Genetic alterations in patients with colorectal cancer associated to an excess of adenomatous polyps and without previous familial history

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Introduction: Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the APC gene on chromosome 5. Early colectomy substantially reduces the cancer risk to patients. Restorative proctocolectomy maintains continence and removes the risk of rectal cancer. Suture lines are prone to carcinogenesis experimentally, which raises concern that pouches might themselves be at risk. Previous studies have confirmed the presence of pouch adenomas in some patients but the long term risk of pouch polyposis and potential for neoplastic transformation is unknown. Our aim was to prospectively evaluate the nature of pouch adenomas in FAP. Methods: Thirty FAP patients (16 male; median age 40 years, range 21-72) were examined using flexible videoendoscopy. All patients had undergone previous restorative proctocolectomy with a median follow-up interval of 6 years (range 2-14 years). The pouch design was J-shaped in 23 patients and W-shaped in 7. All procedures were videotaped and performed unsedated after bowel preparation with two disposable enemas. All suspected adenomas were biopsied. Results: Adenomatous polyps were found in the pouch of 21 (70%) patients. A total of 151 polyps were identified (range, 1-40 per patient). Adenomas were seen in 13/16 (81%) patients whose follow-up since surgery was >5 years but in only 8/14 (57%) whose follow-up period was <5 years. Biopsies revealed tubular adenoma with mild dysplasia in 17 patients and tubular adenoma with moderate dysplasia in I patient. In addition a serrated adenoma, a tubulovillous adenoma with moderate dysplasia and a 1-2cm villous adenoma were found. Discussion: This study has demonstrated the presence of adenomatous polyps in 70% of pouches examined in patients with FAP. There appears to be a trend to increasing development of adenomas with time from surgery. The purpose of the ileal pouch is to allow faecal stasis and this may allow conditions which promote adenoma development. The risk of invasion in this group is unclear but follow-up periods since surgery remain relatively short and a variation in histological type and stage of dysplasia was seen. Endoscopic surveillance is thus recommended along with evaluation of potential therapeutic options.