Resektionsausmaß und Therapiekonzept bei hereditärem, nicht Polyposis-assoziiertem kolorektalem Karzinom (HNPCC) – Indexpatient: chirurgische Strategie

Hereditary nonpolyposis colorectal cancer (HNPCC), clinically defined by the Amsterdam criteria, is caused by highly penetrant germ line mutations in DNA mismatch repair (MMR) genes, mostly in MLH1 and MSH2, infrequently in MSH6 und PMS2. Mutation carriers are at high cumulative risk (52-92%) for developing colorectal cancer (CRC), including syn- and metachronous colorectal carcinomas, with a younger age of onset compared with sporadic CRC. In addition, there is a remarkably increased risk in these mutation carriers for extracolonic carcinomas, especially for endometrial and ovarian carcinomas but also for gastric, ureter and renal pelvis and small bowel cancer. Therefore, the question arises if an individually tailored conception of treatment should be applied to HNPCC patients and mutation carriers. On principle, there are three options of surgical approach conceivable concerning the colorectum: i) prophylactic resection in healthy mutation carriers ii) oncological resection in the case of CRC iii) extended resection with an additional prophylactic intent in the case of first CRC. After critical evaluation of various arguments, the first option cannot be recommended for CRC prevention. However, a final recommendation neither for the second nor the third option of surgical approach can be given at the moment. The indication for a prophylactic hysterectomy and oophorectomy should be weighted in the following postmenopausal patients after intensive genetic, surgical and gynecologic counselling: patients fulfilling the Amsterdam II criteria or who have been identified as mutation carriers of a disease causing germ line mutation in one of the MMR genes and who have to be operated on due to another cause. A precise prediction of the individual risk and age of onset on the basis of the analysis of interactions between endogenous and exogenous modifying factors is the precondition for recommendations concerning individually tailored surveillance or prophylactic surgery.