Su1981 Endoscopic Evaluation of Families With Hereditary Diffuse Gastric Cancer: A Prospective Cohort Study

Abstract

Introduction: Individuals with E-cadherin gene (CDH1) mutation and a family history of hereditary diffuse gastric cancer (HDGC) are recommended to undergo total gastrectomy or annual endoscopic surveillance. Although data is limited, prior reports have suggested that endoscopic surveillance may be ineffective in detecting microscopic disease or malignancy. Aims: To evaluate current recommendations and advance current knowledge on the utility of endoscopic surveillance in patients with CDH1 mutation. Methods: As part of a protocol evaluation at the National Institutes of Health Clinical Center for subjects with confirmed CDH1 gene mutation, patients underwent gastrointestinal evaluation. Endoscopic (high-definition white-light esophagogastroduodenoscopy (EGD), colonoscopy, and wireless capsule endoscopy (WCE)) data, mucosal biopsies, and gastric explant pathology results were collected and analyzed. Results: 24 subjects from 4 families with confirmed CDH1 mutation were evaluated. Prior to elective total gastrectomy in 17 (71%) subjects or elective surveillance in 7 (29%), EGD and colonoscopy were performed in 24 (100%) and 21 (87%) subjects, respectively. The median age at evaluation was 31.5 years and 42% were male. On EGD, the most common finding was gastric polyps (58%) in the gastric body (93%), and only one biopsy revealed evidence of adenocarcinoma. Themost common histopathologic findings included chronic gastritis (54%) and fundic gland polyps (25%). On explant evaluation, 47% of gastrectomy specimens revealed adenocarcinoma, and 17.6% showed adenomatous polyps with high-grade dysplasia (HGD). In those with adenocarcinoma, gastric ulcers and polyps were found in 3/8 (37.5%) subjects, independently. In those with adenomatous polyps with HGD, polyposis was found in all subjects. 11/24 (45.8%) subjects underwent WCE with no remarkable finding. Polyps were found on colonoscopy in 48% of subjects, of which 70% had tubular adenomas (2 with HGD, both >50 years old) and 20% had >5 polyps (both >50 years old). Conclusion: This study expands on the scant knowledge regarding a gastroenterologist's role in the management of patients with Ecadherin (CDH1) gene mutation. EGD surveillance appears to have minimal utility given the lack of correlation between endoscopic and pathologic findings, and prophylactic gastrectomy should remain mainstay of management. Given the colonoscopic findings in this study, the utility of earlier colon cancer screening in these patients should be further explored.