Bile reflux is a risk factor for metachronous recurrence in patients with early gastric cancer

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Aims Although Helicobacter pylori (H. pylori) eradication is widespread for the risk reduction of gastric cancer development, there is the fact that metachronous recurrence (MR) is reported to occur at a frequency of 1-4% per year after endoscopic resection for early gastric cancer (EGC). With the aim of reducing future recurrence of gastric cancer, we analysed the risk of MR in patients after endoscopic submucosal dissection (ESD) for EGC, focusing especially on bile reflux, which has not been given much importance in clinical practice. Methods We conducted a retrospective study of 454 patients who underwent ESD for EGC between January 2010 and December 2018 at our hospital. MR was defined as a newly developed lesion in other parts of the stomach during endoscopic follow-up more than 12 months after curative endoscopic resection for EGC. Gastric mucosal atrophy was classified using the Kimura-Takemoto classification, with the closed type being mild atrophy and the open type being severe atrophy. Bile reflux was defined as the presence of yellowish green mucous lake in the stomach on endoscopy. Results MR was observed in 45 patients (9.9%) within the median observation period of 34.3 months. Among the clinical characteristics, including age, sex, body mass index (BMI), drinking and smoking habits, comorbidity, H.pylori infection status and the endoscopic findings, including the degree of gastric mucosal atrophy and presence of intestinal metaplasia, xanthomas or bile reflux, we demonstrated that older age (HR 2.05, 95%CI 1.11-3.80; p=0.02), severe gastric mucosal atrophy (HR 2.74, 95%CI 1.16-6.48; p=0.02), the presence of xanthoma (HR 2.11, 95%CI 1.17-3.82; p=0.01) and bile reflux (HR 1.98, 95%CI 1.07-3.66; p=0. 03) were extracted for the risk factors of MR. The 5-year rate of MR was significantly higher in the bile reflux group than in the control group (24.2% vs 11.2%, p=0.01). Bile reflux was observed in 115 patients (25.3%), and risk factors for it were then examined. Among the clinical characteristics, diabetes mellitus was extracted as an independent risk factor for bile reflux (OR 2.11, 95%CI 1.26-3.54; p<0. 01). Conclusions Bile reflux is a risk factor for MR after ESD for EGC, and careful endoscopic follow-up is required in patients with bile reflux. Treatments for bile reflux should be considered for the risk reduction of MR. Publication History Article published online: 27 March 2025 © 2025. European Society of Gastrointestinal Endoscopy. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany

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