Familial adenomatous polyposis D12.6

Autosomal dominant inherited (25% new mutations) polyposis syndrome with disseminated polyps of the colon and possibly the entire gastrointestinal tract.

1:10,000, 1% of all colorectal carcinomas

mutations of the APC (Adenomatous Polyposis of the Colon) tumour suppressor gene on chromosome 5q21, one of the two alleles of this gene being inactivated. If a further (somatic) mutation is added, the other allele can also be inactivated. In healthy individuals, the APC protein binds to beta-catenin and mediates its degradation in the proteasome via ubiquitinylation. If beta-catenin can no longer be ubiquitinylated, beta-catenin accumulates. Beta-catenin translocates into the cell nucleus where it acts together with other factors as a transcription factor. The result: promotion of cell growth, increased formation of telomerase, which immortalizes cells (apoptosis is prevented). This leads to an enhancement of the adenoma carcinoma sequence.

Once the responsible mutation has been identified in an affected person, it is possible to test all members of a family for the presence of this mutation within the framework of a human genetic consultation before the first clinical symptoms are observed (predictive or predictive diagnostics). There is an almost 100% risk of disease for proven mutation carriers (carriers). Therefore, intensive preventive or early detection examinations and, if necessary, therapeutic measures should be carried out with regard to an FAP.

Mostly symptomless chance finding within the scope of a colonoscopic examination. Multiple (>100) colorectal adenomas. Extracolonic manifestations of classical FAP are: adenomas of the small intestine, glandular cysts in the stomach (80%), duodenal carcinoma (10%). Possible clinical symptoms are:

• loss of blood and/or mucus from the intestine
• diarrhoea or constipation, or frequent changes between the two
• Flatulence
• pain in the abdomen or rectum
• Weight loss

Digital rectal examination, recto-/colonoscopy; in case of larger rectal adenomas, endorectal ultrasound (ERUS) to clarify invasiveness into the submucosa. Supplementary method: Hydro-MRI of the small intestine and video capsule endoscopy to detect possible small intestine polyps.

Obstruction, carcinoma development of the intestinal adenomas.

The aim is a complete ablation of the polyps of the adenomas in healthy people.

• Adenomas =/<0,5cm: ablation with biopsy forceps
• Adenomas >0,5cm: Total loop removal with recording of the basal parts.
• Larger adenomas which can no longer be safely removed using the loop technique: Transnasal endoscopic microsurgery (TEM) or laparascopic or conventional lararascopy.

Course and prognosis: FAP is an obligatory precancerous disease with a high risk of degeneration from the age of 15. In this respect, if FAP is clinically suspected, a genetic clarification and, if necessary, family counselling must be carried out. FAP patients must be monitored endoscopically from the age of 10. Examination for extracolonic manifestations (see below hereditary polyposis syndromes).

Screening for polyps and colorectal cancer. Aftercare management: clinical controls <3 years (see also http ://familienhilfe-polyposis.de). Long-term therapy with NSAIDs after proctocolectomy can reduce the occurrence of new adenomas in the colonic stump.

The "Attenuated Familial Adenomatous Polyposis" is a rare minus variant of FAP (number of adenomas <100); is the manifestation time of colorectal carcinoma development in the 5th decade of life.

1. Taniguchi L et al (2014) Metabolic factors accelerate colorectal adenoma recurrence. BMC Gastroenterol 14:187.
2. Guidelines for Colonoscopy Surveillance After Polypectomy: A Consensus Update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society, 2006
3. Laiyemo AO et al (2008): Postpolypectomy colonoscopy surveillance guidelines: Predictive accuracy for advanced adenoma at 4 years. Ann Internal Med148:419
4. S3 guideline: Colorectal carcinoma. (AWMF Registry Number: 021-007OL), June 2013 Executive Summary Long version
5. Gerd Herold: Internal Medicine: a lecture-oriented presentation. 2016. edition. Herold, Cologne 2012, ISBN 978-3-9814660-5-8.