By James M. Church, MD
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For people with inherited colorectal cancer predisposition syndromes and their families, the goals of cancer prevention and treatment should be balanced with the preservation of quality of life.
The stakes are high because these patients are often relatively young when they develop multifocal neoplasia, and critical management decisions involve both patients and their as-yet unaffected family members.
At Cleveland Clinic, we monitor both patients and family members very closely and avoid surgery if possible. If colectomy is required, we approach it in way that preserves function and quality of life.
Lynch syndrome and familial adenomatous polyposis (FAP) are the most common and best known of the dominantly inherited colorectal cancer syndromes. Both arise from germline mutations that result in destabilization and deregulation of cell growth. And in both syndromes, there are critical questions involving the type and timing of surgery.
Lynch syndrome: Extensive surgery versus standard surgery and colonoscopy
Patients with Lynch syndrome have a mutation in their DNA that causes repair of DNA mismatches to fail. This creates mutations in multiple genes that predispose to the development of colorectal, endometrial (uterine) and other cancers at an early age.
Patients and families with Lynch syndrome can be identified by testing of their tumors for evidence of the mutation or by family history, where the dominant inheritance creates a typical pattern of multiple cancers in young (< 50 years) relatives.
In the best possible scenario, a diagnosis is made early in a patient with cancer due to Lynch syndrome via testing of the cancer seen during colonoscopy. This allows the surgeon to plan surgery to minimize the risk of further colon cancer. Total colectomy and ileorectal anastomosis can be performed safely, without a stoma, and with an acceptable bowel function and a good quality of life.
Unfortunately, the more common scenario is a standard cancer operation, with testing of the cancer performed only after it has been removed. Then, if the patient turns out to have Lynch syndrome, the options are either to rely on annual colonoscopy to prevent further cancers or to perform reoperation to remove the rest of the colon. Most patients choose annual colonoscopy.
For affected family members with as-yet normal colons, we generally don’t recommend primary prophylactic colectomy unless the individual is particularly worried about developing colorectal cancer and wants the surgery, or the family has a particularly aggressive disease phenotype. In most cases, we instead recommend colonoscopy every one to two years.
When gastroenterologists see a colorectal cancer in a young patient or a patient with a strong family history of colorectal cancer, they should request immunohistochemistry testing of the tumor for evidence of loss of expression of a DNA mismatch repair protein, or microsatellite instability testing. A positive test suggests the possibility of Lynch syndrome and demands further investigation. A negative test largely rules it out.
Familial adenomatous polyposis: Wait to operate
While FAP is also a dominantly inherited form of colorectal cancer, it differs from Lynch in three important ways:
- The risk of colorectal cancer is higher and cancer occurs at younger ages.
- Hundreds to thousands of polyps are an obvious indication of the syndrome, and therefore genetic testing is not so critical to make the diagnosis.
- The rectum is often removed, with the operation of ileal pouch anal anastomosis among the list of alternative surgeries.
The surgical approach to FAP revolves around two decisions: When to do the operation and what operation to do. Because of their high risk of cancer, immediate surgery is necessary for patients who are symptomatic or who have profuse polyposis (1,000 or more adenomas).
But for most others, surgery can be scheduled at a time in the patient’s life — ideally during adulthood — when they are capable of dealing mentally with the stresses involved, when academic and social plans will not be interrupted, and when financial considerations are favorable. At Cleveland Clinic, we monitor these patients’ colons annually, paying attention to the number and size of polyps.
When the risk starts to climb, we intervene with the most conservative procedure possible to reduce the risk of cancer while minimizing complications and allowing better bowel function. We’re also increasingly using minimally invasive techniques that have helped to reduce pain and disability.
For patients with mild FAP, the standard operation is a total colectomy with ileorectal anastomosis. This can be done laparoscopically, with no stoma, minimal hospital stay, little time off work and school, and a small impact on quality of life.
However, severe FAP involving the rectum generally requires pouch surgery, which is more major and often involves a temporary ileostomy, significant changes in bowel habit, longer recovery and greater risk for complications. There is a potential for creating severe problems in the lives of basically asymptomatic patients, so it is essential that pouch surgery be done in a hospital with proven expertise and experience in this demanding procedure.
Occurring in just about 1 in every 8,000 births, FAP is not a condition gastroenterologists see often. But when they do, referral to a specialty center is highly recommended.
Read Dr. Church’s article on Controversies in the surgery of patients with familial adenomatous polyposis and Lynch syndrome in the July 2016 issue of Familial Cancer.