Chapter 36, Ep 3 of 5: Adenomatous Polyposis: FAP and MUTYH

Episode three works the adenomatous polyposis syndromes by their governing logic: if you know the gene, you know the polyp count, the polyp type, and the surgery. APC drives classic FAP toward near-certain colorectal cancer by forty, the same gene at its ends produces the softer attenuated phenotype, and biallelic MUTYH mimics attenuated FAP through an autosomal recessive pattern of affected siblings and unaffected parents. The surgical pivot is not whether to take the colon but whether to take the rectum, which decides itself on polyp burden. After the colon is gone the duodenum becomes the surveillance organ, with Spigelman staging turning ampullary adenomas into an EGD interval and a pancreaticoduodenectomy conversation.   Topics covered Reasoning from gene to polyp count to surgery Classic FAP and APC on Wnt signaling Attenuated FAP and the Ashkenazi variant MUTYH-associated polyposis and recessive inheritance FAP extracolonic stigmata and desmoids Prophylactic colectomy and the rectal decision Spigelman-staged duodenal surveillance Chemoprevention as adjunct not substitute   Key decisions Start annual colonoscopy at puberty, age ten to twelve, in classic FAP, and delay attenuated FAP and MUTYH-associated polyposis to age twenty to twenty-five because the polyps and cancer arise later. Move to prophylactic colectomy for polyps larger than ten millimeters, high-grade dysplasia, rising polyp number, burden too high to clear endoscopically, or symptoms. Let the rectum decide the operation: total proctocolectomy with ileal pouch-anal anastomosis when the rectum carries burden, total colectomy with ileorectal anastomosis with annual rectal surveillance when it can be cleared. Test for biallelic MUTYH in a patient with multiple adenomas who is APC-negative, especially when a sibling is affected and the parents are not, because the pattern is autosomal recessive. Stage the duodenum by Spigelman and set the interval to the stage: EGD every four years at stage zero down to every year at stage three, with side-viewing ampulla inspection each time, because stage four carries a fourteen to thirty-six percent cancer risk and triggers surgical evaluation. Treat sulindac and celecoxib as adjuncts only, since they reduce polyp number but do not prevent colorectal cancer or remove the need for surgery.   For the full chapter with MCQs, tables, and primary-guideline references, visit www.boardpearls.com. Questions or feedback: [email protected]. (00:00) - Gene sets count, histology, and surgery (00:53) - Classic FAP and APC on Wnt signaling (01:39) - Attenuated FAP and the Ashkenazi variant (02:19) - MUTYH-associated polyposis and recessive inheritance (03:30) - Extracolonic stigmata and desmoids (04:52) - Colectomy and the rectal decision (06:00) - Spigelman-staged duodenal surveillance (07:20) - Chemoprevention as adjunct not substitute