Retrospective Study
Copyright ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2017; 23(33): 6147-6154
Published online Sep 7, 2017. doi: 10.3748/wjg.v23.i33.6147
Suspicious brush cytology is an indication for liver transplantation evaluation in primary sclerosing cholangitis
Sonja Boyd, Marko Vannas, Kalle Jokelainen, Helena Isoniemi, Heikki Mäkisalo, Martti A Färkkilä, Johanna Arola
Sonja Boyd, Johanna Arola, Department of Pathology, University of Helsinki and Helsinki University Hospital, HUSLAB, 00029 Helsinki, Finland
Marko Vannas, Helena Isoniemi, Heikki Mäkisalo, Transplantation and Liver Surgery Clinic, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
Kalle Jokelainen, Martti A Färkkilä, Clinic of Gastroenterology, University of Helsinki and Helsinki University Hospital, 00029 Helsinki, Finland
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.
Institutional review board statement: The Ethical committee of Helsinki University Hospital approved this study (Dnro 278/13/03/01/09).
Conflict-of-interest statement: We have no financial relationships to disclose.
Data sharing statement: No additional data are available.
Open-Access: 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. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Sonja Boyd, MD, Department of Pathology, Helsinki University Hospital, HUSLAB, PB 400, 00029 Helsinki, Finland. sonja.boyd@hus.fi
Telephone: +358-50-4270551 Fax: +358-9-47175372
Received: February 21, 2017
Peer-review started: February 22, 2017
First decision: March 16, 2017
Revised: April 16, 2017
Accepted: June 18, 2017
Article in press: June 19, 2017
Published online: September 7, 2017
Processing time: 198 Days and 3.2 Hours
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.

Keywords: Endoscopic retrograde cholangiography; Brush cytology; Cholangiocarcinoma; Biliary dysplasia

Core tip: We investigated markers of high-grade dysplasia for the optimal timing of early liver transplantation (LT) in patients with primary sclerosing cholangitis (PSC). PSC patients in our unit undergo surveillance with endoscopic retrograde cholangiography (ERC) and brush cytology (BC) to identify evidence of dysplasia before progression to cholangiocarcinoma. Carbohydrate antigen 19-9 was higher in patients with cholangiocarcinoma, but no other differences between laboratory values, ERC scores, BC or ploidy analysis between the low-grade, high-grade or CCA groups were observed. Repeated suspicion of neoplasia in BC should be an indication for the evaluation for LT prior to the development of cholangiocarcinoma.