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      Cholangiocarcinoma: Current Knowledge and New Developments

      review-article
      Gut and Liver
      Editorial Office of Gut and Liver
      Cholangiocarcinoma, Bile duct, Cancer, Hepatobiliary, Neoplasia

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          Abstract

          Cholangiocarcinoma (CCA) is the second most common primary malignancy. Although it is more common in Asia, its incidence in Europe and North America has significantly increased in recent decades. The prognosis of CCA is dismal. Surgery is the only potentially curative treatment, but the majority of patients present with advanced stage disease, and recurrence after resection is common. Over the last two decades, our understanding of the molecular biology of this malignancy has increased tremendously, diagnostic techniques have evolved, and novel therapeutic approaches have been established. This review discusses the changing epidemiologic trends and provides an overview of newly identified etiologic risk factors for CCA. Furthermore, the molecular pathogenesis is discussed as well as the influence of etiology and biliary location on the mutational landscape of CCA. This review provides an overview of the diagnostic evaluation of CCA and its staging systems. Finally, new therapeutic options are critically reviewed, and future therapeutic strategies discussed.

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          Most cited references76

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          Cholangiocarcinoma: thirty-one-year experience with 564 patients at a single institution.

          To assess long-term survival and prognostic factors in a large series of patients with bile duct cancer. The incidence of bile duct cancer is low but increasing. Determinants of survival vary in the literature, due to a lack of sufficient numbers of patients in most series. We studied 564 consecutive patients with bile duct cancer operated upon between 1973 and 2004. Patients were divided into intrahepatic, perihilar, and distal groups. Principle outcome measures were complications, 30-day mortality, and survival. Of the 564 patients, 44 (8%) had intrahepatic, 281 (50%) had perihilar, and 239 (42%) had distal tumors. Approximately half (294, 52%) were treated before 1995, while 270 (48%) were treated thereafter. The perioperative mortality rate was 4%. In log-rank analyses, survival was higher in the later time period (P = 0.002), in patients with intrahepatic disease (P = 0.001), with negative resection margins (P < 0.001), with well/moderately differentiated tumors (P < 0.001), and those with negative lymph nodal status (P < 0.001). In multivariate analysis, negative margins (P < 0.001), tumor differentiation (P < 0.001), and negative nodal status (P < 0.001), but not tumor diameter, were significant independent prognostic factors. In R0-resected patients, lymph node status (P < 0.001), but not tumor diameter, histology, or differentiation, further predicted survival. The median survivals for R0-resected intrahepatic, perihilar, and distal tumors were 80, 30, and 25 months, respectively, and the 5-year survivals were 63%, 30%, and 27%, respectively. R0 resection remains the best chance for long-term survival, and lymph node status is the most important prognostic factor following R0 resection.
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            Exome sequencing identifies frequent inactivating mutations in BAP1, ARID1A and PBRM1 in intrahepatic cholangiocarcinomas.

            Through exomic sequencing of 32 intrahepatic cholangiocarcinomas, we discovered frequent inactivating mutations in multiple chromatin-remodeling genes (including BAP1, ARID1A and PBRM1), and mutation in one of these genes occurred in almost half of the carcinomas sequenced. We also identified frequent mutations at previously reported hotspots in the IDH1 and IDH2 genes encoding metabolic enzymes in intrahepatic cholangiocarcinomas. In contrast, TP53 was the most frequently altered gene in a series of nine gallbladder carcinomas. These discoveries highlight the key role of dysregulated chromatin remodeling in intrahepatic cholangiocarcinomas.
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              Burden of digestive diseases in the United States Part III: Liver, biliary tract, and pancreas.

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                Author and article information

                Journal
                Gut Liver
                Gut Liver
                Gut and Liver
                Editorial Office of Gut and Liver
                1976-2283
                2005-1212
                January 2017
                08 December 2016
                : 11
                : 1
                : 13-26
                Affiliations
                Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, TX, USA
                Author notes
                Correspondence to: Boris Blechacz, Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Blvd., Unit 1466, Houston, TX 77030, USA, Tel: +1-713-792-3034, Fax: +1-713-745-9295, E-mail: bblechacz@ 123456mdanderson.org
                Article
                gnl-11-013
                10.5009/gnl15568
                5221857
                27928095
                2b5bc4f6-cff3-4c1c-87c5-bd89945d7822
                Copyright © 2017 by The Korean Society of Gastroenterology, the Korean Society of Gastrointestinal Endoscopy, the Korean Society of Neurogastroenterology and Motility, Korean College of Helicobacter and Upper Gastrointestinal Research, Korean Association the Study of Intestinal Diseases, the Korean Association for the Study of the Liver, Korean Pancreatobiliary Association, and Korean Society of Gastrointestinal Cancer.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 06 November 2015
                : 17 December 2015
                Categories
                Review

                Gastroenterology & Hepatology
                cholangiocarcinoma,bile duct,cancer,hepatobiliary,neoplasia
                Gastroenterology & Hepatology
                cholangiocarcinoma, bile duct, cancer, hepatobiliary, neoplasia

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