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      Suspicious brush cytology is an indication for liver transplantation evaluation in primary sclerosing cholangitis

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          Abstract

          AIM

          To investigate markers for high-grade dysplasia for the optimal timing of liver transplantation in patients with primary sclerosing cholangitis (PSC).

          METHODS

          Earlier data support a dysplasia-carcinoma sequence, even low- to high-grade dysplasia, in PSC-associated cholangiocarcinoma (CCA). Surveillance using endoscopic retrograde cholangiography (ERC) and brush cytology aims to detect cases of biliary dysplasia, and liver transplantation is an option in cases with suspicion of malignancy in brushing. This study investigated markers to identify patients with high-grade biliary dysplasia for optimal timing in early liver transplantation. Patients undergoing surveillance using ERC and brush cytology during 2008-2014 and who were diagnosed with biliary dysplasia in explanted liver or CCA until February 2016 were included in the study. Demographic data, cholangiography findings, laboratory values, cytological morphology and DNA ploidy were analysed.

          RESULTS

          Thirty PSC patients had biliary neoplasia in the explanted liver during the study period. Sixteen of these patients had low-grade dysplasia, 10 patients had high-grade dysplasia, and 4 patients had CCA. Fifteen PSC patients diagnosed with CCA were not transplanted. Patients with low-grade dysplasia were younger. Alkaline phosphatase or carcinoembryonic antigen values did not differ between groups during surveillance, but carbohydrate antigen 19-9 was higher in CCA patients. No difference in PSC duration, ERC scores, suspicious cytology, or ploidy analysis was found between groups. No difference was observed between fibrosis stage in explanted livers. Low- and high-grade dysplasia could not be differentiated before liver transplantation based on liver enzymes, tumour markers, ERC scores, brush cytology or DNA ploidy.

          CONCLUSION

          Repeated suspicion of neoplasia in brush cytology should be an indication for evaluations of liver transplantation prior to the development of CCA.

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          Most cited references23

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          ACG Clinical Guideline: Primary Sclerosing Cholangitis.

          Primary sclerosing cholangitis is a chronic cholestatic liver disease that can shorten life and may require liver transplantation. The cause is unknown, although it is commonly associated with colitis. There is no approved or proven therapy, although ursodeoxycholic acid is used by many on an empiric basis. Complications including portal hypertension, fat-soluble vitamin deficiency, metabolic bone diseases, and development of cancers of the bile duct or colon can occur.
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            Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

            Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.
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              Cancer surveillance in patients with primary sclerosing cholangitis.

              Primary sclerosing cholangitis (PSC) is a chronic fibroinflammatory syndrome involving the biliary tract, often accompanied by inflammatory bowel disease (IBD). This syndrome is a prototype disease linking chronic inflammation to carcinogenesis. Indeed, PSC is associated with an increased risk of cholangiocarcinoma (CCA), gallbladder cancer, hepatocellular carcinoma (HCC), and colorectal cancer. Herein, we review the risk for these malignancies in PSC and discuss rational cancer surveillance strategies for these patients. Where evidence is limited, we suggest a pragmatic approach. In this regard, we recommend interval screening for CCA with noninvasive imaging modalities and serum carbohydrate antigen 19-9 determinations annually. These imaging studies also serve to screen for gallbladder cancer and HCC. Screening for colorectal cancer is more firmly established in PSC patients with IBD and includes colonoscopy at the time of PSC diagnosis and, thereafter, at 1-2-year intervals. We also highlight areas where more information is required, such as management of biliary tract dysplasia and cancer chemoprevention in PSC. Copyright © 2011 American Association for the Study of Liver Diseases.
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                Author and article information

                Contributors
                Journal
                World J Gastroenterol
                World J. Gastroenterol
                WJG
                World Journal of Gastroenterology
                Baishideng Publishing Group Inc
                1007-9327
                2219-2840
                7 September 2017
                7 September 2017
                : 23
                : 33
                : 6147-6154
                Affiliations
                Department of Pathology, University of Helsinki and Helsinki University Hospital, HUSLAB, 00029 Helsinki, Finland. sonja.boyd@ 123456hus.fi
                Transplantation and Liver Surgery Clinic, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
                Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
                Transplantation and Liver Surgery Clinic, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
                Transplantation and Liver Surgery Clinic, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
                Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
                Department of Pathology, University of Helsinki and Helsinki University Hospital, HUSLAB, 00029 Helsinki, Finland
                Author notes

                Author contributions: Boyd S and Vannas M collected the data; Boyd S prepared figures, wrote the first draft of the manuscript and analysed the data; Vannas M participated in the writing of the manuscript; Jokelainen K, Isoniemi H and Mäkisalo H provided clinical advice; Färkkilä MA and Arola J designed the research and supervised the report; Jokelainen K, Isoniemi H, Mäkisalo H, Färkkilä MA and Arola J revised the manuscript.

                Supported by the Sigrid Jusélius Foundation; the Gastroenterological Research Foundation; and State Funding for University-level Health Research from the Helsinki University Hospital .

                Correspondence to: Sonja Boyd, MD, Department of Pathology, Helsinki University Hospital, HUSLAB, PB 400, 00029 Helsinki, Finland. sonja.boyd@ 123456hus.fi

                Telephone: +358-50-4270551 Fax: +358-9-47175372

                Article
                jWJG.v23.i33.pg6147
                10.3748/wjg.v23.i33.6147
                5597506
                28970730
                2c44b9b3-fd20-4203-85f6-910084a7cae6
                ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.

                This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

                History
                : 21 February 2017
                : 16 April 2017
                : 18 June 2017
                Categories
                Retrospective Study

                endoscopic retrograde cholangiography,brush cytology,cholangiocarcinoma,biliary dysplasia

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