What is Familial Adenomatous Polyposis (FAP)?
FAP is an inherited colorectal cancer syndrome and accounts for 1 percent of all cases of colorectal cancer. The “F” stands for familial, meaning it runs in families; “A” stands for adenomatous, the type of polyps detected in the colon and small intestine that can turn into cancer; and “P” stands for polyposis, or the condition of having lots of colon polyps. The gene for FAP is on the long arm of chromosome 5 and is called the APC gene.
Patients with FAP develop hundreds to thousands of colon polyps, usually starting in the teens. All patients will develop colorectal cancer from the colon polyps usually by age 40. Patients with FAP must have the colon, and sometimes the rectum, removed to prevent colon cancer.
Since the abnormal gene that causes FAP is present in all of the body’s cells, other organs may develop growths.
In more than 80 percent of patients with FAP, polyps form in the stomach and small intestine. The polyps found in the upper portion of the stomach are called fundic gland polyps. Some patients have none, while others may have a carpeting of these polyps. These polyps should be biopsied once to confirm their microscopic makeup. Fundic gland polyps do not turn into cancer and usually do not require any special treatment.
The polyps found in the bottom of the stomach (the antrum) most often are precancerous polyps called adenomas. They should be biopsied and completely removed because of the risk of cancer.
Polyps in the duodenum (the first part of the small intestine) are adenomas and also can turn into cancer. In fact, duodenal cancer is the second leading cause of cancer deaths in patients with FAP once the colon has been removed. The overall risk of duodenal cancer in FAP is about 4 percent. If patients have severe or advanced duodenal polyposis, the risk can be as high as 25 percent. Duodenal polyps can be very subtle and hard to detect, or they may be obvious and cover a large segment of the duodenum. Often, they are found at the opening of the bile duct and the duodenum, called the papilla. Because of the great number of polyps, they usually are not removed. However, they need to be checked regularly for the remainder of the patient’s life. Biopsy of any large or concerning duodenal polyps and the papilla, even if the papilla appears normal, should be performed regularly.
The other organs that form tumors include the skin, bones, eyes (congenital hypertrophy of the retinal pigment epithelium CHRPE), thyroid and abdomen (desmoid tumors). Extra teeth may also form in patients with FAP.
Gardner’s syndrome and FAP are due to an inherited mutation in the APC gene. Attenuated FAP is a variant of FAP where there are fewer polyps in the colon. The colorectal polyps and cancer in attenuated FAP usually occur later in life than in FAP; however, the risk of colon cancer and upper gastrointestinal polyps is the same as in FAP.
How is FAP Diagnosed?
The first step in making the diagnosis of FAP is based upon the family history of colorectal polyps and cancer. The majority (60 percent to 70 percent) of patients with FAP have inherited the gene from one of their parents. Therefore, consecutive generations may have FAP. Taking a careful family history is crucial in diagnosing FAP.
In about 30 percent of FAP patients, the abnormal gene was produced at the time of conception. In these patients, no family history of FAP would be found. All of the next generations are at risk of inheriting the newly mutated gene.
A significant breakthrough in the diagnosis of FAP was made with the discovery of the gene on chromosome 5. Now, family members at risk of FAP may have their blood taken and analyzed for the FAP gene mutation (called APC). The APC gene mutation is able to be detected in more than 80 percent of people with FAP. In 20 percent of people with FAP, the gene abnormality cannot be detected with the blood test. Gene tests do not detect cancer or polyps themselves. They only provide evidence that a person has acquired the gene mutation and has FAP.
There are two widely used methods for detecting mutations: One is a protein truncation test, and the other is direct DNA sequencing. Gene testing should first be done on a family member with FAP. If the mutation is found, other family members can be tested. If the mutation is not found, blood testing is not helpful to test family members to see if they have FAP.
Interpreting the results of the FAP genetic test is tricky; therefore, gene testing should only be performed by experts in FAP in the genetic counseling setting. There are many advantages of gene testing. There are also important psychologic and family issues that must be discussed before and after gene tests are performed. It is important to remember that gene tests do not detect cancer or polyps; they only provide evidence that a person has acquired the gene mutation and has FAP.
Because 30 percent of people with FAP have a new (spontaneous) mutation and no family history of polyposis, they may not know they have FAP until symptoms of polyps or cancer develop. Symptoms may include bleeding from the rectum, change in bowel habits, abdominal pain, low blood counts or unexplained weight loss. An examination of the colon to determine the cause of symptoms may reveal polyposis.
There are many ways to examine the colon. These include the use of a thin flexible tube called a scope, or by an x-ray examination called a barium enema. If hundreds to thousands of colorectal polyps are detected on either of these examinations, the diagnosis of FAP is suspected. To confirm the diagnosis of FAP, a scope test should be performed. The scope is the best test to evaluate the lining of the colon, because biopsy or removal of some polyps can be done during the procedure. The short scope that examines only the lower one or two feet of the colon is called a flexible sigmoidoscope.
The examination with the flexible sigmoidoscope takes about five to ten minutes and requires an enema or two just before the scope is inserted. No sedation is given. The examination of the whole six feet of the colon with a longer scope is called a colonoscopy. For the colonoscopy, patients drink a solution to cleanse the colon the night before the test. The doctor usually gives a sedative through the vein just before inserting the scope. The exam takes approximately twenty minutes and is usually not uncomfortable. Someone must drive the patient home (because of the sedative). They leave shortly after the procedure and can resume light duties the rest of the day.
What is the treatment when polyposis is found?
Since colonic polyps form by the hundreds and thousands in FAP, they cannot be removed individually. Surgical removal of the colon is the only effective treatment. While the thought of having surgery may be upsetting, it must be done to prevent colon cancer from forming.
Polyps begin forming as young as puberty. When polyps are detected, a colorectal surgeon should be involved in the care of the patient to help guide the timing of surgery. There have been advances in the way that operations are performed. Depending on the situation, any of the following operations may be performed with the aid of small holes in the abdomen called laparoscopy or through the standard abdominal incision called laparotomy.
The most common surgical treatments are:
Total colectomy and ileorectal anastamosis (IRA)
Patients with few polyps in the rectum usually undergo this procedure. During the operation, the surgeon removes the patient’s colon but leaves five inches of the rectum. The small intestine, or ileum, is then surgically joined to the upper rectum. Afterward, the patient has normal bowel function.
Colectomy with ileoanal pouch (restorative proctocolectomy)
This surgical procedure is successful in selected FAP patients. The surgeon removes the colon and the rectum, leaving the anal canal and the anal sphincter muscles. A new rectum is made from the small intestine and attached to the anal canal. Sometimes a temporary opening in the abdomen, called an ileostomy or stoma, is created. After the first operation has healed, the ileostomy is closed, restoring normal bowel function.
Proctocolectomy and ileostomy
This procedure is recommended for patients with rectal cancer who cannot have the other operations. Both the colon and rectum are removed, and a permanent ileostomy is created. Patients then wear a bag to collect wastes that leave the body through the ileostomy.
How long is the hospital stay?
The length of stay in the hospital depends on the type of surgery performed. The usual stay is less than one week.
What about recovery?
After hospital discharge, recuperation at home is four to six weeks. Patients usually return to work or school in six to eight weeks.Your doctor will discuss this with you at your post-operative visit four to six weeks after surgery.
What lifestyle changes can be expected?
Most patients are able to eat normal diets and lead normal lives following surgery. Some people notice more frequent bowel movements. Otherwise, their lives will be perfectly normal. Their sexual and social activities are unaffected. None of the procedures affects a man’s ability to father children nor a woman’s ability to have a normal pregnancy. However, the way in which a baby is delivered may be affected by the type of surgery and should be discussed with the surgeon.
While surgery is most common for treating the colon polyps, it does not cure the disease. Polyps continue to form in the pouch, rectum or small intestine. A variety of medications have been developed to cause the regression (shrink existing polyps) or prevention of recurrent polyps. While these medications help control the colorectal polyps, they should only be used in conjunction with ongoing check ups and do not replace the usual care of patients with FAP.
The first medication that was found to shrink colon polyps in patients with FAP was an anti-inflammatory medicine called sulindac. It is a commonly used anti-arthritis medicine called NSAID (nonsteroidal anti-inflammatory drug). While it is not approved by the Food and Drug Administration (FDA) for the treatment of FAP, it has been used successfully in pill form in the United States and as an enema in Europe by many gastroenterologists. Unfortunately, many patients experience side effects from sulindac and cannot continue to take it. The majority of the side effects are related the stomach, including discomfort and ulcer.
An arthritis medication called celecoxib was approved by the FDA for the treatment of colon polyps in patients with FAP. The medicine is called a COX-2 inhibitor. It has less of the gastrointestinal side effects than the traditional NSAIDs. In a six-month study, celebrex was found to shrink existing colorectal polyps in patients with FAP. It was also well-tolerated. The dose is 400 mg twice a day. This medication can be used to help control adenomatous polyps on the colon and rectum, in addition to regular colorectal checks and polyp removal when necessary.
What testing is needed to keep patients with FAP or at risk for FAP healthy?
Patients with FAP or family members at risk for FAP should have regular checkups of the colon, rectum or pouch and the upper gastrointestinal tract. This is called surveillance. These checks begin in early adolescence and continue even after surgery or until there is clear evidence that someone has not inherited the FAP gene.
If a relative has had genetic testing and does not carry the family mutation, the person does not have FAP and does not need checkups. For relatives at risk of FAP (brothers, sisters, children of patients with FAP) and patients who have inherited the family FAP mutation, colon checks with a flexible sigmoidoscope or colonoscope should begin at approximately 12 years of age. Examinations are generally performed yearly. The frequency of examinations may change based upon the size and number of polyps detected at the examination. Once polyps are detected, a surgeon with expertise in FAP should be involved in the patient’s care. If no polyps are detected, yearly colonoscopies should continue approximately until age 35. After that age, patients should continue with routine colorectal cancer screening. If patients have attenuated FAP, colon checkups may be required after the age of 35.
After the colon has been removed, checks of the remaining rectum or pouch continue for the rest of the patient’s life. The reason is that polyps will continue to form in the rectum or the pouch after surgery. If polyps are found, they are burned out before turning cancerous. The examination is usually performed with a flexible sigmoidoscope. The interval for the examination is one year, but may vary from three to 12 months depending on the number and size of the polyps detected. Sometimes the polyps in the rectum are so numerous that the doctor may recommend the rectum be surgically removed to minimize the risk of cancer.
The end-viewing endoscope is used to examine the upper GI tract. The papilla cannot be seen adequately with this instrument.
Stomach and Duodenum
Since upper gastrointestinal polyps occur in up to 80 percent of patients with FAP, checks of the stomach, duodenum and especially the papilla are required. Cleveland Clinic specialists recommend the initial upper endoscopic examination be done at the time of colon surgery, or about the age of 20.
Both a forward and a side viewing endoscopic examination with biopsy of the papilla should be performed. The interval for these examinations is three years if the exam is normal or typical FAP polyps are found. If there are more advanced polyps detected on the examination, then the upper endoscopy should be done more frequently.
Prevention Through Participation in a Registry
The goal of the Inherited Colorectal Cancer Registries (ICCR) at Cleveland Clinic is to prevent needless deaths from colon cancer.
To reach this goal, the registries staff tries to make sure that patients receive early diagnosis and treatment. The registries accomplish this by screening family members of patients who may be at risk for colorectal cancer. The staff also ensures that patients diagnosed with the disease are aware of the necessary screenings and follow-up visits to their physicians.
Because colorectal cancer and polyps have such a strong hereditary link, keeping track of patients and their family members through a registry saves lives.
Referrals to the registry vary. Patients often make their own appointments. A community physician may send a patient to one of Cleveland Clinic’s colorectal physicians, or a patient may hear about the registries from other family members who are Cleveland Clinic patients.
The side-viewing duodenoscope allows careful examination of the papilla.
A registries team member then will ask the patient a series of questions about his or her family, in particular which family members have developed polyps or colorectal cancer. With the answers to those questions, the registries coordinator will determine that patient’s family history and construct a family tree. This family tree can help determine other family members’ risk for developing colon cancer.
There are many advantages to being included in the registries. Patients and their family members will receive annual screening letters, booklets and newsletters. The registries team also can answer questions, make appointments, and share new research developments and results from clinical trials with patients and families in the registries.