Duodenal involvement in MUTYH-associated polyposis: findings from an international study and implications for endoscopic surveillance.

Abstract

Objectives: This study aimed to better document incidence and progression of duodenal disease in MUTYH-associated polyposis (MAP).

Methods: Incidences of duodenal cancer, and duodenal polyposis by age and genotype were assessed in individuals with genetically confirmed MAP.

Results: At first endoscopy, 91/679 participants (13.4%) had duodenal adenoma(s) at a median age of 53 years (range 22 to 81 years). 439/679 participants had 1370 further endoscopies, over a median period of 6.3 years (range 1 month to 30 years). This included 365 without adenomas at first endoscopy, of whom 83 (22.7%) developed non-ampullary adenomas during follow-up at a median age of 53 years (range 29-76). Thirty-eight adenomas (5.5%) contained high-grade dysplasia (HGD), of which thirty-five had a known size and 20 (57.1%) of these were 10mm or smaller. Ampullary lesions were uncommon (31/679, 4.6%). Duodenal cancer was diagnosed in 5/679 participants (0.74%) at a median age of 65 years (range 47-83 years) and at a median of 12 months (range 9-24 months) following a surveillance endoscopy. At least four were located distally (in the third or fourth part). The cumulative incidences of duodenal adenomas and cancer at 70 years were 16.5-63.5%, depending on genotype, and 0.58%, respectively. Adenoma incidence was significantly higher in Y179C (hazard ratio 5.33 (2.94-9.67, <0.001) and E480X (4.07 (2.16-7.67), <0.001) than G396D homozygotes.

Conclusions: Future clinical guidelines for MAP should consider genotype-specific recommendations for duodenal surveillance, the importance of assessing the distal duodenum (i.e. D3, D4) and polypectomy of all detectable adenomas.