A 22-year-old Indian male presents to the gastroenterology clinic with a family history of early-onset colorectal cancer. Colonoscopy reveals hundreds of adenomatous polyps throughout the colon. Genetic testing confirms a germline mutation in the structure marked **A** in the adenoma-carcinoma sequence diagram. Which of the following management strategies is most appropriate to reduce his cancer risk?

Explanation

## Why option 1 is correct A germline APC mutation (structure **A**) causes Familial Adenomatous Polyposis (FAP), characterized by hundreds to thousands of colorectal adenomas by age 10–20 years and 100% lifetime colorectal cancer risk if untreated, typically by age 40. The standard of care is prophylactic total colectomy by the mid-20s, most commonly performed as restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) to preserve continence. Critically, APC mutations also predispose to duodenal adenomas (the most common cause of cancer death post-colectomy in FAP patients), necessitating lifelong upper GI surveillance. This is the only option that addresses both the colonic and extracolonic manifestations of APC-driven FAP (Robbins 10e Ch 17; Harrison 21e Ch 80). ## Why each distractor is wrong - **Option 2**: While sulindac and NSAIDs can cause polyp regression in FAP, they do NOT eliminate cancer risk and are insufficient as monotherapy. Surveillance colonoscopy alone without prophylactic colectomy leaves the patient at unacceptable risk of colorectal cancer by age 40. NSAIDs are adjunctive, not curative. - **Option 3**: Observation with annual colonoscopy and delayed segmental colectomy is inappropriate for FAP. The adenomas are innumerable and diffuse; segmental resection leaves residual polyp-bearing mucosa at high cancer risk. Prophylactic total colectomy is the standard, not observation until dysplasia appears. - **Option 4**: Chemoprevention with celecoxib alone, without colectomy, does not address the 100% lifetime cancer risk in FAP. Polypectomy of hundreds of adenomas is impractical and leaves occult dysplasia. Prophylactic colectomy is the definitive intervention. **High-Yield:** APC mutation = FAP = hundreds of adenomas + 100% cancer risk → prophylactic total colectomy by mid-20s + lifelong upper GI surveillance (duodenal adenomas are the leading post-colectomy cancer cause). [cite: Robbins 10e Ch 17; Harrison 21e Ch 80]