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ABSTRACT: Objectives: To investigate the usefulness of the ultrasonography (US) fusion imaging system for radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: Since the US fusion imaging system became available in 2010, we have conducted RFA with this system in all cases. The characteristics of 75 patients with 120 HCCs and 89 patients with 123 HCCs who underwent RFA before the introduction of this system (period A) and after it (period B), respectively, were retrospectively compared. Results: Significant difference in the characteristics of the patients and HCCs between the two periods was found only in the proportion of HCCs with poor conspicuity on grayscale US treated with RFA (1.7%, 2/120 for period A vs. 15.4%, 19/123 for period B, p < 0.01). Among the 19 HCCs with poor conspicuity on grayscale US for period B, 5 and 9 HCCs were identified on grayscale US and contrast-enhanced US, respectively, by the use of the US fusion imaging system, whereas the 5 remaining undetectable HCCs were treated by using the system in conjunction with reference images displayed side-by-side with grayscale US. Conclusion: Since the introduction of the US fusion imaging system, it has become possible to perform RFA for HCCs with poor conspicuity on grayscale US.
Oncology 01/2013; 84 Suppl 1:44-50. · 2.27 Impact Factor
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Yuki Makino,
Yasuharu Imai, Takumi Igura,
Masatoshi Hori,
Kazuto Fukuda,
Yoshiyuki Sawai,
Sachiyo Kogita,
Hideko Ohama,
Yasushi Matsumoto,
Masanori Nakahara,
Shinichiro Zushi,
Masanori Kurokawa,
Keisuke Isotani,
Manabu Takamura,
Norihiko Fujita,
Takamichi Murakami
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ABSTRACT: AIM: To demonstrate the usefulness of the computed tomography (CT) fusion imaging for the evaluation of treatment effect of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). METHODS: Eighty-five patients with 94 HCC with complete ablation judged on conventional side-by-side interpretation of pre-RFA and post-RFA CT at the time of RFA were included in this retrospective study. CT data was retrospectively used to create fusion images of pre-RFA and post-RFA CT using automatic rigid registration and manual correction referring to intrahepatic structures and hepatic contours around a tumor. Clinical factors including a minimal ablative margin (MAM) measured on fusion images were examined to prove risk factors for local tumor progression (LTP). RESULTS: LTP was observed in 13 (13.8%) tumors with a median follow up of 21.0 months (range, 2-75). The mean MAM on the fusion image was 1.4 ± 3.1 mm and 23 tumors (24.5%) were judged to be protruding from the ablation zone. Multivariate analysis revealed that protruding from the ablation zone was the only significant factor for LTP (hazard ratio, 7.09; 95% confidential interval, 2.26-22.3; P < 0.001). CONCLUSION: Some HCC were assessed as incomplete ablation on the CT fusion images, although considered completely ablated on side-by-side images at the time of treatment, and incomplete ablation was revealed to be the only independent risk factor for LTP. The CT fusion imaging enables quantitative and accurate evaluation of treatment effect of RFA.
Hepatology Research 12/2012; · 2.20 Impact Factor
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Yuki Makino, Takumi Igura,
Yasuharu Imai,
Kazuto Fukuda,
Yoshiyuki Sawai,
Sachiyo Kogita,
Naoto Uenoyama,
Yoshinori Doi,
Shinichi Kiso,
Naoki Hiramatsu,
Shinji Tamura,
Norio Hayashi,
Tetsuo Takehara
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ABSTRACT: A 30-year-old man was admitted to Osaka University Hospital for the treatment of gastric varices and assessment of indication for liver transplant. When he was 6 years old, liver dysfunction was pointed out and diagnosed as chronic inactive hepatitis by liver biopsy. At 13 years of age, the second liver biopsy proved congenital hepatic fibrosis (CHF). The third liver biopsy was performed when he was 30 years old, and the progression of hepatic fibrosis was confirmed. Besides CHF, we recognized oligophrenia, cerebellar ataxia, hypoplasia of cerebellar vermis and coloboma, leading to the diagnosis of COACH syndrome. COACH syndrome is quite rare, and our case is especially valuable because he was diagnosed as an adult case and the progression of hepatic fibrosis could be followed through several liver biopsies. We should be aware of COACH syndrome in mind when we encounter CHF patients.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2012; 109(7):1223-9.
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ABSTRACT: A multimodality fusion imaging system has been introduced for the clinical practice of diagnosis and treatment of hepatocellular carcinoma (HCC), especially for loco-regional treatment. An ultrasonography (US) fusion imaging system can provide a side-by-side display of real-time US images and any cross-sectional images of multiplanar reconstruction of CT or MRI that synchronize real-time US. The US fusion imaging system enables us to perform radiofrequency ablation (RFA) for HCCs difficult to detect on conventional US safely. Besides, we can evaluate the treatment effects of RFA easily at the bedside by combining the contrast-enhanced US and the US fusion imaging system. Fusion images of pre- and post-RFA CT have been utilized for the assessment of the treatment effects of RFA. Although the treatment effects of RFA have been conventionally evaluated, comparing pre- and post-RFA CT side-by-side, the evaluation tends to be inaccurate. On CT fusion images, the tumor and the ablation zone are overlaid and we can grasp the positional relation easily, leading to quantitative and more accurate evaluation. The multimodality fusion imaging system has become quite an important tool for loco-regional treatment of HCC because of its usefulness for both the guidance during the RFA procedure and the evaluation of its treatment effects.
Digestive Diseases 01/2012; 30(6):580-7. · 2.37 Impact Factor
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Nihon Naika Gakkai Zasshi 06/2011; 100(6):1657-9.
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ABSTRACT: We report a case of an intrapancreatic accessory spleen in 59-year-old man, in which contrast-enhanced sonography (US) using Sonazoid, a second-generation contrast agent, was useful for the diagnosis. Sonazoid-enhanced US could prove both hypervascularity and the existence of reticuloendothelial cell systems in the mass, which is the key to the diagnosis of an accessory spleen. Sonazoid-enhanced US might become a standard imaging technique for the diagnosis of an accessory spleen.
Journal of Clinical Ultrasound 03/2011; 39(6):344-7. · 0.81 Impact Factor
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Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 01/2011; 108(6):916-27.
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Sachiyo Kogita,
Yasuharu Imai,
Masahiro Okada,
Tonsok Kim,
Hiromitsu Onishi,
Manabu Takamura,
Kazuto Fukuda, Takumi Igura,
Yoshiyuki Sawai,
Osakuni Morimoto,
Masatoshi Hori,
Hiroaki Nagano,
Kenichi Wakasa,
Norio Hayashi,
Takamichi Murakami
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ABSTRACT: To retrospectively investigate enhancement patterns of hepatocellular carcinoma (HCC) and dysplastic nodule (DN) in the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced MRI in relation to histological grading and portal blood flow.
Sixty-nine consecutive patients with 83 histologically proven HCCs and DNs were studied. To assess Gd-EOB-DTPA uptake, we calculated the EOB enhancement ratio, which is the ratio of the relative intensity of tumorous lesion to surrounding nontumorous area on hepatobiliary phase images (post-contrast EOB ratio) to that on unenhanced images (pre-contrast EOB ratio). Portal blood flow was evaluated by CT during arterial portography.
Post-contrast EOB ratios significantly decreased as the degree of differentiation declined in DNs (1.00 ± 0.14) and well, moderately and poorly differentiated HCCs (0.79 ± 0.19, 0.60 ± 0.27, 0.49 ± 0.10 respectively). Gd-EOB-DTPA uptake, assessed by EOB enhancement ratios, deceased slightly in DNs and still more in HCCs, while there was no statistical difference in the decrease between different histological grades of HCC. Reductions in portal blood flow were observed less frequently than decreases in Gd-EOB-DTPA uptake in DNs and well-differentiated HCCs.
Reduced Gd-EOB-DTPA uptake might be an early event of hepatocarcinogenesis, preceding portal blood flow reduction. The hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI may help estimate histological grading, although difficulties exist in differentiating HCCs from DNs.
European Radiology 10/2010; 20(10):2405-13. · 3.22 Impact Factor
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Juichi Fukushima,
Yoshihiro Kamada,
Hitoshi Matsumoto,
Yuichi Yoshida,
Hisao Ezaki,
Takayo Takemura,
Yukiko Saji, Takumi Igura,
Shusaku Tsutsui,
Shinji Kihara,
Tohru Funahashi,
Iichiro Shimomura,
Shinji Tamura,
Shinichi Kiso,
Norio Hayashi
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ABSTRACT: Aim: We reported previously that hypoadiponectinemia enhances hepatic oxidative stress and accelerates progression of nonalcoholic steatohepatitis (NASH) in mice. However, the precise mechanism and preventive effects of adiponectin on NASH remain unclear. The aim of this study was to examine the effects of adiponectin on steatohepatitis using adiponectin-knockout (KO) mice and adenovirus-mediated adiponectin expression system. Methods: We used male KO mice and C57BL6/J (WT) mice fed methionine choline-deficient (MCD)-diet as a steatohepatitis model. Liver histology, hepatic oxidative stress markers, and hepatic gene expression levels were investigated. In addition, Hepa 1-6 cells, a mouse liver cell line, were cultured with or without recombinant adiponectin, and gene expressions were investigated by real-time RT-PCR. Results: After 2-week feeding of MCD diet, hepatic steatosis was enhanced and plasma alanine aminotransferase elevated in KO mice than in WT mice. In KO mice liver, thiobarbituric acid reactive substances increased, glutathione levels decreased, and mRNA expression levels of antioxidant enzymes (catalase, superoxide dismutase-1) downregulated. Adenovirus-mediated adiponectin expression prevented these changes in KO mice. Moreover, Kupffer cell infiltration was enhanced and mRNA levels of anti-inflammatory M2 macrophage markers (interleukin-10, arginase-1) were decreased in KO mice liver. In the in vitro study, adiponectin significantly increased catalase gene expression in Hepa 1-6 cells. Conclusions: Lack of adiponectin enhanced, and adiponectin administration prevented steatohepatitis progression in mice. These changes were due to the anti-oxidative effects of adiponectin, and its effects on Kupffer cells recruitment and phenotype polarization. Augmentation of adiponectin effects could be a useful preventive approach for NASH progression.
Hepatology Research 04/2009; 39(7):724-38. · 2.20 Impact Factor
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Mika Kurokawa,
Naoki Hiramatsu,
Tsugiko Oze,
Kiyoshi Mochizuki,
Takayuki Yakushijin,
Nao Kurashige,
Yuko Inoue, Takumi Igura,
Kazuho Imanaka,
Akira Yamada, [......],
Taizo Hijioka,
Harumasa Yoshihara,
Atsuo Inoue,
Yasuharu Imai,
Michio Kato,
Shinichi Kiso,
Tatsuya Kanto,
Tetsuo Takehara,
Akinori Kasahara,
Norio Hayashi
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ABSTRACT: Aim: The objective of this study was to elucidate the long-term effects of interferon (IFN)alpha-2b plus ribavirin combination therapy and to clarify whether this therapy can reduce the incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C. Methods: A total of 403 patients infected with hepatitis C virus (HCV) were enrolled in a multicenter trial. All patients were treated with a combination of IFN-alpha-2b plus ribavirin therapy. We examined the incidence of HCC after combination therapy and analyzed the risk factors for liver carcinogenesis. Results: A sustained virological response (SVR) was achieved by 139 (34%) of the patients. The cumulative rate of incidence of HCC was significantly lower in SVR patients than in non-SVR patients (P = 0.03), while there was no difference in the cumulative incidence of HCC between the transient response (TR) group and the no response (NR) group. Cox's regression analysis indicated the following risk factors as independently significant in relation to the development of HCC: age being > 60 years (P = 0.006), advanced histological staging (P = 0.033), non-SVR to IFN therapy (P = 0.044). The cumulative incidence rate of HCC was significantly lower in patients who had average serum alanine aminotransferase (ALT) levels of < 40 IU/L than in those who showed average serum ALT levels of >== 40 IU/L after the combination therapy (P = 0.021). Conclusions: These results suggest that the attainment of SVR or continuous normalization of ALT levels after IFN therapy can affect patients apart from HCC development.
Hepatology Research 01/2009; 39(5):432-8. · 2.20 Impact Factor
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Hisao Ezaki,
Yuichi Yoshida,
Yukiko Saji,
Takayo Takemura,
Juichi Fukushima,
Hitoshi Matsumoto,
Yoshihiro Kamada,
Akira Wada, Takumi Igura,
Shinji Kihara,
Tohru Funahashi,
Iichiro Shimomura,
Shinji Tamura,
Shinichi Kiso,
Norio Hayashi
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ABSTRACT: We previously demonstrated that adiponectin has anti-fibrogenic and anti-inflammatory effects in the liver of mouse models of various liver diseases. However, its role in liver regeneration remains unclear. The aim of this study was to determine the role of adiponectin in liver regeneration. We assessed liver regeneration after partial hepatectomy in wild-type (WT) and adiponectin knockout (KO) mice. We analyzed DNA replication and various signaling pathways involved in cell proliferation and metabolism. Adiponectin KO mice exhibited delayed DNA replication and increased lipid accumulation in the regenerating liver. The expression levels of peroxisome proliferator-activated receptor (PPAR) alpha and carnitine palmitoyltransferase-1 (CPT-1), a key enzyme in mitochondrial fatty acid oxidation, were decreased in adiponectin KO mice, suggesting possible contribution of altered fat metabolism to these phenomena. Collectively, the present results highlight a new role for adiponectin in the process of liver regeneration.
Biochemical and Biophysical Research Communications 12/2008; 378(1):68-72. · 2.48 Impact Factor
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ABSTRACT: A 40's-year-old woman who had abdominal pain with fever was referred to our hospital for further examinations. Abdominal computed tomography showed no focal lesion, and no causative lesion was found after a gynecological examination, upper gastrointestinal endoscopy and colonoscopy. Tuberculin test and QuantiFERON-TB were positive, and thus tuberculous peritonitis was suspected. The level of adenosine deaminase (ADA) in ascites was high, and (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET) showed that FDG accumulated diffusely along the peritoneum. These findings supported the findings of tuberculous peritonitis. Final diagnosis of tuberculous peritonitis was done from laparoscopic biopsy. Combination of QuantiFERON-TB, ADA and FDG-PET was useful in diagnosing tuberculous peritonitis.
Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 11/2008; 105(10):1515-22.
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ABSTRACT: The N-glycan structures of the Lens culinaris agglutinin (LCA)-reactive fraction of alpha-fetoprotein (AFP-L3), a tumor marker of hepatocellular carcinomas (HCC), were analyzed in relationship to glycosyltransferases and LCA-affinity electrophoresis. Using HPLC and MALDI-TOF MS, we determined the N-glycan structures of AFP from HCC cell lines, and demonstrated they were affected by N-acetylglucosaminyltransferase III and fucosyltransferase VIII, but not by N-acetylglucosaminyltransferase V. Moreover, we identified the N-glycan structures of AFP in HCC patients.
Journal of Proteome Research 07/2008; 7(6):2222-33. · 5.11 Impact Factor
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Nao Kurashige,
Naoki Hiramatsu,
Kazuyoshi Ohkawa,
Tsugiko Oze,
Yuko Inoue,
Mika Kurokawa,
Takayuki Yakushijin, Takumi Igura,
Shinichi Kiso,
Tatsuya Kanto, [......],
Shinji Tamura,
Akinori Kasahara,
Masahide Oshita,
Taizo Hijioka,
Kazuhiro Katayama,
Harumasa Yoshihara,
Eijirou Hayashi,
Yasuharu Imai,
Michio Kato,
Norio Hayashi
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ABSTRACT: Aim: Lamivudine (LAM) has been widely used to treat chronic hepatitis B (CHB) patients, but the emergence of a LAM-resistant virus greatly limits its therapeutic efficacy. In this study, we tried to identify factors affecting the emergence of a LAM-resistant virus in CHB patients treated with LAM. Methods: The subjects were 190 CHB patients in continuous LAM therapy (139 males, mean age 50 years, 87 HBeAg-positive). The mean duration of follow-up was 39 months (range 12-104). The initial viral response (IVR) was defined as HBV DNA < 4.0 logcopies/mL, and the initial biochemical response (IBR) as normalization of alanine aminotransferase (ALT) (<40 IU/L) at 6 months. Results: IVR was positive in 86% of the patients. The cumulative emergence rates of LAM-resistant virus were 10% at 1 year, 30% at 2 years and 46% at 3 years. In univariate analysis, factors contributing to the emergence of LAM-resistant virus were baseline HBV DNA > 6.5 logcopies/mL (P = 0.0044), HBeAg-positivity (P = 0.0062), IBR (P = 0.01) and IVR (P < 0.0001). The cumulative emergence rates of LAM-resistant virus in IVR-positive and -negative patients were 4% and 41% at 1 year, and 41% and 79% at 3 years. In multivariate analysis, only IVR was an independent factor affecting the emergence of LAM-resistant virus (P < 0.0001). Conclusion: IVR is a useful factor for predicting the emergence of LAM-resistant virus in CHB patients treated with LAM. For IVR-negative patients, therapeutic options other than LAM monotherapy should be used because of the high incidence of the emergence of LAM-resistant virus.
Hepatology Research 05/2008; 38(5):450-6. · 2.20 Impact Factor
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ABSTRACT: Aim: The Rab subfamily plays a role in intracellular transport. Rab5a is, in particular, involved in receptor-mediated endocytosis. Epidermal growth factor (EGF) is known to induce cell migration and promote invasion and angiogenesis. The EGF receptor (EGFR) is actively internalized upon the addition of EGF. The aim of the present study was to clarify the expression of Rab5a in hepatocellular carcinomas (HCC) and to examine its effect on EGF signaling. Methods: The expression of the Rab5a protein in HCC and corresponding non-tumorous tissues from 23 patients with HCC who had undergone surgical resection were analyzed by immunoblotting. A stable transfectant of Rab5a dominant negative (S34N) was established in a human hepatoma cell line, PLC/PRF/5 (PLC/PRF/5/Rab5aDN). Results: High expression (tumor/non-tumor (T/N) ratios >/= 1) of Rab5a protein in HCC compared to the paired non-tumortissues was recognized in 15 patients (65.2%) of 23 samples. The Rab5a antigen was diffusely expressed in the cytoplasm and membranes of the cancer cells. The membrane-associated Rab5a is also enhanced via overexpression in HCC. The EGF-induced endocytosis of EGFR and the phosphorylation of MAP kinase were inhibited in PLC/PRF/5/Rab5aDN cells. The migration of PLC/PRF/5/Rab5aDN cells induced by EGF was also significantly attenuated. Conclusions: These results indicate that the overexpression of Rab5a in HCC may play an important role in EGF signaling.
Hepatology Research 12/2007; 37(11):957-65. · 2.20 Impact Factor
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Yoshihiro Kamada,
Hitoshi Matsumoto,
Shinji Tamura,
Juichi Fukushima,
Shinichi Kiso,
Koji Fukui, Takumi Igura,
Norikazu Maeda,
Shinji Kihara,
Tohru Funahashi,
Yuji Matsuzawa,
Iichiro Shimomura,
Norio Hayashi
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ABSTRACT: Adipose tissue produces a number of adipocytokines, including adiponectin, leptin, and tumor necrosis factor-alpha. Obesity, which is associated with low plasma adiponectin levels, is an independent risk factor for various liver diseases including nonalcoholic steatohepatitis (NASH). The aim of this study was to examine the effects of adiponectin on the progression of NASH to cirrhosis and tumor formation using adiponectin-knockout (KO) mice.
Using a choline-deficient L-amino acid-defined (CDAA) diet-induced mouse NASH model, liver histology and oxidative stress markers were investigated in KO and wild-type (WT) mice.
Hepatic steatosis was enhanced to a greater extent in KO mice, compared to WT mice after a 1-week CDAA diet. After 24 weeks, 6 out of 14 KO mice developed liver cirrhosis and hepatic tumors, whereas the 15 WT mice showed only simple steatosis. In KO mice, hepatic cytochrome P450 2E1 levels were upregulated, and markers of oxidative stress (thiobarbituric acid reactive substances, 8-hydroxydeoxyguanosine-positive cells) were significantly increased compared with WT mice.
Our results indicate that lack of adiponectin enhances the progression of hepatic steatosis, fibrosis, and hepatic tumor formation in an animal model of NASH. Hypoadiponectinemia in obesity could be a risk factor for NASH-related hepatic tumor formation.
Journal of Hepatology 11/2007; 47(4):556-64. · 9.26 Impact Factor
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ABSTRACT: Transforming growth factor βs (TGF-βs) are the potent growth inhibitors for various cell types. Certain transformed cells, however, show poor response to TGF-β–induced growth inhibition, which contributes to their uncontrolled proliferation. Recently, we have reported that TGF-β1 induces degradation of activated Src tyrosine kinase in rat fibroblasts. To elucidate the alteration in TGF-β signaling pathway in tumor cells that cannot respond to the cytokine, we compared the effects of TGF-β1 on Src kinase in two human hepatoma cell lines, TGF-β1–insensitive Mahlavu cells and TGF-β1–sensitive HepG2 cells. TGF-β1 decreased Src kinase activity in HepG2 cells, but increased cellular Src levels and Src kinase activity in Mahlavu cells. Co-incubation of Mahlavu cells with TGF-β1 and 12-O-tetradecanoyl phorbol 13-acetate (TPA) decreased Src protein levels and Src kinase activity, inducing TGF-β1sensitivity. TGF-β1 induced tyrosine dephosphorylation of Ras guanosine triphosphatase–activating protein (Ras-GAP) and Ras inactivation in HepG2 cells, but induced Ras-GAP phosphorylation and Ras activation in Mahlavu cells. The Src kinase inhibitor abolished the increase of Src kinase activity in TGF-β1–treated Mahlavu cells, and induced TGF-β1 sensitivity. These findings suggest that regulation of Src kinase by TGF-β1is altered in Mahlavu cells. The altered regulation of Src may contribute to TGF-β1 insensitivity in this cell line, at least in part through activation of Ras.
Hepatology 08/1998; 28(3):796 - 804. · 11.66 Impact Factor
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Shinichi Kiso,
Sumio Kawata,
Shinji Tamura,
Yasuharu Imai,
Yoshiaki Inui,
Toshihiko Nagase,
Yuichi Maeda,
Eiji Yamasaki,
Hirofumi Tsushima, Takumi Igura,
Seiichi Himeno,
Kouichi Seki,
Yuji Matsuzawa
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ABSTRACT: The efficacy of interferon- therapy in the treatment of chronic hepatitis C is still limited. A combination therapy of interferon- with ursodeoxycholic acid (UDCA) was tested for its efficacy in the treatment of chronic hepatitis C by a randomized controlled study. Eighty consecutive Japanese patients with chronic hepatitis C were randomly divided into two groups: one group was treated with interferon- (group A,n=40) and the other with a combination of interferon- and UDCA (group B,n=40). In both groups, human interferon- (6 million units per day) was intramuscularly injected daily for 2 weeks and then three times a week for 22 weeks: this 24-week period was followed by 24 weeks of observation. In group B, UDCA was also administered, daily at a dose of 600mg orally, from the beginning of the interferon therapy and administration was continued for 48 weeks. The rates for ALT normalization and clearance of hepatitis C virus (HCV) viremia at the end of the 24-week interferon therapy were similar for groups A and B (58% vs 60% and 55% vs 48%, respectively). At the end of the 24-week follow-up, the sustained normalization rates for ALT levels for the two groups were not different (35% vs 43%), while the rate of clearance was higher in group B (40%) than in group A (23%), but the difference was not significant (P=0.14). The sustained complete response, i.e., HCV RNA negativity at the end of the follow-up, as well as the maintenance of ALT normalization during the follow-up period, was more frequent in group B (38%) than in group A (18%) although the difference was not significantP=0.08). The rate of HCV reactivation after interferon was discontinued was significantly lower in group B (16%) than in group A (59%) (P
Journal of Gastroenterology 12/1996; 32(1):56-62. · 4.16 Impact Factor
