Nakahira Hiroko, Takeuchi Yoji, Shimamoto Yusaku, Ishiguro Shingo, Yunokizaki Hiroshi, Ezoe Yasumasa, Fujisawa Fumie, Ishihara Ryu, Takayama Tetsuji, Yoshida Teruhiko, Mutoh Michihiro, Ishikawa Hideki
Department of Gastrointestinal Oncology, Osaka, Japan.
Department of Genetic Oncology, Division of Hereditary Tumors, Osaka International Cancer Institute, Osaka, Japan.
Hered Cancer Clin Pract. 2023 Nov 27;21(1):25. doi: 10.1186/s13053-023-00264-2.
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 progression of non-ampullary duodenal adenomas (NADAs) and risk factors for advanced lesions in patients with FAP.
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 NADAs in patients with FAP, the progression of these adenomas to advanced adenoma during the observation period, and the risk factors for the lifetime development of high-grade dysplasia (HGD), large (≥ 10 mm) duodenal adenomas, and Spiegelman stage IV.
During the median observation period of 7 years, the incidences of patients with NADAs, with more than 20 polyps, with polyps ≥ 10 mm, with HGD, and with stage IV at the last esophagogastroduodenoscopy were increased 1.6-fold, 1.7-fold, 5-fold, 22-fold, and 9-fold, respectively. Intramucosal cancer occurred in three patients (2%), but no patients developed invasive cancer during the observation period because we performed endoscopic intervention for advanced adenomas. Stage progression was observed in 71% of 113 patients. Stage IV was more common in women, patients with a history of colectomy, and those with a 3' side mutation in their adenomatous polyposis coli gene.
NADAs 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.
家族性腺瘤性息肉病（FAP）患者发生十二指肠腺瘤的终生风险接近100%，与普通人群相比，其患十二指肠癌的相对风险较高。我们进行了一项回顾性研究，以调查FAP患者非壶腹十二指肠腺瘤（NADA）的进展情况以及高级别病变的危险因素。
在2家机构的248例患者（139个家系）中，我们评估了151例患者（100个家系），这些患者的腺瘤性息肉病（APC）基因存在致病种系变异，不包括镶嵌变异。我们评估了FAP患者中NADA的患病率、这些腺瘤在观察期内进展为高级别腺瘤的情况，以及发生高级别异型增生（HGD）、大（≥10 mm）十二指肠腺瘤和Spiegelman IV期的终生风险因素。
在中位观察期7年期间，最后一次食管胃十二指肠镜检查时患有NADA、息肉超过20个、息肉≥10 mm、HGD以及处于IV期的患者发病率分别增加了1.6倍、1.7倍、5倍、22倍和9倍。3例患者（2%）发生了黏膜内癌，但在观察期内没有患者发生浸润性癌，因为我们对高级别腺瘤进行了内镜干预。在113例患者中有71%观察到分期进展。IV期在女性、有结肠切除术史的患者以及APC基因3'端突变的患者中更为常见。
FAP患者的NADA经常加重。我们的研究结果表明，对发生十二指肠腺瘤的FAP患者应进行监测，以预防十二指肠癌的发生。
