Prevalence and Predictive Factors of Histopathological Complications in Children with Esophageal Atresia

Abstract

Objectives Endoscopic follow-up after esophageal atresia (EA) tracheoesophageal fistula (TEF) repair is recommended to detect esophageal histopathological complications. We investigated the prevalence of histopathologically proven esophageal complications (peptic esophagitis, gastric metaplasia, and eosinophilic esophagitis) and assessed the predictors of these complications in children with EA-TEF.

Materials and Methods This is a prospective longitudinal cohort study performed between September 2005 and December 2014 comprising 77 children with EA-TEF followed-up until February 2017. Univariate analysis was performed using the Wilcoxon's rank-sum test for continuous variables and the Pearson's chi-square test for categorical variables. Multivariable analysis was performed using a Cox regression hazard model. The association between clinical factors and histopathologically proven complications was estimated using a Cox regression hazard model with time until the appearance of complications as the time scale.

Results All 77 children received proton pump inhibitors (PPIs) (n = 73) or H2 receptor antagonists (H2RA). A total of 252 endoscopies were performed in 73 children (median 2.6/child, range: 1–29). Median age at study completion was 4.9 years (range: 2.3–11.5 years). Histopathologically proven complications occurred in 38 children (52%): peptic esophagitis (n = 32, 44%), eosinophilic esophagitis (n = 15, 21%), and gastric metaplasia (n = 9, 12%). A total of 82% patients were on PPI or H2RA at the time of diagnosis of histological complication. Multivariable Cox regression analysis showed that patients with recurrent anastomotic strictures (>3 dilations) had a higher risk of occurrence of histopathologically proven complications over time (hazard ratio: 3.11, 95% confidence interval [CI]: 1.53–6.34). On univariate analysis, the result of the first endoscopy was not associated with the occurrence of histopathologically proven complications (odds ratio: 0.8, 95% CI: 0.16–3.95).

Conclusion Histopathologically proven complications with potential long-term consequences occurred in approximately 50% of children after EA-TEF repair. A history of recurrent anastomotic strictures is associated with the occurrence of these complications. The result of the first endoscopy does not predict the histopathological outcome. Children with EA-TEF warrant close and systematic long-term follow-up at specialized multidisciplinary clinics with endoscopic evaluation.

Keywords

esophageal atresia - esophagitis - eosinophilic esophagitis - acid reflux - endoscopy

• References

• 1 Spitz L. Oesophageal atresia. Orphanet J Rare Dis 2007; 2: 24
• 2 Lindahl H, Rintala R, Sariola H. Chronic esophagitis and gastric metaplasia are frequent late complications of esophageal atresia. J Pediatr Surg 1993; 28 (09) 1178-1180
• 3 Schalamon J, Lindahl H, Saarikoski H, Rintala RJ. Endoscopic follow-up in esophageal atresia-for how long is it necessary?. J Pediatr Surg 2003; 38 (05) 702-704
• 4 Deurloo JA, Ekkelkamp S, Taminiau JA. , et al. Esophagitis and Barrett esophagus after correction of esophageal atresia. J Pediatr Surg 2005; 40 (08) 1227-1231
• 5 Koivusalo AI, Pakarinen MP, Lindahl HG, Rintala RJ. Endoscopic surveillance after repair of oesophageal atresia: longitudinal study in 209 patients. J Pediatr Gastroenterol Nutr 2016; 62 (04) 562-566
• 6 Pedersen RN, Markøw S, Kruse-Andersen S. , et al. Esophageal atresia: gastroesophageal functional follow-up in 5-15 year old children. J Pediatr Surg 2013; 48 (12) 2487-2495
• 7 Castilloux J, Bouron-Dal Soglio D, Faure C. Endoscopic assessment of children with esophageal atresia: lack of relationship of esophagitis and esophageal metaplasia to symptomatology. Can J Gastroenterol 2010; 24 (05) 312-316
• 8 Dhaliwal J, Tobias V, Sugo E. , et al. Eosinophilic esophagitis in children with esophageal atresia. Dis Esophagus 2014; 27 (04) 340-347
• 9 Schneider A, Michaud L, Gottrand F. Esophageal atresia: metaplasia, Barrett. Dis Esophagus 2013; 26 (04) 425-427
• 10 Hsieh H, Frenette A, Michaud L. , et al. Intestinal metaplasia of the esophagus in children with esophageal atresia. J Pediatr Gastroenterol Nutr 2017; 65 (01) e1-e4
• 11 Krishnan U, Mousa H, Dall'Oglio L. , et al. ESPGHAN-NASPGHAN guidelines for the evaluation and treatment of gastrointestinal and nutritional complications in children with esophageal atresia-tracheoesophageal fistula. J Pediatr Gastroenterol Nutr 2016; 63 (05) 550-570
• 12 Liacouras CA, Furuta GT, Hirano I. , et al. Eosinophilic esophagitis: updated consensus recommendations for children and adults. J Allergy Clin Immunol 2011; 128 (01) 3-20
• 13 Lucendo AJ, Arias Á, Molina-Infante J. Efficacy of proton pump inhibitor drugs for inducing clinical and histologic remission in patients with symptomatic esophageal eosinophilia: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2016; 14 (01) 13-22
• 14 Lopez PJ, Keys C, Pierro A. , et al. Oesophageal atresia: improved outcome in high-risk groups?. J Pediatr Surg 2006; 41 (02) 331-334
• 15 Kovesi T, Rubin S. Long-term complications of congenital esophageal atresia and/or tracheoesophageal fistula. Chest 2004; 126 (03) 915-925