Acid suppression increases rates of Barrett's esophagus and esophageal injury in the presence of duodenal reflux

Abstract

Background: The contribution of gastric acid to the toxicity of alkaline duodenal refluxate on the esophageal mucosa is unclear. This study compared the effect of duodenal refluxate when acid was present, decreased by proton pump inhibitors (PPI), or absent. Methods: We randomized 136 Sprague-Dawley rats into 4 groups: group 1 (n = 33) were controls; group 2 (n = 34) underwent esophagoduodenostomy promoting "combined reflux"; group 3 (n = 34) underwent esophagoduodenostomy and PPI treatment to decrease acid reflux; and group 4, the 'gastrectomy' group (n = 35) underwent esophagoduodenostomy and total gastrectomy to eliminate acid in the refluxate. Esophaguses were examined for inflammatory, Barrett's, and other histologic changes, and expression of proliferative markers Ki-67, proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGFR). Results: In all reflux groups, the incidence of Barrett's mucosa was greater when acid was suppressed (group C, 62%; group D, 71%) than when not suppressed (group B, 27%; P = 0.004 and P