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©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Mar 15, 2019; 11(3): 238-249
Published online Mar 15, 2019. doi: 10.4251/wjgo.v11.i3.238
Risk of cholangiocarcinoma in patients undergoing therapeutic endoscopic retrograde cholangiopancreatography or cholecystectomy: A population based study
Chi-Chih Wang, Ming-Chang Tsai, Wen-Wei Sung, Tzu-Wei Yang, Hsuan-Yi Chen, Yao-Tung Wang, Chang-Cheng Su, Ming-Hseng Tseng, Chun-Che Lin
Chi-Chih Wang, Ming-Chang Tsai, Wen-Wei Sung, Yao-Tung Wang, Chun-Che Lin, Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
Chi-Chih Wang, Ming-Chang Tsai, Wen-Wei Sung, Tzu-Wei Yang, Hsuan-Yi Chen, Yao-Tung Wang, Chun-Che Lin, School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan
Chi-Chih Wang, Ming-Chang Tsai, Tzu-Wei Yang, Hsuan-Yi Chen, Chang-Cheng Su, Chun-Che Lin, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
Wen-Wei Sung, Department of Urology, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
Tzu-Wei Yang, Institute and Department of Biological Science and Technology, National Chiao Tung University, Hsinchu 30010, Taiwan
Yao-Tung Wang, Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
Ming-Hseng Tseng, Department of Medical Informatics, Chung Shan Medical University, Taichung 40201, Taiwan
Ming-Hseng Tseng, Information Technology Office, Chung Shan Medical University Hospital, Taichung 40201, Taiwan
Author contributions: Tseng MH and Lin CC contributed equally to this manuscript; Wang CC, Tseng MH and Sung WW contributed to conception and design; Tseng MH contributed to acquisition of data; Tsai MC, Wang CC, Wang YT and Chen HY contributed to analysis and interpretation of data; Wang CC, Yang TW and Chen HY contributed to drafting of the manuscript; Yang TW, Sung WW and Lin CC contributed to critical revision of the manuscript; Tsai MC, Sung WW and Su CC contributed to statistical analysis; Tseng MH and Lin CC contributed to supervision.
Supported by Chung Shan Medical University Hospital research program, Taichung, Taiwan, No. CSH- 2013-C-032.
Institutional review board statement: This study was approved by the Institutional Review Board of Chung Shan Medical University Hospital, Taiwan.
Informed consent statement: The Institutional Review Board waved the need of informed consent in this study as it is a retrospective study based on the National Health Insurance Research Database.
Conflict-of-interest statement: None.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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/
Corresponding author: Chun-Che Lin, MD, PhD, Attending Doctor, Chief Doctor, Doctor, Professor, Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, No.110, Sec.1, Jianguo N.Rd., Taichung 40201, Taiwan. cshy333@csh.org.tw
Telephone: +886-424730022-11603 Fax: +886-423248130
Received: October 25, 2018
Peer-review started: October 25, 2018
First decision: December 10, 2018
Revised: January 16, 2019
Accepted: January 29, 2019
Article in press: January 30, 2019
Published online: March 15, 2019
ARTICLE HIGHLIGHTS
Research background
Cholangiocarcinoma is a highly lethal disease. There are many well known risk factors of cholangiocarcinoma, most of them result from chronic biliary system inflammation, such as primary sclerosing cholangitis, choledochal cyst disease, specific parasite infection, cholelithiasis, chronic hepatitis B and C infection, diabetes mellitus and Helicobacter infection, but the impacts of advanced biliary interventions, like endoscopic sphincterotomy (ES), endoscopic papillary balloon dilatation (EPBD) and cholecystectomy, are inconsistence in previous literature. It is important to understand the major hypothesis result in cholangiocarcinoma.
Research motivation
We focused on the most common disease, cholelithiasis, which can result in cholangiocarcinoma. We conducted this study using the National Health Insurance Research Database to clarify the risks of cholangiocarcinoma after ES/EPBD, cholecystectomy or no intervention for cholelithiasis.
Research objectives
We try to evaluate hospital base cholelithiasis retrospective cohort and analyzed further cholangiocarcinoma risk in patients underwent ES/EPBD, cholecystectomy or no intervention for cholelithiasis. Further studies, to clarify whether the inflammation location or the different methods of therapeutic managements affect the incidence of cholangiocarcinoma, are needed in this field.
Research methods
Because of cholangiocarcinoma is still a disease with very low incidence in normal population, we collect data of NHIRD 2004-2011 in Taiwan using one million random samples. We selected 7938 cholelithiasis cases as well as 23814 control group cases (matched by sex and age in 1:3 ratio). The incidences of total and subsequent cholangiocarcinoma were calculated in ES/EPBD patients, cholecystectomy patients, cholelithiasis patients without intervention and normal population. This topic is hard to be analyzed because subsequent cholangiocarcinoma incidence is low and both cholelithiasis and the managements for cholelithiasis maybe influence the cholangiocarcinoma rate.
Research results
There are 537 cases underwent ES/EPBD, 1743 cases underwent cholecystectomy and 5658 cases without intervention in our cholelithiasis cohort. Eleven (2.05%), 37 (0.65%) and 7 (0.40%) subsequent cholangiocarcinoma cases diagnosed in ES/EPBD, no intervention and cholecystectomy group respectively and the odds ratio for subsequent cholangiocarcinoma is 3.13 in ES/EPBD group and 0.61 in cholecystectomy group comparing with no intervention group.
Research conclusions
Symptomatic cholelithiasis patients underwent cholecystectomy had the lowest incidence of subsequent cholangiocarcinoma, but the incidence is still higher than normal population. Patients underwent ES/EPBD are in a high risk of subsequent cholangiocarcinoma and a follow-up plane should be needed in these kinds of patients. The hypotheses of these results can be explained by both inflammation at bile ducts increases incidence of cholangiocarcinoma than inflammation at gallbladder, or cholecystectomy reduce recurrent biliary events in cholelithiasis patients and decrease future cholangiocarcinoma rates. We need a series studies to clarify this mystery we left today.
Research perspectives
The future direction of research is to evaluate choledocholithiasis patients, who underwent therapeutic endoscopic retrograde cholangiopancreatography with or without further cholecystectomy, and their subsequent cholangiocarcinoma incidence. Because we think the procedure related cholangiocarcinoma need longer time period to take place, the influences of subsequent cholangiocarcinoma between ES and EPBD may be clarified in whole population based cohort study.
