ORLANDOSurgery 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 Oncologys 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
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.