This pathological specimen shows large bowel mucosa with multiple adenomatous polyps. The patient has
Familial Adenomatous Polyposis (FAP). It is inherited as an autosomal dominant condition with a high degree
(>95%) of penetrance. It should be noted that 25% of those affected have no family history, the condition
arising due to a new gene mutation. It is the commonest single gene disorder giving rise to a cancer. Those who
possess the mutant gene invariably develop multiple colorectal polyps during their teens and untreated progress
to colorectal cancer by their 30s or 40s. The polyps are usually tubular adenomas with over 1000 polyps often
found in a typical patient. The Adenomatous Polyposis Coli (APC) gene is found on the long arm of chromosome 5.
FAP is associated with multiple osteomas and epidermoid cysts (Gardner's Syndrome). Other extra-intestinal
manifestations include gastroduodenal and periampullary polyposis, desmoid tumours and pigmented retinal lesions
(CHRPE = Congenital Hypertrophy of Retinal Pigment Epithelium). Probably all of these manifestations of FAP
arise from the one genetic defect with variable phenotypic expression in different patients.
Prophylactic colectomy is the treatment of choice. There are three surgical options:
- Panproctocolectomy and Brooke Ileostomy
- Subtotal Colectomy with Ileorectal Anastomosis
- Restorative Panproctocolectomy
Panproctocolectomy with ileostomy formation is best avoided if at all possible. Not only does the patient
have to come to terms with a stoma but inevitably other family members will require surgery and compliance is
jeopardised if a stoma is seen as the only outcome of surgery. Total Colectomy and Ileorectal anastomosis (IRA)
preserves a rectal stump the mucosa of which will require life-long surveillance. 15% patients undergoing Total
Colectomy and IRA will develop cancer in the rectal stump during the first 15 to 20 years of follow up. However
rectal cancer accounts for only 2% of deaths in patients undergoing this operation. Restorative
Panproctocolectomy removes all of the large bowel mucosa. The neo-rectum requires continued surveillance as
polyp formation can occur in the ileoanal pouch.
Recent reports suggest that NSAIDs (e.g. Sulindac) reduce the size and number of polyps. A reduction in the
risk of developing cancer has yet to be confirmed. Approximately 5% of patients with FAP develop duodenal or
periampullary carcinoma. Following definitive surgery patients are more likely to die from upper GI malignancy
than carcinoma in their rectal stump.
Pre-symptomatic screening of at risk individuals allow the early recognition of gene carriers. This has been
shown to be of benefit as the prevalence of cancer at diagnosis is about 60 - 70% in symptomatic unscreened
individuals compared to 5 to 10% in a high risk screened population. Rigid sigmoidoscopy is acceptable as a
screening method. Very few patients with FAP have rectal sparing and thus if the rectum is clear they are
unlikely to have proximal polyps. Screening should begin in the early teens and continue with 2 yearly
examination until at least 40 years. If a patient has not developed polyps by the age of 35 years the risk of
them appearing in later life is about 1:1000. The recent development of linkage and mutation analysis may soon
allow the identification of those without the gene mutations in whom repeated clinical screening will be
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