review of literature on clinical pancreatology - The Pancreapedia

window. Later generations tend to have an earlier onset <strong>of</strong> cancer; thus maximum risk is atapproximately the age <strong>of</strong> onset in affected siblings and is somewhat lower than the age <strong>of</strong>onset in affected parents. None <strong>of</strong> screening programmes in action today assume anysignificant positive predictive value for any <strong>of</strong> the blood tests used, but the results may informclinical decisions based on imaging. EUS meets many <strong>of</strong> the criteria as the ideal imagingmodality in screening, but there are limitations. EUS is not good at distinguishing betweenbenign lesions and cancers. In a small study (n=85) aimed at distinguishing between chronicpancreatitis and pancreatic cancer, positive predictive value was only 60 percent based onimaging alone. Initial results have been published by the Johns Hopkins and Washingtongroups. From a total cohort <strong>of</strong> 75 patients, 15 had abnormalities on EUS and ERCP, all <strong>of</strong>whom had surgery (12 total and 3 distal pancreatectomies). The three that had distalpancreatectomy remain under surveillance. Histology results revealed PanIN-3 lesions in 10individuals and the remaining 5 specimens contained PanIN-2. Although no cancers weredetected in the resected participants, 1 individual has developed an unresectable pancreaticmalignancy whilst under imaging surveillance. Screening for early pancreatic cancer remainsdifficult and has yet to be proven to be effective. The detection <strong>of</strong> early tumours will not onlyconfirm the validity <strong>of</strong> the successful screening modality but will reveal more about the earlystages <strong>of</strong> pancreatic cancer development [356].Lynch syndromeLynch syndrome is an inherited cause <strong>of</strong> colorectal cancer caused by mutations <strong>of</strong> DNAmismatch repair (MMR) genes. A number <strong>of</strong> extracolonic tumors have been associated withthe disorder, including pancreatic cancer; however, the risk <strong>of</strong> pancreatic cancer in Lynchsyndrome is uncertain and not quantified. To estimate pancreatic cancer risk in families withgermline MMR gene mutations cancer histories <strong>of</strong> probands and their relatives wereevaluated in MMR gene mutation carriers in two US familial cancer registries. Familiesenrolled before the study start date (June 2008) were eligible. Age-specific cumulative risksand hazard ratio estimates <strong>of</strong> pancreatic cancer risk were calculated and compared with thegeneral population using modified segregation analysis, with correction for ascertainment.Age-specific cumulative risks and hazard ratio estimates <strong>of</strong> pancreatic cancer risk werecalculated. Data on 6342 individuals from 147 families with MMR gene mutations wereanalyzed. Thirty-one families (21 %) reported at least 1 case <strong>of</strong> pancreatic cancer. Fortysevenpancreatic cancers were reported (21 men and 26 women), with no gender-relateddifference in age <strong>of</strong> diagnosis (52 vs 57 years for men and women, respectively). Thecumulative risk <strong>of</strong> pancreatic cancer in these families with gene mutations was 1.3 percent(95 % confidence interval 0.31 % to 2.32 %) up to age 50 years and 3.7 percent (95 %confidence interval 1.5 % to 5.9 %) up to age 70 years, which represents an 8.6-fold increase(95 % confidence interval 4.7 to 15.7) compared with the general population. It wasconcluded that among 147 families with germline MMR gene mutations, the risk <strong>of</strong> pancreaticcancer was increased compared with the US population [357].Clinical aspects <strong>of</strong> Lynch syndromeHereditary nonpolyposis colorectal cancer, or Lynch syndrome, is responsible for 2-3 percent<strong>of</strong> all colorectal cancers. Lynch syndrome is also associated with a high risk <strong>of</strong> extracoloniccancers, including endometrial, stomach, small bowel, pancreas, biliary tract, ovary, urinarytract, brain, and skin cancer. It was now discussed the risks, surveillance tests, andguidelines for the management <strong>of</strong> extracolonic tumours associated with Lynch syndrome. Forall types <strong>of</strong> extracolonic cancer, evidence supporting surveillance is scarce. A benefit <strong>of</strong>surveillance is evident only for endometrial cancer, where transvaginal ultrasound andendometrial sampling detect tumours in early stages. Surveillance is generally recommendedfor urinary tract and gastric cancer, especially in families with more than one member withthese types <strong>of</strong> cancer. For the other types <strong>of</strong> cancer, surveillance is typically notrecommended. Prophylactic hysterectomy and bilateral salpingo-oophorectomy should be