4, 5, 7, 8 The distinction between malignant and inflammatory strictures Idasanutlin mw is confounded in PSC because the inflammation associated with PSC complicates cytological assessment, and access to the bile duct is limited for cytological and tissue acquisition.8–10 CCA are frequently desmoplastic, resulting in acellular sampling, further complicating the diagnosis.8–10 Up to 80% of biliary malignancies exhibit chromosomal abnormalities in the form of structure or the number of chromosomes within the cell.8 Fluorescence in situ hybridization (FISH) uses fluorescently labeled DNA probes to detect aneusomy of individual cells (abnormal loss or gain of chromosomes or chromosomal

loci).10–15 Previous studies evaluating the utility of FISH tests in patients with indeterminate biliary strictures were all limited by the number of PSC patients and the duration of follow-up.10, 13, 16–19 None of these studies addresses the long-term outcomes of the Ulixertinib in vivo tests focused on PSC patients. Selection bias from

assessing patients referred for liver transplantation or surgery for suspected malignancy may have influenced results in some series10, 13, 16–19 because of the high pretest probability of CCA. The aim of the current study was to analyze the outcome of FISH testing in PSC patients and to assess the diagnostic utility of this test in this group of patients in detecting CCA. We also wanted to formulate follow-up guidelines for patients with a positive test result based on our findings. CA 19-9, carbohydrate antigen 19-9; CCA, cholangiocarcinoma; CEP, peri-centromeric

regions of chromosomes; ERCP, endoscopic retrograde cholangiopancreatography; FISH, fluorescence in situ hybridization; HGD, high-grade MCE dysplasia; PSC, primary sclerosing cholangitis. Our patient population comprised consecutive patients with well-defined PSC who were identified using a computerized master diagnosis index of the Mayo Clinic, Rochester, MN. The diagnosis of PSC was based on cholangiographic findings of multifocal strictures and beading of the intrahepatic or extrahepatic bile ducts with compatible biochemical abnormalities and exclusion of secondary causes.20, 21 These patients had FISH testing performed for further evaluation of clinical, laboratory, or radiological abnormalities suspicious for CCA in the setting of PSC at the Mayo Clinic, Rochester, MN, between October 2003 and June 2008. Some of these tests were obtained in PSC patients during an ERCP as a part of the diagnostic workup of cholestatic liver disease during the study period and were not done to address a clinical suspicion of cancer. The study was approved by the Mayo institutional review board, and written informed consent was obtained from all patients for participation in medical research. Dedicated gastrointestinal cytopathologists with particular expertise for each diagnostic test independently interpreted the routine cytology and FISH specimens.