Cholangiocarcinoma among offset colour proof-printing workers exposed to 1,2-dichloropropane and/or dichloromethane

Changes in Laboratory Test Results and Diagnostic Imaging Presentation before the Detection of Occupational Cholangiocarcinoma: Shoji KUBO, et al. Department of Hepato‐Biliary‐Pancreatic Surgery, Osaka City University Graduate School of Medicine— Objectives A cholangiocarcinoma outbreak among workers of an offset color proof‐printing department in a printing company was recently reported. It is important to understand the clinical course leading to occupational cholangiocarcinoma development for investigation of the carcinogenesis process and for surveillance and early detection. We evaluated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma. Methods We investigated the changes in laboratory test results and diagnostic imaging presentation before the detection of cholangiocarcinoma in 2 patients because the data were available. Results The clinical courses observed in the 2 participating patients showed persistent elevation of serum γ‐glutamyl transpeptidase levels with or without elevated serum levels of alanine aminotransferase and/or aspartate aminotransferase before cholangiocarcinoma detection. Dilatation of the bile ducts without tumor‐induced stenosis was observed several years before cholangiocarcinoma detection and progressed gradually in both patients. The serum concentration of carbohydrate 19‐9 also increased prior to cholangiocarcinoma detection in both patients. Eventually, observation of stenosis of the bile duct and a space‐occupying lesion strongly suggested cholangiocarcinoma. Pathological examination of the resected specimens showed chronic bile duct injury and neoplastic lesions, such as “biliary intraepithelial neoplasia” and “intraductal papillary neoplasm of the bile duct” in various sites of the bile ducts, particularly in the dilated bile ducts. Conclusions The changes in laboratory test results and diagnostic imaging might be related to the development of cholangiocarcinoma. It is important to monitor diagnostic imaging presentation and laboratory test results in workers with extended exposure to organic solvents.

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Changes in Laboratory Test Results and Diagnostic Imaging Presentation before the Detection of Occupational Cholangiocarcinoma

Kubo

Takemura

Sakata

et al. 2014

“…Recently, the occurrence of cholangiocarcinoma cases was reported among the employees and former employees of an offset printing company in Osaka, Japan 1) . So far, 11 cancer patients have been diagnosed among 62 workers conducting offset color proof printing in this factory, and this surely shows an extremely high incidence rate of this kind of cancer compared with the national average during the same period.…”

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confidence: 99%

Assessment of the Genotoxicity of 1,2‐Dichloropropane and Dichloromethane after Individual and Co‐exposure by Inhalation in Mice

Suzuki

Yanagiba

Suda

et al. 2014

205Tetsuya SUZUKI, et al.: Genotoxicity of 1,2-dichloropropane and Dichloromethane effects were greatly enhanced by simultaneous exposure to DCM. (J Occup Health 2014; 56: 205-214) Key words: 1,2-Dichloropropane, Co-exposure, Dichloromethane, Genotoxicity, InhalationRecently, the occurrence of cholangiocarcinoma cases was reported among the employees and former employees of an offset printing company in Osaka, Japan 1) . So far, 11 cancer patients have been diagnosed among 62 workers conducting offset color proof printing in this factory, and this surely shows an extremely high incidence rate of this kind of cancer compared with the national average during the same period. In addition, the ages of the workers at diagnosis were 25−45 years, and this is obviously much younger that in the general population. Later, more cases were found in factories, including other offset printing companies, in a national survey sponsored by the occupational health authorities 2) . The occurrence of cholangiocarcinoma in this industry is therefore suspected to be related to some factors in the workplaces.1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) were the substances suspected of causing the cancer, since they were used as the ink cleaners in a large amounts and can easily evaporate into the air, meaning that the workers were therefore exposed to these chlorinated organic solvents at high concentrations. Our colleagues carried out an experiment to reproduce the working environment of the proof-printing room of this company in Osaka and concluded that the exposure concentrations might have been as high as several hundreds ppm for either 1,2-DCP or DCM under the conditions of ordinary work amount 3) , and the latter solvent showed 2-3 fold higher concentration than the former solvent because of the difference in evaporation rate. Other components in the cleaner included 1,1,1-trichloroethane, petroleum- Occurrence of cholangiocarcinoma was recently reported at a high incidence rate among the employees working for an offset printing company in Osaka, Japan. 1,2-Dichloropropane (1,2-DCP) and dichloromethane (DCM) are suspected to be the causes of the cancer, as they had been used as ink cleaners in large amounts. However, it is not clear whether these chlorinated organic solvents played a role in the occurrence of cholangiocarcinoma or why the incidence rate is so high among the workers in this industry. To provide possible evidence for this severe occupational problem, we investigated the genotoxic effects of 1,2-DCP and DCM. Methods: Male B6C3F1 and gpt Delta C57BL/6J mice were exposed by inhalation to the individual solvents or both solvents at multiple concentrations including the levels that were possibly present in the workplaces. The genotoxicity was analyzed by Pig-a gene mutation and micronuclei assays in peripheral blood and gpt mutation and comet assays in the livers of mice after repeated inhalation of 1,2-DCP or/and DCM. Results: The Pig-a mutant frequencies and micronuclei incidences were not significantl...

“…These results indicate that the hepatitis in this patient should be classified into as a hepatocellular type. Recently, an outbreak of cholangiocarcinoma occurred in this same company, and chlorinated organic solvents, particularly DCM and DCP, were suspected to play a causative role 16,17) . In patients with occupational cholangiocarcinoma, laboratory test results showed elevated γ -GTP levels (with or without elevated AST and/or ALT levels), and pathological findings demonstrated chronic bile duct injury and non-injured hepatocytes 17) .…”

Section: Discussionmentioning

confidence: 99%

Severe acute hepatitis in a printing company worker: A case study

Kubo

Matsuzaki

Seki

et al. 2015

Self Cite

Severe acute hepatitis in a printing company worker: A case study: Shoji KUBO, et al. Department of Hepato‐Biliary‐Pancreatic Surgery, Osaka City University Graduate School of Medicine— Objectives It has been reported that chlorinated organic solvent is a cause of hepatitis. Methods we investigate clinical and pathological findings of a patient with severe acute hepatitis who was exposed to chlorinated organic solvents. Results A 34‐year‐old man who was exposed to chlorinated organic solvents including dichloromethane, 1,2‐dichloropropane, and trichloroethylene, presented with general fatigue, vomiting, and diarrhea. At admission, his laboratory test results showed extremely elevated aspartate aminotransferase (4,872 IU/l), alanine aminotransferase (3,000 IU/l), and lactate dehydrogenase (11,600 IU/l) levels and a prothrombin level below normal (41%). No encephalopathy was noted. These findings were indicative of severe acute hepatitis. Viral hepatitis, autoimmune hepatitis, alcoholic disease, bile duct disease, and viral infection were excluded as causes of hepatitis by clinical, laboratory, and imaging findings. After diagnosis, the patient was administered fresh frozen plasma and glucagon‐insulin therapy. Liver function recovered within a few weeks, and a liver biopsy performed 25 days after admission showed the recovery phase after acute liver damage. Conclusions These clinical and pathological findings indicate that exposure to chlorinated organic solvents may have induced severe acute hepatitis in this patient.