Dispelling misconceptions in the management of familial adenomatous polyposis.

Patients with familial adenomatous polyposis require surgical intervention at some point in their lives. The diagnosis is often apparent from their phenotype and family history, however, this is not always the case. Many factors can influence the surgical strategy although the polyposis burden and distribution remain the main consideration. While prophylactic removal of the rectum and colon is often required, sparing the rectum at the index surgery is safe in select patients. This article aims to dispel misconceptions in the diagnosis and treatment of patients with familial adenomatous polyposis.

Screening for an inherited susceptibility to colorectal cancer.

The principal Mendelian disorders predisposing to colorectal cancer are familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC). FAP is caused by mutations in the adenomatous polyposis coli (APC) gene. HNPCC is caused by a mutation in one of at least five mismatch repair genes. It is important to identify individuals with these conditions because colon cancer will occur in at least 80% and onset is earlier than in the general population. Potential benefits of identification include improved compliance with recommended surveillance, early detection of polyps, reduction in cancer mortality, and reassurance for relatives found to be negative with attendant savings in the time and expense of surveillance. For classic FAP, the large number of polyps readily identifies affected persons. For HNPCC, identification of individuals meriting DNA sequencing requires either recognition of a suspect family history or finding high microsatellite instability in a tumor. Individuals accepting the offer of genetic counseling and DNA testing often have more cancers in their family, are motivated to inform relatives, have a larger social network, and have more confidence in their coping ability. Individuals who decline are often concerned about their own or their family's emotional reaction or fear discrimination.

Decision analysis in the management of duodenal adenomatosis in familial adenomatous polyposis.

BACKGROUND: Patients with familial adenomatous polyposis are not only at high risk of developing adenomas in the colorectum but a substantial number of patients also develop polyps in the duodenum. Because treatment of duodenal polyps is extremely difficult and it is unknown how many patients ultimately develop duodenal cancer, the value of surveillance of the upper digestive tract is uncertain. AIMS: (1) To assess the cumulative risk of duodenal cancer in a large series of polyposis patients. (2) To develop a decision model to establish whether surveillance would lead to increased life expectancy. METHODS: Risk analysis was performed in 155 Dutch polyposis families including 601 polyposis patients, and 142 Danish families including 376 patients. Observation time was from birth until date of last contact, death, diagnosis of duodenal cancer, or closing date of the study. RESULTS: Seven Dutch and five Danish patients developed duodenal cancer. The lifetime risk of developing this cancer by the age of 70 was 4% (95% confidence interval 1-7%) in the Dutch series and 3% (95% confidence interval 0-6%) in the Danish series. Decision analysis showed that surveillance led to an increase in life expectancy by seven months. CONCLUSIONS: Surveillance of the upper digestive tract led to a moderate gain in life expectancy. Future studies should evaluate whether this increase in life expectancy outweighs the morbidity of endoscopic examination and proximal pancreaticoduodenectomy.

Genetic counseling in an extended attenauted familial adenomatous polyposis kindred.

OBJECTIVES: To provide DNA-based genetic counseling to family members in the direct genetic lineage of a family fulfilling phenotypical criteria for the autosomal, dominantly inherited, attenuated familial adenomatous polyp (AFAP) syndrome. This enabled highly targeted cancer risk estimation based on cancer phenotype in concert with the presence or absence of the adenomatous polyposis coli (APC) germline mutation. Management recommendations could then be fully responsive to this syndrome's natural history. METHODS: Detailed family history with pathology verification of colonic polyps and cancer was performed on an extended AFAP kindred. Endoscopic gastrointestinal examinations enabled detailed knowledge of the syndrome's upper and lower gastrointestinal tract phenotype. Molecular genetic evaluation of DNA led to the identification of the APC germline mutation which co-segregated with the phenotype. RESULTS: Forty-two members of this extended AFAP family underwent DNA testing, wherein 27 were found to harbor the APC germline mutation,thereby enabling precision in their genetic counseling. Anecdotal examples of this counseling experience, with particular attention to psychological reactions, as well as concerns about such issues as insurance and employer discrimination, have been described. CONCLUSIONS: When DNA-based testing is offered to AFAP family members, genetic counselors must compassionately consider patients' psychological concerns when providing detailed risk status and available surveillance and management programs.