Find best premium and Free Joomla templates at GetJoomlaTemplatesFree.com

Updates in: Oesophageal Atresia with or without Tracheoesophageal Fistula

Alexander L. Macdonald, Simon A. Clarke

Department of Paediatric Surgery, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK

 

Correspondence:

Simon Clarke

Department of Pediatric Surgery

Chelsea and Westminster NHS Foundation Trust

369 Fulham Road, SW10, London, UK

E-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

Phone: 02087468000

 

Abstract

Oesophageal atresia with or without tracheoesophageal fistula represents a spectrum of pathology and over half of infants will have associated congenital co-morbidites which may be life-threating and account for significant morbidity and mortality. Antenatal features are non-specific and detection rates vary considerably requiring prompt post-natal recognition of symptomatic infants. Peri-operative surgical and anaesthetic practice is variable. Recent advances in surgical technique include the adoption of the minimally invasive thoracoscopic approach and outcomes are at least comparable to conventional open repair. Regardless of approach post-operative complications particularly anastomotic stricture are frequent and may require several re-interventions. Long gap oesophageal atresia represents a complex subset of patients who may require oesophageal replacement and the optimum approach to such cases remains contentious. Long-term gastrointestinal and respiratory morbidity is often significant and requires multidisciplinary follow-up. Future advances include tissue engineering techniques which have the potential to produce oesophageal replacement grafts with anatomical and functional attributes equivalent to native tissue. In this highly complex low volume pathology, re-configuration and centralisation of management to higher volumes centres has potential to improve patient outcomes.

Keywords: oesophageal atresia, tracheooesophageal fistula

 

Introduction

The first description of oesophageal atresia (OA) is often attributed to Durston in 1670 and the first successful primary anastomosis was performed by Haight in 1941 [1]. In recent decades advances in perioperative care, surgical approaches and the management of associated co-morbidities has resulted in survival rates that exceed 90%. However, with increased survival both post-operative and long-term morbidity has become more prevalent. Surgical technique and perioperative care still varies considerably amongst institutions and the optimal management of the subset of infants with long-gap OA continues to attract considerable controversy. Thus the management of OA with and without tracheoesophageal fistula (OA/TOF) continues to present numerous challenges for paediatric surgeons. This review aims to provide to provide an overview of the diagnosis and contemporary surgical management of the full spectrum of OA/TOF.

Embryology and Classification

Embryology

The embryology of OA/TOF is complex. Whilst significant advances have been made in understanding the morphogenesis of the trachea and oesophagus and the events leading to OA/TOF, the specifics of the underlying causative mechanism remain poorly understood. At a basic level OA/TOF may be considered as arising as a consequence of a partial failure of the compartmentalisation process during which the oesophagus and trachea arise from their common endodermal origin in the anterior foregut tube. Reproducible models such as the teratogenic adriamycin rodent model are reported and failures in the pattern of expression of particular developmental genes including sonic hedgehog (Shh) have been implicated but considerable research questions remain [1-3].

Classification:

Anatomically OA/TOF is typically described by the overlapping Gross and Vogt classifications which comprise; oesophageal agenesis (Vogt type 1); isolated OA without TOF (7%, Gross type A, Vogt type 2); OA with proximal TOF (1%, Gross type B, Vogt type 3A); OA with distal TOF (85%, Gross type C, Vogt type 3B); OA with proximal and distal TOF (3%, Gross type D, Vogt type 3C); and H-type TOF without OA (4% Gross type E) (Fig. 1).

Figure 1. Anatomical classification of oesophageal atresia with or without tracheoesophageal fistula.

10.3 2 1

In addition to anatomical classification there exist numerous prognostic systems that seek to stratify risk including the Waterston (1969) and Spitz (1994) classifications (Table I). The original Waterston classification stratified 218 infants into 3 risk groups; Group A (95% survival); Group B (68% survival) and Group C (6% survival). The Spitz classification emphasises the impact of birth weight and presence of major cardiac anomaly stratified 372 infants into 3 groups with survival ranging from 97% (Group I) to 22% (Group III). In contemporary practice the presence of associated major cardiac malformations continues to define the risk of mortality [4].

Table 1. Prognostic classification of TOF/OA

Group

Features

Prognosis

Waterston classification

A

Birth weight >2.5kg and no co-morbidity

95% survival

B

Birth weight 1.8-2.5kg, pneumonia and congenital anomaly

68% survival

C

Birth weight <1.8kg, severe pneumonia and congenital anomaly

6% survival

Spitz classification

I

Birth weight >1.5kg and no major cardiac anomaly

97% survival

II

Birth weight <1.5kg or major cardiac anomaly

59% survival

III

Birth weight <1.5kg and major cardiac anomaly

22% survival

Diagnosis and pre-operative care

Antenatal detection

OA/TOF has a reported incidence ranging from 1 per 2,500-4500 live births. In Europe antenatal detection rates vary considerably from >50% to <10% in a multi-national multi-registry population with a reported incidence of 2.43 cases per 10,000 births [5]. Detection rates are significantly higher in tertiary referral centres [6]. Features on foetal ultrasound suggestive of OA/TOF are non-specific and include polyhydramnios (95% of infants with pure OA) and an absent or small stomach bubble (infants with OA without distal TOF). More specific signs such as visualisation of the dilated upper pouch (‘upper pouch sign’) may be evident by the 32nd gestational week but are often only appreciated by experienced foetal sonographers. Features of associated malformations (e.g. spinal and cardiac) may be more readily identified.

Post-natal diagnosis

Where polyhydramnios has been identified antenatally a nasogastric tube should be passed at birth to ascertain the continuity of the oesophagus. However, given the overall low rates of antenatal detection a significant number of infants with OA/TOF will only be identified when they become symptomatic postnatally and the diagnosis should be suspected in infants with excess salivation, cyanotic episodes and/or feeding difficulties. Diagnosis of OA/TOF is confirmed by failure to pass a 10Fr feeding tube beyond 10 – 11 cm from the incisors or 15cms from the nostril [7]. A chest radiograph may further confirm the diagnosis by demonstrating the bulbous gas shadow of the upper pouch (Fig. 2). Where sub diaphragmatic intestinal gas is seen on an abdominal radiograph a presumed diagnosis of OA with distal TOF may be made. In rare circumstances where there is diagnostic doubt, a water-soluble contrast study of the presumed upper pouch may provide clarification but care should be taken to avoid contrast aspiration.

Figure 2. Feeding tube curled in upper pouch of infant with oesophageal atresia

10.3 2 2

Pre-operative care

The condition of the neonate at birth may necessitate resuscitation. Where possible invasive ventilation should be avoided as in the presence of OA with distal TOF, there is a risk of gastric over-distension and perforation. Following appropriate resuscitation, a 10Fr Replogle (double lumen) tube should be passed via the oro-pharynx into the upper oesophageal pouch with the distal tip 0.5cm from the blind end of the pouch. The tube is placed on continuous low pressure (11-25mmHg) suction to ensure clearance of saliva and prevent aspiration and should be monitored and flushed regularly for signs of occlusion by secretions.

OA/TOF is predominately sporadic but is also associated with a number of congenital malformations often as part of the VACTERL (Vertebral, Anorectal, Cardiac, Esophageal, Renal and Limb) constellation. Approximately half of all cases of OA/TOF will have an associated malformation including; cardiac (29%); anorectal (14%); genitourinary (14%); gastrointestinal (13%); vertebral/skeletal (10%); respiratory (6%) and genetic (4%) [1]. A comprehensive clinical examination of the neonate should thus be conducted with particular attention to the perineum, spine and limbs. Ultrasound imaging of the renal tract and spine should be performed in the neonatal period but may be deferred until after surgery.

Given the known association with potentially significant cardiac malformations an echocardiogram is often performed pre-operatively to identify and characterise the severity of any associated cardiac malformation. In addition, pre-operative echocardiogram can be advantageous in that it may identify significant vascular anatomical variants including aberrant right sub-clavian artery (ARSA, 12% of patients with OA/TOF) and right aortic arch (RAA, 6% of patients) [8,9]. However, whilst pre-operative echocardiography may be informative it is not necessarily essential as it has been demonstrated that the findings of a normal clinical examination and normal plain radiographs satisfactorily excludes the presence of any significant cardiac malformation [10]. Additionally, the impact on the choice of surgical approach by knowledge of the aortic anatomy is controversial and convincing evidence that it should dictate the surgical approach is lacking. Rather, in the presence of RAA, the choice of approach should remain at the discretion of the operating surgeon based on their individual experience and training [11].

Surgical approach

Anaesthesia

The anaesthetic management of the infant with OA/TOF is challenging particularly from the perspectives of the anatomy of the airways; the physiological impact of thoracotomy and lung retraction; and the influence of associated malformations (particularly cardiac). The traditional approach to management of the airway is to minimise ventilation via the fistula (and potential gastric distension which if significant can compromise ventilation) by aiming to intubate the trachea distal to the fistula and allowing spontaneous ventilation until the fistula is surgically controlled.

Rigid bronchoscopy with a ventilating bronchoscope is often performed [12,13] and offers the ability to: aid intubation distal to the fistula; delineate the number and location of the fistula(e); identify additional anatomical aberrations of the airway; and assess the degree of tracheomalacia. Bronchoscopy may also be used to isolate the fistula by passage of a Fogarty balloon catheter.

Open surgery

For thoracotomy the infant is positioned on their left side with the neck flexed and arm elevated [1]. A right posterior-lateral thoracotomy is performed via the 4th or 5th intercostal space. The pleura is separated from the chest wall to permit extra-pleural repair where possible. The azygous vein is identified, ligated and divided permitting full exposure of the posterior mediastinum according to surgical preference. The fistula is controlled by placing a sling around it and then transfixed and divided close to the trachea. The upper pouch is identified by the anaesthetist advancing the Replogle tube and is mobilised (a further fistula should be excluded at this point) and anastomosed in and end to end fashion to the lower pouch with a single-layer interrupted 5/0 or 6/0 absorbable sutures. Where possible tension should be avoided but often it is necessary to perform an anastomosis under tension. Prior to completion of the anterior layer of the anastomosis a naso or oro-gastric feeding tube is advanced across the anastomosis in place of the Replogle tube to act as a trans-anastomotic tube (TAT). Following completion of the anastomosis this TAT may be left in place to permit early enteral feeding. If the repair was intra-pleural (deliberately or inadvertently) then a tube thoracostomy may be left in place particularly if any breach occurs to lung parenchyma. Additionally, some surgeons may justify leaving a tube thoracostomy as a means to expectantly manage any anastomotic leak if the anastomosis has been difficult.

Thoracosopic approach

The first thoracoscopic repair was performed by Rothenberg in 1999 [14]. Whilst there is a considerable learning curve for the inexperienced surgeon, current outcome data is at least comparable to the open approach and in experienced centres may be superior to open surgery. Advantages of the thoracoscopic approach include improved cosmesis and the avoidance of the potential chest wall morbidity from a thoracotomy which can be significant [15]. In addition, thoracoscopy may provide superior visualisation of the upper and lower pouches facilitating dissection and mobilisation. Thoracoscopy is potentially contra-indicated in low birth weight infants and those with significant cardiac malformations and/or haemodynamic instability [16].

Operative management of Long-gap

OA Long gap oesophageal atresia LG-OA can present considerable surgical challenge with regard to restoring oesophageal continuity. A precise consensus definition of what constitutes ‘long’ in the context of LG-OA is lacking and for some authors it is a particular gap length measured in cm (e.g. 4cm) whilst for others it is a distance represented in terms of vertebral bodies (e.g. 4 vertebral bodies). Alternatively, LG-OA may simply be considered to encompass all OA lacking a distal fistula [17].

The gap length may be formally assessed by introducing a radio-opaque urethral dilator into the distal pouch via the gastrostomy (usually sited at birth) and measuring under fluoroscopy the distance (in cm or vertebral bodies) between the distal pouch (demarcated by the tip of the urethral dilator) and the proximal pouch (demarcated by the tip of the Replogle tube). The age at which surgical correction of LG-OA is attempted varies with the approach taken to restoring oesophageal continuity but is typically delayed until the infant is 2-3 months of age. Thus a gastrostomy is often placed to permit enteral feeding and decompress the stomach prior to definitive corrective surgery and a Replogle tube is used to drain the upper pouch.

Numerous techniques and approaches are described in the literature for achieving continuity in LG-OA ranging from simple to delayed primary anastomosis to traction techniques and to oesophageal replacement [18]. Delayed primary anastomosis relies on spontaneous growth of the oesophagus and is described in gap lengths up to 7cm although is associated with a high incidence of anastomotic stricture (AS) and gastro-oesophageal reflux disease (GORD). Traction elongation techniques include the Fokker technique [19] whereby external traction sutures are utilised to promote elongation of the upper and lower pouches permitting anastomosis. Modifications of this technique include the use of silastic tubing to prevent sutures under tension cutting through the tissue.

Where the gap is considerable (e.g. greater than 6 vertebral bodies) or other strategies have failed or tissue has been lost due to post-operative complications, oesophageal replacement may be necessary. In such cases often a cervical oesophagostomy is created in the first instance to drain the upper pouch prior to definitive reconstruction. Numerous oesophageal replacement strategies are reported in the literature but the most data is attributed to replacement by gastric pull-up, jejunal interposition graft or colonic interposition grafts. Mortality, anastomotic complications and graft loss are considered to be broadly comparable between the techniques [20-24]. Gastric pull-up is associated with a higher incidence of respiratory complications but fewer gastrointestinal complications than interposition grafts [24,25]. Choice of technique at present depends on surgeon/centre experience. The thoracoscopic approach to LG-OA is feasible with regard to both primary anastomosis and traction elongation techniques and reported outcomes are comparable to open approaches [26,27].

Post-operative care

A number of surgeons electively paralyse patients [12] on the NICU post-operatively (for up to 5 days) with the neck flexed to protect the anastomosis, though this is usually if the repair was under tension. Where a TAT tube is present TAT feeds may be started on post-operative day 1. In the absence of complications oral feeds are typically introduced on post-operative days 3 – 5 [12]. Some surgeons advocate performing an UGI contrast to ascertain that the anastomosis is intact prior to introducing oral feeds [12]. However, the specificity of this practice in identifying a clinically significant leak has been questioned. Parenteral nutrition may be employed whilst enteral feeding is still being established.

Surgical complications

Complications

Whilst overall survival is high the incidence of post-repair morbidity is significant [28]. Important potential complications include anastomotic leak (5-7%); anastomotic stricture (up to 50%) and recurrent fistula (3-5%). Incidence of anastomotic complications is not necessarily related to gap length [29]. Early major anastomotic leak may present with a tension pneumothorax necessitating emergency tube thoracostomy. Later leaks are best managed conservatively with chest drain and TPN though stricture formation is common. Recurrent TOF may present with choking or cyanotic episodes whilst feeding and/or recurrent LRTI. Post-repair complications may often necessitate multiple re-operations and in some cases there may be a need for oesophageal replacement although the majority survive with a functioning native oesophagus [30].

Management of anastomotic strictures

Anastomotic stricture is the most common complication post-repair and approximately one third of infants will develop a clinically significant stricture [31,32]. In some series stricture rates are as high as 53%. LG-OA and staged repair is associated with higher rates of stricture. Gastro-oesophageal reflux disease (GORD) is often considered to be a causative factor in stricture formation and many advocate the use of prophylactic anti-reflux medication to reduce the likelihood of stricture although currently data from large multi-centre studies does not support this practice [33].

Anastomotic strictures may present with increased oral secretions, dysphagia and/or choking episodes. Diagnosis is typically by upper GI contrast. Strictures often require multiple dilatations and this may be performed by bougie dilatation or endoscopically or radiographically by balloon dilatation. No particular technique has been demonstrated as being more effective and the choice is typically based on surgeon/centre experience [31,34,35]. Convincing evidence to support prophylactic dilatation of asymptomatic infants is lacking [36]. Strictures refractory to multiple attempts at bougie and/or balloon dilatation may require adjuvant therapies including; steroid injections; topical mitomycin or oesophageal stenting.

Long-term outcomes

Long term gastrointestinal (GI) and respiratory morbidity related specifically to OA/TOF (as opposed to any associated congenital malformations if present) is common particularly in the first year of life and may be associated with a difficult anastomosis and/or failure to establish full oral feeds [37]. Respiratory morbidity following repair of OA/TOF includes; micro-aspirations and lower respiratory tract infections and/or recurrent bronchitis; chronic asthma and chronic cough [38,39]. Tracheomalacia is a potentially significant entity that is essentially intrinsic to the OA/TOF complex and is typically evident as the classical chronic barking ‘TOF cough’ [40]. However, in some infants tracheomalacia may be significant leading to acute life-threatening events (ALTE) and may necessitate aortopexy.

GI co-morbidities include dysphagia, GORD and failure to thrive in infancy [41]. Dysphagia secondary to oesophageal dysmotility may be of variable severity. A degree of dysmotility will be intrinsic and a product of the abnormal neuromuscular development of the oesophagus but a proportion may be attributed to or exacerbated by the extent of dissection/mobilisation at surgery; stricture formation and presence of GORD [42].

GORD in OA/TOF patients is common (up to 65%) and is primarily a product of the intrinsic oesophageal dysmotility. The management of GORD in OA/TOF is dependent on severity and patient characteristics and may be conservative, pharmacological or surgical. A poor correlation between severity of reflux symptoms and histological changes leads some authors to advocate long-term endoscopic surveillance and pH monitoring for all patients with repaired OA/TOF [43].

In addition to GI and respiratory morbidity OA/TOF patients are susceptible to a degree of neurodevelopmental delay. With a broad range of potential long-term morbidity it is important that as a minimum standard long-term multidisciplinary follow-up be in place for all infants with repaired OA/TOF.

Key guidelines

1. Antenatal features are non-specific and a significant proportion of cases will not be identified antenatally necessitating prompt post-natal recognition of suggestive symptoms.

2. Over 50% of infants will have an associated congenital anomaly which may include significant cardiac malformations that impact upon survival.

3. Perioperative bronchoscopy can be advantageous to aid intubation and delineate the fistula anatomy but is not considered essential practice.

4. LG OA/TOF is a complex entity necessitating highly specialised management.

5. Thoracoscopic surgery is available in specialist centres and offers several potential advantages over thoracotomy and is at least as effective with regard to rates of anastomotic complications.

6. Anastomotic stricture is common and often requires repeated dilatation.

7. Prevention of stricture by the use of prophylactic anti-reflux medication and/or prophylactic dilatation is not supported by current evidence.

8. Long term respiratory and gastrointestinal morbidity is common and demands multidisciplinary follow-up.

Future research directions

Tissue-engineering

Current means of oesophageal replacement such as gastric pull-up and jejunal/colonic interposition grafts are not without complication as is evident from long-term outcome data. Regenerative medicine and oesophageal replacement with bespoke engineered tissue has enormous potential to overcome the majority of the issues associated with current replacement strategies by offering an engineered substitute equivalent to native tissue [44]. However, producing an engineered oesophagus that is that is anatomically and functionally equivalent is a challenging premise with the need for a proliferative epithelium, smooth muscle for propulsive activity and regulating enteric nervous tissue all adding considerable degrees of complexity. Work on the development of relevant viable decellurised scaffolds and epithelial cell sheets has been encouraging and there have been several successful animal studies that demonstrate considerable promise [45]. The gap to clinical trial and application has yet to be satisfactorily bridged and this remains a challenge for the future.

Centralisation of services

In a number of complex infrequently occurring pathologies across the spectrum of medical practice high volume centres have been shown to outperform their low volume counterparts across a variety of patient outcomes measures. OA/TOF is a complex entity where surgeon and centre experience is likely to heavily influence outcomes [46]. In addition, there is considerable morbidity that may be related to associated malformations (particularly cardiac) that necessitates multi-disciplinary care. There is therefore considerable weight to the argument that the management of OA/TOF should be limited to centres or groups of surgeons to enable higher case volumes and where the availability of an appropriately-resourced multidisciplinary team can be assured. National population outcome studies and registry data are required to further delineate the relationship between centre volume and outcome in OA/TOF and to determine if there are significant gain to be made from service re-configuration.

 

References:

1. Spitz L, Bax NM. Esophageal atresia with and without tracheoesophageal fistula. In: Spitz L, Coran A, editors. Operative Pediatric Surgery. 6th ed., London: Hodder Arnold; 2006, p. 109–20.

2. Ioannides AS, Copp AJ. Embryology of oesophageal atresia. Semin Pediatr Surg 2009;18:2–11.

3. El-Gohary Y, Gittes GK, Tovar JA. Congenital anomalies of the esophagus. Semin Pediatr Surg 2010;19:186–93.

4. Malakounides G, Lyon P, Cross K, Pierro A, De Coppi P, Drake D, et al. Esophageal Atresia: Improved outcome in high-risk groups revisited. Eur J Pediatr Surg 2015;26:227–31.

5. Pedersen RN, Calzolari E, Husby S, Garne E. Oesophageal atresia: Prevalence, prenatal diagnosis and associated anomalies in 23 European regions. Arch Dis Child 2012;97:227–32.

6. Bradshaw CJ, Thakkar H, Knutzen L, Marsh R, Pacilli M, Impey L, et al. Accuracy of prenatal detection of tracheoesophageal fistula and oesophageal atresia. J Pediatr Surg 2016; 51(8):1268-72.

7. Smith N. Oesophageal atresia and tracheo-oesophageal fistula. Early Human Development 2014; 90:947–50.

8. Berthet S, Tenisch E, Miron MC, Alami N, Timmons J, Aspirot A, et al. Vascular anomalies associated with Esophageal Atresia and Tracheoesophageal Fistula. J Pediatr 2015; 166:1140–4.e2.

9. Babu R, Pierro A, Spitz L, Drake DP, Kiely EM. The management of oesophageal atresia in neonates with right-sided aortic arch. J Pediatr Surg 2000;35:56–8.

10. Nasr A, McNamara PJ, Mertens L, Levin D, James A, Holtby H, et al. Is routine preoperative 2-dimensional echocardiography necessary for infants with esophageal atresia, omphalocele, or anorectal malformations? J Pediatr Surg 2010; 45:876–9.

11. Parolini F, Armellini A, Boroni G, Bagolan P, Alberti D. The management of newborns with esophageal atresia and right aortic arch: A systematic review or still unsolved problem. J Pediatr Surg 2016;51:304–9.

12. Zani A, Eaton S, Hoellwarth M, Puri P, Tovar J, Fasching G, et al. International survey on the management of Esophageal Atresia. Eur J Pediatr Surg 2013;24:003–8.

13. Touloukian RJ. Thirty-five–Year institutional experience with end-to-side repair for Esophageal Atresia. Arch Surg 2004;139:371.

14. Lobe TE, Rothenberg S, Waldschmidt J, Stroedter L. Thoracoscopic repair of Esophageal Atresia in an infant: A surgical First. Pediatric Endosurgery & Innovative Techniques 1999;3:141–8.

15. Chetcuti P, Myers NA, Phelan PD, Beasley SW, Dickens DRV. Chest wall deformity in patients with repaired esophageal atresia. J Pediatr Surg 1989;24:244–7.

16. Rothenberg S. Thoracoscopic repair of esophageal atresia and tracheo-esophageal fistula in neonates: The current state of the art. Pediatr Surg Int 2014;30:979–85.

17. Bax KMA. Jejunum for bridging long-gap esophageal atresia. Semin Pediatr Surg 2009;18:34–9.

18. Friedmacher F, Puri P. Delayed primary anastomosis for management of long-gap esophageal atresia: A meta-analysis of complications and long-term outcome. Pediatr Surg Int 2012;28:899–906.

19. Foker JE, Kendall Krosch TC, Catton K, Munro F, Khan KM. Long-gap esophageal atresia treated by growth induction: The biological potential and early follow-up results. Semin Pediatr Surg 2009;18:23–9.

20. Spitz L. Esophageal replacement: Overcoming the need. J Pediatr Surg 2014;49:849–52.

21. Ng J, Loukogeorgakis SP, Pierro A, Kiely EM, De Coppi P, Cross K, et al. Comparison of minimally invasive and open gastric transposition in children. J Laparoendosc Adv Surg Tech A 2014; 24:742–9.

22. Lee HQ, Hawley A, Doak J, Nightingale MG, Hutson JM. Long-gap oesophageal atresia: Comparison of delayed primary anastomosis and oesophageal replacement with gastric tube. J Pediatr Surg 2014;49:1762–6.

23. Gallo G, Zwaveling S, Van der Zee DC, Bax KN, de Langen ZJ, Hulscher JBF. A two-center comparative study of gastric pull-up and jejunal interposition for long gap esophageal atresia. J Pediatr Surg 2015;50:535–9.

24. Bairdain S, Foker JE, Smithers CJ, Hamilton TE, Labow BI, Baird CW, et al. Jejunal interposition after failed Esophageal Atresia repair. J Am Coll Surg 2016;222:1001–8.

25. Zwaveling S, Groen H, Van der Zee D, Hulscher J, Gallo G. Long-gap Esophageal Atresia: A Meta-Analysis of Jejunal interposition, colon interposition, and gastric pull-up. Eur J Pediatr Surg 2012;22:420–5.

26. van der Zee DC, Gallo G, Tytgat SHA. Thoracoscopic traction technique in long gap esophageal atresia: Entering a new era. Surg Endosc 2015;29:3324–30.

27. Rothenberg SS, Flake AW. Experience with Thoracoscopic repair of Long Gap Esophageal Atresia in Neonates. J Laparoendosc Adv Surg Tech A 2015;25:932–5.

28. Donoso F, Kassa A-M, Gustafson E, Meurling S, Lilja HE. Outcome and management in infants with esophageal atresia – A single centre observational study. J Pediatr Surg 2016;51(9):1421-5.

29. Thakkar HS, Cooney J, Kumar N, Kiely E. Measured gap length and outcomes in oesophageal atresia. J Pediatr Surg 2014;49:1343–6.

30. Koivusalo AI, Pakarinen MP, Lindahl HG, Rintala RJ. Revisional surgery for recurrent tracheoesophageal fistula and anastomotic complications after repair of esophageal atresia in 258 infants. J Pediatr Surg 2015; 50:250–4.

31. Serhal L, Gottrand F, Sfeir R, Guimber D, Devos P, Bonnevalle M, et al. Anastomotic stricture after surgical repair of esophageal atresia: Frequency, risk factors, and efficacy of esophageal bougie dilatations. J Pediatr Surg 2010; 45:1459–62.

32. Nice T, Tuanama Diaz B, Shroyer M, Rogers D, Chen M, Martin C, et al. Risk factors for Stricture formation after Esophageal Atresia repair. J Laparoendosc Adv Surg Tech A 2016; 26:393–8.

33. Allin B, Knight M, Johnson P, Burge D. Outcomes at One-Year post anastomosis from a national cohort of infants with Oesophageal Atresia. PLoS ONE 2014;9:e106149.

34. Khan KM. Endoscopic management of strictures in pediatrics. Tech Gastrointest Endosc 2013;15:25–31.

35. Thyoka M, Timmis A, Mhango T, Roebuck DJ. Balloon dilatation of anastomotic strictures secondary to surgical repair of oesophageal atresia: A systematic review. Pediatric Radiol 2013;43:898–901.

36. Koivusalo A, Pakarinen MP, Rintala RJ. Anastomotic dilatation after repair of esophageal atresia with distal fistula. Comparison of results after routine versus selective dilatation. Dis Esoph 2009;22:190–4.

37. Schneider A, Blanc S, Bonnard A, Khen-Dunlop N, Auber F, Breton A, et al. Results from the french national Esophageal Atresia register: One-year outcome. Orphanet J Rare Dis 2014;9. 

38. Fragoso AC, Tovar JA. The Multifactorial origin of respiratory morbidity in patients surviving neonatal repair of Esophageal Atresia. Frontiers in Pediatrics 2014;2.

39. Kovesi T. Long-term complications of congenital Esophageal Atresia and/or Tracheoesophageal Fistula. CHEST Jl 2004;126:915.

40. Mirra V, Maglione M, Di Micco LL, Montella S, Santamaria F. Longitudinal follow-up of chronic pulmonary manifestations in Esophageal Atresia: A clinical algorithm and review of the literature. Pediatr Neonatol 2016; 29 pii: S1875-9572(16)30059-6.

41. IJsselstijn H, Gischler SJ, Toussaint L, Spoel M, Zijp MHM van der C, Tibboel D. Growth and development after oesophageal atresia surgery: Need for long-term multidisciplinary follow-up. Paediatr Respir Rev 2016;19:34–8.

42. Mahoney L, Rosen R. Feeding difficulties in children with Esophageal Atresia. Paediatr Respir Rev 2016;19:21–7.

43. Pedersen RN, Markøw S, Kruse-Andersen S, Qvist N, Hansen TP, Gerke O, et al. Esophageal Atresia: Gastroesophageal functional follow-up in 5–15year old children. J Pediatr Surg 2013;48:2487–95.

44. Saxena AK. Tissue engineering and regenerative medicine research perspectives for pediatric surgery. Pediatr Surg Int 2010; 26:557–73.

45. Saxena A. Esophagus tissue engineering: Designing and crafting the components for the “Hybrid Construct” approach. Eur J Pediatr Surg 2014; 24:246–62.

46. Jawaid W, Chan B, Jesudason EC. Subspecialization may improve an esophageal atresia service but has not addressed declining trainee experience. J Pediatr Sur 2012;47:1363–8.