Periampullary adenomas and adenocarcinomas in familial adenomatous polyposis: Cumulative risks and APC gene mutations

Background & Aims: Patients with familial adenomatous polyposis (FAP) have a high prevalence of duodenal adenomas, and the region of the ampulla of Va ter is the predilection site for duodenal adenocarcinomas. This study asses sed the risk of stage IV periampullary adenomas according to the Spigelman classification and periampullary adenocarcinomas in Swedish FAP patients sc reened by esophagogastroduodenoscopy (EGD). The genotype of patients with s tage IV periampullary adenomas and periampullary adenocarcinomas was also i nvestigated. Methods: A retrospective study of 180 patients screened by EGD in :1982-1999 was undertaken. Kaplan-Meier analysis was performed to evalu ate cumulative risk. Mutation analysis was carried out in patients with per iampullary adenocarcinomas diagnosed outside the screening program, in addi tion to patients in the screening group with stage IV periampullary adenoma s and adenocarcinomas. Results: Periampullary adenoma stage IV was diagnose d in 14 patients (7.8%), with a cumulative risk of 20% at age 60 years. Per iampullary adenocarcinoma was diagnosed in 5 patients (2.8%), with a cumula tive risk of :10% at age 60. Three of the adenocarcinomas occurred in patie nts with stage IV periampullary adenomas compared with 2 in patients with l ess severe periampullary adenomatosis at screening (odds ratio, 31; 95% con fidence interval, 4.6-215). Fifteen (88%) of the APC gene mutations were de tected; :12 of these were located downstream from codon 1051 in exon 15. Co nclusions: The life time risk of severe periampullary lesions in FAP patien ts is high, and an association between stage IV periampullary adenomas and a malignant course of the periampullary adenomatosis is strongly suggestive . Mutations downstream from codon 1051 seem to be associated with severe pe riampullary lesions.