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17 The Multi-Society Task Force, in collaboration with invited experts, developed guidelines to assist health care providers with the appropriate provision of genetic testing and management of patients at risk for and affected with Lynch syndrome as follows: Figure 1 provides a colorectal cancer risk assessment tool to screen individuals in the offi ce or endoscopy setting; Figure 2 illustrates a strategy for universal screening for Lynch syndrome by tumor testing of patients diagnosed with colorectal cancer; Figures 3 - 6 provide algorithms for genetic evaluation of affected and at-risk family members of pedigrees with Lynch syndrome; Table 10 provides guidelines for screening at-risk and affected persons with Lynch syndrome; and Table 12 lists the guidelines for the management of patients with Lynch syndrome. A detailed explanation of Lynch syndrome and the methodology utilized to derive these guidelines, as well as an explanation of, and supporting literature for, these guidelines are provided.

Background & Aims We developed and validated a model to estimate the risks of mutations in the mismatch repair (MMR) genes MLH1 , MSH2 , and MSH6 based on personal and family history of cancer. Methods Data were analyzed from 4539 probands tested for mutations in MLH1 , MSH2 , and MSH6 . A multivariable polytomous logistic regression model (PREMM 1,2,6 ) was developed to predict the overall risk of MMR gene mutations and the risk of mutation in each of the 3 genes. The discriminative ability of the model was validated in 1827 population-based colorectal cancer (CRC) cases. Results Twelve percent of the original cohort carried pathogenic mutations (204 in MLH1 , 250 in MSH2 , and 71 in MSH6 ). The PREMM 1,2,6 model incorporated the following factors from the probands and first- and second-degree relatives (odds ratio; 95% confidence intervals [CIs]): male sex (1.9; 1.5–2.4), a CRC (4.3; 3.3–5.6), multiple CRCs (13.7; 8.5–22), endometrial cancer (6.1; 4.6–8.2), and extracolonic cancers (3.3; 2.4–4.6). The areas under the receiver operating characteristic curves were 0.86 (95% CI, 0.82–0.91) for MLH1 mutation carriers, 0.87 (95% CI, 0.83–0.92) for MSH2 , and 0.81 (95% CI, 0.69–0.93) for MSH6 ; in validation, they were 0.88 for the overall cohort (95% CI, 0.86–0.90) and the population-based cases (95% CI, 0.83–0.92). Conclusions We developed the PREMM 1,2,6 model, which incorporates information on cancer history from probands and their relatives to estimate an individual's risk of mutations in the MMR genes MLH1 , MSH2 , and MSH6 . This Web-based decision making tool can be used to assess risk of hereditary CRC and guide clinical management.

Background Laparoscopic techniques are being applied to the surgical management of various intestinal conditions, but few reports describe their use with Crohn's disease. Patients and methods Over a 2-year period, 31 selected patients with Crohn's disease underwent laparoscopic intestinal surgery: 18 women and 13 men, with a median age of 39 years (range 22 to 79). Indications for operation included: primary terminal ileitis (13); recurrent ileitis (2); Crohn's colitis (3); rectovaginal fistula (6); and severe perianal disease (7). Resections were laparoscopically assisted with division of mesentery and anastomosis performed extracorporeally. Diversion procedures were performed using a two-cannula technique. Results Twenty-five of 31 procedures were completed laparoscopically: loop ileostomy or colostomy (12); ileocecectomy (10); segmental colon resection (2); and total abdominal colectomy with ileorectal anastomosis (1). Six cases were converted to conventional surgery secondary to extensive adhesions from prior surgery (2) or severe Inflammation (4). No case was converted because of intraoperative complication. Median operative time for diversion procedures was 53 minutes (range 20 to 90) and for resections 195 minutes (range 90 to 380). Median blood loss was 100 mL (range 10 to 500), and there were no intraoperative complications. Only 1 postoperative complication occurred: a myocardial infarction. Median times to passage of flatus and bowel movement were both 3 days (range 1 to 6). Median time to discharge was 6 days (2 to 21) for diversion patients, and 6 days (3 to 7) for resected patients. Conclusions Laparoscopic intestinal surgery, both for resection and diversion, is feasible and safe for the management of selected patients with Crohn's disease. To determine if real advantages exist for laparoscopy in the surgical treatment of Crohn's disease, further study is needed.