Hiroji Shinkawa

Effects of lamivudine on outcome after liver resection for hepatocellular carcinoma in patients with active replication of hepatitis B virus

Aim:  Patients with high serum hepatitis B virus (HBV) DNA concentrations are at high risk of tumor recurrence after liver resection for HBV‐related hepatocellular carcinoma (HCC).

Iron restriction improves type 2 diabetes mellitus in Otsuka Long-Evans Tokushima fatty rats

Accumulating evidence suggests that alcohol, hepatitis C virus infection, steatosis with obesity, and insulin resistance are accompanied by iron overload states. Phlebotomy and oral iron chelators are effective treatments for these conditions and for hemochromatosis. However, the mechanisms by which iron depletion improves clinical factors remain unclear. We examined the effect of iron depletion in a model of type 2 diabetes, Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Age-matched Long-Evans Tokushima Otsuka (LETO) rats were used as controls for all experiments. Iron restriction was performed by eliminating iron in the diet from 15 wk of age or by phlebotomy. Phlebotomy was commenced at 29 wk of age by removing 4 and 3 ml of blood from the tail vein every week in OLETF and LETO rats, respectively. Rats were euthanized at 43 wk of age, and detailed analyses were performed. The plasma ferritin concentration was markedly higher in OLETF rats and decreased in iron-deficient (ID) diet and phlebotomy rats. Hemoglobin A(1c) (Hb A(1c)) was decreased significantly in OLETF rats fed the ID diet and in the phlebotomy group. Increased levels of triglycerides, glucose, free fatty acids, and total cholesterol were found in ID OLETF rats. Plasma, liver, and pancreas lipid peroxidation and hepatic superoxide production decreased in both groups. Pancreatic fibrosis and insulin levels improved in both groups of OLETF rats. Pancreatic levels of peroxisome proliferator-activated receptor-beta/delta (PPARbeta/delta) ligands and hypoxia-inducible factor (HIF)-1alpha were decreased significantly in OLETF rats. These factors were normalized in both rats fed ID and phlebotomy groups of OLETF rats. In conclusion, iron depletion improved diabetic complications by inhibition of oxidative stress and TGFbeta signal pathways and the maintenance of pancreatic PPARbeta/delta and HIF-1alpha pathways.

Supplementation of α-tocopherol improves cardiovascular risk factors via the insulin signalling pathway and reduction of mitochondrial reactive oxygen species in type II diabetic rats

This study determined the effects of α- and γ-tocopherol supplementation on metabolic control and oxidative stress in type 2 diabetic Otsuka Long–Evans Tokushima Fatty (OLETF) rats. Blood glucose, haemoglobin A1c (HbA1c), urinary protein, plasma free fatty acid, triacylglycerol and plasminogen activator inhibitor-1 (PAI-1) levels in OLETF rats were significantly higher than in non-diabetic control Long–Evans Tokushima Otsuka (LETO) rats. α-Tocopherol inhibited the increase in urinary protein, blood glucose, HbA1c and PAI-1 levels, but γ-tocopherol did not. Plasma and hepatic lipid peroxidation and hepatic steatosis were increased in OLETF rats. α-Tocopherol decreased lipid peroxidation. Mitochondrial reactive oxygen species production and uncoupling protein 2 (UCP2) expression were significantly increased in the heart and aorta of OLETF rats compared with LETO rats. Endothelial NO synthase and aortic nitrotyrosine were increased in OLETF rats. In contrast, the expression of phosphorylated vasodilator-stimulated phosphoprotein and glucose transporter 4 in the aorta was significantly decreased in OLETF rats. These abnormalities were reversed by α-tocopherol. These findings suggest that α-tocopherol may prevent cardiovascular tissues from oxidative stress and insulin signalling disorder resulting from diabetes mellitus.

A simple, noninvasively determined index predicting hepatic failure following liver resection for hepatocellular carcinoma

BACKGROUND A novel index, the serum aspartate aminotransferase activity/platelet count ratio index (APRI), has been identified as a biochemical surrogate for histological fibrogenesis and fibrosis in cirrhosis. We evaluated the ability of preoperative APRI to predict hepatic failure following liver resection for hepatocellular carcinoma. METHODS Potential preoperative risk factors for postoperative hepatic failure (hepatic coma with hyperbilirubinemia, four patients; intractable pleural effusion or ascites, 30 patients; and variceal bleeding, one patient) as well as APRI were evaluated in 366 patients undergoing liver resection for hepatocellular carcinoma. Prognostic significance was determined by univariate and multivariate analyses. RESULTS Hepatic failure developed postoperatively in 30 patients, causing death in four. APRI correlated with histological intensity of hepatitis activity and degree of hepatic fibrosis, and was significantly higher in patients who developed postoperative hepatic failure than in others without failure. Risk of postoperative hepatic failure increased as the serum albumin concentration and platelet count decreased and as indocyanine green retention rate at 15 min, aspartate and alanine aminotransferase activities, and APRI increased. Only APRI was an independent preoperative factor on multivariate analysis. Of the four patients who died of postoperative hepatic failure, three had an APRI of at least 10. CONCLUSIONS Preoperative APRI independently predicted hepatic failure following liver resection for hepatocellular carcinoma. Patients with an APRI of 10 or more have a high risk of postoperative hepatic failure.

Characteristics of printing company workers newly diagnosed with occupational cholangiocarcinoma

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.

Surgical treatment for hepatocellular carcinoma detected after successful interferon therapy.

PurposeInterferon therapy suppresses the development of hepatocellular carcinoma (HCC) and tumor recurrence after a resection of HCC in patients with chronic hepatitis C. However, the value of a liver resection and which method is best for the treatment of HCC detected after successful interferon therapy remains to be clarified. The risk factors for tumor recurrence after a liver resection for HCC detected after successful interferon therapy were investigated to determine the appropriate operative method for such HCC.MethodsRisk factors including the clinicopathologic findings and the operative methods for tumor recurrence were evaluated by univariate and multivariate analyses in 24 patients who underwent liver resection for HCC detected after successful interferon therapy (sustained viral response or biochemical response).ResultsAccording to a univariate analysis, large tumor (>2 cm, P = 0.0326), multiple tumors (P = 0.0372), nonanatomic resection (P = 0.0103), and positive surgical margin (<5 mm of a free surgical margin, P = 0.0245) were possible risk factors for short tumor-free survival time after surgery. A multivariate analysis showed that large tumor (P = 0.0407), nonanatomic resection (P = 0.0215), and positive surgical margin (P = 0.0253) were independent risk factors for a short tumor-free survival time after surgery.ConclusionAn anatomic resection with an appropriate surgical margin (≥5 mm of a free surgical margin) is recommended for patients with HCC detected after successful interferon therapy.

Effect of interferon therapy on first and second recurrence after resection of hepatitis C virus-related hepatocellular carcinoma

Aim:  Several investigators have shown that interferon (IFN) therapy can suppress the recurrence of hepatocellular carcinoma (HCC) after curative treatment. We investigated the effect of IFN therapy on the first and second HCC recurrence following hepatic resection of hepatitis C virus (HCV)‐related HCC.

Management of hepatitis B virus infection during treatment for hepatitis B virus-related hepatocellular carcinoma.

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.

The influence of postoperative glycemic control on recurrence after curative resection in diabetics with hepatitis C virus-related hepatocellular carcinoma

To elucidate the influence of diabetes on tumor recurrence after curative resection for hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC).

Outcomes of Pure Laparoscopic versus Open Hepatic Resection for Hepatocellular Carcinoma in Cirrhotic Patients: A Case-Control Study with Propensity Score Matching

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.