Abstract

This is one of a series of statements discussing the use of GI endoscopy in common clinical situations. The Standards of Practice Committee of the American Society for Gastrointestinal Endoscopy prepared this text. In preparing this guideline, a search of the medical literature was performed using PubMed. Additional references were obtained from the bibliographies of the identified articles and from recommendations of expert consultants. When limited or no data exist from well-designed prospective trials, emphasis is given to results of large series and reports from recognized experts. Guidelines for appropriate use of endoscopy are based on a critical review of the available data and expert consensus at the time the guidelines are drafted. Further controlled clinical studies may be needed to clarify aspects of this guideline. This guideline may be revised as necessary to account for changes in technology, new data, or other aspects of clinical practice. The recommendations were based on reviewed studies and were graded on the strength of the supporting evidence (Table 1).1Guyatt G.H. Oxman A.D. Vist G.E. et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google Scholar The strength of individual recommendations is based on both the aggregate evidence quality and an assessment of the anticipated benefits and harms. Weaker recommendations are indicated by phrases such as “we suggest,” whereas stronger recommendations are typically stated as “we recommend.”TABLE 1GRADE system for rating the quality of evidence for guidelinesAdapted from Guyatt et al.1Guyatt G.H. Oxman A.D. Vist G.E. et al.GRADE: an emerging consensus on rating quality of evidence and strength of recommendations.BMJ. 2008; 336: 924-926Crossref PubMed Google ScholarQuality of evidenceDefinitionSymbolHigh qualityFurther research is very unlikely to change our confidence in the estimate of effect.⊕⊕⊕⊕Moderate qualityFurther research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.⊕⊕⊕Low qualityFurther research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.⊕⊕Very low qualityAny estimate of effect is very uncertain.⊕ Open table in a new tab This guideline is intended to be an educational device to provide information that may assist endoscopists in providing care to patients. This guideline is not a rule and should not be construed as establishing a legal standard of care or as encouraging, advocating, requiring, or discouraging any particular treatment. Clinical decisions in any particular case involve a complex analysis of the patient's condition and available courses of action. Therefore, clinical considerations may lead an endoscopist to take a course of action that varies from these guidelines. Endoscopy plays an important role in the diagnosis and management of premalignant conditions of the esophagus. Early recognition of premalignant conditions provides an opportunity to prevent esophageal cancer or to diagnose it at an early stage. This guideline discusses the role of endoscopy in the management of premalignant conditions of the esophagus. The primary condition addressed will be Barrett's esophagus (BE), the only known precursor of adenocarcinoma of the esophagus, but the guideline also covers the role of endoscopy as it applies to the neoplastic potential of achalasia, aerodigestive cancers, tylosis, and caustic injuries, which have been suggested to be risk factors for squamous cell carcinoma. Discussion of other rare conditions such as esophageal GI stromal cell tumors, granular cell tumors, adenomatous polyps, and papillomas is outside the scope of this guideline. BE has been defined in the United States by the presence of specialized intestinal metaplasia of the tubular esophagus and is recognized as a precursor lesion to esophageal adenocarcinoma (EAC). The development of BE is believed to be a reparative response to reflux-induced damage to the native squamous epithelium, with subsequent replacement with a metaplastic intestinalized epithelium, BE. Metaplastic BE is associated with increased cellular proliferation and turnover that may result in progression to dysplasia. Early studies reported up a 30- to 40-fold increased risk of the development of EAC,2Van der Veen A.H. Dees J. Blankensteijn J.D. et al.Adenocarcinoma in Barrett's oesophagus: an overrated risk.Gut. 1989; 30: 14-18Crossref PubMed Scopus (222) Google Scholar but estimates of the risk of EAC associated with BE have been steadily decreasing in more recent, better controlled trials. In a recent population-based cohort study, the presence of BE conferred a relative risk of EAC of 11.3 over that of the general population (95% CI, 8.8-14.4).3Hvid-Jensen F. Pedersen L. Drewes A.M. et al.Incidence of adenocarcinoma among patients with Barrett's esophagus.N Engl J Med. 2011; 365: 1375-1383Crossref PubMed Scopus (1094) Google Scholar Although some caution should be exercised in the interpretation of this analysis because of its retrospective nature and relatively short mean follow-up period of 5 years, these findings are consistent with the trend of decreasing risk estimates observed in multiple other studies over the past 5 to 10 years,4Bhat S. Coleman H.G. Yousef F. et al.Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study.J Natl Cancer Inst. 2011; 103: 1049-1057Crossref PubMed Scopus (559) Google Scholar, 5Rubenstein J.H. Scheiman J.M. Sadeghi S. et al.Esophageal adenocarcinoma incidence in individuals with gastroesophageal reflux: synthesis and estimates from population studies.Am J Gastroenterol. 2011; 106: 254-260Crossref PubMed Scopus (74) Google Scholar, 6Sikkema M. de Jonge P.J.F. Steyerberg E.W. 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: 235-244Abstract Full Text Full Text PDF PubMed Scopus (303) Google Scholar, 7Thomas T. Abrams K.R. De Caestecker J.S. et al.Meta analysis: cancer risk in Barrett's oesophagus.Aliment Pharmacol Ther. 2007; 26: 1465-1477Crossref PubMed Scopus (139) Google Scholar, 8Chang E.Y. Morris C.D. Seltman A.K. et al.The effect of antireflux surgery on esophageal carcinogenesis in patients with Barrett esophagus: a systematic review.Ann Surg. 2007; 246: 11-21Crossref PubMed Scopus (171) Google Scholar, 9Yousef F. Cardwell C. Cantwell M.M. et al.The incidence of esophageal cancer and high grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis.Am J Epidemiol. 2008; 168: 237-249Crossref PubMed Scopus (324) Google Scholar although the optimal prospective study has not been conducted. BE is histologically graded as nondysplastic (NDBE), indeterminate-grade dysplasia (IGD), low-grade dysplasia (LGD), high-grade dysplasia (HGD), intramucosal carcinoma (IMC), or invasive EAC.10Hornick J.L. Odze R.D. Neoplastic precursor lesions in Barrett's esophagus.Gastroenterol Clin North Am. 2007; 36: 775-796Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Management recommendations for BE typically do not include the approach to or management of IGD. IGD is considered by pathology experts to be an interim diagnosis, typically encountered in the presence of significant inflammation or ulceration or when technical issues related to biopsy specimens preclude a definitive diagnosis of dysplasia. This diagnosis requires clarification after aggressive medical therapy of esophageal inflammation or additional specimen processing or pathology consultation.10Hornick J.L. Odze R.D. Neoplastic precursor lesions in Barrett's esophagus.Gastroenterol Clin North Am. 2007; 36: 775-796Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar BE has a characteristic appearance endoscopically, described as a salmon or pink color in contrast to the light gray appearance of esophageal squamous mucosa, but it should be emphasized that histologic examination of esophageal biopsy samples is required to confirm the diagnosis of BE. The sensitivity of white-light endoscopy alone for the detection and diagnosis of BE ranges from 80% to 90%.11Eloubeidi M.A. Provenzale D. Does this patient have Barrett's esophagus? The utility of predicting Barrett's esophagus at the index endoscopy.Am J Gastroenterol. 1999; 94: 937-943Crossref PubMed Google Scholar, 12Kim S.L. Waring J.P. Spechler S.J. et al.Department of Veterans Affairs Gastroesophageal Reflux Study GroupDiagnostic inconsistencies in Barrett's esophagus.Gastroenterology. 1994; 107: 945-949Abstract Full Text PDF PubMed Google Scholar, 13Woolf G.M. Riddell R.H. Irvine E.J. et al.A study to examine agreement between endoscopy and histology for the diagnosis of columnar lined (Barrett's) esophagus.Gastrointest Endosc. 1989; 35: 541-544Abstract Full Text PDF PubMed Scopus (71) Google Scholar During endoscopy, special attention and targeted biopsies should be focused on lesions such as nodules, ulcers, and other mucosal irregularities because these lesions are more likely to demonstrate dysplasia or cancer. Adjuncts to white-light endoscopy used to improve the sensitivity for the detection of BE and dysplastic BE include chromoendoscopy, electrical enhanced imaging, magnification, and confocal endoscopy. These techniques are still in development and are discussed in detail elsewhere.14Song L.M.W.K. Adler D.G. Chand B. et al.Chromoendoscopy.Gastrointest Endosc. 2007; 66: 639-649Abstract Full Text Full Text PDF PubMed Scopus (127) Google Scholar, 15Kantsevoy S.V. Adler D.G. Conway J.D. et al.Confocal laser endomicroscopy.Gastrointest Endosc. 2009; 70: 197-200Abstract Full Text Full Text PDF PubMed Scopus (66) Google Scholar Risk factors for BE and EAC include male sex, white race, age older than 50 years, family history of BE, increased duration of reflux symptoms, smoking, and obesity.16Gerson L.B. Edson R. Lavori P.W. et al.Use of a simple symptom questionnaire to predict Barrett's esophagus in patients with symptoms of gastroesophageal reflux.Am J Gastroenterol. 2001; 96: 2005-2012Crossref PubMed Google Scholar, 17Eloubeidi M.A. Provenzale D. Clinical and demographic predictors of Barrett's esophagus among patients with gastroesophageal reflux disease: a multivariable analysis in veterans.J Clin Gastroenterol. 2001; 33: 306-309Crossref PubMed Scopus (125) Google Scholar, 18El-Serag H.B. Kvapil P. Hacken-Bitar J. et al.Abdominal obesity and the risk of Barrett's esophagus.Am J Gastroenterol. 2005; 100: 2151-2156Crossref PubMed Scopus (191) Google Scholar Endoscopic screening for BE is controversial because no randomized, controlled trials (RCTs) have demonstrated a decrease in mortality, either in general or from EAC, as a result of screening.19Corley D.A. Levin T.R. Habel L.A. et al.Surveillance and survival in Barrett's adenocarcinomas: a population-based study.Gastroenterology. 2002; 122: 633-640Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar, 20Bytzer P. Christensen P.B. Damkier P. et al.Adenocarcinoma of the esophagus and Barrett's esophagus: a population-based study.Am J Gastroenterol. 1999; 94: 86-91Crossref PubMed Scopus (261) Google Scholar, 21Rubenstein J.H. Taylor J.B. Meta-analysis: the association of oesophageal adenocarcinoma with symptoms of gastro-oesophageal reflux.Aliment Pharmacol Ther. 2010; 32: 1222-1227Crossref PubMed Scopus (163) Google Scholar Because of the lack of RCT evidence of the efficacy of screening, some have used models in an attempt to establish a rationale for screening for BE. One such cost-effectiveness model of EGD screening of 50-year-old white men with GERD, with surveillance reserved for those with dysplastic BE, demonstrated $10,440/quality-adjusted life-year saved with screening compared with no screening or surveillance.22Inadomi J.M. Sampliner R. Lagergren J. et al.Screening and surveillance for Barrett's esophagus in high-risk groups: a cost-utility analysis.Ann Intern Med. 2003; 138: 176-186Crossref PubMed Scopus (354) Google Scholar The cost-effectiveness of traditional EGD is limited by the associated costs of the procedure and sedation. Screening modalities other than sedated EGD include esophageal capsule endoscopy (ECE) and unsedated transnasal endoscopy. A meta-analysis of ECE compared with EGD for diagnosing BE showed pooled sensitivities of 77% and 86%, respectively, by using EGD and/or histologically-confirmed intestinal metaplasia as the reference.23Bhardwaj A. Hollenbeak C.S. Pooran N. et al.A meta-analysis of the diagnostic accuracy of esophageal capsule endoscopy for Barrett's esophagus in patients with gastroesophageal reflux disease.Am J Gastroenterol. 2009; 104: 1533-1539Crossref PubMed Scopus (116) Google Scholar The authors concluded that the sensitivity and specificity of ECE were moderate and insufficient to recommend ECE over EGD as a screening test. A Markov model of 50-year-old men with chronic GERD undergoing screening with either EGD or ECE suggested that EGD was the preferred screening modality, but did not take patient preference into account.24Rubenstein J.H. Inadomi J.M. Brill J.V. et al.Cost utility of screening for Barrett's esophagus with esophageal capsule endoscopy versus conventional upper endoscopy.Clin Gastroenterol Hepatol. 2007; 5: 312-318Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar A randomized, blinded study evaluating unsedated transnasal endoscopy versus traditional EGD demonstrated comparable rates of NDBE detection and preference for transnasal endoscopy by study volunteers.25Jobe B.A. Hunter J.G. Chang E.Y. et al.Office-based unsedated small-caliber endoscopy is equivalent to conventional sedated endoscopy in screening and surveillance for Barrett's esophagus: a randomized and blinded comparison.Am J Gastroenterol. 2006; 101: 2693-2703Crossref PubMed Scopus (105) Google Scholar There are no data to support screening of the general population or of patients with a solitary risk factor for BE. Additionally, repeat endoscopy has a low yield for detecting BE in previously screened patients with normal findings. A review of the Clinical Outcomes Research Initiative National Endoscopic Database identified 24,406 patients who had undergone 2 endoscopies in a 5-year period. Suspected BE, based on the endoscopic appearance, was found in 2.4% of patients who did not have BE when their initial endoscopy was performed.26Rodriguez S. Mattek N. Lieberman D. et al.Barrett's esophagus on repeat endoscopy: should we look more than once?.Am J Gastroenterol. 2008; 103: 1892-1897Crossref PubMed Scopus (33) Google Scholar Suspected BE was identified significantly more often among patients for whom the follow-up EGD indication was reflux compared with those with another indication (5% vs 1.6%, P < .0001) and among those with previous esophagitis compared with those without previous esophagitis (9.9% vs 1.8%, P < .0001). A prospective study followed 100 subjects who underwent EGD for a variety of indications with neither histologic nor endoscopic evidence of BE.27Meining A. Ott R. Becker I. et al.The Munich Barrett follow up study: suspicion of Barrett's oesophagus based on either endoscopy or histology only–what is the clinical significance?.Gut. 2004; 53: 1402-1407Crossref PubMed Scopus (73) Google Scholar At a mean of 38 months of follow-up, all subjects had undergone repeat EGD and only 1 subject had confirmed BE. Once identified, a variety of endoscopic management options are available for patients with BE, based on the presence and grade of BE-associated dysplasia (Table 2). Despite pathology confirmation and consensus regarding the presence of dysplasia on specific biopsy specimens, there is the potential for variability with respect to the pathologic grades and natural history of BE-associated dysplasia in individual patients.TABLE 2Endoscopic management strategies for Barrett's esophagusHistologyIntervention optionsNDBE Consider no surveillance.If surveillance is elected, perform EGD every 3 to 5 years with 4-quadrant biopsies every 2 cm.Consider endoscopic ablation in select cases. IGD Clarify presence and grade of dysplasia with expert GI pathologist.Increase antisecretory therapy to eliminate esophageal inflammation.Repeat EGD and biopsy to clarify dysplasia status. LGD Confirm with expert GI pathologist.Repeat EGD in 6 months to confirm LGD.Surveillance EGD every year, 4-quadrant biopsies every 1 to 2 cm.Consider endoscopic resection or ablation. HGD Confirm with expert GI pathologist.Consider surveillance EGD every 3 months in select patients, 4-quadrant biopsies every 1 cm.Consider endoscopic resection or RFA ablation.Consider EUS for local staging and lymphadenopathy.Consider surgical consultation. NDBE, Nondysplastic Barrett's esophagus; IGD, indeterminate for dysplasia; LGD, low-grade dysplasia; HGD, high-grade dysplasia; RFA, radiofrequency ablation. Open table in a new tab NDBE, Nondysplastic Barrett's esophagus; IGD, indeterminate for dysplasia; LGD, low-grade dysplasia; HGD, high-grade dysplasia; RFA, radiofrequency ablation. The primary purpose of surveillance of BE is to identify incident dysplasia and early EAC. Because the risk of EAC varies based on the grade of dysplasia, surveillance guidelines also vary depending on histology. Surveillance in patients with NDBE is also controversial, primarily because screening will detect prevalent neoplasia, whereas surveillance will only detect incident cases. It is maintained that screening results in higher rates of neoplasia detection compared with surveillance. Systematic surveillance of all BE patients has not been shown to be cost-effective, and no RCTs have been conducted to compare surveillance with the natural history of BE. Rates of progression from NDBE to EAC are estimated to be as high as 0.6% per year28Yousef F. Cardwell C. Cantwell M.M. et al.The incidence of esophageal cancer and high-grade dysplasia in Barrett's esophagus: a systematic review and meta-analysis.Am J Epidemiol. 2008; 168: 237-249Crossref PubMed Scopus (321) Google Scholar or as low as 0.12% per year.3Hvid-Jensen F. Pedersen L. Drewes A.M. et al.Incidence of adenocarcinoma among patients with Barrett's esophagus.N Engl J Med. 2011; 365: 1375-1383Crossref PubMed Scopus (1094) Google Scholar A recent multicenter study showed a rate of progression to EAC of 0.27% per year and a rate of progression to HGD of 0.48% per year.29Wani S. Falk G. Hall M. et al.Patients with nondysplastic Barrett's esophagus have low risks for developing dysplasia or esophageal adenocarcinoma.Clin Gastroenterol Hepatol. 2011; 9 (quiz e26): 220-227Abstract Full Text Full Text PDF PubMed Scopus (186) Google Scholar In this study, 97.1% of patients with NDBE were cancer free at 10 years. A recent population-based study showed the incidence of HGD and EAC in patients with BE to be 0.38% per year.4Bhat S. Coleman H.G. Yousef F. et al.Risk of malignant progression in Barrett's esophagus patients: results from a large population-based study.J Natl Cancer Inst. 2011; 103: 1049-1057Crossref PubMed Scopus (559) Google Scholar Sharma et al30Sharma P. Falk G.W. Weston A.P. et al.Dysplasia and cancer in a large multicenter cohort of patients with Barrett's esophagus.Clin Gastroenterol Hepatol. 2006; 4: 566-572Abstract Full Text Full Text PDF PubMed Scopus (378) Google Scholar found that half of patients who developed HGD or EAC demonstrated only NDBE on a previous biopsy, suggesting that not all cases of EAC develop in a stepwise fashion from NDBE to LGD to HGD and then to EAC. Nevertheless, studies of patients whose EAC was detected through surveillance EGD have consistently demonstrated improved survival over patients whose EAC was not detected through surveillance, although this observation likely represents lead time bias.19Corley D.A. Levin T.R. Habel L.A. et al.Surveillance and survival in Barrett's adenocarcinomas: a population-based study.Gastroenterology. 2002; 122: 633-640Abstract Full Text Full Text PDF PubMed Scopus (450) Google Scholar, 31Fountoulakis A. Zafirellis K.D. Dolan K. et al.Effect of surveillance of Barrett's oesophagus on the clinical outcome of oesophageal cancer.Br J Surg. 2004; 91: 997-1003Crossref PubMed Scopus (131) Google Scholar, 32Wong T. Tian J. Nagar A.B. Barrett's surveillance identifies patients with early esophageal adenocarcinoma.Am J Med. 2010; 123: 462-467Abstract Full Text Full Text PDF PubMed Scopus (50) Google Scholar Biopsy protocols for NDBE surveillance have been published.33Abela J.E. Going J.J. Mackenzie J.F. et al.Systematic four-quadrant biopsy detects Barrett's dysplasia in more patients than nonsystematic biopsy.Am J Gastroenterol. 2008; 103: 850-855Crossref PubMed Scopus (121) Google Scholar For patients with NDBE, 4-quadrant biopsies every 2 cm with large-capacity forceps performed every 3 to 5 years is commonly recommended, although not evidence based. A recent study demonstrated similar rates of adequate specimens with large-capacity forceps (2.8 mm) compared with jumbo forceps (3.2 mm).34Gonzalez S. Yu W.M. Smith M.S. et al.Randomized comparison of 3 different-sized biopsy forceps for quality of sampling in Barrett's esophagus.Gastrointest Endosc. 2010; 72: 935-940Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Recently, endoscopic ablation has been proposed as an alternative to surveillance for NDBE. Although ablation is expensive, it could be considered if it obviates the need for surveillance. A multicenter study of radiofrequency ablation (RFA) of NDBE achieved complete eradication of BE in 98.4% of patients at 2.5 years and 92% at 5 years, with no patients progressing past NDBE during follow-up.35Fleischer D.E. Overholt B.F. Sharma V.K. et al.Endoscopic radiofrequency ablation for Barrett's esophagus: 5-year outcomes from a prospective multicenter trial.Endoscopy. 2010; 42: 781-789Crossref PubMed Scopus (203) Google Scholar Endoscopic ablation therapy as an alternative to surveillance of NDBE has been suggested to be cost-effective in a cost-utility model36Inadomi J.M. Somsouk M. Madanick R.D. et al.A cost-utility analysis of ablative therapy for Barrett's esophagus.Gastroenterology. 2009; 136 (e1-6): 2101-2114Abstract Full Text Full Text PDF PubMed Scopus (154) Google Scholar and may be a preferred management option in select patients with NDBE, such as those with a family history of EAC.37Sampliner R.E. Management of nondysplastic Barrett esophagus with ablation therapy.Gastroenterol Hepatol. 2011; 7: 461-464Google Scholar Additional research evaluating this management strategy is eagerly awaited. The development of biomarkers to identify patients at high risk of dysplasia would likely change the need for surveillance or ablation and is an area of ongoing research.38Fritcher E.G. Brankley S.M. Kipp B.R. et al.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: 1128-1135Crossref PubMed Scopus (64) Google Scholar The natural history of BE with LGD is unknown, but available data indicate that LGD carries a slightly higher risk of progression to EAC rather than NDBE. The diagnosis of LGD should be confirmed by an expert GI pathologist because the rate of progression of LGD may be higher in situations in which 2 expert GI pathologists agree on the diagnosis. A large Dutch cohort study demonstrated a rate of progression from LGD to EAC of 0.77% per year.39de Jonge P.J. van Blankenstein M. Looman C.W. et al.Risk of malignant progression in patients with Barrett's oesophagus: a Dutch nationwide cohort study.Gut. 2010; 59: 1030-1036Crossref PubMed Scopus (239) Google Scholar A recent meta-analysis found similar rates of progression in studies of patients in surveillance programs: 0.7% per year in the United Kingdom, 0.7% per year in the United States, and 0.8% per year in Europe.40Thomas T. Abrams K.R. De Caestecker J.S. et al.Meta analysis: cancer risk in Barrett's oesophagus.Aliment Pharmacol Ther. 2007; 26: 1465-1477Crossref PubMed Scopus (138) Google Scholar LGD was not an independent predictor of higher rates of progression in this meta-analysis. A multicenter outcomes study also failed to link LGD progression to HGD.41Wani S. Falk G.W. Post J. et al.Risk factors for progression of low-grade dysplasia in patients with Barrett's esophagus.Gastroenterology. 2011; 141: 1179-1186Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar The American Gastroenterological Association and American College of Gastroenterology still advocate biannual to annual surveillance for patients with LGD.42Spechler S.J. Sharma P. Souza R.F. et al.American Gastroenterological Association medical position statement on the management of Barrett's esophagus.Gastroenterology. 2011; 140: 1084-1091Abstract Full Text Full Text PDF PubMed Scopus (552) Google Scholar, 43Wang K.K. Sampliner R.E. Updated guidelines 2008 for the diagnosis, surveillance and therapy of Barrett's esophagus.Am J Gastroenterol. 2008; 103: 788-797Crossref PubMed Scopus (979) Google Scholar Published biopsy protocols involving LGD typically follow the Seattle protocol (see the following) with targeted plus 4-quadrant biopsies every 1 to 2 cm along the length of the BE.41Wani S. Falk G.W. Post J. et al.Risk factors for progression of low-grade dysplasia in patients with Barrett's esophagus.Gastroenterology. 2011; 141: 1179-1186Abstract Full Text Full Text PDF PubMed Scopus (206) Google Scholar, 44Srivastava A. Hornick J.L. Li X. et al.Extent of low-grade dysplasia is a risk factor for the development of esophageal adenocarcinoma in Barrett's esophagus.Am J Gastroenterol. 2007; 102: 483-493Crossref PubMed Scopus (104) Google Scholar Some experts advocate endoscopic ablation of BE in the setting of LGD, given the unpredictable natural history of LGD, the cumulative risk of the development of EAC, and the lack of cost-effectiveness data regarding surveillance of LGD. A recent multicenter, sham-controlled trial of RFA achieved complete eradication of dysplasia in 90.5% of patients and complete eradication of BE in 81% of patients with LGD with 2-year follow-up data demonstrating complete eradication of dysplasia and BE in 98% of patients.45Shaheen N.J. Sharma P. Overholt B.F. et al.Radiofrequency ablation in Barrett's esophagus with dysplasia.N Engl J Med. 2009; 360: 2277-2288Crossref PubMed Scopus (1206) Google Scholar The annual rate of neoplastic progression in this study was 1 per 73 patient-years; however, no subjects (sham or ablation) progressed from LGD to cancer.46Shaheen N.J. Overholt B.F. Sampliner R.E. et al.Durability of radiofrequency ablation in Barrett's esophagus with dysplasia.Gastroenterology. 2011; 141: 460-468Abstract Full Text Full Text PDF PubMed Scopus (386) Google Scholar It should be noted that the length of follow-up was short and the development of cancer would not have been expected in this cohort. Comprehensive large studies in this population will be challenging because of the requisite long-term follow-up. Ablation as an alternative to surveillance should be considered and discussed with these patients. There are scant published clinical data available to direct surveillance protocols after successful ablation of LGD; therefore, surveillance strategies after endoscopic ablation of LGD should be individualized.47Hur C. Choi S.E. Rubenstein J.H. et al.The cost effectiveness of radiofrequency ablation for Barrett's esophagus.Gastroenterology. 2012; 143: 567-575Abstract Full Text Full Text PDF PubMed Scopus (133) Google Scholar The purpose of surveillance in patients with HGD is to detect foci of IMC or EAC. A biopsy demonstrating HGD requires review and confirmation by a second expert GI pathologist. One of the most widely recognized surveillance strategies is the Seattle protocol,48Levine D.S. Haggitt R.C. Blount P.L. et al.An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus.Gastroenterology. 1993; 105: 40-50Abstract Full Text PDF PubMed Google Scholar which involves targeted biopsies of mucosal abnormalities, such as nodules and ulcers, plus 4-quadrant biopsies obtained every 1 cm by using large-capacity forceps for the length of the BE segment. With the use of this protocol, no unsuspected invasive cancer has been demonstrated in their cohort.48Levine D.S. Haggitt R.C. Blount P.L. et al.An endoscopic biopsy protocol can differentiate high-grade dysplasia from early adenocarcinoma in Barrett's esophagus.Gastroenterology. 1993; 105: 40-50Abstract Full Text PDF PubMed Google Scholar A less intensive protocol that uses 4-quadrant biopsies every 1 to 2 cm with regular- or large-capacity forceps found a similar rate of missed cancers compared with the Seattle protocol in patients with HGD undergoing esophagectomy.49Kariv R. Plesec T.P. Goldblum J.R. et al.The Seattle protocol does not more reliably predict the detection of cancer at the time of esophagectomy than a less intensive surveillance protocol.Clin Gastroenterol Hepatol. 2009; 7: 653-658Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar Because safe and effective methods of endoscopic treatment of HGD and early EAC have emerged, continued surveillance of BE with HGD should be offered only to patients unfit or unwilling to undergo operative or ablative therapy. Endoscopic therapy has evolved as a safe and effective method of treating dysplastic BE and IMC. Endoscopic therapy can be divided into therapies that ablate dysplastic mucosa