Abstract
Abbreviations and Acronyms:
ACG (American College of Gastroenterology), ACP (American College of Physicians), AGA (American Gastroenterological Association), ASGE (American Society of Gastrointestinal Endoscopy), EMR (endoscopic mucosal resection), GEJ (gastroesophageal junction), GERD (gastroesophageal reflux disease), PDT (photodynamic therapy), RFA (radiofrequency ablation), SSIM (subsquamous intestinal metaplasia)- ▪US medical societies require intestinal metaplasia with goblet cells in esophageal biopsy specimens as a diagnostic criterion for Barrett esophagus.
- ▪The risk of esophageal adenocarcinoma for patients with nondysplastic Barrett esophagus ranges from 0.12% to 0.38% per year.
- ▪Endoscopic screening for Barrett esophagus is recommended currently for patients with multiple risk factors for esophageal adenocarcinoma, including chronic gastrointestinal reflux disease, age of 50 years or older, male sex, white race, hiatal hernia, elevated body mass index, intra-abdominal body fat distribution, nocturnal reflux symptoms, and tobacco use.
- ▪Despite the lack of proof that endoscopic surveillance for Barrett esophagus reduces mortality from esophageal cancer or is cost-effective, we still recommend the regular endoscopic surveillance for patients with Barrett esophagus endorsed by the gastroenterology societies.
- ▪Radiofrequency ablation of high-grade dysplasia in Barrett esophagus has been reported to prevent its progression to cancer in a randomized controlled trial.
- ▪Major issues that must be resolved before recommending radiofrequency ablation to treat nondysplastic Barrett esophagus include the importance of subsquamous intestinal metaplasia and the frequency and extent with which Barrett metaplasia recurs after eradication.
- ▪Ongoing research that might help to address some of these controversies includes investigations on the use of molecular markers, advanced endoscopic imaging techniques, and risk stratification models to quantify cancer risk for individual patients with Barrett esophagus.
Controversy 1: The Definition of Barrett Esophagus—Are Goblet Cells Required for the Diagnosis?


Watson A, Heading RC, Shepherd N. Guidelines for the Diagnosis and Management of Barrett's Columnar-Lined Oesophagus: A Report of the Working Party of the British Society of Gastroenterology. London, England: British Society of Gastroenterology; August 2005. www.bsg.org.uk. Accessed August 26, 2013.
Controversy 2: Does Endoscopic Surveillance of Patients With Barrett Esophagus Prevent Deaths From Esophageal Cancer and Should Endoscopic Surveillance be Performed?
Watson A, Heading RC, Shepherd N. Guidelines for the Diagnosis and Management of Barrett's Columnar-Lined Oesophagus: A Report of the Working Party of the British Society of Gastroenterology. London, England: British Society of Gastroenterology; August 2005. www.bsg.org.uk. Accessed August 26, 2013.
Controversy 3: Who Should be Screened to Identify Barrett Esophagus?
Controversy 4: Which Patients With Barrett Esophagus Should be Treated With Endoscopic Eradication Therapy (and How Well Does it Work)?
High-Grade Dysplasia
Low-Grade Dysplasia
Nondysplastic Barrett Metaplasia
Subsquamous Intestinal Metaplasia
Anders M, Lucks Y, El-Masry MA, et al. Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett's esophagus [published online July 23, 2013]. Clin Gastroenterol Hepatol. http://dx.doi.org/10.1016/j.cgh.2013.07.013.
Anders M, Lucks Y, El-Masry MA, et al. Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett's esophagus [published online July 23, 2013]. Clin Gastroenterol Hepatol. http://dx.doi.org/10.1016/j.cgh.2013.07.013.
Recurrent Barrett Metaplasia
Conclusion
Supplemental Online Material
References
- Prevalence of Barrett's esophagus in the general population: an endoscopic study.Gastroenterology. 2005; 129: 1825-1831
- Screening for Barrett's esophagus in colonoscopy patients with and without heartburn.Gastroenterology. 2003; 125: 1670-1677
- Esophageal adenocarcinoma incidence: are we reaching the peak?.Cancer Epidemiol Biomarkers Prev. 2010; 19: 1468-1470
- Barrett esophagus and risk of esophageal cancer: a clinical review.JAMA. 2013; 310: 627-636
- History, molecular mechanisms, and endoscopic treatment of Barrett's esophagus.Gastroenterology. 2010; 138: 854-869
- American Gastroenterological Association technical review on the management of Barrett's esophagus.Gastroenterology. 2011; 140: e18-e52
- Barrett's esophagus: is the goblet half empty?.Clin Gastroenterol Hepatol. 2012; 10: 1237-1238
- Pathophysiology of Barrett's esophagus.Semin Thorac Cardiovasc Surg. 1997; 9: 270-278
- Histologic definition of gastro-esophageal reflux disease.Curr Opin Gastroenterol. 2013; 29: 460-467
- Intestinal differentiation in metaplastic, nongoblet columnar epithelium in the esophagus.Am J Surg Pathol. 2009; 33: 1006-1015
- Metaplastic esophageal columnar epithelium without goblet cells shows DNA content abnormalities similar to goblet cell-containing epithelium.Am J Gastroenterol. 2009; 104: 816-824
Watson A, Heading RC, Shepherd N. Guidelines for the Diagnosis and Management of Barrett's Columnar-Lined Oesophagus: A Report of the Working Party of the British Society of Gastroenterology. London, England: British Society of Gastroenterology; August 2005. www.bsg.org.uk. Accessed August 26, 2013.
- British Society of Gastroenterology guidelines on the diagnosis and management of Barrett's oesophagus.Gut. 2014; 63: 7-42
- Cardiac rather than intestinal-type background in endoscopic resection specimens of minute Barrett adenocarcinoma.Hum Pathol. 2009; 40: 65-74
- Barrett's oesophagus: intestinal metaplasia is not essential for cancer risk.Scand J Gastroenterol. 2007; 42: 1271-1274
- Effects of dropping the requirement for goblet cells from the diagnosis of Barrett's esophagus.Clin Gastroenterol Hepatol. 2012; 10: 1232-1236
- Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study.J Natl Cancer Inst. 2011; 103: 1049-1057
- Chronic peptic ulcer of the oesophagus and ‘oesophagitis’.Br J Surg. 1950; 38: 175-182
- Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus.Am J Gastroenterol. 2008; 103: 788-797
- The role of endoscopy in Barrett's esophagus and other premalignant conditions of the esophagus.Gastrointest Endosc. 2012; 76: 1087-1094
- Dysplasia in Barrett's esophagus: limitations of current management strategies.Am J Gastroenterol. 2005; 100: 927-935
- The incidence of oesophageal adenocarcinoma in non-dysplastic Barrett's oesophagus: a meta-analysis.Gut. 2012; 61: 970-976
- Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma.Clin Gastroenterol Hepatol. 2011; 9: 220-227
- Incidence of adenocarcinoma among patients with Barrett's esophagus.N Engl J Med. 2011; 365: 1375-1383
- Persistence of nondysplastic Barrett's esophagus identifies patients at lower risk for esophageal adenocarcinoma: results from a large multicenter cohort.Gastroenterology. 2013; 145: 548-553
- Improving surveillance for Barrett's oesophagus: AspECT and BOSS trials provide an evidence base.BMJ. 2006; 332: 1512
- Effect of surveillance of Barrett's oesophagus on the clinical outcome of oesophageal cancer.Br J Surg. 2004; 91: 997-1003
- Surveillance and survival in Barrett's adenocarcinomas: a population-based study.Gastroenterology. 2002; 122: 633-640
- Upper endoscopy as a screening and surveillance tool in esophageal adenocarcinoma: a review of the evidence.Am J Gastroenterol. 2002; 97: 1319-1327
- Medical decision analysis of endoscopic surveillance of Barrett's oesophagus to prevent oesophageal adenocarcinoma.Aliment Pharmacol Ther. 2002; 16: 41-50
- Screening and surveillance for Barrett esophagus in high-risk groups: a cost-utility analysis.Ann Intern Med. 2003; 138: 176-186
- Cost-effectiveness model of endoscopic screening and surveillance in patients with gastroesophageal reflux disease.Clin Gastroenterol Hepatol. 2004; 2: 868-879
- Cost-effectiveness of aspirin chemoprevention for Barrett's esophagus.J Natl Cancer Inst. 2004; 96: 316-325
- Outcome of adenocarcinoma arising in Barrett's esophagus in endoscopically surveyed and nonsurveyed patients.J Thorac Cardiovasc Surg. 1994; 108: 813-821
- Impact of endoscopic surveillance on mortality from Barrett's esophagus-associated esophageal adenocarcinomas.Gastroenterology. 2013; 145: 312-319
- Acetic acid spray is an effective tool for the endoscopic detection of neoplasia in patients with Barrett's esophagus.Clin Gastroenterol Hepatol. 2010; 8: 843-847
- Endoscopic trimodal imaging versus standard video endoscopy for detection of early Barrett's neoplasia: a multicenter, randomized, crossover study in general practice.Gastrointest Endosc. 2011; 73: 195-203
- Standard endoscopy with random biopsies versus narrow band imaging targeted biopsies in Barrett's oesophagus: a prospective, international, randomised controlled trial.Gut. 2013; 62: 15-21
- In vivo endomicroscopy improves detection of Barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video).Gastrointest Endosc. 2014; 79: 211-221
- Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.Gut. 2013; 62: 1676-1683
- A comparison of conventional cytology, DNA ploidy analysis, and fluorescence in situ hybridization for the detection of dysplasia and adenocarcinoma in patients with Barrett's esophagus.Hum Pathol. 2008; 39: 1128-1135
- DNA methylation as an adjunct to histopathology to detect prevalent, inconspicuous dysplasia and early-stage neoplasia in Barrett's esophagus.Clin Cancer Res. 2013; 19: 878-888
- A multicenter, double-blinded validation study of methylation biomarkers for progression prediction in Barrett's esophagus.Cancer Res. 2009; 69: 4112-4115
- Prediction of Barrett's esophagus among men.Am J Gastroenterol. 2013; 108: 353-362
- Population-based study reveals new risk-stratification biomarker panel for Barrett's esophagus.Gastroenterology. 2012; 143: 927-935
- Upper endoscopy for gastroesophageal reflux disease: best practice advice from the clinical guidelines committee of the American College of Physicians.Ann Intern Med. 2012; 157: 808-816
- Guidelines for the diagnosis and management of gastroesophageal reflux disease.Am J Gastroenterol. 2013; 108: 308-328
- Gastroesophageal reflux symptoms in patients with adenocarcinoma of the esophagus or cardia.Cancer. 2006; 107: 2160-2166
- Symptomatic gastroesophageal reflux as a risk factor for esophageal adenocarcinoma.N Engl J Med. 1999; 340: 825-831
- Preoperative prevalence of Barrett's esophagus in esophageal adenocarcinoma: a systematic review.Gastroenterology. 2002; 122: 26-33
- Cost utility of screening for Barrett's esophagus with esophageal capsule endoscopy versus conventional upper endoscopy.Clin Gastroenterol Hepatol. 2007; 5: 312-318
- Barrett's esophagus: development of dysplasia and adenocarcinoma.Gastroenterology. 1989; 96: 1249-1256
- Incidence of esophageal adenocarcinoma in patients with Barrett's esophagus and high-grade dysplasia: a meta-analysis.Gastrointest Endosc. 2008; 67: 394-398
- 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
- Radiofrequency ablation in Barrett's esophagus with dysplasia.N Engl J Med. 2009; 360: 2277-2288
- Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial.Gastrointest Endosc. 2005; 62: 488-498
- Endoscopic eradication therapy for mucosal neoplasia in Barrett's esophagus.Curr Opin Gastroenterol. 2013; 29: 446-453
- Efficacy and durability of radiofrequency ablation for barrett's esophagus: systematic review and meta-analysis.Clin Gastroenterol Hepatol. 2013; 11: 1245-1255
- Safety and efficacy of multiband mucosectomy in 1060 resections in Barrett's esophagus.Endoscopy. 2011; 43: 177-183
- Long-term results and risk factor analysis for recurrence after curative endoscopic therapy in 349 patients with high-grade intraepithelial neoplasia and mucosal adenocarcinoma in Barrett's oesophagus.Gut. 2008; 57: 1200-1206
- The risk of lymph-node metastases in patients with high-grade dysplasia or intramucosal carcinoma in Barrett's esophagus: a systematic review.Am J Gastroenterol. 2012; 107: 850-862
- Five-year efficacy and safety of photodynamic therapy with Photofrin in Barrett's high-grade dysplasia.Gastrointest Endosc. 2007; 66: 460-468
- Reproducibility of the diagnosis of dysplasia in Barrett esophagus: a reaffirmation.Hum Pathol. 2001; 32: 368-378
- Low-grade dysplasia in Barrett's esophagus: overdiagnosed and underestimated.Am J Gastroenterol. 2010; 105: 1523-1530
- Risk factors for progression of low-grade dysplasia in patients with Barrett's esophagus.Gastroenterology. 2011; 141: 1179-1186
- The case for endoscopic treatment of non-dysplastic and low-grade dysplastic Barrett's esophagus.Dig Dis Sci. 2010; 55: 1918-1931
- Routine polypectomy for colorectal polyps and ablation for Barrett's esophagus are intellectually the same.Gastroenterology. 2011; 140: 386-388
- Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.Endoscopy. 2010; 42: 781-789
- Buried metaplasia after endoscopic ablation of Barrett's esophagus: a systematic review.Am J Gastroenterol. 2011; 106: 1899-1908
- Development of subsquamous high-grade dysplasia and adenocarcinoma after successful radiofrequency ablation of Barrett's esophagus.Gastroenterology. 2012; 143: 564-566
- Squamous overgrowth is not a safety concern for photodynamic therapy for Barrett's esophagus with high-grade dysplasia.Gastroenterology. 2009; 136: 56-64
Anders M, Lucks Y, El-Masry MA, et al. Subsquamous extension of intestinal metaplasia is detected in 98% of cases of neoplastic Barrett's esophagus [published online July 23, 2013]. Clin Gastroenterol Hepatol. http://dx.doi.org/10.1016/j.cgh.2013.07.013.
- Advanced pathology under squamous epithelium on initial EMR specimens in patients with Barrett's esophagus and high-grade dysplasia or intramucosal carcinoma: implications for surveillance and endotherapy management.Gastrointest Endosc. 2009; 70: 417-421
- Adequacy of esophageal squamous mucosa specimens obtained during endoscopy: are standard biopsies sufficient for postablation surveillance in Barrett's esophagus?.Gastrointest Endosc. 2012; 75: 11-18
- Biopsy depth after radiofrequency ablation of dysplastic Barrett's esophagus.Gastrointest Endosc. 2010; 72: 490-496
- Properties of the neosquamous epithelium after radiofrequency ablation of Barrett's esophagus containing neoplasia.Am J Gastroenterol. 2009; 104: 1366-1373
- Remission of Barrett's esophagus with early neoplasia 5 years after radiofrequency ablation with endoscopic resection: a Netherlands cohort study.Gastroenterology. 2013; 145: 96-104
- Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.Gastroenterology. 2011; 141: 460-468
- Effective treatment of early Barrett's neoplasia with stepwise circumferential and focal ablation using the HALO system.Endoscopy. 2008; 40: 370-379
- Detection of intestinal metaplasia after successful eradication of Barrett's esophagus with radiofrequency ablation.Dig Dis Sci. 2011; 56: 1996-2000
- Recurrence of esophageal intestinal metaplasia after endoscopic mucosal resection and radiofrequency ablation of Barrett's esophagus: results from a US multicenter consortium.Gastroenterology. 2013; 145: 79-86
- Barrett's esophagus without dysplasia: wait or ablate?.Dig Dis Sci. 2011; 56: 1926-1928
- The cost effectiveness of radiofrequency ablation for Barrett's esophagus.Gastroenterology. 2012; 143: 567-575
- American Gastroenterological Association medical position statement on the management of Barrett's esophagus.Gastroenterology. 2011; 140: 1084-1091
Article Info
Publication History
Footnotes
Potential Competing Interests: Dr Spechler has served as a consultant for Takeda Pharmaceuticals and has received research support from BARRX Medical Inc .