An unusual risk factor for intrahepatic cholangiocarcinoma
Authors: Tetsuji Fujita
Journal: Journal of Hepatology (2012)

Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinomaJournal of HepatologyVol. 57Issue 1PreviewWell established risk factors for intrahepatic cholangiocarcinoma such as biliary tract inflammation and liver flukes are not present in most Western countries patients. Although cirrhosis and other causes of chronic liver disease have been implicated, their contribution as risk factors for cholangiocarcinoma is unclear and our aims were to analyze these emerging potential risk factors by systematic examination of case–control series from geographically diverse regions. Full-Text PDF In the July 2012 issue of the Journal of Hepatology, on the basis of the meta-analysis of 11 studies, Palmer and Patel [[1]Palmer W.C. Patel T. Are common factors involved in the pathogenesis of primary liver cancers? A meta-analysis of risk factors for intrahepatic cholangiocarcinoma.J Hepatol. 2012; 57: 69-76Abstract Full Text Full Text PDF PubMed Scopus (366) Google Scholar] reported that hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) share common risk factors of tumour development, such as cirrhosis and chronic viral hepatitis. These findings may support the hypothesis that both HCC and ICC are derived from hepatic progenitor cells, and may explain the pathogenesis of combined hepatocellular and cholangiocellular carcinoma. In the report, extrahepatic cholangiocarcinoma (ECC) was excluded from the analysis because the clinicopathological features of ECC were different from ICC, and the specific risk factors for ICC, such as primary sclerosing cholangitis, hepatolithiasis, and biliary malformations were not within the scope of the analysis. At the annual meeting of the Japan Society for Occupational Medicine held on May 31, 2012, Shinji Kumagai and colleagues reported five cases with cholangiocarcinoma among 40 workers at a printing company in Osaka, Japan [[2]Available at: <http://jsoh85.umin.jp/program/images/5_31_ippan_kouen.pdf> (in Japanese).Google Scholar]. Kumagai and colleagues estimated that the incidence of cholangiocarcinoma among employees of the printing company was about 600 times higher than the national average, which raised the discussion about health hazards caused by chemicals. Soon after the report by Kumagai and colleagues, seven additional employees who had worked at the printing firm between 1991 and 2003 were identified and presented with cholangiocarcinoma. Seven out of 12 employees with cholangiocarcinoma died at the average age of 37, being about half the national average age of death from cholangiocarcinoma [3Mainichi Daily News (June 29, 2012). Editorial: Gov't must take lead in facing high cancer rate in printing industry. Available at: <www.mainichi.jp/english/english/perspective/news/>.Google Scholar, 4Mainichi Daily News (June 30, 2012). 7 workers at Osaka printing company dies of cancer between ages 27 and 46. Available at: <www.mainichi.jp/english/english/newsselect/news/>.Google Scholar, 5Mainichi Daily News (July 03, 2012). Poor ventilation at Osaka printing company likely behind cancer cases. Available at: <www.mainichi.jp/english/english/newsselect/news/>.Google Scholar]. On July 11, 2012, the Health, Labor and Welfare Ministry in Japan stated that a total of 17 cholangiocarcinoma patients with a mortality rate of 47% were identified from former and current workers of printing companies across Japan [6Daily Yomiuri Online (July 11, 2012). Bile duct cancers hit print firm workers. Available at: <www.yomiuri.co.jp/dy/national/T120710004529>.Google Scholar, 7Daily Yomiuri Online (July 12, 2012). Cancer reports highlight loose regulations/Government fails to clamp down on printing companies handling harmful chemicals. Available at: <htmhttp://www.yomiuri.co.jp/dy/national/T120711003755.htm>.Google Scholar]. Of the first five cholangiocarcinomas found at a printing company, four were ICCs [[8]Available at: <www.homepage3.nifty.com/junko-nakanishi/zak696_600html> (in Japanese).Google Scholar], while details about the remaining cases have not been elucidated. Exposure to large amounts of volatile organic compounds, such as methylene chloride (dichloromethane), dichloropropane, and ethylene chloride, without adequate ventilation is assumed to be responsible for the development of cholangiocarcinoma in the printing firm [6Daily Yomiuri Online (July 11, 2012). Bile duct cancers hit print firm workers. Available at: <www.yomiuri.co.jp/dy/national/T120710004529>.Google Scholar, 7Daily Yomiuri Online (July 12, 2012). Cancer reports highlight loose regulations/Government fails to clamp down on printing companies handling harmful chemicals. Available at: <htmhttp://www.yomiuri.co.jp/dy/national/T120711003755.htm>.Google Scholar]. These organic compounds are solved in cleansers to wash ink off of printing machines. More than 20 years ago, excess mortality from liver and biliary tract cancer among cellulose fiber production workers in the Unites States was reported [[9]Lanes S.F. Cohen A. Rothman K.J. Dreyer N.A. Soden K.J. Mortality of cellulose fiber production workers.Scand J Work Environ Health. 1990; 16: 247-251Crossref PubMed Scopus (49) Google Scholar]. Since during the cellulose triacetate production process, employees were mainly exposed to the solvent methylene chloride, the association between methylene chloride exposure and development of liver and biliary tract cancer was suggested. Further, women from bookprinting and offset printing industries in Denmark had an odds ratio of developing liver cancer (HCC, ICC, and combined carcinoma) in excess of 10.0 [[10]Dessing M. Petersen K.T. Vyberg M. Olsen J.H. Liver cancer among employees in Denmark.Am J Ind Med. 1997; 32: 248-254Crossref PubMed Scopus (20) Google Scholar]. However, according to a 36.8-year follow-up of 1473 workers, exposed to methylene chloride on average for 9 years at a concentration of 19 ppm, at a plant producing cellulose triacetate film base, methylene chloride exposure was not associated with any cancer death [[11]Tomenson J.A. Update of a cohort mortality study of workers exposed to methylene chloride employed at a plant producing cellulose triacetate film base.Int Arch Occup Environ Health. 2011; 84: 889-897Crossref PubMed Scopus (7) Google Scholar]. The data collected at printing companies in Japan and genetic polymorphisms of the glutathione pathway involved in the metabolism of organic compounds suggest that inhalation of organic compounds may be a risk factor for ICC in a population, when exposure exceeds a threshold dose. The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.