An inherited colonic disorder
This gastrointestinal specimen was taken from a 25 year old man. 1. What does it show? 2. What is the mode of inheritance? 3. What operation is he likely to have undergone?
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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 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 unnecessary. Recent PapersCampbell W J, Spence R A J, Parks T G. Familial adenomatous polyposis. Br J Surg 1994; 81: 1722-1733. Cunningham C, Dunlop M G. Familial adenomatous polyposis. Curr Pract Surg 1993: 5: 181-185. Giardiello F M, Yang V W, Hylind L M. Primary chemoprevention of familial adenomatous polyposis with Sulindac. N Eng J Med 2002; 346: 1054-1059. Sagar P M, Pemberton J H. Operations for familial adenomatous polyposis. Surg Oncol Clin N Am 1996; 5: 675-688. Stephenson B M, Hall N R, Finan P J, Bishop T. Inherited predisposition to colorectal neoplasia. Br J Hosp Med 1994; 51: 15-22. Wyman A, Shorthouse A J. Familial adenomatous polyposis: an update. J Roy Soc Med 1996; 89: 224-228
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