Familial Adenomatous Polyposis (FAP)

In the classical form of familial adenomatous polyposis (FAP), numerous polyps are found in the colon and rectum (often numbering more than 100). Although polyps are generally benign, without treatment some will become malignant over time. Symptoms can occur that signal the presence of polyps and may include changes in the stool pattern, diarrhea, blood or mucus in the stool, and abdominal pain. However, polyps generally cause no symptoms.

When FAP is known to occur in a family, disease can be detected at an early stage by means of a colon examination (colonoscopy), and with appropriate treatment, cancer can be prevented.

Polyps are also found in the stomach and duodenum in a majority of patients (50 to 90%). While polyps in the stomach have a very low risk of becoming malignant, the risk of malignancy is higher for polyps in the duodenum (about 10%) but is still far lower than for polyps found in the large intestine. In addition to polyps in the colon, rectum and/or duodenum, polyposis patients may have other abnormalities such as skin cysts (in 50% of patients), changes in the retina of the eye (in 80%), and benign bone tumors known as osteomas (in 80%). These abnormalities are almost always benign in nature. In 5-10% of polyposis patients, connective tissue tumors (desmoid tumors) develop in the abdominal wall or abdominal cavity. Although benign, these tumors may cause symptoms as they sometimes block the small intestine or the ureters.

Heredity

The body is made up of cells, each of which has a nucleus containing 23 pairs of chromosomes, thus 46 in total. Chromosomes contain tightly packed DNA, parts of which act as genes, the DNA ‘blueprints’ for a hereditary trait. For each of your 23 pairs of chromosomes, one came from your mother and the other from your father, and which chromosome from each pair is inherited is entirely random. In FAP, an altered gene that predisposes to disease is passed from parent to offspring. Every child of a FAP patient has a 50% chance of inheriting a gene carrying the predisposition to disease. This of course also means that there is a 50% chance that a child will not inherit the predisposition, and his or her children will also have no increased risk of developing polyposis. In some cases polyposis develops spontaneously, without one of the parents having the disease. However, subsequent children will have a 50% chance of developing polyposis.

Familial adenomatous polyposis is caused by a change (mutation) in a gene called APC. Most families have different mutations, as almost every mutation in the APC gene is unique to one family. FAP is a dominant hereditary disease, which means that the disease develops even when only one mutation is present in one of the two APC gene copies. Carriers of an APC mutation have a very high risk (almost 100%) of developing the disease.

Genetic investigation
When someone is diagnosed with polyposis, a family tree will be drawn that contains medical data from family members. Whether polyposis occurs in a family will then be determined on the basis of the information collected. If this is the case, DNA testing of a family member affected by polyposis can be used to determine whether the APC mutation is present in the family. DNA material for mutation analysis is obtained from a blood sample. In approximately 70% of families in which an APC mutation is identified it is possible to check other family members for the same mutation. Family members without the APC mutation will not have an increased risk of polyposis, and do not need (further) colonoscopic examinations of the colon.

Regular preventive examination
It is very important that polyposis is detected and treated in time. Many polyps, some even malignant, may be present without causing any symptoms. Regular colonoscopic screening of first-degree family members of FAP patients is therefore essential, even when there are no complaints.

Most people diagnosed with familial adenomatous polyposis during regular bowel exams are between 10 and 30 years old. In the case of families in which an APC mutation cannot be demonstrated, it is advisable to begin endoscopic examinations (sigmoidoscopy or colonoscopy) of the large intestine between the ages of 10 and 12 years and repeat every 2 years. The length of the screening interval also depends on what is found during a sigmoidoscopy or colonoscopy. It is particularly important that children who undergo an endoscopic examination for the first time are well informed about what the procedure entails. It is advisable that parents/caregivers and doctors allow plenty of time when explaining the procedure to a young patient, and good preparation will ensure that children are less anxious. In children, the investigation is usually carried out under sedation with Propofol.

The chance of the classic form of polyposis occurring above the age of 40 is small. In persons aged 40 or older, and provided that they are free of polyps, the interval between examinations may therefore be extended (for example 1x every 3-5 years). When no polyps have been found by the age of 50, endoscopic examinations can be stopped. Family members with a proven change in the APC gene (APC mutation carriers) are advised to continue regular colonoscopies life-long.

Examination of the colon
Investigation in FAP may include a sigmoidoscopy, a procedure in which the last 40-50 cm of the colon is examined, or a colonoscopy, in which the entire colon is examined. These procedures require that a flexible camera tube (an endoscope) is inserted into the colon via the anus, allowing the doctor to accurately view the mucous membrane of the large intestine. For accurate inspection of the intestinal wall, the intestines must be clean. A patient will therefore be asked to drink one or more liters of water, together with a laxative (usually Moviprep or Picoprep), the day before the examination. As many people find colonoscopy quite stressful, a sedative (2-3 mg dormicum as a sleeping aid) and a painkiller (25-75 microgram fentanyl) are recommended.

Treatment:
Once a person has been diagnosed with polyposis, an operation is the only treatment, the timing of which depends on the number and size of the polyps. In all cases, the entire colon will be surgically removed. The following surgical techniques are possible:

Colectomy with ileorectal anastomosis (IRA)

In this procedure, the large intestine is removed and the small intestine is connected to the rectum. An advantage of this operation is that the risk of complications is low. After the operation, the frequency of stools will average 3-4x per day. A disadvantage of the operation is that polyps may develop from the residual rectal mucous membrane. It is therefore advisable to examine this part of the intestine every 6 months. If after the operation many polyps develop in the rectum, it may eventually become necessary to remove the entire rectum. About half of all patients will need additional surgery.

Proctocolectomy with Ileal Pouch-Anal anastomosis (IPAA)

In this operation, both the large intestine and the rectum are removed and the small intestine is connected to the anus. The last part of the small intestine is used to make a reservoir (pouch) to collect the stool.

Because this surgical technique is more complex, there is a somewhat higher risk of complications, particularly leakage of the gut between reservoir and anus, bleeding or infections. Sometimes a stoma will be temporarily installed. The average stool frequency after an ileo-anal anastomosis is similar to an ileorectal anastomosis, 3-4x a day, but may occasionally be somewhat more frequent.

An advantage of this operation is that the risk of polyp development is much lower than with the first technique. Nevertheless, monitoring of the pouch/reservoir remains necessary because polyps may still develop in this part of the intestine.

When choosing between the two surgical techniques, in the first place it is important to consider how seriously the rectum is affected by polyps. If many polyps are present, the best surgical choice is to remove both the large intestine and rectum (proctocolectomy with Ileal pouch- anal anastomosis). However, when the rectum is free of polyps either operation can be considered and the choice depends on a careful consideration of the advantages and disadvantages. Ask your attending physician to carefully explain your options as regards surgery.

Examination of stomach and duodenum
As previously mentioned, FAP patients may also have polyps in the stomach and duodenum. Consequently, it is recommended that a gastroduodenoscopy is regularly performed from the age of 25-30, usually once every 3 to 5 years, with the interval between examinations depending on what the doctor finds in the duodenum. In this procedure, a thin tube (scoop) is inserted through the mouth and lowered through the esophagus and stomach into the duodenum. This allows the doctor to accurately examine the mucous membrane of the stomach and duodenum and, if necessary, take a sample of tissue (biopsy) for further examination.

Treatment
When only a few polyps are present in the duodenum, they can be removed during an endoscopy. However, with more severe forms of polyposis (large and numerous polyps) surgery will be needed. A common operation involves removal of the duodenum and part of the pancreas (Whipple operation), but removal of only the duodenum in a pancreas-sparing operation is an alternative option.