Natural History of Duodenal Neoplasia in Patients with Familial Adenomatous Polyposis

Abstract Objective Patients with familial adenomatous polyposis (FAP) have a lifetime risk of developing duodenal adenomas approaching 100%, and the relative risk for duodenal cancer compared with the general population is high. We conducted a retrospective study to investigate the natural history of non-ampullary duodenal adenomas and risk factors for advanced lesions in patients with FAP. Methods Of 248 patients with 139 pedigrees at 2 institutes, we assessed 151 patients with 100 pedigrees with a pathogenic germline variant in the adenomatous polyposis coli gene, excluding mosaic variants. We evaluated the prevalence of duodenal non-ampullary adenomas in patients with FAP; the natural history of these adenomas during the observation period; and the risk factors for lifetime development of high-grade dysplasia, large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV until the end of observation. Results During the median observation period of 7 years, the incidence of patients with adenomas increased by 1.6 times, with more than 20 polyps increased by 1.7 times, with polyps of ≥ 10 mm increased by 5 times, with severe dysplasia increased by 22 times, and with stage IV at the last esophagogastroduodenoscopy increased by 9 times. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period. Stage progression was observed in 71% of 113 patients. Conclusions Non-ampullary duodenal adenomas in patients with FAP frequently become exacerbated. Our findings suggest that patients with FAP who develop duodenal adenomas should be surveyed to prevent the development of duodenal cancer.