Bile Reflux is a Risk Factor for Metachronous Development in Patients with Early Gastric Cancer.

Background/Aims The eradication of Helicobacter pylori reduces gastric cancer risk; however, the rate of metachronous development (MD) after endoscopic resection for early gastric cancer (EGC) is 1-4% annually. Hence, we evaluated various risk factors for MD after endoscopic submucosal dissection (ESD), specifically bile reflux, which has received limited clinical attention. Methods/Results We retrospectively analyzed clinical data from 454 patients who underwent ESD for EGC between 2010 and 2018. MD was defined as the presence of a newly developed lesion more than 12 months after ESD. Bile reflux was assessed under standardized second-look endoscopy the day after ESD. During a median follow-up of 34.3 months, MD was observed in 45 patients (9.9%). Multivariate analysis revealed older age, severe gastric mucosal atrophy, xanthoma, and bile reflux as independent risk factors for MD. The 5-year MD rate was significantly greater in the bile reflux group than in the control group (24.2% vs. 11.2%, p = 0.01). Notably, in the bile reflux group, MD was significantly more frequently observed in the antrum or lower gastric body (61.1% vs. 29.6%, p = 0.036). Diabetes mellitus was identified as an independent risk factor for bile reflux. Conclusions Bile reflux is a significant and independent risk factor for MD after ESD for EGC, particularly in gravity-dependent areas. Patients with bile reflux represent a high-risk subgroup requiring intensive endoscopic surveillance, such as every 6 months, to facilitate early detection of metachronous lesions.