Familial Adenomatous Polyposis

DefinitionTop

Familial adenomatous polyposis (FAP) is an autosomal dominant disease caused by a germline mutation in the APC gene (chromosome 5). In the classic form of the disease, the large intestine of the patient has >1000 adenomatous polyps and the risk of developing colorectal cancer during a lifetime is 100%.

In the mild form (attenuated familial adenomatous polyposis [AFAP]), patients have fewer polyps (10-100) and the risk of cancer is lower. FAP is also associated with an increased risk of developing other cancers including duodenal periampullary adenocarcinoma, thyroid cancer, central nervous system tumors (ie, Turcot syndrome), and hepatoblastoma in children. There are also a number of benign conditions that FAP predisposes to, including osteomas, desmoid tumors, epidermoid cysts, and congenital hypertrophy of retinal pigmented epithelium (CHRPE).

TreatmentTop

Given the 100% lifetime risk of developing colon cancer, patients with FAP should undergo prophylactic total proctocolectomy with either ileal pouch–anal anastomosis (ie, J-pouch) or end ileostomy sometime between the ages of 18 to 25 years. Patients normally choose to undergo operative intervention after finishing high school (aged ~18-20 years). This should be done at tertiary care centers with an adequate volume of these procedures performed annually. Patients with AFAP who have a manageable polyp burden may defer surgery and only proceed if the polyp burden becomes unmanageable endoscopically or if they develop invasive cancer.

In patients with polyp burden in the rectum manageable endoscopically, total abdominal colectomy with ileorectal anastomosis could be chosen (lower-risk surgery). However, if the polyp burden in the rectum is not manageable endoscopically or the patient is not reliably available for routine endoscopic follow-up, total proctocolectomy with either J-pouch reconstruction or end ileostomy is usually offered.

SurveillanceTop

In carriers of the APC gene mutation, colonoscopy or flexible sigmoidoscopy should be performed every 1 to 2 years starting at 12 to 15 years of age until prophylactic proctocolectomy is performed (indicated before the age of 25). In patients with AFAP colonoscopy should be performed every 1 to 2 years, starting at 18 to 20 years of age. If the patient defers surgery for AFAP because of a manageable polyp burden, they can increase the interval of their surveillance colonoscopies to every 3 years starting at 35 years old. After the operation in patients who underwent J-pouch reconstruction, endoscopic supervision every 1 to 2 years with pouchoscopy is indicated (given the risk of cancer development at the rectal cuff). Patients with FAP have an increased risk of adenomatous polyps in the gastric fundus and duodenum with the potential of development of periampullary duodenal cancer and should therefore undergo endoscopy of the upper gastrointestinal tract (with a side-viewing endoscope) every 6 months to 5 years, starting at the age of 25 to 30 years or since the diagnosis of polyposis in the large intestine.

If duodenal adenomas are diagnosed, the frequency of surveillance may be altered as per the Spigelman criteria, which take into account the number of polyps (1-4, 5-20, >20), their maximum size in mm (1-4, 5-10, >10), histology (tubular, tubulovillous, villous), and degree of dysplasia (mild, moderate, severe), assigning 1, 2, or 3 points in each category. Repeat endoscopy is suggested in 5 years (up to 4 points), in 2 to 3 years (5-6 points), and in 6 to 12 months with surgical consultation (7-12 points).Evidence 1Low Quality of Evidence (low confidence that we know true effects of the intervention). Quality of Evidence lowered due to the observational nature of studies. Steele SR, Hull TL, Hyman N, et al, eds. The ASCRS Textbook of Colon and Rectal Surgery. 4th ed. Springer Nature; 2022. Annual assessment of the thyroid gland (palpation, ultrasonography) is also recommended. In children aged 6 months to 7 years, serum alpha-fetoprotein (AFP) testing and abdominal ultrasonography should be performed every year due to the risk of hepatoblastoma.