Combined molecular and clinical approach for decision making for surgery in HNPCC patients: a report on three cases in two families

Hereditary nonpolyposis colorectal cancer (HNPCC) is associated with highly penetrant germline mutations in mismatch repair genes. Due to a high lifet ime risk in gene carriers for synchronous and for metachronous colorectal c ancer and endometrial cancer in women, prophylactic and extended surgery ar e considered as options for gene carriers. A 54-year-old patient with a his tory of metachronous rectal cancer and a family history fulfilling the Amst erdam criteria presented with carcinoma of the cecum and highly dysplastic adenomas of the splenic flexure and descending colon. As a result of these findings, medical history and molecular diagnosis, the decision was made to perform colectomy and prophylactic hysterectomy with oophorectomy; histolo gical examination of the specimen showed three synchronous colon carcinomas . The 31-year-old son carrying the pathogenic mutation refused to be includ ed in the HNPCC surveillance program. One year later he presented with symp toms of bowel obstruction, and a carcinoma of the descending colon was diag nosed. Intraoperatively, in addition to the colon cancer, a small bowel can cer and peritoneal carcinomatosis were found. In another family fulfilling the Amsterdam criteria without known germline mutation a woman presented wi th synchronous cancer of the ascending colon and the lower rectum at the ag e of 49 years. Proctocolectomy and prophylactic hysterectomy were performed , which revealed an additional colon cancer and endometrial cancer. We disc uss approaches for individual decision making for surgery in HNPCC patients . Is a subtotal colectomy indicated in the case of first colon cancer in HN PCC patients, or if the first tumor occurs in the lower rectum, should a pr octocolectomy or a restorative proctocolectomy be considered'? The aim of p rospective clinical studies should be to assess acceptability, survival rat es, mortality, and the quality of life in HNPCC patients who have undergone surveillance and standard oncological resections versus extended or prophy lactic surgery.