A 45-year-old woman from Bangalore undergoes colonoscopy for family history of colorectal cancer and is found to have 15 adenomatous polyps in the colon. Genetic testing reveals a pathogenic APC mutation (familial adenomatous polyposis, FAP). She has no current symptoms. What is the most appropriate next step in management?

Explanation

## Familial Adenomatous Polyposis (FAP) Pathophysiology FAP is an autosomal dominant syndrome caused by germline APC (adenomatous polyposis coli) mutations. APC is a critical tumor suppressor that regulates Wnt/β-catenin signaling. **Key Point:** FAP patients develop hundreds to thousands of adenomatous polyps throughout the colon by age 30–40. Without intervention, colorectal cancer develops in nearly 100% of patients by age 50. ## Natural History and Risk in FAP | Feature | Details | |---------|----------| | Number of polyps | 100–1000+ (vs. <5 in sporadic cases) | | Age of onset | Typically 20–30 years | | Cancer risk (untreated) | ~100% by age 50 | | Polyp size | Mix of small and large adenomas; risk correlates with size | | Extracolonic manifestations | Duodenal adenomas (5–10% cancer risk), desmoid tumors, osteomas, congenital hypertrophy of retinal pigment epithelium (CHRPE) | ## Definitive Management: Prophylactic Colectomy **High-Yield:** Once FAP is diagnosed, prophylactic colectomy is the standard of care to eliminate cancer risk. The choice of procedure depends on rectal involvement: 1. **Total proctocolectomy with IPAA** — preferred if rectal polyp burden is high; preserves continence 2. **Total abdominal colectomy with ileostomy** — alternative if IPAA is not feasible **Clinical Pearl:** Surveillance colonoscopy alone is inadequate because: - Polyp burden is too high for safe polypectomy - Missed polyps and field effect increase cancer risk - Prophylactic surgery eliminates colonic cancer risk entirely **Mnemonic:** FAP = **F**amilial **A**denomatous **P**olyposis → **P**rophylactic colectomy (not surveillance). ## Why Chemoprevention Is Insufficient Celecoxib (a COX-2 inhibitor) may reduce polyp number/size but does NOT eliminate cancer risk and carries cardiovascular toxicity. It is used as an adjunct in selected cases but never as monotherapy for established FAP. [cite:Robbins 10e Ch 7]