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?

Question

Accepted Answer

A. Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) or total abdominal colectomy with ileostomy. ## 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]

Answer

B. Celecoxib 400 mg twice daily to induce polyp regression

Answer

C. Surveillance colonoscopy every 1–2 years with polypectomy of adenomas >1 cm

Answer

D. Observation without intervention; adenomatous polyps rarely progress to cancer

Explanation

Familial Adenomatous Polyposis (FAP) Pathophysiology

Natural History and Risk in FAP

Definitive Management: Prophylactic Colectomy

Why Chemoprevention Is Insufficient

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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)