ORLANDO—Surgery remains the mainstay of treatment for familial adenomatous polyposis (FAP) and for hereditary nonpolyposis colorectal cancer (HNPCC), also known as the Lynch syndrome, David Ota, MD, said at the Society of Surgical Oncology’s 52nd Annual Cancer Symposium. Dr. Ota is professor of surgery, University of Missouri Ellis Fischel Cancer Center, Columbia.
The Gene Mutations
Familial adenomatous polyposis results from an autosomal dominant mutation in the adenomatous polyposis coli gene located on the long arm of chromosome 5 in band q21. The mutation is found in 1% to 2% of patients diagnosed with colon cancer. HNPCC, which is five times more common than FAP, is also an autosomal dominant mutation and is thought to account for 1% to 5% of colon cancers.
Patients with FAP develop hundreds of polyps throughout the gastrointestinal tract, particularly in the colon. Unless treated with prophylactic colectomy, nearly all affected individuals will develop colorectal cancer.
Dr. Ota said that patients who have the FAP gene should be examined endoscopically every 1 to 2 years. Standards for prophylactic surgery have not yet been formalized. He said that the most widely used approach for patients who develop expression of the polyposis is total colectomy and ileorectal anastomoses, although this leaves some risk of recurrence in the rectal stump.
An Area of Controversy
“An area of controversy is, do you remove the rectal stump,” he said. “The more stump that remains, the better the function will be, but there is the risk of recurrence.”
For this reason, Dr. Ota emphasized that patients who have ileorectal anastomoses must return every 6 months for surveillance. Otherwise, he recommends total colectomy, mucosal proctectomy, ileoanal anastomosis, and pouch.
For patients with the HNPCC mutation who develop colon cancer, Dr. Ota recommends subtotal colectomy with ileorectal anastomoses. Over time, HNPCC tends to appear at multiple sites on the large intestine, and this “high incidence of metachronous disease at a later date” is the reason behind the recommendation for such extensive surgery.
Most cases of HNPCC are due to defects in two genes: MLH1 and MSH2. These mutations can be identified using DNA testing. Dr. Ota advised that individuals who are asymptomatic but who are at risk for HNPCC based on family history and DNA testing should be followed with colonoscopic (not procto-scopic) examination every 1 to 2 years.
A high-risk individual would be one who has three relatives with colon cancer, whose family has colon cancer cases in two generations, and who has one relative diagnosed before age 50.
