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Considering Prophylactic Surgery, Part IIby Ellen McDonald
Undergoing prophylactic surgery to prevent a cancer caused by a genetic mutation is a life-altering event, however effective the operation may be. This is the issue faced by people with multiple endocrine neoplasia type 2 (MEN2), familial adenomatous polyposis (FAP), or hereditary nonpolyposis colorectal cancer (HNPCC). All three conditions result from inherited or spontaneously mutated genes and can often be effectively treated with well-timed prophylactic surgery. MEN2 is characterized by medullary thyroid carcinoma, pheochromocytoma, and hyperparathyroidism. A well-timed thyroidectomy, usually in childhood, can often prevent the development—or at least the spread—of cancer. “Surgery to remove the thyroid gland is always recommended when a RET mutation is detected,” said Robert F. Gagel, M.D., a professor in the Department of Endocrine Neoplasia and Hormonal Disorders and the head of the Division of Internal Medicine at M. D. Anderson Cancer Center. He explained that the disease manifests itself in two forms: MEN2A and MEN2B, the latter being a more aggressive form that typically results from a spontaneous mutation and that all too often is not diagnosed until after tumor growth and metastasis have occurred. Because of the aggressive nature of MEN2B, thyroidectomy should be performed as early in life as possible—at 6 months or sooner in some cases. “It is hard to cure a child with MEN2B,” Dr. Gagel admitted. “However, children with MEN2A can be cured, assuming they have a thyroidectomy at a relatively young age. Our best estimate is that we can cure approximately 85% of MEN2A patients by removing the thyroid gland before the age of 13. “However, an intriguing question currently under study at M. D. Anderson and elsewhere is whether we can cure 100% of these patients by removing the thyroid by age 5. Some evidence suggests that it’s possible to cure at least 95% of them. But given that the genetic test that definitively identifies people with this mutation has been available for only 10 years, we probably won’t really have the answer to this question for another 20 years or more.” Suzanne Shapiro, a genetic counselor in the Department of Surgical Oncology, explained that timing of prophylactic thyroidectomy is key for children with MEN2A—early enough in life to prevent the development or metastasis of medullary carcinoma and yet late enough to minimize the number of years daily thyroid hormone replacement therapy will be required. “Appropriate timing also depends on a family’s specific experience with the disease,” she added. “Some parents may not feel comfortable waiting until a child is 5 years old, especially if there’s a family history of aggressive thyroid cancer. Timing of the surgery, therefore, shouldn’t be set in stone, but should be based on the current literature, family medical history, and the parent’s wishes.” One parent who knew no hesitation is Phyllis Fischer, whose own thyroid cancer led to a diagnosis of MEN2A in 2003. Prior to that, no one in her family had suspected the presence of a familial genetic mutation, although in retrospect she believes that her paternal grandmother and other family members may have died of complications of MEN2A. “At first it was scary finding out that I had the disease, extremely so,” Fischer explained, “but I did my own research, asked a lot of questions, and learned everything I could about it.” She persuaded everyone in her large family to be tested, and five of them, including two of her daughters, ages 11 and 21, were found to carry a RET mutation. She encouraged her daughters to undergo prophylactic thyroidectomies, the results of which showed very little cancer development and no lymph node involvement in either daughter. While age is not as major a factor for familial adenomatous polyposis (FAP) or hereditary nonpolyposis colorectal cancer (HNPCC), the treatment approach certainly is. Prophylactic colectomy is widely accepted as the optimal treatment for patients with FAP, a genetic syndrome associated with a germline mutation in the APC gene. The surgery typically involves removal of the abdominal colon and an abdominal or total colectomy. It may also involve removal of the rectum and connection of the small bowel reservoir to the anus to establish bowel continuity. The type of procedure performed depends on many factors, but more importantly on the location and number of polyps, which can range from the hundreds to the thousands. “Most patients who carry such a mutation will develop cancer by age 50 without the surgery,” said Miguel A. Rodriguez-Bigas, M.D., a professor in the Department of Surgical Oncology at M. D. Anderson. “Retrospective studies have shown that the surgery can improve their survival time by approximately 20 years.” Nevertheless, the data are not so clear regarding HNPCC. “Prophylactic surgery is more controversial in the management of HNPCC, or the Lynch syndrome,” Dr. Rodriguez-Bigas continued, “because there are as of yet no data showing a major improvement in survival time with the surgery, and 15 to 20% of people with HNPCC will not develop colorectal cancer.” (Despite its name, HNPCC is not a type of colorectal cancer but a disorder that puts those affected at higher risk for colorectal cancer, and these people will develop polyps before they develop cancer.) Therefore, based on the individual circumstances of the case and his judgment as a surgeon, Dr. Rodriguez-Bigas may offer prophylactic surgery as an option to patients with HNPCC. Such patients are identified by having both the requisite family history of non–FAP-related colorectal cancer and a genetic mutation in a mismatch repair gene, such as hMSH2, hMLH1, or HMSH6. “We generally try to see patients with either disorder as early as possible,” noted Patrick M. Lynch, M.D., an associate professor in the Department of Gastrointestinal Medicine and Nutrition. “Ideally, we’d like to see patients before they have any signs of disease, such as polyps, bleeding, or obstruction. “In the case of FAP, we currently have a clinical trial specifically designed for children with the genetic mutation. The trial includes a fairly active chemoprevention program and close surveillance, usually with colonoscopy, to study whether we can postpone the day when prophylactic colectomy will be needed. Our genetic counselors work closely with physicians throughout this process and will track families with the genetic mutations through several generations.” Despite recommending that patients delay the surgery until their polyp burden is at least moderate, Dr. Lynch always encourages the patient and, if applicable, the patient’s parents, to get to know the surgeon long before the need for surgery exists. “This gives them ample opportunity to get a second opinion if desired, discuss the type of surgery required based on the trajectory and progression of the polyp involvement, bond with the doctor, and prepare themselves emotionally for the physical and psychological consequences of the surgery.” Although he hopes that advances in medical treatment will one day make prophylactic colectomy—which even in the best of circumstances is a radical treatment—unnecessary, Dr. Lynch believes that until that day comes, he best serves his patients by giving them this time to prepare.For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789. Other articles in OncoLog, June 2005 issue:
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