Gotaro Toda

The Jikei University School of Medicine, Edo, Tōkyō, Japan

Are you Gotaro Toda?

Claim your profile

Publications (282)757.26 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the efficacy of percutaneous radiofrequency ablation (RFA) using flat-panel detector angiographic CT (FACT) for hepatocellular carcinoma (HCC), we performed RFA using FACT for 23 HCC lesions in 16 patients. After transcatheter arterial chemoembolization or infusion chemotherapy using miriplatin as a sustained-release suspension in iodized oil and/or gelatin sponge, we performed RFA. RFA needle was inserted into the target lesion under US guide. Using FACT, we could confirm whether the needle tip inserted at the target assuming enough coagulative necrosis area from all angles in all lesions. Enough ablative margins could be obtained in all lesions. No serious adverse events were observed. RFA using FACT contributed more accurate insertion for HCC. Therefore, FACT would be a more useful tool for RFA.
    Kanzo 01/2013; 54(1):87-91. DOI:10.2957/kanzo.54.87
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Rapid virological response (RVR) is very important in achieving sustained virological response (SVR) to triple therapy with peginterferon alfa-2b, ribavirin and telaprevir for chronic hepatitis C. To analyze baseline factors associated with RVR, 128 Japanese patients infected with hepatitis C virus (HCV) genotype1b were subjected to this study. By univariate analysis, prior treatment response (naïve or relapse), high platelet count, low AST level, low viral load contributed significantly to RVR. By multivariate analysis, prior treatment (naïve or relapse) and low viral load were significant independent factors. Further investigation is required to clarify whether these factors may contribute to SVR and develop novel individualized treatment algorithm.
    Kanzo 01/2012; 53(10):627-632. DOI:10.2957/kanzo.53.627
  • [Show abstract] [Hide abstract]
    ABSTRACT: The safety and efficacy of treatment with ursodeoxycholic acid (UDCA) of the patients with primary biliary cirrhosis (PBC) were investigated by following 1462 and 1327 patients, respectively, for 3 to 5 years after the start of treatment. No serious adverse events related to UDCA treatment occurred in the patients investigated and the start of treatment induced the significant fall of serum alkaline phosphatase (Al-P), γGTP, AST, ALT and total bilirubin concentration (T-Bil), which was sustained throughout the investigation period, indicating that the prolonged UDCA treatment was safe and effective in the improvement of liver function tests. In the final visit, however, little or no improvement of Al-P, γGTP, AST, ALT and T-Bil was noticed in some of the patients treated. The stratification of the patients according to the daily dose of UDCA revealed that in each of the liver function tests, the frequency of those who showed little or no improvement decreased with the increase in the dose, suggesting that the increase in the dose improved the liver function tests in these patients. Twenty three patients died of liver-related causes or received liver transplantation. Multivariate Cox regression analysis indicated that the base line T-Bil greater than 1.2 mg/dl, advanced histological stage and decrease less than 30% of base line level in T-Bil or AST at 6 months after the start of treatment were the predictors for liver-related death or liver transplantation. The response of T-Bil or AST to UDCA treatment is useful to identify the patients who need additional treatment for improvement of prognosis.
    Kanzo 01/2011; 52(9):584-601. DOI:10.2957/kanzo.52.584
  • Naoaki Hashimoto · Yusei Ikeda · Gotaro Toda ·

    Nippon rinsho. Japanese journal of clinical medicine 06/2010; 68 Suppl 6:697-700.

  • Nippon rinsho. Japanese journal of clinical medicine 06/2010; 68 Suppl 6:717-20.

  • 01/2010; 76(2):78-79. DOI:10.11641/pde.76.2_78

  • 01/2010; 76(2):104-105. DOI:10.11641/pde.76.2_104
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated the early virological response (EVR) to peginterferon (Peg-IFN) α-2a plus ribavirin (RBV) and Peg-IFNα-2b plus RBV therapy in 125 Japanese patients infected with hepatitis C virus (HCV) genotype 1b. The rate of EVR, defined as HCV-RNA undetectable by COBAS TaqMan HCV test at 12 weeks after the start of treatment, was not significantly different between Peg-IFNα-2a plus RBV therapy and Peg-IFNα-2b plus RBV therapy (50.0% vs. 52.4%). However, the effect of previous interferon therapy did not influence the EVR rate in both groups. Multiple regression analysis showed that only serum albumin concentration (>4.1 g/dL) was a factor to contribute EVR. Further investigation is necessary, to compare the SVR rate, adverse events, and those in extended combination therapy between the two groups.
    Kanzo 01/2009; 50(10):584-587. DOI:10.2957/kanzo.50.584
  • [Show abstract] [Hide abstract]
    ABSTRACT: We investigated "Response-guided therapy" 48 weeks vs. 72 weeks in 250 Japanese chronic hepatitis C patients infected with genotype 1b and high viral load to peginterferon (Peg-IFN) α-2b plus ribavirin (RBV). SVR rate was 100% of patients with RVR. Although patients with cEVR did not significantly improve SVR rate with extended treatment to 72 weeks, patients with pEVR were significantly improved with extended treatment (8.0% vs. 59.6%, p<0.0001). In patients with non-RVR except for NVR, extended treatment to 72 weeks significantly improved SVR rate compared with 48-week treatment (57.8% vs. 72.4%, p = 0.0413). Multivariate analysis identified low-density lipoprotein cholesterol (≥86 mg/dL), total dose of RBV per body weight (≥3 g/kg), cEVR, periods to the intial HCV-RNA negative to 20 weeks as significant determinants of SVR. When non-RVR cases with HCV-RNA reduction during 0-4 weeks less than 2 Log 10 IU/mL and that achieved LVR, total dose of RBV per body weight more than 3 g/kg and extended treatment to 72 weeks may increase SVR rate. Response-guided therapy is useful strategy in the treatment for chronic hepatitis C with genotype 1b and high viral load.
    Kanzo 01/2009; 50(12):687-702. DOI:10.2957/kanzo.50.687
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Aim: Treatment with ursodeoxycholic acid (UDCA) improves the survival of stage I and II primary biliary cirrhosis (PBC) patients. However, new therapeutic options are needed for patients who are refractory to UDCA and for those whose disease is at an advanced stage. Bezafibrate could be useful in PBC treatment, since it increases phospholipid output into the bile and reduces the cytotoxicity of hydrophobic bile acids, which are increased with cholestasis. Methods: We conducted two prospective, multicenter randomized open studies in non-cirrhotic patients with PBC to evaluate the efficacy of bezafibrate. One study compared UDCA and bezafibrate monotherapy (study 1: 45 patients [37 females], mean age 55.9 years), and the other evaluated the addition of bezafibrate to patients who were refractory to UDCA (study 2: 21 patients [18 females], mean age 54.1 years). Results: Study 1 demonstrated that bezafibrate monotherapy was as effective as UDCA and study 2 revealed that bezafibrate combined with UDCA was effective in improving and maintaining biliary enzymes where the ineffectiveness of long-term treatment with UDCA was confirmed. Conclusion: This multicenter, randomized, open study revealed that combination therapy of bezafibrate and UDCA improved biliary enzymes in non-cirrhotic Japanese patients with PBC refractory to UDCA. Further studies are needed to evaluate whether combination therapy improves histological staging and prognosis.
    Hepatology Research 04/2008; 38(6):557 - 564. DOI:10.1111/j.1872-034X.2007.00305.x · 2.74 Impact Factor

  • Gastroenterology 04/2008; 134(4). DOI:10.1016/S0016-5085(08)62633-5 · 16.72 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We performed a national survey in 2003, and demonstrated characteristic features of primary sclerosing cholangitis (PSC) patients in Japan. In this study, we aimed to clarify the outcome and prognostic factors of Japanese PSC patients. Questionnaires were sent to gastroenterologists in Japan, and 391 patients with PSC were registered and enrolled in the current study. The median follow-up was 5.3 years (range 0.1-20.8 years). The cumulative incidence for survival was analysed using the Kaplan-Meier method. Univariate and multivariate analyses were performed using the Cox-proportional hazards regression model for determining prognostic variables. The estimated median survival of all patients was 13.1 years, with a 5-year survival rate of 74.5%. Thirty-eight patients (9.7%) who underwent liver transplantation (LT) had a 5-year survival rate of 92.0%. Both univariate and multivariate analysis demonstrated that younger age [below 49 years old; odds ratio (OR)=1.76, 1.12-2.76, P=0.0136] and lower total bilirubin (below 3.0 mg/dl; OR=2.50, 1.60-3.89, P<or=0.0001) were independent prognostic factors for LT-free survival of PSC patients in Japan. Cholangiocarcinoma (CCA) was found in 14 (3.6%) patients, and only two out of 125 PSC patients exhibited a history of inflammatory bowel diseases. Although several characteristic features existed, the outcome as well as prognostic factors of Japanese PSC patients appeared to be similar to those from the United States and European countries. In contrast, the incidence of CCA in PSC appeared to be lower in Japan.
    Liver international: official journal of the International Association for the Study of the Liver 04/2008; 28(7):983-9. DOI:10.1111/j.1478-3231.2008.01726.x · 4.85 Impact Factor
    [Show abstract] [Hide abstract]
    ABSTRACT: The occurrence of antibodies to interferon-α2a (anti-IFN-α2a) to recombinant human IFN-α2a was examined in chronic liver disease by a sensitive enzyme-linked immunosorbent assay (ELISA). Naturally occurring IgG and/or IgM anti-IFN-α2a were found in one of 12 cases of chronic persistent hepatitis, four of 18 cases of chronic active hepatitis (CAH), two of 12 cases of liver cirrhosis, six of seven cases of primary biliary cirrhosis, nine of 11 cases of auto-immune CAH and none of 21 normal control subjects. Fifteen patients with viral CAH were treated with recombinant IFN-α2a. Two of them were positive prior to receipt of IFN-α2a and their titres increased after the therapy. Two patients became positive for anti-IFN-α2a after the therapy. Absorption experiments revealed that anti-IFN-α2a cross-reacted with native human leucocyte IFN-α and recombinant IFN-α2b but not with recombinant IFN-β and -γ. The immunoblotting experiment confirmed the binding of antibodies to IFN. The results of anti-IFN-α2a obtained by antiviral, cytopathic effect assay were in good agreement with those of IgG anti-IFN-α2a, but not with those of IgM antibodies obtained by the ELISA. The ELISA described in the present study is a simple, sensitive and quantitative assay for anti-IFN-α2a. It should be useful in assessing sub-specificities of anti-IFN and provide valuable information to predict the effect of IFN therapy and to elucidate the immunological abnormality in liver disease.
    Journal of Gastroenterology and Hepatology 03/2008; 4(5):411 - 418. DOI:10.1111/j.1440-1746.1989.tb01738.x · 3.50 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Combined pegylated interferon and ribavirin has improved chronic hepatitis C (CH-C) therapy; however, sustained virological response is achieved in only about half of the patients with a 1b genotype infection. We assessed oral ursodeoxycholic acid (UDCA) on serum biomarkers as a possible treatment for interferon non-responders. CH-C patients with elevated alanine aminotransferase (ALT) were assigned randomly to 150 (n = 199), 600 (n = 200) or 900 mg/day (n = 197) UDCA intake for 24 weeks. Changes in ALT, aspartate aminotransferase (AST) and gamma-glutamyl transpeptidase (GGT) were assessed. This study is registered at, identifier NCT00200343. ALT, AST and GGT decreased at week 4 and then remained constant during drug administration. The median changes (150, 600 and 900 mg/day, respectively) were: ALT, -15.3, -29.2 and -36.2%; AST, -13.6, -25.0 and -29.8%; GGT, -22.4, -41.0 and -50.0%. These biomarkers decreased significantly less in the 150 mg/day than in the other two groups. Although changes in ALT and AST did not differ between the 600 and 900 mg/day groups, GGT was significantly lower in the 900 mg/day group. In subgroup analysis, ALT decreased significantly in the 900 mg/day group when the baseline GGT exceeded 80 IU/l. Serum HCV-RNA did not change in any group. Adverse effects were reported by 19.1% of the patients, with no differences between groups. A 600 mg/day UDCA dose was optimal to decrease ALT and AST levels in CH-C patients. The 900 mg/day dose decreased GGT levels further, and may be preferable in patients with prevailing biliary injuries.
    Gut 01/2008; 56(12):1747-53. DOI:10.1136/gut.2007.120956 · 14.66 Impact Factor

  • Kanzo 01/2008; 49(12):537-548. DOI:10.2957/kanzo.49.537
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Interleukin-12 (IL-12), a cytokine with antitumor activity, was examined for the suppressive effect on hepatocellular carcinoma (HCC) in mouse model, and its mechanism of antitumor activity was analyzed. Mice implanted with MIH-2 HCC cells were treated with recombinant mouse IL-12 (500 ng/mouse). Involvement of CD4(+), CD8(+), NK cells and interferon (IFN)-gamma on tumor suppression by IL-12 was examined by treatment of mice with each antibody. Interferon-gamma (IFN-gamma) production by tumor infiltrating cells was analyzed by immunofluorescence microscopy and flow cytometric analysis. Signal transduction for apoptosis induction was examined by immunoblot analysis. The growth of implanted MIH-2 tumors was significantly suppressed by IL-12 and the suppression was inhibited by depletion of CD8(+)T cells. IL-12 treatment caused numerous IFN-gamma-producing CD8(+)T cells to infiltrate into MIH-2 tumors. Antitumor activity of IL-12 was blocked by treating mice with anti-IFN-gamma mAb. CD8(+)T cells from IL-12-treated mice attached to MIH-2 cells and produced IFN-gamma in vitro. Cell attachment might be associated with intercellular adhesion molecule-1 induced by IFN-gamma. In vitro treatment with IFN-gamma induced apoptosis of MIH-2 cells via a mitochondria-dependent pathway. IL-12 suppressed HCC growth in mouse model. IFN-gamma produced by IL-12-activated tumor-infiltrating CD8(+)T cells directly induced apoptosis of HCC cells.
    Journal of Hepatology 12/2006; 45(5):662-72. DOI:10.1016/j.jhep.2006.05.018 · 11.34 Impact Factor
  • Source
    S Homma · Y Sagawa · M Ito · T Ohno · G Toda ·
    [Show abstract] [Hide abstract]
    ABSTRACT: Dendritic cell (DC) vaccines might induce both anti-tumour immunity and autoimmunity. In this report, we demonstrate elevated levels of anti-nuclear antibody (ANA) in the sera of patients with cancer who had received immunotherapy with a dendritic/tumour-fusion vaccine. Twenty-two patients were treated with DC vaccine of fusion cells composed of autologous DCs and tumour cells (DC/tumour-fusion vaccine), which was generated by treating each cell type with polyethylene glycol. Nine of the 22 patients were treated with both the DC/tumour-fusion vaccine and systemic administration of recombinant human interleukin (rhIL)-12. Serum levels of ANA were examined with an enzyme-linked immunosorbent assay kit. One patient with gastric carcinoma (patient 1, DC/tumour-fusion vaccine alone), one patient with breast cancer (patient 2, DC/tumour-fusion vaccine alone) and one patient with ovarian cancer (patient 3, DC/tumour-fusion vaccine + rhIL-12) showed significant elevations of serum ANA levels during treatment. In patient 1 malignant ascitic effusion resolved and serum levels of tumour markers decreased. Patients 2 and 3 remained in good physical condition during treatment for 24 and 9 months, respectively. Immunoblot analysis indicated antibody responses to autologous tumour cells after vaccination in patient 2. None of the treated patients showed clinical symptoms suggesting autoimmune disease. Patients with elevated serum levels of ANA had significantly longer treatment periods than those without it. Elevated serum levels of ANA after DC/tumour-fusion cell vaccine might be associated with anti-tumour immune response induced by the vaccination.
    Clinical & Experimental Immunology 05/2006; 144(1):41-7. DOI:10.1111/j.1365-2249.2006.03029.x · 3.04 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The liver enzymes, alcohol dehydrogenase (ADH) and aldehyde de-hydrogenase (ALDH), which are responsible for the oxidative metabolism of ethanol, are polymorphic in humans. Cytochrome P450IIE1, an ethanol-inducible isozyme of liver microsomal P450, is also important in ethanol metabolism. Genetic polymorphisms in the 5′-flanking region of the human cytochrome P450IIE1 gene have recently been reported. We hypothesized that the polymorphisms of ADH, ALDH, and P450IIE1 modify the susceptibility to development of alcoholism. We determined the genotypes of the ADH2, ALDH2, and P450IIE1 loci of 96 Japanese alcoholics and 60 healthy male subjects, using leukocyte DNA by the restriction fragment-length polymorphism by polymerase chain reaction. The alcoholics had significantly higher frequencies of the ADH21 and ALDH21 alleles than did the healthy subjects. No significant difference in the frequency of the P45011E1 genotype was observed between the alcoholics and the healthy subjects. In conclusion, genetic polymorphisms of the ADH and ALDH genes, but not of the P45011E1 gene, influence the risk of developing alcoholism in Japanese.
    Alcoholism Clinical and Experimental Research 04/2006; 19(4):951 - 954. DOI:10.1111/j.1530-0277.1995.tb00972.x · 3.21 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Alcohol abuse can induce brain atrophy, but it only occurs in some alcoholics. Many inflammatory cytokines such as tumor necrosis factor (TNF) are produced rapidly in the brain by experimental or clinical injury.Method: To investigate whether genetic polymorphism of TNF was related to alcoholic brain atrophy, we determined restriction fragment-length polymorphisms of the TNF-β genes in 72 male alcoholics. Computed tomography was used to determine the severity of brain atrophy.Results: Digestion with Nco I and Msp I after polymerase chain reaction amplification showed that the TNFB1 allele frequency was significantly higher in patients with brain atrophy than in those without brain atrophy (χ2= 10.20, p= 0.0034). A multivariate analysis that included age, total alcohol intake, ADH2 genotype, and TNF-β genotype showed that the ADH21/21 genotype and TNFB1/B1 genotype are independently associated with alcoholic brain atrophy. These findings suggest that the TNFB1 allele may be associated with alcoholic brain atrophy.
    Alcoholism Clinical and Experimental Research 04/2006; 25(s2):7S - 10S. DOI:10.1111/j.1530-0277.2001.tb02409.x · 3.21 Impact Factor
  • Fumio Sakauchi · Mitsuru Mori · Mikio Zeniya · Gotaro Toda ·
    [Show abstract] [Hide abstract]
    ABSTRACT: We examined patients who showed laboratory and histological evidence of primary biliary cirrhosis (PBC) in the absence of antimitochondrial antibody (AMA) to elucidate the characteristics of AMA negative PBC. From a total of 5,805 patients with symptomatic PBC, 2,419 cases (41.7%) were selected in the present study, who were diagnosed using the following criterion; chronic non-suppurative destructive cholangitis was histologically observed and laboratory data did not contradict PBC. The information collected from records included sex, age, symptoms, physical findings, and complicated autoimmune diseases. We then evaluated these data according to the positivity of AMA. Of the total subjects, 470 cases (19.4%) were found to be negative for AMA. The proportion of female patients was higher among the AMA negative group than among the AMA positive one. Pruritus was found less frequently among patients with AMA negative PBC than among those with AMA positive PBC. Levels of alkaline phosphatase,gamma-glutamyl transpeptidase, and IgM were significantly lower among patients with AMA negative PBC than among those with AMA positive PBC. Complications such as Sjögren's syndrome, rheumatoid arthritis, and scleroderma, including CREST syndrome, were found with significantly higher frequency among patients with AMA negative PBC than among those with AMA positive PBC. Considering serum level of IgM and frequencies of complicated autoimmune diseases, it is possible that Japanese patients with AMA negative PBC are consistent with the disease entity of autoimmune cholangitis reported in western countries.
    Journal of Epidemiology 02/2006; 16(1):30-4. DOI:10.2188/jea.16.30 · 3.02 Impact Factor

Publication Stats

4k Citations
757.26 Total Impact Points


  • 1993-2008
    • The Jikei University School of Medicine
      • • Division of Gastroenterology and Hepatology
      • • Institute of DNA Medicine
      • • Department of Internal Medicine
      Edo, Tōkyō, Japan
  • 1975-2008
    • The University of Tokyo
      • • Division of Internal Medicine
      • • School of Medicine
      Edo, Tōkyō, Japan
  • 2001-2004
    • Kashiwa City Hospital
      Kashiwa, Chiba, Japan
    • Musashino Red Cross Hospital
      Edo, Tōkyō, Japan
  • 1999
    • ICL
      Londinium, England, United Kingdom
  • 1997
    • Toyama Medical and Pharmaceutical University
      Тояма, Toyama, Japan
  • 1992
    • Nagai Internal Medicine Clinic
      Okayama, Okayama, Japan
  • 1991
    • Teikyo University
      • Department of Internal Medicine
      Edo, Tōkyō, Japan