Ethanol injection therapy for small hepatocellular carcinomas located beneath a large vessel using a curved percutaneous ethanol injection therapy needle.

Percutaneous ethanol injection therapy (PEIT) has been administered as a safe therapeutic modality for patients with small hepatocellular carcinoma (HCC). Due to the nature of the straight approaching line of a PEIT or radiofrequency ablation needle, penetrating the vessels that are interposed between the dermal insertion point and the nodule is unavoidable. A device with an overcoat needle and coaxial curved PEIT needle was created that facilitated a detour around interposing large vessels in order to avoid unnecessary harmful effects that result from the PEIT procedure.

Clinical characteristics of patients with hepatitis C virus-related chronic liver disease seropositive for anticentromere antibody.

The association between anticentromere antibody (ACA) and hepatitis C virus (HCV) infection remains unclear. We subjected eight patients with HCV-related chronic liver disease (CLD) seropositive for ACA to a battery of clinical and laboratory tests. The patient cohort was dominated by females, and four of the eight (50%) patients had a concomitant autoimmune disease.

Efficacy of zinc administration in patients with hepatitis C virus-related chronic liver disease.

Objective: Zinc supplementation has been shown to contribute to inhibition of liver fibrosis and improvement in hepatic encephalopathy. However, little is known about the anti-inflammatory effect of zinc on hepatitis C virus (HCV)-related chronic liver disease (CLD). We therefore examined the effects of zinc administration on inflammatory activity and fibrosis in the liver of patients with HCV-related CLD.

Vitamins K2, K3 and K5 exert antitumor effects on established colorectal cancer in mice by inducing apoptotic death of tumor cells.

Although a number of studies have shown that vitamin K possesses antitumor activities on various neoplastic cell lines, there are few reports demonstrating in vivo antitumor effects of vitamin K, and the antitumor effect on colorectal cancer (CRC) remains to be examined. Therefore, antitumor effects of vitamin K on CRC were examined both in vitro and in vivo. Vitamins K2, K3 and K5 suppressed the proliferation of colon 26 cells in a dose-dependent manner, while vitamin K1 did not.

Analysis of CD28 and bcl-2 expression on peripheral blood and liver-infiltrating mononuclear cells in patients with autoimmune hepatitis.

Because the underlying mechanism of hepatocellular damages in autoimmune hepatitis (AIH) still remains unclear, analysis of CD28 and bcl-2 molecules, which are critical for T cell activation and survival, was performed in patients with AIH. The number of CD28(+)CD4(+) peripheral blood mononuclear cells (PBMC) in corticosteroid (CS)-treated patients was comparable to normal control individuals but decreased in untreated AIH patients. In contrast, the number of CD28(+)CD8(+) PBMC was decreased in both CS-treated and untreated AIH patients.

Usefulness of liver infiltrating CD86-positive mononuclear cells for diagnosis of autoimmune hepatitis.

Aim: Although the pathogenic mechanism underlying autoimmune hepatitis (AIH) remains unclear, the immune system is thought to be critical for the progression of the disease. Cellular immune responses may be linked to the hepatocellular damage in AIH. Recently, much attention has been focused on the critical functions of costimulatory molecules expressed on mononuclear cells in the generation of effective T cell-mediated immune responses.

Relationship between the proliferative capability of hepatocytes and the intrahepatic expression of hepatocyte growth factor and c-Met in the course of cirrhosis development in rats.

Liver cirrhosis is the fatal end stage of various chronic liver diseases. One of the most important causes of liver cirrhosis appears to be an impaired proliferative capability of hepatocytes caused by continuous hepatic damage. Hepatocyte growth factor (HGF) and its specific receptor, c-Met, play a pivotal role in hepatocyte proliferation.

Time-lag performance of radiofrequency ablation after percutaneous ethanol injection for the treatment of hepatocellular carcinoma.

We have previously reported that the combination therapy of percutaneous ethanol injection and radiofrequency ablation (PEI-RFA) was more effective than RFA alone to induce wider coagulated necrosis for the treatment of hepatocellular carcinoma (HCC). In the present study, the effect of time-lag performance of RFA after PEI was evaluated under the same ablation condition as PEI-RFA by analyzing the volume of coagulated necrosis, the energy requirement for ablation and the amount of ethanol injected into HCC. The comparative study between time-lag PEI-RFA and no time-lag PEI-RFA showed that the total energy requirement and the energy requirement per unit volume for whole and marginal coagulated necrosis were significantly smaller in the time-lag group than in the no time-lag PEI-RFA group.

Repetitive and safe transgene expression in rat liver is achievable by adenoviral infusion into the common bile duct.

To examine the feasibility of adenovirus-mediated gene transfer into the liver, we examined whether adenoviral infusion into the common bile duct could induce repetitive and safe transgene expression in rat livers. Recombinant adenovirus carrying a reporter lacZ gene was repetitively infused retrogradely into the common bile duct of rats. LacZ expression in rat livers was estimated histochemically by X-gal staining and quantitatively by a chemiluminescent reporter gene assay after the first, second and third adenoviral infusion into the common bile duct.

Vitamins K2, K3 and K5 exert in vivo antitumor effects on hepatocellular carcinoma by regulating the expression of G1 phase-related cell cycle molecules.

A number of studies have shown that various vitamins K, specifically vitamin K2, possessed antitumor activity on various types of rodent- and human-derived neoplastic cell lines. However, there are only a small number of reports demonstrating in vivo antitumor effects of vitamins K. Furthermore, the mechanism of antitumor effects of vitamins K still remains to be examined.

Diffuse large B-cell primary gastric lymphoma treated successfully with the CD20 monoclonal antibody (rituximab): a case with severe liver dysfunction due to liver cirrhosis and hepatocellular carcinoma.

Primary gastric lymphoma is relatively rare in the scope of gastric malignancies. Here we report a case of diffuse large B-cell primary gastric lymphoma treated successfully with the CD20 monoclonal antibody, rituximab, alone. Because the patient had a complication of severe liver dysfunction due to hepatitis C virus induced-liver cirrhosis and hepatocellular carcinoma, it was difficult to treat the primary gastric lymphoma using standard therapy such as surgical resection and cocktail chemotherapy.

Safe and efficient transgene expression in rat hepatocytes induced by adenoviral administration into the biliary tract.

We examined whether retrograde intrabiliary adenoviral administration could induce safe and efficient transgene expression in hepatocytes. We administered recombinant adenovirus carrying a reporter lacZ gene retrogradely into the common bile duct of rats and evaluated the transduction efficiency of the lacZ gene in the liver histochemically by X-gal staining, and also quantitatively by a chemiluminescent reporter gene assay. Retrograde administration of adenovirus into the common bile duct was shown to successfully induce transgene expression in the liver.

In vitro and in vivo antitumor effects of vitamin K5 on hepatocellular carcinoma.

Although a number of studies have shown that vitamins K1, K2 and K3 exerted antitumor effects on various types of rodent- and human-derived neoplastic cell lines, it has not been examined whether or not vitamin K5 also possesses antitumor activity. In the present study, we examined the antitumor effects of vitamin K5 on PLC/PRF/5 human hepatocellular carcinoma (HCC) cells in vitro and in vivo. Furthermore, we examined the mechanisms of antitumor actions of vitamin K5 not only in vitro but also in vivo.

Comparison between combination therapy of percutaneous ethanol injection and radiofrequency ablation and radiofrequency ablation alone for patients with hepatocellular carcinoma.

Aim: In the present study, the characteristics of PEI-RFA treatment were further elucidated by analyzing the relationship between the volume of coagulated necrosis and the energy requirement for ablation or the amount of ethanol injected into HCC.

Methods: The volume of coagulated necrosis, total energy requirement and energy requirement for coagulation of per unit volume were examined in the groups of PEI-RFA and RFA alone using the Cool-tip RF system.

Results: The results showed that the volume of coagulated necrosis induced was significantly larger in PEI-RFA group than in routine RFA group, when the total energy administered was comparable in both groups.

Comparison study of the expressions of myristoylated alanine-rich C kinase substrate in hepatocellular carcinoma, liver cirrhosis, chronic hepatitis, and normal liver.

The myristoylated alanine-rich C kinase substrate (MARCKS) is a prominent substrate for protein kinase C (PKC) in a variety of cells. The aim of this study was not only to evaluate the expression and localization of MARCKS in various pathological liver tissues, including HCC, but also to analyze the difference in MARCKS expression between hepatitis virus-induced HCC and cirrhosis. The level of MARCKS and its phosphorylated proteins, as well as its localization, were determined using Western blot and/or immunohistochemistry in HCC and other pathological liver tissues.

Adenovirus-mediated gene transfer into rat livers: comparative study of retrograde intrabiliary and antegrade intraportal administration.

To examine the feasibility of liver-directed in vivo gene therapy, we administered recombinant adenoviruses carrying a reporter lacZ gene retrogradely into the common bile duct of rats, as well as antegradely into the portal vein. Transduction efficiency of the lacZ gene in the liver was estimated not only histochemically by X-gal staining, but also quantitatively by a chemiluminescent reporter gene assay. Retrograde infusion of adenoviruses into the common bile duct was shown to successfully induce transgene expression in the liver.

Successful laparoscopic radiofrequency ablation of hepatocellular carcinoma adhered to the mesentery after transcatheter arterial embolization.

A 54-year-old male with hepatocellular carcinoma (HCC) underwent transcatheter arterial embolization (TAE) at a nearby hospital. He was then referred to our hospital for the purpose of additional treatment of HCC. Because TAE was not a complete therapy and HCC was growing and protruding from the left lobe of the liver, laparoscopic radio-frequency ablation (RFA) was chosen for the treatment of HCC.

Efficacy of combination therapies of percutaneous or laparoscopic ethanol-lipiodol injection and radiofrequency ablation.

Percutaneous radiofrequency ablation (RFA) is able to destroy hepatocellular carcinoma (HCC) in a few sessions without major complications. We have previously shown that not only the combined use of percutaneous ethanol injection and RFA (PEI-RFA) but also injection of mixture of ethanol and lipiodol (PELIT) was useful for the treatment of HCC. In the present study, we further developed the combined use of PELIT and RFA through percutaneous or laparoscopic approach (PELI-RFA or LELI-RFA) and evaluated its usefulness.

Enhanced tumor-specific long-term immunity of hemagglutinating [correction of hemaggluttinating] virus of Japan-mediated dendritic cell-tumor fused cell vaccination by coadministration with CpG oligodeoxynucleotides.

Immunization with dendritic cells (DCs) using various Ag-loading approaches has shown promising results in tumor-specific immunotherapy and immunoprevention. Fused cells (FCs) that are generated from DCs and tumor cells are one of effective cancer vaccines because both known and unknown tumor Ags are presented on the FCs and recognized by T cells. In this study, we attempted to augment antitumor immunity by the combination of DC-tumor FC vaccination with immunostimulatory oligodeoxynucleotides containing CpG motif (CpG ODN).

Reduced expression of cell cycle regulator p18(INK4C) in human hepatocellular carcinoma.

Cyclins, cyclin-dependent kinases (Cdks), and Cdk inhibitors (CdkIs) are frequently altered in human cancer. p18INK4C, a member of the INK4 family of CdkIs, is a potential tumor-suppressor gene product. However, the expression of p18INK4C in hepatocellular carcinoma (HCC) remains unknown.

CD28-negative CD8-positive cytotoxic T lymphocytes mediate hepatocellular damage in hepatitis C virus infection.

The pathogenic mechanism for hepatocellular damage in hepatitis C virus (HCV) infection has not been clearly understood. Analysis of costimulatory molecules on lymphocytes may give us insight into the pathogenic mechanism of hepatocellular damage in HCV infection. Peripheral blood mononuclear cells (PBMCs) and liver infiltrating mononuclear cells (LIMCs) isolated from the HCV-infected patients were analyzed with antibodies directed against a variety of costimulatory molecules by flow cytometry.

Combination therapy of percutaneous ethanol injection and radiofrequency ablation against hepatocellular carcinomas difficult to treat.

Radiofrequency ablation (RFA) is an effective modality for the treatment of hepatocellular carcinoma (HCC), because it can induce large coagulated necrosis in a few sessions. We have recently reported that the combination therapy of percutaneous ethanol injection (PEI) with RFA (PEI-RFA) created enhancement of coagulated necrosis compared with RFA alone. In the present study, we adopted PEI-RFA for the treatment of HCCs located in the regions that are difficult to treat with RFA alone.

Enhanced expression of Bcl-2 in lymphocytes infiltrating into the liver of patients with primary biliary cirrhosis.

The Bcl-2 family proteins are important regulators of apoptosis and have been implicated in the occurrence of autoimmune diseases. There have been reports that Bcl-2-positive lymphocytes play important roles in pathogenesis of at least some types of autoimmune diseases, including autoimmune hepatitis. In this study, we examined the role of Bcl-2-positive lymphocytes in the development of primary biliary cirrhosis (PBC).