Mary Fredericksen

Three-tiered risk stratification model to predict progression in Barrett's esophagus using epigenetic and clinical features

Background Barretts esophagus predisposes to esophageal adenocarcinoma. However, the value of endoscopic surveillance in Barretts esophagus has been debated because of the low incidence of esophageal adenocarcinoma in Barretts esophagus. Moreover, high inter-observer and sampling-dependent variation in the histologic staging of dysplasia make clinical risk assessment problematic. In this study, we developed a 3-tiered risk stratification strategy, based on systematically selected epigenetic and clinical parameters, to improve Barretts esophagus surveillance efficiency. Methods and Findings We defined high-grade dysplasia as endpoint of progression, and Barretts esophagus progressor patients as Barretts esophagus patients with either no dysplasia or low-grade dysplasia who later developed high-grade dysplasia or esophageal adenocarcinoma. We analyzed 4 epigenetic and 3 clinical parameters in 118 Barretts esophagus tissues obtained from 35 progressor and 27 non-progressor Barretts esophagus patients from Baltimore Veterans Affairs Maryland Health Care Systems and Mayo Clinic. Based on 2-year and 4-year prediction models using linear discriminant analysis (area under the receiver-operator characteristic (ROC) curve: 0.8386 and 0.7910, respectively), Barretts esophagus specimens were stratified into high-risk (HR), intermediate-risk (IR), or low-risk (LR) groups. This 3-tiered stratification method retained both the high specificity of the 2-year model and the high sensitivity of the 4-year model. Progression-free survivals differed significantly among the 3 risk groups, with p = 0.0022 (HR vs. IR) and p<0.0001 (HR or IR vs. LR). Incremental value analyses demonstrated that the number of methylated genes contributed most influentially to prediction accuracy. Conclusions This 3-tiered risk stratification strategy has the potential to exert a profound impact on Barretts esophagus surveillance accuracy and efficiency.

Which Chronic Upper Airway Symptoms May Be Due to Acid Reflux

G A A b st ra ct s NSAID use and erosive esophagitis and/or esophageal strictures. Most studies were published 10 years ago and significant heterogeneity was seen between studies. Limited data suggest that use of NSAIDs was not significantly increased in patients with esophageal injury compared with controls, with a magnitude of effect size smaller than that reported with gastroduodenal ulcers. More evidence is required to have a clearer picture of esophageal injury caused by NSAIDs.