High Prevalence of Barrett’s Esophagus and Esophageal Squamous Cell Carcinoma After Repair of Esophageal Atresia

Published:November 10, 2017DOI:

      Background & Aims

      Esophageal atresia is rare, but improved surgical and intensive care techniques have increased rates of survival in children, so there are now many adults with this disorder. Many patients with esophageal atresia develop gastroesophageal reflux (GER), raising concerns about increased risk of Barrett’s esophagus (BE; prevalence of 1.3%–1.6% in general population) and esophageal carcinoma. We assessed the prevalence of BE and esophageal carcinoma in this population.


      We performed a prospective study of 289 patients with esophageal atresia at the Department of Gastroenterology and Hepatology at Erasmus MC University Medical Center in The Netherlands, from May 2012 through March 2017. A total of 151 (median age, 25.4 y; age range, 16.8–68.6 y) underwent upper endoscopies as part of a surveillance program for (pre)malignant esophageal lesions. Biopsies were collected and analyzed by histology. We collected data on patients’ use of medications, tobacco, and alcohol; gastrointestinal symptoms; ability to swallow; complaints of GER; and type of atresia and surgeries. Prevalence of esophageal squamous cell carcinoma (ESCC) was determined using data from The Netherlands Cancer Registry. The number of persons alive on January 1, 2016, in the esophageal atresia cohort and in the general Dutch population were used to calculate the 10-year prevalence of ESCC per 100,000 persons in both populations.


      Forty-seven percent of patients with esophageal atresia had a history of GER and 20.5% had undergone fundoplication surgery. Endoscopy revealed normal esophagus in 68.2% of patients, esophagitis in 7.3%, and columnar-lined esophagus in 24.5%. Histology revealed normal mucosa in 50.3% of patients, esophagitis in 23.2%, gastric metaplasia in 17.2%, and BE in 6.6% (at a median age of 31.6 years). A history of fundoplication surgery was associated with BE (P = .03). Three ESCCs developed, in 2 men, at ages 42, 44, and 60 years. This corresponded to a prevalence of 0.7% in patients with esophageal atresia—a value 108-fold higher than in the same age group in the general population.


      The prevalence of BE is 4-fold higher in young adults with esophageal atresia, and the prevalence of ESCC is 108-fold higher than in the general population. This finding could have important implications for transition of young adults from pediatric care to adult gastroenterology departments to receive life-long endoscopic follow-up evaluation to facilitate early diagnosis of relevant lesions.


      Abbreviations used in this paper:

      ACG (American College of Gastroenterology), BE (Barrett’s esophagus), EA (esophageal atresia), EAC (esophageal adenocarcinoma), ESCC (esophageal squamous cell carcinoma), GEJ (gastroesophageal junction/gastric folds), GER (gastroesophageal reflux), GM (gastric metaplasia), IM (intestinal metaplasia)
      To read this article in full you will need to make a payment
      AGA Member Login
      Login with your AGA username and password.

      Purchase one-time access:

      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Pedersen R.N.
        • Calzolari E.
        • Husby S.
        • et al.
        Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions.
        Arch Dis Child. 2012; 97: 227-232
        • Wang B.
        • Tashiro J.
        • Allan B.J.
        • et al.
        A nationwide analysis of clinical outcomes among newborns with esophageal atresia and tracheoesophageal fistulas in the United States.
        J Surg Res. 2014; 190: 604-612
        • Vergouwe F.W.
        • IJsselstijn H.
        • Wijnen R.M.
        • et al.
        Screening and surveillance in esophageal atresia patients: current knowledge and future perspectives.
        Eur J Pediatr Surg. 2015; 25: 345-352
        • Wang K.K.
        • Sampliner R.E.
        • Practice Parameters Committee of the American College of Gastroenterology
        Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus.
        Am J Gastroenterol. 2008; 103: 788-797
        • Ronkainen J.
        • Aro P.
        • Storskrubb T.
        • et al.
        Prevalence of Barrett's esophagus in the general population: an endoscopic study.
        Gastroenterology. 2005; 129: 1825-1831
        • Zagari R.M.
        • Fuccio L.
        • Wallander M.A.
        • et al.
        Gastro-oesophageal reflux symptoms, oesophagitis and Barrett's oesophagus in the general population: the Loiano-Monghidoro study.
        Gut. 2008; 57: 1354-1359
        • Zagari R.M.
        • Eusebi L.H.
        • Rabitti S.
        • et al.
        Prevalence of upper gastrointestinal endoscopic findings in the community: a systematic review of studies in unselected samples of subjects.
        J Gastroenterol Hepatol. 2016; 31: 1527-1538
        • Spechler S.J.
        • Sharma P.
        • et al.
        • American Gastroenterological Association
        American Gastroenterological Association medical position statement on the management of Barrett's esophagus.
        Gastroenterology. 2011; 140: 1084-1091
        • Deurloo J.A.
        • van Lanschot J.J.
        • Drillenburg P.
        • et al.
        Esophageal squamous cell carcinoma 38 years after primary repair of esophageal atresia.
        J Pediatr Surg. 2001; 36: 629-630
        • Jayasekera C.S.
        • Desmond P.V.
        • Holmes J.A.
        • et al.
        Cluster of 4 cases of esophageal squamous cell cancer developing in adults with surgically corrected esophageal atresia–time for screening to start.
        J Pediatr Surg. 2012; 47: 646-651
        • Adzick N.S.
        • Fisher J.H.
        • Winter H.S.
        • et al.
        Esophageal adenocarcinoma 20 years after esophageal atresia repair.
        J Pediatr Surg. 1989; 24: 741-744
        • Alfaro L.
        • Bermas H.
        • Fenoglio M.
        • et al.
        Are patients who have had a tracheoesophageal fistula repair during infancy at risk for esophageal adenocarcinoma during adulthood?.
        J Pediatr Surg. 2005; 40: 719-720
        • Pultrum B.B.
        • Bijleveld C.M.
        • de Langen Z.J.
        • et al.
        Development of an adenocarcinoma of the esophagus 22 years after primary repair of a congenital atresia.
        J Pediatr Surg. 2005; 40: e1-e4
        • Esquibies A.E.
        • Zambrano E.
        • Ziai J.
        • et al.
        Pulmonary squamous cell carcinoma associated with repaired congenital tracheoesophageal fistula and esophageal atresia.
        Pediatr Pulmonol. 2010; 45: 202-204
        • LaQuaglia M.P.
        • Gray M.
        • Schuster S.R.
        Esophageal atresia and ante-thoracic skin tube esophageal conduits: squamous cell carcinoma in the conduit 44 years following surgery.
        J Pediatr Surg. 1987; 22: 44-47
        • 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: 550-570
        • Vergouwe F.W.
        • Spoel M.
        • van Beelen N.W.
        • et al.
        Longitudinal evaluation of growth in oesophageal atresia patients up to 12 years.
        Arch Dis Child Fetal Neonatal Ed. 2017; 102: F417-F422
        • Gross R.E.
        The surgery of infancy and childhood.
        W B Saunders Company, Philadelphia1953: 441-444
        • Katz P.O.
        • Gerson L.B.
        • Vela M.F.
        Guidelines for the diagnosis and management of gastroesophageal reflux disease.
        Am J Gastroenterol. 2013; 108 (quiz 329): 308-328
        • Hashimoto C.L.
        • Iriya K.
        • Baba E.R.
        • et al.
        Lugol's dye spray chromoendoscopy establishes early diagnosis of esophageal cancer in patients with primary head and neck cancer.
        Am J Gastroenterol. 2005; 100: 275-282
        • Lundell L.R.
        • Dent J.
        • Bennett J.R.
        • et al.
        Endoscopic assessment of oesophagitis: clinical and functional correlates and further validation of the Los Angeles classification.
        Gut. 1999; 45: 172-180
        • Sharma P.
        • Dent J.
        • Armstrong D.
        • et al.
        The development and validation of an endoscopic grading system for Barrett's esophagus: the Prague C & M criteria.
        Gastroenterology. 2006; 131: 1392-1399
        • Levine D.S.
        • Blount P.L.
        • Rudolph R.E.
        • et al.
        Safety of a systematic endoscopic biopsy protocol in patients with Barrett's esophagus.
        Am J Gastroenterol. 2000; 95: 1152-1157
      1. Netherlands Cancer Registry managed by the Netherlands Comprehensive Cancer Organisation (IKNL). Available from: Accessed May 17, 2017.

        • Ross-Innes C.S.
        • Becq J.
        • Warren A.
        • et al.
        Whole-genome sequencing provides new insights into the clonal architecture of Barrett's esophagus and esophageal adenocarcinoma.
        Nat Genet. 2015; 47: 1038-1046
        • Rubin D.B.
        Multiple Imputation for Nonresponse in Surveys..
        John Wiley and Sons, New York1987
        • Paquet K.J.
        Prophylactic endoscopic sclerosing treatment of the esophageal wall in varices – a prospective controlled randomized trial.
        Endoscopy. 1982; 14: 4-5
        • Fitzgerald R.C.
        • di Pietro M.
        • Ragunath K.
        • et al.
        British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.
        Gut. 2014; 63: 7-42
        • Kamangar F.
        • Chow W.H.
        • Abnet C.C.
        • et al.
        Environmental causes of esophageal cancer.
        Gastroenterol Clin North Am. 2009; 38 (vii): 27-57
        • Sistonen S.J.
        • Koivusalo A.
        • Nieminen U.
        • et al.
        Esophageal morbidity and function in adults with repaired esophageal atresia with tracheoesophageal fistula: a population-based long-term follow-up.
        Ann Surg. 2010; 251: 1167-1173
        • Dent J.
        • El-Serag H.B.
        • Wallander M.A.
        • et al.
        Epidemiology of gastro-oesophageal reflux disease: a systematic review.
        Gut. 2005; 54: 710-717
        • Connor M.J.
        • Springford L.R.
        • Kapetanakis V.V.
        • et al.
        Esophageal atresia and transitional care-step 1: a systematic review and meta-analysis of the literature to define the prevalence of chronic long-term problems.
        Am J Surg. 2015; 209: 747-759
        • Deurloo J.A.
        • Ekkelkamp S.
        • Taminiau J.A.
        • et al.
        Esophagitis and Barrett esophagus after correction of esophageal atresia.
        J Pediatr Surg. 2005; 40: 1227-1231
        • 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: 312-316
        • Deurloo J.A.
        • Ekkelkamp S.
        • Bartelsman J.F.
        • et al.
        Gastroesophageal reflux: prevalence in adults older than 28 years after correction of esophageal atresia.
        Ann Surg. 2003; 238: 686-689
        • Koivusalo A.I.
        • Pakarinen M.P.
        Outcome of surgery for pediatric gastroesophageal reflux-clinical and endoscopic follow-up after 300 fundoplications in 279 consecutive patients.
        Scand J Surg. 2017; (Epub ahead of print)
        • Mauritz F.A.
        • van Herwaarden-Lindeboom M.Y.
        • Zwaveling S.
        • et al.
        Laparoscopic Thal fundoplication in children: a prospective 10- to 15-year follow-up study.
        Ann Surg. 2014; 259: 388-393
        • Zhang S.K.
        • Guo L.W.
        • Chen Q.
        • et al.
        The association between human papillomavirus 16 and esophageal cancer in Chinese population: a meta-analysis.
        BMC Cancer. 2015; 15: 1096
        • Pajecki D.
        • Zilberstein B.
        • Cecconello I.
        • et al.
        Larger amounts of nitrite and nitrate-reducing bacteria in megaesophagus of Chagas' disease than in controls.
        J Gastrointest Surg. 2007; 11: 199-203
        • Sandler R.S.
        • Nyren O.
        • Ekbom A.
        • et al.
        The risk of esophageal cancer in patients with achalasia. A population-based study.
        JAMA. 1995; 274: 1359-1362
        • Rintala R.J.
        • Pakarinen M.P.
        Long-term outcome of esophageal anastomosis.
        Eur J Pediatr Surg. 2013; 23: 219-225
        • Burjonrappa S.C.
        • Youssef S.
        • St-Vil D.
        What is the incidence of Barrett's and gastric metaplasia in esophageal atresia/tracheoesophageal fistula (EA/TEF) patients?.
        Eur J Pediatr Surg. 2011; 21: 25-29
        • Koivusalo A.I.
        • Pakarinen M.P.
        • Lindahl H.G.
        • et al.
        Endoscopic surveillance after repair of oesophageal atresia: longitudinal study in 209 patients.
        J Pediatr Gastroenterol Nutr. 2016; 62: 562-566