FAP & DUODENAL CANCER
• • • Adenomatous polyps of the stomach, duodenum, and small bowel occur in 90-100% of patients with FAP. Gastric cystic fundic gland polyps are common but rarely associated with malignancy. The second portion of the duodenum, especially the periampullary area, is the one prone to adenomatous transformation ○ 3-8% of patients eventually have duodenal or periampullary cancer ○ a risk that increases if there is a family history of such occurrence. Adenomas of the gastric antrum and other portions of the small bowel also occur but with lesser frequency. In 1989, Spigelman et al published an endoscopic and histological classification system for evaluation of the severity of duodenal adenomatosis.
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SPIGELMAN CLASSIFICATION points # of polyps Polyp size (mm) Histology Dysplasia 1 1-4 1-4 Tubular Mild 2 5-20 5-10 Tubulovillous Moderate 3 > 20 > 10 Villous Severe Stage I, 1-4 points; stage II, 5-6 points; stage III, 7-8 points; stage IV, 9-12 points Duodenal adenomatosis in familial adenomatous polyposis Gut, March 2004 • 368 patients examined by gastroduodenoscopy at two year intervals. • 65% had duodenal adenomas at the first endoscopy. • The cumulative incidence of adenomatosis at age 70 years was 90%, and of Spigelman stage IV was 52%. • In 20% of the patients without visible polyps, random biopsies showed adenomatous changes. • Two patients had asymptomatic duodenal carcinoma at their first endoscopy while four developed carcinoma during the study at a median age of 52. • The cumulative incidence rate of cancer was 4.5% at age 57 years and the risk was higher in patients with Spigelman stage IV at their first endoscopy than in those with stages 0– III. • Decision analysis demonstrated that regular surveillance by gastroduodenoscopy resulted in an increase in life expectancy of seven months. Duodenal cancer in patients with familial adenomatous polyposis (FAP): results of a 10 year prospective study Gut, May 2002 • Ten year follow up of 114 patients with FAP who were prospectively screened for the presence and severity of duodenal adenomas. • Six of 114 patients (median age 67 years) developed duodenal adenocarcinoma. ○ Four of these were from 11 patients who originally had Spigelman stage IV disease, which gives a 36% risk within this group of developing cancer. ○ All six patients have died: five were inoperable and one had recurrence three years after a pancreaticoduodenectomy.
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There was no association between duodenal cancer and site of germline mutation of the APC gene. Prophylactic pancreaticoduodenectomy should be considered in Spigelman stage IV.
A randomized, double blind, placebo controlled study of celecoxib, a selective cyclooxygenase 2 inhibitor, on duodenal polyposis in familial adenomatous polyposis Gut 2002 • This was a randomized, double blind, placebo controlled study of celecoxib (100 mg twice daily (n=34) or 400 mg twice daily (n=32)) versus placebo (n=17), given orally for six months to patients with FAP. • Efficacy was assessed by blinded review of endoscopy videotapes comparing the extent of duodenal polyposis at entry and at six months. • A panel of five endoscopists found a significant reduction in duodenal polyposis after six months of treatment with celecoxib 400 mg twice daily, especially in patients with clinically significant disease at baseline (>5% covered by polyps). Worldwide survey among polyposis registries of surgical management of severe duodenal adenomatosis in FAP Br J Surg, June 2003 • Invasive duodenal carcinoma in FAP has a poor prognosis, even if these carcinomas are detected during surveillance. • Therefore, surgical treatment of duodenal adenomatosis should ideally take place before endoscopic biopsy reveals invasive cancer. • Unfortunately this is complicated by the fact that endoscopic biopsy is often not representative of the entire lesion. ○ Ten of 36 patients with Spigelman IV disease were found to have invasive cancer. ○ The mean age of patients at the time of surgery for invasive carcinoma (53 years) was 10 years higher than that of patients treated for severe adenomatosis (43 years). ○ This suggests that major surgery, such as (pylorus-preserving) pancreatoduodenectomy, may be postponed until the fifth decade of life. • The surgical options: ○ Ampullectomy and duodenotomy with surgical polypectomy are associated with an adenoma recurrence rate of almost 100%. ○ Even after extensive surgical procedures such as (pylorus-preserving) pancreatoduodenectomy, small bowel adenomas may recur. ○ In addition, almost half of these extensive surgical procedures were accompanied by major morbidity. ○ However, in most patients, such as those with carpet-like polyposis, extensive surgery offers the only chance of cure or a prolonged disease-free interval. ○ Operative and endoscopic measures fail in controlling duodenal adenomatosis in the long term.
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Proposed program for surveillance and treatment of duodenal adenomatosis Endoscopy* at intervals of 5 y Endoscopy at intervals of 5 y Endoscopy at intervals of 3 y Endoscopy at intervals of 1–2 y Endoscopic ultrasonography Consider pancreas sparing or pylorus sparing duodenectomy *Including multiple random biopsies from mucosal folds in patients without visible polyps. Including multiple biopsies from polyps. Spigelman stage 0 Spigelman stage I Spigelman stage II Spigelman stage III Spigelman stage IV
Einat Carmon, M.D. March 28, 2005
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