary brain tumors and Clinical signs/symptoms related to increased
several genetic syndromes have been recognized intracranial pressure were the most common at
[116]. In these tumor predisposition syndromes, presentation and were indicated as the reason for
individuals inherit a germline mutation in a seeking for medical advice in 31 patients (44.2%).
tumor suppressor gene. Tumors arise when the Hydrocephalus and macrocrania were reported in
remaining copy of the tumor suppressor is 17 patients (24.3%) each. It is relevant that 5
mutated or silenced, giving rise to cells with a patients (7.1%) on admission already had a
growth advantage. Because tumorigenesis reduced level of consciousness.
requires the accumulation of multiple mutations In our series of 94 patients, the predominant
in cells, these individuals are at an increased histotypes were astrocytomas (37%), embryonal
tumor risk because all cells carry an initial muta- tumors (24%), mixed neuronal-glial tumors
tion [125]. In addition, these syndromes could be (18%), and choroid plexus tumor (16%).
caused by de novo mutations (“primary”). Teratomas, ependymomas, and pineoblastomas
Therefore, it is crucial to clarify the clinical and were less common (4%, 1%, and 1% respec-
molecular mechanisms at the basis of these tively), which is not in line with most of the rel-
tumors [126]. evant medical literature on congenital CNS
tumors, where teratomas are generally referred to
as the most common histology.
49.6 Clinical Series The discrepancies in the histotype incidence
may depend on many factors, e.g., the number of
A retrospective evaluation was performed with cases, the age range considered, and the year of
the use of a query that investigated the elec- publication of the study. The scant medical litera-
tronic database where all the patients are ture on congenital tumors is insufficient to evalu-
recorded in our Unit of Neurosurgery. The query ate the exact frequency of each histotype.
asked to look for patients with the word “tumor” Moreover, the frequency of some histotypes is
in the diagnosis and that had a maximum “365” age-related. In particular, intracranial teratomas
days of life when first recorded and/or diag- are more often diagnosed during intrauterine
nosed in our center. During the past 20  years, development and in newborns; thus, studies that
under the care of the senior author (Lorenzo consider this age range could report a higher inci-
Genitori), 94 patients younger than 1 year of age dence of these tumors [127]. Furthermore, older
were admitted for a CNS tumor diagnosed when studies did not consider tumors that have been
they were younger than 365 days. Of these, we described in more recent years (i.e., AT/RT and
considered 83 patients, because 11 were admit- atypical choroid plexus papilloma). On the other
676 B. Spacca et al.

hand, some histologies are no longer included in With this surgical strategy, 31 patients were
the current WHO classification of CNS tumors operated for tumor resection more than once.
and therefore will disappear from the medical lit- Four patients, 2 diagnosed when younger than
erature to come, but are of course mentioned in 2 months of age and 2 diagnosed when older than
the studies published in the past (i.e., PNET). 2  months of age, were operated four times for
In our experience, low-grade and high-grade craniotomy and resection of the tumor.
lesions are equally distributed among astrocyto- One patient diagnosed at birth died during
mas. The most frequent low-grade astrocytoma is surgery. The patient had a massive bleeding fol-
pilocytic astrocytoma, whereas the most frequent lowed by cardiac arrest and on scans presented a
high-grade astrocytoma is glioblastoma. right-sided hemispheric lesion that on testing
Embryonal tumors are the second most frequent turned out to be a glioblastoma multiforme.
diagnosis in our series. We diagnosed PNETs Mean follow-up was 53  months (minimum
(PNET has been now removed from the diagnos- 1 month and maximum 18 years). At the last fol-
tic lexicon) and AT/RTs with equal frequency and low-up, 20 patients (28.6%) had died (11 in the
then medulloblastomas. Mixed neuronal-glial group diagnosed when younger than 2 months of
tumors in most cases were gangliogliomas. Our age [44%], 9 in the group diagnosed when older
series also includes two desmoplastic infantile than 2  months of age [20%]), 22 (31.4%) were
gangliogliomas, one with areas of melanotic dif- alive with evidence of disease (6  in the group
ferentiation and one with an unusually high diagnosed when younger than 2  months of age
mitotic index. In the group of choroid plexus [24%], 16  in the group diagnosed when older
tumors, the most frequently encountered lesions than 2  months of age [35.6%]), and 28 (40%)
were choroid plexus papillomas, followed by were alive with no evidence of disease on brain
atypical choroid plexus papilloma and carcinoma and spine MRI (8 in the group diagnosed when
(one case). We observed congenital teratomas in younger than 2 months of age [32%], 20 in the
a small number of cases, probably as a conse- group diagnosed when older than 2  months of
quence of the age range considered. All our tera- age [44.4%]). Relevant clinical data referring to
tomas affected infants less than 2 months of age the 70 patients included in the analysis are sum-
at diagnosis. Ependymomas and pineoblastomas marized in Tables 49.2 and 49.3.
were the rarest congenital tumors diagnosed in
our series.
Surgical treatment was offered to all the 49.7 Conclusions
patients to obtain a diagnosis, to reduce/remove
the mass, and to control the hydrocephalus. In the Children younger than 12  months with CNS
series of 70 patients analyzed, the first surgical tumors are still burdened with a high mortality. It
approach in 33 cases consisted of a procedure appears from our experience that there is a cutoff
aiming to deal with hydrocephalus and/or cystic of different mortality between strictly congenital
components of the tumor and/or to obtain a (diagnosis before 2 months of age) and children
biopsy of the tumor (11 patients). A craniotomy diagnosed when older than 2  months of age.
was offered directly to 37 patients. Several Treatment is challenging because of the higher
patients were treated surgically using a multistep risk associated with surgery, especially of bleed-
approach, aiming to control the intracranial pres- ing, and because adjuvant treatments are limited
sure first and then to remove the tumor. If neces- as they are associated with unacceptable side
sary, patients were offered multistep surgery to effects. Multistep surgery to control intracranial
remove the tumor. hypertension and to gradually resect the tumor
Table 49.2  Summary of essential clinical elements of 25 patients diagnosed with brain tumors when younger than 2 months in our series
AT/RT Choroid plexus tumors Glioneuronal HGG LGG Medulloblastomas PNET Mature teratomas Immature teratomas Others Total
Male 2 1 2 2 1 1 3 3 15
49  Central Nervous System Congenital Tumors

Female 1 1 2 3 1 2 10
Supratentorial 1 3 4 1 2 3 3 17
Subtentorial 3 1 1 2 7
Supra-subtentorial 1 1
Increased IIC 2 2 2 1 1 2 1 11
Seizures
AWD 2 1 3 6
NED 1 1 2 1 2 1 8
DOD 3 1 3 1 1 1 1 11
Total 3 1 3 4 – 1 3 1 4 5 25
677
 678

Table 49.3  Summary of essential clinical elements of 45 patients diagnosed with brain tumors when older than 2 months in our series
AT/RT Choroid plexus tumors Glioneuronal HGG LGG Medulloblastomas PNET Mature teratomas Immature teratomas Others Total
Male 1 5 3 4 12 1 2 4 32
Female 2 3 1 3 1 3 13
Supratentorial 1 7 4 5 11 1 6 35
Subtentorial 1 3 2 1 7
Supra-subtentorial 1 1 1 3
Increased IIC 1 5 1 2 6 2 2 1 20
AWD 2 2 7 1 4 16
NED 6 4 6 1 1 2 20
DOD 1 1 3 2 1 1 9
Total 1 7 6 5 15 2 2 7 45
B. Spacca et al.
49  Central Nervous System Congenital Tumors 679

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 Part X
Miscellaneous
 Vascular Anomalies in Children
50
Oumama El Ezzi and Anthony de Buys Roessingh

50.1 Introduction under sedation or anesthesia. They allow the iden-

tification of the nature and extent of the lesion.
Vascular anomalies are rare but frequently When the diagnosis remains uncertain, biopsy
encountered in the pediatric population. It is fun- and histopathological examination are necessary.
damental to distinguish between vascular tumors Most of these vascular anomalies do not
and vascular malformations. require treatment. But when treatment is needed,
Vascular tumors are proliferative lesions due it is complicated and requires a multidisciplinary
to an accelerated turnover of endothelial cells. approach. A proper diagnosis is the starting point
Vascular malformations are structural anomalies for an optimal treatment.
due to innate errors in the embryonic develop-
ment of blood vessels. They are generally classi-
fied according to their dominant abnormal vessel: 50.2 Vascular Tumors
venous (70%), lymphatic (15%), capillary (10%),
arteriovenous (5%), or combined malformations. The majority of vascular tumors are benign, and
We also commonly divide them into low- or 95% are infantile hemangioma.
high-flow malformation.
Thanks to the work of Mulliken and Glowacki
in 1982 [1] and the classification of the International 50.2.1 Hemangiomas
society for the study of vascular anomalies (ISSVA)
in 1996, [2] the understanding of vascular anoma- Hemangiomas are principally divided into two
lies has been considerably structured. The ISSVA groups: infantile hemangiomas and congenital
classification was updated at the April 2014 General hemangiomas. Other types are much less fre-
Assembly in Melbourne, Australia [3]. quent. They are proliferative vascular lesions due
The diagnosis is often determined by the medi- to an accelerated turnover of endothelial cells.
cal history and the clinical findings. In case of
uncertainty, or when treatment is considered, 50.2.1.1 Infantile Hemangioma (IH)
ultrasonography, Doppler flow imaging, and mag- IHs are the most common benign tumors in
netic resonance imaging (MRI) may be indicated, infancy, present in 10% of children under the age
of 1 year [1]. A high incidence has been reported
O. El Ezzi (*) · A. de Buys Roessingh in premature infants and girls [4].
Department of Pediatric Surgery, Centre Hospitalier Sixty percent are located in the cervicofacial
Universitaire Vaudois (CHUV), region, while the others arise on the trunk and the
Lausanne, Switzerland
e-mail: [email protected] extremities. They generally appear within a few

© Springer Nature Switzerland AG 2019 687

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8_50
688 O. El Ezzi and A. de Buys Roessingh

weeks after birth and then rapidly grow during hemangiomas of the face or scalp are at risk of
early infancy, up to the age of 1 year. This phase PHACES syndrome: posterior fossa anomalies,
is followed by a stable period of a few months hemangioma, arterial lesions, cardiac anomalies/
and then a spontaneous involution over several aortic coarctation, abnormalities of the eye and
years [5]. The involution may be complete or par- sternal clefting and/or supraumbilical raphe [7]
tial, and the residual skin may be atrophic and (Fig. 50.2). They need to undergo imaging of the
telangiectatic (Fig. 50.1). Eighty percent are soli- head, neck, and chest and ophthalmological and
tary lesions. However, multiple (more than five) skin examinations [8].
hemangiomas can be present and are likely to be IHs located in the lumbosacral, perineal, or
associated with visceral lesions, most often lower extremities may be part of the LUMBAR
hepatic and gastrointestinal. An abdominal ultra- syndrome: lower body IH and other skin
sound is then recommended in this case [6]. defects, urogenital anomalies and ulceration,
A more extensive medical evaluation is indi- myelopathy, bony deformities, anorectal mal-
cated in certain circumstances, namely, depend- formations, arterial anomalies, and renal anom-
ing on the location of the IH.  Several locations alies. They also require further investigation [9]
need particular attention. Infants who have large (Fig. 50.3).

Fig. 50.1  Infantile hemangioma: cutaneous, subcutaneous, Mixed

50  Vascular Anomalies in Children 689

Periorbital hemangiomas may cause visual Anal and vulvar hemangiomas may develop
impairment with amblyopia or anisometro- ulceration by irritation. In this case, alginate or
pia. An MRI is necessary to evaluate the hydrocolloids dressings with Eosin® 2% can be
extent of this kind of hemangioma [10] used for local treatment in addition to systemic
(Fig. 50.4). treatment.

Fig. 50.2  PHACE syndrome, frontal pachygyria and complex malformation of the willis circle

Fig. 50.3  LUMBAR syndrome: Sacral hemangioma, intradural lipoma, and marrow fixed in S2
690 O. El Ezzi and A. de Buys Roessingh

Fig. 50.4  Periorbital hemangioma

Hemangioma of the nasal tip, also called respiratory problems such as bronchiolitis or
“Cyrano hemangioma,” may be very large. It asthma were contraindications to commencing
can cause significant esthetic and functional treatment.
impairment such as ulceration, nasal obstruc- Clinical condition, weight, heart rate, and
tion, and disturbance of visual field. This blood pressure are checked at each visit and the
lesion can also interfere with the development dosage of propranolol adapted according to body
of the nose [11]. Their treatment is still con- weight every 8 weeks [12].
troversial, but late surgery is always necessary This treatment has proved to be safe and effec-
to remove the remaining scar tissue and repair tive, with very few side effects. The feared effects
the nasal tip. of propranolol are bradycardia, hypotension,
The vast majority of IHs do not require bronchospasm, and hypoglycemia [15].
treatment. Management during the prolifera- There are nowadays far fewer indications for
tion phase is reserved for hemangiomas which surgical treatment. It is reserved for some facial
may cause airway obstruction, functional or lesions and essentially for the sequelae of the
psychological problems, bleeding, and ulcer- involuted hemangiomas. Pulsed dye laser may
ation; this is the case in approximately 10% of reduce superficial discoloration of residual telan-
IHs [12]. giectasia and better control ulcerated hemangio-
Propranolol, a nonselective β-blocker, is the mas [16].
first-line treatment [13]. Its mechanism of action
includes vasoconstriction, angiogenesis inhibi- 50.2.1.2 Congenital Hemangioma (CH)
tion, and endothelial cell apoptosis [14]. The Congenital hemangiomas are distinct from the
most common dosage of propranolol is 1–3 mg/ infantile hemangiomas that appear after birth, in
kg/day, given in 2–3 doses up to the age of 1 year. that they are fully developed at birth. Depending
In our practice, before the initiation of proprano- on their evolution, they are divided into two cat-
lol treatment, blood glucose levels and renal egories: rapidly involuting congenital hemangio-
function were first monitored, and a cardiac ultra- mas (RICHs) and non-involuting congenital
sound and electrocardiogram (ECG) were per- hemangiomas (NICHs). RICHs involute com-
formed by pediatric cardiologists. Blood pressure pletely by the age of 14 months, whereas NICHs
and cardiac rhythm were checked every 30 min do not regress but rather continue to grow pro-
for 4 h after the first dose. The treatment is initi- gressively [17, 18]. RICHs present as a volumi-
ated with 1 mg/kg/day in the first 24 h and then nous, pink or purplish, infiltrating mass
2 mg/kg/day from the second day onward on an surrounded by a white halo. NICHs are usually
outpatient setting. Heart malformations and smaller [19, 20] (Fig.  50.5). RICHs can
50  Vascular Anomalies in Children 691

Fig. 50.5  Congenital hemangioma: RICH (a) and NICH (b)

692 O. El Ezzi and A. de Buys Roessingh

s­ometimes be associated with a moderate and 50.3 Vascular Malformations

transient coagulopathy. When associated with
acute cardiac failure, they may require emer- Vascular malformations affect 0.5% of the popu-
gency embolization to reduce arteriovenous lation. They result from errors in the embryonic
shunting [20]. development of blood vessels and are character-
Unlike IHs, neither RICHs nor NICHs ized by the lack of smooth muscle with mature
expressed glucose transporter-1 protein (GLUT-­ endothelial channels [24]. Malformations pres-
1), a protein involved in glucose transport [21]. ent at birth may not be clinically evident. They
grow proportionally to body growth with no
spontaneous involution. They are subclassified
50.2.2 Tufted Angioma/Kaposiform according to the vessels involved and the rate of
Hemangioendothelioma flow. Slow-­ flow lesions include capillary,
venous, and lymphatic malformations. Fast-flow
These seem to be two different expressions for the lesions are mainly represented by arteriovenous
same tumor spectrum. They present as a rapidly malformations. Combined anomalies may be
progressing tumor located in the skin or soft tis- present.
sue of the extremities and trunk. They derive from
vascular endothelial cells, are locally aggressive,
and have a great capacity of proliferation. They 50.3.1 Low-Flow Malformations
can be associated with the Kasabach-­Merritt phe-
nomenon characterized by important thrombocy- 50.3.1.1 Capillary Malformations
topenia, hemolytic anemia, and disseminated CMs are congenital vascular malformations of
intravascular coagulation that may result in life- the skin characterized by ectatic capillaries and
threatening hemorrhage [22, 23] (Fig. 50.6). postcapillary venules in the dermis. Also called
port-wine stains (PWS), they are present in 0.4%
of newborns, with no difference between sexes.
In 83% of cases, the lesion is present on the head
and neck [24]. They are caused by the dilation of
capillaries whose diameter ranges from 10 to
150 μm. They are present at birth, and their diam-
eter remains stable throughout life. Their color,
however, gradually changes from red to deep
purple. Over time, they can lead to hypertrophy
or nodule formation as they invade and deform
mucous membranes, the lips in particular.
Depending on their localization, PWS may
reveal the presence of certain syndromes, princi-
pally the Sturge-Weber syndrome (SWS). SWS
is characterized by cerebral nervous system and
ocular anomalies associated to a PWS in the area
of the ophthalmic (V1) and maxillary (V2) tri-
geminal nerve. It originates from a failure of
regression of a vascular plexus around the
cephalic portion of the neural tube which is des-
tined to become facial skin. This results in resid-
ual vascular tissue which forms angiomas of the
leptomeninges, face, and ipsilateral eye [25]
Fig. 50.6  Kaposiform hemangioendothelioma (Fig. 50.7).
50  Vascular Anomalies in Children 693

Fig. 50.7  Sturge-Weber Syndrome, PWS before and after Laser treatment

In some cases, the patient may develop neuro- stork’s bite. They often discolor spontane-
logical problems such as epilepsy, cognitive defi- ously within the first 1 or 2 years of life. They
cits, and mental retardation. Seizures first occur do not need to be investigated for underlying
during the first year of life in 75% of patients and malformations [27].
before the second year in 90%. MRI is the imag- The standard treatment for capillary malfor-
ing technique of choice for diagnosis of SWS, mation is the pulsed dye laser (PDL) that pro-
showing the leptomeningeal vascular malforma- duces selective photothermolysis on vessels at a
tion that confirms the diagnosis. It is generally chosen wavelength of 595  nm. This effect will
recommended to realize this exam by the age of shut the microcirculation in small blood vessels,
1 year, as structural changes are more evident at thus toning down the color of the angioma and
that time. Early diagnosis and management can making it less visible.
minimize subsequent seizure. Glaucoma is one of In standard clinical practice, laser treatment
the serious ocular manifestations in SWS, affect- must be repeated several times, with an interval
ing approximately 30–70% of patients. It is not of 6–8 weeks between each session, in order to
always present at birth. Patient should then be be effective and to cover the entire affected sur-
assessed by an ophthalmologist every 3 months face. The procedure may take place under gen-
for the first years of life and annually thereafter. eral anesthesia, and metal lenses must be worn
Choroidal hemangioma is present in 40–50% of to avoid the risk of retinal lesions. Several
patients with SWS [26]. ­parameters can be modified, such as the fluence
Capillary malformations of the forehead, (J/cm2) of the laser beam, the diameter (mm) of
eyelids, nose, and nuchal region are very the light bundle, the duration (ms) of the pulse,
common. They are usually defined as nevus the cooling of the skin, and the time interval
simplex, salmon patch, and angel kiss or between each session [27].
694 O. El Ezzi and A. de Buys Roessingh

Prognosis is thought to be improved if treat- cera, bone, and soft tissues. Their imaging assess-
ment is started by 6 months of age [20]. ment is essentially based on ultrasound and MRI.
In hypertrophic forms, generally affecting the LMs are classified according to their size as
lips and eyelid, debulking surgery, skin grafting microcystic (less than 2  cm) or macrocystic
of facial esthetic units, and reconstructive flaps (greater than 2 cm), but they can also be mixed
are sometimes indicated as the patient grows. (Fig. 50.9). On physical examination, macrocys-
Capillary telangiectasia is a less frequent tic lesions are solitary soft subcutaneous masses
anomaly affecting capillaries. It consists in per- with normal overlying skin. They are compress-
manent dilation of superficial dermal capillaries. ible, anechoic cysts with specific thin septations
It can be congenital, generally related to heredi- without Doppler flow. Microcystic lesions usu-
tary hemorrhagic telangiectasia (HHT) or Rendu-­ ally appear as vesicles filled with lymphatic fluid.
Osler-­Weber syndrome, an autosomal dominant They present as tiny cavities with a hyperechoic
vascular anomaly associating multiple mucocuta- and solid appearance [24] (Fig. 50.10).
neous and visceral vascular lesions. Telangiectasia The indication for treatment is based on the
looks the same as spider-like, red maculopapule, age of the patient, the site, size and type of the
usually of 1–4 mm in diameter. When acquired, lesion, and functional symptoms such as swell-
they can reveal a hepatocellular insufficiency. ing, bleeding, recurrent infection, dysphagia,
Finally, angiokeratomas are solitary hyper- respiratory distress, or cosmetic deformity.
keratotic papules or plaques with a verrucous sur- Severe forms may require treatment based on
face, ranging in color from deep red to blue-black. sclerotherapy or surgical resection.
PDL therapy is the treatment of choice. The Percutaneous sclerotherapy is considered as
Nd:YAG laser has been used successfully [28] the first-line treatment of LMs and has a greater
(Fig. 50.8). success with macrocystic LMs. Many agents are
used, for instance, doxycycline, bleomycin,
50.3.1.2 Lymphatic Malformations absolute ethanol, Betadine, OK-432 (lyophi-
Lymphatic malformations (LMs) are benign, lized Streptococcus), and alcoholic zein solu-
slow-flow vascular anomalies composed of tion. Under imaging guidance, the sclerosant
dilated lymphatic channels and cysts that affect agent is injected by direct approach after decom-
1/200–4000 live births, without significant differ- pression of the cyst. The aim is to induce an
ence between sexes. LMs may involve any part of inflammatory reaction in lymph-vessel endothe-
the body, but the majority (48–75%) is found lium, resulting in size reduction. These proce-
in the cervicofacial region. 20–42% are found on dures are generally performed under general
the extremities [29]. LMs can be revealed as a anesthesia. Complications include local extrav-
sudden mass with a bluish discoloration that asation, skin necrosis, cellulitis, and compres-
signs a bleeding event. They can infiltrate the vis- sion of nearby structures such as airways and
nerves [30, 31]. Sclerotherapy probably carries
less risk than surgery. A complete excision is
challenging because of the proximity to vital
structures.
Laser therapy and radiofrequency ablation can
be considered as other therapeutic modalities,
particularly in microcystic forms of LM.

50.3.1.3 Venous Malformations

Venous malformations (VMs) are the most
common congenital, dysplastic vascular mal-
formations [32]. Histologically, they are char-
Fig. 50.8  Angiokeratoma of the wrist acterized by ectatic and tortuous venous
50  Vascular Anomalies in Children 695

Fig. 50.9  Lymphatic malformation: macrocystic (a) and microcystic (b)

696 O. El Ezzi and A. de Buys Roessingh

Fig. 50.10  Lymphatic malformation, MRI aspect

channels delimited by normal endothelium with manoeuvers or depending on the position of the
decreased perivascular cell coverage [33]. patient. They do not have a palpable pulse or
The gene TIE2 has been implicated in VMs thrill. Like LMs, venous malformations can be
and cutaneomucosal venous malformations well circumscribed in the cutaneous or subcuta-
[34]. neous tissue or diffuse and infiltrating muscles,
Their prevalence is about 1% with an inci- bones, and intra-articular cavities, resulting in
dence of 1 in 10,000. More than 40% of lesions functional impairment and cosmetic disturbance
are found on the head and neck, 40% on the (Fig. 50.11).
extremities, and 20% on the trunk [35]. Although VMs are generally asymptomatic,
Sometimes present at birth, MVs usually grow complications such as pain, inflammation, local-
discreetly during childhood and may expand rap- ized intravascular coagulopathy, and recurrent
idly with puberty under the influence of hor- thrombotic episodes may occur.
mones. Clinically, they appear as bluish, soft, Temporo-masseterian MVs may have exten-
depressible tumors. They refill during Valsalva sion to the jaw, the buccal floor, and the
50  Vascular Anomalies in Children 697

Fig. 50.11  Venous malformation

pharyngo-­laryngeal region leading to respiratory MVs can be isolated or be part of syndromes

or swallowing disorders. Labial and jugal MVs such as the Blue rubber bleb naevus (BRBN)
can be responsible of disorder of the dental syndrome, characterized by the presence of mul-
articulation. tiple cutaneous and visceral venous malforma-
The imaging investigation of choice is US tions, particularly in the digestive tract. The
Doppler that shows slow-flow compressible cutaneous lesions appear as bluish, protruding
lesion without flow voids and occasionally masses, disseminated all over the teguments
thrombus or phlebolith [36, 37]. especially on the palm and sole and increasing
Treatment options include compression and with age. Gastrointestinal tract malformations
pain management. Compression garments can are a source of chronic bleeding and hemorrhage,
help to decrease pain and swelling especially in thus dominating the prognosis. Surgical treat-
extremities [20]. ment of these lesions by endoscopic fulguration
For most lesions, no further intervention is or intestinal resection may be required in some
indicated. However, if necessary, percutaneous cases.
sclerotherapy or surgery can be performed. As in Management is often multidisciplinary and
LMs, sclerotherapy consists in puncturing the can include medical, interventional radiological,
malformation and injecting the sclerosing agent and surgical treatment [39, 40].
into the cavities under radiographic control. Rarely, venous malformations present as glo-
Sclerotherapy is commonly used as primary ther- mangiomas: dark and tender venous nodules
apy or to shrink VMs before surgery. The surgical characterized histologically by the presence of
approach is designed to treat well-defined lesions smooth muscle-like glomus cells.
of small dimension and, at a lower level of effec- Finally, although it is not a venous malforma-
tiveness, to debulk diffuse ones and minimize tion in the true sense of the term, Sinus pericranii
aesthetic sequelae. (SP) is an entity that must be known. SP is a rare
Upper aerodigestive tract venous malforma- congenital or acquired disorder characterized by
tions can be treated by 980-nm diode endovascu- a communication between an extracranial vein
lar laser that greatly reduces dysphagia and sleep and an intracranial venous sinus, through diploic
apnea symptoms [38]. veins. It presents as a subcutaneous mass which
698 O. El Ezzi and A. de Buys Roessingh

changes with the head’s position or a blue or red AVMs are the most challenging lesions to
macular discoloration or alopecia localized on manage and have high rates of morbidity and
the scalp close to the midline. MRI is the imaging recurrence. No single modality of treatment is
technique of choice; it shows dilated vascular effective, and multimodal therapy is often neces-
structures communicating through the cranial sary. The aim of the treatment is to obliterate the
vault. SP may have potentially serious complica- nidus. The present management of AVMs is
tions, including thrombosis and massive hemor- based on superselective embolization of the feed-
rhage. Treatment is proposed for cosmetic or ing arteries and nidus, followed, if necessary, by
prophylactic reasons. Conventional surgery, a surgical excision of the AVM.  Embolization
endovascular therapy, and percutaneous injection alone may not be sufficient and may lead to an
have been described [41]. early revascularization, making the vascular sup-
ply more complex by stimulating angiogenesis
and collateralization. It is often reserved for non-­
50.3.2 Fast-Flow Malformations operable AVMs in order to palliate symptoms
(Fig.  50.12). But it may also be used preopera-
50.3.2.1 Arteriovenous tively to delineate the lesion in order to reduce
Malformations (AVMs) intraoperative bleeding [46, 47]. The surgical
AVMs are congenital malformations and result approach entails the risk of life-threatening
from an abnormal and direct connection between bleeding and leads to a high probability of recur-
arteries and veins, bypassing capillary beds. rence if partial. It is reserved for very well-­
Vessels become dilated, veins become arterial- defined lesions.
ized, and pressure remains high. AVMs are char-
acterized by a nidus and a complex network of
feeding arteries and draining veins [42]. They 50.3.3 Combined Malformations
occur in 0.1% of the general population. Clinically,
they present as warm cutaneous or subcutaneous There are several patients who present a mixed
tumors that may resemble capillary malforma- vessel-type malformation. These patients often
tions with a possible palpable thrill. They may have significant morbidity, and their management
cause pain, ulceration, or hemorrhage. is obviously more complicated.
AVMs are present at birth, remain dormant
during childhood, and may become symptomatic 50.3.3.1 Klippel-Trenaunay
at puberty or after a direct traumatism that stimu- Syndrome (KTS)
lates their expansion [43]. They are progressive, KTS is characterized by the presence of a cap-
invasive, and destructive. Their clinical progres- illary malformation associated with bone and/
sion is illustrated by the Schobinger classification or soft tissue overgrowth and superficial or
[44] (Table 50.1). deep venous system anomalies of the affected
The diagnosis is confirmed by Doppler ultra- limb. Bleeding angiokeratomas can appear on
sound, MRI, and arteriography. They show a the skin area affected by the capillary malfor-
high-flow malformation with AV shunting and mation. An intrapelvic extension with the pres-
arterialized veins [45]. ence of ­submucosal venous varicosities leading
to rectal bleeding is extremely rare [25]
Table 50.1  Schobinger classification of arteriovenous
(Fig. 50.13).
malformation
Stage Features
50.3.3.2 Parkes Weber Syndrome
I Quiescence Skin discoloration, pink/blue (PWS)
and warm PWS associates large cutaneous capillary mal-
II Expansion Audible pulsation, bruit, thrill formation, underlying arteriovenous shunting,
III Destruction Ulceration, bleeding, infection and bony and soft tissues hypertrophy. It is
IV Compensation Congestive cardiac failure caused by mutations in RASA1, mapped to
50  Vascular Anomalies in Children 699

Fig. 50.12  Arteriovenous malformation, nidus on arteriography

Fig. 50.13  Klippel-Trenaunay Syndrome

700 O. El Ezzi and A. de Buys Roessingh

Fig. 50.14  Parkes Weber Syndrome

5q14.3 [48, 49] (Fig.  50.14). Limb enlarge- Table 50.2  Simplified ISSVA classification of vascular
ment may be significant and lead to an early anomalies
asymmetry. Orthopedic follow-up is Vascular tumors
recommended. Infantile hemangioma
Congenital hemangioma
 Rapidly involuting congenital hemangiomas
50.3.3.3 W  yburn Mason Syndrome  Non-involuting congenital hemangiomas
(Syndrome de Bonnet Kaposiform hemangioendothelioma
Dechaume Blanc) Others
It is a rare condition characterized by arteriove- Vascular malformations
nous malformations in the central nervous sys- Slow-flow vascular malformations
tem and the retina and an upper facial port-wine  Venous malformations
stain.  Lymphatic malformations
 Capillary malformations
The syndrome can cause seizures, subarach-
Fast-flow vascular malformation
noid hemorrhage, and focal neurologic deficits.  Arteriovenous malformations/fistulas
Present at birth, it generally worsens with time. Combined complex vascular malformations
Treatment is symptomatic and supportive [28]. ISSVA International Society for the Study of Vascular
Anomalies
50.3.3.4 Cobb Syndrome
Cobb syndrome is a rare metameric disorder,
characterized by a spinal vascular abnormality in 50.4 Conclusion
association with vascular skin lesion of the same
metamer. Vascular anomalies are a rare disease that presents
Patients can remain asymptomatic for a long with a large spectrum of clinical symptoms and a
time, but the evolutive risk is essentially neuro- different biological behavior. They can lead to seri-
logical secondary to an acute medullary ous functional disorders and cosmetic impairment.
bleeding. It is essential to distinguish between vascular
Radiological exploration, especially medul- tumors and malformations.
lary MRI, must be realized each time a meta- The ISSVA classification is a valuable tool
meric angioma of the trunk is diagnosed. that offers a better understanding of this ­pathology
Current treatment is based on embolization and/ and allows the practice of a common scientific
or surgery [50]. language (Table 50.2).
50  Vascular Anomalies in Children 701

The keystone of a good management of vascu- h­emangiomas in infants: contribution of MRI.  J

Radiol. 2004;85:2019–28.
lar anomalies is a precise diagnosis, adequate 11. Eivazi B, Cremer HJ, Mangold C, Teymoortash A,
investigation, and appropriate treatment. Wiegand S, Werner JA. Hemangiomas of the nasal tip:
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 Index

A management, 11
Abdominal pain, 210, 240, 274, 294, 410 neurotoxicity, 7
Abdominal tube vaginostomy, 597, 598 pharmacology, 11
Abdominal wall cellulitis, 303–304 regional, 20
Abdomino-PSARP)/abdomino-perineal pull-through Anesthesiologist, 10
(APPT), 347 Anorectal malformations (ARMs)
Acquired chylothorax, 157 anal dilatation programme, 332, 333
Acute tongue swelling, 106 associated anomalies, 331
Adrenal gland classification systems for, 326–327
left, 476 clinical examination, 329–331
primary tumour, 476 clinical features of, 327
right, 476 embryology
Advanced Trauma Life Support (ATLS), 12 abnormal cloacal development, 323, 324
Agenesis, 124 normal cloacal development, 323, 324
AIEOP Wilms Tumor Working Group study, 487 recanalization abnormalities of anal orifice, 324
Airway branching pattern, 167–168 etiologic factors
Airway problems, 14 anal canal anatomy, 325–326
Albumin, 10 anorectal malformations, pathologic anatomy in,
“A-lines,” 154 326
ALK mutation, 472 associated anomalies, 325
Allometric equation, 20 on genetic and environmental influences,
Alpha-2A-interferon, 480 324–325
Alpha-fetoprotein (α-FP), 479–481, 508, 671 pelvic floor and anal canal anatomy, 325
Altman classification of SCT, 500–503 incidence, 323
Alveolar bone graft, 88–89 long-term bowel function, 337
American College of Chest Physicians (ACCP), 13 mild (see (Mild ARMs))
Amniocentesis, 75 mortality in, 323
Amnioinfusion, 583 operative management, 323
Amyloidosis, 104 outcomes, 336–337
Anaplastic astrocytomas, 663, 672 severe (see (Severe ARMs))
Anatomic hepatectomy, 482–483 Antenatal hydronephrosis (ANH), 516
Anderson–Hynes pyeloplasty, 521–522 Anterior abdominal wall defects (AAWD), 213
Anemia, 210 Anterior hernia, 177, 178
Anesthesia Anterior-posterior diameter (APD), 515–517, 534–536
inguinal hernia Anterior sagittal anorectoplasty (ASARP), 332–333
airway management, 353 Anti-reflux surgery, 215
clonidine, 353 Anti-siphoning devices, 625
intranasal administration of drugs, 353–354 APD, (see Anterior-posterior diameter (APD))
intravenous anesthetics, 353 Apgar score, 152
midazolam, 353 Aplasia cutis congenita, 636
and pre-anesthetic medication, 352–353 Apoptosis, 19
regional, 353 Aqueductal agenesia, 617
risks in premature infants, 354 Aqueductal forking, 617
sevoflurane, 353 Aqueductal occlusion, 617

© Springer Nature Switzerland AG 2019 703

M. Lima, O. Reinberg (eds.), Neonatal Surgery, https://doi.org/10.1007/978-3-319-93534-8
704 Index

Aqueductal stenosis Kelly procedure, 449

anatomy, 616 Mitchell’s technique, 448–449
classification Ransley’s technique, 447–448
chemical, 617 ventral approach of corpora cavernosa, 447
developmental, 616 Baby’s feeding difficulties, 75–76
developmental stenosis, 617 Barium meal study, 214, 228, 235
genetic, 616 Barrett’s esophagus, 199
infectious, 617 Basal encephaloceles, 634–636
malformative, 616–617 “Bec-de-lièvre,” 79
neoplastic, 617 Beckwith-Wiedemann syndrome (BWS), 104, 486
vascular, 617 BEEC, (see Bladder exstrophy-epispadias complex
diagnosis (BEEC))
fetal, 617 Benign biliary diseases, 409
postnatal, 617–618 Beta-human chorionic gonadotropin (β-HCG), 671
embryology, 616 Betamethasone, 170
Arachnoid cyst Bifid cost, 124
convexity cyst, 619 Bifid penis, 610
interhemispheric cyst, 619 Bifid scrotum, 611
marsupialization, 623–624 Bifid sternum, 130–132
posterior fossa cyst, 619–620 Bilateral hydronephrosis, 521, 558
septum pellucidum, velum interpositum and Bilateral labio-maxillary-palatal cleft, 74
quadrigeminal cyst, 619 Biliary atresia (BA), 38
spinal cyst, 620 adjuvant therapy for
suprasellar cyst, 619 antiviral treatment for CMV IgM + ve BA, 395
sylvian cyst, 618–619 corticosteroids, 394
Arches, 112 postoperative therapy after KPE, 393–394
ARMs, (see Anorectal malformations (ARMs)) ursodeoxycholic acid, 394–395
Arterial catheterization, 13–14 aetiological pathways, 388, 389
Arteriovenous malformations (AVMs) cellular kinetics and inflammation, 390, 391
management of, 698 characteristics, 387
nidus on arteriography, 698, 699 clinical features, 390
Schobinger classification of, 698 cystic, 388, 389
Artificial urinary sphincter, 453 cytomegalovirus-associated, 388–390
Ascites, 396 developmental, 388
Associazione Italiana Ematologia Oncologia Pediatrica— diagnostic assessment
Italian Association for Pediatric Hematology abdominal ultrasound, 391
and Oncology (AIEOP) study, 485, 653 direct cholangiography, 392
Astrocytomas, 671 liver biochemistry, 390–391
anaplastic, 663, 672 radioisotope hepatobiliary imaging, 391–392
glioblastomas, 663, 664 epidemiology, 387
pilocytic, 663 extrahepatic bile duct development, 388–389
SEGAs, 663, 664 incidence, 387
AST-to-platelet ratio index (APRi), 391 isolated, 388, 390
Asymmetry index (AI), 121 Japanese classification, 387–388
Atretic encephaloceles, 636 management
Atypical teratoid/rhabdoid tumors (AT/RT), 666, 673, maximally invasive surgery, 392, 393
676 minimally invasive surgery, 392–393
Audiometry, 86–87 primary liver transplant, 392
Autologous stem cell rescue (ASCR), 673 origins of, 397
AVMs, (see Arteriovenous malformations (AVMs)) outcomes, 396–397
population screening programmes for, 392
postoperative complications, 395
B ascites, 396
BA, (see Biliary atresia (BA)) cholangitis, 395
Baby boy hepatopulmonary syndrome, 396
classical bladder exstrophy, 442 portal hypertension and oesophageal varices,
epispadiac genital tubercle and urethra surgery, 395–396
447–449 syndromic, 388
Cantwell-Ransley procedure, 449 Biliary atresia splenic malformation (BASM) syndrome,
derotation of corpora cavernosa, 448 388–389
Index 705

Birth defects, congenital, 2 Brachycefphaly, 632

Bladder and bowel dysfunction (BBD), 541 Brain damage, 211
Bladder exstrophy-epispadias complex (BEEC), 455 Brain growth spurt period, 19
anatomical features Branchial remnants, 112
bony anomalies, 442 Breast hypoplasia/aplasia, 128
classical bladder exstrophy in boy, 442 British National Confidential Enquiry into Perioperative
classical bladder exstrophy in girl, 442, 443 Deaths (NCEPOD), 1, 2
cloacal exstrophy, 443 Bronchial atresia, 29
female epispadias, 445 Bronchial reactivity, 210
incontinent (posterior) male epispadias, 444 Bronchogenic cysts, 144
pelvic ring in exstrophy, 445 Bronchogenic duplication cysts, 280, 284
split symphysis variants, 442 Bronchopulmonary dysplasia (BPD), 117–118
classic stepwise approach, 444 Bronchoscopy, 14, 191
closure of bladder plate, 444–447 flexible, 14–15
CPRE, 453–454 rigid, 15–16
delimitation process, 441 Bulking agents, 541
diagnosis, 443–444
epispadiac genital tubercle and urethra surgery in boy
Cantwell-Ransley procedure, 449 C
derotation of corpora cavernosa, 448 CA, (see Choanal atresia (CA))
Kelly procedure, 449 Calretinin, 315
Mitchell’s technique, 448–449 Canadian Congenital Diaphragmatic Hernia
Ransley’s technique, 447–448 Collaborative guidelines, 180–181
ventral approach of corpora cavernosa, 447 Cantwell-Ransley procedure, 449
female epispadias Capillary malformations (CMs), 692–694
surgical landmarks, 450 Capillary telangiectasia, 694
urethroplasty, 451 Cardiac/renal anomalies, 129
incidence, 442 Caroli’s disease, (see Congenital biliary dilatation)
incontinence surgery Catheterization
artificial urinary sphincter, 453 arterial, 13–14
bladder neck closure, 453 central
cervicocystoplasty, 452–453 central-inserted (CICC), 13
cloacal exstrophy, 453 peripherally inserted (PICC), 12–13
complementary procedures, 453 indication, 12
introitoplasty, 453 infection risk-complications, 13
peri-cervical injection, 451 intraosseous, 12
phalloplasty, 453 peripheral, 12–13
umbilicoplasty, 453 umbilical, 12
management at birth, 444 Caudal lipoma, 642–643
objectives, 444 CDH, (see Congenital diaphragmatic hernia (CDH))
outcomes Cecoureterocele, 556
cosmetic, 454 Central Brain Tumor Registry of the United States
dryness, 454–455 (CBTRUS), 653
sexual and psychological dysfunctions, 455 Central hernia, 177, 178
recurrence risk, 442 Central-inserted central catheter (CICC), 13
sex ratio, 442 Centralization, benefits of, 2
zip down process, 441 Central nervous system (CNS) congenital tumors
Bladder outlet obstruction (BOO), 556, 569, 570 clinical considerations, 657, 662
“B-lines,” 154 choroid plexus carcinoma, 658
Blocksom technique, 464 consciousness, reduced level of, 658, 659
Blood volume, 10 hydrocephalus, 659–661
Blue rubber bleb naevus (BRBN), 697 increasing head circumference, 658
Bochdalek’s hernia, (see Posterolateral hernia) intracranial hypertension, 658
Boix-Ochoa’s operations, 216 macrocrania, 658, 660, 661
BOO, (see Bladder outlet obstruction (BOO)) multiple spinal metastasis, 660
Borel-Maisonny score, 87 neuronal plasticity, 658
Bowel atresia and stenosis skull plasticity and neural immaturity/plasticity,
incidence, 243 659
management, 243 supratentorial location, 659
prenatal diagnosis, 243 clinical series, 675–678
706 Index

Central nervous system (continued) myelomeningocele, 647–649

definition, 653, 654 prenatal hydrocephalus, 647
epidemiology of, 653 hydrocephalus and CSF-related disturbances
histology aqueductal stenosis, 615–618
astrocytomas, 662–664 neuroendoscopy, 620–625
choroid plexus tumors, 664–665 new minimally invasive surgical techniques,
differential diagnosis, 667 treatment of craniosynostosis, 631–633
embryonal tumors, 665–666 shunt complications
ependymal tumors, 667 infection, 628
glioneuronal tumors, 666–667 mechanical problems, 628
teratoma, 662 obstruction, 627–628
IACR, 654 postoperative period, 628
incidence of, 654 preoperative period, 628
medical treatment, 671–675 shunt procedure, 628
risk factors shunt surgery techniques
genetic syndromes, 655, 656 external ventricular drainage, 626
high birth weight, 657 procedure, 626–627
ionizing radiation, 657 ventriculoatrial shunt, 627
neurofibromatosis (NF) type 1 and type 2, 655 ventriculoperitoneal shunt, 626
nitrite intake, high level of, 657 spinal dethetering technique
TCS, 654 adhesions, bands, thick filum and
tuberous sclerosis complex, 654 diastematomyelia, 644–645
surgical treatment dermal sinus, 645–646
anesthesia and surgical position, 668 lipomas, 641–644
cerebral collapse, 669, 670 surgical procedures, 615, 616
instrumentation, 669–671 Cerebrocostomandibular syndrome, 127
risk of bleeding, 668–669 Cerebrospinal fluid (CSF)
Central nervous system (CNS) malformations hydrocephalus and CSF-related disturbances
arachnoid cyst aqueductal stenosis, 615–618
convexity cyst, 619 neuroendoscopy, 620–625
interhemispheric cyst, 619 shunt valves
posterior fossa cyst, 619–620 anti-siphoning devices, 625
septum pellucidum, velum interpositum and differential pressure presettled valves, 625
quadrigeminal cyst, 619 flow-regulating valves, 626
spinal cyst, 620 programmable valves, 625–626
suprasellar cyst, 619 Cervical ectopia cordis, 129
sylvian cyst, 618–619 Cervical swellings, 111–112
cephaloceles excision Cervical teratoma, 508–509
atretic encephaloceles, 636 Cervicocystoplasty, 452–453
basal encephaloceles, 634–636 CF, (see Cystic fibrosis (CF))
congenital defects of the scalp, 636 CFHC, (see Congenital hepatic foregut cysts (CFHC))
cranial vault cephaloceles, 634 CHARGE syndrome, 67, 68
fronto-ethmoidal/sincipital encephaloceles, 634 Chemotherapy, 471, 475, 482, 487
intrateutoria cephaloceles, 633–634 Chest neonatal imaging, 25
Chiari type I anomaly computed tomography, 28–30
posterior fossa decompression for, 637–639 magnetic resonance imaging, 27–28
surgical pathology, 636–637 radiography, 26–27
craniofacial dysmorphism, craniofacial repair for, ultrasonography, 27
628–629 Chest wall anomalies, 128
cranial vault remodeling, 630 Chest wall malformations (CWMs), 117
craniectomy and suturectomy, 629–630 classification, 118
fronto-orbital advancement and remodeling, clavicular malformations, 134
630–632 combined malformations, 134
preoperative assessment, 629 costal anomalies
CSF shunt valves classification, 123
anti-siphoning devices, 625 complex, 123–125
differential pressure presettled valves, 625 double malformations, 125
flow-regulating valves, 626 simple, 123–124
programmable valves, 625–626 syndromic, 125–127
fetal surgery, 646 imaging studies, 119
Index 707

intermamillary distance, 119 treacher collins syndrome, 68

pectus carinatum, 122 Choanal atresia/coloboma, anal, renal, gastrointestinal
asymmetric, 122 and ear/hearing (CHARGE), 325
classification, 122–23 Choledochal cysts, 38–39, 60, 62
clinical presentation, 123 diagnosis, 410
etiopathogenesis, 122 follow-up, 412
imaging, 123 giant, 410
management, 123 laparoscopic surgery, 412
pectus excavatum long-term complication, 410–411
characteristics, 119 with pancreaticobiliary maljunction, 412
clinical evaluation, 121 in pediatric population, 410
etiopathogenesis, 119–120 postoperative complication, 411
imaging, 121 symptoms, 410
management, 121 Todani classification, 410, 411
pathophysiology, 120 types, 411
Poland syndrome Choroidal hemangioma, 693
clinical presentation and assessment, 128–129 Choroid plexus carcinoma, 658
diagnostic criterion, 127 Choroid plexus tumors, 664–665
etiopathogenesis, 127 Chromosomal disorders, 75
scapular malformations, 134 Chyle, 157
spinal deformities, 134–135 Chylothorax, 198
Sternal anomalies characteristics, 156
cervical ectopia cordis, 129–130 clinical manifestations, 156–158
sternal cleft, 130–132 congenital, 156
thoracic ectopia cordis, 129 diagnosis, 158–159
thoracoabdominal ectopia cordis, 129 embryology and anatomy, 156–157
thoracic circumference, 118 etiology, 157
thoracic index, 119 physiopathology, 157
Chest X-ray, 26, 134 prenatal management, 161–162
congenital diaphragmatic hernia, 179 therapy
congenital pulmonary airway malformations, 171 chest tube insertion, 159
mediastinal masses, 142 medium-chain triglyceride, 159
pneumothorax, 153 nutritional support, 159
Chiari type I anomaly pharmacological, 160
posterior fossa decompression for, 637–639 pleurodesis, 161
surgical pathology, 636–637 pleuroperitoneal shunt, 161
Chiari type II anomaly, 641, 648, 649 povidone-iodine, 161
Children’s Cancer Group (CCG), 674 somatostatin/octreotide treatment, 160
Children’s Oncology Group (COG), 481, 487 supportive and conservative methods, 159
Choanal atresia (CA) surgical, 159
associated comorbidities, 68 total parenteral nutrition, 159
bony frame, 67 traditional surgical technique, 160
characteristics, 67 Cinefluoroscopy, 87
CHARGE syndrome, 68 Cisplatin, 481
clinical presentation, 68 Clavicular malformations, 134
diagnosis, 68–69 Cleft palate (CP)
embryological models, 67 antenatal diagnosis, 75
heterogeneity, 67 baby’s feeding difficulties, 75–76
incidence, 67 embryology, epidemiology, and genetics, 73–75.
management See also Primary surgery; Secondary surgery
definitive, 69 Clonidine, 353
endoscopic repair, 70 Clostridium difficile, 313, 317
McGovern nipple, 69 Codeine, 19
primary corrective surgery, 71 Colloid molecules, 10
puncture, 69 Colonic atresia and stenosis, 33
soft silicon tubes, 70 associated malformations, 260
tracheotomy, 69 classification,259
transpalatal approach, 69 diagnosis, 259
urethral bougies, 71 incidence, 259
nasobuccal membrane, 67 and neonatal X-rays, 259
708 Index

prenatal diagnosis, 259 NICHs, 690–692

treatment, 260 RICHs, 690–692
Colonic duplication cysts, 280–281, 286, 287 Congenital hepatic cysts
Coloplasty, 346–347 ciliated hepatic foregut cyst
Combined malformations, 134 antenatally diagnosed, 405
“Comet-tail artifacts,” 154 characteristics, 405
Common bile duct (CBD), 387 clinical presentation, 406
Common hepatic duct (CHD), 387 histological feature of, 405–406
Complete androgen insensitivity (CAIS), 603 prognosis, 406
Complete primary repair of exstrophy (CPRE), 453–454 treatment, 406
Complex costal anomalies, 125 incidence, 401
Computed tomography (CT) intrahepatic choledochal malformation, 406
chest neonatal imaging, 28–30 mesenchymal hamartoma
choanal atresia, 68–69 aetiology, 403–404
congenital pulmonary airway malformations, 172 clinical features, 404
gastrointestinal neonatal imaging, 40 management, 404–405
liver cysts, 406 prognosis, 405
malignant change, 396 simple hepatic cysts
malrotation, 379 aetiology, 402
Meckel diverticulum, 435, 436 antenatal detection with imaging, 402, 406–407
mediastinal masses, 142–143 clinical presentation, 402
urachal abnormality, 438 histological features, 401
urogenital neonatal imaging, 46 management, 402–403
Computer-assisted neuroendoscopy, 624 prognosis, 403
Congenital adrenal hyperplasia (CAH), 602 Congenital hepatic foregut cysts (CFHC)
Congenital anomalies of the kidney and urinary tract antenatally diagnosed, 405
(CAKUT), 518 characteristics, 405
Congenital biliary dilatation, 412 clinical presentation, 406
characteristics, 409 histological feature of, 405–406
complication, 409 prognosis, 406
conservative treatment, 409–410 treatment, 406
diagnosis, 409 Congenital hypothyroidism (CH), 104–105
differential diagnosis, 409 Congenital lobar overinflation/congenital lobar
types, 409 emphysema, 28
Congenital central hypoventilation syndrome (CCHS), 472 Congenital megacolon, (see Hirschsprung’s disease (HSCR))
Congenital cervical teratoma, 508 Congenital obstructing posterior urethral membrane
Congenital chylothorax, 157 (COPUM), 579
Congenital CNS tumors, (see Central nervous system Congenital pouch colon (CPC)
(CNS) congenital tumors) aetiological factors, 342
Congenital diaphragmatic hernia (CDH), 2, 8 anatomical criteria, 339
antenatal management, 180 associated anomalies, 343–344
birth prevalence, 177 classification, 340
classification, 177 clinical examination, 343
complications, 183 clinical presentation, 343
diagnosis and clinical features complete, 340
antenatal, 179 cystourethroscopic examination, 343
misdiagnosed, 180 definition, 339
neonatal period, 179 diagnosis, 343
embryology, 177–178 distribution, 339
etiology, 177 embryopathogenesis, 342
gastroesophageal reflux disease, 212–213 examination under anaesthesia, 343
natural history, 177 follow-up examination, 347
outcome, 183 future perspectives, 348
postnatal management, 180 histopathology, 342–343
repair model, 59 incidence, 339
surgical repair incomplete, 340–342
open transabdominal repair, 181–182 management
surgical timing, 180–181 algorithm, 345
video-assisted thoracoscopic repair, 183 complete pouch, 345–347
Congenital hemangioma (CH) complications, 347
Index 709

incomplete pouch, 345 Currarino-Silverman syndrome, 123

preoperative resuscitation, 345 Cutoff sign, 316
outcome and prognosis, 347–348 CWMs, (see Chest wall malformations (CWMs))
Congenital pulmonary airway malformations (CPAM), Cyrano hemangioma, 690
27–29, 167 Cystic biliary atresia, 388, 389
genes’ involvement, 168 Cystic fibrosis (CF)
histopathology, 167 CFTR gene, 265, 267
lung development, 167–168 complications, 274
postnatal management gastroesophageal reflux disease, 274
at birth, 171–172 incidence, 265
treatment, 172–174 nutrition, 273–274
prenatal diagnosis, 169 post-operative management, 273
MRI, 170 prognosis, 275
neonatal respiratory distress, 169 respiratory support, 274
parent counseling, 170–171 testing method, 267
signs of fetal distress, 170 Cystic intestinal duplications, 294
Congenital pyloric atresia (CPA), 233 Cystosonography (CSG), 540
diagnosis, 234 Cytomegalovirus-associated BA, 388–390
etiology, 233
history and physical examination, 234
management, 234 D
operative technique, 234–235 Dandy–Walker complex, 619
pathology, 233 Deformational PRS, 76
prognosis, 235 Denys-Drash syndrome, 485
typical presentation, 234 Dermal sinus, 645–646
Congenital scrotal agenesis (CSA), 610, 611 Desmoplastic infantile astrocytomas/gangliogliomas
Consensus Statement on Management of Intersex (DIAs/DIGs), 666
Disorders, 601 Dextranomer/hyaluronic acid (Dx/HA), 541
Continuous positive airway pressure (CPAP), 77 Diaphragmatic eventration hernia, 177, 178
Contralateral patent processus vaginalis (CPPV), 351, Diaphragmatic hernia, (see Congenital diaphragmatic
357, 361, 363 hernia (CDH))
Contrast enema (CE) Diastematomyelia, 644–645
and anal manometry, 317 Diethylenetriamine penta-acetic acid (DTPA), 557
Hirschsprung disease, 316 Differential renal function (DRF), 520, 521
malrotation, 379 Different sexual development (DSD)
Convexity cyst, 619 definition, 601
Corticosteroids, 394 gonadal treatment, 602–604
Costal anomalies G1, 604
classification, 123–124 G2, 604
complex, 123–125 G3, 605
double malformations, 124 presentation and diagnosis, 601–602
simple, 123–124 surgeon, role of, 602
syndromic, 125–127 Diffuse hyperplastic perilobar nephroblastomatosis, 486
Costal fusion, 124, 125 Dimercaptosuccinic acid (DMSA) renal scan
Costal hypoplasia, 123 MCDK, 529
CP, (see Cleft palate (CP)) VUR, 538–540
CPA, (see Congenital pyloric atresia (CPA)) Distal intestinal obstruction syndrome (DIOS), 274
CPAM, (see Congenital pulmonary airway Distal pouch elongation, 197
malformations (CPAM)) Diuretic renal scintigraphy, 519, 520
CPC, (see Congenital pouch colon (CPC)) Doppler sonography, 41
CPPV, (see Contralateral patent processus vaginalis Doppler ultrasound, 304–305
(CPPV)) gastroschisis and omphalocele, 418
Cranial vault cephaloceles, 634 necrotizing enterocolitis
Cranial vault remodeling, 630 inflamed oedematous bowel, 300, 301
Craniectomy, 629–630 ischaemic necrosis and perforation, 300–303
Craniopharyngiomas, 666, 667, 671 Y-sign perfusion, 300, 302
CSF, (see Cerebrospinal fluid (CSF)) Double bubble sign, 245–246
CTNNB1 mutations, 667 Double costal anomalies, 125
CT scan, (see Computed tomography (CT)) Double-lumen Replogle tube, 191
Cupid’s bow, 80, 81 Double-wall sign, 281
710 Index

Down’s syndrome, 103–104, 243, 244, 247, 251, 260, for pineal region, 621
329 role of, 621
Doxorubicin, 481 Endoscopy-biopsy, 214
Drain track, 155 Enteric duplication cysts, 294
DSD, (see Different sexual development (DSD)) Esophageal atresia (EA), 31, 247
Dumbbell UC, 556, 557 classification, 188–190
Duodenal atresia and stenosis clinical and syndromic associations, 188
associated malformations, 247 complications
complications anastomotic leak, 198
anastomotic leaks, 251–252 chylothorax, 198
death after open surgery, 250–251 dysphagia and esophageal dysmotility, 199
postoperative, 250–251 esophageal stricture, 198
diagnosis at birth, 246–247 gastroesophageal reflux, 199
Down’s syndrome, 247 long-term, 199
vs. jejunoileal atresia, 260 persistent respiratory symptoms, 199–200
lesions type, 246 predictors of, 198
prenatal diagnosis, 245–246 recurrent tracheoesophageal fistula, 198–199
prevalence, 245 short-term, 198
prognosis, 252 definition, 187
vs. SBA, 246 diagnosis
surgical treatment at birth, 190–191
antimesenteric tapering duodenoplasty, 249 delayed, 191
comparing open and laparoscopic neonatal prenatal, 190
procedure, 250 epidemiology, 187
diamond-shaped anastomosis, 248–250 gastroesophageal reflux disease, 211–212
duodeno-duodenostomy, 248 management, 191
duodenojejunostomies, 247 airway anomalies, 203
endoscopic treatment, 250, 251 brain monitoring, 200
gastrostomy tubes placement, 249 centre for upper GI and airway pathology,
Kimura’s anastomosis, 249 200–202
neonatal minimally invasive surgery, 248, 249 follow-up, 203
side-to-side anastomosis, 248 long-gap, 202–203
web resection and transverse suture, 250 minimal invasive surgery, 200
US investigation, 245 prospective study, 200
Duodenal atresia (DA) model, 56, 58–59 thoracoscopic repair, 200
Duodenal duplication cyst, 280 pathogenesis, 187–188
Dysmorphic cost, 124 surgery
Dysmotility, 199 correction, 192
Dysphagia, 199 with distal tracheoesophageal fistula, 192–195
long-gap, 196–197
prematurity, 194–196
E staging approach, 192
EA, (see Esophageal atresia (EA)) type V, 197–198
Ear, nose, and throat problems, 86–87 with tracheoesophageal fistula model, 56, 57
Eccentric pectus excavatum, 121 Esophageal duplication cysts, 280, 282, 283
Echocardiography Esophageal mesentery, 178
mediastinal masses, 142 Esophageal stenosis, 202
uses, 9 Esophageal stricture, 198
Echo-enhanced cystosonography (CSG), 540 Esophagograms, 191
ECLS, (see Extracorporeal life support (ECLS/ECMO)) ETV, (see Endoscopic third ventriculostomy (ETV))
ECMO, (see Extracorporeal life support (ECLS/ECMO)) European Consensus Statement Guidelines, 10
Ectopic scrotum, 612 European Society of Pediatric Radiology, 515
Ectopic UC, 555, 556, 560, 561 European Surveillance of Congenital Anomalies system
Electrolyte therapy, 9–11 (EUROCAT), 243
Embryonal tumors European Union of Medical Specialists (EUMS), 2
AT/RT, 666 Eventration hernia, 177, 178
medulloblastoma, 665 EXIT procedure, 141
End colostomy, 346 External anal sphincter (EAS), 325, 326
Endoscopic pyloromyotomy, 231 External male genitalia, congenital anomalies
Endoscopic retrograde cholangiopancreatography bifid scrotum, 611
(ERCP), 392 buried/hidden penis, 609–610
Endoscopic third ventriculostomy (ETV), 620, 641, 649 duplication of the penis (diphallia) and bifid penis, 610
Index 711

ectopic scrotum, 612 replacement, 10

micropenis, 609 treatment, 229
penile agenesis (aphallia), 608–609 Follicle-stimulating hormone (FSH), 609
penoscrotal transposition, 610, 611 Food and Drug Administration (FDA), 7
scrotal agenesis, 610, 611 Foreign body
External traction, 196 airway, 15–16
Extracellular fluid (ECF), 9 esophageal, 15
Extracorporeal life support (ECLS/ECMO) Franceschetti-Klein syndrome, (see Treacher collins
cardiac, 17 syndrome (TCS))
circuit, 17 Fredet-Ramstedt pyloromyotomy, 230
heparin-bonded, 16 Fronto-ethmoidal/sincipital encephaloceles, 634
venoarterial, 17 Funnel chest, (see Pectus excavatum (PE))
veno-venous, 17 Furlow technique, 85
complications, 18
congenital diaphragmatic hernia, 16
contraindications, 17 G
extracorporeal circuit, 17 GABA-A receptor, 19
indications, 16 Gangliogliomas, 666
MRI total lung volume, 16–17 Ganglioneuroma, 145
observed-to-expected lung-to-head ratios, 16–17 Gastric duplication cysts, 36, 280, 282, 284
pump Gastric volvulus (GV)
cannulation, 16 abdominal, 239
centrifugal, 16 classification, 239
registry, 16 clinical presentation, 240
respiratory, 16, 17 combined/mixed volvulus, 239
selection criteria, 17 historical background, 239
strategy, 18 incidence, 240
Extracorporeal sliding knots, 60 intrathoracic, 239
Extrathoracic elongation, 196 management
conservative, 241–242
drug therapy, 242
F surgical, 242
Facial cleft mesentericoaxial, 239, 240
causes of, 73 organoaxial, 239, 240
orthodontics and alveolar bone graft, 88–89 radiologic investigation, 240–241
Failure to thrive, 210 Gastroesophageal reflux disease (GERD), 33, 36, 77,
FB, (see Flexible bronchoscopy (FB)) 199, 241, 274
F508del mutation, 267 causes and mechanisms, 209
Female epispadias with concurrent conditions
anatomy, 445 anterior abdominal wall defects, 213
surgical landmarks, 450 brain damage, 211
urethroplasty in, 451 congenital diaphragmatic hernia, 212–213
Female genitourinary system, 43 esophageal atresia, 211–212
Fetal diagnosis, rapid advances in, 1 respiratory tract disease, 211
Fetoscopic tracheal occlusion (FETO), 180 tracheoesophageal fistula, 211–212
Fibroblast growth factor (FGF) signaling pathway, 168 diagnostic tests
Fibrosing colonopathy, 274 below 1 year with comorbidities, 214
Fistulectomy, 113 below 1 year without comorbidities, 214
Flaccid leg paralysis, 473 endoscopy and biopsy, 213
Flexible bronchoscopy (FB) laryngoscopy, 213
complications, 15 manometry, 213
contraindications, 15 ultrasonography, 213
indications, 14–15 frequent, 209–210
Fluid symptoms, 210
administration, 9–11 treatment
extracellular (ECF), 9 first year of life, 216–217
hypotonic, 10 non-operative, 215
interstitial, 9 results, 217–218
intracellular (ICF), 9 surgical, 215–216
intravascular, 9 without concurrent diseases, 210–211
maintenance, 10 Gastrografin, 270
712 Index

Gastrointestinal neonatal imaging, 30 pain, 286, 288

computed tomography, 40 cystic duplications, 280
contrast studies diagnosis, 281–282
barium formulations, 32 duodenal duplication cyst, 280
colonic atresia, 33 esophageal duplication cysts, 280, 282, 283
continuous fluoroscopy technique, 32 gastric duplication cysts, 280, 282, 284
contrast enema, 33–34 history, 279
contrast media, 32–33 incidence, 279
gastroesophageal reflux disease, 33 location, 279
generic diagnosis, 33 occurrence, 279
Hirschsprung disease, 34 pathogenesis, 279–280
lower GI tract, 33 pathology, 280–281
meconium ileus, 33–34 prognosis, 288–290
meconium peritonitis, 34 treatment, 282
modern pediatric radiologist, 32 Genetic polymorphism, 19
neonatal low intestinal obstruction, 33 GERD, (see Gastroesophageal reflux disease (GERD))
obstruction, 34 Germ cells tumors (GCT), 604, 605
proximal digestive tracts, 33 Germ cell tumors, 145–146
tracheoesophageal fistula, 33 Gestational age (GA), 515, 517
magnetic resonance imaging, 39–40 Giant subcortical heterotopia, 667
radiography Giant supratentorial tumor, 661
abdominal, 30, 32 Gladiator concept, 60
after birth, 30 Glasgow Coma Scale (GCS), 658
esophageal atresia, 31 Glioblastomas, 663, 664
intramural gas, 31–32 Glioneuronal tumors
necrotizing enterocolitis, 31 craniopharyngiomas, 666, 667
obstructions, 30 DIAs/DIGs, 666
pneumoperitoneum, 30–31 gangliogliomas, 666
portal venous gas, 32 Gold standard test, 267
ultrasonography Gonadotropin-releasing hormone (GnRH), 609
advantages, 35 Gorlin syndrome, 672
biliary atresia, 38 Grand Canyon, 121
choledochal cysts, 38–39 GTD, (see Gatrointestinal tract duplications (GTD))
complications, 39 GV, (see Gastric volvulus (GV))
conventional transabdominal approach, 35
small and large bowel, 36–38
triangular cord sign, 38 H
upper GI tract, 35–36 Haemangioendothelioma, 479–481
Gastroschisis Haller index (HI), 121
antenatal screening, 418 Hall-Hittner syndrome, (see CHARGE syndrome)
associated anomalies, 418–419 Harelip, 79
clinical features, 420 Heel-prick test, 267
complication, 417, 424 Hemangioma
delivery issues, 419 CH, 690–692
early outcomes, 425 IH, 687–690
embryology, 418 Heminephrectomy, 573–575
follow-up, 418 Hemispheric cyst, 618
incidence, 417 Hemivertebra, 135
management of, 417, 422–424 Hemorrhagic cysts, 43
pathophysiology, 418 Hendren’s technique, 547
small developmental abdominal defect, 417 Hensen’s node, 500
Gastrostomy, 235 Hepatic artery ligation, 481
Gatrointestinal tract duplications (GTD) Hepaticojejunostomy model, 60, 62
bronchogenic duplication cysts, 280, 284 Hepatic tumours
clinical presentation, 281 benign and malignant neoplasms, 479, 480
colonic duplication cysts, 280–281, 286, 287 computed tomography, 479
complications hepatoblastoma
carcinomas, 288 clinical behaviour, 480
intussusception, 288 PRETEXT system, 480–481
malignancies formation, 288 tumour biopsy, 480
Index 713

US screening, 480 Rehbein’s procedure, 318

Wnt signalling pathway, 480 robotic surgery, 319
MRI, 479 transanal approach, 318–319
surgery of Histamine-2 receptors (H2RAS), 215
atypical resections (nonanatomic resection), 482 HMC, (see Hydrometrocolpos (HMC))
liver transplantation, 481, 483 Hodgkin lymphoma (LH), 147
partial liver resection (anatomic hepatectomy), Homovanillic acid (HVA), 473
482–483 Horner’s syndrome, 473
ultrasound, 479 HSCR, (see Hirschsprung’s disease (HSCR))
vascular neoplasm, 479, 480 Human chorionic gonadotropin (β-HCG), 508
Hepatobiliary scintigraphy (HBS), 39 Human chorionic gonadotropin (HCG), 607
Hepatoblastoma 100 and 40 mL working area, 52, 53
clinical behaviour, 480 Hybrid model 1, 55
multifocal PRETEXT IV, 483 Hydrocele
PRETEXT system, 480–481 clinical examination, 352
treatment of, 482 diagnosis, 352
tumour biopsy, 480 management, 364–365
unifocal PRETEXT IV, 483 postoperative, 363
US screening, 480 surgical procedure, 365
Wnt signalling pathway, 480 Hydrocephalus
Hepatocellular carcinoma (HCC), 396 and multiple spinal metastasis, 660
Hepato-duodenal ligament, 482 obstructive, 661
Hepatopulmonary syndrome (HPS), 396 Hydrocephalus and CSF-related disturbances
Hereditary hemorrhagic telangiectasia (HHT), 694 aqueductal stenosis, 615, 617
Hereditary multiple intestinal atresia, 244 anatomy, 616
Hernia mesocolica, 373, 374 chemical, 617
High-dose chemotherapy (HDCT), 673 developmental, 616
Hill model, allometric equation and corrective factors of, 20 developmental stenosis, 617
Hirschsprung disease, 34 embryology, 616
Hirschsprung’s disease (HSCR) fetal diagnosis, 617
causes, 311 infectious, 617
clinical grading system, 314 malformative, 616–617
development of neoplastic, 617
intestinal microbiome abnormalities, 313–314 postnatal diagnosis, 617–618
predisposing factors for, 313, 314 prognosis, 618
diagnosis of vascular, 617
anorectal manometry, 317 neuroendoscopy, 620–621
clinical aspects, 312–314 arachnoid cysts marsupialization, 623–624
radiological evaluation, 316–317 computer-assisted, 624
rectal suction biopsy, 314–315 endoscope, 621
etiology, 311–312 functional neurosurgery, 624–625
history, 311 placement of catheters, 624
initial symptoms of, 314 septostomy, 622, 623
mortality rate, 313 third ventriculocisternostomy, 621–623
occurrence, 313 Hydrocolon, 37
pathogenesis, 312 Hydrodistension implantation technique (HIT), 541, 542
postoperative management and outcome, 319 Hydrometrocolpos (HMC)
postoperative risk, 313 abdominoperineal repair of vagina, 598–599
preoperative management, 317 antenatal diagnosis, 592
treatment associated anomalies and syndromes, 594
Duhamel procedure, 318 clinical presentation
endorectal pull-through procedure, 318 infection, 594
goal, 317–318 late presentation, 594
laparoscopic biopsy, 318 perineal examination, 592
minimally invasive surgery, 318 upper vagina, 592
oral/intravenous metronidazole, 317 vaginal atresia, 592
preoperative intravenous antibiotic, 318 definition, 591
preventing method, 317 drainage procedures
radical resection of aganglionic bowel, 318 abdominal vaginostomy, 597, 598
rectal irrigations, 317 Hydrometrocolpos (HMC) (continued)
714 Index

hymenotomy/hymenectomy, 596–597 UTD

perineal vaginostomy, 597, 598 antenatally detected hydronephrosis, 521
embryopathogenesis, 591 classification system, 517
secretory, 592 postnatally detected hydronephrosis, 521
urinary, 592 Hymenotomy/hymenectomy, 596–597
investigations Hyperdiploid, 472
dye study, 595 Hypertrophy, 189
echocardiogram, 595 Hypo-atrophy, 44
endoscopy, 595 Hypocapnia, 8
intravenous urography, CT scan and MRI, 595 Hyponatremia, 10
MCU, 595 Hypoplastic distal esophagus, 189
plain X-ray of the abdomen, 594 Hypotension, 8
renogram studies, 595 Hypothalamic hamartoma (HH), 624–625
RGU, 595
skeletal X-rays, 595
USG, 595 I
management IHPS, (see Infantile hypertrophic pyloric stenosis (IHPS))
early neonatal surgery, 595 123
I-meta-iodo benzyl guanidine (123I-mIBG),
management algorithm for, 596 474
preoperative resuscitation, 596 Immature teratoma, 662
temporary decompression, 595 Immunoreactive trypsin (IRT), 267
results and follow-up, 599 Incomplete recanalization theory, 280
TUM, 599 Incomplete twinning theory, 280
types of, 592, 593 Induction chemotherapy, 475
vaginal replacement and PSARVUP, 599 Indwelling catheter, 597
Hydronephrosis Infantile haemangioendothelioma, 479, 480
ANH, 516 Infantile hemangioma (IH)
APD classification, 515, 516 cutaneous, subcutaneous, mixed, 688
clinical manifestation, 518–519 high incidence, 687
definition, 515 LUMBAR syndrome, 688, 689
diagnosis periorbital hemangiomas, 689, 690
diuretic renal scintigraphy, 519, 520 PHACE syndrome, frontal pachygyria and complex
intravenous urography, 519 malformation, 688, 689
magnetic resonance imaging, 519 propranolol, 690
postnatal ultrasound, 519 Infantile hypertrophic pyloric stenosis (IHPS)
VCUG, 519 associated anomalies, 228
differential diagnosis, 518 clinical presentation, 227
embryogenesis, 517, 518 complications, 233
epidemiology, 518 diagnosis, 228–229
etiology and physiopathology, 518 differential diagnosis, 228
prenatal (see (Prenatal hydronephrosis, VUR)) epidemiology, 226
SFU classification, 515 etiology, 226–227
bilateral hydronephrosis SFU III and IV, 521 history, 225
grade 0, 516 management, 229
grade 1, 516 nonoperative treatment, 232–233
grade 2, 516 operative treatment
grade 3, 516 endoscopic pyloromyotomy, 231
grade 4, 516 laparoscopic pyloromyotomy, 231
SFU I and II monolateral hydronephrosis, 520 microlaparoscopic pyloromyotomy, 231
SFU III and IV unilateral hydronephrosis, 520 open surgical approach, 230
surgical correction, criteria for, 521 pyloromyotomy, 229–231
surgical treatment single-incision laparoscopic pyloromyotomy
Anderson–Hynes pyeloplasty (dismembered technique, 231
pyeloplasty), 521–522 single-port laparoscopic-assisted pyloromyotomy,
complications, 524 231–232
laparoscopic approach, 522 pathology, 227
OTAP, 522–523 physiopathology, 227–228
postoperative follow-up, 524 postoperative care, 232
retroperitoneoscopic approach, 522 Inferior triangle flap technique, 82
robotic surgery, 522 Infusion therapy, 10
of upper pole, 558 Inguinal hernia (IH)
Index 715

anesthesia neonatal X-rays, 253, 254

airway management, 353 ultrasonography studies, 253
clonidine, 353 occurrence, 252
intranasal administration of drugs, 353–354 pathogenesis, 252–253
intravenous anesthetics, 353 prenatal diagnosis, 252, 253
midazolam, 353 surgical treatment
and pre-anesthetic medication, 352–353 laparoscopy-assisted surgery, 256
regional, 353 MIS, 254, 256
risks in premature infants, 354 transverse laparotomy, 254
sevoflurane, 353 Jeune syndrome, 125–126
bilateral, 351
clinical examination, 352
diagnosis, 352 K
incidence, 351 Kalicinski’s technique, 547
laparoscopic inguinal hernia repair (see Kaposiform hemangioendothelioma, 692
(Laparoscopic inguinal hernia repair)) Kasai portoenterostomy (KPE), 387, 395
management of incarceration, 360–361 Kelly procedure, 449
open repair (see (Open herniotomy (OH))) Klippel-Trenaunay syndrome (KTS), 698, 699
timing of surgical repair, 354–355
Inhaled nitric oxide (iNO), 9, 180
Instructors, neonatal minimally invasive surgery (NMIS), L
56 Labio-maxillary cleft, 74
Interhemispheric cyst, 619 Labioplasty, 81–82, 95
Intermamillary distance, 119 Lactate dehydrogenase levels (LDH), 473
Internal anal sphincter (IAS), 325, 326 Laparoscopic inguinal hernia repair
International Neuroblastoma Risk Group (INRG) Staging advantages, 351, 363–364
System, 475 extracorporeal techniques, 356
International Neuroblastoma Staging System (INSS) Montupet’s technique, 357, 358
guidelines, 474 outcome analysis, 361, 362
International Reflux Study Committee, 540 hydrocele, 363
Interstitial cells of Cajal (ICC), 226 iatrogenic cryptorchidism, 363
Intracavitary pyloromyotomy, 225 literature reports, 361
Intracellular fluid (ICF), 9 recurrence rate, 361
Intracorporeal sliding knot, 60 testicular atrophy, 363
Intracranial hypertension, 658 wound infection, 361, 363
Intrahepatic bile ducts, 388 PIRS technique, 357, 359
Intramural gas, 31–32 Schier’s technique, 357, 358
Intraosseous catheters, 12 technical point of view, 359–360
Intraperitoneal shunting, 583 transperitoneal approach, 356
Intrateutoria cephaloceles, 633–634 trocars screw, 356
Intrauterine antegrade transvesical laser valve ablation Laparoscopic pyloromyotomy (LP), 231
(ITVLA), 583, 584 Laparotomy, 181
Intravenous pyelogram (IVP), 558–560 Laryngeal mask airway (LMA), 78
Intravenous urography, 46, 519 Lateral cysts, 112–113
Ipsilateral ureteroureterostomy (IUU), 571–573 Lateral pectus carinatum, 122
Iron deficiency, 210 Le Mesurier technique, 81
Isocytrate dehydrogenase (IDH), 663 Lingual duct, 111
Isolated enteric duplication cysts (IEDCs), 281 Lipomas
Isolated hemihypertrophy, 486 caudal, 642–643
of filum terminale, 641, 642
lipomyelomeningocele, 643, 644
J total/near-total resection, 643, 644
Jarcho-Levin syndrome, 127 Lipomyelomeningocele, 643
Jejunal duplication cyst, 280 Liver transplantation
Jejunoileal atresia multifocal PRETEXT IV hepatoblastoma, 483
anastomosis, 256 unifocal PRETEXT IV hepatoblastoma, 483
associated malformations, 252 LMs, (see Lymphatic malformations (LMs))
classification, 253–254 Lobectomy model, 60, 61
clinical presentation, 253 Long-axis view (LAX), 11
diagnosis at birth Long-gap esophageal atresia, 196–197, 202–203
716 Index

Longitudinal segmental atresia, 234 associated anomalies, 373–375

Loss of heterozygosity (LOH), 487 classification, 371
Lower esophageal sphincter (LES), 209, 210 complete nonrotation, 371
Lower urinary tract obstruction (LUTO), 521, 568, 569 partial (incomplete) malrotation, 371–372
Low-grade gliomas, 663 reversed, 372–373
LUMBAR syndrome, 688, 689 clinical presentation, 375
Lung branching morphogenesis, 168 complications of, 375
Lung mass volume ratio (LMVR), 170 diagnostic imaging investigations
Lung organogenesis, 167–168 computed tomography, 379
Lung-point sign, 154 contrast enema, 379
Lung pulse, 154 MRI, 379
Lung-to-head ratio (LHR), 179 plain abdominal radiographs, 375–378
Luteinizing hormone (LH), 607 SMV/SMA orientation, 379
8-L working area, 52 US, whirlpool sign, 378–379
Lymphangiomas, 144–145, 294 embryological development of midgut, 370–371
Lymphatic malformations (LMs), 105 epidemiology, 369
laser therapy and radiofrequency ablation, 694 history, 369
macrocystic, 694, 695 postoperative course, 381–382
microcystic, 694, 695 during second rotation, 372, 373
MRI aspect, 696 surgical treatment
percutaneous sclerotherapy, 694 appendectomy, 380
sclerotherapy, 694 asymptomatic midgut volvulus, 381
Lymphoid tumors, 147–148 complications, 381
Lymphoscintigraphy, 159 indications, 379
Ladd’s procedure, 379, 380
laparotomy, 380
M minimally invasive surgical techniques, 380
Macrocrania, 661 open vs. laparoscopic approaches, 381
and increasing head circumference, 658 patient positioning, 380
and Russel syndrome, 660 Management of Myelomeningocele Study (MOMS), 649
Macroglossia Mass-to-thorax ratio (MTR), 169
causes, 101 Maternal serum alpha-fetoprotein (AFP), 418
classification, 101 Mature teratoma, 501
clinical features, 101, 102 Maxillofacial surgery
definition, 101 during growth process, 89
diagnostic approach, 101–103 impairment of growth, 90
associated comorbidities, 103–105 indications, 92
workflow, 105–106 lateral cephalograms, 91
nonsurgical management, 106 orthognathic surgery, 91
surgical management, 106–108 MCDK, (see Multicystic dysplastic kidney (MCDK))
treatment, 101 McGovern nipple, 69
Magnetic resonance cholangiopancreatography (MRCP), MD, (see Meckel diverticulum (MD))
39 Mechanical simulators, with faithful models, 2–3
Magnetic resonance imaging (MRI), 25 Meckel diverticulum (MD)
chest neonatal imaging, 27–28 clinical presentation
congenital diaphragmatic hernia, 179 appendicitis, 434
gastrointestinal neonatal imaging, 39–40 gastrointestinal bleeding, 434
gastroschisis, 418 hernia, 434
gatrointestinal tract duplications, 281–282 inflammation, 434–435
liver cysts, 406–407 intestinal obstruction, 434
malignant change, 396 intestinal perforation, 435
malrotation, 379 malignancies, 435
mediastinal masses, 143 mechanism of bleeding, 434
mesenteric and omental cysts, 295–297 mesodiverticular band, 434
omphalocele, 418, 421–422 diagnosis
urachal abnormality, 438 CT scan, 435, 436
urogenital neonatal imaging, 45–47 Meckel scan, 435
Malek technique, 81 mesenteric angiography, 435
Malformational PRS, 76 SPECT, 435
Malrotation technetium-99 m-labeled study, 436
Index 717

ultrasound, 435, 436 and posterior urethral dilatation, 582

wireless capsule endoscopy, 436 Megalourethra, 461
history, 433 Membranous pyloric obstruction, 234
incidence, 433 Mercaptoacetyltriglycine (MAG3) scans, 557, 559
pathology, 433–434 Mesenchymal hamartoma (MH), 479, 481
prevalence, 433 aetiology, 403–404
treatment, 436–437 clinical features, 404
Meconium ileus (MI), 33–34 management, 404–405
causes, 265 prognosis, 405
classification, 265 Mesenteric and omental cysts
clinical presentation, 267–268 classification, 293
complex, 272–273 cystic intestinal duplications, 294
conservative management definition, 293
Gastrografin enema administration, 270 diagnosis
instillation of contrast enema, 268–269 abdominal ultrasounds, 295, 296
with cystic fibrosis (see (Cystic fibrosis (CF))) MRI, 295–297
incidence, 265 enteric cysts, 294
initial management, 268 historical background, 293
obturator-type obstruction, 265 location, 293
plain abdominal radiograph studies, 268 lymphangiomas, 294
prenatal diagnosis, 267 mesothelial cysts, 294
surgical management recurrence, 297
enterotomy, 271–272 symptoms, 294–295
ileostomy, 272 treatment
indications, 270 laparoscopy-assisted transumbilical procedure,
laparotomy, 270 297, 298
meconium disimpaction, 270 primary end-to-end anastomosis, 297
survival rates for, 275 surgical intervention, 297
Meconium peritonitis, 34 Mesentericoaxial gastric volvulus, 239, 240
Meconium pseudocyst, 265, 268 Mesothelial cysts, 294
Mediastinal masses Metachronous inguinal hernia (MIH), 363
bronchogenic cysts, 144 MH, (see Mesenchymal hamartoma (MH))
classification, 140 MI, (see Meconium ileus (MI))
clinical implication, 140 Microlaparoscopic pyloromyotomy, 231
diagnostic tools Micropenis, 609
chest X-ray, 142 Micro-/retrognathia, 75
computed tomography, 142–143 Micturating cystourethrogram (MCU), 595
echocardiography, 142 Midazolam, 353
laboratory data, 141 Midgut volvulus, 36.
magnetic resonance imaging, 143 See also Malrotation.
positron emission tomography, 143 Midline cervical swellings, 111–112
ultrasounds, 142 Mild ARMs
upper gastrointestinal tract X-ray, 142 anterior anus with/without anal stenosis
embryology, 139–140 clinical feature, 327–328
esophageal duplications, 143–144 Hegar dilatations, 331
germ cell tumors, 145–146 perineal fistula and anal stenosis in males
incidence, 139 clinical feature, 328
lymphangiomas, 144–145 colostomy, 332
lymphoid tumors, 147–148 minimally invasive management, 331, 332
neurogenic tumors, 145 standard anoplasty, 331–332
prenatal and perinatal management, 140–141 Millard procedure, 81
teratomas, 145–146 Minimal invasive surgery (MIS), 2, 200, 252, 260
thymic tumors, 147 Mitchell’s technique, 448–449
Mediastinal neuroblastoma, 476, 477 Mixed hepatoblastomas, 480
Mediastinum, definition, 139 MMC, (see Myelomeningocele (MMC))
Medium-chain triglyceride (MCT), 159 Monolateral hydronephrosis, 515, 520
Medulloblastomas, 665, 672, 673 Montupet’s technique, 358
Megacystis, 460–461 Morgagni-Larrey hernia, 177, 178
definition, 581 Morphine, 19
and keyhole sign, 582 Morphine-6-glucuronide (M6G), 19
718 Index

MRI, (see Magnetic resonance imaging (MRI)) imaging appearance

Mucopolysaccharidoses (MPS), 104 complex heterogeneous ovarian cyst, 492–493
Multicystic dysplastic kidney (MCDK) cystic torsion, 493
associated anomalies, 527–528 internal echoes and normal ovarian vascularity
definition, 527 and flow, 492
diagnosis pre-and postnatal sonographic appearance, 492
postnatal presentation, 528 simple anechoic ovarian cyst, 492
prenatal diagnosis, 528 laparoscopic interventions
epidemiology, 527 aspiration, 494
etiology, 527 gynecological procedures, room setup for, 495
management needle hitch technique, 496
DMSA renal scan, 529 patient positioning, 495
equivocal diagnosis, 529 preoperative assessment, 495
intestinal compression, 529 surgical excision, 495
RUS, 529 three punctiform scars, 496
VCUG, 529 trocar positioning, 495
natural history, 528 lower abdominal laparotomy, 496
nephrectomy perioperative and operative facilities, 496
minimally invasive approach, 530 prenatal detection rate for, 491
one-trocar-assisted nephrectomy, 530 robotic surgery approach, 496
open approach, 529, 530 ultrasound-guided cyst aspiration, 494
patient position, 530 Neonatal PTX (nPTX), 151.
video-assisted retroperitoneoscopic approach, 530 See also Pneumothorax (PTX).
Multidisciplinary cleft team, 96–97 Neonatal surgical procedures, 1
Myeloablative therapy, 475 Nephroblastoma, (see Wilms tumor (WT))
Myelomeningocele (MMC), 620, 639–641, 647–649 Nephropathy, 485
Myer classification, 101 Neuhauser’s sign, 268
Myotomy, 196 Neuroblastoma
clinical features, 473
diagnosis
N bone marrow aspirate/trephine biopsy, 474
N-Acetylcysteine (NAC), 271 CT, 473
N-acetyl-p-benzoquinone imine (NAPQI), 20 123
I-mIBG, 474
NASPGHAN-ESPGHAN, 216 MRI, 473
Nearinfrared spectrometry (NIRS), 200, 201 ultrasound scanning, 473
Necrotizing enterocolitis (NEC), 31, 299 unequivocal pathological diagnosis, 474
surgical (see (Surgical necrotizing enterocolitis epidemiology, 471–472
(SNEC))) genetic and risk factors
Neonatal intensive care unit (NICU), 201, 354, 584 ALK, 472
Neonatal low intestinal obstruction, 33 allelic loss/imbalance of 11q, 472
Neonatal minimally invasive surgery (NMIS) allelic loss of 1p, 472
course contents, 52–56 DNA index/ploidy, 472–473
curriculum, 52–53 MYCN amplification, 472
instructors, 56 PHOX2B, 472
knots, 60 unbalanced 17q gain, 472
models, 56 pathology, 473
congenital diaphragmatic hernia repair, 59 prognostic factors and risk stratification, 474–475
duodenal atresia, 56, 58–59 surgery of neonatal neuroblastoma
esophageal atresia with tracheoesophageal fistula, left adrenal gland, 476, 477
56, 57 mediastinal neuroblastoma, 476, 477
hepaticojejunostomy, 60, 62 primary tumour from adrenal gland, 476
lobectomy, 60, 61 right adrenal gland, 476
simulation, 51 therapeutic management
spiral education method, 51 high risk, 475
training skills, 51 intermediate risk, 475
Neonatal ovarian cyst (NOC) low risk, 475
clinical manifestations and complications, 493 Neuroendoscopy, 620–621
differential diagnosis, 493–494 arachnoid cysts marsupialization, 623–624
etiology of, 491 computer-assisted, 624
expectant management, 494 endoscope, 621
Index 719

functional neurosurgery, 624–625 testicular atrophy, 363

placement of catheters, 624 wound infection, 361, 363
septostomy, 622, 623 Opsoclonus-myoclonus syndrome, 473
third ventriculocisternostomy, 621–623 Oral sildenafil, 160
Neurofibromatosis (NF), 655 Organoaxial gastric volvulus, 239, 240
Neurofibromatosis type 1 (NF-1), 671, 672 Oronasal fistula, 95
Neurogenic tumors, 145 Orthodontics, 88–89
Neurotoxicity, hypothesis of anesthetic, 7 Orthognathic surgery, 91
Neurotransmitters, 19 Osmotic pressure, 10
Newborn’s glomerular filtration rate, 10 Oxytetracycline, 161
Nissen procedure, 54
Nitric oxide, 160
NMDA receptor, 19 P
NMIS, (see Neonatal minimally invasive surgery (NMIS)) Pain
NOC, (see Neonatal ovarian cyst (NOC)) acute, 19
Non-Hodgkin lymphomas (LnH), 147, 148 algometric scale, 20
Non-involuting congenital hemangiomas (NICHs), PIPP scale, 19
690–692 control
Non-opioid analgesics, 20 non-pharmacological, 19
pharmacological, 19
regional anesthesia, 20
O Palatal cleft, 74, 82
Observed-to-expected lung-to-head ratio (o/e LHR), 169 Pancreatic duplications, 284
Obstructive sleep apnea syndrome (OSAS), 105 Pancreatic enzyme replacement therapy (PERT),
Octreotide, 160 273–274
OH, (see Open herniotomy (OH)) Paracetamol, 20
Oligohydramnios, 581 Paraneoplastic syndromes, 473
Omphalocele Parkes Weber syndrome (PWS), 698, 700
abdominal wall and muscles defect, 417 Partial androgen insensitivity (PAIS), 603
antenatal screening, 418 Partial ureterectomy, 573–575
associated anomalies, 418–420 PC, (see Pectus carinatum (PC))
cephalo-caudal fold defect, 417 PE, (see Pectus excavatum (PE))
clinical features, 419 Pectus carinatum (PC),122
complication, 421 asymmetric, 122
delivery issues, 419 classification, 122
early outcomes, 425 clinical presentation, 123
follow-up, 418 etiopathogenesis, 122
incidence, 417 imaging, 123
management, 417, 420–422 management, 123
pathogenesis, 418 Pectus excavatum (PE)
treatment, 417 characteristics, 119
Omphalomesenteric duct remnants clinical evaluation, 121
clinical presentations and complications, 430, 432 etiopathogenesis, 119–120
cysts, 431 imaging, 121–122
fistula, 430, 431 management, 122
Meckel diverticulum (see (Meckel diverticulum pathophysiology, 120
(MD))) Pediatric surgeon, 1, 3
normal embryology, 429–430 Pediatric surgery
sinus, 431 history, 2
umbilical polyp, 431 training programs, 52–53
One-trocar-assisted nephrectomy, 530 Pediatric Toronto model, 52, 53
One–trocar–assisted pyeloplasty (OTAP), 522–523 Penile agenesis, 608–609
Open herniotomy (OH) Percutaneous internal ring suturing (PIRS) technique,
inguinal incision, 355 357, 359
laparoscopic video column, 356 Pericardio-peritoneal canals, 139
outcome analysis, 361, 362 Perineal vaginostomy, 597, 598
hydrocele, 363 Perinephric urinoma, 581
iatrogenic cryptorchidism, 363 Perioperative period, fluid administration and electrolyte
literature reports, 361 balance, 9–11
recurrence rate, 361 Periorbital hemangiomas, 689, 690
720 Index

Peripheral blood stem cells (PBSCs), 674 Posterior sagittal anorecto–vagino–urethroplasty

Peripherally inserted central catheters (PICC), (PSARVUP), 599
12–13 Posterior urethral valves (PUVs), 533, 537, 566, 567, 570
Peripheral venous catheters (PC), 12 and consequent bilateral reflux, 539
Perlman syndrome, 486 COPUM, 579, 580
Personalized professional training, 53–54 dysmorphic urinary tract, 580, 581
PHACES syndrome, 688, 689 postnatal management
Pharmacology, 11 bilateral vesicoureteral reflux, 587
Pharyngeal flap, 93–95 catheterization, 585
Pharyngeal obstruction, 77 creatinine serum values, 586
Pharyngoplasty, 93–95 dilated posterior urethra, 587
PHOX2B mutations, 472 diuresis, 586
Pierre Robin Sequence (PRS) high diversion, 586–589
airway obstruction, 76 nephrological consultation, 586
continuous positive airway pressure, 77 physical examination, 585
etiology, 76 respiratory insufficiency, 585
feeding difficulty, 78 transperineal ultrasound, 588
glossopexy, 78 urinary diversion, 586
glossoptosis, 76 urinary retention, abnormal flow and voiding
laryngeal mask airway, 78 problems, 585
mandibular hypoplasia, 76 UTI, 585
nasopharyngeal tube, 78 valve ablation, 586, 588
palatal plaque, 78 VCUG, 586
pharyngeal obstruction, 77 prenatal aspects
respiratory obstruction, 77 amnioinfusion, 583
surgical methods, 78 antenatal detection, 582
types, 76 bladder prolapse, 584
velocardiofacial syndrome, 79 fetal ascites/perinephric urinoma, 581
Pilocytic astrocytoma, 663 fetal intervention, 583
Plagiocephaly, 630, 631 fetal urine markers, 584
Pleuroperitoneal membranes, 178 future renal prognosis, 582
Pleuroperitoneal shunt, 161 ITVLA, 583, 584
Pleuropulmonary blastoma (PPB), 28–29, 169 megacystis, 581, 582
PNET, (see Primitive neuroectodermal tumor (PNET)) oligohydramnios, 581
Pneumonia, 210 VAS, 583, 584
Pneumothorax (PTX) type I, 579, 580
classification, 151 type II, 579, 580
diagnostic tools type III, 579, 580
chest X-ray, 153 Posterolateral hernia, 177, 178
power Doppler, 154 Posterolateral thoracotomy, 476
sonography, 153–154 Povidone-iodine, 161
transillumination, 154 Power Doppler, 154
incidence, 151 Power slide, 154
Malaysian study, 152 Premature Infant Pain Profile (PIPP) scale, 19
management, 155 Prematurity, 194–195
outcome, 156 Prenatal hydrocephalus, 647
risk factors, 152 Prenatal hydronephrosis, VUR
sign and symptoms, 152–153 physical examination, 534
Poland syndrome (PS) PUVs, 537
clinical presentation and assessment, 128–129 SERP, 534
diagnostic criterion, 127 SFU grading scale, 534–536
etiopathogenesis, 127–128 US cortical abnormalities, 537
Polyhydramnios, 179, 190, 508, 509 Prepyloric antral diaphragm, 235
Portal venous gas, 32 Presacral artery, 506, 507
Port-wine stains, 692, 693 Primary palate, 73
Positron emission tomography (PET), 143 Primary surgery
Posterior fossa cyst, 619–620 age of surgery, 79
Posterior plagiocephaly, 630 historical elements, 79
Posterior sagittal anorectoplasty (PSARP), 333–335 labioplasty, 81–82
palatal repair, 82–84
Index 721

preparation for surgery, 79–80 abdominal wall reconstruction, 465–466

principles, 80–81 orchidopexy, 466
staphylorraphy, 83, 85 temporary urinary diversion, 464–465
veloplasty, 83, 84 urinary tract reconstruction, 465
Primary valve ablation vesicostomy, 464
type 1, 550 “wait and” (see approach, 464)
type 3, 550 yolk sac defect, 459
Primary VUR surgical treatment PS, (see Poland syndrome (PS))
Cohen reimplantation, 542 Psychological impact, 92–93
5/0 absorbable suture, 549 PTX, (see Pneumothorax (PTX))
6/0 absorbable sutures, 549 Pulmonary hypertension, 9
dissection, 546 Pulmonary sequestration, 29
feeding tube, 544 Pulsed dye laser (PDL), 693
prevesical and subcutaneous spaces, 549 PUVs, (see Posterior urethral valves (PUVs))
Reynolds scissors, 545, 548 Pyloric aplasia, 234
stay suture, 544, 545 Pyloromyotomy, 229–231
submucosal tunnel, 546, 547 Pyriform sinus fistulas, 113
transverse suprapubic incision, 543
ureteric orifice, 548
endoscopic VUR treatment Q
complications, 542 Quadrangular flap plasty, 81
Dx/HA, 541, 542 Quadrigeminal cyst, 619
HIT, 541, 542
meta-analysis, 542
STING, 541, 542 R
Primitive hydronephrosis, (see Hydronephrosis) Radiography
Primitive neuroectodermal tumor (PNET), 665, 672, 673, chest neonatal imaging, 26–27
676 gastrointestinal neonatal imaging
Progressive training concept, 51 abdominal, 30, 32
Propranolol, 690 after birth, 30
Proton pump inhibitors (PPI), 215 esophageal atresia, 31
PRS, (see Pierre Robin Sequence (PRS)) intramural gas, 31–32
Prune-belly syndrome necrotizing enterocolitis, 31
antibiotic prophylaxis, 464 obstructions, 30
associated anomalies, 461 pneumoperitoneum, 30–31
categories of clinical presentation, 462 portal venous gas, 32
clinical features Radiotherapy, 475
abdominal wall, 460 Ramstedt’s pyloromyotomy, 232.
bladder, 460–461 See also Fredet-Ramstedt pyloromyotomy.
epididymis, 461 Randomized controlled trials (RCT), 1
prostate, 461 Randomized Intervention for Children with
seminal vesicles, 461 Vesicoureteral Reflux (RIVUR) trial, 541
testis, 461 Ransley’s technique, 447–448, 453
ureters, 460 Rapidly involuting congenital hemangiomas (RICHs),
urethra, 461 690–692
urinary tract, 460 RB, (see Rigid bronchoscopy (RB))
cutaneous pyelostomy, 464 Rectal duplications, 286
definition, 459 Rectal suction biopsy (RSB), 314–315
diagnosis of Reflux nephropathy, 539
postnatal, 463–464 Regional anesthesia, 20
prenatal, 462–463 Remifentanil, 20
epidemiology, 459 Renal cortical scintigraphy, 539, 540
fetal outlet obstruction, 459 Renal dysplasia, 460
genetic defect, 460 Renal function, 10
infertility associated with, 460 Renal ultrasonography (RUS), 519–521, 524, 528, 529
long-term outcomes, 466 Rendu-Osler-Weber syndrome, 694
mesodermal arrest theory, 459 Respiratory distress syndrome (RDS), 152
pathophysiology, 459 Respiratory obstruction, 77
pseudoprune belly syndrome, 462 Respiratory tract disease, 210, 211
surgical management Retrograde genitourethrogram (RGU), 595
722 Index

Rhinoplasty, 96 type III, 500, 501

Rigid bronchoscopy (RB) type IV, 500, 501
complications, 16 Safetots initiative, 7
foreign body extraction, 15–16 SBA, (see Small bowel atresia (SBA))
indications, 15 Scaphocefaly, 630
obstruction of central airways, 15 Scapular malformations, 134
pediatric, 15 Schier’s technique, 358
Rotavirus, 313 Schwannian stroma cells, 473
RSB, (see Rectal suction biopsy (RSB)) Sclerotherapy, 697
RUS, (see Renal ultrasonography (RUS)) Scrotal agenesis, 610, 611
Russel syndrome, 659, 660 Scrotal extratesticular calcifications, 44
SCT, (see Sacrococcygeal teratoma (SCT))
Secondary palate, 73
S Secondary surgery
Sacrococcygeal teratoma (SCT) labioplasty, 95
epidemiology, 500 oronasal fistula, 95
etiologies, 500 pharyngeal flap, 93–95
follow-up rhinoplasty, 96
β-HCG, 508 Secondary VUR surgical treatment
fecal complications, 507 catheter drainage, 550
αFP, 508 foetal cystoscopy, 549–550
long-term, 507 foetal intervention, 549
long-term functional sequelae, 507 high urinary tract diversion, 551
orthopedic sequelae, 508 primary valve ablation, 550
renal impairment, 508 vesicostomy, 550, 551
sexual activity, 508 Secretory otitis media (OMS), 86
total resection, 508 Sedative anesthetic drugs, 19
urologic complications, 508 SEGAs, (see Subependymal giant cell astrocytomas
malignant, 501 (SEGAs))
mature, 501 Septostomy, 622, 623
mid-sixteenth to mid-seventeenth century, 499 Septum transversum, 178
in modern era, 500 Severe ARMs
postnatal preoperative cares and surgery cloaca
early excision, 505 clinical features, 327
ECMO, 506 contrast study of patient, 335
presacral artery, 506, 507 definitive reconstruction in, 336
PSARP, 506 endoscopy, 336
total resection, 505 hydrometrocolpos, 336
transverse section, sacrum and coccyx, 506 initial colostomy, 336
prenatal diagnosis and treatments, 502 pre-operative investigations, 335
accurate prenatal diagnosis, 505 imperforate anus without fistula
close monitoring, 504 clinical feature, 329
effects of, 504 posterior sagittal approach, 335
EXIT procedure, 505 perineal vestibular fistula in female
external, 505 anterior sagittal anorectoplasty, 332–333
inadequate placental flow, 504 clinical features, 328, 329
laser coagulation, 505 rectourethral fistula
MRI, 503 clinical features, 328, 330
prognostic groups, 504 laparoscopic dissection, 334–335
radiofrequency ablation, 505 micturating cystourethrogram, 333, 334
TFR ratio, 504 posterior sagittal anorectoplasty, 333–334
THR ratio, 504 Sevoflurane, 353
urogenital anomalies, 503 Short-axis view (SAX), 11
vascular disruption defects, 504 Simple costal anomalies, 123–124
WGA, 504, 505 Simple hepatic cysts
recurrences and prognosis, 507 aetiology, 402
types and classifications, 502, 503 antenatal detection with imaging, 402, 406–407
benign, 502 clinical presentation, 402
Gonzalez-Crussi’s grading system, 502 histological features, 401
type I, 500, 501 management, 402–403
type II, 500, 501 prognosis, 403
Index 723

Simple lymphatic cysts, 294 Spitz classification, 190

Simple pneumothorax, 151 Split notochord theory, 279
Simpson-Golabi-Behmel syndrome, 486 Spontaneous pneumothorax, 151
Simulation, MIS training programs, 51–53 Sprengel deformity, 134
Single-gene disorder, 75 Square knot/surgeon knot, 60
Single photon emission computed tomography (SPECT), Stabilization, 8–9
435 Staphylorraphy, 83, 85
Sinus of neck, 112–113 Stenotic UC, 556
Sinus pericranii (SP), 697, 698 Sternal anomalies
SIOPEL 4 study, 481 cervical ectopia cordis, 129
SIOPEN HR-NBL-1, 475 sternal cleft, 130–132
Sistrunk technique, 112 thoracic ectopia cordis, 129
Skeletal deformities, 128 thoracoabdominal ectopia cordis, 129
Small bowel atresia (SBA) Sternal cleft (SC), 130–132
associated anomalies, 243, 244 Sternal depression index (SDI), 121
classification, 254, 255 Sternocleidomastoid (SCM) muscle, 627
vs. duodenal atresia and stenosis, 246 Steroids, 170
incidence, 243 Steroid therapy, 480
postoperative complications, 259 Stocker’s classification, 170
surgical options for Stomach, muscular tunica of, 227
Bishop-Koop enterostomy, 257, 258 Strange malformations, 125
double barrel Mikulicz enterostomy, 257 Sturge-Weber syndrome (SWS), 692, 693
laparoscopy-assisted surgery, 256 Subcutaneous cleft palate, 73
pathogenesis, 244–245 Subcutaneous tissue and muscles, 192
procedures, 258 Subependymal giant cell astrocytomas (SEGAs),
Santulli enterostomy, 257, 258 654–655, 663
Willital technique, 257 Subureteral transurethral injection (STING), 541, 542
Small bowel duplication cysts, 280, 284–286 Superior moiety (SM) salvage procedures, 572–573
SMARCB1 gene, 666 Superior pectus excavatum, 120
SMOFlipid, 304, 308 Supernumerary cost, 124
SNEC, (see Surgical necrotizing enterocolitis (SNEC)) Suprasellar cyst, 619
Sober Y ureterostomy, 588, 589 Surgical diseases, 40–41
Society of Fetal Urology (SFU) classification, 515 Surgical emergencies, 8–9
grade 0, 516, 517 Surgical necrotizing enterocolitis (SNEC), 308
grade 1, 516, 517 Bell’s staging system, 299, 300
grade 2, 516, 517 causes, 299
grade 3, 516, 517 diagnostic features
grade 4, 516, 517 abdominal wall discolouration and cellulitis, 303, 304
postnatal management foul stools, 303
bilateral hydronephrosis SFU III and IV, 521 metabolic acidosis, 303
SFU I and II monolateral hydronephrosis, 520 multiple stenoses and damaged bowel, 303–305
SFU III and IV unilateral hydronephrosis, 520 ultrasonological findings, 303
surgical correction, criteria for, 521 long-term prognosis, 299
Solo-rectal biopsy tool, 315 management, 299, 305
Somatostatin, 160 abdominal imaging finding, 304–306
Sonographically evident renal pelvis (SERP), 534 concomitant abdominal massage, 304
Sonography deterioration, 306
congenital diaphragmatic hernia, 179 enteral feeding, 304
pneumothorax, 153–154 nutrition, 304
Sotos syndrome, 486 positive pressure nasopharyngeal support, 304
Speech routine sepsis investigation, 304
articulation errors, 87 mortality and morbidity, 308
intelligible, 87 pathophysiology, 300–303
perceptual evaluation, 87 surgical intervention
therapy, 88, 106 abdominal surgery, 307
velopharyngeal insufficiency, 87, 88 drainage, 306–307
Sphincteric UC, 556 ‘housekeeping’ laparotomie, 307–308
Sphincterostenotic UC, 556 indications for, 306
Spina bifida aperta, 639–641 laparoscopic intervention, 307
Spinal cyst, 620 Surgical simulators and models, 3
Spinal deformities, 134–135 Surgical success, 94–95
724 Index

Suturectomy, 629–630 pathogenesis, 187–188

Swallowing therapy, 106 surgery
Sylvian cyst, 618–619 correction, 192
Synaptogenesis, 19 with distal tracheoesophageal fistula, 192–195
Syndromic cleft lip, 74 long-gap, 196–197
Syndromic costal anomalies prematurity, 194–196
cerebrocostomandibular syndrome, 127 staging approach, 192
Jarcho-Levin syndrome, 127 type V, 197–198
Jeune syndrome, 125–126 Tracheomalacia, 189
Synthetic colloids, 10 Tracheotomy, 69
Systemic amyloidosis, 104 Transillumination, 154
Trans sphenoidal encephalocele, 635
Transurethral puncture (TUP), 561, 562, 564–566
T Transversal pectus excavatum, 121
Technetium 99m (99mTc), 557 Traumatic pneumothorax, 151
TEF, (see Tracheoesophageal fistula (TEF)) Treacher collins syndrome (TCS), 67, 68
Tennison procedure, 81–82 Triangular cord sign, 38, 391
10-N principles, 7–8 Trisomies, 460
Teratogenic agents, 73 Tuberous sclerosis complex, 654
Teratoma Turner’s syndrome, 460
cervical, 508–509 Tympanometry, 86–87
SCT (see (Sacrococcygeal teratoma (SCT)))
Teratomas, 145–146, 662, 671
Third ventriculocisternostomy, 621–623 U
Thoracentesis, 155 UCs, (see Ureteroceles (UCs))
Thoracic circumference, 118 Ultrasonography (USG)
Thoracic deformities, 117 biliary tract system in children, 412
Thoracic ectopia cordis, 129 chest neonatal imaging, 27
Thoracic index, 119 choledochal cyst, 410
Thoracic intercostal muscle groups, 178 gastroesophageal reflux disease, 213
Thoracoabdominal ectopia cordis, 129 gastrointestinal neonatal imaging
Thoracoamniotic shunt, 172 advantages, 35
Thoracoscopy, 160 biliary atresia, 38
Thymic tumors, 147 choledochal cysts, 38–39
Thyroglossal cyst (TC), 111, 112 complications, 39
Tongue reduction techniques, 107 conventional transabdominal approach, 35
Total body water (TBW), 9 small and large bowel, 36–38
Total parenteral nutrition (TPN), 159 triangular cord sign, 38
Total urogenital mobilization (TUM), 599 upper GI tract, 35–36
Tracheoesophageal fistula (TEF) gatrointestinal tract duplications, 281, 282
classification, 188–190 mesenteric and omental cysts, 295, 296
clinical and syndromic associations, 188 urogenital neonatal imaging
complications after birth, 41
anastomotic leak, 198 genital system, 42–44
chylothorax, 198 urinary system, 41–42
dysphagia and esophageal dysmotility, 199 Ultrasound (US)
esophageal stricture, 198 biliary atresia, 391
gastroesophageal reflux, 199 CAKUT in HRSC patients, 317
long-term, 199 Doppler (see (Doppler ultrasound))
persistent respiratory symptoms, 199–200 hydrocele, 365
predictors of, 198 malrotation, 378–379
recurrent tracheoesophageal fistula, 198–199 Meckel diverticulitis, 435, 436
short-term, 198 mediastinal masses, 142
definition, 187 of neck, 111
diagnosis urachal abnormality, 438
at birth, 190–191 vascular access, 11
delayed, 191 Umbilical catheters (UV), 12
prenatal, 190 Unilateral cleft lip and palate (UCLP), 73, 74, 91
epidemiology, 187 Unilateral hydronephrosis, 520
esophageal atresia (EA), 56, 57 Unilateral labio-maxillary-palatal cleft, 74
gastroesophageal reflux disease, 211–212 UPJ obstruction, (see Ureteropelvic junction (UPJ))
Index 725

Upper esophageal flap, 196 classification system, 517

Upper gastrointestinal tract X-ray, 142 high-risk group, 517
Upper limb anomalies, 129 low-risk group, 517
Upper pouch bougienage, 196 postnatally detected hydronephrosis, 521
Urachal remnants Urinary tract infections (UTIs), 533, 585
causes, 437 VUR
classification, 437, 438 EAU/ESPU guideline, 538
clinical presentation, 437–438 and reflux nephropathy, 539
diagnosis, 438 renal US, 538
epidemiology, 437 signs and symptoms of, 537
treatment, 439 urine culture, 538
Ureteroceles (UCs) Urogenital neonatal imaging
classification computed tomography, 46
cecoureterocele, 556 contrast studies, 44–45
duplex system, 556 intravenous urography, 46
ectopic, 555, 556 magnetic resonance imaging, 45–47
intravesical, 556 plain film, 46
simple, 555 prenatal ultrasonography, 40
single system, 556 surgical diseases, 40–41
sphincteric, 556 ultrasonography
sphincterostenotic, 556 after birth, 41
stenotic, 556 genital system, 42–44
conservative management, 561 urinary system, 41–42
definition and demographics, 555 Urogenital sinus (UGS), 591
diagnosis Ursodeoxycholic acid (UDCA), 394–395
cystoscopy, 560 USG, (see Ultrasonography (USG))
diagnostic workup, 557 UTD, (see Urinary tract dilation (UTD))
distended bladder, 556, 558 UTIs, (see Urinary tract infections (UTIs))
DMSA scan, 557
ectopic, 560
goals of, 557 V
intravenous pyelogram, 558–560 VACTERL spectrum, 188
MAG3 scan, 557, 559 Vaginostomy
postnatal US, 557 abdominal, 597, 598
VCUG, 557, 559 perineal, 597, 598
embryology, 555 Vanillylmandelic acid (VMA), 473
fetal intervention, 568–571 VAS, (see Vesicoamniotic shunting (VAS))
goals of treatment, 561 Vascular access
lower tract approaches arterial catheterization, 13–14
superior moiety salvage procedures, 572–573 peripheral and central venous catheterization,
total reconstruction, 571–572 11–12
nonoperative management, 562–564 central-inserted central catheter, 13
presentation peripherally inserted central catheters, 12–13
dumbbell, 556, 557 peripheral venous catheters, 12
perineal mass, 556, 557 umbilical catheters, 12
surgical management ultrasound, 11
endoscopic puncture, 566 vessel visualization, 11
holmium:yttrium aluminum garnet (Ho:YAG) Vascular anomalies
laser, 567, 568 ISSVA classification of, 700
laser fibers, 568 vascular malformations
neodymium-doped: yttrium aluminum garnet Cobb syndrome, 700
(Nd:YAG) laser, 566 fast-flow malformations, 698, 699
TUP, 564–566 KTS, 698, 699
upper tract approaches, 573–575 low-flow malformations, 692–698
Ureteropelvic junction (UPJ), 515, 517–519, 522 PWS, 698, 700
Ureteropelvic junction obstruction (UPJO), 41, 42 Wyburn Mason syndrome, 700
Urethra, 461 vascular tumors
Urethroplasty, 451 congenital hemangioma, 690–692
Urinary catecholamines, 473 infantile hemangioma, 687–690
Urinary tract dilation (UTD), 515 tufted angioma/kaposiform
antenatally detected hydronephrosis, 521 hemangioendothelioma, 692
726 Index

Vascular malformations secondary VUR surgical treatment, 549–550

AVMs, 698, 699 high urinary tract diversion, 551
Cobb syndrome, 700 primary valve ablation, 550
KTS, 698, 699 vesicostomy, 550, 551
low-flow malformations Video-assisted thoracoscopic surgery (VATS), 183
capillary malformations, 692–694 Video nasopharyngeal endoscopy, 87
lymphatic malformations, 694–696 VMs, (see Venous malformations (VMs))
venous malformations, 694, 696–698 Vogel classification, 101
PWS, 698, 700 Voiding cystourethrogram (VCUG), 44–45, 519, 520
Wyburn Mason syndrome, 700 MCDK, 529
Vascular neoplasm, 479, 480 PUV, 586
Vascular tumors UC, 557, 559
hemangioma VUR, 537–540
CH, 690–692 Voiding urosonography (VUS), 45, 519
IH, 687–690 Vomiting, 210, 214, 216, 229
tufted angioma/kaposiform hemangioendothelioma, bilious, 254, 267, 312, 343, 375
692 non-bilious, 227, 228, 234, 235, 240
Vascular ultrasound, 11 Von Hippel-Lindau disease, 655
Vasoactive intestinal peptide syndrome (VIP), 473 Vulvar hemangiomas, 689
VATS, (see Video-assisted thoracoscopic surgery (VATS)) VUR, (see Vesicoureteral reflux (VUR))
VCFS, (see Velocardiofacial syndrome (VCFS)) VURD syndrome, 589
VCUG, (see Voiding cystourethrogram (VCUG)) VUS, (see Voiding urosonography (VUS))
Vein visualization
in-plane, 11
out-of-plane, 11 W
Velocardiofacial syndrome (VCFS), 79 WAGR syndrome, 485
Velopharyngeal insufficiency (VPI), 87, 88 Wardill palatoplasty, 82
Veloplasty, 83, 84 Warm/hot intrahepatic choledochal cyst, 406
Venous malformations (VMs), 694 Waterston classification, 189
complications, 696 Whirlpool sign, 379
gene TIE2, 696 Wilms tumor (WT)
imaging investigation, 697 clinical features, 486
prevalence, 696 diagnosis
sclerotherapy, 697 CT, 487
sinus pericranii, 697, 698 MRI, 487
upper aerodigestive tract, 697 ultrasonography, 486–487
Ventricular shunt placement, 649 genetic and risk factors
Ventriculoatrial shunt, 627 Beckwith-Wiedemann syndrome, 486
Ventriculoperitoneal shunt, 626 Denys-Drash syndrome, 485
Vertebral, anal, cardiac, tracheo-esophageal, renal, limb isolated hemihypertrophy, 486
(VACTERL), 325 Perlman syndrome, 486
Vertex craniectomies, 629 Simpson-Golabi-Behmel syndrome, 486
Vesicoamniotic shunting (VAS), 569, 583, 584 Sotos syndrome, 486
Vesicostomy, 550, 551 WAGR syndrome, 485
Vesicoureteral reflux (VUR), 460, 589 WT1 gene, 485
clinical presentation and diagnostic pathway pathology, 486
febrile urinary tract infections/pyelonephritis, prognostic factors and risk stratification, 487
537–538 surgery of
prenatal hydronephrosis, 534–537 complication of, 489
siblings/offspring of reflux patients, 537 para-aortic lymph nodes, 488
conservative approach, 540–541 renal artery, 488
definition, 533 renal vein, 488
epidemiology, 533–534 retroperitoneal space, 488
imaging transverse upper abdominal incision, 488
DMSA renal scan, 539, 540 ureter, 488
echo-enhanced CSG, 540 therapeutic management
renal and bladder ultrasound, 538–539 chemotherapy, 487
VCUG, 539, 540 NWTSG, 487
primary VUR surgical treatment radiotherapy, 487
endoscopic VUR treatment, 541–542 SIOP, 487
ureteral reimplantation, 542–549 VLRWT, 487
Index 727

Wilms tumor 1 (WT1) gene, 485 congenital pouch colon, 343, 344
Window colostomy, 346 gatrointestinal tract duplications, 281
WT, (see Wilms tumor (WT)) NEC perforation with free gas, 302–303
Wyburn Mason syndrome, 700 rectourethral fistula, 331

X Y
X-ray Young-Dees-Leadbetter procedure, 453
chest, 26, 134
congenital diaphragmatic hernia, 179
congenital pulmonary airway malformations, 171 Z
mediastinal masses, 142 Z-plasty, 80, 82
pneumothorax, 153