Columnar islands in Barrett's esophagus: Do they impact Prague C&M criteria and dysplasia grade?

BACKGROUND AND AIM: The standard for classifying Barrett's metaplasia on endoscopy, the Prague C&M criteria, ignores all islands of metaplastic-appearing tissue. The aims of the present study were to measure the prevalence of columnar islands, quantify their impact on metaplasia extent, and determine if they harbor advanced dysplasia. METHODS: Data from two prospective patient cohorts were retrospectively analyzed. They included adults who underwent upper endoscopy to evaluate for gastroesophageal reflux disease, Barrett's esophagus (BE), dysplasia, or adenocarcinoma between 2003 and 2012 at tertiary care centers in the USA and Germany. The BE pattern, location, and pathology were examined. The extent of BE as defined by the Prague criteria (disregarding the location of islands) was compared with the complete maximal extent of BE (incorporating the location of islands). RESULTS: A total of 555 patients underwent endoscopy (mean age 60.1 years, 67.2% male, 91.9% white). Among those patients, 191 (34.4%) showed metaplastic-appearing mucosa in islands. Endoscopically, in 101 (52.9%) cases, islands were proximal to the farthest segment of BE as defined by the Prague M location. Histologically, intestinal metaplasia was confirmed in 60 (58.8%) of the 102 esophagogastroduodenoscopies (EGDs) where islands were biopsied. In 41 (40.2%) cases, the histologically confirmed BE islands extended farther than the maximal segment based on the Prague criteria. Pathology from biopsies of islands either changed the diagnosis or worsened the BE dysplasia grade in 16 (15.7%) of the 102 patients. CONCLUSIONS: Columnar islands are commonly seen on EGD. The Prague C&M criteria may underestimate the maximal extent of BE and overlook the area of highest dysplasia grade.

Treatment of Barrett's esophagus with a novel focal cryoablation device: a safety and feasibility study.

BACKGROUND AND AIMS: Currently, eradication of Barrett's epithelium is preferably achieved using radiofrequency ablation (RFA) or spray cryoablation (SCA). However, both modalities suffer from drawbacks such as the need for sizing, multiple deployment steps, large controller units (RFA), imprecise dosing and need for gas-venting (SCA). The new Cryoballoon Focal Ablation System (CbFAS) may address these limitations. This study assessed the safety, feasibility, and dose response of the CbFAS in patients with flat Barrett's epithelium with or without dysplasia. PATIENTS AND METHODS: In this multicenter, prospective non-randomized trial, 39 patients were each treated with one or two ablations of 6, 8, or 10 seconds. Symptoms were assessed immediately and 2 days post-cryoablation. Follow-up endoscopy was performed 6-8 weeks post-procedure to assess response. Outcome parameters were incidence of adverse events, pain, esophageal stricture formation, and ablation response by cryogen dose. RESULTS: Of 62 ablations, 56 (10 with 6 seconds, 28 with 8 seconds, 18 with 10 seconds) were successfully performed. Six ablations failed because of device malfunction (n=3) and procedural or anatomic issues (n=3). Median procedure time was 7 minutes (interquartile range [IQR] 4-10). No major adverse events occurred; six patients experienced a minor mucosal laceration requiring no intervention. Mild pain was reported by 27% of patients immediately after cryoablation and by 14% after 2 days. No strictures were evident at follow-up.  Full squamous regeneration was seen in 47 treated areas (6 [60%] of the 6-second areas; 23 [82%] of the 8-second areas; 18 [100%] of 10-second areas). CONCLUSIONS: Focal cryoablation of Barrett's epithelium with the CbFAS is feasible and safe, resulting in squamous regeneration in the majority of patients.

DNA promoter hypermethylation of p16 and APC predicts neoplastic progression in Barrett's esophagus.

OBJECTIVES: Prediction of progression to cancer in patients with Barrett's esophagus (BE) is difficult using current techniques. We determined whether DNA promoter hypermethylation of genes frequently methylated in esophageal adenocarcinoma (p16 and APC) could be used as predictors of progression in BE. METHODS: We first performed a cross-sectional study to evaluate the prevalence of gene hypermethylation in biopsies from patients with normal esophagus (n=17), BE (n=102), and adenocarcinoma (n=42). We then performed a nested case-control study comparing gene hypermethylation in BE patients who progressed from baseline pathology to high-grade dysplasia or cancer (n=7) vs. patients who did not progress (n=50). RESULTS: None of the patients with normal esophagus had p16 or APC hypermethylation. Hypermethylation was prevalent in BE without dysplasia or low-grade dysplasia (p16=31% and APC=50%; P<0.01) and high-grade dysplasia or adenocarcinoma (p16=54% and APC=68%; P<0.001) compared with normal esophagus (not detected). Patients who progressed from baseline pathology to high-grade dysplasia or cancer had higher prevalence of hypermethylation in their initial esophagus biopsies compared with those who did not progress for both p16 (100 vs. 33%; P=0.008) and APC (86 vs. 40%; P=0.02). Hypermethylation of both p16 and APC was a strong predictor of subsequent progression to high-grade dysplasia or cancer during a mean follow-up time of 4.1 years (odds ratio (95% confidence interval)=14.97 (1.73,inf), P=0.01). Among patients who were negative for both p16 and APC hypermethylation, none progressed from baseline pathology to high-grade dysplasia or cancer. CONCLUSIONS: Hypermethylation of both p16 and APC strongly predicts progression to high-grade dysplasia or cancer in patients with BE. Absence of p16 and APC hypermethylation is associated with a benign course.