PMID- 28017843 OWN - NLM STAT- MEDLINE DCOM- 20180212 LR - 20221115 IS - 1542-7714 (Electronic) IS - 1542-3565 (Linking) VI - 15 IP - 6 DP - 2017 Jun TI - Mutation Profile and Fluorescence In Situ Hybridization Analyses Increase Detection of Malignancies in Biliary Strictures. PG - 913-919.e1 LID - S1542-3565(16)31237-X [pii] LID - 10.1016/j.cgh.2016.12.013 [doi] AB - BACKGROUND & AIMS: It is a challenge to detect malignancies in biliary strictures. Various sampling methods are available to increase diagnostic yield, but these require additional procedure time and expertise. We evaluated the combined accuracy of fluorescence in situ hybridization (FISH) and polymerase chain reaction-based DNA mutation profiling (MP) of specimens collected using standard brush techniques. METHODS: We performed a prospective study of 107 consecutive patients treated for biliary strictures by endoscopic retrograde cholangiopancreatography from June 2012 through June 2014. We performed routine cytology and FISH analyses on cells collected by standard brush techniques, and analyzed supernatants for point mutations in KRAS and loss-of-heterozygosity mutations in tumor-suppressor genes at 10 loci (MP analysis was performed at Interpace Diagnostics). Strictures were determined to be nonmalignant based on repeat image analysis or laboratory test results 12 months after the procedure. Malignant strictures were identified based on subsequent biopsy or cytology analyses, pathology analyses of samples collected during surgery, or death from biliary malignancy. We determined the sensitivity and specificity with which FISH and MP analyses detected malignancies using the exact binomial test. RESULTS: Our final analysis included 100 patients; 41% had biliary malignancies. Cytology analysis identified patients with malignancies with 32% sensitivity and 100% specificity. Addition of FISH or MP results to cytology results increased the sensitivity of detection to 51% (P < .01) without reducing specificity. The combination of cytology, MP, and FISH analyses detected malignancies with 73% sensitivity (P < .001). FISH identified an additional 9 of the 28 malignancies not detected by cytology analysis, and MP identified an additional 8 malignancies. FISH and MP together identified 17 of the 28 malignancies not detected by cytology analysis. CONCLUSIONS: Addition of FISH and mutation analyses to cytology analysis significantly increased the level of sensitivity with which we detected malignancy in biliary strictures, with 100% specificity. These techniques can be performed using standard brush samples collected during endoscopic retrograde cholangiopancreatography, with mutations detected in free DNA in supernatant fluid of samples. The tests are complementary and therefore should be used sequentially in the diagnostic evaluation of biliary strictures. CI - Copyright (c) 2017 AGA Institute. Published by Elsevier Inc. All rights reserved. FAU - Gonda, Tamas A AU - Gonda TA AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. Electronic address: tg2214@cumc.columbia.edu. FAU - Viterbo, Domenico AU - Viterbo D AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Gausman, Valerie AU - Gausman V AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Kipp, Claudine AU - Kipp C AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Sethi, Amrita AU - Sethi A AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Poneros, John M AU - Poneros JM AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Gress, Frank AU - Gress F AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Park, Tina AU - Park T AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Khan, Ali AU - Khan A AD - Division of Digestive and Liver Disease, Department of Medicine, Columbia University Medical Center, New York, New York. FAU - Jackson, Sara A AU - Jackson SA AD - Interpace Diagnostics Corporation, Pittsburgh, Pennsylvania. FAU - Blauvelt, Megan AU - Blauvelt M AD - Interpace Diagnostics Corporation, Pittsburgh, Pennsylvania. FAU - Toney, Nicole AU - Toney N AD - Interpace Diagnostics Corporation, Pittsburgh, Pennsylvania. FAU - Finkelstein, Sydney D AU - Finkelstein SD AD - Interpace Diagnostics Corporation, Pittsburgh, Pennsylvania. LA - eng PT - Evaluation Study PT - Journal Article DEP - 20161223 PL - United States TA - Clin Gastroenterol Hepatol JT - Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association JID - 101160775 SB - IM MH - Adult MH - Aged MH - Aged, 80 and over MH - Biliary Tract Neoplasms/*diagnosis/pathology MH - Cholestasis, Extrahepatic/*etiology/pathology MH - Constriction, Pathologic/*etiology/pathology MH - Female MH - *Genotyping Techniques MH - Humans MH - *In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Molecular Diagnostic Techniques/*methods MH - Mutation MH - Prospective Studies MH - Sensitivity and Specificity OTO - NOTNLM OT - Cancer Detection OT - Diagnosis OT - ERCP OT - Mutation Profile EDAT- 2016/12/27 06:00 MHDA- 2018/02/13 06:00 CRDT- 2016/12/27 06:00 PHST- 2016/08/09 00:00 [received] PHST- 2016/12/09 00:00 [revised] PHST- 2016/12/12 00:00 [accepted] PHST- 2016/12/27 06:00 [pubmed] PHST- 2018/02/13 06:00 [medline] PHST- 2016/12/27 06:00 [entrez] AID - S1542-3565(16)31237-X [pii] AID - 10.1016/j.cgh.2016.12.013 [doi] PST - ppublish SO - Clin Gastroenterol Hepatol. 2017 Jun;15(6):913-919.e1. doi: 10.1016/j.cgh.2016.12.013. Epub 2016 Dec 23.