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.

Although hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for intrahepatic cholangiocarcinoma (ICC), few sizeable studies have tested this hypothesis. We investigated ICC risk factors, with special reference to HCV infection. We conducted a hospital-based case-control study including 50 ICC patients and 205 other surgical patients without primary liver cancer. HCV seropositivity was detected in 36% of ICC patients and 3% of controls. By univariate analysis, the odds ratio (OR) for association of anti-HCV antibodies with development was 16.87 (95% confidence interval (CI), 5.69 to 50.00). History of blood transfusion or diabetes mellitus, elevated serum total bilirubin, elevated aspartate aminotransferase and alanine aminotransferase, decreased serum albumin and decreased platelet count were identified as other possible ICC risk factors. By multivariate analysis, anti-HCV antibodies (adjusted OR, 6.02; 95% CI, 1.51 to 24.1), elevated alanine aminotransferase, decreased serum albumin, and decreased platelet count were found to be independent risk factors for ICC development. As liver status worsened, the adjusted OR for ICC tended to increase. HCV infection is a likely etiology of ICC in Japan. ntrahepatic cholangiocarcinoma (ICC), a malignant tumor arising from bile duct epithelium, is the second most common primary liver cancer, following hepatocellular carcinoma (HCC). Established risk factors for HCC include chronic active hepatitis, and hepatic fibrosis induced by hepatitis virus infection or heavy alcohol intake. On the other hand, risk factors for ICC remain uncertain. Hepatitis C virus (HCV)-related cirrhosis has been suggested as a risk factor for ICC, 1, 2) but confirmation is required. We therefore investigated risk factors for ICC, with special reference to HCV infection. Patients and MethodsWe conducted a hospital-based study using a matched case-control design, including 50 patients with pathologically diagnosed ICC and 205 other surgical patients without primary liver cancer including ICC.Patients. Fifty patients were treated for ICC between January 1991 and December 2002 in the two major medical centers of Osaka City (Department of Gastroenterological and HepatoBiliary-Pancreatic Surgery, Osaka City University Hospital; Department of Gastrointestinal Surgery, Osaka City General Hospital). ICC was diagnosed by pathologic examination. Two to five control patients at the two medical centers were matched with each ICC patient according to gender, 5-year age group, and operation date (within 1 year). Patients with HCC were excluded from the control group since hepatitis B virus (HBV) infection and HCV infection are established etiologic agents of HCC. In all, control patients numbered 205. This study was conducted in accordance with the Helsinki Declaration and the guidelines of the ethics committees at our institutions.Etiologic factors and data collection. Factors evaluated for association with ICC risk included habits such as alcohol consumption and smoking; family histor...

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Lamivudine therapy improved tumor-free survival rate after curative resection of HBV-related HCC in patients with high serum concentrations of HBV DNA, although careful follow up proved necessary for the detection of YMDD mutant viruses.

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Vancomycin hydrochloride (VCM), a glycopeptide antibiotic, has a broad spectrum against methicillin-resistant Staphylococcus aureus (MRSA). As it is known to induce renal dysfunction, the dose and the duration of its administration are limited. Moreover, the mechanism of VCM-induced renal dysfunction remains to be unclear. To evaluate the involvement of free radical on VCM-induced renal dysfunction, we carried out analysis with a hexamethylenediamine-conjugated superoxide dismutase (AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Male Wistar rats (weighing 200-210 g) were intraperitonealy administered with 200 mg/kg of VCM twice a day for 7 days. AH-SOD 5 mg/kg/day was subcutaneously injected 5 min before every VCM injection. VCM induced renal injury dose-dependently. Biochemical analyses revealed that plasma levels of blood urea nitrogen and creatinine significantly increased in the VCM-treated group by an AH-SOD-inhibitable mechanism. VCM simultaneously elicited an increase of 8-OHdG levels and chemiluminescence intensity of free radical generation in the kidney. Histological examination revealed that VCM also elicited a marked destruction of glomeruli and necrosis of proximal tubules. AH-SOD inhibited these phenomena in the kidney. These results suggested that oxidative stress might underlie the pathogenesis of VCM-induced nephrotoxicity and targeting SOD and/or related antioxidants to renal proximal tubules might permit the administration of higher doses of VCM sufficient for eradication of MRSA without causing renal injury.

We investigated risk factors for delirium in 100 patients who underwent liver resection for hepatocellular carcinoma. Postoperative delirium developed in 17 (17%). Univariate analysis revealed that advanced age (especially = 70 years old), a history of smoking, a decreased serum albumin concentration (especially < 3.8 g/dl), advanced cancer stage (II-IV), major hepatectomy, prolonged operating time, and large intraoperative blood loss were possible risk factors for postoperative delirium. When patients' preoperative condition and laboratory test results were subjected to multivariate analysis, only advanced age [odds ratio (OR) 1.201; confidence interval (CI) 1.063-1.357] and a decreased serum albumin concentration (OR 0.151; CI 0.025-0.900) were independent risk factors for the delirium. The percentages of patients with high aspartate and alanine aminotransferase activities, a high indocyanine green retention rate at 15 minutes, a low platelet count, and advanced cancer stage (II-IV) were higher in patients with a low (< 3.8 g/dl), rather than high (= 3.8 g/dl) serum albumin concentration. These findings indicate that multiple factors, including advanced age, impaired liver function, and advanced cancer stage, affect the development of postoperative delirium after liver resection for hepatocellular carcinoma.

This study was conducted to clarify the role of cytoglobin (Cygb), a globin expressed in hepatic stellate cells (HSCs), in the development of liver fibrosis and cancer in nonalcoholic steatohepatitis (NASH). Cygb expression was assessed in patients with NASH and hepatocellular carcinoma. Mouse NASH model was generated in Cygb-deficient (Cygb(-/-)) or wild-type (WT) mice by giving a choline-deficient amino acid-defined diet and, in some of them, macrophage deletion and N-acetyl cysteine treatment were used. Primary-cultured mouse HSCs isolated from WT (HSCs(Cygb-wild)) or Cygb(-/-) (HSCs(Cygb-null)) mice were characterized. As results, the expression of CYGB was reduced in patients with NASH and hepatocellular carcinoma. Choline-deficient amino acid treatment for 8 weeks induced prominent inflammation and fibrosis in Cygb(-/-) mice, which was inhibited by macrophage deletion. Surprisingly, at 32 weeks, despite no tumor formation in the WT mice, all Cygb(-/-) mice developed liver cancer, which was ameliorated by N-acetyl cysteine treatment. Altered expression of 31 genes involved in the metabolism of reactive oxygen species was notable in Cygb(-/-) mice. Both HSCs(Cygb-null) and Cygb siRNA-transfected-HSCs(Cygb-wild) exhibited the preactivation condition. Our findings provide important insights into the role that Cygb, expressed in HSCs during liver fibrosis, plays in cancer development with NASH.