Familial Polyposis

views updated

Familial Polyposis

Definition

Familial polyposis is an inherited condition which primarily affects the large intestine (colon and rectum). Large numbers of projecting masses of swollen and thickened or tumorous membrane (polyps) develop on the inner lining of this part of the bowel. The polyps eventually become malignant.

Description

Familial polyposis (FP) is known by many synonyms, most include some combination of words which reflect what is known about the disease. As the disease is inherited, the word, family, is often included. Because these mushroom-like growths are the most obvious manifestation of the disorder, the word, polyp, is usually in the term as well. Adenoma refers to the particular kind of polyp that is typically discovered. Some of the names found in medical texts and journals include polyposis coli, familial colonic polyposis, multiple familial polyposis, familial adenomatous colon polyposis, adenomatosis of the colon and rectum (ACR), and familial adenomatous polyposis (FAP). The last term and its abbreviation have been commonly used since the early 1990s. It will be used in this discussion.

Familial polyposis or familial adenomatous polyposis (FAP) is a premalignant disease. This means that a person with FAP, if left untreated, will invariably develop cancer. Individuals with this disorder grow hundreds of polyps throughout their large intestines. The polyps, which may also be called adenomas, commonly develop just after puberty. Approximately half of all FAP patients will have polyps by age 14. Ninety percent will have detectable polyps by age 25. Usually by age 35-40, one or more of these polyps will become cancerous.

FAP is a rare disease. One in 8,000 people in the United States have FAP. However, it may be very common in affected families. FAP is inherited in an autosomal dominant pattern. This means that a person with FAP has a 50% chance of passing the condition down to each of their children. FAP can also develop in someone with no family history of the disorder, due to a new genetic mutation in that individual. It is thought that approximately one percent of all colorectal cancers in the United States can be attributed to FAP.

Causes and symptoms

FAP is caused by a portion of a gene that mutates or changes. The original cause of the mutation is unknown. Its exact role in FAP is not completely clear. Researchers theorize that the normal gene directs the manufacture of a protein which helps control cell growth. The mutated gene section in FAP generates an abnormal protein which does not perform its normal function. Cells grow out of control, causing the development of multiple, sometimes hundreds, of polyps. One or more of these eventually becomes cancerous.

Many individuals develop polyps without displaying any symptoms. Others experience such gastrointestinal problems as diarrhea, constipation, abdominal cramps, blood in the stool, or weight loss. FAP patients may also develop nonmalignant tumors (desmoid tumors), and/or some bone and dental abnormalities. In addition, they may exhibit a "spot" on the retina of the eye (congenital hypertrophy of the retinal pigment epithelium, or CHRPE).

Relatives of individuals with diagnosed FAP are at high risk of having the disease themselves. There are no other known risk factors for this condition.

Diagnosis

The abnormal portion of the gene that causes FAP in most patients can be detected. A blood test can then be performed which identifies family members who have the same mutation. They will eventually develop the condition. Children who have a parent with FAP, and siblings of affected patients whose parental history is incomplete, should be evaluated. The polyps characteristic of FAP have been found in children as young as age five. Testing of appropriate individuals should take place as soon as the diagnosis of FAP is established in one member of a family.

Relatives of people with diagnosed FAP should exercise caution regarding where they seek advice and testing. One study of a commercially available blood test found that less than 20% of patients received any genetic counseling, and almost one third of their physicians misinterpreted the test results.

Registries for FAP patients can be found at many sites in the United States. Such a registry specializes in identification, assistance, and education of people with a particular disease, and is usually a separate department in a research hospital. A team of health professionals who have expertise in the disorder staff the registry.

Testing within a research setting and/or at a facility with a registry of patients with FAP is more likely to safeguard against problems, such as the misunderstanding of test results. As part of a research project, sometimes counseling as well as blood tests are available at no charge to the patient. Insurance coverage varies. Concerns about confidentiality, and future insurance and employment discrimination, may prompt individuals to pay for the examination out of pocket. Commercial blood tests cost approximately $250 per sample.

If the abnormal gene is found in a family member, annual screening for colon polyps is recommended, beginning at age 11. Flexible sigmoidoscopy is used for this examination. It is usually done in a physician's office, or in a hospital department, most often by a gastroenterologist or a surgeon. Food intake may be restricted for 24 hours prior to the procedure. Before the study, the intestine is cleared of stool by one or more small enemas. Some physicians prefer to sedate the patient, to help them relax. Then a flexible, lighted, hollow tube (sigmoidoscope) is inserted into the anus and maneuvered into the large intestine. The physician examines the wall of the colon to look for polyps. If polyps are found, one or more may be removed for biopsy.

Most patients report little discomfort during the examination. The procedure itself takes five to fifteen minutes. The patient may be at the facility an hour, or more, if recovery from sedation is needed. If no medication was administered, driving and resumption of normal activities are permitted immediately. The cost of the procedure varies widely, but, as of 1997, it was covered by Medicare, indicating the likelihood of other types of insurance coverage.

In some cases the portion of the gene responsible for FAP cannot be identified. Family members of these patients cannot have a predictive blood test. The current recommendation is for these patients to have the same annual examination with flexible sigmoidoscopy as patients with a diagnosed FAP gene. A noninvasive screening eye examination to detect CHRPE, associated with FAP, may also be performed.

Treatment

The only definitive treatment for FAP is surgical removal of the lower intestine. Since the goal is to prevent cancer, the operation is done as soon as adenomatous polyps are found on sigmoidoscopy. Waiting until a polyp becomes malignant is unsafe, as the cancer may invade surrounding tissues.

There are several choices about the type of surgery to treat this condition. Some authorities advocate removal of the colon, leaving the rectum or lowest portion of the intestine in place. The small intestine can be attached to the rectum, allowing normal bowel function. This is often called ileorectal anastomosis. Others argue that this section is also liable to develop polyps, needs to be monitored regularly, and may require eventual removal.

Excision of the entire lower intestine with preservation of normal bowel function is possible. This entails a more complex surgical procedure. The patient may experience more complications and a longer recovery period. However, the risk of polyp development in this area is very low. Periodic examination of the intestine may not be needed once healing is complete.

The more intricate surgery may be referred to as a J-pouch procedure, an ileal pouch-anal anastomosis, a restorative proctocolectomy, or an ileoanal reservoir procedure. It involves creating a "pouch" of tissue from the small intestine, which is attached to the anus. This serves as a reservoir or holding area for stool, much as the rectum does normally. The surgery is often done in several stages. A temporary ileostomy, which creates an opening of the small intestines onto the abdomen, is required. When all procedures are completed, and after a recuperation period, the patient regains normal bowel function through the anus.

Some researchers suggest that as genetic testing becomes more developed, the specific portion of the gene involved may dictate the type of surgery chosen. Those at high risk of developing rectal polyps may be advised to have the more complex operation. FAP patients felt to be at lower risk for rectal polyps might be counseled to consider the less radical surgery.

Medical therapy to treat the adenomatous polyps has been attempted. Some nonsteroidal anti-inflammatory drugs have been effective in reducing the number and size of the polyps. It is possible that these agents will be used as an additional treatment for FAP, but they are unlikely to replace surgery.

Individuals with FAP are at increased risk for cancers of the upper digestive tract including the upper portion of the small bowel (dudodenum) and the channels where bile flows (biliary tract). Cancers of the thyroid, pancreas, and adrenal gland are also more commonly found among FAP patients. Periodic examination for the development of malignancy in these areas is considered part of the treatment of FAP. In some cases, such as cancer involving the duodenum, the tests themselves carry a chance of complications. The risk of the study must be weighed against the potential benefits of knowing the results. Nonmalignant growths, called desmoid tumors, also occur more frequently in patients with FAP. Although they are not malignant, they grow quickly into surrounding tissues, causing many difficulties, even death in some cases.

Prognosis

The major cause of death in many patients with FAP remains colorectal cancer. One study suggested that even with improved disease recognition, social and emotional factors, such as fear of surgery, may significantly delay a patient's treatment. In recent years, the trend is towards mortality from other causes, such as desmoid tumors or cancers other than colorectal. It has been estimated that a patient with known FAP has a relative risk of dying over three times greater than that of the average population, at a given age.

Prevention

FAP cannot be prevented. Aggressive diagnosis, treatment, and follow-up monitoring are keys to successful management of the disease.

Resources

ORGANIZATIONS

Familial Polyposis Registry. Department of Colorectal Surgery. Cleveland Clinic Foundation. 9500 Euclid Ave., Cleveland OH 44195-5001. (216) 444-6470.

National Organization for Rare Disorders. PO Box 8923, New Fairfield, CT 06812-8923. (800) 999-6673. 〈http://www.rarediseases.org〉.