Risk of neoplastic progression in Barrett’s esophagus diagnosed as indefinite for dysplasia: a nationwide cohort study

Background and study aims: A histological diagnosis of “indefinite for dysplasia” (IND) in Barrett’s esophagus is used when a diagnosis of genuine dysplasia is equivocal. The aim of the present study was to assess the risk of progression to high grade dysplasia (HGD) or esophageal adenocarcinoma (EAC) after a diagnosis of IND in a nationwide cohort of patients with Barrett’s esophagus.

Patients and methods: Patients with a first diagnosis of IND in Barrett’s esophagus between 2002 and 2011 were selected from a nationwide registry of histopathology diagnoses in The Netherlands. Patients were followed up until treatment for HGD, detection of EAC, or date of last endoscopy contact with biopsy sampling.

Results: In total, 1258 patients met the inclusion criteria, of whom 842 (66.9 %) underwent endoscopic follow-up. Patients were followed for a total of 2585 person-years (mean ± SD 3.01 ± 2.6). Median duration until first follow-up endoscopy was 1.2 years (interquartile range 0.3 – 1.8 years). The progression rate from IND to the combined end point of HGD or EAC was 2.0 (95 % confidence interval [CI] 1.5 – 2.6) per 100 person-years and progression to EAC was 1.2 (95 %CI 0.8 – 1.6). After excluding cases with HGD or EAC within 1 year after IND diagnosis (n = 16), the progression rates were 1.4 (95 %CI 1.0 – 1.9) and 0.8 (95 %CI 0.5 – 1.2) per 100 person-years for HGD or EAC and EAC, respectively.

Conclusion: In this large, population-based, cohort of patients with Barrett’s esophagus, the incidence rate of HGD or EAC following a diagnosis of IND was 1.4 per 100 person-years. The results demonstrate the need for additional studies to select the subgroup of IND patients with an increased risk of neoplastic progression.

• References

• 1 Spechler SJ, Sharma P, Souza RF et al. American Gastroenterological Association medical position statement on the management of Barrett’s esophagus. Gastroenterology 2011; 140: 1084-1091
• 2 Sikkema M, de Jonge PJ, Steyerberg EW et al. Risk of esophageal adenocarcinoma and mortality in patients with Barrett’s esophagus: a systematic review and meta-analysis. Clin Gastroenterol Hepatol 2010; 8: 235-244
• 3 Cook MB, Chow WH, Devesa SS. Oesophageal cancer incidence in the United States by race, sex, and histologic type, 1977–2005. Br J Cancer 2009; 101: 855-859
• 4 Dikken JL, Lemmens VE, Wouters MW et al. Increased incidence and survival for oesophageal cancer but not for gastric cardia cancer in the Netherlands. Eur J Cancer 2012; 48: 1624-1632
• 5 Pech O, May A, Manner H et al. Long-term efficacy and safety of endoscopic resection for patients with mucosal adenocarcinoma of the esophagus. Gastroenterology 2014; 146: 652-660
• 6 Sikkema M, Looman CW, Steyerberg EW et al. Predictors for neoplastic progression in patients with Barrett’s esophagus: a prospective cohort study. Am J Gastroenterol 2011; 106: 1231-1238
• 7 Varghese S, Lao-Sirieix P, Fitzgerald RC. Identification and clinical implementation of biomarkers for Barrett’s esophagus. Gastroenterology 2012; 142: 435-441
• 8 Schlemper RJ, Riddell RH, Kato Y et al. The Vienna classification of gastrointestinal epithelial neoplasia. Gut 2000; 47: 251-255
• 9 Dixon MF. Gastrointestinal epithelial neoplasia: Vienna revisited. Gut 2002; 51: 130-131
• 10 Desai TK, Krishnan K, Samala N et al. The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett’s oesophagus: a meta-analysis. Gut 2012; 61: 970-976
• 11 de Jonge PJ, van Blankenstein M, Looman CW et al. Risk of malignant progression in patients with Barrett’s oesophagus: a Dutch nationwide cohort study. Gut 2010; 59: 1030-1036
• 12 Hvid-Jensen F, Pedersen L, Drewes AM et al. Incidence of adenocarcinoma among patients with Barrett's esophagus. N Engl J Med 2011; 365: 1375-1383
• 13 Wani S, Falk GW, Post J et al. Risk factors for progression of low-grade dysplasia in patients with Barrett’s esophagus. Gastroenterology 2011; 141: 1179-1186
• 14 Verbeek RE, van Oijen MG, ten Kate FF et al. Surveillance and follow-up strategies in patients with high-grade dysplasia in Barrett’s esophagus: a Dutch population-based study. Am J Gastroenterol 2012; 107: 534-542
• 15 Haggitt RC. Barrett’s esophagus, dysplasia, and adenocarcinoma. Hum Pathol 1994; 25: 982-993
• 16 Montgomery E, Goldblum JR, Greenson JK et al. Dysplasia as a predictive marker for invasive carcinoma in Barrett esophagus: a follow-up study based on 138 cases from a diagnostic variability study. Hum Pathol 2001; 32: 379-388
• 17 Sonwalkar SA, Rotimi O, Scott N et al. A study of indefinite for dysplasia in Barrett’s oesophagus: reproducibility of diagnosis, clinical outcomes and predicting progression with AMACR (alpha-methylacyl-CoA-racemase). Histopathology 2010; 56: 900-907
• 18 Casparie M, Tiebosch AT, Burger G et al. Pathology databanking and biobanking in The Netherlands, a central role for PALGA, the nationwide histopathology and cytopathology data network and archive. Cell Oncol 2007; 29: 19-24
• 19 Cote RA, Robboy S. Progress in medical information management. Systematized nomenclature of medicine (SNOMED). JAMA 1980; 243: 756-762
• 20 Younes M, Lauwers GY, Ertan A et al. The significance of “indefinite for dysplasia” grading in Barrett metaplasia. Arch Pathol Lab Med 2011; 135: 430-432
• 21 Curvers WL, ten Kate FJ, Krishnadath KK et al. Low-grade dysplasia in Barrett’s esophagus: overdiagnosed and underestimated. Am J Gastroenterol 2010; 105: 1523-1530
• 22 Dulai GS, Shekelle PG, Jensen DM et al. Dysplasia and risk of further neoplastic progression in a regional Veterans Administration Barrett’s cohort. Am J Gastroenterol 2005; 100: 775-783
• 23 Skacel M, Petras RE, Gramlich TL et al. The diagnosis of low-grade dysplasia in Barrett’s esophagus and its implications for disease progression. Am J Gastroenterol 2000; 95: 3383-3387
• 24 Montgomery E, Bronner MP, Goldblum JR et al. Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation. Hum Pathol 2001; 32: 368-378
• 25 Coco DP, Goldblum JR, Hornick JL et al. Interobserver variability in the diagnosis of crypt dysplasia in Barrett esophagus. Am J SurgPathol 2011; 35: 45-54
• 26 Lomo LC, Blount PL, Sanchez CA et al. Crypt dysplasia with surface maturation: a clinical, pathologic, and molecular study of a Barrett’s esophagus cohort. Am J Surg Pathol 2006; 30: 423-435
• 27 Kerkhof M, Kusters JG, van Dekken H et al. Biomarkers for risk stratification of neoplastic progression in Barrett esophagus. Cell Oncol 2007; 29: 507-557
• 28 Kastelein F, Biermann K, Steyerberg EW et al. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett’s oesophagus. Gut 2013; 62: 1676-1683
• 29 Kerkhof M, Steyerberg EW, Kusters JG et al. Aneuploidy and high expression of p53 and Ki67 is associated with neoplastic progression in Barrett esophagus. Cancer Biomark 2008; 4: 1-10
• 30 Curvers Wl, Festen HP, Hammeeteman W et al. Current surveillance policy for Barrett’s oesophagus in the Netherlands. Tijdschr Geneeskd 2007; 151: 1879-1884