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Objective: The present study aimed to investigate the impact of preoperative C-reactive protein to albumin (CRP/Alb) ratio on the long-term outcomes of patients with intrahepatic cholangiocarcinoma (ICC). Methods: 82 patients who underwent hepatic resection for mass-forming type of ICC were evaluated. The relationship between preoperative CRP/Alb ratio and survival outcomes was investigated. Results: The optimal cutoff value of CRP/Alb ratio for assessing overall survival (OS) was determined as 0.089. Univariate analysis for recurrence-free survival (RFS) showed that CRP/Alb ratio >0.089, carbohydrate antigen 19-9 (CA 19-9) >37 U/mL, lymph node metastasis, vascular invasion, and multiple tumors were significantly associated with postoperative recurrence. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.006), and multiple tumors (p < 0.001). Univariate analysis for OS showed that CRP/Alb ratio >0.089, CA 19-9 >37 U/mL, lymph node metastasis, vascular invasion, multiple tumors, and positive surgical margin were significantly associated with overall death. On multivariate analysis, the independent prognostic factors identified were CRP/Alb ratio >0.089 (p < 0.001), lymph node metastasis (p = 0.01), and multiple tumors (p = 0.005). Conclusion: Preoperative CRP/Alb ratio may predict poor long-term outcomes after hepatic resection in patients with ICC.

Introduction We investigated the indications for laparoscopic liver resection (LLR) of mass-forming intrahepatic cholangiocarcinoma (MF-ICC), including the need for lymph node dissection for improved postoperative prognosis. Methods This study involved 36 patients who underwent surgery for solitary peripheral MF-ICC. Fifteen patients underwent LLR, and 21 underwent open liver resection (OLR). Surgical outcomes and prognostic factors were investigated to determine the indications for LLR. Results No significant differences were observed in perioperative outcomes between patients who underwent LLR and OLR. A significantly worse disease-free survival (DFS) rate was observed in patients who preoperatively had a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum carbohydrate antigen (CA) 19-9 and carcinoembryonic antigen (CEA) levels. A significantly worse overall survival (OS) rate was observed in patients with a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 levels. Therefore, a tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels were determined to be preoperative prognostic factors. DFS and OS rates were significantly better in patients without these factors. Moreover, in six patients without these factors who underwent LLR, neither lymph node metastasis nor postoperative recurrence was observed. Conclusion A tumor diameter ≥3 cm, vascular invasion on diagnostic imaging, and elevated serum CA19-9 and CEA levels are preoperative prognostic factors for peripheral MF-ICC. LLR is indicated for patients without these factors.

Background: Although studies have reported on long-term (10-year) survival after hepatic resection for hepatocellular carcinoma (HCC), they did not focus on patients with hepatitis C virus (HCV)-related HCC, and the contribution of antiviral therapy to long-term survival (especially ≥15 years) has not been adequately examined. We investigated the long-term outcome after hepatic resection for HCV-related HCC, including the effects of interferon (IFN) therapy, and the changes in prognostic factors according to postoperative duration. Methods: The data of 207 patients who underwent hepatic resection for HCV-related HCC between January 1992 and December 2001 were retrospectively reviewed. We investigated the disease-free and overall survival rates after surgery and analyzed the prognostic factors at 5, 10, and 15 years postoperatively. Results: The proportion of patients who survived at 5, 10, and 15 years after hepatic resection was 52% (n = 107), 18% (n = 38), and 9% (n = 19). The overall survival rate was significantly higher in patients who achieved sustained virological response (SVR) with IFN therapy than in those without SVR. Tumor-related factors such as multiple tumor, microscopic vascular invasion, and a high indocyanine green retention rate at 15 min (ICGR15) were unfavorable prognostic factors for 5-year survival. Conversely, a low ICGR15 and SVR were favorable prognostic factors at 10 years, and SVR alone was a favorable prognostic factor at 15 years postoperatively; no tumor-related factors were prognostic factors at 10 and 15 years postoperatively. Conclusion: The prognostic factors varied according to the duration after hepatic resection for HCV-related HCC. Tumor-related factors were unfavorable prognostic factors in the early postoperative period, whereas SVR and good liver function were favorable prognostic factors at 10 and 15 years postoperatively. Achievement of SVR with IFN therapy is essential for long-term (≥15 years) survival after hepatic resection for HCV-related HCC.

A cluster of cholangiocarcinoma among printing company workers who were exposed to 1,2‐dichloropropane and/or dichloromethane was classified by the Ministry of Health, Labour and Welfare of Japan on 1 October 2013 as “occupational cholangiocarcinoma”. At the time of the diagnosis of cholangiocarcinoma, levels of γ‐glutamyl transferase, and aspartate and alanine aminotransferases were elevated, and had been elevated in some patients several years prior to the diagnosis. Regional dilatation of intrahepatic bile ducts without tumor‐induced obstruction was characteristic in diagnostic imaging. Pathological examination found chronic bile duct injury with DNA damage, precancerous/preinvasive lesions such as biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct in various sites of the large bile ducts, and invasive cholangiocarcinoma such as mass‐forming type and intraductal growth‐type intrahepatic cholangiocarcinoma and mainly papillary‐type extrahepatic cholangiocarcinoma. Whole‐exome analysis of the cancerous tissues showed hypermutation, substantial strand bias, and unique trinucleotide mutational changes. Patients seemed to suffer high incidence of postoperative complications including intra‐abdominal, which might be related to chronic bile duct injury. Postoperative recurrence from multicentric origins occurred in some patients, as DNA‐injured bile ducts have high carcinogenic potential. Aggressive treatment, including second resections for such multicentric recurrences, appeared to be effective. In 2014, the International Agency for Research on Cancer classified 1,2‐dichloropropane as Group 1 (carcinogenic to humans) and dichloromethane as Group 2A (probably carcinogenic to humans) carcinogens.

Intrahepatic metastasis (IM) of hepatocellular carcinoma (HCC) occurs via vascular invasion; the tumor diameter that affects the risk of micro intra-hepatic metastasis (MIM) should be larger than that which affects the risk of micro vessel invasion (MVI). The aim of the present study was to determine the optimum tumor diameter cut-off value for predicting the presence of MIM in HCC patients without treatment history and HCC patients with a treatment history and to compare these diameters between cases of MVI and MIM. This retrospective study included 621 patients without macroscopic vessel invasion or intrahepatic metastasis on preoperative imaging who underwent hepatectomy. The cut-off tumor diameter for predicting the presence of MIM was determined by a receiver operating characteristic curves analysis. The optimum cut-off value for predicting the presence of MIM in HCC patients without treatment history was 43 mm. In contrast, the optimum cut-off value for predicting the presence of MIM in HCC patients with a treatment history was 20 mm. Among 46 HCC patients with MIM without treatment history, there were 20 patients with MIM without MVI who were considered to have potential multi-centric (MC) tumors rather than IM. The cumulative overall survival rates in patients with MIM without MVI (potential MC) was significantly better than that in patients with both MIM and MVI (P = 0.022). The tumor diameter cut-off value for predicting MIM differed between HCC patients without treatment history and with a treatment history and slightly smaller than those for predicting MVI beyond our expectation.

This study aimed to evaluate survival outcomes in patients with non-B non-C hepatocellular carcinoma (NBNC-HCC) with reference to patients with HCC achieving sustained virological response (SVR) by preoperative interferon (IFN) treatment for chronic hepatitis C. We examined 781 patients who underwent hepatic resection for HCC. They were classified into NBNC-HCC, SVR-HCC, and non-SVR HCC groups. Multivariate analysis for recurrence-free survival (RFS) and overall survival (OS) revealed that the adjusted hazard ratios (HR) of NBNC-HCC and non-SVR HCC groups with reference to the SVR-HCC group were 1.46 (p = 0.10) and 2.10 (p

Background Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease. Methods Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated. Results Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients. Conclusions The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.

BACKGROUND An outbreak of cholangiocarcinoma has been reported among workers of an offset color proof-printing department at a printing company in Japan. In this study, we compared the clinicopathological findings of this type of intrahepatic cholangiocarcinoma (occupational ICC) and non-occupational ICC. METHODS The clinical records of 51 patients with perihilar-type ICC who underwent liver resection, including five patients with occupational ICC were retrospectively reviewed. The clinicopathological features were compared. RESULTS In the occupational group, the patients were significantly younger (P

Background This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC). Methods This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH. Results In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma-glutamyl transpeptidase (γ-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of γ-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014). Conclusion NASH is a possible risk factor for ICC development. J. Surg. Oncol. © 2016 Wiley Periodicals, Inc.

Objective: The present study aimed to identify the clinical significance of fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) imaging in patients with occupational cholangiocarcinoma. Methods: This study included 10 men with occupational cholangiocarcinoma who were former or current workers at a printing company in Osaka, Japan. Of the 10 patients, 2 had 2 main tumors and 1 had 3 main tumors. Twelve FDG-PET imaging findings in the 10 patients could be analyzed. We evaluated the relationships between FDG-PET imaging parameters and clinicopathological findings of occupational cholangiocarcinoma. Results: Abnormal FDG uptake was observed in 8 of the 14 main tumors, with maximum standardized uptake values ranging from 2.9 to 11.0, and the sensitivity was 57.1%. Four patients had lymph node metastases, and abnormal marrow uptake was detected in all these patients. Although precancerous lesions, such as biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB) without any invasion, were not detected, abnormal FDG uptake was demonstrated in 2 of 4 patients with IPNB having an associated invasive carcinoma.Conclusions: Although FDG-PET may be useful for assessing tumor progression factors, such as lymph node metastasis, it cannot accurately detect precancerous lesions, such as BilIN and IPNB without invasive carcinoma.

Aim Some patients who achieve a sustained virological response (SVR) to interferon (IFN) treatment for chronic hepatitis C prior to hepatic resection for hepatocellular carcinoma (HCC) experience postoperative recurrence. This study investigated the relationship between obesity and postoperative HCC recurrence in SVR patients. Methods Fifty‐nine patients who had achieved SVR before hepatic resection were evaluated. Patients had a solitary tumor ≤5 cm in diameter or ≤3 lesions each ≤3 cm in size with no macroscopic vascular invasion (Milan criteria). Patient characteristics potentially associated with recurrence risk were investigated. Results Three‐, 5‐, and 7‐year recurrence‐free survival after surgery were 65%, 44%, and 41%, respectively. Univariate analysis showed that obesity (P < .01), hypertension (P = .038), and non‐anatomical resection (P = .022) were significantly associated with a lower recurrence‐free survival rate. In a multivariate analysis, obesity (hazard ratio, 2.8; 95% confidence interval [CI] 1.3‐6.1; P < .01) and non‐anatomical resection (hazard ratio, 2.7; 95% CI 1.1‐6.2; P = .025) were independently associated with postoperative recurrence. Three‐, 5‐, and 7‐year overall survival rates after surgery were 100%, 80%, and 64% in obese patients and 100%, 92%, and 82% in non‐obese patients, respectively (P = .014). However, other variables showed no significant difference in the overall survival rate. Conclusions Obesity and non‐anatomical resection were independent risk factors for HCC recurrence after hepatic resection and successful IFN therapy. Obesity is an important clinical problem to consider to improve postoperative outcomes in such patients.

Background We aimed to identify the pathological characteristics of occupational cholangiocarcinoma. Methods We examined the location and distribution of the carcinomas: atypical epithelium including biliary intraepithelial neoplasia (BilIN) and intraductal papillary neoplasm of the bile duct (IPNB); and chronic bile duct injuries in operative or autopsy liver specimens from 16 patients. We examined the detailed pathological findings and diagnostic imaging of three patients. Immunohistochemical analysis using primary antibodies against γH2AX and S100P was performed. Results BilIN and chronic bile duct injury were observed in 16 patients, and IPNB or invasive IPNB was observed in 11 patients. BilIN, IPNB, and/or chronic bile duct injury were observed in almost all the large bile ducts. Regional dilatation of the bile ducts without tumor-induced obstruction revealed such pathological changes. Highly positive results for the γH2AX and S100P markers were noted in invasive carcinoma, BilIN, and IPNB, whereas positive results for γH2AX and negative results for S100P were noted in non-neoplastic biliary epithelium. Conclusions The carcinogenic process of occupational cholangiocarcinoma comprised chronic bile duct injury and DNA damage in almost all the large bile ducts, along with induction of precancerous lesions and development of invasive carcinoma. Such pathological findings reflected radiological changes on diagnostic imaging.

AIM Percutaneous radiofrequency ablation (P-RFA) therapy is a widely applied treatment for small hepatocellular carcinoma (HCC); however, local recurrence is a major issue of HCC located at the surface of the liver (surface HCC). The aim of this study was to compare the outcome of laparoscopic hepatic resection (LH) and P-RFA for surface HCC in case-control patient groups using the propensity score. METHODS Between 2011 and 2013, 40 and 52 patients underwent LH and P-RFA for surface HCC (≤3 cm, 1-3 nodules). To correct the difference in clinicopathological factors between the two groups, propensity score matching was used at a 1:1 ratio, which resulted in a comparison of 27 patients/group. We compared outcomes between the two groups, with special reference to local recurrence. RESULTS Clinicopathological variables were well balanced between the two groups. One patient in the LH group was converted to open surgery due to adhesion. The incidence of complications was 0% in the P-RFA group and 15% (four patients) in the LH group (P = 0.11); however, none of these four patients in the LH group sustained severe complications. The duration of hospitalization following treatment was longer in the LH group than in the P-RFA group (12.6 vs 7.6 days, P

Long-term surgical outcomes after hepatic resection for hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) in patients who achieved a sustained virological response (SVR) to interferon (IFN) therapy remain inconclusive. Clinical records of 277 patients who underwent hepatic resection for HCV-related early stage HCC (met the Milan criteria) between 1993 and 2012 were retrospectively reviewed. Thirty-seven patients achieved the SVR during HCC detection (pre-SVR group), whereas 23 achieved SVR using adjuvant interferon therapy after hepatic resection (post-SVR group). The control group included remaining 217 patients. We investigated the SVR effects on surgical outcomes. Disease-free survival (DFS) rates at 5/10/15 years after hepatic resection were significantly greater in the pre and post-SVR groups than in the control group (46/30/30per cent and 61/36/27 per cent vs 23/7/7 per cent, respectively; P < 0.001). Overall survival (OS) rates at 10/15 years after hepatic resection were better in the pre- and post-SVR groups than in the control group (68/68 percent and 78/78 per cent vs 13/11 per cent, respectively; P < 0.001). On multivariate analysis, pre- and post-SVR were independent factors for no recurrence (pre-SVR: hazard ratio (HR), 0.48, P = 0.002; post-SVR: HR, 0.41, P = 0.001) and improved survival (pre-SVR: HR, 0.36, P = 0.002; post-SVR: HR, 0.122, P < 0.001). Achievement of SVR in patients with HCV-related HCC was associated with long-term disease-free survival and OS after hepatic resection.

Background Focal nodular hyperplasia (FNH) is the second most common benign hepatic tumor and is very rarely complicated by hemorrhage or rupture. Although thought to be extremely rare, there have been several reports of hemorrhage caused by ruptured FNH. Herein, we report the case of a patient with ruptured FNH, who subsequently developed hemorrhage during follow-up. Case presentation A 32-year-old man was admitted to our department for an asymptomatic hepatic tumor in segments 4 and 5 (S4/5), which measured 8 cm in diameter and observed to project from the liver. Imaging and pathologic examination of a biopsy specimen confirmed the diagnosis of FNH. Three years after the diagnosis, the patient was readmitted to our hospital because of sudden onset of upper abdominal pain. Dynamic abdominal computed tomography revealed ascites around the tumor with high-density areas that were considered to represent hematoma caused by ruptured FNH. Transcatheter arterial embolization (TAE) was performed to stop the hemorrhage. One month after TAE, S4/5 of the liver was resected; macroscopic findings revealed that a large part of the tumor was composed of necrotic tissue and hematoma. Pathological examination using hematoxylin–eosin staining and immunohistochemical examination indicated a final diagnosis of FNH rupture and hemorrhage. Conclusion Although a well-established diagnosis of FNH usually requires no treatment or surveillance, careful examination remains necessary when the FNH is large and projects from the liver because of the possibility of rupture and hemorrhage.

Cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane is recognized as occupational cholangiocarcinoma. The aim of this study was to investigate the outcomes after resection of occupational cholangiocarcinoma to establish a treatment strategy for this disease.Clinicopathological findings and outcomes after surgical intervention in 20 patients with occupational cholangiocarcinoma were investigated.Of 20 the patients, curative resection was performed in 16 patients. Three patients underwent radiation at the stump of the bile ducts. Adjuvant chemotherapy was performed in 12 patients. Biliary intraepithelial neoplasia, intraductal papillary neoplasm of the bile duct, and/or chronic bile duct injury was detected in most subjects. Intraabdominal infection developed after surgery in nine patients. Cholangiocarcinoma recurred in 12 of the 20 patients. The recurrent tumors in five patients developed at a different part of the bile duct from the primary tumor and a second resection was performed in four of these five patients.The incidence of postoperative complications including intraabdominal infection was high in patients with occupational cholangiocarcinoma. Multicentric recurrence occurred not infrequently after surgery because the bile ducts had a high potential for the development of carcinoma. The aggressive treatment including second resection for the multicentric recurrence appeared to be effective.

This study aimed to investigate the association between non-alcoholic steatohepatitis (NASH) and intrahepatic cholangiocarcinoma (ICC).This was a case control study of patients who underwent surgical resection either for ICC or for a metastatic liver tumor (the control group). We assessed their clinical characteristics, pathological findings, and the prevalence of known ICC risk factors. For patients without known risk factors, we compared other factors including the prevalence of NASH.In the patients without known risk factors, 15 of 34 patients in the ICC group and 13 of 69 patients in the control group were diagnosed with NASH. Univariate analysis showed significantly higher values in the ICC group for age (P = 0.0478), prevalence of obesity (P = 0.0365) and NASH (P = 0.0078), and serum levels of albumin (P = 0.0051), and gamma-glutamyl transpeptidase (γ-GTP) (P = 0.0006) compared with the control group. Multivariate analysis showed that age and serum levels of γ-GTP and NASH were independent risk factors for ICC. In patients with NASH, the proportion of patients with hepatic fibrosis was significantly higher in the ICC group than in the control group (P = 0.0014).NASH is a possible risk factor for ICC development. J. Surg. Oncol. 2016;113:779-783. © 2016 Wiley Periodicals, Inc.

Although liver resection is considered the most effective treatment for hepatocellular carcinoma (HCC), treatment outcomes are unsatisfactory because of the high rate of HCC recurrence. Since we reported hepatitis B e-antigen positivity and high serum hepatitis B virus (HBV) DNA concentrations are strong risk factors for HCC recurrence after curative resection of HBV-related HCC in the early 2000s, many investigators have demonstrated the effects of viral status on HCC recurrence and post-treatment outcomes. These findings suggest controlling viral status is important to prevent HCC recurrence and improve survival after curative treatment for HBV-related HCC. Antiviral therapy after curative treatment aims to improve prognosis by preventing HCC recurrence and maintaining liver function. Therapy with interferon and nucleos(t)ide analogs may be useful for preventing HCC recurrence and improving overall survival in patients who have undergone curative resection for HBV-related HCC. In addition, reactivation of viral replication can occur after liver resection for HBV-related HCC. Antiviral therapy can be recommended for patients to prevent HBV reactivation. Nevertheless, further studies are required to establish treatment guidelines for patients with HBV-related HCC.

Percutaneous radiofrequency ablation (P-RFA) therapy is a widely applied treatment for small hepatocellular carcinoma (HCC); however, local recurrence is a major issue of HCC located at the surface of the liver (surface HCC). The aim of this study was to compare the outcome of laparoscopic hepatic resection (LH) and P-RFA for surface HCC in case-control patient groups using the propensity score.Between 2011 and 2013, 40 and 52 patients underwent LH and P-RFA for surface HCC (≤3 cm, 1-3 nodules). To correct the difference in clinicopathological factors between the two groups, propensity score matching was used at a 1:1 ratio, which resulted in a comparison of 27 patients/group. We compared outcomes between the two groups, with special reference to local recurrence.Clinicopathological variables were well balanced between the two groups. One patient in the LH group was converted to open surgery due to adhesion. The incidence of complications was 0% in the P-RFA group and 15% (four patients) in the LH group (P = 0.11); however, none of these four patients in the LH group sustained severe complications. The duration of hospitalization following treatment was longer in the LH group than in the P-RFA group (12.6 vs 7.6 days, P 0.01). The incidence of local recurrence was lower in the LH group (0%) than in the P-RFA group (eight patients [30%], P = 0.004).LH is an effective treatment for surface HCC with regard to control of local recurrence.

Background/Purpose: Laparoscopic hepatic resection (LH) for hepatocellular carcinoma (HCC) has gradually gained ground as a safe and minimally invasive treatment, although LH for cirrhotic patients remains challenging. Methods: Between January 2007 and August 2014, 28 and 57 patients with histologically proven cirrhosis (histological activity index, fibrosis score 4) underwent pure LH and open hepatic resection (OH; less than segmentectomy), respectively, for peripheral HCC ≤5 cm. To correct the difference in clinicopathological factors, including difficulty scores, between the two groups, propensity score matching was used at a 1:1 ratio, which resulted in a comparison of 20 patients per group. We compared the short- and long-term outcomes of LH and OH to investigate the efficacy of LH. Results: Clinicopathological variables, including difficulty scores, were well balanced between the two groups. The incidence of complications and mean intraoperative blood loss were lower in the LH group than the OH group (0 vs. 45% and 180 vs. 440 ml, p = 0.001 and 0.04, respectively). The 3-year disease-free survival rate was 42% in the LH group and 30% in the OH group (p = 0.533), whereas the 5-year overall survival rates were 46 and 60%, respectively (p = 0.606). Conclusions: LH is a safe and effective treatment option for cirrhotic patients with HCC in terms of intraoperative blood loss and morbidity.

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.

In order to detect the activated platelets, plasma beta-thromboglobulin (β-TG) levels and nucleotide pools in platelets were determined in blood samples from 34 diabetic patients with various vascular complications i. e. retinopathy, nephropathy, ischemic heart disease, cerebral thrombosis and obstruction of arteries in the extremities.β-TG levels were measured using RIA kit (Radiochemical Center, Amersham). Higher plasma, β-TG levels than 50ng/ml were found in seven patients (21%).Nucleotide pools in platelets were determined with high pressure liquid chromatography. ATP and ADP levels in platelets were decreased in 47% and 35 of the patients, respectively. ATP/ADP ratio in those cases was ranged between 0.9 and 2.8. Amount of GTP in platelets was elevated in 3 cases and decreasedd in 2 cases. All three cases whose plasma β-TG levels elevated more than 100ng/ml showed decrease of both ATP and ADP in the platelets.Measurement of nucleotide pools in platelets is a more sensitive method to detect the evidence of platelet activation in patients with arteriosclerosis.