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Objectives: Endoscopic management of unresectable hilar malignant biliary obstruction (HMBO) is technically challenging, and effectiveness of stent-in-stent using large-cell, metal stents was reported. A new, large-cell stent with a 6F tapered delivery system was recently developed. The aim of this study was to compare clinical outcomes of slim-delivery and conventional large-cell stents., Methods: This was a multicenter retrospective comparative study of stent-in-stent methods using slim-delivery stents (Niti-S Large Cell SR Slim Delivery [LC slim-delivery]) and conventional stents (Niti-S large-cell D-type; LCD) for unresectable HMBO., Results: Eighty-three patients with HMBO were included; 31 LC slim-delivery and 52 LCD. Overall technical and clinical success rates were 100% and 90% in LC slim-delivery group and 98% and 88% in LCD group. Use of the LC slim-delivery was associated with shorter stent placement time in the multiple regression analysis, with a stent placement time of 18 and 23 min in LC slim-delivery and LCD groups, respectively. The early adverse event (AE) rate of LC slim-delivery was 10%, with no cholangitis or cholecystitis as compared to 23% in the LCD group. Recurrent biliary obstruction (RBO) rates and time to RBO were comparable between the two groups: 35% and 44%, and 8.5 and 8.0 months in LC slim-delivery and LCD groups, respectively. The major cause of RBO was tumor ingrowth (82%) in the LC slim-delivery group and sludge (43%) and ingrowth (48%) in LCD group., Conclusion: Stent-in-stent methods using LC slim-delivery shortened stent placement time with low early AE rates and comparable time to RBO in patients with HMBO., (© 2023 The Authors. Digestive Endoscopy published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.)

Background: Studies have demonstrated a prognostic role of sarcopenia (i.e., loss of skeletal muscle volume and functionality) in patients with various cancer types. In patients with biliary tract cancer, the quantity and quality of skeletal muscles and their serial changes have not been fully investigated in relation to survival outcomes., Methods: We identified 386 patients with unresectable or recurrent biliary tract cancer and calculated skeletal muscle index (SMI) and skeletal muscle density (SMD) to estimate muscular quantity and quality, respectively, based on computed tomography images. Using the Cox regression model with adjustment for potential confounders, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for progression-free survival (PFS) and overall survival (OS) according to skeletal muscle status and its serial change., Results: Compared to patients without sarcopenia, patients with sarcopenia were associated with shorter PFS (multivariable HR, 1.60; 95% CI, 1.15-2.22; P = 0.005), but not with OS (P = 0.027) at the adjusted α level of 0.013. SMD at baseline was associated with OS (multivariable HR comparing the extreme quartiles, 1.52; 95% CI, 1.07-2.14; P trend  = 0.012), but not with PFS (P trend  = 0.13). A reduction in SMI rather than that in SMD was associated with OS. Progressive disease was a risk factor for reductions in SMI and SMD., Conclusions: Skeletal muscle quantity and quality and their serial changes were associated with survival outcomes in patients with advanced biliary tract cancer. Our data highlight the importance of designing nutritional and physical interventions for improvements in skeletal muscle status., (© 2024. The Author(s).)

Objectives: This study aimed to evaluate the relationship between cumulative exposure to 1,2-dichloropropane (1,2-DCP) and incidence risk of cholangiocarcinoma among workers in the offset proof-printing section of a small printing company in Osaka, Japan., Methods: We identified 95 workers of a printing company (78 men and 17 women) who had been exposed to 1,2-DCP between 1987 and 2006, and calculated the standardised incidence ratio (SIR) of cholangiocarcinoma from 1987 to 2012. We estimated cumulative exposure to 1,2-DCP and calculated SIRs in four exposure categories. We also calculated incidence rate ratios (RRs) adjusted by sex, age, calendar year and dichloromethane (DCM) exposure for three exposure categories using Poisson regression analysis., Results: Cumulative exposures to 1,2-DCP ranged from 32 to 3433 ppm-years (mean, 851 ppm-years) and the SIR was 1171 (95% CI 682 to 1875). In the analysis of the four exposure categories, SIRs increased significantly in the three highest exposure categories, but not in the lowest category. Adjusted RRs in the middle and high exposure categories were 14.9 (95% CI 4.1 to 54.3) and 17.1 (95% CI 3.8 to 76.2), respectively, in the analysis without lag time, and were 11.4 (95% CI 3.3 to 39.6) and 32.4 (95% CI 6.4 to 163.9), respectively, in the analysis with a 5-year lag. The trend analysis revealed a significant increase in RR in association with increasing cumulative exposure to 1,2-DCP. DCM exposure was not significantly associated with the development of cholangiocarcinoma., Conclusions: The present study demonstrated an exposure-response relationship between exposure to 1,2-DCP and the development of cholangiocarcinoma., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Purpose: This study aimed to establish an efficient strategy for screening and surveillance for occupational cholangiocarcinoma., Methods: We evaluated the consecutive changes in laboratory findings during regular health examinations and in abdominal ultrasonography findings before the diagnosis of occupational cholangiocarcinoma in nine patients. The results of laboratory tests and abdominal ultrasonography at the time of diagnosis were also examined., Results: In all patients, the serum γ-glutamyl transpeptidase (γ-GTP) activity increased several years before the diagnosis of cholangiocarcinoma. The serum alanine aminotransferase (ALT) activity also increased several years before the diagnosis, following an increase in the serum aspartate aminotransferase (AST) activity in most patients. Abdominal ultrasonography before the diagnosis revealed regional dilatation of the bile ducts, which continued to enlarge. At the time of diagnosis, the γ-GTP, AST, and ALT activities were increased in nine, seven, and seven patients, respectively. The regional dilatation of bile ducts without tumor-induced stenosis, dilated bile ducts due to tumor-induced stenosis, space-occupying lesions, and/or lymph node swelling were observed. The serum concentrations of carbohydrate antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) were increased in all patients., Conclusions: Regular health examinations with a combination of ultrasonography and laboratory tests including the γ-GTP, AST, ALT, CA 19-9, and CEA levels are useful for screening and surveillance for occupational cholangiocarcinoma.

Objective: This study aimed to identify the chemicals used by five printing workers and one coating worker who developed cholangiocarcinoma and estimate the workers' levels of chemical exposure., Methods: We obtained information on chemicals from the Ministry of Health, Labour and Welfare, Japan, and estimated working environment concentrations of the chemicals in printing and coating rooms and exposure concentrations during the ink and dirt removal processes. We also calculated shift time-weighted averages of exposure concentrations., Results: All five printing workers were exposed to both 1,2-dichloropropane (1,2-DCP) and dichloromethane (DCM). The estimated maximum exposure concentrations for each of the five workers were 190 to 560 ppm for 1,2-DCP and 300 to 980 ppm for DCM, and the estimated shift average exposure concentrations were 0 to 230 ppm for 1,2-DCP and 20 to 470 ppm for DCM. The coating worker was exposed to 1,2-DCP, but not DCM. He did not use ink, and thus was subjected to different conditions than the printing workers. The estimated maximum exposure concentration of 1,2-DCP was 150 ppm, and the estimated shift time-weighted average exposure concentration was 5 to 19 ppm., Conclusions: Our findings support the notion that 1,2-DCP contributes to the development of cholangiocarcinoma in humans and the notion that DCM may also be a contributing factor. The finding that the coating worker was exposed to 1,2-DCP at a lower exposure concentration is important for determining the occupational exposure limit. Furthermore, the subject did not use ink, which suggests that ink did not contribute to the development of cholangiocarcinoma.

Objectives: We conducted a retrospective cohort study to examine the risk of bile duct cancer among current and former workers in the offset color proof printing department at a printing company in Osaka, Japan., Methods: Standardized incidence ratios (SIRs) between January 1, 1985, and December 31, 2012, were estimated for the cumulative years of exposure to two chemicals, dichloromethane (DCM) and 1,2-dichloropropane (1,2-DCP), using the national incidence level as a reference. In addition, we examined risk patterns by the calendar year in which observation started., Results: Among 106 workers with a total of 1,452.4 person-years of exposure, 17 bile duct cancer cases were observed, resulting in an estimated overall SIR of 1,132.5 (95% confidence interval (CI): 659.7-1,813.2). The SIR was 1,319.9 (95% CI: 658.9-2,361.7) for those who were exposed to both DCM and 1,2-DCP, and it was 1,002.8 (95% CI: 368.0-2,182.8) for those exposed to 1,2-DCP only. SIRs tended to increase according to years of exposure to 1,2-DCP but not DCM when a 5-year lag time was assumed. The SIRs were higher for the cohorts in which observation started in 1993-2000, particularly in cohorts in which it started in 1996-1999, compared with those in which it started before or after 1993-2000., Conclusions: We observed an extraordinarily high risk of bile duct cancer among the offset color proof printing workers. Elevated risk may be related to cumulative exposure to 1,2-DCP, but there remains some possibility that a portion of the risk is due to other unidentified substances.

Objective: In several Japanese printing plants, printing workers have suffered from cholangiocarcinoma. 1,2-dichloropropane (1,2-DCP) is considered to be a causative agent, and whether or not other chemicals also contribute to the development of this disease has not been conclusively determined. This study aimed to identify the chemicals used by seven printing workers who developed cholangiocarcinoma, as well as to estimate the levels of chemical exposure among them., Methods: Information was obtained from the Ministry of Health, Labour and Welfare, Japan, to identify chemicals used by printing workers who developed cholangiocarcinoma and to estimate chemical exposure concentrations. Working environment concentrations of the chemicals in the printing rooms were estimated using a well-mixed model, and exposure concentrations during the ink removal operation were estimated using a near-field and far-field model. Shift time-weighted averages of exposure concentrations were also calculated., Results: Four of the seven printing workers were exposed to both 1,2-DCP and dichloromethane (DCM). The estimated maximum exposure concentrations for each of the four workers were 230 to 420 ppm for 1,2-DCP and 58 to 720 ppm for DCM, and the estimated shift average exposure concentrations were 0 to 210 ppm for 1,2-DCP and 15 to 270 ppm for DCM. The remaining three workers were exposed to DCM but not 1,2-DCP. The estimated maximum exposure concentrations of DCM for each of the three workers were 600 to 1,300 ppm, and the estimated shift average exposure concentrations were 84 to 440 ppm., Conclusions: Our findings suggest that DCM may contribute to the development of cholangiocarcinoma in humans.

Background: Cholangiocarcinoma has been reported in workers exposed to chlorinated organic solvents and has consequently been classified as an occupational disease (occupational cholangiocarcinoma) by the Japanese Ministry of Health, Labour and Welfare. This study aimed to identify the characteristics of nine workers newly diagnosed with occupational cholangiocarcinoma., Methods: This study was a retrospective study conducted in 13 hospitals and three universities. Clinicopathological findings of nine occupational cholangiocarcinoma patients from seven printing companies in Japan were investigated and compared with 17 cholangiocarcinoma patients clustered in a single printing company in Osaka., Results: Patient age at diagnosis was 31-57 years. Patients were exposed to 1,2-dichloropropane and/or dichloromethane. Serum γ-glutamyl transpeptidase activity was elevated in all patients. Regional dilatation of the intrahepatic bile ducts without tumor-induced obstruction was observed in two patients. Four patients developed intrahepatic cholangiocarcinoma and five developed hilar cholangiocarcinoma. Biliary intraepithelial neoplasia and/or intraductal papillary neoplasm of the bile duct was observed in four patients with available operative or autopsy specimens., Conclusions: Most of these patients with occupational cholangiocarcinoma exhibited typical findings, including high serum γ-glutamyl transpeptidase activity, regional dilatation of the bile ducts, and precancerous lesions, similar to findings previously reported in 17 occupational cholangiocarcinoma patients in Osaka., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: An outbreak of cholangiocarcinoma occurred among workers in the offset color proof-printing department at a printing company in Japan. The aim of this study was to clarify the characteristics of the patients with cholangiocarcinoma., Methods: This was a retrospective study conducted in 13 Japanese hospitals between 1996 to 2013. The clinicopathological findings of cholangiocarcinoma developed in 17 of 111 former or current workers in the department were investigated. Most workers were relatively young., Results: The cholangiocarcinoma was diagnosed at 25-45 years old. They were exposed to chemicals, including dichloromethane and 1,2-dichloropropane. The serum γ-glutamyl transpeptidase activity was elevated in all patients. Dilated intrahepatic bile ducts without tumor-induced obstruction were observed in five patients. The cholangiocarcinomas arose from the large bile ducts. The precancerous or early cancerous lesions, such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile ducts, as well as non-specific bile duct injuries, such as fibrosis, were observed in various sites of the bile ducts in all eight patients for whom operative specimens were available., Conclusions: The present results showed that cholangiocarcinomas occurred at a high incidence in relatively young workers of a printing company, who were exposed to chemicals including chlorinated organic solvents., (© 2014 Japanese Society of Hepato-Biliary-Pancreatic Surgery.)

Background: A report of multiple cases of bile duct cancer at a Japanese printing company raised concern about such cancers. We examined long-term trends in bile duct cancer in Japan., Methods: Data from 4 population-based cancer registries were used to calculate incidence between 1985 and 2007, and vital statistics were used to estimate mortality between 1985 and 2011. Age-standardized rates were calculated and analyzed using a joinpoint regression model., Results: Among men, the incidence rate of intrahepatic bile duct cancer increased throughout the observation period; among women, it increased until 1996-1998 and remained stable thereafter. The incidence rate of extrahepatic bile duct cancer was stable in men and decreased from 1993-1995 in women. In people aged 30 to 49 years, the incidence rates of intra- and extrahepatic bile duct cancer remained stable or decreased. The mortality rate of intrahepatic bile duct cancer increased in both sexes and in all age groups since 1996, while that of extrahepatic bile duct cancer decreased since 1992. In people aged 30 to 49 years, the mortality rates of intra- and extrahepatic bile duct cancer remained stable and decreased, respectively., Conclusions: The incidence and mortality rates of intrahepatic bile duct cancer remained stable or increased throughout the observation period. The incidence rate of extrahepatic bile duct cancer remained stable or decreased, and the mortality rate decreased since 1992. In people aged 30 to 49 years, the incidence and mortality rates of intra- and extrahepatic bile cancer remained stable or decreased.

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.

Objective: This study aimed to identify chemicals used by printing workers with cholangiocarcinoma, as well as the levels of exposure to the chemicals., Methods: Information necessary to identify chemicals used by printing workers with cholangiocarcinoma and to estimate chemical exposure concentrations was obtained from the Ministry of Health, Labour and Welfare, Japan. Working environment concentrations of the chemicals in the printing rooms were estimated using a well-mixed model, and exposure concentrations during the ink removal operation were estimated using a near-field and far-field model. Shift time- weighted averages (TWA) of exposure concentrations were also calculated., Results: Two workers from each of three small printing plants examined suffered from cholangiocarcinoma, and all six of these workers had been exposed to 1,2-dichloropropane (1,2-DCP) for 10-16 years. The estimated working environment concentrations of 1,2-DCP in the printing rooms were 17-180 ppm and estimated exposure concentrations during the ink removal operation were 150-620 ppm. Shift TWA values were estimated to be 62-240 ppm. Four of the six workers had also been exposed to dichloromethane (DCM) at estimated working environment concentrations of 0-98 ppm and estimated exposure concentrations during the ink removal operation of 0-560 ppm. Shift TWA values were estimated to be 0-180 ppm. Other chlorinated organic solvents (1,1,1-trichloroethane, 1,1-dichloro-1-fluoroethane) and petroleum solvents (gasoline, naphtha, mineral spirit, mineral oil, kerosene) were also used in the ink removal operation., Conclusions: All six printing workers with cholangiocarcinoma were exposed to very high levels of 1,2-DCP for a long term.

Objectives: The aim of this study was to assess the risk of developing bile duct cancer among workers in the other printing industry in comparison with workers in all industries in general., Methods: Prevalence of bile duct cancer was compared between workers in the printing industry and age-standardized controls in all other industries using the claims database of the Japan Health Insurance Association, which insures workers of small-medium sized employers of all industries., Results: Young (aged 30-49) male workers in the printing industry showed an elevated but insignificant standardized prevalence rate ratio (SPRR) for bile duct cancer in comparison with workers in all other industries (SPRR: 1.78; 95%CI: 0.63-5.00). The risk was higher for intrahepatic bile duct cancer but remained insignificant (SPRR: 3.03; 95%CI: 0.52-17.56)., Conclusions: The sharply elevated risk of bile duct cancer observed among proof-printing workers of a printing factory in Osaka may not be generalizable to workers in the printing industry nationwide.