詳細

萩原　智 （ハギハラ　サトル）

  • 医学科　特命准教授
Last Updated :2024/04/23

コミュニケーション情報 byコメンテータガイド

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    肝臓の疾患を専門にしています。

研究者情報

学位

  • 医学博士（2007年03月）

ホームページURL

J-Global ID

研究キーワード

  • 肝炎   肝癌   肝発癌機序   線維化   線維芽細胞   TGF-β   integrin α11   shRNA   インテグリン   タンパク質   integrin   創傷治癒   CTGF   transgelin   two-hybrid   fibronectin   CIB1   

現在の研究分野（キーワード）

    肝臓の疾患を専門にしています。

研究分野

  • ライフサイエンス / 消化器内科学

経歴

  • 2022年04月  近畿大学医学部特命准教授
  • 2008年 - 2017年  近畿大学医学部講師

研究活動情報

論文

  • Satoru Hagiwara; Toru Takase; Itsuki Oda; Yoriaki Komeda; Naoshi Nishida; Akihiro Yoshida; Tomoki Yamamoto; Takuya Matsubara; Masatoshi Kudo
    Clinical Journal of Gastroenterology 2024年03月 
    Abstract A 53-year-old woman was diagnosed with liver dysfunction in August 20XX. Computed tomography (CT) revealed multiple hepatic AV shunts, and she was placed under observation. In March 20XX + 3, she developed back pain, and CT performed during an emergency hospital visit showed evidence of intrahepatic bile duct dilatation. She was referred to our gastroenterology department in May 20XX + 3. We conducted investigations on suspicion of hereditary hemorrhagic telangiectasia (HHT) with hepatic AV shunting based on contrast-enhanced CT performed at another hospital. HHT is generally discovered due to epistaxis, but there are also cases where it is diagnosed during examination of liver damage.
  • Tomoko Aoki; Masatoshi Kudo; Kazuomi Ueshima; Masahiro Morita; Hirokazu Chishina; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Yasunori Minami; Masakatsu Tsurusaki; Naoshi Nishida
    Liver cancer 13 1 56 - 69 2024年02月 
    INTRODUCTION: Programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) signaling blockade is the most effective strategy for the treatment of immune evading hepatocellular carcinoma (HCC). While immune checkpoint inhibitor has revolutionized the concept of cancer treatment, it has also led to unexpected tumor growth. Regulatory T cells express PD-1 and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) receptors, which are proliferated and activated by antibody binding, and their ratio to CD8+ T cells is altered, which is one of the causes for hyper progressive disease (HPD). We examined the frequency of HPD in anti-PD-1/PD-L1 monotherapy and combination therapy with vascular endothelial growth factor (VEGF) antibody and anti-CTLA-4 antibodies. METHODS: This was a prospective and retrospective cohort study which enrolled 198 patients with unresectable HCC from January 2015 to December 2021 at the Kindai University Hospital. Fifty-eight patients received anti-PD-1/PD-L1 monotherapy, 119 patients combination with VEGF antibody, and 21 patients combination with anti-CTLA-4 antibody. We defined HPD as tumor growth rate (TGR) ratio ≥4, ΔTGR ≥40%, and tumor growth kinetics ratio ≥4. RESULTS: The HPD rate was 10.3% (6/58) in anti-PD-1/PD-L1 monotherapy, 1.7% (2/119) in combination with VEGF antibody, and 4.8% (1/21) in combination with anti-CTLA-4 antibody (p = 0.034). The odds ratio for HPD in the combined anti-CTLA-4 antibody group was 0.433 (95% confidence interval [CI]: 0.05-3.83) when compared to the anti-PD-1/PD-L1 monotherapy group and 2.93 (95% CI: 0.25-33.79) when compared to the combined VEGF antibody group. CONCLUSION: The frequency of HPD in unresectable HCC compared to anti-PD-1/PD-L1 monotherapy was decreased with the combination with anti-VEGF antibody and not increased with anti-CTLA-4 antibody. Anti-PD-1/PD-L1 combined with anti-CTLA-4 antibody is now available in real-world and needs to be further validated with accumulated clinical practice.
  • Satoru Hagiwara; Junko Tanizaki; Hidetoshi Hayashi; Yoriaki Komeda; Naoshi Nishida; Akihiro Yoshida; Tomoki Yamamoto; Takuya Matsubara; Masatoshi Kudo
    Cancer reports (Hoboken, N.J.) e1960  2024年01月 
    BACKGROUND: Immune checkpoint inhibitors have been reported to have excellent therapeutic effects on various malignant tumors. However, immune-related adverse events can occur, targeting various organs. CASE PRESENTATION: A 49-year-old male with lung carcinoma was started on carboplatin + pemetrexed + nivolumab (every 3 weeks) + ipilimumab (every 6 weeks), and nivolumab/ipilimumab was administered in the 3rd course. Subsequently, fever and fatigue developed, and grade 3 liver damage was also noted, so he was admitted to Kindai University Hospital. A bone marrow aspirate examination was performed on the third day of illness, and a definitive diagnosis of hemophagocytic lymphohistiocytosis (HLH) was made. It was determined that immediate therapeutic intervention was necessary, and pulse therapy with methylprednisolone was started on the third day of illness. After 3 days of pulse treatment, a rapid recovery of platelet values, a decrease in ferritin levels, and a decrease in lactate dehydrogenase were observed. Subjective symptoms such as fever and fatigue also quickly improved. CONCLUSION: Early diagnosis and treatment for HLH resulted in a positive response. The number of HLH cases may increase in the future due to the expansion of immune checkpoint inhibitor indications.
  • Satoru Hagiwara; Koichi Nakagawa; Yoriaki Komeda; Naoshi Nishida; Akihiro Yoshida; Tomoki Yamamoto; Takuya Matsubara; Masatoshi Kudo
    Internal Medicine 2024年
  • 萩原 智; 上嶋 一臣; 西田 直生志; 依田 広; 三長 孝輔; 南 康範; 田北 雅弘; 青木 智子; 盛田 真弘; 千品 寛和; 松原 卓哉; 大丸 直哉; 稲村 昇; 工藤 正俊
    肝臓 64 11 567 - 574 (一社)日本肝臓学会 2023年11月 
    症例は30代男性.幼少期に完全大血管転位III型に対してFontan手術が施行され,近医に定期的に通院していた.20XX年7月腹部USで多発肝腫瘤を指摘され当院紹介受診となった.造影CTにて最大13cmの多発肝細胞癌と判明した(BCLC stage B).画像上は門脈圧亢進所見や明らかな肝形態異常を認めなかったが,肝生検でCongestive Hepatic Fibrosis Score 3であり,実際には線維化の進展を認めていた.肝内多発のため外科手術やRFAの適応外であった.また最大径の腫瘍は肝外に突出しており,腹腔内破裂の危険性もあることから,まずTACEを施行した.再発に応じて各種抗癌剤治療を行い,生存中である.画像上は肝線維化を示唆する所見はなかったが,Fontan術後の特殊な循環動態では,肝線維化が進展している可能性があり,本症例を通して肝癌サーベイランスの重要性を再考する.(著者抄録)
  • Yoriaki Komeda; George Tribonias; Masashi Kono; Kohei Handa; Shunsuke Omoto; Mamoru Takenaka; Satoru Hagiwara; Naoko Tsuji; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    Inflammatory Intestinal Diseases 2023年10月 
    Introduction: Ustekinumab is an IgG1 kappa monoclonal antibody directed against the common p40 subunit of interleukin-12 and interleukin-23, which activate Th1- and Th17-mediated immune responses, respectively. It has proven efficacy for the treatment of moderate to severe ulcerative colitis (UC) in the UNIFI Phase III clinical trial; however, data on its efficacy in the real world is limited. In this study, we aimed to assess the real-world efficacy of ustekinumab.Methods: This observational study included 30 patients with UC who received ustekinumab from April 2020 to April 2022. We examined demographic information, disease type and activity (Mayo score, partial Mayo score [PMS]), use of biologics, concomitant use of predonisolone (PSL), 8-week ustekinumab clinical response rate, remission induction rate, 44- and 152-week remission maintenance rate, continuation rate, and 44-week steroid-free remission rate. The primary outcomes were the short- and long-term efficacy of ustekinumab.Results: Included patients (53% women; mean age: 41.2 years [16–80 years]) had an average disease duration of 86 weeks. Mayo’s score (median) was 7.4 and the PMS was 5.4. Two (7%), 24 (80%), and four (13%) patients had a Mayo endoscopic sub-score (MES) of MES1, MES2, and MES3, respectively. The median serum CRP was 1.0 mg/dL. Five patients had no history of biotherapy (naive), while 8 and 17 had a history of one and two or more biologic agents, respectively. Eight patients were PSL-resistant and 22 were PSL-dependent. The 8-week clinical response rate was 73%, and the clinical remission induction rate was 70%. The remission maintenance rates at 44 and 152 weeks were 67% and 63%, respectively. The ustekinumab retention rate was 67% (86-week mean follow-up period). Regarding biologic failure cases, the clinical response rate in the failure group with up to one biologic agent (including naive cases) was 84.6%, which was higher than the 58.0% rate in the failure group with two or more biologic agents (p=0.06). Steroid-free remission rates at 44 and 152 weeks were 63% each. In the logistic regression analysis parameters for discontinuation of ustekinumab, only PMS remained significant after multivariate analysis (p=0.018).Conclusion: Our study showed short-term and long-term ustekinumab effectiveness, especially with comparative low disease activity.
  • Masashi Kono; Yoriaki Komeda; George Tribonias; Saki Yoshida; Kenji Nomura; Kohei Handa; Tomoyuki Nagai; Satoru Hagiwara; Shunsuke Omoto; Mamoru Takenaka; Naoshi Nishida; Naoko Tsuji; Hiroshi Kashida; Masatoshi Kudo
    JGH Open 2023年08月 
    Abstract Background and Aim Serum leucine‐rich alpha‐2 glycoprotein level has been reported to be a useful biomarker in assessing mucosal healing in patients undergoing biotherapy, where mucosal lesions caused by ulcerative colitis are difficult to assess endoscopically. However, no such reports have been reported in biotherapy‐naïve cases. Methods Sixty‐eight patients with ulcerative colitis (UC) who were biotherapy‐naïve at Kindai University Hospital between October 2021 and October 2022 were enrolled. We prospectively examined the correlation between leucine‐rich alpha‐2 glycoprotein (LRG), C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR), and Geboes scores with clinical endoscopic activity using the Mayo endoscopic subscore (MES). Results Mucosal healing was achieved in 39 (57%) patients. Univariate analysis revealed that the factors associated with mucosal healing were LRG (P = 0.0024), CRP (P = 0.1078), ESR (P = 0.0372), and Geboes scores (P = 0.0075). Logistic regression analysis identified LRG and Geboes scores as independent factors associated with mucosal healing assessed using MES (P = 0.0431 for LRG and P = 0.0166 for Geboes scores). Conclusion LRG was found to be the easiest marker to monitor disease activity and mucosal inflammation in UC patients with biotherapy‐naïve cases, with a performance equivalent to that of Geboes scores.
  • 【超高齢社会における肝胆膵疾患診療】高齢者に対する肝炎ウイルス治療の留意点
    萩原 智; 工藤 正俊
    肝胆膵 86 6 685 - 690 (株)アークメディア 2023年06月
  • Naoshi Nishida; Tomoko Aoki; Masahiro Morita; Hirokazu Chishina; Masahiro Takita; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima; Masatoshi Kudo
    Cancers 15 8 2023年04月 
    Cholangiocarcinoma (CCA) is a refractory cancer; a majority of CCAs represents a non-inflamed tumor phenotype that should be resistant to treatment, including immune checkpoint inhibitors (ICIs). In this study, we aimed to understand the molecular characteristics associated with non-inflamed CCAs. The genetic/epigenetic status of 36 CCAs was obtained from the Cancer Genome Atlas (PanCancerAtlas). CCAs were classified based on immune class using hierarchical clustering analysis of gene expressions related to tumor-infiltrating lymphocytes. The associations between immune class and genetic/epigenetic events were analyzed. We found that the tumors with alterations in FGFR2 and IDH1/2 had a "non-inflamed" tumor phenotype. A significant association was observed between the non-inflamed group and the downregulation of genes involved in antigen presentation (p = 0.0015). The expression of antigen-presenting machineries was inversely correlated with their DNA methylation levels, where 33.3% of tumors had an upregulation/low-methylation pattern, and 66.7% of tumors had a downregulation/high-methylation pattern. All tumors in the "inflamed" group exhibited an upregulation/low-methylation pattern. In contrast, 24 of 30 tumors in the non-inflamed group represent the downregulation/high-methylation pattern (p = 0.0005). Methylation with downregulation of antigen-presenting machineries is associated with the "non-inflamed" tumor phenotype of CCAs. This evidence provides important insights for developing new strategies for treating CCA.
  • Masahiro Morita; Naoshi Nishida; Tomoko Aoki; Hirokazu Chishina; Masahiro Takita; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima; Masatoshi Kudo
    Cancers 15 8 2023年04月 
    Recently, the therapeutic combination of atezolizumab and bevacizumab was widely used to treat advanced hepatocellular carcinoma (HCC). According to recent clinical trials, immune checkpoint inhibitors (ICIs) and molecular target agents are expected to be key therapeutic strategies in the future. Nonetheless, the mechanisms underlying molecular immune responses and immune evasion remain unclear. The tumor immune microenvironment plays a vital role in HCC progression. The infiltration of CD8-positive cells into tumors and the expression of immune checkpoint molecules are key factors in this immune microenvironment. Specifically, Wnt/β catenin pathway activation causes "immune exclusion", associated with poor infiltration of CD8-positive cells. Some clinical studies suggested an association between ICI resistance and β-catenin activation in HCC. Additionally, several subclassifications of the tumor immune microenvironment were proposed. The HCC immune microenvironment can be broadly divided into inflamed class and non-inflamed class, with several subclasses. β-catenin mutations are important factors in immune subclasses; this may be useful when considering therapeutic strategies as β-catenin activation may serve as a biomarker for ICI. Various types of β-catenin modulators were developed. Several kinases may also be involved in the β-catenin pathway. Therefore, combinations of β-catenin modulators, kinase inhibitors, and ICIs may exert synergistic effects.
  • B型肝炎診療の未来予想図(現状と課題) 免疫チェックポイント阻害剤投与に伴うHBV再活性化および抗ウイルス効果についての検討
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 64 Suppl.1 A51 - A51 (一社)日本肝臓学会 2023年04月
  • 遺伝・代謝性肝疾患の未来予想図(現状と課題) Erythropoietic porphyria(EPP)関連肝障害における瀉血治療の有効性
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 64 Suppl.1 A111 - A111 (一社)日本肝臓学会 2023年04月
  • NASH/ASHの病態解明とTransrational Research 非アルコール性脂肪肝疾患におけるDNAメチル化に関連する臨床的・病理学的特徴
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 64 Suppl.1 A208 - A208 (一社)日本肝臓学会 2023年04月
  • 非硬変肝から発生したFontan術後HCCの1例
    有山 武尊; 萩原 智; 西田 直生志; 工藤 正俊
    肝臓 64 Suppl.1 A324 - A324 (一社)日本肝臓学会 2023年04月
  • B型慢性肝炎患者に対するTAFの効果および安全性の検討
    萩原 智; 盛田 真弘; 千品 寛和; 青木 智子; 田北 雅弘; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    肝臓 64 Suppl.1 A425 - A425 (一社)日本肝臓学会 2023年04月
  • 高アンモニア血症に対するレボカルニチン自体の効果について
    萩原 智; 盛田 真弘; 千品 寛和; 青木 智子; 田北 雅弘; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    肝臓 64 Suppl.1 A432 - A432 (一社)日本肝臓学会 2023年04月
  • 切除不能HCCに対するABC conversion療法と造影超音波によるclinical CRの補助診断
    青木 智子; 南 康範; 依田 広; 千品 寛和; 田北 雅弘; 萩原 智; 上嶋 一臣; 鶴崎 正勝; 西田 直生志; 工藤 正俊
    超音波医学 50 Suppl. S598 - S598 (公社)日本超音波医学会 2023年04月
  • Satoru Hagiwara; Naoshi Nishida; Masatoshi Kudo
    Cancers 15 7 2023年03月 
    Immune checkpoint inhibitors (ICIs) aim to induce immune responses against tumors and are less likely to develop drug resistance than molecularly targeted drugs. In addition, they are characterized by a long-lasting antitumor effect. However, since its effectiveness depends on the tumor's immune environment, it is essential to understand the immune environment of hepatocellular carcinoma to select ICI therapeutic indications and develop biomarkers. A network of diverse cellular and humoral factors establishes cancer immunity. By analyzing individual cases and classifying them from the viewpoint of tumor immunity, attempts have been made to select the optimal therapeutic drug for immunotherapy, including ICIs. ICI treatment is discussed from the viewpoints of immune subclass of HCC, Wnt/β-catenin mutation, immunotherapy in NASH-related HCC, the mechanism of HPD onset, and HBV reactivation.
  • Yasuo Otsuka; Yoriaki Komeda; Masayuki Takeda; Takayuki Takahama; Masashi Kono; Mamoru Takenaka; Satoru Hagiwara; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    Case Reports in Medicine 2023 1 - 4 2023年02月 
    A 76-year-old woman presented with lower abdominal pain and nausea and was referred to the gastroenterology department in our institution. Previous contrast-enhanced computed tomography (CE-CT) for follow-up after breast cancer surgery had indicated a soft tissue mass below the right diaphragm, which was considered a benign change. CE-CT performed at the first visit to our department revealed further thickening of the soft tissue mass with extension to the liver surface. In addition, ascites and nodules were observed in the abdominal cavity. Histopathological examination of a biopsy specimen revealed peritoneal invasion of atypical epithelioid cells with trabecular and glandular patterns. The tumor cells were positive for AE1/AE2, calretinin, WT-1, D2-40, HEG1, EMA, BAP1, and MTAP and negative for carcinoembryonic antigen, MOC-31, Ber-Ep4, ER, PgR, TTF-1, claudin 4, and desmin. A diagnosis of epithelioid mesothelioma was made. The patient received chemotherapy with cisplatin (75 mg/m2) and pemetrexed (500 mg/m2). After six courses of combined chemotherapy, pemetrexed was administered as a single agent. At the time of writing this report, she was undergoing over the 30th course of chemotherapy without any significant side effects. Diffuse malignant peritoneal mesothelioma is a rare, fatal, and progressive disease. Our patient achieved long-term survival of more than 5 years with maintenance therapy using single-agent pemetrexed.
  • Hiroki Kato; Satoru Hagiwara; Naoshi Nishida; Yoriaki Komeda; Akihiro Yoshida; Masatoshi Kudo
    Clinical Journal of Gastroenterology 2023年02月
  • Masatoshi Kudo; Tomoko Aoki; Kazuomi Ueshima; Kaoru Tsuchiya; Masahiro Morita; Hirokazu Chishina; Masahiro Takita; Satoru Hagiwara; Yasunori Minami; Hiroshi Ida; Naoshi Nishida; Chikara Ogawa; Tetsu Tomonari; Noriaki Nakamura; Hidekatsu Kuroda; Atsushi Takebe; Yoshifumi Takeyama; Masaaki Hidaka; Susumu Eguchi; Stephen L. Chan; Masayuki Kurosaki; Namiki Izumi
    LIVER CANCER 2023年02月 
    Introduction: Atezolizumab plus bevacizumab therapy is extremely effective in the treatment of intermediate-stage hepatocellular carcinoma (HCC), with a response rate of 44%, as reported in the IMbrave150 trial. When tumor shrinkage is obtained, achieving complete response (CR) is possible in many cases using curative conversion with resection, ablation, or super selective transarterial chemoembolization (TACE) with curative intent. This concept, i.e., curative conversion by combining systemic therapy and locoregional therapy, has not been reported before. This multicenter proof-of-concept study was conducted to show the value of curative conversion in immunotherapy-treated intermediate-stage HCC meeting TACE-unsuitable criteria.Methods: This study included 110 consecutive Child-Pugh A patients who received atezolizumab plus bevacizumab as first-line treatment for unresectable and TACE-unsuitable intermediate-stage HCC at seven centers in Japan. CR rate, drug-free rate, time to CR, change in liver function, efficacy in positron emission tomography (PET)-positive HCC, progression-free survival (PFS), and overall survival (OS) were assessed in patients who achieved CR using resection, ablation, super selective TACE with curative intent following atezolizumab plus bevacizumab or atezolizumab plus bevacizumab alone.Results: Clinical or pathological CR was achieved in 38 patients (35%) (median observation period: 21.2 months). The modalities of curative conversion in 35 patients were as follows: resection, 7; ablation, 13; and superselective TACE, 15. Three patients achieved clinical CR with atezolizumab plus bevacizumab therapy alone. Among the 38 CR patients, 25 achieved drug-free status. PFS was not reached, and three patients experienced recurrence after reaching CR. Regarding OS, there were no deaths in any of the CR patients. The albumin-bilirubin score did not deteriorate after locoregional therapy or resection. Of seven PET-positive patients who achieved CR with atezolizumab plus bevacizumab followed by curative conversion, five achieved drug-free status.Discussion/Conclusion: The achievement of CR rate by curative conversion in patients treated with atezolizumab plus bevacizumab as the preceding therapy for unresectable and TACE-unsuitable intermediate-stage HCC was 35%. Overall, 23% of patients achieved drug-free status and no recurrence was observed from this patient subgroup with CR and drug free status. Thus, achieving CR and/or drug-free status should be a therapeutic goal for patients with intermediate-stage HCC without vascular invasion or extrahepatic spread.
  • Naoshi Nishida; Masatoshi Kudo; Takafumi Nishimura; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Naosuke Yokomichi; Takeshi Nagasaka; Ajay Goel
    PLOS ONE 18 1 2023年01月
  • Yoriaki Komeda; Hideki Ishikawa; Teruhiko Yoshida; Mineko Ushiama; Saki Yoshida; Kenji Nomura; Masashi Kono; Shunsuke Omoto; Mamoru Takenaka; Satoru Hagiwara; Hiroshi Kashida; Masatoshi Kudo
    Internal Medicine 2023年
  • Yoriaki Komeda; Masashi Kono; Hiroshi Kashida; George Tribonias; Sho Masaki; Ryutaro Takada; Tomoyuki Nagai; Satoru Hagiwara; Naoshi Nishida; Mamoru Takenaka; Hajime Honjo; Shigenaga Matsui; Naoko Tsuji; Masatoshi Kudo
    Annals of gastroenterology 36 1 97 - 102 2023年 
    BACKGROUND: The standard therapy for acute severe ulcerative colitis (ASUC) is intravenous corticosteroids; however, 30% of ulcerative colitis (UC) patients do not recover with corticosteroids alone. Few studies have reported the efficacy and safety of tofacitinib for ASUC with steroid resistance. We report a case series of successful first-line treatment consisting of tofacitinib (20 mg/day) administered to ASUC patients with steroid resistance. METHODS: Patients diagnosed with ASUC at our institution between October 2018 and February 2020 were retrospectively evaluated. They were administered a high dose of tofacitinib (20 mg) after showing no response to steroid therapy in a dose of 1-1.5 mg/kg/day. RESULTS: Eight patients with ASUC, 4 (50%) men, median age 47.1 (range 19-65) years, were included. Four patients were newly diagnosed, and the median UC duration was 4 (range 0-20) years. Six of the 8 patients were able to avoid colectomy. One patient (patient 2) had no response; however, remission was achieved after switching from tofacitinib to infliximab. One patient (patient 6) with no response to tofacitinib underwent total colectomy. Only one patient (patient 4) experienced an adverse event, local herpes zoster, treated with acyclovir without tofacitinib discontinuation. CONCLUSIONS: Clinical remission without serious adverse events can be achieved with high probability and colectomy can be avoided by first administering high-dose tofacitinib to steroid-resistant ASUC patients. Tofacitinib may be one of the first-line treatment options for steroid-resistant ASUC.
  • Soo Ki Kim; Takako Fujii; Soo Ryang Kim; Atsushi Nakai; Young-Suk Lim; Satoru Hagiwara; Masatoshi Kudo
    Liver cancer 11 6 497 - 510 2022年12月 
    BACKGROUND: Long-term therapy with nucleos(t)ide analogs (NAs) such as entecavir (ETV) and tenofovir disoproxil fumarate (TDF) favorably affects the incidence of hepatocellular carcinoma (HCC) on the basis of data from randomized or matched control studies. Recent data suggest a lower HCC incidence after 5 years of ETV or TDF therapy in chronic hepatitis B (CHB) patients, especially those with baseline cirrhosis. SUMMARY: Three controversial issues remain to be resolved regarding hepatitis B virus (HBV) treatment and HCC. (1) The efficacy of antiviral treatment for the prevention of HCC is not established. The guidelines of the American Association for the Study of Liver Diseases (AASLD), the Asian Pacific Association for the Study of the Liver (APASL), and the European Association for the Study of the Liver (EASL) for the management of HBV infection state that antiviral treatment of HBV with interferon and NAs prevents the development of HCC. Among experts in CHB treatment, however, there is disagreement on the HCC prevention effects of antiviral treatment. (2) The rationale for antiviral management in patients with high HBV DNA and normal levels of alanine aminotransferase is unclear. The AASLD, EASL, and APASL guidelines do not recommend antiviral treatment for immune-tolerant CHB patients, and the terms and methods of treating such patients remain to be clarified. (3) The efficacy of first-line treatment with NAs, including ETV, TDF, and tenofovir alafenamide fumarate (TAF), to prevent HCC in CHB patients remains unknown. Several studies have produced controversial results regarding the effects of NAs on the risk and prevention of HCC. In the present review, we discuss these 3 issues, citing recent studies and clinical management guidelines from major international associations. KEY MESSAGES: Suggested approaches for reaching a consensus including applying the propensity score matching method, performing randomized controlled studies, and performing clinical studies with larger numbers of subjects and longer follow-up.
  • Satoru Hagiwara; Naoshi Nishida; Hiroshi Ida; Kazuomi Ueshima; Yasunori Minami; Masahiro Takita; Tomoko Aoki; Masahiro Morita; Hirokazu Chishina; Yoriaki Komeda; Akihiro Yoshida; Ah-Mee Park; Masako Sato; Akira Kawada; Hajime Nakano; Hiroshi Nakagawa; Masatoshi Kudo
    Scientific Reports 12 1 6100 - 6100 2022年12月 
    Abstract Liver damage affects the prognosis of patients with erythropoietic protoporphyria (EPP). However, there is no radical cure for EPP patients with severe liver damage. This study aims to investigate the effectiveness of phlebotomy in patients with severe liver damage. We examined seven patients diagnosed with EPP and liver damage between 2010 and 2020. Of the 7 cases, phlebotomy was performed in 3 cases with severe hepatic disorder, and the improvement effect of hepatic disorder was observed in all cases. In addition, as an additional study, we also investigated the mechanism by which liver damage becomes more severe. Liver biopsy samples were stained with hematoxylin and eosin and immunohistochemistry was used to examine the expression of adenosine triphosphate-binding transporter G2 (ABCG2). Liver biopsies were performed in 3 of 7 patients with EPP. Of these three patients, ABCG2 expression was low in two patients, especially in the protoporphyrin (PP) deposition area. Two patients with reduced ABCG2 expression subsequently developed severe liver damage. However, the causal relationship between the decreased expression of ABCG2 and the exacerbation of liver damage has not been directly proved, and further investigation is required in the future. This study demonstrated the effectiveness of phlebotomy in EPP patients with severe liver damage.
  • Satoru Hagiwara; Yoriaki Komeda; Naoshi Nishida; Akihiro Yoshida; Masatoshi Kudo
    Cancer Reports 5 11 e1721  2022年10月 
    BACKGROUND: Although reports of gastrointestinal perforation after immune-related adverse events (irAE) enteritis are rare, the anti- vascular endothelial growth factor (VEGF) effect of bevacizumab may be involved in gastrointestinal perforation. We report a rare case of gastrointestinal perforation in a patient with hepatocellular carcinoma treated with atezolizumab/bevacizumab combination therapy and infliximab before steroid use. CASE: A 72-year-old man, who received seven courses of atezolizumab/bevacizumab for hepatocellular carcinoma due to hepatitis B, was admitted to our department with idiopathic abdominal pain and diarrhea (grade 2 [G2]). Computed tomography (CT) and colonoscopy confirmed edema in the gastrointestinal tract. Perforation of the jejunum was observed in a CT performed on the third day and an emergency operation was performed. Intraoperative findings showed severe edema of the jejunum and leakage of feces into the abdominal cavity. The patient was diagnosed with irAE enteritis comprehensively with severe wall thickening on CT and colonoscopy, negative stool culture, and pathological findings of CD8-positive cells. Infliximab was administered before initiating steroids, to prevent reperforation. The enteritis improved by the 22nd day; however, CT performed on the 35th day of illness showed relapse of gastrointestinal wall thickening and G2 diarrhea symptoms; therefore, prednisolone (PSL) 60 mg/day was started on the 36th day of illness. After introducing PSL, enteritis did not reoccur, and the patient was discharged on the 63rd day of illness after admission. CONCLUSION: There are no reports of gastrointestinal perforation by atezolizumab/bevacizumab for hepatocellular carcinoma, and prior administration of infliximab. We therefore report the clinical course and management.
  • Yasunori Minami; Tomoko Aoki; Hirokazu Chishina; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    Cancers 14 19 2022年10月 
    BACKGROUND: The treatment of the hepatitis C virus (HCV) has reduced the risk of hepatocellular carcinoma (HCC)-related mortality. Many patients with advanced HCC have achieved longer survival through systemic chemotherapy. However, survivors of HCC may develop liver cancer during and after treatment. Therefore, the present study investigated prognostic factors for survival in patients with HCV-related HCC in the new era of molecular targeted therapy. METHODS: A total of 359 patients with HCV-related HCC treated with first-line chemotherapy were reviewed. A Cox proportional hazards model and Kaplan-Meier curve were used to identify prognostic factors associated with survival outcomes. RESULTS: The median follow-up duration was 16.0 months (range, 1.0-115.7) and the median duration of first-line systemic therapy was 3.73 months (range, 0.7-86.9). The achievement of a sustained virological response (SVR) (p  <  0.001), albumin-bilirubin (ALBI) grade II/III (p  <  0.001), Barcelona Clinic Liver Cancer (BCLC) stage C (p  =  0.005), extrahepatic spread (p < 0.001), baseline AFP (alpha-fetoprotein) level ≥ 90 (p = 0.038), baseline DCP (des-γ-carboxy prothrombin) level ≥ 500 (p < 0.001), and a fibrosis-4 (FIB-4) index ≥ 4 (p  =  0.003) were identified as prognostic factors for overall survival. CONCLUSIONS: The achievement of SVR was most strongly associated with overall survival. Other factors, such as the BCLC stage, extrahepatic spread, baseline tumor marker (AFP/DCP) levels, ALBI grade, and FIB-4 index need to be considered in the management of patients with HCV-related HCC.
  • 代謝性肝疾患の標準治療確立のためのエビデンス構築 NAFLD関連肝癌における背景肝のエピゲノム変異の蓄積
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 63 Suppl.3 A654 - A654 (一社)日本肝臓学会 2022年10月
  • B型慢性肝炎患者におけるETVとTAFの効果・安全性の比較
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 63 Suppl.3 A768 - A768 (一社)日本肝臓学会 2022年10月
  • 発症早期から進行期までを観察しえたirAE胆管炎の1例
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 63 Suppl.3 A793 - A793 (一社)日本肝臓学会 2022年10月
  • irAE腸炎による消化管穿孔に対してステロイド前のinfliximab先行投与により救命できた1例
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 63 Suppl.3 A794 - A794 (一社)日本肝臓学会 2022年10月
  • Satoru Hagiwara; Takeshi Yoshida; Naoshi Nishida; Hiroshi Ida; Kazuomi Ueshima; Yasunori Minami; Masahiro Takita; Tomoko Aoki; Masahiro Morita; Hirokazu Cishina; Yoriaki Komeda; Akihiro Yoshida; Hidetoshi Hayashi; Kazuhiko Nakagawa; Masatoshi Kudo
    Hepatology research : the official journal of the Japan Society of Hepatology 52 10 888 - 892 2022年07月 
    AIM: We report a rare case of immune-related cholangitis in which the natural course could be demonstrated. CASE PRESENTATION: Eight courses of pembrolizumab maintenance therapy were given as first-line treatment for squamous cell lung cancer; however, the patient was subsequently hospitalized due to a rapid increase in hepatobiliary enzymes. On endoscopic ultrasound, the common bile duct was dilated to 11 mm, and the wall, throughout its length from the papilla, was thickened. Endoscopic retrograde cholangiopancreatography showed no obvious stenosis in the lower bile duct; however, a parapapillary diverticulum was found, and papillary incision and bile duct plastic stent insertion were carried out. However, the liver disorder did not improve and overt jaundice appeared subsequently; therefore, an immune-related cholangitis was suspected, and prednisolone (PSL) 35 mg/day was introduced from day 59 of admission. Following PSL initiation, a decrease in serum bilirubin level was observed; however, significant decrease was not observed in alkaline phosphatase. Given the history of recurrent infectious cholangitis, magnetic resonance cholangiopancreatography was carried out on day 70 of admission. The intrahepatic bile duct showed stenosis and dilated findings, which was considered to be a factor for repeated infectious cholangitis. CONCLUSION: No previous case reports have described the changes and progression in bile duct images in immune-related adverse events. Therefore, this case is noteworthy for considering the progression of immune-related cholangitis.
  • Satoru Hagiwara; Naoshi Nishida; Hiroshi Ida; Kazuomi Ueshima; Yasunori Minami; Masahiro Takita; Tomoko Aoki; Masahiro Morita; Hirokazu Cishina; Yoriaki Komeda; Akihiro Yoshida; Hidetoshi Hayashi; Kazuhiko Nakagawa; Masatoshi Kudo
    Hepatology Research 52 9 754 - 761 2022年05月 
    AIM: The risk of hepatitis B virus (HBV) reactivation with immune checkpoint inhibitors (ICIs) is an important issue that has not yet been fully investigated. ICI is also expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect. We herein investigated the risk of HBV reactivation and the antiviral effect of ICI administration. METHODS: This study included 892 patients on ICIs between September 2014 and May 2021 at our hospital. The frequency of HBV reactivation and antiviral effects were investigated. RESULTS: Among the 892 patients who underwent ICI, 27 were hepatitis B surface antigen (HBsAg) positive. HBV reactivation was evaluated in 24 cases, among which 4.1% (1/24) had HBV reactivation. Nucleic acid analog prophylaxis was not administered to patients with reactivation. In a study of 15 cases, the amount of HBsAg decreased from baseline; 2.18 ± 0.77 log to 48 weeks later; 1.61 ± 1.38 log (p = 0.17). Forty-eight weeks after the start of ICI, disappearance of HBsAg was observed in two out of 15 cases (13.3%), and one case each with and without nucleic acid analog. CONCLUSION: In rare cases, HBsAg-positive patients may be reactivated by ICI administration. On the other hand, when ICI is administered, it is expected to have an antiviral effect on HBV due to its immune tolerance inhibitory effect, and future drug development is expected.
  • 治療起因性肝障害のマネジメント-DILI・HBV再活性化・irAE・IRIS 免疫チェックポイント阻害剤投与に伴うirAE肝障害・HBV再活性化についての検討
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 63 Suppl.1 A95 - A95 (一社)日本肝臓学会 2022年04月
  • 治療起因性肝障害のマネジメント-DILI・HBV再活性化・irAE・IRIS 免疫チェックポイント阻害剤投与に伴うirAE肝障害・HBV再活性化についての検討
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 63 Suppl.1 A95 - A95 (一社)日本肝臓学会 2022年04月
  • 萩原 智; 西田 直生志; 工藤 正俊
    日本消化器病学会雑誌 119 臨増総会 A214 - A214 (一財)日本消化器病学会 2022年03月
  • 萩原 智; 西田 直生志; 工藤 正俊
    日本消化器病学会雑誌 119 臨増総会 A214 - A214 (一財)日本消化器病学会 2022年03月
  • 肝炎ウイルスコントロール下における課題へのアプローチ ICI投与とHBVフォローにおける問題点
    盛田 真弘; 萩原 智; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部例会プログラム・抄録集 116回 73 - 73 日本消化器病学会-近畿支部 2022年02月
  • 免疫チェックポイント阻害剤をめぐる諸問題 免疫チェックポイント阻害剤投与後に発現した肝障害の臨床的、病理学的検討
    萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部例会プログラム・抄録集 116回 79 - 79 日本消化器病学会-近畿支部 2022年02月
  • 上・下腸間膜動静脈奇形に伴う門脈圧亢進からの難治性腹水及び循環血液量低下に伴う血圧低下に対し血管内治療(IVR)にて改善しえた1例
    上原 広樹; 田北 雅弘; 杉森 啓伸; 岡井 夏輝; 野村 健司; 盛田 真弘; 千品 寛和; 青木 智子; 萩原 智; 依田 広; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部例会プログラム・抄録集 116回 88 - 88 日本消化器病学会-近畿支部 2022年02月
  • Satoru Hagiwara; Naoshi Nishida; Kazuomi Ueshima; Yasunori Minami; Yoriaki Komeda; Tomoko Aoki; Masahiro Takita; Masahiro Morita; Hirokazu Chishina; Akihiro Yoshida; Hiroshi Ida; Masatoshi Kudo
    Cells 10 11 2021年11月 
    The incidence of hepatocellular carcinoma (HCC) related to non-alcoholic fatty liver disease (NAFLD) is increasing worldwide. We analyzed 16 surgically resected HCC cases in which the background liver was pathologically diagnosed as NAFLD. Specimens with Brunt classification grade 3 or higher were assigned as the fibrotic progression group (n = 8), and those with grade 1 or lower were classified as the non-fibrosis progression group (n = 8). Comprehensive mutational and methylome analysis was performed in cancerous and noncancerous tissues. The target gene mutation analysis with deep sequencing revealed that CTNNB1 and TP53 mutation was observed in 37.5% and TERT promoter mutation was detected in 50% of cancerous samples. Furthermore, somatic mutations in non-cancerous samples were less frequent, but were observed regardless of the progression of fibrosis. Similarly, on cluster analysis of methylome data, status for methylation events involving non-cancerous liver was similar regardless of the progression of fibrosis. It was found that, even in cases of non-progressive fibrosis, accumulation of gene mutations and abnormal methylation within non-cancerous areas were observed. Patients with NAFLD require a rigorous liver cancer surveillance due to the high risk of HCC emergence based on the accumulation of genetic and epigenetic abnormalities, even when fibrosis is not advanced.
  • ATP-binding cassette transporter G2(ABCG2)の発現低下はerythropoietic porphyria(EPP)における肝障害の重症化と関連する
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 62 Suppl.3 A737 - A737 (一社)日本肝臓学会 2021年11月
  • Segmental arterial mediolysis(SAM)に伴う肝動脈瘤破裂に対して肝動脈塞栓術を施行した1例
    加藤 弘樹; 千品 寛和; 瀬海 郁衣; 盛田 真弘; 青木 智子; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    肝臓 62 Suppl.3 A824 - A824 (一社)日本肝臓学会 2021年11月
  • Tomoko Aoki; Naoshi Nishida; Kazuomi Ueshima; Masahiro Morita; Hirokazu Chishina; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Yasunori Minami; Akira Yamada; Keitaro Sofue; Masakatsu Tsurusaki; Masatoshi Kudo
    Liver cancer 10 6 615 - 628 2021年11月 
    Introduction: Immune checkpoint inhibitors (ICIs) are promising agents for the treatment of hepatocellular carcinoma (HCC). However, the establishment of noninvasive measure that could predict the response to ICIs is challenging. This study aimed to evaluate tumor responses to ICIs using the hepatobiliary phase of gadolinium-ethoxybenzyl-diethylenetriamine (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI), which was shown to reflect Wnt/β-catenin activating mutation. Methods: A total of 68 intrahepatic HCC nodules from 18 patients with unresectable HCC and Child-Pugh class A liver function who received anti-programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) monotherapy were enrolled in this study. All patients had viable intrahepatic lesions evaluable using the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI within the 6 months prior to the treatment. The relative enhancement ratio was calculated, and the time to nodular progression (TTnP) defined as 20% or more increase in each nodule was compared between higher or hypo-enhancement HCC nodules. Then, the progression-free survival (PFS) and objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) were compared between patients with and without HCC nodules with higher enhancement on hepatobiliary phase images. Results: The median PFS was 2.7 (95% confidence interval [CI]: 1.4-4.0) months in patients with HCC nodules with higher enhancement (n = 8) and 5.8 (95% CI: 0.0-18.9) months in patients with hypointense HCC nodules (n = 10) (p = 0.007). The median TTnP of HCC nodules with higher enhancement (n = 23) was 1.97 (95% CI: 1.86-2.07) months and that of hypointense HCC nodules (n = 45) was not reached (p = 0.003). The ORR was 12.5% (1/8) versus 30.0% (3/10); the disease control rate was 37.5% (3/8) versus 70.0% (7/10), respectively, in patients with or without higher enhancement intrahepatic HCC nodules. Conclusion: The TTnP on HCC nodules with higher enhancement and the median PFS in patients who carried higher enhancement intrahepatic HCC nodules were significantly shorter than those in hypointense HCC nodules with anti-PD-1/PD-L1 monotherapy. The intensity of the nodule on the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI is a promising imaging biomarker for predicting unfavorable response with anti-PD-1/PD-L1 monotherapy in patients with HCC.
  • Yasunori Minami; Masahiro Morita; Hirokazu Chishina; Tomoko Aoki; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    Ultrasound in medicine & biology 47 10 2930 - 2935 2021年10月 
    Developments in image fusion technology made it possible to visualize the ablative margin on ultrasound (US). The purpose of the present study was to assess the ablative area of radiofrequency ablation for hepatocellular carcinoma and compare it with the ablative hyperechoic zone with a non-enhanced area on contrast-enhanced US/contrast-enhanced computed tomography (CEUS/CECT) in the same cross-section. This retrospective study included 25 patients with 27 hepatocellular carcinomas. The long and short dimensions of the ablative hyperechoic zone were measured using B-mode US, and those of the non-enhanced area were assessed with CEUS/CECT on the same cross-section measured with B-mode US, using image fusion techniques. The technical effectiveness of ablation with an adequate ablative margin in a single session was determined in all patients. The long and short dimensions of the ablative hyperechoic zone ranged between 15.0 and 40.7 mm (mean: 27.3 ± 6.9 mm) and between 14.0 and 33.0 mm (mean: 23.3 ± 5.8 mm), respectively. R values for the long and short dimensions were 0.99 and 0.98, respectively, between B-mode US and CEUS, and 0.96 and 0.92, respectively, between B-mode US and CECT. The ablative hyperechoic zone may be regarded as a necrotic lesion after radiofrequency ablation.
  • 薬物性肝障害の実態 免疫チェックポイント阻害剤投与後に発現した肝障害の臨床的、病理学的検討
    萩原 智; 西田 直生志; 工藤 正俊
    肝臓 62 Suppl.2 A515 - A515 (一社)日本肝臓学会 2021年09月
  • Gd-EOB-DTPA-enhanced MRI肝細胞相で高信号の肝細胞癌は、PD-1/PD-L1療法への一次耐性を反映し予後不良である
    青木 智子; 上嶋 一臣; 盛田 真弘; 千品 寛和; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 鶴崎 正勝; 西田 直生志; 工藤 正俊
    肝臓 62 Suppl.2 A552 - A552 (一社)日本肝臓学会 2021年09月
  • Satoru Hagiwara; Naoshi Nishida; Masatoshi Kudo
    Liver cancer 10 5 535 - 538 2021年09月
  • Ryutaro Takada; Kosuke Minaga; Akane Hara; Yasuo Otsuka; Shunsuke Omoto; Ken Kamata; Kentaro Yamao; Mamoru Takenaka; Satoru Hagiwara; Hajime Honjo; Shigenaga Matsui; Takaaki Chikugo; Tomohiro Watanabe; Masatoshi Kudo
    Journal of Clinical Medicine 10 16 3716 - 3716 2021年08月 
    Due to the tendency of gastric linitis plastica (GLP) to cause extensive submucosal infiltration, a superficial endoscopic biopsy sometimes yields no evidence of malignancy, hindering definite diagnosis. The present study was a single-center retrospective analysis of 54 consecutive patients diagnosed with GLP between 2016 and 2020 to evaluate EUS-guided fine-needle aspiration (EUS-FNA) biopsy outcomes in patients with negative endoscopic biopsy findings. A pathological GLP diagnosis was achieved by endoscopic biopsy in 40 patients (74.1%). EUS-FNA biopsy with a 22-gauge needle was performed in 13 of the remaining 14 patients, and GLP diagnosis was confirmed in 10 patients, with a median of three needle passes. The remaining four patients were laparoscopically diagnosed with GLP. The diagnostic ability of EUS-FNA biopsy for GLP was 76.9%, and EUS-FNA biopsy contributed to GLP diagnosis in 18.5% (10/54) of all cases. None of the 13 patients exhibited EUS-FNA biopsy-related adverse events. Univariable and multivariable analyses revealed an absence of superficial ulcerations as a predictor of false-negative endoscopic biopsy findings in patients with GLP. These results suggest EUS-FNA biopsy as a minimally invasive and safe alternative diagnostic modality for GLP in cases where conventional endoscopic biopsy fails to verify malignancy, although prospective studies with larger cohorts are warranted to confirm these findings.
  • Kota Takashima; Yoriaki Komeda; Toshiharu Sakurai; Sho Masaki; Tomoyuki Nagai; Shigenaga Matsui; Satoru Hagiwara; Mamoru Takenaka; Naoshi Nishida; Hiroshi Kashida; Konosuke Nakaji; Tomohiro Watanabe; Masatoshi Kudo
    World Journal of Gastrointestinal Pharmacology and Therapeutics 12 4 79 - 89 2021年07月 
    BACKGROUND: Preparation for colon capsule endoscopy (CCE) requires a large liquid laxative volume for capsule excretion, which compromises the procedure's tolerability. AIM: To assess the safety and utility of castor oil-boosted bowel preparation. METHODS: This prospective cohort study including 20 patients (age range, 16-80 years; six men and 14 women) suspected of having colorectal disease was conducted at Kindai University Hospital from September 2017 to August 2019. All patients underwent CCE because of the following inclusion criteria: previous incomplete colonoscopy in other facility (n = 20), history of abdominal surgery (n = 7), or organ abnormalities such as multiple diverticulum (n = 4) and adhesion after surgery (n = 6). The exclusion criteria were as follows: Dysphagia, history of allergic reactions to the drugs used in this study (magnesium citrate, polyethylene glycol, metoclopramide, and castor oil), possibility of pregnancy, possibility of bowel obstruction or stenosis based on symptoms, or scheduled magnetic resonance imaging within 2 wk after CCE. The primary outcome was the capsule excretion rate within the battery life, as evaluated by the total large bowel observation rate, large bowel transit time, and bowel creasing level using a five-grade scale in different colorectal segments. The secondary outcomes were complications, colorectal lesion detection rates, and patients' tolerability. RESULTS: The castor oil-based regimen was implemented in 17 patients. Three patients cancelled CCE because they could tolerate castor oil, but not liquid laxatives. The capsule excretion rate within the battery life was 88% (15/17). The mean large bowel transit time was 236 min. Approximately 70% of patients had satisfactory colon cleansing levels. CCE detected colon polyps (14/17, 82%) and colonic diverticulum (4/12, 33%). The sensitivity, specificity, and diagnostic accuracy rates for detecting colorectal polyps (size ≥ 6 mm) were 76.9%, 75.0%, and 76.4%, respectively. The sensitivity, specificity, and diagnostic accuracy rates for detection of diverticulum were 100% each. Twelve patients (71%) rated CCE as more than "good", confirming the new regimen's tolerability. No serious adverse events occurred during this study. CONCLUSION: The castor oil-based regimen could reduce bowel preparation dose and improve CCE tolerability.
  • Masahiro Morita; Naoshi Nishida; Kazuko Sakai; Tomoko Aoki; Hirokazu Chishina; Masahiro Takita; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima; Kazuto Nishio; Yukari Kobayashi; Kazuhiro Kakimi; Masatoshi Kudo
    Liver Cancer 10 4 380 - 393 2021年07月 
    Introduction: Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Methods: Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Results: Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γresponse, inhibitory molecules, and regulatory T cells. Discussion/Conclusion: The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI.
  • Yoriaki Komeda; Hisashi Handa; Ryoma Matsui; Shohei Hatori; Riku Yamamoto; Toshiharu Sakurai; Mamoru Takenaka; Satoru Hagiwara; Naoshi Nishida; Hiroshi Kashida; Tomohiro Watanabe; Masatoshi Kudo
    PLOS ONE 16 6 e0253585 - e0253585 2021年06月 
    Convolutional neural networks (CNNs) are widely used for artificial intelligence (AI)-based image classification. Residual network (ResNet) is a new technology that facilitates the accuracy of image classification by CNN-based AI. In this study, we developed a novel AI model combined with ResNet to diagnose colorectal polyps. In total, 127,610 images consisting of 62,510 images with adenomatous polyps, 30,443 with non-adenomatous hyperplastic polyps, and 34,657 with healthy colorectal normal mucosa were subjected to deep learning after annotation. Each validation process was performed using 12,761 stored images of colorectal polyps by a 10-fold cross validation. The efficacy of the ResNet system was evaluated by sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and diagnostic accuracy. The sensitivity, specificity, PPV, NPV, and diagnostic accuracy for adenomatous polyps at WLIs were 98.8%, 94.3%, 90.5%, 87.4%, and 92.8%, respectively. Similar results were obtained for adenomatous polyps at narrow-band imagings (NBIs) and chromoendoscopy images (CEIs) (NBIs vs. CEIs: sensitivity, 94.9% vs. 98.2%; specificity, 93.9% vs. 85.8%; PPV, 92.5% vs. 81.7%; NPV, 93.5% vs. 99.9%; and overall accuracy, 91.5% vs. 90.1%). The ResNet model is a powerful tool that can be used for AI-based accurate diagnosis of colorectal polyps.
  • Satoru Hagiwara; Tomohiro Watanabe; Masatoshi Kudo; Kosuke Minaga; Yoriaki Komeda; Ken Kamata; Masatomo Kimura; Hidetoshi Hayashi; Kazuhiko Nakagawa; Kazuomi Ueshima; Yasunori Minami; Tomoko Aoki; Masahiro Takita; Masahiro Morita; Hirokazu Cishina; Hiroshi Ida; Ah-Mee Park; Naoshi Nishida
    Scientific reports 11 1 9242 - 9242 2021年04月 
    Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) are widely used to treat advanced metastatic cancers. Neutralisation of PD-1 or CTLA-4 by ICIs results in immune-related adverse events (irAEs). The clinicopathological features of twelve patients with hepatic irAEs were evaluated and compared to those of ten patients with autoimmune hepatitis (AIH) or graft-versus-host disease (GVHD). No significant difference was seen in serum levels of transaminases, whereas serum levels of IgG and anti-nuclear antibody were higher in patients with AIH than in those with GVHD or hepatic irAEs. Inflammation was limited to the liver lobes in patients with GVHD or hepatic irAEs, whereas patients with AIH exhibited both portal and lobular inflammation. Immunohistochemical analyses revealed a predominant infiltration of CD8+ T cells and defective accumulation of regulatory T cells (Tregs) expressing forkhead box p3 (FOXP3) in the lobular areas of patients with hepatic irAEs and GVHD. In contrast, periportal lesions of patients with AIH were characterised by an infiltration of CD4+ T cells, CD8+ T cells, CD20+ B cells, and FOXP3+ Tregs. Overall, the activation of CD8+ T cells in the absence of activation of Tregs potentially underlies the immunopathogenesis of hepatic irAEs.
  • Satoru Hagiwara; Naoshi Nishida; Kazuomi Ueshima; Akihiro Yoshida; Yasunori Minami; Masatoshi Kudo
    Hepatology research : the official journal of the Japan Society of Hepatology 51 7 767 - 774 2021年04月 
    AIM: Both entecavir (ETV) and tenofovir alafenamide fumarate (TAF) are widely used to treat chronic hepatitis B (CHB) in Japan. However, it remains unclear whether the efficacy of TAF in decreasing the hepatitis B surface antigen (HBsAg) level, and its safety, are superior to those of ETV. This study aimed to report the long-term effects and safety of 96-week ETV and TAF treatment in patients with CHB. METHODS: A prospective comparative observational study was undertaken on the following two groups: patients with CHB who received continuous ETV (n = 32) and patients with CHB who were switched from ETV to TAF upon request (n = 48). The HBsAg, urinary β2-microglobulin (β2MG)/creatinine (Cr), urinary N-acetyl-β-D-glucosaminidase (NAG)/Cr, and serum alanine aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR), and bone mineral density (lumbar spine and femur) at 96 weeks were compared. RESULTS: The two groups did not significantly differ with respect to mean age, male / female patient ratio, or rate of hepatitis B e antigen-positive status. The mean changes in serum HBsAg level and eGFR at 96 weeks were not significantly different between the two groups. The β2MG/Cr and NAG/Cr levels at 96 weeks were similar between the two groups. Additionally, the bone mineral density of the lumbar spine and femur as well as the serum ALT did not significantly differ. CONCLUSIONS: When compared with patients who received continuous ETV, those who were introduced to TAF after ETV showed similar effects in terms of the decrease in HBsAg level and safety.
  • Ikue Sekai; Satoru Hagiwara; Tomohiro Watanabe; Masatoshi Kudo
    Clinical journal of gastroenterology 14 4 1191 - 1196 2021年03月 
    Systemic administration of anti-programmed cell death 1 (PD-1) antibody (Ab) has achieved remarkable success in metastatic cancers. The blockade of PD-1-mediated signaling pathways sometimes cause immune-related adverse events (irAEs) due to restored anti-cancer as well as anti-self immunity. Although the liver is a preferential organ for irAEs, the immuno-pathogenesis underlying hepatic irAEs has been poorly understood. We describe a 57-year-old man with Stage IV lung cancer who underwent the first-line regimen composed of carboplatin and paclitaxel. Nivolumab treatment (3.2 mg/kg, every 3 weeks) was initiated when the disease progressed after the first chemotherapy. Sequential occurrence of irAEs involving the multiorgan systems was observed. He developed hepatic irAEs (Grade 3) after endocrine, lung, and cutaneous irAEs. Lobular hepatitis characterized by predominant infiltration of CD8+ T cells was seen in the liver biopsy specimens. Interestingly, defective accumulation of regulatory T cells (Tregs) expressing forkhead box protein P3 (FOXP3) was evident in this case with hepatic irAEs as compared with typical cases with autoimmune hepatitis. This case suggests that hepatic irAEs are characterized not only by lobular infiltration of CD8+ T cells but also by defective accumulation of FOXP3+ Tregs.
  • Yoriaki Komeda; Toshiharu Sakurai; Kazuko Sakai; Yasuyoshi Morita; Arito Hashimoto; Tomoyuki Nagai; Satoru Hagiwara; Itaru Matsumura; Kazuto Nishio; Masatoshi Kudo
    World journal of clinical cases 8 24 6389 - 6395 2020年12月 
    BACKGROUND: Concomitant ulcerative colitis (UC) and idiopathic thrombocytopenic purpura (ITP) is a rare phenomenon. The management of UC with ITP can be challenging, since a decreased platelet count augments UC. CASE SUMMARY: A 24-year-old man with UC and steroid-resistant ITP experienced UC flare. Although continuous infusion of cyclosporine was initiated, UC did not improve. The administration of tofacitinib subsequently led to the induction of remission. The patient has maintained remission of UC and ITP for over one year on tofacitinib treatment. Whole transcriptomic sequencing was performed for inflamed rectal mucosae obtained before and after the initiation of Janus kinase (JAK) inhibitor, suggesting that distinct molecular signatures seemed to be regulated by JAK inhibitors and other conventional therapies including tumor necrosis factor lockers. CONCLUSION: Tofacitinib should be considered in refractory cases of UC with ITP.
  • 進行肝癌に対する免疫チェックポイント阻害薬後レンバチニブ療法の画像評価
    青木 智子; 依田 広; 盛田 真弘; 南 知宏; 田北 雅弘; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    超音波医学 47 Suppl. S167 - S167 (公社)日本超音波医学会 2020年11月
  • 鑑別診断において造影超音波が有用であった多血性の肝内胆管癌の1例
    盛田 真弘; 南 康範; 青木 智子; 田北 雅弘; 萩原 智; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    超音波医学 47 Suppl. S275 - S275 (公社)日本超音波医学会 2020年11月
  • 進歩する化学療法時代に注意すべき肝細胞癌の遠隔転移
    吉田 早希; 青木 智子; 上嶋 一臣; 盛田 真弘; 千品 寛和; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 鶴崎 正勝; 西田 直生志; 工藤 正俊
    肝臓 61 Suppl.3 A924 - A924 (一社)日本肝臓学会 2020年11月
  • 難治性腹水に対するデンバーシャント術の試み
    家村 郁衣; 青木 智子; 上嶋 一臣; 盛田 真弘; 千品 寛和; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 鶴崎 正勝; 西田 直生志; 工藤 正俊
    肝臓 61 Suppl.3 A946 - A946 (一社)日本肝臓学会 2020年11月
  • Tomoko Aoki; Masatoshi Kudo; Kazuomi Ueshima; Masahiro Morita; Hirokazu Chishina; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Yasunori Minami; Masakatsu Tsurusaki; Naoshi Nishida
    Cancers 12 10 2020年10月 
    Although programmed cell death protein 1 (PD-1)/PD-ligand 1 (PD-L1) blockade is effective in a subset of patients with hepatocellular carcinoma (HCC), its therapeutic response is still unsatisfactory. Alternatively, the potential impact of the lenvatinib in patients who showed tumor progression on PD-1/PD-L1 blockade is unknown. In this work, we evaluated the safety and efficacy of lenvatinib administration after PD-1/PD-L1 checkpoint blockade. The outcome and safety of lenvatinib administered after PD-1/PD-L1 blockade failure was analyzed retrospectively in 36 patients. Tumor growth was assessed every 4-8 weeks using modified Response Evaluation Criteria in Solid Tumors. The mean relative dose intensity of lenvatinib was 87.6% and 77.8% in patients receiving a starting dose of 8 (interquartile range (IQR), 77.5-100.0) mg and 12 (IQR, 64.4-100.0) mg, respectively. Since lenvatinib therapy initiation, the median progression-free survival was 10 months (95% confidence interval (CI): 8.3-11.8) and the median overall survival was 15.8 months (95% CI: 8.5-23.2). The objective response rate was 55.6%, and the disease control rate was 86.1%. No particular safety concerns were observed. Lenvatinib demonstrated considerable antitumor effects with acceptable safety in patients with progressive and unresectable HCC when administered right after PD-1/PD-L1 blockade failure.
  • 消化器癌化学療法の進歩と課題 切除不能進行肝癌に対する免疫チェックポイント阻害薬不応後の二次治療を見据えて
    青木 智子; 萩原 智; 上嶋 一臣; 工藤 正俊
    日本消化器病学会近畿支部例会プログラム・抄録集 113回 54 - 54 日本消化器病学会-近畿支部 2020年10月
  • 鑑別診断に造影超音波が有用であった多血性の肝内胆管癌の1例
    吉田 早希; 南 康範; 盛田 真弘; 青木 智子; 田北 雅弘; 萩原 智; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部例会プログラム・抄録集 113回 103 - 103 日本消化器病学会-近畿支部 2020年10月
  • 全身化学療法により生存利益を得られる切除不能C型肝細胞癌の特徴
    青木 智子; 上嶋 一臣; 盛田 真弘; 千品 寛和; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 西田 直生志; 鶴崎 正勝; 工藤 正俊
    肝臓 61 Suppl.2 A647 - A647 (一社)日本肝臓学会 2020年09月
  • 切除不能肝細胞癌に対する免疫チェックポイント阻害薬不応後のレンバチニブ二次療法
    青木 智子; 上嶋 一臣; 盛田 真弘; 千品 寛和; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 西田 直生志; 鶴崎 正勝; 工藤 正俊
    肝臓 61 Suppl.2 A654 - A654 (一社)日本肝臓学会 2020年09月
  • Naoshi Nishida; Kazuko Sakai; Masahiro Morita; Tomoko Aoki; Masahiro Takita; Satoru Hagiwara; Yoriaki Komeda; Mamoru Takenaka; Yasunori Minami; Hiroshi Ida; Kazuomi Ueshima; Kazuto Nishio; Masatoshi Kudo
    Liver cancer 9 4 426 - 439 2020年08月 [査読有り]
     
    Background and Aim: Immune checkpoint inhibitors are promising agents for the treatment of hepatocellular carcinomas (HCC) refractory to conventional therapies. To enhance the efficacy of this treatment, immunological and molecular characteristics of HCC with programmed cell death ligand 1 (PD-L1) should be explored. Methods: Clinical backgrounds, PD-L1 expression, and the amount of CD8+ tumor-infiltrating mononuclear cells (TIMCs) were analyzed in 154 HCCs. The expression of 3 stem cell markers and co-inhibitory receptors on tumor cells and TIMCs, respectively, were examined by immunohistochemical analysis. Somatic mutations in the 409 cancer-associated genes and TERT promoter were determined; HCCs were classified based on the presence of gene alterations affecting the 8 oncogenic pathways. The results were validated using the dataset from the Cancer Genome Atlas. Results: The expression of PD-L1 in the HCCs was positively correlated with progressive tumor features, the presence of cytokeratin 19 (CK19), Sal-like protein 4 (SALL4), and the mutations of genes involving the phosphatidyl inositol 3-kinase (PI3K)-Akt pathway. Although CD8+ cells were densely infiltrated in PD-L1-positive tumors, these TIMCs frequently expressed multiple co-inhibitory receptors. However, a subset of PD-L1-positive tumors characterized by activating mutations of the PI3K-Akt pathway showed a low degree of TIMCs. Conversely, PD-L1-negative HCCs were associated with mutations in the β-catenin pathway and a small number of TIMCs, although the expression of co-inhibitory receptors was rare. Conclusions: PD-L1-positive HCCs frequently showed an inflamed phenotype with stem cell features; a subset of PD-L1-positive HCCs with mutations in the PI3K-Akt pathway showed a non-inflamed phenotype. In HCCs with dense infiltration of TIMCs, CD8+ cells expressed multiple co-inhibitory receptors, suggesting T cell exhaustion. On the other hand, PD-L1-negative HCCs showed mutations leading to β-catenin activation and exhibited a non-inflamed background. These characteristics should be taken into consideration for developing novel combination therapies using immune checkpoint inhibitors.
  • 大塚 康生; 青木 智子; 南 知宏; 田北 雅弘; 萩原 智; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本消化器病学会雑誌 117 臨増総会 A291 - A291 (一財)日本消化器病学会 2020年07月
  • 金村 宙昌; 林 秀敏; 原谷 浩司; 米阪 仁雄; 中川 和彦; 萩原 智; 工藤 正俊; 大谷 知之; 伊藤 彰彦
    肺癌 60 2 149 - 150 (NPO)日本肺癌学会 2020年04月
  • B型慢性肝炎患者(CH-B)に対する,ETVとTAFの前向き比較観察研究
    萩原 智; 盛田 真弘; 青木 智子; 田北 雅弘; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    肝臓 61 Suppl.1 A423 - A423 (一社)日本肝臓学会 2020年04月
  • B型慢性肝炎患者(CH-B)に対する,ETVとTAFの前向き比較観察研究
    萩原 智; 盛田 真弘; 青木 智子; 田北 雅弘; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 工藤 正俊
    肝臓 61 Suppl.1 A423 - A423 (一社)日本肝臓学会 2020年04月 [査読有り]
  • Hiroaki Kanemura; Hidetoshi Hayashi; Satoru Hagiwara; Tomoyuki Otani; Koji Haratani; Kimio Yonesaka; Akihiko Ito; Masatoshi Kudo; Kazuhiko Nakagawa
    Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 15 3 e39-e42  2020年03月 [査読有り]
  • Yasunori Minami; Tomohiro Minami; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    Hepatology research : the official journal of the Japan Society of Hepatology 50 1 67 - 74 2020年01月 [査読有り]
     
    AIM: To retrospectively investigate the potential benefit of ultrasound-ultrasound (US-US) overlay fusion guidance for local controllability of radiofrequency ablation (RFA) in the treatment of hepatocellular carcinoma (HCC). METHODS: Patients (n = 101) with 121 HCCs (mean ± SD, 1.8 ± 0.7 cm) who underwent RFA guided by US-US overlay fusion were included in the retrospective study. By overlaying pre/postoperative US, the tumor image could be projected onto the ablative hyperechoic zone. The ablative margin could thereby be evaluated three-dimensionally during the RFA procedure. As a control group, all 325 patients with 453 HCCs who underwent conventional RFA during the same study period were selected. RESULTS: The total number of RF needle insertions per tumor for ablation was significantly more in the US overlay fusion group (mean 1.9 vs. 1.2; P < 0.01). The technical success rates of ablation after a single session were 100% (101/101) and 96.6% (314/325) for the US overlay fusion group and the control group, respectively. For early assessment of RFA response, 5-mm safety margins were achieved in 89.3% (108/121) and 47.0% (213/453) of nodules in the US overlay fusion group and the control group, respectively (P < 0.01). During the follow-up period (median 19 months), the 2-year local tumor progression rates were 0.8% (1/121) and 6.0% (27/453) in the US overlay fusion group and the control group, respectively (P = 0.022, log-rank test). CONCLUSIONS: US-US overlay fusion guidance can be highly effective for safety margin achievement in RFA for HCC, providing a lower risk of local tumor progression.
  • 鑑別診断において造影超音波が有用であった多血性の肝内胆管癌(腫瘤形成型)の1例
    友岡 瑞樹; 盛田 真弘; 南 康範; 依田 広; 南 知宏; 青木 智子; 田北 雅弘; 萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊
    肝臓 60 Suppl.3 A926 - A926 (一社)日本肝臓学会 2019年11月 [査読有り]
  • Satoru Hagiwara; Naoshi Nishida; Hiroshi Ida; Kazuomi Ueshima; Yasunori Minami; Masahiro Takita; Yoriaki Komeda; Masatoshi Kudo
    Journal of medical virology 91 10 1804 - 1810 2019年10月 [査読有り]
     
    Tenofovir alafenamide (TAF) is a newly developed prodrug of tenofovir (TFV). We divided 48 chronic hepatitis B patients who had taken entecavir (ETV) for ≥2 years into two groups: the ETV continuation (n = 24) and the TAF switching (n = 24) groups, and compared the antiviral effects and safety until 48 weeks after the start of the study. There were no significant differences in the alterations in the serum levels of HBs antigen (HBsAg) level between the ETV continuation and the TAF switching groups at 24 or 48 weeks. We also examined the effect of baseline HBsAg level on the decrease of HBsAg during the treatment; in the TAF switching group, the decrease of HBsAg level at 48 weeks was more significant in patients with low baseline HBsAg (<800 IU/mL) than those with high baseline HBsAg ( >800 IU/mL) (change of HBsAg; - 0.029 vs - 0.132 for high and low baseline HBsAg, respectively, P = .007). Also, the effect on renal function was found to be comparable between the TAF switch group and the ETV continuation group. In this study, switching from ETV to TAF may represent higher efficacy for a decrease of HBsAg than a continuation of ETV among the patients with low baseline HBsAg level.
  • 難治性腹水に対して行われたデンバーシャント術の報告
    青木 智子; 田北 雅弘; 大塚 康生; 南 知宏; 萩原 智; 南 康範; 依田 広; 上嶋 一臣; 西田 直生志; 鶴崎 正勝; 工藤 正俊
    日本門脈圧亢進症学会雑誌 25 3 146 - 146 (一社)日本門脈圧亢進症学会 2019年09月 [査読有り]
  • Masatoshi Kudo; Kazuomi Ueshima; Stephan Chan; Tomohiro Minami; Hirokazu Chishina; Tomoko Aoki; Masahiro Takita; Satoru Hagiwara; Yasunori Minami; Hiroshi Ida; Mamoru Takenaka; Toshiharu Sakurai; Tomohiro Watanabe; Masahiro Morita; Chikara Ogawa; Yoshiyuki Wada; Masafumi Ikeda; Hiroshi Ishii; Namiki Izumi; Naoshi Nishida
    Cancers 11 8 pii: E1084  2019年07月 [査読有り]
     
    Although transcatheter arterial chemoembolization (TACE) is the standard of care for intermediate-stage hepatocellular carcinoma (HCC), this is a largely heterogeneous disease that includes a subgroup of patients who do not benefit from TACE. The treatment strategy for this subgroup of patients currently remains an unmet need in clinical practice. Here, we performed a proof-of-concept study that lenvatinib may be a more favorable treatment option over TACE as an initial treatment in intermediate-stage HCC patients with large or multinodular tumours exceeding the up-to-seven criteria. This proof-of-concept study included 642 consecutive patients with HCC initially treated with lenvatinib or conventional TACE (cTACE) between January 2006 and December 2018. Of these patients, 176 who received lenvatinib or cTACE as an initial treatment and met the eligibility criteria (unresectable, beyond the up-to-seven criteria, no prior TACE/systemic therapy, no vascular invasion, no extrahepatic spread and Child-Pugh A liver function) were selected for the study. Propensity score matching was used to adjust for patient demographics. After propensity-score matching, the outcome of 30 patients prospectively treated with lenvatinib (14 in clinical trials, one in an early access program and 15 in real world settings) and 60 patients treated with cTACE as the initial treatment was compared. The change of albumin-bilirubin (ALBI) score from baseline to the end of treatment were -2.61 to -2.61 for 30 patients in the lenvatinib group (p = 0.254) and -2.66 to -2.09 in the cTACE group (p < 0.01), respectively. The lenvatinib group showed a significantly higher objective response rate (73.3% vs. 33.3%; p < 0.001) and significantly longer median progression-free survival than the cTACE group (16.0 vs. 3.0 months; p < 0.001). Overall survival was significantly longer in the lenvatinib group than in the cTACE group (37.9 vs. 21.3 months; hazard ratio: 0.48, p < 0.01). In patients with large or multinodular intermediate-stage HCC exceeding the up-to-seven criteria with Child-Pugh A liver function, who usually do not benefit from TACE, lenvatinib provides a more favorable outcome than TACE.
  • Kentaro Yamao; Mamoru Takenaka; Tomoe Yoshikawa; Rei Ishikawa; Ayana Okamoto; Tomohiro Yamazaki; Atsushi Nakai; Shunsuke Omoto; Ken Kamata; Kosuke Minaga; Satoru Hagiwara; Toshiharu Sakurai; Naoshi Nishida; Yasutaka Chiba; Tomohiro Watanabe; Masatoshi Kudo
    Internal medicine (Tokyo, Japan) 58 14 1993 - 2002 2019年07月 [査読有り]
     
    Objective Although modified FOLFIRINOX (mFOLFIRINOX, mFFX) is widely used for patients with advanced pancreatic ductal adenocarcinoma (PDAC), maintenance of the standard dose intensity is often difficult due to the high incidence of neutropenic events. Pegylated granulocyte colony-stimulating factor (G-CSF) (Peg G) is a long-lasting G-CSF agent that is applicable for prophylaxis against neutropenic complications. The aim of this study was to assess the clinical safety and efficacy of mFFX combined with secondary prophylaxis using Peg G in advanced PDAC patients. Methods Advanced PDAC patients who had received more than two cycles of mFFX were analyzed. The clinical safety and efficacy were compared between patients in the Peg G group and those in the non-Peg G group in a retrospective manner. Results Among 45 patients treated with mFFX, 28 exhibited grade 3-4 neutropenia or febrile neutropenia. Among these 28 patients, 4 who received only 1 or 2 mFFX cycles were excluded from this study. Finally, 11 patients in the Peg G group and 13 in the non-Peg G group were enrolled. The combination therapy with Peg G and mFFX markedly prolonged the progression-free survival compared with the non-Peg G group, and its effects were associated with a reduced incidence of neutropenic events as well as lower rates of dosage reduction, delayed chemotherapy due to neutropenic events and altered blood cell counts after chemotherapy. Conclusion The scheduled administration of secondary prophylactic Peg G prolonged the progression-free survival in patients treated with mFFX. The combination therapy of Peg G and mFFX may be recommended in patients who exhibit grade 3-4 neutropenic events after prior mFFX cycles.
  • Masashi Kono; Toshiharu Sakurai; Kazuki Okamoto; Tomoyuki Nagai; Yoriaki Komeda; Hiroshi Kashida; Kosuke Minaga; Ken Kamata; Mamoru Takenaka; Satoru Hagiwara; Tomohiro Watanabe; Naoshi Nishida; Eisuke Enoki; Hiroaki Inoue; Itaru Matsumura; Masatoshi Kudo
    Internal medicine (Tokyo, Japan) 58 14 2029 - 2033 2019年07月 [査読有り]
     
    Autoimmune diseases including inflammatory bowel disease (IBD) occur in association with myelodysplastic syndrome (MDS). MDS-associated IBD frequently demonstrates a complicated course. We herein report the first case with MDS-associated IBD that was successfully treated with ustekinumab (UST), an anti-interleukin (IL) 12/23p40 monoclonal antibody. A 63-year-old man with a 7-year history of MDS was referred for examination of diarrhea, abdominal pain and fever. A blood examination revealed a marked elevation of C-reactive protein. Colonoscopy showed multiple ulcers in the terminal ileum. He was resistant to anti-tumor necrosis factor (TNF)-α antibody and azacitidine. Subsequently, UST treatment reduced colonic IL-17 and IL-6 expression and the patient currently maintains a state of remission.
  • Kazuomi Ueshima; Naoshi Nishida; Satoru Hagiwara; Tomoko Aoki; Tomohiro Minami; Hirokazu Chishina; Masahiro Takita; Yasunori Minami; Hiroshi Ida; Mamoru Takenaka; Toshiharu Sakurai; Tomohiro Watanabe; Masahiro Morita; Chikara Ogawa; Atsushi Hiraoka; Philip Johnson; Masatoshi Kudo
    Cancers 11 7 pii: E952.  2019年07月 [査読有り]
     
    BACKGROUND: This study investigated the impact of baseline liver function according to the Child-Pugh score and ALBI (albumin-bilirubin) grade on the outcomes of patients with unresectable hepatocellular carcinoma treated with lenvatinib. METHODS: A total of 82 lenvatinib treated patients were included. The correlations of baseline liver function according to the Child-Pugh score and ALBI grade with treatment outcomes, including objective response rate per mRECIST (modified Response Evaluation Criteria in the Solid Tumor), time to treatment failure, treatment duration, and likelihood of treatment discontinuation due to adverse events, were assessed in patients with hepatocellular carcinoma treated with lenvatinib. Patients were divided into four groups: (1) Child-Pugh score 5 and ALBI grade 1 (group 1), (2) Child-Pugh score 5 and ALBI grade 2 (group 2), (3) Child-Pugh score 6 (group 3), and (4) Child-Pugh score ≥7 (group 4). Univariate and multivariate analyses were performed to identify the factors contributing to the objective response rate and likelihood of discontinuation due to adverse events. Results: Among the 82 patients analyzed, group 1 had the highest objective response rate (57.1%) and the lowest likelihood of treatment discontinuation because of adverse events (11.1%) among the four groups (p < 0.05 and p < 0.05). Multivariate analysis identified ALBI grade 1 and baseline AFP level <200 ng/mL as the significant predictors of a high objective response rate (p < 0.05 and p < 0.01), and confirmed that patients with ALBI grade 1 had the lowest probability of treatment discontinuation due to adverse events (p < 0.01). Conclusions: Patients with Child-Pugh score of 5 and ALBI grade 1 predicted a higher response rate and lower treatment discontinuation due to adverse events by lenvatinib treatment.
  • Yoriaki Komeda; Tomohiro Watanabe; Toshiharu Sakurai; Masashi Kono; Kazuki Okamoto; Tomoyuki Nagai; Mamoru Takenaka; Satoru Hagiwara; Shigenaga Matsui; Naoshi Nishida; Naoko Tsuji; Hiroshi Kashida; Masatoshi Kudo
    World journal of gastroenterology 25 12 1502 - 1512 2019年03月 [査読有り]
     
    BACKGROUND: Risk factors for local recurrence after polypectomy, endoscopic mucosal resection (EMR), and endoscopic submucosal dissection (ESD) have not been identified. Additionally, the appropriate interval for endoscopic surveillance of colorectal tumors at high-risk of local recurrence has not been established. AIM: To clarify the clinicopathological characteristics of recurrent lesions after endoscopic colorectal tumor resection and determine the appropriate interval. METHODS: Three hundred and sixty patients (1412 colorectal tumors) who underwent polypectomy, EMR, or ESD and received endoscopic surveillance subsequently for more than one year to detect local recurrence were enrolled in this study. The clinicopathological factors associated with local recurrence were determined via univariate and multivariate analyses. RESULTS: Local recurrence was observed in 31 of 360 (8.6%) patients [31 of 1412 (2.2%) lesions] after colorectal tumor resection. Piecemeal resection, tumor size of more than 2 cm, and the presence of villous components were associated with colorectal tumor recurrence after endoscopic resection. Of these three factors, the piecemeal resection procedure was identified as an independent risk factor for recurrence. Colorectal tumors resected into more than five pieces were associated with a high risk of recurrence since the average period from resection to recurrence in these cases was approximately 3 mo. The period to recurrence in cases resected into more than 5 pieces was much shorter than that in those resected into less than 4 pieces (3.8 ± 1.9 mo vs 7.9 ± 5.0 mo, P < 0.05). CONCLUSION: Local recurrence of endoscopically treated colorectal tumors depends upon the outcome of first endoscopic procedure. Piecemeal resection was the only significant risk factor associated with local recurrence after endoscopic resection.
  • Toshiharu Sakurai; Yoriaki Komeda; Tomoyuki Nagai; Ken Kamata; Kosuke Minaga; Kentarou Yamao; Mamoru Takenaka; Satoru Hagiwara; Tomohiro Watanabe; Naoshi Nishida; Hiroshi Kashida; Kazuhiko Nakagawa; Masatoshi Kudo
    Digestion 100 3 192 - 200 2019年 [査読有り]
     
    BACKGROUND: Although Gankyrin is overexpressed in many malignancies, the role of Gankyrin for tumorigenesis and chemoresistance remains to be elucidated in sporadic colorectal cancer (CRC). AIMS: We investigate whether Gankyrin affects Adenomatous polyposis coli (Apc) inactivation-induced tumorigenesis and therapeutic response to anti-angiogenic agents. METHODS: Epithelial cell-specific APC and/or Gankyrin-deficient mice were used. The patients with metastatic CRC (n = 53) who were enrolled in this study underwent resection of primary cancer followed by systemic chemotherapy containing bevacizumab. We determined whether gene expression in CRC tissues before chemotherapy is associated with radiological responses. RESULTS: Deletion of Gankyrin in epithelial cell reduced the expression of c-Myc, a critical mediator of the APC signaling pathway, and interleukin-6. Gankyrin deficiency decreased the expression of Bmi1, a downstream molecule of c-Myc, and the activity of V-Akt murine thymoma viral oncogene homolog and extracellular signal-regulated protein kinase, leading to reduced Apc inactivation-induced tumorigenesis. Of 53 patients, 38 (72%) had increased Gankyrin expression in tumor cells. The enhanced Gankyrin expression in tumor cells was associated with unfavorable progression-free survival (log-rank test p = 0.026). CONCLUSION: Gankyrin in epithelial cell contributes to the development of sporadic CRC and the expression could serve as a biomarker to predict therapeutic response in patients with metastatic CRC.
  • Naoshi Nishida; Takafumi Nishimura; Toshimi Kaido; Kosuke Minaga; Kentaro Yamao; Ken Kamata; Mamoru Takenaka; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Tomohiro Watanabe; Masatoshi Kudo
    Cancers 10 10 367 - 367 2018年09月 [査読有り]
     
    Hepatocellular carcinoma (HCC) causes one of the most frequent cancer-related deaths; an HCC subset shows rapid progression that affects survival. We clarify molecular features of aggressive HCC, and establish a molecular scoring system that predicts metastasis after curative treatment. In total, 125 HCCs were examined for TP53, CTNNB1, and TERT promoter mutation, methylation of 8 tumor suppressor genes, and 3 repetitive DNA sequences to estimate promoter hypermethylation and global hypomethylation. A fractional allelic loss (FAL) was calculated to represent chromosomal instability through microsatellite analysis. Molecular subclasses were determined using corresponding and hierarchical clustering analyses. Next, twenty-five HCC patients who underwent liver transplantation were analyzed for associations between molecular characteristics and metastatic recurrence; survival analyses were validated using a publicly available dataset of 376 HCC cases from the Cancer Genome Atlas (TCGA). An HCC subtype characterized by TP53 mutation, high FAL, and global hypomethylation was associated with aggressive tumor characteristics, like vascular invasion; CTNNB1 mutation was a feature of the less-progressive phenotype. A number of molecular risk factors, including TP53 mutation, high FAL, significant global hypomethylation, and absence of CTNNB1 mutation, were noted to predict shorter recurrence-free survival in patients who underwent liver transplantation (p = 0.0090 by log-rank test). These findings were validated in a cohort of resected HCC cases from TCGA (p = 0.0076). We concluded that molecular risks determined by common genetic and epigenetic alterations could predict metastatic recurrence after curative treatments, and could be a marker for considering systemic therapy for HCC patients.
  • Yasunori Minami; Tomohiro Minami; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Takamichi Murakami; Masatoshi Kudo
    European Radiology 28 5 1986 - 1993 2018年05月 [査読有り]
     
    Objectives: To assess the clinical feasibility of US-US image overlay fusion with evaluation of the ablative margin in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Methods: Fifty-three patients with 68 HCCs measuring 0.9–4.0 cm who underwent RFA guided by US-US overlay image fusion were included in this retrospective study. By an overlay of pre-/postoperative US, the tumor image could be projected onto the ablative hyperechoic zone. Therefore, the ablative margin three-dimensionally could be shown during the RFA procedure. US-US image overlay was compared to dynamic CT a few days after RFA for assessment of early treatment response. Accuracy of graded response was calculated, and the performance of US-US image overlay fusion was compared with that of CT using a Kappa agreement test. Results: Technically effective ablation was achieved in a single session, and 59 HCCs (86.8 %) succeeded in obtaining a 5-mm margin on CT. The response with US-US image overlay correctly predicted early CT evaluation with an accuracy of 92.6 % (63/68) (k = 0.67 95 % CI: 0.39–0.95). Conclusion: US-US image overlay fusion can be proposed as a feasible guidance in RFA with a safety margin and predicts early response of treatment assessment with high accuracy. Key points: • US-US image overlay fusion visualizes the ablative margin during RFA procedure. • Visualizing the margin during the procedure can prompt immediate complementary treatment. • US image fusion correlates with the results of early evaluation CT.
  • Masashi Kono; Yoriaki Komeda; Toshiharu Sakurai; Ayana Okamoto; Kosuke Minaga; Ken Kamata; Satoru Hagiwara; Hiroaki Inoue; Eisuke Enoki; Itaru Matsumura; Tomohiro Watanabe; Masatoshi Kudo
    Journal of Crohn's and Colitis 12 4 499 - 502 2018年03月 [査読有り]
  • Satoru Hagiwara; Naoshi Nishida; Tomohiro Watanabe; Hiroshi Ida; Toshiharu Sakurai; Kazuomi Ueshima; Masahiro Takita; Yoriaki Komeda; Norihiro Nishijima; Yukio Osaki; Masatoshi Kudo
    Antiviral therapy 23 6 513 - 521 2018年 [査読有り]
     
    BACKGROUND: Although the efficacy of combination therapy with lamivudine or tenofovir and pegylated interferon (PEG-IFN) has been reported in patients with chronic hepatitis B (CHB), the long-term effect of the combination based on the observation of clinical course remains to be clarified. We previously reported the efficacy of combination therapy with entecavir (ETV) and PEG-IFN. Here, we investigated the long-term effect of this combination in patients with CHB. METHODS: We administered both ETV and PEG-IFN-α2a or -2b simultaneously to 26 patients with HBV genotype C infection. Treatment was continued for 48 weeks followed by 24 weeks of observation period; we examined the virological and biochemical responses. We also analysed characteristics related to the post-treatment relapse. Finally, we investigated the long-term therapeutic effects. RESULTS: Average reduction of intra-hepatic cccDNA level was 1.2 log copies/μg at the completion of administration. Pretreatment hepatitis B surface antigen (HBsAg) level with more than 3.5 log U/ml was identified as a predictive factor for relapse. Furthermore, the cumulative rates of HBsAg-negative patients at 1, 3 and 5 years after the completion of administration were 3.8, 8.4 and 15%, respectively (mean follow-up period: 4.8 years). CONCLUSIONS: Baseline HBsAg level with more than 3.5 log U/ml is a useful predictor for relapse 24 weeks after the completion of administration in patients treated with combination therapy. Combination with ETV and PEG-IFN could be an option for treatment of CHB patients especially in those with baseline HBsAg levels of less than 3.5 log U/ml.
  • Kazuki Okamoto; Tomohiro Watanabe; Yoriaki Komeda; Ayana Okamoto; Kosuke Minaga; Ken Kamata; Kentaro Yamao; Mamoru Takenaka; Satoru Hagiwara; Toshiharu Sakurai; Tomonori Tanaka; Hiroki Sakamoto; Kiyoshige Fujimoto; Naoshi Nishida; Masatoshi Kudo
    Frontiers in immunology 9 918 - 918 2018年 [査読有り]
     
    Cap polyposis is a rare gastrointestinal disease characterized by multiple inflammatory polyps located between the distal colon and the rectum. Despite the lack of clarity regarding its pathogenesis, mucosal prolapse, chronic inflammatory responses, and Helicobacter pylori infection are considered key contributors to the development of this disease entity. Although it is now generally accepted that dysbiosis of gut microbiota is associated with intestinal and extra-intestinal diseases, alterations of intestinal microbiota have been poorly defined in cap polyposis. Here, we report a patient with H. pylori-negative cap polyposis who was successfully treated with antibiotics and exhibited dramatic alterations in intestinal microbiota composition after antibiotic treatment. The patient was treated with oral administration of ampicillin and metronidazole and showed regression of cap polyposis 6 months after antibiotic treatment. Fecal microbiota analysis using the next-generation sequencing technology revealed a significant alteration in the intestinal microbiota composition following antibiotic treatment-a marked reduction of Blautia, Dorea, and Sutterella was observed concomitant with a marked increase in Fusobacterium. These data suggest that cap polyposis may originate from dysbiosis and that microbiome-targeted therapy may be useful in this disorder.
  • Akihiro Yoshida; Satoru Hagiwara; Tomohiro Watanabe; Naoshi Nishida; Hiroshi Ida; Toshiharu Sakurai; Yoriaki Komeda; Kentaro Yamao; Mamoru Takenaka; Eisuke Enoki; Masatomo Kimura; Masako Miyake; Akira Kawada; Masatoshi Kudo
    Internal medicine (Tokyo, Japan) 57 17 2505 - 2509 2018年 [査読有り]
     
    A 27-year-old man bearing an erythropoietic protoporphyria (EPP)-associated ferrochelatase (FECH) mutation was admitted to our hospital for general malaise and marked elevation of the serum levels of hepatobiliary enzymes and bilirubin. Initial treatment with plasma exchange did not reduce the blood protoporphyrin or serum liver enzyme levels, so phlebotomy was started. Surprisingly, weekly phlebotomy normalized the serum levels of liver enzymes, accompanied by a marked reduction in the blood protoporphyrin levels. The clinical course of this case strongly suggests that phlebotomy may be a suitable treatment option for EPP-related hepatopathy.
  • Yoriaki Komeda; Tomohiro Watanabe; Shigenaga Matsui; Hiroshi Kashida; Toshiharu Sakurai; Masashi Kono; Kosuke Minaga; Tomoyuki Nagai; Satoru Hagiwara; Eisuke Enoki; Masatoshi Kudo
    JGH open : an open access journal of gastroenterology and hepatology 1 2 74 - 75 2017年10月 [査読有り]
     
    This study showed that we need to bear in mind the possibility of gastric adenocarcinoma of the fundic gland type upon encounter with such elevated lesions originating from Helicobacter pylori (H. pylori)-negative gastric mucosa. We believe that our study makes a significant contribution to the literature because small invasive gastric adenocarcinoma of the fundic gland type is a rare disease entity, which exhibits a submucosal tumor-like or superficial flat-type elevated lesion on H. pylori-negative gastric mucosa in the endoscopic examinations.
  • Toshiharu Sakurai; Norihisa Yada; Satoru Hagiwara; Tadaaki Arizumi; Kosuke Minaga; Ken Kamata; Mamoru Takenaka; Yasunori Minami; Tomohiro Watanabe; Naoshi Nishida; Masatoshi Kudo
    CANCER SCIENCE 108 10 1996 - 2003 2017年10月 [査読有り]
     
    Most hepatocellular carcinomas (HCC) develop as a result of chronic liver inflammation. We have shown that the oncoprotein gankyrin is critical for inflammation-induced tumorigenesis in the colon. Although the invitro function of gankyrin is well known, its role invivo remains to be elucidated. We investigated the effect of gankyrin in the tumor microenvironment of mice with liver parenchymal cell-specific gankyrin ablation (Alb-Cre;gankyrin(f/f)) and gankyrin deletion both in liver parenchymal and non-parenchymal cells (Mx1-Cre;gankyrin(f/f)). Gankyrin upregulates vascular endothelial growth factor expression in tumor cells. Gankyrin binds to Src homology 2 domain-containing protein tyrosine phosphatase-1 (SHP-1), mainly expressed in liver non-parenchymal cells, resulting in phosphorylation and activation of signal transducer and activator of transcription 3 (STAT3). Gankyrin deficiency in non-parenchymal cells, but not in parenchymal cells, reduced STAT3 activity, interleukin (IL)-6 production, and cancer stem cell marker (Bmi1 and epithelial cell adhesion molecule [EpCAM]) expression, leading to attenuated tumorigenic potential. Chronic inflammation enhances gankyrin expression in the human liver. Gankyrin expression in the tumor microenvironment is negatively correlated with progression-free survival in patients undergoing sorafenib treatment for HCC. Thus, gankyrin appears to play a critical oncogenic function in tumor microenvironment and may be a potential target for developing therapeutic and preventive strategies against HCC.
  • Contribution of C1485T mutation in the HBx gene to human and murine hepatocarcinogenesis
    Hagiwara S; Nishida N; Park AM; Komeda Y; Sakurai T; Watanabe T; Kudo M
    Sci Rep 7 1 10440  2017年09月 [査読有り]
  • Yoriaki Komeda; Hiroshi Kashida; Toshiharu Sakurai; Masashi Kono; Tomoyuki Nagai; Yutaka Asakuma; Satoru Hagiwara; Shigenaga Matsui; Tomohiro Watanabe; Takaaki Chikugo; Masatoshi Kudo
    AMERICAN JOURNAL OF GASTROENTEROLOGY 112 6 833 - 833 2017年06月 [査読有り]
  • Tomohiro Watanabe; Kouhei Yamashita; Yasuyuki Arai; Kosuke Minaga; Ken Kamata; Tomoyuki Nagai; Yoriaki Komeda; Mamoru Takenaka; Satoru Hagiwara; Hiroshi Ida; Toshiharu Sakurai; Naoshi Nishida; Warren Strober; Masatoshi Kudo
    J Immunol 198 10 3886 - 3896 2017年05月 [査読有り]
     
    In previous studies, we found that human IgG4-related autoimmune pancreatitis (AIP) and murine AIP are driven by activation of plasmacytoid dendritic cells (pDCs) producing IFN-alpha. In the present studies we examined additional roles of pDC-related mechanisms in AIP pathogenesis, particularly those responsible for induction of fibrosis. We found that in murine AIP (MRL/Mp mice treated with polyinosinic-polycytidylic acid) not only the pancreatic infiltration of immune cells but also the development of fibrosis were markedly reduced by the depletion of pDCs or blockade of type I IFN signaling; moreover, such treatment was accompanied by a marked reduction of pancreatic expression of IL-33. Conversely, polyinosinic-polycytidylic acid-induced inflamed pancreatic tissue in murine AIP exhibited increased expression of type I IFNs and IL-33 (and downstream IL-33 cytokines such as IL-13 and TGF-beta 1). pDCs stimulated by type I IFN were the source of the IL-33 because purified populations of these cells isolated from the inflamed pancreas produced a large amount of IL-33 upon activation by TLR9 ligands, and such production was abrogated by the neutralization of type I IFN. The role of IL-33 in murine AIP pathogenesis was surprisingly important because blockade of IL-33 signaling by anti-ST2 Ab attenuated both pancreatic inflammation and accompanying fibrosis. Finally, whereas patients with both conventional pancreatitis and IgG4-related AIP exhibited increased numbers of acinar cells expressing IL-33, only the latter also exhibited pDCs producing this cytokine. These data thus suggest that pDCs producing IFN-alpha and IL-33 play a pivotal role in the chronic fibro-inflammatory responses underlying murine AIP and human IgG4-related AIP.
  • Toshiharu Sakurai; Hiroaki Higashitsuji; Hiroshi Kashida; Tomohiro Watanabe; Yoriaki Komeda; Tomoyuki Nagai; Satoru Hagiwara; Masayuki Kitano; Naoshi Nishida; Takaya Abe; Hiroshi Kiyonari; Katsuhiko Itoh; Jun Fujita; Masatoshi Kudo
    ONCOTARGET 8 15 24762 - 24776 2017年04月 [査読有り]
     
    Although long-standing colonic inflammation due to refractory inflammatory bowel disease (IBD) promotes the development of colitis-associated cancer (CAC), the molecular mechanisms accounting for the development of CAC remains largely unknown. In this study, we investigated the role of gankyrin in the development of CAC since gankyrin is overexpressed in sporadic colorectal cancers. We analyzed gene expression of colon tissues obtained from 344 patients with IBD and CAC and found that expression of gankyrin was much higher in colonic mucosa of patients with refractory IBD than in those with IBD in remission. Expression of gankyrin was upregulated in inflammatory cells as well as tumor cells in colonic mucosa of patients with CAC. Over-expressing studies utilizing tagged ganlyrin-cDNA identified physical interaction between ganlyrin and Src homology 2-containing protein tyrosine phosphatase-1 (SHP-1). Importantly, the interaction between ganlyrin and SHP1 leads to inhibition of STAT3 activation and to enhancement of TNF-alpha and IL-17 in inflammatory cells. To further address the role of gankyrin in the development of CAC, we created mice with intestinal epithelial cell-specific gankyrin ablation (Vil-Cre; Gankyrin(f/f)) and deletion of gankyrin in myeloid and epithelial cells (Mx1Cre; Gankyrin(f/f)). Gankyrin deficiency in myeloid cells, but not in epithelial cells, reduced the activity of mitogen activated protein kinase and the expression of stem cell markers, leading to attenuated tumorigenic potential. These findings provide important insights into the pathogenesis of CAC and suggest that gankyrin is a promising target for developing therapeutic and preventive strategies against CAC.
  • Toshiharu Sakurai; Hiroshi Kashida; Yoriaki Komeda; Tomoyuki Nagai; Satoru Hagiwara; Tomohiro Watanabe; Masayuki Kitano; Naoshi Nishida; Jun Fujita; Masatoshi Kudo
    INFLAMMATORY BOWEL DISEASES 23 1 66 - 74 2017年01月 [査読有り]
     
    Background: Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and often results from refractory inflammatory bowel disease (IBD). Stress response proteins Cirp and heat shock protein A4 are involved in the refractory clinical course and development of CAC. RNAbinding motif protein 3 (RBM3) is induced in response to various stresses and is upregulated in several cancers. However, the role of RBM3 in CAC is unclear. Methods: We assessed RBM3 expression and function in 263 human intestinal mucosa samples from patients with IBD and in Rbm3-deficient (Rbm3(-/-)) mice. Results: Expression of RBM3 was correlated with the expression of stress response proteins Cirp, heat shock protein A4, and HSP27 in the colonic mucosa of patients with IBD. Significant correlation was observed between the expression of RBM3 and that of Bcl-xL or stem cell markers. RBM3 expression increased and significantly correlated with R-spondin expression in the colonic mucosa of patients with refractory IBD, a condition associated with increased cancer risk, and RBM3 was overexpressed in human CACs. In the murine CAC model, Rbm3 deficiency decreased R-spondin and Bcl-xL expression and increased apoptotic cell number in the colonic mucosa, leading to reduced tumor multiplicity. Transplantation of wild-type and Rbm3(-/-) bone marrow did not alter tumor burden, indicating the importance of RBM3 in epithelial cells. Conclusions: Our findings indicated that RBM3 was required for efficient inflammatory carcinogenesis in the murine CAC model and suggested that RBM3 could be a predictive biomarker of CAC risk and a new therapeutic target for cancer prevention in patients with IBD.
  • Identification of a HBx mutation that enhances human hepatocarcinogenesis through the activation of the JNK and Wnt pathways.
    Hagiwara S; Nishida N; Sakurai T; Park AM; Komeda Y; Kitano M; Kudo M
    BMC Cancer in press 2017年 [査読有り]
  • Umehara Y; Hagiwara S; Nishida N; Sakurai T; Ida H; Minami Y; Takita M; Minami T; Chishina H; Ueshima K; Komeda Y; Arizumi T; Watanabe T; Kudo M
    Dig Dis 35 6 548 - 555 2017年 [査読有り]
     
    OBJECTIVE: It is a generally accepted fact that eradication of hepatitis virus C inhibits the subsequent development of hepatocellular carcinoma (HCC). On the contrary, a significant population of patients developed HCC despite sustained virological responses (SVRs) to interferon (IFN) therapy. METHODS: A total of 415 patients with chronic hepatitis C, who were treated at our hospital between 2004 and 2014, were enrolled for this study. We examined the risk factors for HCC development after IFN therapy. RESULTS: After analyzing various clinical parameters, it was concluded that a serum albumin (ALB) level <4.0 g/dL and the presence or absence of SVR achievement were risk factors for the development of HCC. When analyzing pre- and posttreatment factors, only a serum ALB level <4.0 g/dL was considered a significant risk factor. The presence or absence of liver fibrosis progression was not identified as a risk factor. CONCLUSIONS: In patients with a serum ALB level <4.0 g/dL before IFN therapy, hepatic carcinogenesis after SVR achievement need to be considered. Furthermore, the serum ALB level may be more useful than the degree of fibrosis for the prediction of HCC after SVR in chronic hepatitis C.
  • Unique Characteristics Associated with Sustained Liver Damage in Chronic Hepatitis C Patients Treated with Direct Acting Antivirals
    Kono M; Nishida N; Hagiwara S; Minami T; Chishina H; Arizumi T; Minaga K; Kamata K; Komeda Y; Sakurai T; Takenaka M; Takita M; Yada N; Ida H; Minami Y; Ueshima K; Watanabe T; Kudo M
    Dig Dis 35 6 556 - 564 2017年 [査読有り]
  • Hepatocellular Carcinoma after Achievement of Sustained Viral Response with Daclatasvir and Asunaprevir in Patients with Chronic Hepatitis C Virus Infection
    Ida H; Hagiwara S; Kono M; Minami T; Chishina H; Arizumi T; Takita M; Yada N; Minami Y; Ueshima K; Nishida N; Kudo M
    Dig Dis 35 6 565 - 573 2017年 [査読有り]
  • Impact of Tumor Factors on Survival in Patients with Hepatocellular Carcinoma Classified Based on Kinki Criteria Stage B2
    Arizumi T; Minami T; Chishina H; Kono M; Takita M; Yada N; Hagiwara S; Minami Y; Ida H; Ueshima K; Kamata K; Minaga K; Komeda Y; Takenaka M; Sakurai T; Watanabe T; Nishida N; Kudo M
    Dig Dis 35 6 583 - 588 2017年 [査読有り]
  • Time to Transcatheter Arterial Chemoembolization Refractoriness in Patients with Hepatocellular Carcinoma in Kinki Criteria Stages B1 and B2
    Arizumi T; Minami T; Chishina H; Kono M; Takita M; Yada N; Hagiwara S; Minami Y; Ida H; Ueshima K; Kamata K; Minaga K; Komeda Y; Takenaka M; Sakurai T; Watanabe T; Nishida N; Kudo M
    Dig Dis 35 6 589 - 597 2017年 [査読有り]
  • Ultrasound-ultrasound image overlay fusion improves real-time control of radiofrequency ablation margin in the treatment of hepatocellular carcinoma
    Minami Y; Minami T; Hagiwara S; Ida H; Ueshima K; Nishida N; Murakami T; Kudo M
    Eur Radiol 1 - 8 2017年 [査読有り]
  • Yoriaki Komeda; Hisashi Handa; Tomohiro Watanabe; Takanobu Nomura; Misaki Kitahashi; Toshiharu Sakurai; Ayana Okamoto; Tomohiro Minami; Masashi Kono; Tadaaki Arizumi; Mamoru Takenaka; Satoru Hagiwara; Shigenaga Matsui; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    Oncology 93 1 30 - 34 2017年 [査読有り]
  • Yoriaki Komeda; Hiroshi Kashida; Toshiharu Sakurai; Yutaka Asakuma; George Tribonias; Tomoyuki Nagai; Masashi Kono; Kosuke Minaga; Mamoru Takenaka; Tadaaki Arizumi; Satoru Hagiwara; Shigenaga Matsui; Tomohiro Watanabe; Naoshi Nishida; Takaaki Chikugo; Yasutaka Chiba; Masatoshi Kudo
    Oncology 93 1 49 - 54 2017年 [査読有り]
  • Toshiharu Sakurai; Teppei Adachi; Masashi Kono; Tadaaki Arizumi; Ken Kamata; Kosuke Minaga; Kentaro Yamao; Yoriaki Komeda; Mamoru Takenaka; Satoru Hagiwara; Tomohiro Watanabe; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    Oncology 93 1 27 - 29 2017年 [査読有り]
  • Mitsunari Yamada; Toshiharu Sakurai; Yoriaki Komeda; Tomoyuki Nagai; Ken Kamata; Kosuke Minaga; Kentaro Yamao; Mamoru Takenaka; Satoru Hagiwara; Shigenaga Matsui; Tomohiro Watanabe; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    Oncology 93 1 20 - 26 2017年 [査読有り]
  • Serum microRNA profile that predict initial effect of sorafenib in patients with advanced hepatocellular carcinoma
    Nishida N; Arizumi T; Hagiwara S; Ida H; Sakurai T; Kudo M
    Liver Cancer 6 113 - 125 2017年 [査読有り]
  • Tadaaki Arizumi; Kazuomi Ueshima; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Hiroshi Ida; Yoriaki Komeda; Mamoru Takenaka; Toshiharu Sakurai; Tomohiro Watanabe; Naoshi Nishida; Masatoshi Kudo
    LIVER CANCER 6 3 227 - 235 2017年 [査読有り]
     
    Aim/Background: The ultimate aim of any treatment for hepatocellular carcinoma (HCC) is to improve overall survival (OS); however, the clinical significance of time to progression (TTP) after transarterial chemoembolization (TACE) is unclear. This retrospective study examined the association between OS and the newly defined time to TACE progression (TTTP) to assess whether TTTP can be an alternative to OS in HCC patients with Barcelona Clinic Liver Cancer (BCLC) stage B. Methods: Between January 2006 and December 2013, 592 patients with HCC (BCLC B1, n = 118; BCLC B2, n = 170) underwent TACE. TTTP was then redefined as time to progression from the first image taken after TACE. The relationship between TTTP and OS was then examined based on survival time. Results: Survival analysis revealed significant differences in the OS of patients with BCLC B1 and those with BCLC B2 (median OS: 42.3 months, 95% confidence interval [CI] 34.4-50.7; and 29.3 months, 95% CI 26.1-37.6, respectively, p = 0.0348). The median TTTP values were 9.5 months (95% CI 7.0-10.9) and 5.3 months (95% CI 4.6-6.7), respectively (p = 0.0078). There was a moderate positive correlation between OS and TTTP for both B1 (R-2 = 0.6563, p = 0.0045) and B2 (R-2 = 0.6433, p = 0.0052) substages. There was also a positive correlation between OS and TTTP for the combined B1 and B2 substages (R-2 = 0.6590, p = 0.0024). Conclusions: There was a moderate correlation between the TTTP and OS of patients with HCC after TACE therapy, where the patients with short TTTP represented short OS, indicating that TTTP is an alternative parameter for survival analysis of HCC patients with BCLC stage B tumors who undergo TACE. (C) 2017 S. Karger AG, Basel
  • Norihisa Yada; Toshiharu Sakurai; Tomohiro Minami; Tadaaki Arizumi; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 92 10 - 15 2017年 [査読有り]
     
    Objective: In order to evaluate the influence of liver inflammation on liver stiffness measurement (LSM) by the simultaneous use of shear wave and strain imaging (combinational elastography), shear wave and strain imaging were compared before and after initial therapy for autoimmune hepatitis (AIH). Methods: Nine AIH patients initially treated with steroid were enrolled. Transient elastography and real-time tissue elastography were performed just before and 1 month after the start of initial steroid treatment. Blood samples, LSM, and the liver fibrosis index (LFI) were compared. Results: Aspartate aminotransferase (p = 0.002) and alanine aminotransferase (ALT) (p = 0.015) were significantly decreased after initial treatment. The LSM was 15.5 +/- 9.6 kPa at baseline, decreasing to 7.2 +/- 2.3 kPa after initial treatment p = 0.034). The LFI was 1.67 +/- 0.67 at baseline and 1.61 +/- 0.66 after initial treatment; no significant change in LFI was recognized (p = 0.842). Between Delta ALT and Delta LSM, a significant regression equation could be calculated as follows: Delta ALT = -0.55 + 0.654 x Delta LSM. Conclusions: Combinational elastography was useful in evaluating not only the degree of liver fibrosis, but also the degree of liver inflammation in AIH. (C) 2017 S. Karger AG, Basel
  • Satoru Hagiwara; Naoshi Nishida; Tomohiro Watanabe; Toshiharu Sakurai; Hiroshi Ida; Yasunori Minami; Masahiro Takita; Tomohiro Minami; Mina Iwanishi; Hirokazu Chishina; Kazuomi Ueshima; Yoriaki Komeda; Tadaaki Arizumi; Masatoshi Kudo
    ONCOLOGY 92 3 - 9 2017年 [査読有り]
     
    Introduction: Recently, the treatment of chronic hepatitis C has markedly advanced. A phase III clinical study of combination therapy with sofosbuvir (SOF) and ledipasvir (LDV) was conducted in Japan, and the additive therapeutic effects were reported. In this study, we report the results of treatment in our hospital. Methods: Of 147 patients with chronic type C liver disease who had consulted our hospital since September 2015 and received SOF/LDV therapy, in 91 subjects a sustained virological response of 12 weeks (SVR12) could be evaluated. Results: In all 91 patients, end treatment response was achieved. Subsequently, recrudescence was noted in 1 before the completion of treatment (week 12); an SVR12 was achieved in 90 patients (99%). The following adverse reactions were observed in 3 patients (3.3%): bradycardia, paroxysmal atrial fibrillation, and heart failure with QT prolongation, which were associated with heart disease. Conclusion: A favorable SVR was achieved by SOF/LDV therapy even in elderly patients, those with liver cirrhosis, or those having undergone radical treatment of liver cancer. Furthermore, a high tolerance was demonstrated, but adverse reactions associated with the heart may appear in patients with heart disease as an underlying disease; strict management during treatment is necessary. (C) 2016 S. KargerAG, Basel
  • Wing Yee Kwok; Satoru Hagiwara; Naoshi Nishida; Tomohiro Watanabe; Toshiharu Sakurai; Hiroshi Lda; Yasunori Minami; Masahiro Takita; Tomohiro Minami; Mina Lwanishi; Hirokazu Chishina; Masashi Kono; Kazuomi Ueshima; Yoriaki Komeda; Tadaaki Arizumi; Eisuke Enoki; Takuya Nakai; Tsutomu Kumabe; Osamu Nakashima; Fukuo Kondo; Masatoshi Kudo
    ONCOLOGY 92 16 - 28 2017年 [査読有り]
     
    The patient was a 20-year-old male in whom a hepatic hyper vascular mass accompanied by intratumoral hemorrhage was detected on examination for epigastric pain. Based on the enlargement of the mass and diagnostic imaging, hepatocellular adenoma (HCA) was suspected and hepatectomy was performed. The lesion was diagnosed as malignant transformation of P-catenin-activated HCA. There are only few reports of cases with malignant transformation of HCA in Japan; it is necessary to accumulate cases to investigate it. (C) 2016 S. Karger AG, Basel
  • Masashi Kono; Yasunori Minami; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Tadaaki Arizumi; Yoriaki Komeda; Toshiharu Sakurai; Masahiro Takita; Norihisa Yada; Hiroshi Ida; Satoru Hagiwara; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 92 29 - 34 2017年 [査読有り]
     
    Objective: To compare contrast tissue harmonic imaging (THI) with low mechanical index (MI) and conventional contrast harmonic imaging (CHI) with respect to lesion visibility of hepatocellular carcinoma (HCC). Methods: One hundred and twenty-five patients (84 men and 41 women, age range 39-94 years, mean age 74 years) with 100 naive HCCs and 30 lesions after radiofrequency ablation (RFA) for HCC were evaluated. One hundred and four patients had liver cirrhosis of Child-Pugh class A, and the remaining 21 had Child-Pugh class B cirrhosis. The lesion conspicuity and intratumoral echogenicity during the postvascular phase were compared using conventional CHI and contrast THI with low MI. Results:The MI values ranged from 0.20 to 0.30 on conventional CHI and from 0.30 to 0.35 on contrast THI. Regarding HCC lesion conspicuity, contrast THI with low MI was clearer in 79 lesions (60.8%), equal in 34 lesions (26.2%), and less clear in 17 lesions (13.1%) when compared with conventional CHI. The lesion conspicuity with contrast THI was significantly better than that with conventional CHI (p < 0.01). All of the postablative lesions were well delineated in patients who received RFA. Conclusion: Low-MI contrast THI was superior to conventional CHI with respect to lesion visibility of HCCs and might offer good imaging for the guiding of RFA. (C) 2016 S. Karger AG, Basel
  • Yoriaki Komeda; Hiroshi Kashida; Toshiharu Sakurai; George Tribonias; Kazuki Okamoto; Masashi Kono; Mitsunari Yamada; Teppei Adachi; Hiromasa Mine; Tomoyuki Nagai; Yutaka Asakuma; Satoru Hagiwara; Shigenaga Matsui; Tomohiro Watanabe; Masayuki Kitano; Takaaki Chikugo; Yasutaka Chiba; Masatoshi Kudo
    WORLD JOURNAL OF GASTROENTEROLOGY 23 2 328 - 335 2017年01月 [査読有り]
     
    AIM To compare the efficacy and safety of cold snare polypectomy (CSP) and hot forceps biopsy (HFB) for diminutive colorectal polyps. METHODS This prospective, randomized single-center clinical trial included consecutive patients >= 20 years of age with diminutive colorectal polyps 3-5 mm from December 2014 to October 2015. The primary outcome measures were en-bloc resection (endoscopic evaluation) and complete resection rates (pathological evaluation). The secondary outcome measures were the immediate bleeding or immediate perforation rate after polypectomy, delayed bleeding or delayed perforation rate after polypectomy, use of clipping for bleeding or perforation, and polyp retrieval rate. Prophylactic clipping after polyp removal wasn't routinely performed. RESULTS Two hundred eight patients were randomized into the CSP (102), HFB (106) and 283 polyps were evaluated (CSP: 148, HFB: 135). The en-bloc resection rate was significantly higher with CSP than with HFB [99.3% (147/148) vs 80.0% (108/135), P < 0.0001]. The complete resection rate was significantly higher with CSP than with HFB [80.4% (119/148) vs 47.4% (64/135), P < 0.0001]. The immediate bleeding rate was similar between the groups [8.6% (13/148) vs 8.1% (11/135), P = 1.000], and endoscopic hemostasis with hemoclips was successful in all cases. No cases of perforation or delayed bleeding occurred. The rate of severe tissue injury to the pathological specimen was higher HFB than CSP [52.6% (71/135) vs 1.3% (2/148), P < 0.0001]. Polyp retrieval failure was encountered CSP (7), HFB (2). CONCLUSION CSP is more effective than HFB for resecting diminutive polyps. Further long-term follow-up study is required.
  • Naoshi Nishida; Tadaaki Arizumi; Satoru Hagiwara; Hiroshi Ida; Toshiharu Sakurai; Masatoshi Kudo
    LIVER CANCER 6 2 113 - 125 2017年 [査読有り]
     
    Background: Several studies suggest the role of circulating microRNAs (miRNAs) as biomarkers of hepatocellular carcinoma (HCC). However, the serum miRNA profile associated with the response to sorafenib remains to be elucidated. The aim of this study was to clarify the specific miRNAs in serum that could predict the early response of HCC to sorafenib treatment. Summary: Analyzing the sera from 16 HCC patients, we selected five miRNAs that showed differences in serum levels between patients with and without tumor responses among 179 known secretory miRNAs by using locked nucleic acid probe -based quantitative PCR. Through further analysis using a validation cohort that included 53 HCC patients who underwent sorafenib treatment and 8 healthy control subjects, we found that miR-181a-5p and miR-3395p showed significant differences in serum levels among patients with partial response (PR), stable disease (SD), and progressive disease (PD), where PR patients showed the highest and PD the lowest levels. We also analyzed the factors associated with disease control (DC; PR or SD) 3 months after the initiation of sorafenib treatment; patients with DC showed a significantly higher level of serum miR-181a-5p than non -DC patients or healthy control subjects (p = 0.0349 and 0.0180 for DC vs. non -DC and control vs. non -DC by Tukey-Kramer test, respectively). We further conducted multivariate analysis among HCC patients with Barcelona Clinic Liver Cancer stage C using extrahepatic metastasis, serum decarboxyprothrombin, and miR-181a-5p levels as covariables; serum miR-181a-5p was the only independent factor for achieving DC (p = 0.0092, odds ratio 0.139, and 95% confidence interval 0.011-0.658). In addition, miR-181a-5p level was also the only independent factor affecting overall survival (p = 0.0194, hazard ratio 0.267, and 95% confidence interval 0.070-0.818). Key Messages: A high serum level of miR-181a-5p before treatment is associated with DC after the initiation of sorafenib. (C) 2016 S. Karger AG, Basel
  • Stress response protein RBM3 promotes the development of colitis-associated cancer
    Sakurai T; Kashida H; Komeda Y; Nagai T; Hagiwara S; Watanabe T; Kitano M; Nishida N; Fujita J; Kudo M
    Inflamm Bowel Dis 23 66 - 74 2017年 [査読有り]
  • Naoshi Nishida; Norihisa Yada; Satoru Hagiwara; Toshiharu Sakurai; Masayuki Kitano; Masatoshi Kudo
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 9 1646 - 1653 2016年09月 [査読有り]
     
    Background and AimNon-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC). Previously, we reported that DNA oxidation induced epigenetic alteration of tumor suppressor genes (TSGs) and contributed to HCC emergence. Here, we examine the associations between clinicopathological characteristics of NAFLD and advanced oxidative DNA damage that is associated with TSG methylation in the NAFLD liver. MethodsLiver biopsies from 65 NAFLD patients were analyzed for clinicopathological features and oxidative DNA damage using immunohistochemistry of 8-hydroxydeoxyguanosine (8-OHdG). Abnormal DNA methylation in the promoters of 6 TSGs, HIC1, GSTP1, SOCS1, RASSF1, CDKN2A, and APC, was examined using MethyLight. Associations between clinicopathological characteristics, methylation of TSGs, and accumulation of 8-OHdG were analyzed. ResultsWe found that aspartate aminotransferase/alanine aminotransferase ratio, the fibrosis-4 index, and serum -fetoprotein (AFP) level were associated with degree of 8-OHdG, and AFP was an independent factor among them (P=0.0271). Regarding pathological findings, hepatocellular ballooning and stage of fibrosis were also associated with oxidative DNA damage (P=0.0021 and 0.0054); ballooning was an independent risk for detecting high degree of 8-OHdG in hepatocytes (odds ratio 7.38, 95% confidence interval 1.41-49.13, P=0.0171). Accumulation of methylated TSGs was significantly associated with deposition of 8-OHdG (P=0.0362). ConclusionsPatients with high serum AFP and high degree of ballooning showed accumulation of oxidative DNA damage that could be a seed of DNA methylation responsible for hepatocarcinogenesis. These characteristics could be risk of HCC; such patients require urgent intervention such as lifestyle modification.
  • Satoru Hagiwara; Naoshi Nishida; Hirokazu Chishina; Hiroshi Ida; Toshiharu Sakurai; Yoriaki Komeda; Masayuki Kitano; Masatoshi Kudo
    INTERNAL MEDICINE 55 22 3273 - 3277 2016年 [査読有り]
     
    The patient was a 67-year-old female with liver cirrhosis due to hepatitis C. She was administered furosemide at 20 mg/day and spironolactone at 25 mg/day, but the ascites did not improve. Despite the additional administration of tolvaptan at 3.75 mg/day, the response to ascites was still poor. While the dose of tolvaptan was thereafter increased to 7.5 mg/day on the 7th hospital day, the ascites still persisted. However, she continued to receive tolvaptan (7.5 mg/day) because the worsening of her subjective symptoms was mild and she wished to do so. The ascites was later found to have almost completely disappeared on computed tomography (CT) at 6 months.
  • Reply: Hepatocyte damage due to protoporphyrin deposition
    Hagiwara S; Nishida N; Kudo M
    Hepatology 64 306  2016年 [査読有り]
  • Tomoyuki Nagai; Tokuzo Arao; Kazuto Nishio; Kazuko Matsumoto; Satoru Hagiwara; Toshiharu Sakurai; Yasunori Minami; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Kazuko Sakai; Nagahiro Saijo; Kanae Kudo; Hiroyasu Kaneda; Daisuke Tamura; Keiichi Aomatsu; Hideharu Kimura; Yoshihiko Fujita; Seiji Haji; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 702 - 707 2016年 [査読有り]
     
    Background: Epithelial-mesenchymal transition (EMT) is considered to play a critical role in cancer progression and metastasis. However, the impact of EMT on the prognosis of hepatocellular carcinoma (HCC) is still elusive. In this study, we examined the relationship between the expression of EMT markers and recurrence-free survival (RFS) and overall survival (OS) in HCC patients after hepatic resection. Summary:The mRNA expression of 15 genes related to EMT was assessed by quantitative real-time polymerase chain reaction in cancerous tissues from 72 patients who underwent hepatic resection of HCC between January 2005 and December 2010 at our hospital. The upregulation of TWIST and the downregulation of tight junction protein ZO-1 (TJP1) were significantly associated with shorter RFS as well as OS. Increased levels of TWIST and decreased levels of TJP1 should be predictive markers for poor prognosis in patients with HCC after hepatectomy; those could serve as potential biomarkers for the treatment of HCC. Key Messages: A low level of TJP1 and high level of TWIST expression were prognostic factors predicting HCC after hepatic resection. (C) 2016 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshima; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Hiroshi Ida; Toshiharu Sakurai; Masayuki Kitano; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 671 - 678 2016年 [査読有り]
     
    Background: The standard treatment option that is available for patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) is transarterial chemoembolization (TACE). However, the condition of the patients with BCLC stage B disease is heterogeneous showing different tumor statuses and Child Pugh scores; treatment strategies other than TACE are frequently employed for the patients in this stage. Based on the subclassification system proposed by Bolondi et al. [Semin Liver Dis 2012;32:348-359], we developed the Kinki criteria focusing on a substaging for BCLC stage B disease, which is simpler and should be more suitable in actual clinical setting in Japan. In this study, we evaluated the performance of Kinki criteria. Summary: This study included 1,633 HCC patients who received first line treatment at the Kindai University Hospital. Patients were classified into subgroups based on the Kinki criteria and the survival time was estimated for each group. There were 156 (33.3%) patients in subclass B1, 278 (59.3%) in B2, and 35 (7.4%) in B3. The median overall survival times and 95% CI for BCLC B subclasses B1, B2, and B3 were 4.3 years (3.7-4.9), 2.9 years (2.2-3.4), and 1.1 years (0.5-1.8), respectively (p < 0.001). Key Messages: Classification of HCC patients in BCLC stage B based on the Kinki criteria showed statistically significant differences in survival, indicating the performance of Kinki criteria, which takes Child Pugh score and tumor status into account for determining treatment options for HCC in BCLC stage B. (C) 2016 S. Karger AG, Basel
  • Norihisa Yada; Toshiharu Sakurai; Tomohiro Minami; Tadaaki Arizumi; Masahiro Takita; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 650 - 653 2016年 [査読有り]
     
    Objective: We have reported about real-time tissue elastography (RTE), which displays relative strain by measuring the relative distortion of the tissue, and found this information to be useful for diagnosing liver fibrosis. However, its use in predicting hepatocellular carcinoma has not been reported as yet. Here, we investigated RTE to predict liver carcinogenesis in patients with chronic hepatitis C virus (HCV) infection. Methods: We enrolled 160 patients with chronic HCV, who were followed up for 39.9 +/- 22.9 weeks (median). They underwent RTE and then ultrasounds every 3-6 months. Results: Respective cumulative liver cancer incidences for years 1, 2, 3, 4, and 5 were, for the entire cohort: 2.0, 5.6, 8.8, 13.1, and 23.9%; for those whose liver fibrosis index (LFI) was <= 2.0: 0.0, 0.0, 0.0, 0.0, and 0.0%; for those whose LFI was 2-2.8:0.0, 7.4, 7.4, 13.2 and 19.9%; and for those whose LFI was >2.8: 12.9, 12.9, 21.7, 31.4, and 31.4% (p = 0.011; log-rank test). Conclusions: Measurements of LFI by strain imaging can effectively predict liver cancer risk in patients with chronic HCV infection. (C) 2016 S. Karger AG, Basel
  • Yasunori Minami; Tomohiro Minami; Hirokazu Chishina; Masashi Kono; Tadaaki Arizumi; Masahiro Takita; Norihisa Yada; Satoru Hagiwara; Hiroshi Ida; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 687 - 691 2016年 [査読有り]
     
    Objective: Radiofrequency ablation (RFA) induces gas bubbles in ablation zones, and the ablative margin cannot be evaluated accurately on ultrasound (US) during and immediately after RFA. This study assessed the usefulness of US-US fusion imaging to visualize the ablative margin of RFA for liver metastasis. Methods: RFA guided by US-US fusion imaging was performed on 12 targeted tumors in 10 patients. Secondary hepatic malignancies included patients with colorectal cancer (n = 4), breast cancer (n = 2), lung cancer (n = 1), gastrointestinal stromal tumor (n = 1), pancreatic neuroendocrine tumor (n = 1), and adrenocortical carcinoma (n = 1). The maximal diameter of the tumors ranged from 0.8 to 4.0 cm (mean SD 1.6 +/- 0.9 cm). Results: The mean number of electrode insertions was 1.6 per session (range 1-3). Technically, effective ablation was achieved in a single session in all patients, and safety ablative margins were confirmed on contrast-enhanced CT for early assessment of tumor response. There were no serious adverse events or procedure-related complications. During the follow-up period (median 220 days, range 31-417 days), none of the patients showed local tumor progression. Conclusion: US-US fusion imaging could show the tumor images before ablation and the ablative area on US in real time. The image overlay of US-US fusion imaging made it possible to evaluate the ablative margin three dimensionally according to the US probe action. Therefore, US-US fusion imaging can contribute to RFA therapy with a safety margin, that is, the so-called precise RFA. (C) 2016 S. Karger AG, Basel
  • Hirokazu Chishina; Satoru Hagiwara; Naoshi Nishida; Kazuomi Ueshima; Toshiharu Sakurai; Hiroshi Ida; Yasunori Minami; Masahiro Takita; Masashi Kono; Tomohiro Minami; Mina Iwanishi; Yasuko Umehara; Tomohiro Watanabe; Yoriaki Komeda; Tadaaki Arizumi; Masotoshi Kudo
    DIGESTIVE DISEASES 34 6 659 - 664 2016年 [査読有り]
     
    Objective: Refractory ascites reduces the quality of life of liver cirrhosis patients. Albumin preparation and diuretics, such as furosemide, have been used to treat refractory ascites, but the effect was poor in many patients. In this study, we analyzed patients treated with tolvaptan (TLV) at our hospital and investigated predictors of the effect. Methods: The subjects were 70 patients for whom TLV was introduced to treat refractory ascites who could be analyzed between November 2013 and March 2015 at our hospital. Patient background before initiation of oral TLV treatment, the dose of diuretics, and each item of biochemical tests of blood and urine were investigated, and factors correlated with the treatment effect were analyzed. An increase of >= 1,000 ml in the daily urine volume from the day before oral treatment or a decrease of kg in the body weight within 7 days as an early effect was observed in 33 patients and not observed in 37 patients. TLV treatment was continued for 60 days or longer in 12 of the 37 patients in whom no early effect was observed, and the presence or absence of a delayed effect and predictors of the effect were investigated. A decrease in as cites on abdominal CT with improvement of subjective symptoms at 60 days was defined as a delayed effect. Results: When early predictors of the effect were investigated by univariate analysis, serum blood urea nitrogen (BUN) and serum creatinine (Cr) were significantly higher in the non responder group (BUN: p = 0.03, Cr: p = 0.04), but no factor independently associated with the treatment effect was extracted on multivariate analysis. The delayed effect was noted in 4 (33.3%) of the 12 patients, but no predictor of the effect before treatment was identified. However, reactions, such as an increase in serum Na and reduction of urinary osmotic pressure, were observed early after TLV administration in some patients in whom the delayed effect was observed. Conclusions: The diuretic effect of TLV may decrease in renal hypofunction patients. Since the delayed effect was noted in a specific ratio of patients, continuation of TLV administration is an option even though the early treatment effect is poor unless ascites aggravates or adverse effects develop. (C) 2016 S. Karger AG, Basel
  • Masahiro Takita; Mina Iwanishi; Tomohiro Minami; Masashi Kono; Hirokazo Chishina; Tadaaki Arizumi; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Hiroshi Ida; Kazuomi Ueshima; Nishida Naoshi; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 654 - 658 2016年 [査読有り]
     
    Objective: The objective of treatment for polycystic liver disease is to reduce the liver volume and reduce or resolve compression symptoms such as abdominal fullness and abdominal pain due to hepatomegaly. Liver cysts are treated internally by puncture and aspiration of the cyst contents or hepatic artery embolization and surgically by cyst fenestration or hepatectomy, but no clear consensus has been reached concerning their selection. We introduced monoethanolamine oleate (EO) sclerotherapy therapy for liver cysts in 1999 and reported its effectiveness. In this study, cases were added, and the results including those of long-term follow-up were evaluated. Subjects: Twenty-two patients (5 males and 17 females, mean age 65.2) who underwent EO infusion therapy for liver cysts between January 1999 and June 2011 were evaluated. Methods: Liver cysts were punctured under ultrasound guidance, and a 7Fr pigtail catheter was inserted. After aspirating the cyst contents, EO was infused, and a clamp was applied for 24 h. Then, the catheter was declamped, cyst contents were aspirated again, and the catheter was removed. After the treatment, the cyst size was measured, and the patients were followed up. Results: Eight simple cysts in 8 patients (simple cyst group) and 21 cysts in 14 patients with multiple cysts (polycystic liver disease group) were treated and followed up over a median of 78 months (0-203 months). The mean volume reduction rate was 99% in the simple cyst group and 91% in the polycystic liver disease group (p = 0.04). One procedural accident resulting in liver abscess formation was observed in 1 patient 1 week after discharge, and it required drain placement and antibiotic administration. While mild abdominal pain was observed in a few patients, it was resolved spontaneously under observation. Conclusion: EO infusion therapy achieves fairly high treatment response in the volume reduction (99%) and sustained shrinkage over long-term follow-up. Therefore, this is a breakthrough technique in the treatment of polycystic liver disease as well as simple cyst and should be a standard of care in the treatment of this disease. (C) 2016 S. Karger AG, Basel
  • Naoshi Nishida; Masashi Kono; Tomohiro Minami; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Norihisa Yada; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima; Tashiharu Sakurai; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 632 - 639 2016年 [査読有り]
     
    Background: An interferon-free regimen including sofosbuvir and ribavirin (RBV) for patients with hepatitis C virus (HCV) genotype 2 (G2) infection leads to a drastic improvement of sustained virological response (SVR). However, the safety, tolerability, and efficacy in patients aged 75 or older have not been completely understood. Summary: Fifty-six patients with HCV G2 infection who were treated with sofosbuvir and weight-based dose of RBV were enrolled. Thirty-seven patients aged and 19 patients aged were classified as the aged and non-aged groups, respectively. The aged group was characterized by significantly more number of women, history of hepatocellular carcinoma, low serum albumin (ALB) level, low hemoglobin (Hb) concentration, low estimated glomerular filtration rate (eGFR), and high fibrosis-4 index (p = 0.0029). Forty-one patients were evaluated for SVR at 12 weeks after the end of therapy (SVR12); of them, all but one completed the treatment scheduled for 12 weeks. The aged group showed lower SVR12 rate than the non aged group (81.3%for aged and 96.0%for non-aged groups). Although the Hb concentration and eGFR are significantly lower in the aged group throughout the clinical course, all patients in the aged group completed the 12-week treatment with a gradual increase of serum ALB level. Key Messages: The combination of sofosbuvir plus RBV is tolerable and beneficial in patients aged >75. However, intensive management of anemia by dose reduction of RBV is necessary, which could lead to a low SVR12 rate compared to that observed in patients younger than 75 years. (C) 2016 S. Karger AG, Basel
  • Satoru Hagiwara; Naoshi Nishida; Tomohiro Watanabe; Toshiharu Sakurai; Hiroshi Ida; Yasunori Minami; Masahiro Takita; Tomohiro Minami; Mina Iwanishi; Hirokazu Chishina; Kazuomi Ueshima; Yoriaki Komeda; Tadaaki Arizumi; Masatoshi Kudo
    DIGESTIVE DISEASES 34 6 620 - 626 2016年 [査読有り]
     
    Objective: Treatment for chronic hepatitis C has recently developed in a very rapid manner. In Japan, in September 2014, IFN-free asunaprevir (ASV) and daclatasvir (DCV) became available for combination therapy. We report the treatment outcomes achieved at our hospital using this combination therapy. Methods: Sustained virological response (SVR) 24 could be evaluated in 120 of 125 patients with chronic liver disease type C who visited our hospital and were treated with ASV/DCV after September 2014, and these patients were analyzed. Results: SVR24 was achieved in 106 patients (88%). End-of-treatment response was not achieved in 10 patients (8.3%). Five of them carried multiple-resistant NS3/4A or NS5A region, and administration was discontinued early in 4 patients due to adverse effects. After ASV/DCV treatment, hepatocellular carcinoma (HCC) developed in 2 patients (1.7%) and recurred in 5 (4.2%). Conclusions: ASV/DCV treatment achieved favorable SVR in elderly and hepatic cirrhosis patients and patients in whom HCC was cured. However, an increase in the incidence of HCC development in patients who markedly respond to direct-acting antivirals treatment is expected and surveillance of HCC becomes more important. (C) 2016 S. Karger AG, Basel
  • Hagiwara S; Nishida N; Kudo M
    Hepatology 63 1744 - 1745 2016年 [査読有り]
  • Satoru Hagiwara; Naoshi Nishida; Ah-Mee Park; Toshiharu Sakurai; Akira Kawada; Masatoshi Kudo
    HEPATOLOGY 62 5 1638 - 1639 2015年11月 [査読有り]
  • 上腸間膜静脈血栓症による急性腸管虚血に対しTIPSを施行した1例
    沼本 勲男; 鶴崎 正勝; 柳生 行伸; 渡口 真史; 山川 美帆; 任 誠雲; 松木 充; 村上 卓道; 萩原 智; 工藤 正俊; 吉藤 竹仁; 船内 正憲
    IVR: Interventional Radiology 30 3 283 - 283 (一社)日本インターベンショナルラジオロジー学会 2015年09月
  • Toshiharu Sakurai; Yoshihisa Okazaki; Yoriaki Komeda; Teppei Adachi; Satoru Hagiwara; Shigenaga Matsui; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    GASTROENTEROLOGY 148 4 S141 - S141 2015年04月 [査読有り]
  • Toshiharu Sakurai; Hiroshi Kashida; Satoru Hagiwara; Naoshi Nishida; Tomohiro Watanabe; Jun Fujita; Masatoshi Kudo
    DIGESTIVE DISEASES AND SCIENCES 60 4 850 - 857 2015年04月 [査読有り]
     
    Aims and Methods Heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, regulates the immune response in the gut. Here, we assessed the involvement of HSPA4 in gastric ulcer healing by using fibroblasts from wild-type and HSPA4-deficient mice, a murine gastric ulcer model, and samples from 65 patients with gastric cancer. Results HSPA4 expression was inversely correlated with gastric ulcer healing following endoscopic resection of gastric cancer. In the human gastric mucosa, the expression of HSPA4 was inversely correlated with the expression of stromal cell-derived factor 1 (SDF-1), its cognate receptor CXC chemokine receptor 4(CXCR4), the stromal cell marker vimentin, and the epithelial-mesenchymal transition regulator Twist. HSPA4 was overexpressed in stromal cells as well as in human gastric cancer cells. HSPA4 deficiency increased the expression of SDF-1 and CXCR4, as well as the number of fibroblast-specific protein 1-positive cells, leading to accelerated ulcer healing in the murine gastric ulcer model. Deletion of HSPA4 promoted cell migration in mouse fibroblasts through increased expression of SDF-1 and Twist. Conclusion HSPA4 regulates the expression of SDF-1 and Twist in fibroblasts, thereby controlling gastric ulcer healing.
  • Toshiharu Sakurai; Norihisa Yada; Tomohiro Watanabe; Tadaaki Arizumi; Satoru Hagiwara; Kazuomi Ueshima; Naoshi Nishida; Jun Fujita; Masatoshi Kudo
    CANCER SCIENCE 106 4 352 - 358 2015年04月 [査読有り]
     
    Most hepatocellular carcinomas (HCCs) develop in the context of chronic liver inflammation. Oxidative stress is thought to play a major role in the pathogenesis of HCC development. In this study, we examined whether cold-inducible RNA-binding protein (Cirp) controls reactive oxygen species (ROS) accumulation and development of HCC by using murine models of hepatocarcinogenesis and human liver samples. Cirp expression, ROS accumulation, and CD133 expression were increased in the liver of tumor-harboring mice. Cirp deficiency reduced production of interleukin-1 and interleukin-6 in Kupffer cells, ROS accumulation, and CD133 expression, leading to attenuated hepatocarcinogenesis. Thioacetamide treatment enhanced hepatic expression of CD133 and phosphorylated signal transducer and activator of transcription 3 (STAT3), which was prevented by treatment with the antioxidant butylated hydroxyanisole. Intriguingly, the risk of human HCC recurrence is positively correlated with Cirp expression in liver. Cirp appears to play a critical carcinogenic function and its expression might be a useful biomarker for HCC risk prediction.
  • 発癌予測バイオマーカーとしてのエピゲノム変化
    萩原 智; 西田直生志; 工藤正俊
    最新肝癌学 73 403 - 407 2015年 [査読有り]
  • Tadaaki Arizumi; Kazuomi Ueshima; Tomohiro Minami; Masashi Kono; Hirokazu Chishina; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Naoshi Nishida; Masatoshi Kudo
    LIVER CANCER 4 4 253 - 262 2015年 [査読有り]
     
    Background and Aims: Patients with intermediate-stage hepatocellular carcinoma (HCC) refractory to transcatheter arterial chemoembolization (TACE) are considered to be candidates for sorafenib. The aim of this study was to evaluate the superiority of conversion of treatment to sorafenib on overall survival (OS) for cases refractory to TACE. Methods: This was a retrospective cohort study carried out on 497 patients with HCC who were treated with TACE therapy at our hospital between January 2008 and December 2013. Fifty-six patients were diagnosed as refractory to TACE during their clinical course and they were divided into two cohorts, (1) those who switched from TACE to sorafenib and (2) those who continued TACE. The overall survival (OS) after the time of being refractory to TACE was evaluated between the two groups. Results: After refractoriness to TACE therapy was confirmed, 24 patients continued with TACE (TACE-group) and 32 patients underwent treatment conversion to sorafenib (sorafenib-group). The median OS was 24.7 months in the sorafenib-group and 13.6 months in the TACE-group ( p=0.002). Conclusions: Conversion to sorafenib significantly improves the OS in patients refractory to TACE therapy with intermediate-stage HCC. Administration of sorafenib is therefore recommended in such circumstances of TACE treatment failure. Copyright (C) 2015 S. Karger AG, Basel
  • Kazuomi Ueshima; Masatoshi Kudo; Masatoshi Tanaka; Takashi Kumada; Hobyung Chung; Satoru Hagiwara; Tatsuo Inoue; Norihisa Yada; Satoshi Kitai
    LIVER CANCER 4 4 263 - 273 2015年 [査読有り]
     
    We conducted a phase I/II study in patients with advanced hepatocellular carcinoma (HCC) to determine the recommended dose, as well as the safety and efficacy, of combination therapy of sorafenib with hepatic arterial infusion chemotherapy (HAIC) using low dose cisplatin (CDDP) and 5-fluorouracil (5FU). Cohorts consisting of 3-6 patients with HCC received an escalated dose of CDDP and 5-FU until a maximum-tolerated dose was achieved. The treatment regimen was as follows: oral administration of sorafenib (400 mg twice daily for 28 days) combined with HAIC using CDDP (14-20 mg/m(2), on days 1 and 8) and 5-FU (170-330 mg/m(2), continuously on days 1-5 and 8-12) via an implanted catheter system). Each treatment cycle consisted of 28 days and three cycles of combination therapy. At the end of the first cycle, adverse events were evaluated and future dose escalation was determined. Eighteen patients with advanced HCC were enrolled. Dose-limiting toxicity was observed in two patients from cohort 1 (erythema multiforme and grade 4 thrombocytopenia) and in one patient from cohort 2 (erythema multiforme). Seven of the 18 patients achieved a partial response, seven showed stable disease, two were diagnosed as progressive disease, and two were not assessable. The response rate was 38.9% and the disease control rate was 77.8%. The time-to-progression was 9.7 months and the 1-year survival rate was 88.2%. Oral administration of 400 mg of sorafenib twice daily, 20 mg/m(2) of intra-arterial infusion of CDDP, and 5-FU at 330 mg/m(2) are the recommended doses for combination therapy, which was well tolerated and efficacious. This combination therapy may be a promising treatment for patients with advanced HCC. Copyright (C) 2015 S. Karger AG, Basel
  • Satoru Hagiwara; Naoshi Nishida; Masatoshi Kudo
    World Journal of Hepatology 7 23 2427 - 2431 2015年 [査読有り]
     
    The ideal goal of chronic hepatitis B (CHB) treatment should be suppression of emergence of hepatocellular carcinoma through the disappearance of hepatitis B s antigen (HBsAg) rather than the control of serum hepatitis B virus-DNA level. For this purpose, various types of combination therapies using nucleoside analogs (NAs) and interferon (IFN) have been conducted. The therapeutic effects of combination of two different kinds of agents are better than those of the monotherapy using NAs or IFN alone, probably because different pharmaceutical properties might act in a coordinated manner. Recently, combination therapies with NAs and IFN and sequential therapies with NAs administration followed by IFN therapy have been routinely employed. We previously reported that combination therapy using entecavir (ETV) and pegylated (PEG)-IFN showed antiviral effects in 71% of CHB patients the effect of this combination was better than that using lamivudine (LAM) and PEG-IFN. This is partially explained by the better antiviral effects of ETV than those of LAM. In our analysis, the cohort of CHB consisted of the patients who showed a flare-up of hepatitis before antiviral therapy, and their baseline HBsAg levels were relatively low. Therefore, in addition to the combination of the agents, the appropriate selection of patients is critical to achieve a good viral response.
  • Norihisa Yada; Toshiharu Sakurai; Tomohiro Minami; Tadaaki Arizumi; Masahiro Takita; Satoru Hagiwara; Kazuomi Ueshima; Hiroshi Ida; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 89 53 - 59 2015年 [査読有り]
     
    Objective: The aim of this study was to prospectively assess the usefulness of the reliability index, namely the percentage of the net amount of effective shear wave velocity (VsN). Methods: One hundred and sixty-eight patients with chronic liver disease, who underwent ultrasound elastography, were consecutively enrolled. Shear wave measurement (SWM), FibroScan, virtual touch quantification, and shear wave elastography were performed for all patients, and the variations in the measurement results were compared with VsN. The absolute average value of the difference between SWM_Vs and Vs measured using other elastography devices is termed vertical bar Delta Vs vertical bar. VsN was classified into three groups: 50, <50, and 0 (failure measurement). In these groups, there was a significant difference in abdominal circumference, body mass index, the distance between the ultrasound probe surface and the liver, and vertical bar Delta Vs vertical bar. When the distance between the ultrasound probe surface and the liver was >2cm, VsN tended to be significantly lower (p < 0.001). Results: When VsN was <50, bVsI became high, and there was variation in the results between each device. Conclusions:The results of this study show that VsN is a useful value to decide whether Vs is appropriate or not. (C) 2015 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshima; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Hiroshi Ida; Yasunori Minami; Toshiharu Sakurai; Masayuki Kitano; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 89 47 - 52 2015年 [査読有り]
     
    Introduction: Barcelona Clinic Liver Cancer (BCLC) stage B, an intermediate stage, includes various conditions of hepatocellular carcinoma (HCC). This heterogeneity of the patients with intermediate-stage HCC makes it difficult to predict their survival rates. In the present study, we examined the validity of the modified Bolondi classification (Kinki criteria) as a subclassification of patients with BCLC stage B HCC. Methods: Of 906 patients who underwent conventional transarterial chemoembolization at Kinki University Hospital, 753, who met the inclusion criteria, were examined. Of these 753 patients, 425 (56.4%) with BCLC stage B were subclassified using the Kinki criteria to examine the survival rate. Results: According to the Kinki criteria, 158 (37.2%) were subclassified into subclass B1,236 (55.53) into B2, and 31(7.3%) into B3. The comparison of the survival rates showed that the median overall survival was 3.9 years (95% CI, 3.2-4.6) in the BCLC subclass B1 group, 2.5 years (95% Cl, 2.2-3.1) in the B2 group, and 1.1 years (95% Cl, 0.6-1.5) in the B3 group (p < 0.001). Conclusion: When the BCLC stage B patients were subclassified according to the Kinki criteria, survival curves were stratified with significant differences, suggesting that the Kinki criteria were suitable for the subclassification of the intermediate-stage HCC patients. (C) 2015 S. Karger AG, Basel
  • Yasunori Minami; Tomohiro Minami; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Masakatsu Tsurusaki; Yukinobu Yagyu; Kazuomi Ueshima; Naoshi Nishida; Takamichi Murakami; Masatoshi Kudo
    ONCOLOGY 89 27 - 32 2015年 [査読有り]
     
    Objective: To investigate whether balloon-occluded transcatheter arterial chemoembolization (b-TACE) can produce a more dense accumulation of iodized oil in various stages of hepatocellular carcinoma (HCC), from single to uncountable, to overcome inferior local control. Materials and Methods: We studied 27 patients with HCC, including single to uncountable multiple lesions, who underwent b-TACE between August 2013 and April 2015. Dynamic CT was performed at baseline and 1-3 months after b-TACE. The treatment effect (TE) after b-TACE was evaluated using the Response Evaluation Criteria in Cancer of the Liver (RECICL) proposed by the Liver Cancer Study Group of Japan. Results: In the countable HCC group, contrast-enhanced CT demonstrated RECICL TE4 in 43.8% (14/32), TE3 in 12.5% (4/32), TE2 in 37.5% (12/32), and TEl in 6.3% (2/32) of patients. For the TACE-naive cohort, the objective response rate was 52.9%. The objective response rate was 60% for the previously lACE-treated cohort. In the uncountable multiple HCC group, the objective response rate was 0% (0/10), with progressive disease in 90% (9/10) of patients. Conclusion: Our observations suggested that b-TACE did not reduce the efficacy of retreatment for HCC with an insufficient outcome from conventional TACE, but it could not improve the efficacy of treatment for uncountable multiple HCCs. (C) 2015 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshima; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Hiroshi Ida; Yasunori Minami; Toshiharu Sakural; Naoshi Nishida; Masayuki Kitano; Masatoshi Kudo
    ONCOLOGY 89 4 - 10 2015年 [査読有り]
     
    Objective: Transarterial chemoembolization (TACE) is recommended as a first-line therapy for hepatocellular carcinoma (HCC) patients ineligible for curative therapy and without portal invasion. The Assessment for Retreatment with TACE (ART) scoring system was recently proposed for identifying patients who would not show sufficient survival benefit from repeated TACE. We reevaluated the performance of ART in HCC patients treated in Japan, where selective TACE is commonly used. Methods: Between 2000 and 2013, 988 patients with HCC underwent TACE at Kinki University Hospital, and 627 received >= 2 sessions of TACE. Seventy-six patients who underwent >= 2 TACE sessions within 90 days were investigated for their performance of the ART score in the context of overall survival (OS). Results: Only 12% (76/627) of patients underwent >= 2 TACE sessions within 90 days. Of those, 52 patients showed a low ART score (0-1.5), and 24 had a high ARTscore (>= 2.5); the median OS was 20.2 and 37.6 months, respectively (p = 0.8207). Conclusion:The ART scoring system did not demonstrate a sufficiently predictive impact on OS among the patients who underwent 2 TACE sessions within 90 days. Application of the ART score should be carefully considered because differences in TACE procedures and post-TACE treatment can affect the results while evaluating OS. (C) 2015 S. Karger AG, Basel
  • Naoshi Nishida; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshirna; Toshiharu Sakurai; Masayuki Kitano; Masatoshi Kudo
    DIGESTIVE DISEASES 33 6 745 - 750 2015年 [査読有り]
     
    Objectives: Several studies revealed that the proportion of hepatocellular carcinoma (HCC) without hepatitis virus infection (NBNC-HCC) is increasing. On the other hand, epigenetic alterations are reportedly responsible for HCC development. Here, we identified HCC risk factors that are associated with DNA methylation in the background liver tissue of NBNC-HCC patients. Methods: We performed methylation analysis in 37 pairs of virus-positive and 22 pairs of NBNC-HCC and non-cancerous livers using a HumanMethylation450 BeadChip array. After the selection of differentially methylated CpGs (DM-CpGs) in cancerous and non-cancerous livers, we analyzed DNA methylation of DM-CpGs within the adjacent non-cancerous liver tissue that is affected by specific HCC risk factors. Results: A total of 38,331 CpGs were selected as DM-CpGs using the following criteria: difference of beta-value between HCC and non-cancerous liver and false discovery rate (FDR) q < 1.0E-12. We subsequently selected the DM-CpGs that had methylation differences with the background liver tissue (that has FDR q < 0.35). Among the virus-positive patients, the type of hepatitis virus was mostly associated with differences in methylation within the background liver tissues. However, we found that background methylation patterns were most significantly associated with aging in NBNC patients. Interestingly, age-related methylation differences in DM-CpGs were also observed in NBNC-HCC tissues. Conclusions: Hepatitis viruses affect the methylation profiles within background liver tissues. However, difference in background methylation was mostly associated with age in NCBC-HCC patients; some age-related methylation events could contribute to emergence of NBNC-HCC in elderly individuals. (C) 2015 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshima; Mina Iwanishi; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Hiroshi Ida; Yasunori Minami; Toshiharu Sakurai; Naoshi Nishida; Masayuki Kitano; Masatoshi Kudo
    DIGESTIVE DISEASES 33 6 728 - 734 2015年 [査読有り]
     
    Objectives: Sorafenib has become a standard therapy for advanced hepatocellular carcinoma following the demonstration of significant increase in progression-free survival as well as overall survival (OS) in the 2-phase III trials. We examined efficacy and adverse events (AEs) in patients treated with sorafenib over a 6-year period since approval in Japan. Methods: Two hundred and forty-one patients treated with sorafenib at the Kinki University Hospital were retrospectively analyzed clinically for the factors related to survival periods, tumor response evaluated by the Response Evaluation Criteria In Cancer of the Liver (RECICL) and AEs. Results: OS was 14.3 months. According to the RECICL, the objective response and disease control rates were 18.6% (43 of 241) and 61.1% (137 of 241), respectively. AEs were seen in 77.3% (187 of 241), with Grade 3 or higher in 23.6% (57 of 241). The most frequent AE was hand-foot skin reaction in 109 patients (45.0%), and 28 patients (11.8%) showed Grade 3 or higher. Significant factors contributing to the OS were treatment duration (p = 0.0204), up-to-7 criteria (p = 0.0400), increase of Child-Pugh score (p = 0.0008) and tumor response determined by the RECICL (p = 0.0007). Conclusion: Based on the analysis, using many cases at a single center, we concluded that continuation of treatment with sorafenib for >= 90 days without decrease of liver function was critical if tumor response was determined as stable disease or higher. (C) 2015 S. Karger AG, Basel
  • Naoshi Nishida; Mina Iwanishi; Tomohiro Minami; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Hiroshi Ida; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Masayuki Kitano; Masatoshi Kudo
    DIGESTIVE DISEASES 33 6 708 - 714 2015年 [査読有り]
     
    Objectives: Triple therapy using peg-interferon, ribavirin and simeprevir (PEG-IFN/RBV/SMV) has reportedly resulted in high-sustained virological response (SVR) rates in patients with chronic hepatitis C (CHC), especially in naive cases and relapsers to prior PEG-IFN/RBV therapy. Here, we retrospectively analyzed the antiviral response associated with a triple regimen, in the context of early reduction of viral load during treatment. Methods: Forty-six CHC patients with HCV genotype 1b were treated with PEG-IFN/RBV/SMV triple therapy: 20 were naive cases, 12 were relapsers and 14 were non-responders to prior PEG-IFN/RBV therapy. We evaluated rapid virological response (RVR), complete early virological response (EVR), viral clearance at the end of the treatment (EOT) and at 12 weeks after the EOT (SVR12). In addition, we quantified the serum HCV-RNA on the 1st day and the 7th day after initiating treatment. Results: Multivariate analysis revealed that response to prior treatment was identified as an independent factor for achieving SVR12 after triple therapy (p = 0.0005). The achievement of serum HCV-RNA <2 log(10) IU/ml on day 7, RVR, EVR and EOT were associated with SVR12 (p = 0.0050, p = 0.0002, p = 0.0009 and p = 0.0002, respectively). Conclusions: Rapid decline of HCV is a predictive factor for the achievement of SVR12, even in antiviral triple therapy with PEG-IFN/RBV/SMV. An extended treatment period should be applied for patients who show detectable serum HCV-RNA at week 4. (C) 2015 S. Karger AG, Basel
  • Teppei Adachi; Toshiharu Sakurai; Hiroshi Kashida; Hiromasa Mine; Satoru Hagiwara; Shigenaga Matsui; Koji Yoshida; Naoshi Nishida; Tomohiro Watanabe; Katsuhiko Itoh; Jun Fujita; Masatoshi Kudo
    INFLAMMATORY BOWEL DISEASES 21 1 31 - 39 2015年01月 [査読有り]
     
    Background: Expression of heat shock protein A4 (HSPA4, also called Apg-2), a member of the HSP110 family, is induced by several forms of stress. The physiological and pathological functions of HSPA4 in the intestine remain to be elucidated. Methods: We assessed HSPA4 expression and function by generating HSPA4-deficient mice and using 214 human intestinal mucosa samples from patients with inflammatory bowel disease (IBD). Results: In the colonic mucosa of patients with IBD, a significant correlation was observed between the expression of HSPA4 and antiapoptotic protein Bcl-2, a T-cell-derived cytokine IL-17 or stem cell markers, such as Sox2. In refractory ulcerative colitis, a condition associated with increased cancer risk, expression of HSPA4 and Bcl-2 was increased in inflammatory cells of colonic mucosae. HSPA4 was overexpressed both in cancer cells and immune cells of human colorectal cancers. Patients with high expression of HSPA4 or Bmi1 showed significantly lower response rates upon subsequent steroid therapy as compared with patients with low expression of each gene. HSPA4-deficient mice exhibit more apoptosis and less expression of IL-17/IL-23 in inflammatory cells and less number of Sox(2+) cells after administration of dextran sodium sulfate than control mice. Transduction of HspaA4(+/-) bone marrow into wild-type mice reduced the immune response. Conclusions: Upregulation of Bcl-2 and IL-17 by HSPA4 would control apoptosis of inflammatory cells and immune response in the gut, which might develop treatment resistance in IBD. HSPA4 and Bmi1 would be a useful biomarker for refractory clinical course and a promising approach for a therapeutic strategy in patients with IBD.
  • Tadaaki Arizumi; Kazuomi Ueshima; Haruhiko Takeda; Yukio Osaki; Masahiro Takita; Tatsuo Inoue; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Naoshi Nishida; Masatoshi Kudo
    JOURNAL OF GASTROENTEROLOGY 49 12 1578 - 1587 2014年12月 [査読有り]
     
    To test the hypothesis that use of the response evaluation criteria in cancer of the liver (RECICL), an improved evaluation system designed to address the limitations of the response evaluation criteria in solid tumors 1.1 (RECIST1.1) and modified RECIST (mRECIST), provides for more accurate evaluation of response of patients with hepatocellular carcinoma (HCC) to treatment with sorafenib, a molecularly targeted agent, as assessed by overall survival (OS). The therapeutic response of 156 patients with advanced HCC who had been treated with sorafenib therapy for more than 1 month was evaluated using the RECIST1.1, mRECIST, and RECICL. After categorization as showing progressive disease (PD), stable disease (SD), or objective response, the association between OS and categorization was examined using the Kaplan-Meier method to develop survival curves. The 141 cases categorized as PD or SD by the RECIST1.1, but objective response by the mRECIST and RECICL, were further analyzed for determination of the association between OS and categorization. Only categorization using the RECICL was found to be significantly correlated with OS (p = 0.0033). Among the patients categorized as SD or PD by the RECIST1.1, reclassification by the RECICL but not the mRECIST was found to be significantly associated with OS and allowed for precise prediction of prognosis (p = 0.0066). Only the use of the RECICL allowed for identification of a subgroup of HCC patients treated with sorafenib with improved prognosis. The RECICL should, therefore, be considered a superior system for assessment of therapeutic response.
  • Toshiharu Sakurai; Hiroshi Kashida; Tomohiro Watanabe; Satoru Hagiwara; Tsunekazu Mizushima; Hideki Iijima; Naoshi Nishida; Hiroaki Higashitsuji; Jun Fujita; Masatoshi Kudo
    CANCER RESEARCH 74 21 6119 - 6128 2014年11月 [査読有り]
     
    Colitis-associated cancer (CAC) is caused by chronic intestinal inflammation and is reported to be associated with refractory inflammatory bowel disease (IBD). Defective apoptosis of inflammatory cell populations seems to be a relevant pathogenetic mechanism in refractory IBD. We assessed the involvement of stress response protein cold-inducible RNA-binding protein (Cirp) in the development of intestinal inflammation and CAC. In the colonic mucosa of patients with ulcerative colitis, expression of Cirp correlated significantly with the expression of TNF alpha, IL23/IL17, antiapoptotic proteins Bcl-2 and Bcl-xL, and stem cell markers such as Sox2, Bmi1, and Lgr5. The expression of Cirp and Sox2 was enhanced in the colonic mucosae of refractory ulcerative colitis, suggesting that Cirp expression might be related to increased cancer risk. In human CAC specimens, inflammatory cells expressed Cirp protein. Cirp(-/-) mice given dextran sodium sulfate exhibited decreased susceptibility to colonic inflammation through decreased expression of TNF alpha, IL23, Bcl-2, and Bcl-xL in colonic lamina propria cells compared with similarly treated wild-type (WT) mice. In the murine CAC model, Cirp deficiency decreased the expression of TNF alpha, IL23/IL17, Bcl-2, Bcl-xL, and Sox2 and the number of Dclk1(+) cells, leading to attenuated tumorigenic potential. Transplantation of Cirp(-/-) bone marrow into WT mice reduced tumorigenesis, indicating the importance of Cirp in hematopoietic cells. Cirp promotes the development of intestinal inflammation and colorectal tumors through regulating apoptosis and production of TNF alpha and IL23 in inflammatory cells. (C) 2014 AACR.
  • Sakurai T; Kashida H; Watanabe T; Hagiwara S; Mizushima T; Iijima H; Nishida N; Higashitsuji H; Fujita J; Kudo M
    Cancer Res 74 6119 - 6128 2014年 [査読有り]
  • Norihisa Yada; Toshiharu Sakurai; Tomohiro Minami; Tadaaki Arizumi; Masahiro Takita; Tatsuo Inoue; Satoru Hagiwara; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 87 118 - 123 2014年 [査読有り][招待有り]
     
    Objective: To investigate the relationship between tissue elasticity before and after antiviral therapy and shear wave as well as strain elastography. Methods: FibroScan and real-time tissue elastography were performed before and after antiviral therapy for chronic hepatitis C, and treatment efficacy and elastographic findings were comparatively analyzed. Elasticity was evaluated by measuring liver stiffness (LS) in kilopascals using FibroScan, and the liver fibrosis index (LFI) was assessed by real-time tissue elastography. Results: LS and LFI correlated well before and after therapy (r = 0.567, p = 0.003 and r = 0.576, p = 0.002, respectively). In the group without a sustained virological response (SVR), LS increased in 4 of 5 patients. Patients with an increase in both LS and LFI were all in the non-SVR group (3/3, 100%). In addition, LS increased in all patients except 1 in the non-SVR group (4/5, 80%). In the SVR group, both LS and LFI decreased in all patients except 1 (18/19, 94.7%). In the patient with an increase in LS despite achieving SVR, LS decreased quickly after alcohol cessation. Conclusions: With a few exceptions, SVR improved LS. All patients with an increase in LFI were in the non-SVR group, even though LFI decreased in 2 patients. Our findings suggest that an LFI increase indicates lack of treatment efficacy with antiviral therapy. LFI may be useful for the assessment of treatment efficacy in patients with worsening of LS despite achieving SVR with antiviral therapy. (C) 2014 S. Karger AG, Basel
  • Masahiro Takita; Satoru Hagiwara; Masatoshi Kudo; Masashi Kono; Hirokazu Chishina; Tadaaki Arizumi; Satoshi Kitai; Norihisa Yada; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima
    ONCOLOGY 87 110 - 117 2014年 [査読有り]
     
    Background: Telaprevir-based antiviral therapy has been the primary treatment for chronic hepatitis C genotype 1 at a high viral load since November 2011. On the other hand, a number of patients have been reported to require withdrawal from or reduced doses of drugs due to side effects, such as eruptions, anemia, and renal dysfunction. In addition, as hepatitis C patients are growing older, it is imperative to investigate the tolerability of triple combination therapy for elderly patients. Subjects and Methods: The study subjects comprised 35 patients who received telaprevir combination therapy after November 2011. They were divided into group A (age: <65 years; n = 21) and group B (age: >= 65 years; n = 14) in order to compare the treatment completion rate, sustained virological response at week 24 (SVR24), and adverse events between the groups. Results: The treatment completion rate was 82.8% (29/35) in all subjects, 90.4% (19/21) in group A, and 78.5% (11/14) in group B. The rate was lower in group B but without a significant difference between the groups (p = 0.804). The SVR24 rate was 88.5% (31/35) in all subjects, 90.4% (19/21) in group A, and 85.7% (12/14) in group B, without a significant difference between the groups (p = 0.161). Conclusion: Although the incidence of anemia was higher in group B, there was no significant difference in the treatment completion or SVR24 rate between the groups. Telaprevir combination therapy is suggested to be tolerable for elderly hepatitis C patients. (C) 2014 S. Karger AG, Basel
  • Tomohiro Minami; Yasunori Minami; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Tatsuo Inoue; Satoru Hagiwara; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 87 55 - 62 2014年 [査読有り]
     
    Purpose: The purpose of this study was to evaluate the usefulness of the combination guidance of contrast-enhanced US (CEUS) and fusion imaging in radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) with poor conspicuity on B-mode US and CEUS/fusion imaging. Materials and Methods: We conducted a retrospective cohort study, which included 356 patients with 556 HCCs that were inconspicuous on B-mode US. A total of 192 patients with 344 HCCs, 123 patients with 155 HCCs, and 37 patients with 57 HCCs underwent RFA under CEUS guidance, fusion imaging guidance, and the combination of CEUS and fusion imaging guidance. Results: The average number of treatment sessions was 1.1 (range: 1-2) in the CEUS guidance group, 1.1 (range: 1-2) in the fusion imaging guidance group, and 1.1 (range: 1-3) in the combination of CEUS and fusion imaging guidance group. Treatment analysis did not reveal significantly more RFA treatment sessions in the combination guidance group than in the other groups (p = 0.97, Student's t test). During the follow-up period (1.1-85.3 months, mean +/- SD, 43.2 +/- 59.5), the 3-year local tumor progression rates were 4.9, 7.2, and 5.9% in the CEUS guidance group, the fusion imaging guidance group, and the combination guidance group, respectively (p = 0.84, log-rank test). Conclusion: In spite of selection bias, session frequency and local tumor progression were not different under the combination guidance with CEUS and fusion imaging in RFA. The combination of fusion imaging and CEUS guidance in RFA therapy is an effective treatment for HCC with poor conspicuity on B-mode US and CEUS/fusion imaging. (C) 2014 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshima; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Naoshi Nishida; Masatoshi Kudo
    ONCOLOGY 87 32 - 36 2014年 [査読有り]
     
    Background: Transcatheter arterial chemoembolization (TACE) failure or refractoriness is an indication for sorafenib therapy in patients with advanced hepatocellular carcinoma. The study evaluated the validity of the definition of TACE failure or refractoriness as proposed by the Liver Cancer Study Group of Japan (LCSGJ) through a retrospective analysis of sorafenib treatment. Methods: Out of 265 patients with advanced hepatocellular carcinoma who were treated with sorafenib at our hospital, 45 experienced TACE failure or refractoriness and were included in this study and retrospectively analyzed. Results: Multivariate analysis only identified the number of ineffective TACE procedures performed before starting sorafenib treatment as significant factors. Overall survival (OS) after starting sorafenib was statistically longer in patients treated with <= 2 consecutive ineffective TACE procedures before sorafenib administration than in patients treated with >= 3 consecutive ineffective TACE procedures (p < 0.005). This result matched the LCSGJ criteria. Conclusion: In patients treated with sorafenib, OS was extended with <= 2 consecutive ineffective TACE procedures compared to that with >= 3 consecutive ineffective TACE procedures. Thus, if tumors are uncontrolled, TACE should not be repeated. The result of this study supports the definition of TACE failure or refractoriness proposed by the LCSGJ. (C) 2014 S. Karger AG, Basel
  • Naoshi Nishida; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Masatoshi Kudo
    DIGESTIVE DISEASES 32 6 740 - 746 2014年 [査読有り]
     
    Objectives: DNA methylation-dependent transcriptional inactivation of tumor suppressor genes (TSGs) is critical for the pathogenesis of hepatocellular carcinoma (HCC). This study identifies potential TSGs in HCCs using methylation profiling and pharmacological unmasking of methylated TSGs. Methods: Methylation profiling was performed on 22 pairs of HCCs and their corresponding noncancerous liver tissues using the Infinium HumanMethylation27 BeadChip. We also determined the gene reexpression after treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) and trichostatin A (TSA) in 5 HCC cell lines. Results: We selected CpGs that exhibited a significant increase in methylation in HCC tissues compared with that of the noncancerous control group. Two hundred and thirteen CpGs on different gene promoters with a mean difference in the beta value >= 0.15 and a value of p < 0.05 were selected. Of the 213 genes, 45 genes were upregulated in 3 or more HCC cell lines with multiplier value of differences after 5-Aza-dC and TSA treatment. Conclusions: We identified several potential TSGs that participate in transcription inactivation through epigenetic interactions in HCC. The results of this study are important for the understanding of functionally important epigenetic alterations in HCC. (C) 2014 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshima; Hirokazu Chishina; Masashi Kono; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 32 6 733 - 739 2014年 [査読有り]
     
    Background: Sorafenib is a multikinase inhibitor targeting Raf and protein tyrosine kinases, which are involved in cell growth and tumor angiogenesis. Sorafenib administration induces temporary inhibition of tumor growth and a decrease in arterial blood flow in a considerable number of hepatocellular carcinoma (HCC) patients. We retrospectively evaluated the association between decreased blood flow and the overall survival (OS) of HCC patients after the initiation of sorafenib therapy. Patients and Methods: Therapeutic responses of 158 advanced HCC patients with hypervascular tumors who had received sorafenib for more than 1 month were analyzed. To assess their therapeutic response, patients underwent radiological evaluation before and every 4-6 weeks after the initiation of sorafenib treatment. After the classification of patients into three groups based on the change in arterial enhancement during treatment (no change, decrease and disappearance), the OS of each group was compared using the Kaplan-Meier method. Results:Statistically significant differences in OS were observed among the three groups (p < 0.001). A decrease or disappearance of arterial enhancement was significantly associated with improved OS compared to patients with no change in arterial enhancement; the median OS was 19.9 months (95% confidence interval, CI, 16.4-24.5 months) and 6.0 months (95% CI, 4.0-8.8 months), respectively (p < 0.001). However, there was no difference in OS between the decrease and disappearance groups (p = 0.88). Conclusion: We conclude that decreased arterial enhancement during sorafenib treatment was associated with the longest OS and could therefore reflect an effective response. (C) 2014 S. Karger AG, Basel
  • Tadaaki Arizumi; Kazuomi Ueshirna; Hirokazu Chishina; Masashi Kono; Mashiro Takita; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 32 6 705 - 710 2014年 [査読有り]
     
    Background: Sorafenib is a molecular-targeting agent showing improved overall survival (OS) for advanced hepatocellular carcinoma (HCC). Although tumor dormancy, characterized by stable tumor status or stable disease (SD) without tumor regression, is a unique feature of sorafenib treatment, the contribution of SD to OS remains debatable. This study aimed to clarify the correlation between SD periods and OS in patients with HCC treated with sorafenib. Methods: From May 2009 to January 2013, 269 patients with advanced-stage HCC were treated with sorafenib at the Kinki University Hospital. The antitumor response of sorafenib was evaluated in 158 patients using the modified Response Evaluation Criteria in Solid Tumors, and patients with SD were divided into two subgroups according to the median duration of SD: short SD (<3 months) and long SD (>= 3 months). The relationship between the duration of SD and OS was analyzed among patients with complete (CR) and partial response (PR), and long and short SD using the Kaplan-Meier method. Results:The median OS was 5.7 months in the short SD, 20.8 months in the long SD and 17.9 months in the CR + PR group. Although the duration of OS was significantly longer in the long SD group than the short SD group, no difference in OS was detected between the patients with CR + PR and patients with long SD. The impact of long SD on OS could be as strong as that of CR + PR. Conclusion: Achievement of long SD is one of the important goals for improving survival in patients with HCC treated with sorafenib. (C) 2014 S. Karger AG, Basel
  • Masashi Kono; Tatsuo Inoue; Masatoshi Kudo; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Kazuorni Ueshima; Naoshi Nishida; Takamichi Murakami
    DIGESTIVE DISEASES 32 6 670 - 677 2014年 [査読有り]
     
    Objective:The purpose of this study was to evaluate the risk factors for local recurrence with radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) measuring <= 2 cm. Methods: This study involved 234 patients with 274 HCCs measuring cm who had undergone RFA as the initial treatment. The mean tumor diameter was 1.478 cm. The median follow-up period was 829 days. We evaluated the post-RFA cumulative local recurrence rate and analyzed the risk factors contributing to clinical outcomes. Results: Cumulative local recurrence rates were 9, 19 and 19% at 1,2 and 3 years, respectively. Among the 145 cases with a complete safety margin (SM) after RFA, only 4 developed local tumor recurrence and the cumulative rates of local tumor recurrence at 1, 2 and 3 years were 2, 3 and 3%, respectively. Among the 129 cases with incomplete SM, local tumor recurrence developed in 34 and the cumulative rates of local tumor progression at 1, 2 and 3 years were 14, 36 and 36%, respectively. In multivariate analysis, significant risk factors were tumor location (liver surface), irregular gross type and SM <5 mm. Conclusion: Even with HCC measuring cm, location and gross type of tumor should be carefully evaluated before RFA is performed. (C) 2014 S. Karger AG, Basel
  • Naoshi Nishida; Takafumi Nishimura; Takuya Nakai; Hirokazu Chishina; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Masatoshi Kudo
    DIGESTIVE DISEASES 32 6 658 - 663 2014年 [査読有り]
     
    Objective: To clarify the progression pattern of abnormal DNA methylation during the development of hepatocellular carcinoma (HCC) using a comprehensive methylation assay. Methods: We used an Infinium HumanMethylation450 BeadChip array that can analyze >485,000 CpG sites distributed throughout the genome for a comprehensive methylation study of 117 liver tissues consisting of 59 HCC and 58 noncancerous livers. Altered DNA nnethylation patterns during tumor progression were also analyzed. Results: We identified 38,330 CpG sites with significant differences in methylation levels between HCCs and noncancerous livers (DM-CpGs) using strict criteria. Of the DM-CpGs, 92% were hypomethylated and only 3,051 CpGs (8%) were hypermethylated in HCC. The DM-CpGs were more prevalent within intergenic regions with isolated CpGs. In contrast, DM-CpGs that were hypermethylated in HCC were predominantly located within promoter regions and CpG islands (p < 0.0001). The association between methylation profiles of DM-CpGs and tumor size was statistically significant, especially in hepatitis C virus (HCV)-positive cases (p = 0.0001). Conclusions: We clarified the unique characteristics of DM-CpGs in human HCCs. The stepwise progression of alterations in DNA methylation was a common feature of HCV-related hepatocarcinogenesis. (C) 2014 S. Karger AG, Basel
  • Naoshi Nishida; Masatoshi Kudo; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Tatsuo Inoue; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Kazuomi Ueshima; Takeshi Nagasaka; Ajay Goel
    HEPATOLOGY 58 1065A - 1066A 2013年10月 [査読有り]
  • Hiromasa Mine; Toshiharu Sakurai; Hiroshi Kashida; Shigenaga Matsui; Naoshi Nishida; Tomoyuki Nagai; Satoru Hagiwara; Tomohiro Watanabe; Masatoshi Kudo
    Digestive Diseases and Sciences 58 8 2337 - 2344 2013年08月
  • ソラフェニブ治療におけるJNK活性の重要性-CD133との関連も含めて
    萩原 智; 櫻井 俊治; 上嶋 一臣; 永井 知行; 西田 直生志; 工藤 正俊
    The Liver Cancer Journal The Liver Cancer Journal 5 58 - 59 2013年06月 [査読有り]
  • Satoru Hagiwara; Masatoshi Kudo; Yukio Osaki; Hiroo Matsuo; Tadashi Inuzuka; Akihiro Matsumoto; Eiji Tanaka; Toshiharu Sakurai; Kazuomi Ueshima; Tatsuo Inoue; Norihisa Yada; Naoshi Nishida
    Journal of Medical Virology 85 6 987 - 995 2013年06月 
    The ideal approach to treat chronic hepatitis B remains controversial. This pilot study aimed to evaluate the effectiveness of peginterferon (PEG-IFN) α-2b and entecavir hydrate (ETV) as a combination therapy for patients with chronic hepatitis B, particularly in the context of virological response and the reduction of intrahepatic covalently closed circular DNA (cccDNA). A total of 17 patients with hepatitis B virus (HBV) genotype C were enrolled in this study. All subjects were treated with this combination therapy for 48 weeks and observed for an additional 24 weeks. All patients underwent liver biopsy before and after the therapy period. Changes in cccDNA levels and liver histology were monitored between biopsies. Among the 11 patients who exhibited pre-therapy hepatitis B e antigen (HBeAg), 8 (73%) showed evidence of HBeAg seroconversion by the end of the follow-up period. Serum HBV DNA levels decreased by 5.2 and 3.3log copies/ml (mean) by the end of the therapy and follow-up periods, respectively. In addition, intrahepatic cccDNA decreased significantly to 1.4logcopies/μg (mean) by the end of the therapy period. Among the 11 patients who did not experience viral relapse, only 2 (18%) exhibited high levels of cccDNA (> 4.5logcopies/μg) by the end of the treatment period. In contrast, all relapsed subjects exhibited significantly higher levels of cccDNA than subjects who did not relapse (P=0.027). The combination regimen is a promising approach to treat chronic hepatitis B and may achieve significant reduction in serum HBV DNA and intrahepatic cccDNA. © 2013 Wiley Periodicals, Inc.
  • Yoshiaki Nagata; Toshiharu Sakurai; Masaki Takayama; Tomoyuki Nagai; Masanori Kawasaki; Yutaka Asakuma; Satoru Hagiwara; Naoshi Nishida; Shigenaga Matsui; Hiroshi Kashida; Masatoshi Kudo
    GASTROENTEROLOGY 144 5 S883 - S883 2013年05月 [査読有り]
     
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  • Norihisa Yada; Satoru Hagiwara; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    GASTROENTEROLOGY 144 5 S1041 - S1041 2013年05月 [査読有り]
     
    0
  • Tokuzo Arao; Kazuomi Ueshima; Kazuko Matsumoto; Tomoyuki Nagai; Hideharu Kimura; Satoru Hagiwara; Toshiharu Sakurai; Seiji Haji; Akishige Kanazawa; Hisashi Hidaka; Yukihiro Iso; Keiichi Kubota; Mitsuo Shimada; Tohru Utsunomiya; Masashi Hirooka; Yoichi Hiasa; Yoshikazu Toyoki; Kenichi Hakamada; Kohichiroh Yasui; Takashi Kumada; Hidenori Toyoda; Shuichi Sato; Hiroyuki Hisai; Teiji Kuzuya; Kaoru Tsuchiya; Namiki Izumi; Shigeki Arii; Kazuto Nishio; Masatoshi Kudo
    HEPATOLOGY 57 4 1407 - 1415 2013年04月 
    The response rate to sorafenib in hepatocellular carcinoma (HCC) is relatively low (0.7%-3%), however, rapid and drastic tumor regression is occasionally observed. The molecular backgrounds and clinico-pathological features of these responders remain largely unclear. We analyzed the clinical and molecular backgrounds of 13 responders to sorafenib with significant tumor shrinkage in a retrospective study. A comparative genomic hybridization analysis using one frozen HCC sample from a responder demonstrated that the 11q13 region, a rare amplicon in HCC including the loci for FGF3 and FGF4, was highly amplified. A real-time polymerase chain reactionbased copy number assay revealed that FGF3/FGF4 amplification was observed in three of the 10 HCC samples from responders in which DNA was evaluable, whereas amplification was not observed in 38 patients with stable or progressive disease (P = 0.006). Fluorescence in situ hybridization analysis confirmed FGF3 amplification. In addition, the clinico-pathological features showed that multiple lung metastases (5/13, P = 0.006) and a poorly differentiated histological type (5/13, P = 0.13) were frequently observed in responders. A growth inhibitory assay showed that only one FGF3/FGF4-amplified and three FGFR2-amplified cancer cell lines exhibited hypersensitivity to sorafenib in vitro. Finally, an in vivo study revealed that treatment with a low dose of sorafenib was partially effective for stably and exogenously expressed FGF4 tumors, while being less effective in tumors expressing EGFP or FGF3. Conclusion: FGF3/FGF4 amplification was observed in around 2% of HCCs. Although the sample size was relatively small, FGF3/FGF4 amplification, a poorly differentiated histological type, and multiple lung metastases were frequently observed in responders to sorafenib. Our findings may provide a novel insight into the molecular background of HCC and sorafenib responders, warranting further prospective biomarker studies. (HEPATOLOGY 2013)
  • Yoshiaki Nagata; Masatoshi Kudo; Tomoyuki Nagai; Tomohiro Watanabe; Masanori Kawasaki; Yutaka Asakuma; Satoru Hagiwara; Naoshi Nishida; Shigenaga Matsui; Hiroshi Kashida; Toshiharu Sakurai
    DIGESTIVE DISEASES AND SCIENCES 58 2 381 - 388 2013年02月 
    Intestinal-type gastric carcinomas progress through several sequential steps, including atrophic gastritis, intestinal metaplasia, dysplasia, and cancer. We investigated heat shock protein 27 (HSP27) expression in gastric neoplasia and background gastric mucosa to assess its involvement in gastric carcinogenesis. We used real-time quantitative polymerase chain reaction to examine HSP27 expression in gastric neoplasias and background gastric mucosae of 30 patients with intraepithelial neoplasias and in gastric mucosae of 30 patients without gastric neoplasia. Immunohistochemical staining was performed on 30 advanced gastric cancer tissues. HSP27 expression was negatively associated with atrophic gastritis. HSP27 expression in the background gastric mucosa of neoplasia-bearing patients was significantly lower than in the mucosa of those without gastric neoplasia. In tumor necrosis factor alpha-treated gastric cancer cells, HSP27 knockdown increased cell death and accumulation of the reactive oxygen species that link inflammation to cancer. Poorly differentiated tumors most frequently had high HSP27 levels. Dedifferentiation of cancer cells is associated with an epithelial-mesenchymal transition (EMT) signaling pathway. In gastric cancer MKN-1 cells, HSP27 knockdown upregulated E-cadherin and downregulated vimentin and smooth muscle actin, but this did not occur in MKN-74 cells. HSP27 expression in gastric mucosae is inversely correlated with intraepithelial neoplasia, a probable precursor to gastric cancer, and HSP27 expression in cancer is positively correlated with poor differentiation.
  • Tatsuo Inoue; Masatoshi Kudo; Kinuyo Hatanaka; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Toshiharu Sakurai; Kazuomi Ueshima; Naoshi Nishida
    ONCOLOGY 84 51 - 57 2013年 
    Objective: Contrast-enhanced ultrasonography (CEUS) with Sonazoid and dynamic computed tomography (CT) were used to evaluate radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC). Local recurrence rate was used as the gold standard of evaluation. Methods: From January 2007 to December 2011,86 HCCs from 70 patients were treated with RFA. CEUS with Sonazoid and dynamic CT were then used to evaluate the effect of RFA. For CEUS and dynamic CT, effects were classified as follows: (1) complete ablated response with safety margin >5 mm (CRSM+); (2) complete ablated response but with safety margin <5 mm (CRSM-); (3) incomplete, residual tumor detected after treatment. Results: CEUS judged 33 cases as CRSM+, while dynamic CT identified 49 cases. None of these 33 cases from the CEUS group had local recurrences, while dynamic CT had 1 case. CEUS judged 49 cases as CRSM-, compared to 34 cases with dynamic CT. Of these, 9 cases of CEUS and 8 cases of dynamic CT showed local recurrences. Two cases diagnosed as 'incomplete' by CEUS and dynamic CT had recurrences within 1 year. Conclusion: CEUS can be used to assess the efficacy of RFA for HCC, with the potential to reduce the number of CT scans required for confirmation. Copyright (C) 2013 S. Karger AG, Basel
  • Naoshi Nishida; Tadaaki Arizumi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Masatoshi Kudo
    Digestive Diseases 31 5-6 459 - 466 2013年 
    Chronic hepatitis C (CHC) triggers oxidative stress and contributes to the emergence of hepatocellular carcinoma (HCC). We previously reported that tumor suppressor gene (TSG) methylation is a critical factor during the early stages of hepatocarcinogenesis. In this study, we clarify the association between oxidative stress and epigenetic alterations during hepatocarcinogenesis. We examined DNA oxidation and methylation profiles in 128 liver biopsy samples from CHC patients. The DNA oxidation and methylated TSG numbers were quantified using immunohistochemical analysis of 8-hydroxydeoxyguanosine (8-OHdG) and quantitative PCR for 11 TSGs, respectively. The quantitative chromatin immunoprecipitation-PCR (ChIP-qPCR) assay in HepG2 and fetal liver Hc cells treated with H< inf> 2< /inf> O< inf> 2< /inf> was used to quantify trimethyl-H3K4, acetylated-H4K16 (an active chromatin marker), trimethyl-H3K27 (a repressive chromatin marker) and 8-OHdG. We analyzed 30 promoters of 25 different TSGs by qPCR. The high levels of 8-OHdG was the only variable that was significantly associated with the increased number of methylated TSGs in CHC (p < 0.0001). The ChIP-qPCR revealed that after H< inf> 2< /inf> O< inf> 2< /inf> treatment of the cell lines, the 8-OHdG-bound promoters showed a modification from an active chromatin (trimethyl-H3K4 and acetylated-H4K16 dominant) to a repressive chromatin (trimethyl-H3K27 dominant) status. We conclude that oxidative stress alters the chromatin status, which leads to abnormal methylation of TSGs, and contributes to hepatocarcinogenesis in CHC patients.
  • Toshiharu Sakurai; Masatoshi Kudo; Tomohiro Watanabe; Katsuhiko Itoh; Hiroaki Higashitsuji; Tadaaki Arizumi; Tatsuo Inoue; Satoru Hagiwara; Kazuomi Ueshima; Naoshi Nishida; Manabu Fukumoto; Jun Fujita
    DIGESTIVE DISEASES 31 5-6 440 - 446 2013年 
    Objective: Mild hypothermia (32-33 degrees C) shows protective effects in patients with brain damage and cardiac arrest. Although cold-inducible RNA-binding protein (CIRP) contributes to the protective effects of hypothermia through extracellular signal-regulated kinase activation in fibroblasts, the effects of hypothermia in the liver remain unclear. Methods: We analysed the effects of cold temperature on fulminant hepatitis, a potentially fatal disease, using the D-galactosamine (GalN)/lipopolysaccharide (LPS) and concanavalin (con) A-induced hepatitis models in mice. After GalN/LPS administration and anaesthesia, mice in the hypothermia group were kept at 25 degrees C and those in control group were kept at 35 degrees C. After concanavalin A (con A) administration, the mice in the hypothermia group were placed in a chamber with an ambient temperature of 6 degrees C for 1.5 h. Results: Hypothermia attenuated liver injury and prolonged survival. Activation of c-Jun N-terminal kinase and Akt, which are involved in reactive oxygen species (ROS) accumulation, was suppressed by low temperature. Hypothermia significantly decreased oxidized protein levels, and treatment with N-acetyl-L-cysteine, an antioxidant, attenuated GalN/LPS-induced liver injury. In con A-induced hepatitis, CIRP expression was upregulated and Bid expression was downregulated, resulting in decreased apoptosis of hepatocytes in the hypothermia group. Conclusions: These data suggest that hypothermia directly protects hepatocytes from cell death via reduction of ROS production in fulminant hepatitis. (C) 2013 S. Karger AG, Basel
  • Naoshi Nishida; Shinichi Iwamura; Hiroshi Ida; Satoshi Hagiwara; Yoshinori Kagioka; Yasunori Minami; Yoji Maetani; Kyo Itoh; Masatoshi Kudo
    DIGESTIVE DISEASES 31 5-6 408 - 414 2013年 
    Budd-Chiari syndrome (BCS) is a rare condition characterized by hepatic venous outflow obstruction. In this report, we present 4 cases of BCS with complete and incomplete obstruction of the inferior vena cava (IVC) and hepatic vein (HV). Each case showed different and unique features of liver damage, which were attributed to the site and degree of obstruction. Interestingly, improved liver functions such as increased serum albumin levels, decreased hyaluronic acid levels and a normal indocyanine green clearance test were evident within 1 month of the balloon angioplasty. Pericellular fibrosis and hypervascular regenerative nodules were also reversible after obstruction removal. Therefore, it is very important to manage this rare disease before it progresses to liver cirrhosis. (C) 2013 S. Karger AG, Basel
  • Naoshi Nishida; Tadaaki Arizumi; Masahiro Takita; Tonnoyuki Nagai; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Kazuonni Ueshima; Toshiharu Sakurai; Hiroshi Ida; Masatoshi Kudo
    ONCOLOGY 84 82 - 87 2013年 
    Objectives: Hepatocellular carcinoma (HCC) is one of the common cancers worldwide. Accurate diagnosis of tumor progression is critical for the appropriate management of HCC. Here, we established a sensitive assay to detect and quantify tumor-derived DNA in the serum of HCC patients. Methods: Aberrant methylation of the APC gene was quantified in 23 HCC patients and 8 healthy volunteers using 100 mu l of serum. For sensitive detection and accurate quantification of tumor DNA, we combined seminested polymerase chain reaction (PCR) with TaqMan PCR, which could amplify the APC gene regardless of the methylation status and detect the methylated and unmethylated sequences separately. The ratio of methylated to unmethylated sequences was quantified. Results: The methylated APC gene was detected in all HCC patients examined, but no healthy volunteers showed amplification of methylated sequences in serum. HCC patients with portal vein thrombosis showed a significantly higher methylated to unmethylated APC gene ratio in serum than those without portal vein thrombosis (p = 0.0029). Conclusions: Considering the strong association between the ratio of the methylated to unmethylated APC sequences in serum and the presence of portal vein thrombosis, methylation status of APC sequences could be a promising marker for improving HCC management. Copyright (C) 2013 S. Karger AG, Basel
  • Unique association between global DNA hypomethylation and hromosomal alterations in human hepatocellular carcinoma
    Nishida N; Kudo M; Nishimura T; Arizumi T; Takita M; Kitai S; Yada N; Hagiwara S; Inoue T; Minami Y; Ueshima K; Sakurai T; Yokomichi N; Nagasaka T; Goel A
    Plos One 8 9 e72312  2013年 [査読有り]
  • 当院における肝細胞癌分子標的治療の現状
    上嶋 一臣; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊
    第6回日本肝がん分子標的治療研究会 記録 SORAFENIB PRACTICE BOOK: Sorafenib治療の実践!!多数症例の使用経験を踏まえた治療の実践と問題点の解決を示す 25 - 30 アークメディア 2012年10月
  • Tatsuo Inoue; Masatoshi Kudo; Mina Komuta; Sosuke Hayaishi; Taisuke Ueda; Masahiro Takita; Satoshi Kitai; Kinuyo Hatanaka; Norihisa Yada; Satoru Hagiwara; Hobyung Chung; Toshiharu Sakurai; Kazuomi Ueshima; Michiie Sakamoto; Osamu Maenishi; Tomoko Hyodo; Masahiro Okada; Seishi Kumano; Takamichi Murakami
    J Gastroenterol 47 9 1036 - 1047 2012年09月 [査読有り]
     
    We aimed to evaluate gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for the detection of hepatocellular carcinomas (HCCs) and dysplastic nodules (DNs) compared with dynamic multi-detector row computed tomography (MDCT), and to discriminate between HCCs and DNs. Eighty-six nodules diagnosed as HCC or DNs were retrospectively investigated. Gd-EOB-DTPA-enhanced MRI and dynamic MDCT were compared with respect to their diagnostic ability for hypervascular HCCs and detection sensitivity for hypovascular tumors. The ability of hepatobiliary images of Gd-EOB-DTPA-enhanced MRI to discriminate between these nodules was assessed. We also calculated the EOB enhancement ratio of the tumors. For hypervascular HCCs, the diagnostic ability of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of MDCT for tumors less than 2 cm (p = 0.048). There was no difference in the detection of hypervascular HCCs between hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI (43/45: 96%) and dynamic MDCT (40/45: 89%), whereas the detection sensitivity of hypovascular tumors by Gd-EOB-DTPA-enhanced MRI was significantly higher than that by dynamic MDCT (39/41: 95% vs. 25/41: 61%, p = 0.001). EOB enhancement ratios were decreased in parallel with the degree of differentiation in DNs and HCCs, although there was no difference between DNs and hypovascular well-differentiated HCCs. The diagnostic ability of Gd-EOB-DTPA-enhanced MRI for hypervascular HCCs less than 2 cm was significantly higher than that of MDCT. For hypovascular tumors, the detection sensitivity of hepatobiliary phase images of Gd-EOB-DTPA-enhanced MRI was significantly higher than that of dynamic Gd-EOB-DTPA-enhanced MRI and dynamic MDCT. It was difficult to distinguish between DNs and hypovascular well-differentiated HCCs based on the EOB enhancement ratio.
  • Ah-Mee Park; Masatoshi Kudo; Satoru Hagiwara; Masaki Tabuchi; Tomohiro Watanabe; Hiroshi Munakata; Toshiharu Sakurai
    FREE RADICAL BIOLOGY AND MEDICINE 52 11-12 2284 - 2291 2012年06月 
    Mitogen-activated protein kinases (MAPKs) are ubiquitous proteins that function in both normal and stress-related pathophysiological states of the cell. This study aimed to analyze the importance of p38MAPK in pancreatic injury using WBN/Kob rats with spontaneous chronic pancreatitis. Male WBN/Kob rats were injected with the p38MAPK inhibitor SB203580, starting at the age of 4 weeks, and sacrificed 6 weeks later. Compared with vehicle-treated rats, p38 inhibitor-treated rats exhibited a significant increase in pancreatic cell death and inflammation as assessed by histologic examination and myeloperoxidase activity, respectively. p38 inhibition decreased the expression of heat shock protein 27 (HSP27), an antioxidant protein, and enhanced accumulation of reactive oxygen species (ROS). In addition, the proapoptotic protein BAD was increased in the pancreas of rats treated with p38 inhibitor. In a pancreatic cell line (PANC-1), HSP27 knockdown augmented reactive oxygen species accumulation and cell death induced by tumor necrosis factor-alpha plus actinomycin D. In conclusion, p38MAPK suppresses chronic pancreatitis by upregulating HSP27 expression and downregulating BAD expression. (C) 2012 Elsevier Inc. All rights reserved.
  • S. Hagiwara; M. Kudo; T. Nagai; T. Inoue; K. Ueshima; N. Nishida; T. Watanabe; T. Sakurai
    BRITISH JOURNAL OF CANCER 106 12 1997 - 2003 2012年06月 
    BACKGROUND: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. While sorafenib, a multikinase inhibitor targeting the Raf/extracellular signal-regulated protein kinase (ERK) pathway, has been shown recently to provide a survival advantage to patients with advanced HCC, a predictive biomarker has not been developed. We studied whether c-Jun N-terminal kinase (JNK), which promotes liver carcinogenesis in mice, affects therapeutic response to sorafenib in HCC patients. METHODS: We collected pathological specimens from 39 patients with advanced HCC before starting sorafenib treatment, and measured JNK activity in HCCs. RESULTS: In patients treated with sorafenib, the expression of phospho-c-Jun in HCC, as a read out of JNK activity, was significantly higher (P<0.001) in the non-responder group than in the responder group. c-Jun N-terminal kinase activation in HCC was associated with a decreased time to progression and a poor overall survival (P = 0.0028 and P = 0.0008, respectively). CONCLUSION: In addition, JNK activity was significantly correlated with CD133 expression level. Correspondingly, high expression level of CD133 was linked to a poor response to sorafenib. Furthermore, D-JNKi, a specific JNK inhibitor, reduced the growth of xenografted CD133(+) cells in athymic mice. In conclusion, JNK activation was positively correlated with CD133 expression level and inversely correlated with the therapeutic response to sorafenib, suggesting that JNK activity may be considered as a new predictive biomarker for response to sorafenib treatment. British Journal of Cancer (2012) 106, 1997-2003. doi:10.1038/bjc.2012.145 www.bjcancer.com Published online 17 May 2012 (C) 2012 Cancer Research UK
  • Toshiharu Sakurai; Satoru Hagiwara; Tatsuo Inoue; Kazuomi Ueshima; Shigenaga Matsui; Naoshi Nishida; Hiroshi Kashida; Masatoshi Kudo
    GASTROENTEROLOGY 142 5 S452 - S452 2012年05月 [査読有り]
  • Naoshi Nishida; Masatoshi Kudo; Tadaaki Arizumi; Sosuke Hayaishi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Tatsuo Inoue; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Takeshi Nagasaka; Ajay Goel
    GASTROENTEROLOGY 142 5 S910 - S911 2012年05月 [査読有り]
  • Yasunori Minami; Kinuyo Hatanaka; Tadaaki Arizumi; Sosuke Hayaishi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Tatsuo Inoue; Satoru Hagiwara; Kazuomi Ueshima; Naoshi Nishida; Masatoshi Kudo
    GASTROENTEROLOGY 142 5 S1002 - S1002 2012年05月 [査読有り]
  • Satoru Hagiwara; Masatoshi Kudo; Hobyung Chung; Kazuomi Ueshima; Tatsuo Inoue; Seiji Haji; Tomohiro Watanabe; Ah-Mee Park; Hiroshi Munakata; Toshiharu Sakurai
    HEPATOLOGY RESEARCH 42 4 394 - 400 2012年04月 [査読有り]
     
    Aim: Hepatocellular carcinoma (HCC) ranks as the third leading cause of cancer deaths worldwide. Hepatic resection is the mainstay of curative treatment for early stage HCC. Although c-Jun N-terminal kinase (JNK) activation contributes to hepatocyte proliferation and HCC development in mice, the extent of involvement of JNK in human HCC development is unknown. The aim of this study is to assess the predictive value of JNK for postoperative recurrence in HCC. Methods: From April 2005 to March 2008, 159 patients underwent curative resection for HCC. From the 159 patients, 20 patients each matched for age, gender and etiology were registered as three groups: (i) without recurrence (no recurrence group), (ii) with recurrence within one year after surgery (early recurrence group), and (iii) with recurrence at one year or more after surgery (late recurrence group) (a cross- sectional control study). We investigated factors contributing to postoperative early and late phase recurrence. Results: Multivariate analysis using a Logistic regression model showed that JNK activity in non- cancerous liver tissue was correlated with postoperative late recurrence. (P = 0.02, odds ratio; 5.79, 95% confidence interval [CI]; 1.33- 25.36). Conclusions: JNK activity in non- cancerous liver tissue is considered as a reliable predictive biomarker for postoperative recurrence in HCC.
  • 経皮的ラジオ波焼灼術後の後出血予防における穿刺経路焼灼の有効性の検討
    早石 宗右; 南 康範; 足立 哲平; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 鄭 浩柄
    日本消化器病学会雑誌 109 臨増総会 A282 - A282 (一財)日本消化器病学会 2012年03月
  • 造影超音波 肝癌に対するラジオ波焼灼療法の治療効果判定造影USと造影CTの比較検討
    井上 達夫; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    超音波医学 39 2 191 - 191 (公社)日本超音波医学会 2012年03月
  • 組織弾性イメージング 肝エラストグラフィ 各モダリティーにおける測定原理と結果の解釈
    矢田 典久; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    超音波医学 39 2 193 - 193 (公社)日本超音波医学会 2012年03月
  • 体外式超音波穿刺用コンベックスプローブEUP-B715の使用経験
    矢田 典久; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    超音波医学 39 2 201 - 201 (公社)日本超音波医学会 2012年03月
  • Satoru Hagiwara; Toshiharu Sakurai; Masahiro Takita; Kazuomi Ueshima; Yasunori Minami; Tatsuo Inoue; Norihisa Yada; Satoshi Kitai; Tomoyuki Nagai; Sousuke Hayaishi; Tadaaki Arizumi; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 30 6 561 - 567 2012年 
    Objective: Increasing evidence suggests the efficacy of maintenance therapy with interferon (IFN) for chronic hepatitis C (CHC) in reducing the risk of hepatocellular carcinoma (HCC). The aim of this study was to determine clinical characteristics on the risk of occurrence of HCC in CHC patients receiving maintenance IFN therapy. Methods: A total of 55 patients were treated in a single center with PEG-IFN alpha-2a monotherapy for CHC and evaluated for variables predictive of the occurrence of HCC. Results: The cumulative incidences of HCC were 0.092, 0.117 and 0.161 at 3, 5 and 7 years, respectively. Serum ALT level (>40 IU/l) in the 6th month after commencement of IFN therapy and BMI >25 were associated with shorter time-to-HCC emergence using multivariate analysis (relative risk 16.034, p = 0.01 for ALT >40 IU/I; relative risk 6.020, p = 0.026 for BMI >25, respectively). The IL28B SNP was extracted as a significant factor for the occurrence of HCC. Conclusions: Maintenance therapy with the use of long-term low-dose PEG-IFN alpha-2a is effective for preventing HCC occurrence irrespective of the IL28B SNP, at least for a subset of CHC patients. The initial response of serum ALT levels and BMI provides a prognostic value for determining the risk of developing HCC later in life. Copyright (C) 2012 S. Karger AG, Basel
  • Naoshi Nishida; Tadaaki Arizumi; Sosuke Hayaishi; Masahiro Takita; Satoshi Kitai; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Toshiharu Sakurai; Iwao Ikai; Masatoshi Kudo
    DIGESTIVE DISEASES 30 6 547 - 553 2012年 
    Objectives: A unique causative aspect of hepatocellular carcinoma (HCC) is a gender difference in its incidence. To determine the specific factors that contribute to a male predominance, we analyzed the clinicopathological factors, and genetic and epigenetic alterations of HCCs in male and female patients. Methods: We retrospectively analyzed three cohorts of patients: the first cohort consisted of 547 patients identified with the first event of HCC, the second cohort included 176 HCC patients, and the third 127 patients with chronic hepatitis C (CHC). Results: Male patients were found to have HCC more frequently than female patients in cases of non-cirrhotic liver (p = 0.0030 by the chi(2) test), especially in hepatitis C-positive cases. However, there were no gender-specific differences in the genetic and epigenetic alterations of cancer-related genes. Deposition of iron was more severe in male CHC patients than in female patients. Conclusions: Male patients with CHC develop HCC more frequently when they have a non-cirrhotic liver than do female patients. This gender difference could be, at least partially, attributed to a different degree of iron deposition, which contributes to the development of HCC in the absence of liver cirrhosis in men with CHC. Copyright (C) 2012 S. Karger AG, Basel
  • Satoru Hagiwara; Toshiharu Sakurai; Shinichi Nishina; Kaoru Tanaka; Masafumi Ikeda; Kazuomi Ueshima; Yasunori Minami; Tatsuo Inoue; Norihisa Yada; Satoshi Kitai; Masahiro Takita; Tomoyuki Nagai; Sousuke Hayaishi; Tadaaki Arizumi; Ah-Mee Park; Hiroshi Munakata; Naoshi Nishida; Masatoshi Kudo
    DIGESTIVE DISEASES 30 6 541 - 546 2012年 
    Objective: A number of studies have reported reactivation of hepatitis B during intensive immunosuppressive therapy such as cases of hematological malignancy, whereas little has been reported for characteristics of reactivation triggered by chemotherapy for solid cancer. Methods: A total of 130 patients underwent chemotherapy for treatments of common solid cancer between May 2011 and May 2012 at Kinki University Hospital. Among them, 27 patients were suspected for a past infection of hepatitis B virus (HBV), showing positive for hepatitis B core antibody or surface antibody but negative for hepatitis B surface antigen, and were eligible for this study. Results: Hepatitis B reactivation was observed in 2 of 27 cases (7.4%). The duration between the start of chemotherapy and increase of serum HBV load was 30 days in both cases. Conclusions: We reported the 2 cases of hepatitis B reactivation receiving chemotherapy for solid cancer in terms of patterns and characteristics of reactivation. Accumulation of such cases will help in clarifying the clinical importance of hepatitis B reactivation during treatment of solid malignancies. Copyright (C) 2012 S. Karger AG, Basel
  • IL28B型との関連からみたResponse-guided therpy. C型肝炎-新時代の治療戦略
    萩原 智; 工藤正俊
    消化器の臨床 15 2012年 [査読有り]
  • 有住 忠晃; 上嶋 一臣; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 工藤 正俊
    新薬と臨牀 60 12 2516 - 2516 (株)医薬情報研究所 2011年12月
  • 上嶋 一臣; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 工藤 正俊
    The Liver Cancer Journal 3 4 336 - 337 (株)メディカルレビュー社 2011年12月
  • 肝血管肉腫の2例
    有住 忠晃; 萩原 智; 大本 俊介; 早石 宗右; 上田 泰輔; 田北 雅弘; 北井 聡; 南 康範; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    肝臓 52 Suppl.2 A680 - A680 (一社)日本肝臓学会 2011年09月
  • 櫻井 俊治; 萩原 智; 上嶋 一臣; 工藤 正俊
    The Liver Cancer Journal 3 2 150 - 151 (株)メディカルレビュー社 2011年06月
  • Hagiwara S; Kudo M
    Nihon rinsho. Japanese journal of clinical medicine 69 Suppl 4 546 - 550 日本臨床社 2011年05月 [査読有り]
  • B型慢性肝炎に対するPEG-IFNα2bとエンテカビル48週併用療法の有効性について
    萩原 智; 峯 宏昌; 有住 忠晃; 早石 宗右; 上田 泰輔; 田北 雅弘; 畑中 絹世; 北井 聡; 矢田 典久; 井上 達夫; 鄭 浩柄; 櫻井 俊治; 上嶋 一臣; 工藤 正俊; 犬塚 義; 大崎 往夫
    日本消化器病学会雑誌 108 臨増総会 A251 - A251 (一財)日本消化器病学会 2011年03月
  • 萩原 智; 工藤 正俊; 上嶋 一臣; 鄭 浩柄; 山口 真未; 田北 雅弘; 土師 誠二; 木村 雅友; 荒尾 徳三; 西尾 和人; Ah-Mee Park; 宗像 浩
    J Gastroenterol 46 2 212 - 221 2011年02月 
    Combination therapy with the oral fluoropyrimidine anticancer drug S1 and interferon is reportedly effective for the treatment of advanced hepatocellular carcinoma (HCC), but selection criteria for this therapy have not been clarified. In this study, we attempted to identify factors predicting the effectiveness of this combination therapy. Pathological specimens of HCC were collected before treatment from 31 patients with advanced HCC who underwent S1+ pegylated-interferon (PEG-IFN) alpha-2b therapy between January 2007 and January 2009. In these pathological specimens, the expression levels of CD133, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and interferon-receptor 2 (IFNR2) proteins were determined by Western blot assay. The presence or absence of p53 gene mutations was determined by direct sequencing. The relationships between these protein expression levels and the response rate (RR), progression-free survival (PFS), and overall survival (OS) were evaluated. The CD133 protein expression level was significantly lower in the responder group than in the nonresponder group. Comparing the PFS and OS between high- and low-level CD133 expression groups (n = 13 and 18, respectively) revealed that both parameters were significantly prolonged in the latter group. The expression levels of TS, DPD, and IFNR2 protein and the presence of p53 gene mutations did not correlate with the RR. CD133 was identified as a predictor of the therapeutic effect of S1+ PEG-IFN alpha-2b therapy against advanced HCC.
  • Masahiro Takita; Satoru Hagiwara; Tadaaki Arizumi; Sousuke Hayaishi; Taisuke Ueda; Satoshi Kitai; Norihisa Yada; Tatsuo Inoue; Yasunori Minami; Hobyung Chung; Kazuomi Ueshima; Toshiharu Sakurai; Masatoshi Kudo
    DIGESTION 84 S1 56 - 61 2011年 
    Background: Pegylated interferon (PEG-IFN) plus ribavirin therapy is the current standard treatment for chronic hepatitis C (CHC) genotype 1 with high viral load. A common genetic variation near the IL28B gene has been found to affect the response to PEG-IFN plus ribavirin therapy for CHC. The aims of this study were to analyze the association between the rs8099917 genotype and treatment response in a cohort study of CHC. Methods: This study evaluated clinical and laboratory parameters retrospectively in a cohort of 122 patients with chronic hepatitis C with genotype 1 and a high viral load who received PEG-IFN plus ribavirin therapy. We carried out univariate and multivariate statistical analyses of parameters and clinical responses. Results: Sixty-three of 122 patients (51.6%) had sustained virological responses (SVRs). Patients with the rs8099917 genotype TT achieved significantly higher SVR rates (p < 0.01). Univariate analysis revealed that SVRs were associated with BMI, fibrosis, albumin, total cholesterol, PEG-IFN dose, ribavirin dose and the rs8099917 genotype. Multivariate analysis revealed that the rs8099917 genotype (odds ratio 7.434, 95% CI 2.278-24.257, p = 0.001) and total PEG-IFN dose (odds ratio 7.162, 95% CI 1.565-18.15, p = 0.007) were significant factors. Conclusions: The rs8099917 genotype and total PEG-IFN dose were associated with SVR in patients with hepatitis C virus genotype 1. Copyright (C) 2011 S. Karger AG, Basel
  • Sosuke Hayaishi; Hobyung Chung; Masatoshi Kudo; Emi Ishikawa; Masahiro Takita; Taisuke Ueda; Satoshi Kitai; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima
    DIGESTIVE DISEASES 29 3 326 - 332 2011年 
    Background: It has been reported that branched-chain amino acid (BCAA) supplementation can improve nutritional status and prevent liver-related complications in patients with decompensated cirrhosis. We investigated the effects of oral BCAA supplementation on the incidence of hepatocellular carcinoma (HCC) and liver-related events in patients with compensated and decompensated cirrhosis. Methods: We enrolled 211 patients with cirrhosis including 152 patients with Child-Pugh A cirrhosis, but no history of HCC. Of these, 56 received oral administration of 12 g/day BCAA for 6 6 months (BCAA group), and 155 were followed-up without BCAA treatment (control group). The HCC occurrence and event-free survival rates were compared between the two groups. We used a propensity score analysis to overcome selection bias of this retrospective analysis. Results: The HCC occurrence rate was significantly lower and event-free survival rate was significantly higher in the BCAA group than in the control group. Multivariate analyses showed BCAA supplementation was significantly associated with reduced incidence of HCC (hazard ratio (HR) 0.416, 95% confidence interval (CI) 0.216-0.800, p = 0.0085). BCAA supplementation also reduced the incidence of liver-related events in patients with Child-Pugh A cirrhosis, although the difference did not reach statistical significance (HR 0.585, 95% CI 0.336-1.017, p = 0.0575). Conclusions: Oral BCAA supplementation is associated with reduced incidence of HCC in patients with cirrhosis and seems to prevent liver-related events in patients with Child-Pugh A cirrhosis. Copyright (C) 2011 S. Karger AG, Basel
  • 上嶋 一臣; 工藤 正俊; 田北 雅弘; 永井 知行; 辰巳 千栄; 上田 泰輔; 北井 聡; 石川 恵美; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 鄭 浩柄; 櫻井 俊治
    Digest Dis 29 3 321 - 325 2011年 
    Objective: The purpose of this study was to evaluate the role of des-gamma-carboxyprothrombin (DCP) as a marker for the efficacy of sorafenib therapy for hepatocellular carcinoma (HCC). Methods: Patients with advanced HCC treated with sorafenib were retrospectively evaluated, focusing on DCP levels and clinical characteristics. Results: 50 patients with advanced HCC were treated with sorafenib alone. In 25 of these patients, the serum levels of DCP were evaluated twice (pretreatment and within 2 weeks after starting therapy). The time to progression was significantly longer in patients in whom the DCP level at 2 weeks after starting sorafenib was 6 2-fold higher than the pretreatment levels, as compared with patients without an increase in DCP (p = 0.0296). Conclusions: The serum level of DCP is a surrogate marker for tissue hypoxia and can be a predictive marker to assess the tumor response to sorafenib therapy. Copyright (C) 2011 S. Karger AG, Basel
  • B型肝癌根治後の再発抑制治療と有用性.
    萩原 智; 工藤 正俊
    日本臨床 69 4 546 - 550 2011年 [査読有り]
  • 上嶋 一臣; 土師 誠二; 早石 宗右; 上田 泰輔; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 鄭 浩柄; 櫻井 俊治; 工藤 正俊
    新薬と臨牀 59 12 2409 - 2410 (株)医薬情報研究所 2010年12月
  • 非閉塞性腸管虚血を発症した悪性リンパ腫の一例
    宮田 剛; 井上 達夫; 有住 忠晃; 早石 宗右; 上田 泰輔; 辰巳 千栄; 田北 雅弘; 北井 聡; 石川 恵美; 矢田 典久; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    日本消化器病学会雑誌 107 臨増大会 A828 - A828 (一財)日本消化器病学会 2010年09月
  • 造影エコーによる肝細胞癌の診断能、Gd-EOB-MRI、Dynamic CTとの比較検討
    井上 達夫; 畑中 絹世; 早石 宗右; 上田 泰輔; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    肝臓 51 Suppl.2 A564 - A564 (一社)日本肝臓学会 2010年09月
  • 線維化進行C型肝炎患者における脾摘後のインターフェロン導入における問題点 好中球数の変化について
    鄭 浩柄; 上田 泰輔; 早石 宗右; 田北 雅弘; 北井 聡; 畑中 絹代; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 土師 誠二
    肝臓 51 Suppl.2 A600 - A600 (一社)日本肝臓学会 2010年09月
  • Yasunori Minami; Masatoshi Kudo; Kinuyo Hatanaka; Satoshi Kitai; Tatsuo Inoue; Satoru Hagiwara; Hobyung Chung; Kazuomi Ueshima
    LIVER INTERNATIONAL 30 5 759 - 764 2010年05月 [査読有り]
     
    Aim: Conventional contrast harmonic sonography has the technical problem of a short enhancement time during targeting of hepatic malignancies for radiofrequency (RF) ablation. This study investigated the effectiveness of contrast harmonic sonographic guidance using perfluorocarbon microbubbles (Sonazoid) during RF ablation of hepatic malignancies. Materials and Methods: Nodules were detected on contrast-enhanced computed tomography, but could not be resolved clearly by B-mode sonography. Sixty-six patients (51 men, 15 women; mean age, 65.8 years) with 108 hepatic malignancies were enrolled. Fifty-one patients with hepatocellular carcinoma and 15 patients with liver metastases were treated by RF ablation guided by contrast harmonic sonography using perfluorocarbon microbubbles for a target lesion identified as a defect image after the administration of contrast medium. Results: The maximal diameters of all tumours ranged from 0.7 to 3.5 cm (mean +/- SD, 1.7 cm +/- 0.9) on sonography. Complete tumour necrosis was achieved by a single session of RF ablation in 62 (94%) of the 66 patients, while two sessions were required for the remaining four (6%) patients. The average number of treatment sessions was 1.1 +/- 0.3. In the post-vascular phase, 105 (97%) of a total of 108 malignant hepatic tumours were depicted as a defect with a margin. Clinical courses have been satisfactory without any signs of local tumour progression during 1-12 months of follow-up (mean, 4.3 months). Conclusion: Using perfluorocarbon microbubbles, contrast harmonic sonographic-guided RF ablation is an efficient approach for guiding further ablation of hepatic malignancies that are not clearly demarcated by B-mode sonography.
  • Kazuomi Ueshima; Masatoshi Kudo; Masahiro Takita; Tomoyuki Nagai; Chie Tatsumi; Taisuke Ueda; Satoshi Kitai; Emi Ishikawa; Norihisa Yada; Tatsuo Inoue; Satoru Hagiwara; Yasunori Minami; Hobyung Chung
    ONCOLOGY 78 148 - 153 2010年 
    Background: Although hepatic arterial infusion chemotherapy (HAIC) using low-dose 5-fluorouracil (5-FU) and cisplatin (low-dose FP) is commonly used for advanced hepatocellular carcinoma (HCC) with vascular invasion in Japan, few reports have investigated the efficacy and safety of this approach. We investigated the efficacy and toxicity of HAIC using low-dose FP for patients with advanced HCC as a phase II trial. Methods: Low-dose FP consisted of a continuous arterial infusion of 5-FU (250-500 mg/day, 5 days/week, for the first 2 weeks) and cisplatin (10 mg/day, 5 days/week, for the first 2 weeks). Then, 5-FU (1,000 mg/body for 5 h) and cisplatin (10 mg/body) were administered once weekly. Results: In these patients treated with low-dose FP, the response rate was 38.5%, the median time to progression was 4.1 months (95% CI 2.1-6.1 months) and the median survival time was 15.9 months (95% CI 9.8-22.0 months). The most frequent adverse events were myelosuppression such as neutropenia or thrombocytopenia. Conclusions: HAIC using low-dose FP is an effective treatment option for locally advanced HCC. However, it is not well tolerated hematologically because of potent pancytopenia and poor hepatic reserve. Therefore, this regimen should be performed carefully with regular monitoring of hematological function. Copyright (C) 2010 S. Karger AG, Basel
  • Tatsuo Inoue; Yasunori Minami; Hobyung Chung; Sousuke Hayaishi; Taisuke Ueda; Chie Tatsumi; Masahiro Takita; Satoshi Kitai; Kinuyo Hatanaka; Emi Ishikawa; Norihisa Yada; Satoru Hagiwara; Kazuomi Ueshima; Masatoshi Kudo
    ONCOLOGY 78 94 - 101 2010年 
    Purpose: To confirm the safety and effectiveness of techniques to assist radiofrequency ablation (RFA) for difficult cases, we retrospectively evaluated successful treatment rates, early complications and local tumor progressions. Patients and Methods: Between June 1999 and April 2009, a total of 341 patients with 535 nodules were treated as difficult cases. Artificial pleural effusion assisted ablation was performed on 64 patients with 82 nodules. Artificial ascites-assisted ablation was performed on 11 patients with 13 nodules. Cooling by endoscopic nasobiliary drainage (ENBD) tube-assisted ablation was performed on 6 patients with 8 nodules. When the tumors were not well visualized with conventional B-mode ultrasonography (US), contrast-enhanced US-assisted ablation with Levovist (R) or Sonazoid (R) or virtual CT sonography-assisted ablation was performed. Contrast-enhanced US-assisted ablation was performed on 139 patients with 224 nodules and virtual CT sonography-assisted ablation was performed on 121 patients with 209 nodules. Results: In total, complete ablation was achieved in 514 of 535 (96%) nodules in difficult cases. For RFA with artificial pleural effusion, artificial ascites and ENBD, complete response was confirmed in all cases. For contrast-enhanced US-and CT sonography-assisted ablation, complete response was 95%. Early complications were recognized in 24 cases (4.5%). All cases recovered with no invasive treatment. Local tumor recurrence was investigated in 377 nodules of 245 patients, and 69 (18%) nodules were positive. Tumor recurrences in each assisted technique were 14.7% in artificial pleural effusion cases, 7% in artificial ascites, 12.5% in ENBD tube cases, 31% in virtual CT sonography, and 8.5% in contrast-enhanced US. Conclusion: Although local tumor progression needs to be carefully monitored, assisted techniques of RFA for difficult cases are well tolerated and expand the indications of RFA. Copyright (C) 2010 S. Karger AG, Basel
  • 畑中 絹世; 鄭 浩柄; 工藤 正俊; 土師 誠二; 南 康範; 前川 清; 早石 宗右; 永井 知行; 田北 雅弘; 工藤 可苗; 上田 泰輔; 辰巳 千栄; 北井 聡; 石川 恵美; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣
    Oncology 78 53 - 59 2010年 [査読有り]
  • 矢田 典久; 工藤 正俊; 鄭 浩柄; 早石 宗右; 田北 雅弘; 上田 泰輔; 辰巳 千栄; 畑中 絹世; 北井 聡; 石川 恵美; 井上 達夫; 萩原 智; 上嶋 一臣
    Intervirology 53 1 60 - 65 2010年 [査読有り]
     
    Objectives: We investigated the significance of serum ferritin levels in pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy for chronic hepatitis C (CHC) and examined its correlation with serum alanine aminotransferase (ALT) levels during therapy and response to the therapy. Methods: A total of 175 patients with CHC received the combination therapy. Correlations between serum ferritin levels and serum ALT levels at 12 and 24 weeks of therapy were examined. Differences in serum ferritin levels during therapy between patients with sustained viral response (SVR) and non-SVR were also examined. Results: Only 24 (13.7%) and 20 (11.4%) patients showed elevated serum ALT levels (6 70 IU/l) at 12 and 24 weeks of therapy, respectively. There was no correlation between serum ferritin levels and ALT levels. Ninety-five (54.3%) of 175 patients achieved SVR. Serum ferritin levels increased dramatically in both SVR and non-SVR groups after starting the therapy and were significantly higher in the SVR group throughout the therapy. Conclusions: Serum ferritin level increases during PEG-IFN and RBV combination therapy; however, it did not correlate with either serum ALT level or the total dose of RBV. Higher serum ferritin levels during combination therapy appear to be associated with favorable therapeutic response. Copyright (C) 2010 S. Karger AG, Basel
  • Taisuke Ueda; Hobyung Chung; Masatoshi Kudo; Emi Ishikawa; Sousuke Hayaishi; Chie Tatsumi; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima
    INTERVIROLOGY 53 1 55 - 59 2010年 [査読有り]
     
    Objective: The extension of treatment duration has been proposed in late virological responders with hepatitis C virus (HCV) genotype 1 and high viral load. However, the effectiveness of extended treatment in patients whose serum HCV RNA become undetectable later than 24 weeks of treatment (ultra-late virological responder; ULVR) has not yet been determined. Methods: A total of 130 patients infected with HCV genotype 1 and who had high viral load were treated with pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy. We retrospectively analyzed 10 ULVR who received extended combination treatment beyond 48 weeks. Results: The duration of the combination treatment for ULVR ranged between 59 and 119 weeks, and the mean duration was 80 weeks. Although the majority of ULVR were older female patients (>= 60 years) with factors related to poor therapeutic response, 8 patients (80%) achieved sustained virological response (SVR). The SVR rate correlated well with the duration of the treatment. Five ULVR achieved SVR when treatment was continued until serum HCV RNA remained undetectable for longer than 48 weeks. Conclusion: The extended duration of PEG-IFN and RBV combination treatment is a possible strategy to improve treatment response in HCV genotype 1 infection, even for ULVR. Copyright (C) 2010 S. Karger AG, Basel
  • Chie Tatsumi; Masatoshi Kudo; Kazuomi Ueshima; Satoshi Kitai; Emi Ishikawa; Norihisa Yada; Satoru Hagiwara; Tatsuo Inoue; Yasunori Minami; Hobyung Chung; Kiyoshi Maekawa; Kenji Fujimoto; Michio Kato; Akiko Tonomura; Tsuyoshi Mitake; Tsuyoshi Shiina
    INTERVIROLOGY 53 1 76 - 81 2010年 [査読有り]
     
    Objective: The aim of this study was to investigate liver fibrosis using non-invasive Real-time Tissue Elastography(R) (RTE) and transient elastography (FibroScan(R)) methods. Methods: RTE, FibroScan and percutaneous liver biopsy were all performed on patients with chronic liver disease, particularly hepatitis C, to investigate liver fibrosis. Results: FibroScan and RTE were compared for fibrous liver staging (F stage), which was pathologically classified using liver biopsy. In FibroScan, significant differences were observed between F1/F3 and F2/F4, but no such differences were observed between F1/F2, F2/F3 and F3/F4. In RTE, significant differences were observed between F1/F2, F2/F3 and F2/F4. But for F3/F4, no significant differences were observed. Conclusion: FibroScan and RTE correlated well with F staging of the liver. In particular RTE was more successful than FibroScan in diagnosing the degree of liver fibrosis. Copyright (C) 2010 S. Karger AG, Basel
  • Taisuke Ueda; Hobyung Chung; Masatoshi Kudo; Emi Ishikawa; Sousuke Hayaishi; Chie Tatsumi; Tatsuo Inoue; Norihisa Yada; Satoru Hagiwara; Yasunori Minami; Kazuomi Ueshima
    INTERVIROLOGY 53 1 55 - 59 2010年 
    Objective: The extension of treatment duration has been proposed in late virological responders with hepatitis C virus (HCV) genotype 1 and high viral load. However, the effectiveness of extended treatment in patients whose serum HCV RNA become undetectable later than 24 weeks of treatment (ultra-late virological responder; ULVR) has not yet been determined. Methods: A total of 130 patients infected with HCV genotype 1 and who had high viral load were treated with pegylated interferon (PEG-IFN) and ribavirin (RBV) combination therapy. We retrospectively analyzed 10 ULVR who received extended combination treatment beyond 48 weeks. Results: The duration of the combination treatment for ULVR ranged between 59 and 119 weeks, and the mean duration was 80 weeks. Although the majority of ULVR were older female patients (>= 60 years) with factors related to poor therapeutic response, 8 patients (80%) achieved sustained virological response (SVR). The SVR rate correlated well with the duration of the treatment. Five ULVR achieved SVR when treatment was continued until serum HCV RNA remained undetectable for longer than 48 weeks. Conclusion: The extended duration of PEG-IFN and RBV combination treatment is a possible strategy to improve treatment response in HCV genotype 1 infection, even for ULVR. Copyright (C) 2010 S. Karger AG, Basel
  • Kinuyo Hatanaka; Hobyung Chung; Masatoshi Kudo; Seiji Haji; Yasunori Minami; Kiyoshi Maekawa; Sousuke Hayaishi; Tomoyuki Nagai; Masahiro Takita; Kanae Kudo; Taisuke Ueda; Chie Tatsumi; Satoshi Kitai; Emi Ishikawa; Norihisa Yada; Tatsuo Inoue; Satoru Hagiwara; Kazuomi Ueshima
    ONCOLOGY 78 53 - 59 2010年 [査読有り]
     
    Objective: The purpose of this study was to assess the usefulness of post-vascular phase (PVP) images of contrast-enhanced ultrasonography (CE-US) in the evaluation of the gross types of hepatocellular carcinoma (HCC) that is closely related to the malignant potential of the tumor. Methods: A total of 29 patients with 40 HCCs of <5 cm in diameter, who underwent hepatic resection, were enrolled. The gross type of the tumor was evaluated using real-time scanning during the PVP of CE-US with Sonazoid prior to surgery. The tumors were classified into three types based on the macroscopic classification of the Liver Cancer Study Group of Japan: single nodular (SN) type, single nodular with extranodular growth (SNEG) type, and confluent multinodular (CMN) type. The ability of CE-US to correctly depict the gross type of HCC was evaluated. Results: 26 tumors were macroscopically diagnosed as the SN type, 11 tumors as the SNEG type, and 3 tumors as the CMN type. The sensitivity, specificity and accuracy of CE-US were 96, 80 and 90%, respectively. Conclusion: The PVP image of CE-US with Sonazoid is a useful tool in the evaluation of the gross type of HCC and is considered essential in deciding treatment strategy. Copyright (C) 2010 S. Karger AG, Basel
  • 特異な経過をたどったアルコール性肝硬変に合併した肝細胞癌の一例
    早石 宗右; 鄭 浩柄; 辰巳 千栄; 永井 知行; 上田 泰輔; 高橋 俊介; 北井 聡; 石川 恵美; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    肝臓 50 Suppl.1 A292 - A292 (一社)日本肝臓学会 2009年04月
  • Gd-EOB MRIによる肝細胞癌の診断能 造影超音波検査、Dynamic CTとの比較検討
    井上 達夫; 畑中 絹世; 早石 宗右; 永井 知行; 田北 雅弘; 上田 泰輔; 高橋 俊介; 北井 聡; 石川 恵美; 矢田 典久; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    肝臓 50 Suppl.1 A368 - A368 (一社)日本肝臓学会 2009年04月
  • ウイルス性慢性肝炎.
    萩原 智; 工藤 正俊
    近畿大学医学雑誌 33 335 - 341 2009年 [査読有り]
  • 矢田 典久; 工藤 正俊; 鄭 浩柄; 早石 宗右; 田北 雅弘; 上田 泰輔; 辰巳 千栄; 畑中 絹世; 北井 聡; 石川 恵美; 井上 達夫; 萩原 智; 上嶋 一臣
    Intervirology 53 60 - 65 2009年
  • Kazuomi Ueshima; Masatoshi Kudo; Tomoyuki Nagai; Chie Tatsumi; Taisuke Ueda; Shunsuke Takahashi; Kinuyo Hatanaka; Satoshi Kitai; Emi Ishikawa; Tatsuo Inoue; Satoru Hagiwara; Yasunori Minami; Hobyung Chung
    Oncology 75 1 106 - 113 2008年12月 [査読有り]
     
    Purpose: There are currently no effective treatments for patients with advanced hepatocellular carcinoma (HCC) with vascular invasion or extrahepatic metastases. We evaluated the efficacy and safety of combination therapy with S-1 and pegylated interferon (PEG-IFN)-α for advanced HCC. Methods: A total of 22 patients received combination therapy with S-1 and PEG-IFN. One cycle of the combination therapy consists of oral S-1 (80 mg/m2) administration and subcutaneous PEG-IFN injection (PEG-IFN-α-2a 90 μg weekly or PEG-IFN-α-2b 50 μg weekly) for 4 weeks with 1- to 2-week intervals. Results: One patient was evaluated as complete response, 6 as partial response, 8 as stable disease, and 6 as progressive disease. One patient was not evaluable because therapy had to be discontinued as a result of jaundice. The median survival time was 15.3 months (95% CI: 4.4-26.2 months). The 1- and 2-year survival rates were 54.9 and 36.6%, respectively. The overall response rate was 31.8% and the disease control rate was 68.2%. Grade 3 neutropenia (18.2%), leukopenia (9.1%), anemia (9.1%), and thrombocytopenia (18.2%) were observed. Grade 4 toxicities were not observed. Conclusion: Combination therapy with S-1 and PEG-IFN is effective and feasible, and is therefore a promising regimen for advanced HCC. Copyright © 2008 S. Karger AG.
  • Yu Xia; Masatoshi Kudo; Yasunori Minami; Kinuyo Hatanaka; Kazuomi Ueshima; Hobyung Chung; Satoru Hagiwara; Tatsuo Inoue; Emi Ishikawa; Satoshi Kitai; Shunsuke Takahashi; Chie Tatsumi; Taisuke Ueda; Sosuke Hayaishi; Kiyoshi Maekawa
    Oncology 75 1 99 - 105 2008年12月 [査読有り]
     
    Background: The purpose of this study was to investigate if Sonazoid-enhanced harmonic ultrasonography (US) could be used to evaluate the responses of hepatocellular carcinomas (HCCs) to treatment with transcatheter arterial chemoembolization (TACE). Patients and Methods: Forty-three HCCs that had been treated by TACE were evaluated by Sonazoid-enhanced harmonic US and dynamic computed tomography (CT) approximately 1 week after their treatment. The detection rates of residual tumor blood supply using the two modalities were compared. Two months after chemoembolization, 16 of the 43 HCCs, which had no additional local treatment, were followed up with dynamic CT. The results of contrast-enhanced harmonic US and dynamic CT 1 week after chemoembolization were analyzed and compared with follow-up dynamic CT results. Results: The detection rates of positive enhancement with Sonazoid-enhanced harmonic US and dynamic CT 1 week after TACE were 25 (58.1%) of 43 lesions and 17 (39.5%) of 43 lesions, respectively. Sonazoid-enhanced harmonic US was significantly more sensitive than dynamic CT in depicting the residual tumor blood supply to HCCs 1 week after TACE (p < 0.01 χ2 test). The Sonazoid-enhanced harmonic US results of the 16 lesions 1 week after chemoembolization were consistent with the follow-up results of dynamic CT 2 months after chemoembolization. Conclusions: Sonazoid-enhanced harmonic US appears to be a highly sensitive and accurate modality for evaluating responses of HCCs shortly after TACE. Copyright © 2008 S. Karger AG.
  • Tatsuo Inoue; Masatoshi Kudo; Kinuyo Hatanaka; Syunsuke Takahashi; Satoshi Kitai; Taisuke Ueda; Emi Ishikawa; Satoru Hagiwara; Yasunori Minami; Hobyung Chung; Kazuomi Ueshima; Kiyoshi Maekawa
    Oncology 75 1 48 - 54 2008年12月 [査読有り]
     
    Purpose: To evaluate the usefulness of vascular phase images of contrast-enhanced ultrasonography (CE-US) with Sonazoid for hepatocellular carcinomas (HCCs), a retrospective, comparative study was conducted of images of HCCs obtained by CE-US and superparamagnetic iron oxide (SPIO) magnetic resonance imaging (MRI) and evaluated qualitatively and quantitatively. Methods: Seventy-seven patients with 88 HCCs who received CE-US and SPIO-MRI were reviewed. The ratio of the echogenicity of the tumor and nontumor areas was calculated with postvascular phase CE-US (postvascular phase ratio). The ratio of the intensity of the nontumor to tumor areas on SPIO-enhanced MRI (SPIO intensity index) was also calculated. The Pearson correlations were calculated for all values between the postvascular phase ratio and SPIO intensity index for quantitative comparison. These images were also compared qualitatively for the detection rate of the tumors. Results: The sensitivities of CE-US and SPIO-MRI in detecting tumors were 98 and 95%, respectively (nonsignificant, χ2 test). The postvascular phase ratio correlated with the SPIO intensity index for HCCs (Pearson r = 0.803, p < 0.05). The image conformity of the result from the liver parenchymal phase CE-US and SPIO-MRI was 92%. Dedifferentiation spots of nodule-in-nodule HCCs were detected in 4 (80%) of 5 on postvascular phase images of CE-US, and in 2 (40%) of 5 on SPIO-MRI (nonsignificant, χ2 test). Conclusions: Postvascular phase images of CE-US with Sonazoid appear promising as an alternative to SPIO-enhanced MRI. Further study cases are needed to confirm the usefulness of postvascular phase images of CE-US compared to SPIO-MRI for the detection of dedifferentiation foci in hepatic tumors. Copyright © 2008 S. Karger AG.
  • ソナゾイド造影超音波検査におけるpostvascular phase imagingとSPIO-MRIとの比較検討
    井上 達夫; 畑中 絹世; 上田 泰輔; 辰巳 千栄; 北井 聡; 高橋 俊介; 石川 恵美; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣; 工藤 正俊; 横川 美加; 前野 知子; 市島 真由美; 前川 清
    肝臓 49 Suppl.2 A575 - A575 (一社)日本肝臓学会 2008年09月
  • 進行肝細胞癌に対するS-1・ペグインターフェロン併用療法
    上嶋 一臣; 早石 宗右; 辰巳 千栄; 上田 泰輔; 北井 聡; 高橋 俊介; 石川 恵美; 井上 達夫; 萩原 智; 南 康範; 鄭 浩柄; 工藤 正俊
    日本消化器病学会雑誌 105 臨増大会 A841 - A841 (一財)日本消化器病学会 2008年09月
  • Defect Re-injection imagingの有用性について
    畑中 絹世; 南 康範; 北井 聡; 辰巳 千栄; 高橋 俊介; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    超音波医学 35 Suppl. S626 - S626 (公社)日本超音波医学会 2008年04月
  • 肝画像診断の進歩 肝線維化評価における非侵襲的測定法(Real-time tissue elastography)の有用性に関する検討
    辰巳 千栄; 上嶋 一臣; 今井 元; 上田 泰輔; 川崎 正憲; 北井 聡; 萩原 智; 井上 達夫; 石川 恵美; 南 康範; 鄭 浩柄; 工藤 正俊
    肝臓 49 Suppl.1 A55 - A55 (一社)日本肝臓学会 2008年04月
  • 進行肝細胞癌に対するS-1、ペグインターフェロン併用療法
    上嶋 一臣; 早石 宗右; 辰巳 千栄; 上田 泰輔; 北井 聡; 高橋 俊介; 石川 恵美; 井上 達夫; 萩原 智; 南 康範; 鄭 浩柄; 工藤 正俊
    肝臓 49 Suppl.1 A278 - A278 (一社)日本肝臓学会 2008年04月
  • Defect Re-injection Testの有用性について
    畑中 絹世; 北井 聡; 上田 泰輔; 辰巳 千恵; 井上 達夫; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣; 前川 清; 工藤 正俊
    日本消化器病学会雑誌 105 臨増総会 A218 - A218 (一財)日本消化器病学会 2008年03月
  • Hobyung Chung; Masatoshi Kudo; Shunsuke Takahashi; Satoru Hagiwara; Yasuhiro Sakaguchi; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima; Toyokazu Fukunaga; Takashi Matsunaga
    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 23 3 445 - 452 2008年03月 [査読有り]
     
    Background and Aim: Although various staging systems for hepatocellular carcinoma (HCC) have been developed in recent years, there is no worldwide consensus which staging system is best. The aim of the present study was to compare the performance of the currently developed three staging systems: the Japan integrated staging (JIS) score, new Barcelona Clinic Liver Cancer (BCLC) staging classification, and the Tokyo score. Methods: A total of 290 consecutive patients with HCC before initial treatment at Kinki University between January 1999 and December 2001 were included. The patients were stratified according to the three staging systems, and the performance of the staging systems was compared using survival time as the only outcome measure. Results: There were significant differences between all stages in the JIS score, while no significant difference was found between stages C and D in the BCLC staging classification and between all the scores, except between scores 0 and 1 and 2 and 3 in the Tokyo score. For all patients (n = 290), the radical treatment group (n = 208) and the non-radical treatment group (n = 82), the likelihood ratio chi(2)-test showed the highest value, and the Akaike information criterion value was lowest in the JIS score. Conclusion: The JIS score provided the best prognostic stratification in a Japanese cohort of HCC patients who were mainly diagnosed at early stages and treated with radical therapies.
  • Satoshi Kitai; Masatoshi Kudo; Yasunori Minami; Kazuomi Ueshima; Hobyung Chung; Satoru Hagiwara; Tatsuo Inoue; Emi Ishikawa; Shunsuke Takahashi; Yutaka Asakuma; Seiji Haji; Yukio Osaki; Hiroko Oka; Toshihito Seki; Hiroshi Kasugai; Yo Sasaki; Takashi Matsunaga
    INTERVIROLOGY 51 86 - 94 2008年 
    Objectives: The Japan Integrated Staging (JIS) score has been reported to have good stratification ability in patients with hepatocellular carcinoma (HCC). However, the JIS score could not estimate malignant grade of HCC. The aim of this study was to evaluate the performance of a new staging system: the biomarker combined JIS (bm-JIS) which includes three tumor markers: alpha-fetoprotein (AFP), Lens culinaris agglutininreactive AFP and des-gamma-carboxy prothrombin with the conventional JIS score. Methods: A total of 1,924 HCC patients were included in this study. We compared their overall survival, the stratification ability and suitability as a prognostic model according to the bm-JIS score and the conventional JIS score. Results: There were significant differences between the survival curves for all bm-JIS scores. For the conventional JIS scores of 0, 1, 2 and 3, the survival curves differed greatly according to the bm-JIS score ( p < 0.0001). The independent homogenizing ability and the stratification value of the JIS score and the bm-JIS score determined by the likelihood ratio test using the Cox proportional hazard regression model showed the bm- JIS score to have a higher value (chi(2) = 717.348) than the JIS score (chi(2) = 668.91). Conclusions: The bm- JIS score showed superior stratification ability and thus was found to be a better predictor of the prognosis than the conventional JIS score, especially for the patients with good prognosis. Copyright (c) 2008 S. Karger AG, Basel.
  • Kinuyo Hatanaka; Masatoshi Kudo; Yasunori Minami; Taisuke Ueda; Chie Tatsumi; Satoshi Kitai; Shunsuke Takahashi; Tatsuo Inoue; Satoru Hagiwara; Hobyung Chung; Kazuomi Ueshima; Kiyoshi Maekawa
    INTERVIROLOGY 51 61 - 69 2008年 
    Objective: To clarify the value of contrast-enhanced harmonic ultrasonography ( US) with Sonazoid, a second-generation US contrast agent, in the differential diagnosis of liver tumors compared to dynamic CT. Methods: A total of 249 hepatic nodules in 214 patients were studied; these included 177 hepatocellular carcinomas ( HCCs), 42 liver metastases, 20 liver hemangiomas, 6 dysplastic nodules and 4 focal nodular hyperplasias ( FNHs). After the injection of Sonazoid, nodules were scanned using real-time contrast-enhanced harmonic US in the vascular phases, i. e. the early and late vascular phases, and the Kupffer phase. Results: Six enhancement patterns were identified to be significant for the differential diagnosis of hepatic tumors. In HCCs, the presence of intratumoral vessels supplied from the periphery and fast washout ( sensitivity, 96.6%; specificity, 94.4%) were the most typical characteristics. In metastases, the presence of rim- like enhancement with peripheral tumor vessels ( sensitivity, 88.1%; specificity, 100%) was the typical pattern. In hemangiomas, the presence of intratumoral hypoperfusion images with globular or cotton wool-like pooling, which continue to the late vascular phase ( sensitivity, 90.0%; specificity, 99.6%), was typical. In dysplastic nodules, the presence of portal enhancement without arterial supply in the early vascular phase and the presence of intratumoral uptake in the Kupffer phase ( sensitivity, 83.3%; specificity, 100%) were the most typical patterns. In FNHs, the presence of a spoke-wheel pattern in the early vascular phase with dense staining in the late vascular phase, and positive uptake within the nodule in the Kupffer phase ( sensitivity, 100%; specificity, 100%) were the most typical patterns. Conclusion: Contrast-enhanced harmonic US with Sonazoid allowed intimate vascular and Kupffer imaging and, therefore, is useful for the differential diagnosis of hepatic tumors. Copyright (c) 2008 S. Karger AG, Basel.
  • S. Hagiwara; M. Kudo; T. Nakatani; Y. Sakaguchi; M. Nagashima; N. Fukuta; M. Kimura; S. Hayakawa; H. Munakata
    BRITISH JOURNAL OF CANCER 97 11 1532 - 1537 2007年11月 
    When the tumour suppressor p53 is activated by DNA damage, it stimulates the transcription of its target genes, which then induce cell cycle arrest or apoptosis. Here, we examined the role p53 plays in the antitumour effect of combination treatment with pegylated interferon (PEG-IFN)-alpha and 5-fluorouracil (5-FU), which has been shown to effectively treat advanced hepatocellular carcinoma (HCC). Nude mice were injected subcutaneously with cultured HepG2 cells, in which p53 is functional. They were treated a week later with PEG-IFN and/or 5-FU for 7 weeks, after which we measured and examined their tumours. Combination groups showed significantly lower tumour volumes and higher tumour cell apoptosis than the other groups. Combination treatment and PEG-IFN monotherapy also significantly elevated the p53 protein and mRNA levels in the tumour but only combination treatment increased the degree of p53 phosphorylation at serine46 and induced p53-regulated apoptosis-inducing protein I (p53AIPI) expression. The antitumour effects of combination treatment is due in part to the elevation by PEG-IFN of p53 protein and mRNA expression and in part to the DNA damage that is generated by 5-FU, which induces p53 serine46 phosphorylation, which in turn upregulates p53AIPI expression.
  • Minoru Suzuki; Yoshinori Sakurai; Satoru Hagiwara; Shinichiro Masunaga; Yuko Kinashi; Kenji Nagata; Akira Maruhashi; Masatoshi Kudo; Koji Ono
    JAPANESE JOURNAL OF CLINICAL ONCOLOGY 37 5 376 - 381 2007年05月 [査読有り]
     
    A 60-year-old man with multiple hepatocellular carcinomas (HCCs) was enrolled as the first patient in a pilot study for treating multiple liver tumors with boron neutron capture therapy (BNCT). Because of compromised liver function, the multiple tumors in the right liver lobe were treated with BNCT and those in the left lobe with hepatic arterial chemoembolization. The feasibility and clinical outcome of this first case was assessed. During the treatment and follow-up period, no adverse effect as a result of BNCT was observed except for temporary temperature elevation to 38.3 degrees C, and the AST and ALT being higher than 200 IU/I. For 1 month, the tumors treated with BNCT remained stable in size. The BNCT-treated tumors showed regrowth 3.5 months after BNCT and the patient died of liver dysfunction caused by progression of HCC 10 months after BNCT. The feasibility of BNCT for HCC is confirmed in this first case.
  • Masatoshi Kudo; Yasuhiro Sakaguchi; Hobyung Chung; Kinuyo Hatanaka; Satoru Hagiwara; Emi Ishikawa; Shunsuke Takahashi; Satoshi Kitai; Tatsuo Inoue; Yasunori Minami; Kazuomi Ueshima
    ONCOLOGY 72 132 - 138 2007年 
    Objective: To assess whether low-dose, long-term maintenance interferon (IFN) therapy inhibits recurrence after complete ablation of hepatocellular carcinoma (HCC) and improves patient survival. Methods and Patients: From June 1999 through May 2006, a total of 127 HCC cases that met the requirements of both tumor diameter 3 cm or less, and number of tumors three or fewer, were curatively treated by radiofrequency ablation therapy (RFA). Among them, 43 patients received three million IU of IFN-alpha 2b twice per week or pegylated IFN-alpha 2a 90 mu g once per week or once per 2 weeks without discontinuation (IFN maintenance group). The remaining 84 patients, whose sex, age, and platelet counts were randomly matched to those of the IFN maintenance group, did not receive IFN treatment (control group). Results: Cumulative first, second, and third recurrence rates were significantly reduced in the IFN maintenance group compared with the control group by Kaplan-Meier estimate. The 5-year survival rate was 66% for the control group and 83% for the IFN maintenance group (p = 0.004). Multivariate analysis using the Cox proportional hazards model identified IFN maintenance therapy as an independent risk factor for survival, and the risk ratio was 0.21 (95% CI: 0.05-0.73). In conclusion, low-dose, long-term maintenance IFN therapy after curative RFA therapy of HCC significantly inhibits recurrence, and consequently improves patient survival.
  • 南 康範; 工藤 正俊; 鄭 浩柄; 井上 達夫; 高橋 俊介; 畑中 絹世; 上田 泰輔; 萩原 智; 北井 聡; 上嶋 一臣; 福永 豊和; 塩﨑 均
    Oncology 72 111 - 116 2007年
  • Review of current staging systems for hepatocellular carcinoma
    Chung H; Kudo M; Takahashi S; Hagiwara S; Sakaguchi Y; Inoue T; Minami Y; Ueshima K; Fukunaga T
    Hepatol Res 37 210 - 215 2007年 [査読有り][招待有り]
  • Kinuyo Hatanaka; Masatoshi Kudo; Toyokazu Fukunaga; Kazuomi Ueshima; Hobyung Chung; Yasunori Minami; Yasuhiro Sakaguchi; Satoshi Hagiwara; Akio Orino; Yukio Osaki
    INTERVIROLOGY 50 1 24 - 31 2007年 [査読有り]
     
    Objective: To clarify the frequency and trends of both HBsAg and HCVAb negative hepatocellular carcinoma (NonBNonC-HCC) in all HCC, to clarify the etiology of NonBNonC-HCC, and to elucidate the clinical characteristics of NonBNonC-HCC compared with those of HBsAg-positive HCC (B-HCC) and HCVAb-positive HCC (C-HCC). Methods: A total of 2,542 patients with HCC examined at three institutions between 1991 and 2004 were categorized based on their serum viral antigen/antibody positivities, and compared between groups for the etiology, annual trend of the incidence, and clinical characteristics. Results: For the etiology, C-HCC was most prevalent, followed by B-HCC, NonBNonC-HCC, and both HBsAg and HCVAb-positive HCC (BC-HCC) in order. For survival, C-HCC had the most favorable prognosis, followed by NonBNonC-HCC, and B-HCC patients had the poorest prognosis in the three groups (C-HCC, B-HCC, and NonBNonC-HCC). In tumor-node metastasis (TNM) stages I+II, however, NonBNonC-HCC patients took the most favorable clinical course. The incidence of NonB-NonC-HCC in all HCC was 5 - 8% from 1991 to 1998, and has increased to 10 - 12% since 1999. Additionally, the incidence of HBcAb-positive HCC in NonBNonC-HCC declined each year. Among NonBNonC-HCC patients, the morbidity of diabetic complications was significantly higher in HBcAb-negative patients than in HBcAb-positive patients. Conclusion: Although the incidence of NonBNonC-HCC among all HCC has an increasing trend recently, the incidence of HBcAb-positive HCC in NonBNonC-HCC has a tendency of decreasing. This fact suggest its etiology might be changing from occult HBV related HCC to unknown etiology such as nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH) related HCC. The prognosis of NonBNonC-HCC was fairly good if the HCC was found in its early stage.
  • Satoru Hagiwara; Masatoshi Kudo; Toshihiko Kawasaki; Miki Nagashima; Yasunori Minami; Hobyung Chung; Toyokazu Fukunaga; Masayuki Kitano; Tatsuya Nakatani
    JOURNAL OF GASTROENTEROLOGY 41 12 1214 - 1219 2006年12月 [査読有り]
     
    Background. Factors involved in portal venous invasion (PVI) must be clarified to enable better determination of therapeutic strategies and outcomes in patients with hepatocellular carcinoma (HCC). Methods. Of 365 patients with HCC who consulted our department between January 1999 and January 2003, 53 with PVI at the initial consultation were excluded, and the other 312 without PVI were included in this study. Of these patients, we compared liver function, tumor markers, and initial treatment between 287 patients without PVI during follow-up (until December 2004) and 25 patients who developed PVI, and investigated prognostic factors. Results. Multivariate analysis using a COX regression model showed that a Lens culinaris A-reactive fraction of alpha-fetoprotein (AFP-L3) rate of 15% or more, a des-gamma-carboxy prothrombin (DCP) level of 100 mAU/ml or more, multiple tumors, and a platelet count of 130 000/mm(3)p or more were correlated with PVI. Conclusions. HCC frequently infiltrated the portal vein in patients with a high rate of AFP-L3, a high level of DCP, or multiple tumors. Furthermore, the incidence of PVI was significantly higher in patients with a platelet count of 130000/mm(3) or more.
  • Miki Nagashima; Masatoshi Kudo; Hobyung Chung; Emi Ishikawa; Satoru Hagiwara; Tatsuya Nakatani; Kensaku Dote
    HEPATOLOGY RESEARCH 36 4 288 - 293 2006年12月 [査読有り]
     
    Background/Aims: Elevated serum ferritin and hepatic iron concentrations are frequently observed in chronic hepatitis C (CHC), which may be related to hepcidin. Because the role of hepcidin in CHC patients remains unknown, we aimed in this study to generate some information about hepcidin in CHC. Methods: To determine whether serum hepcidin correlates with markers of iron status in patients with viral hepatitis, we measured serum prohepcidin levels in patients with hepatitis C virus (HCV) and hepatitis B virus (HBV) infection and in healthy controls. Results: Serum prohepcidin and ferritin levels were negatively correlated (r = -0.182, P = 0.037) in HCV patients and positively correlated in HBV patients and in healthy controls. The total iron scores in liver specimens from HCV patients were also negatively correlated ( r = -0.403, P = 0.013). Serum prohepcidin levels in patients with liver cirrhosis (LC) were significantly lower than in patients with chronic hepatitis (CH). In both CH and LC patients, serum prohepcidin levels were significantly lower in HCV patients than in HBV patients. Conclusion: Failure of homeostatic regulation of serum prohepcidin concentrations may be induced by HCV infection, resulting in elevation of serum ferritin levels, which leads to the progression of liver injury by iron overload in CHC patients. (c) 2006 Elsevier Ireland Ltd. All rights reserved.
  • 肝癌の経皮的ラジオ波焼灼術におけるReal-time Virtual Sonographyの有用性について
    南 康範; 工藤 正俊; 鄭 浩柄; 福永 豊和; 上嶋 一臣; 萩原 智; 坂口 康浩; 高橋 俊介; 畑中 絹代; 井上 達夫
    日本消化器病学会雑誌 103 臨増総会 A144 - A144 (一財)日本消化器病学会 2006年03月
  • S Hagiwara; M Kudo; Y Minami; HY Chung; T Nakatani; T Fukunaga; Y Osaki; Y Yamashita; K Kajimura
    INTERVIROLOGY 49 4 200 - 206 2006年 [査読有り]
     
    It has been shown that clinical and virological characteristics vary among hepatitis B virus (HBV) genotypes. In this study, we measured the virus level, disease severity, and presence or absence of core promoter (CP)/pre-core (PC) mutations in 241 HBV carriers, and investigated the clinical significance of measuring the HBV genotype. In genotype C HBV carriers, the proportion of hepatitis B e antigen (HBeAg)-positive patients was significantly higher than that in genotype B HBV carriers (0 vs. 34.4%, p < 0.05), and the virus level was higher (4.9 vs. 4.05 LGE/ ml). In the genotype B HBV carriers, the incidence of PC mutation was significantly higher (69 vs. 34%, p < 0.05). In the genotype C HBV carriers, the incidence of CP mutation was significantly higher (13 vs. 78%, p < 0.05). We compared patients with the wild (W)/mutant (M) pattern in the CP/PC regions to those with the M/W pattern in the CP/PC regions among the genotype C HBV carriers. Both the proportion of HBeAg-positive patients (65.8 vs. 15.4%, p < 0.05) and the alanine aminotransferase (ALT) level (48 vs. 21.5 IU, p < 0.05) were higher in the patients with the M/W pattern in the CP/PC regions, and the disease severity was deteriorated. In conclusion, genotype B HBV may more frequently induce HBe seroconversion via PC mutation compared to genotype C HBV. Among the genotype C HBV carriers, hepatitis activity and the deterioration of the disease severity were significantly inhibited in the group in which PC mutation initially occurred, in comparison to the group in which CP mutation initially occurred.
  • 南 康範; 鄭 浩柄; 畑中 絹代; 井上 達夫; 坂口 康浩; 萩原 智; 上嶋 一臣; 福永 豊和; 工藤 正俊; 土師 誠二; 中居 卓也; 大柳 治正
    胆と膵 26 3 279 - 283 医学図書出版(株) 2005年03月 
    ラジオ波焼灼術(RFA)は高い局所制御能から肝細胞癌の局所治療として用いられており,外科治療と共に根治性の高い治療法として位置づけられている.しかし,全ての肝細胞癌がRFAで治療可能である訳ではない.肝細胞癌治療には外科切除,RFA,経カテーテル的治療など複数の選択肢があり,治療法選択には病期や肝予備能に基づいて内科・外科・放射線科など各科を横断したトータル・マネージメントが必要である.基本的に内科より外科治療が考慮される症例として, 1)外科治療の根治性がより高い場合, 2)経皮的RFAが困難な場合, 3)合併症が危惧される場合が挙げられるが,臨床の場で大切なことは内科と外科との意見交換からコンセンサスを築くことである(著者抄録)
  • 肝細胞癌脈管浸潤の診断. 特集「肝切除における血管合併切除とその成績」
    萩原 智; 工藤正俊
    外科 66 621 - 626 2004年 [査読有り]
  • 画像診断の新しい展開 1）超音波
    南 康範; 鄭 浩柄; 井上達夫; 坂口康浩; 萩原 智; 福永豊和; 工藤正俊
    肝胆膵 49 885 - 893 2004年 [査読有り]
  • 肝癌の超音波診断. 特集「肝炎から肝がんまで」
    井上達夫; 萩原 智; 福永豊和; 工藤正俊
    臨床と研究 81 59 - 65 2004年 [査読有り]
  • 萩原 智; 笠原 勝宏; 矢田 典久; 毛利 陽一; 木村 昇; 高谷 晴夫; 梶村 幸三
    日本消化器病學會雜誌 = The Japanese journal of gastro-enterology 100 9 1134 - 1139 The Japanese Society of Gastroenterology 2003年09月 
    症例は68歳, 男性. 原田病にて近医通院中, 肝機能障害指摘. 膵管の彌慢性狭細像, IgG高値より, 自己免疫性膵炎と診断した. ステロイド投与にて膵画像所見のみならず, 大動脈壁肥厚や, 顎下腺腫脹も著明に改善し, 全身の諸臓器に広範な線維化をおこすmultifocal fibrosclerosis1)との関連が推察された. また自己免疫性疾患である原田病を合併し, 多臓器に自己免疫を出現させた可能性も示唆された.
  • 萩原 智; 藤本 美香; 盛岡 幸恵; 矢田 裕人; 小牧 克守; 山内 孝哲; 西村 明芳; 北野 元一; 荒井 宏司; 大野 恭裕
    日本内分泌学会雑誌 76 1 197 - 197 (一社)日本内分泌学会 2000年04月
  • 上島 真以子; 西村 明芳; 矢田 裕人; 萩原 智; 小牧 克守; 藤本 美香; 荒井 宏司; 大野 恭裕; 青木 矩彦
    日本内分泌学会雑誌 76 108 - 108 (一社)日本内分泌学会 2000年02月

書籍

  • 当院における肝細胞癌分子標的治療の現状
    上嶋一臣; 有住忠晃; 早石宗右; 田北雅弘; 北井 聡; 矢田典久; 井上達夫; 萩原 智; 南 康範; 櫻井俊治; 西田直生志; 工藤正俊 (担当:範囲:第6回日本肝がん分子標的治療研究会 記録「SORAFENIB PRACTICE BOOK-Sorafenib治療の実践!! 多数症例の使用経験を踏まえた治療の実践と問題点の解決を示す-」監・編集 市田隆文)アークメディア, 東京 2012年 pp25-30
  • 新時代のウイルス性肝炎学, B型肝癌根治後の再発抑制治療と有用性.
    萩原 智; 工藤 正俊 (担当:共著範囲:)日本臨牀, 大阪 2011年
  • 症例から学ぶウイルス肝炎の治療戦略, B型肝炎 ペグインターフェロンとエンテカビル投与によって薬剤フリーが得られているB型肝炎症例.
    萩原 智; 工藤 正俊 (担当:共著範囲:)診断と治療社, 東京 2010年

講演・口頭発表等

  • アルコールによる肝障害について  [招待講演]
    萩原 智
    市民公開講座 2023年02月 口頭発表（一般）
  • アルコール関連問題啓発フォーラムin OSAKA 2022  [招待講演]
    萩原 智
    Kowa Web Conference 2022年12月 口頭発表（一般）
  • 複数の臓器に発症したirAE  [招待講演]
    萩原 智
    irAE WEBカンファランス 2022年12月 口頭発表（一般）
  • 特別講演「C型慢性肝疾患について考える～慢性肝炎から肝癌まで～」  [招待講演]
    萩原 智
    Next Generation Liver Conference in Saitama 2022 2022年12月 口頭発表（招待・特別） TKP大宮駅西口カンファレンスセンターホール5A, 埼玉
  • 特別講演「C型肝炎治療の最近の話題」  [招待講演]
    萩原 智
    第467回北九州肝臓病懇話会 2022年11月 口頭発表（招待・特別）
  • 特別講演「栄養代謝性肝疾患の基本的なマネージメント～アルコール性肝障害も含めて～」  [招待講演]
    萩原 智
    アルコール関連問題啓発フォーラムin OSAKA 2022 2022年11月 口頭発表（招待・特別）
  • 特別講演「C型慢性肝疾患の未来について考える～慢性肝炎から肝癌まで～」  [招待講演]
    萩原 智
    第7回東京・神奈川肝疾患研究会 2022年11月 口頭発表（招待・特別）
  • コメンテーター; 難渋症例から振り返るimAEマネジメントの注意点  [招待講演]
    萩原 智
    imAE Clinical Conference for Lung Cancer 2022年11月 その他
  • B型肝炎治療の最近の話題  [招待講演]
    萩原 智
    兵庫肝疾患フォーラム 2022年10月 口頭発表（一般） ANAクラウンプラザホテル神戸, 兵庫
  • 肝細胞がんにおける上手な免疫チェックポイント阻害剤の使い方  [招待講演]
    萩原 智
    第27回がん薬物療法研修 2022年10月 口頭発表（一般）
  • ランチョンセミナー「B型肝炎の最新の治療戦略」  [招待講演]
    萩原 智
    日本消化器病学会近畿支部第117回例会 2022年10月 公開講演，セミナー，チュートリアル，講習，講義等 大阪国際交流センター, 大阪
  • B型肝炎治療の最近の話題  [招待講演]
    萩原 智
    Hepatitis Web Seminar 2022年09月 口頭発表（一般）
  • 免疫複合療法時代における肝疾患診療～C型肝炎の話題も含めて～.  [招待講演]
    萩原 智
    The Professionals AbbVie Live Seminar 2022年08月 口頭発表（一般）
  • 実臨床における上手な免疫チェックポイント阻害剤の使い方  [招待講演]
    萩原 智
    南大阪肝疾患フォーラム 2022年07月 口頭発表（一般） スイスホテル南海大阪, 大阪
  • 線維化非進展例からのNASH関連肝癌発症様式の検討  [招待講演]
    萩原 智
    第6回関西肝疾患フォーラム 2022年07月 口頭発表（一般） シェラトン都ホテル大阪, 大阪
  • 座長; 高TG血症を合併した慢性肝疾患に対するペマフィブラートへの期待  [招待講演]
    萩原 智
    Kowa Web Conference 2022年07月 その他
  • ABC LEN-TACE Sandwich療法にてcancer free, drug freeが得られたPET陽性肝癌の1例  [招待講演]
    萩原 智; 大丸直哉; 松原卓哉; 千品寛和; 盛田真弘; 青木智子; 田北雅弘; 南 康範; 依田 広; 上嶋一臣; 西田直生志; 工藤正俊
    第68回大阪肝穿刺生検治療研究会 2022年06月 口頭発表（一般）
  • ランチョンセミナー「B型肝炎診療における最近の話題～肝発がん抑制からHBV再活性化対策まで～」  [招待講演]
    萩原 智
    第58回日本肝臓学会総会 2022年06月 公開講演，セミナー，チュートリアル，講習，講義等 パシフィコ横浜, 神奈川
  • 実臨床における上手な免疫チェックポイント阻害剤の使い方  [招待講演]
    萩原 智
    第19回大阪消化器化学療法懇話会 2022年05月 口頭発表（一般）
  • 萩原 智  [招待講演]
    HBV治療の最新情報; 肝発癌抑制に向けたTAFの有用性とは
    G-Station Plusベムリディ特別番組 2022年02月 口頭発表（招待・特別）
  • 座長; 高TG血症を合併した慢性肝疾患に対するペマフィブラートへの期待  [招待講演]
    萩原 智
    Kowa Web Conference 2022年02月 その他
  • HBV治療の最新情報;肝発癌抑制に向けたTAFの有用性とは  [招待講演]
    萩原 智
    G-Station Plusベムリディ特別番組 2022年02月 口頭発表（招待・特別）
  • ICI投与とHBVフォローにおける問題点, ワークショップ1「肝炎ウイルスコントロール下における課題へのアプローチ」
    盛田真弘; 萩原 智; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第116回例会 2022年02月 シンポジウム・ワークショップパネル（公募） 大阪国際会議場, 大阪
  • 免疫チェックポイント阻害剤投与後に発現した肝障害の臨床的、病理学的検討, ワークショップ2「免疫チェックポイント阻害剤をめぐる諸問題」
    萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第116回例会 2022年02月 シンポジウム・ワークショップパネル（公募） 大阪国際会議場, 大阪
  • ランチョンセミナー「核酸アナログ治療の肝発癌に対する現状と課題」  [招待講演]
    萩原 智
    第44回日本肝臓学会西部会 2021年12月 公開講演，セミナー，チュートリアル，講習，講義等
  • 特別講演「実臨床における上手な免疫チェックポイント阻害剤の使い方～C型肝炎の話題も含めて～」  [招待講演]
    萩原 智
    The Professionals AbbVie Live Seminar 2021年11月 口頭発表（招待・特別）
  • ランチョンセミナー「どうするHBV再活性化と発がん対策、ベムリディへの期待」  [招待講演]
    萩原 智
    日本消化器病学会近畿支部第115回例会 2021年09月 公開講演，セミナー，チュートリアル，講習，講義等
  • 特別講演「どうする再活性化対策と肝発がん予防」  [招待講演]
    萩原 智
    第383回福岡市医師会消化器病研究会 2021年09月 口頭発表（招待・特別）
  • 特別講演「B型肝炎治療Up to Date」  [招待講演]
    萩原 智
    GILEAD HBV Online Seminar 2021年05月 口頭発表（招待・特別）
  • 特別講演「C型肝炎は完治する時代へ」  [招待講演]
    萩原 智
    The Eliminators AbbVie Live Seminar 2021年05月 口頭発表（招待・特別）
  • 免疫チェックポイント阻害剤投与後のリスクマネジメントについて  [招待講演]
    萩原 智
    第5回関西肝疾患フォーラム 2021年05月 口頭発表（一般）
  • 特別講演「肝疾患におけるカルニチン補充の重要性」  [招待講演]
    萩原 智
    Carnitine Webセミナー 2021年04月 口頭発表（招待・特別）
  • 免疫チェックポイント阻害剤による肝機能障害について  [招待講演]
    萩原 智
    第1回ireAE WEBカンファランス 2021年03月 口頭発表（招待・特別）
  • アテゾリズマブ（テセントリク）による多臓器障害に対してHDF/PEを施行した一例  [招待講演]
    萩原 智
    第141回京滋臨床肝臓研究会 2020年12月 口頭発表（招待・特別） ザ・サウザンドキョウト, 京都
  • 免疫チェックポイント阻害剤による免疫関連有害事象～irAE肝障害のメカニズムと診断・対策～  [招待講演]
    萩原 智
    大日本住友webセミナー 2020年12月 口頭発表（招待・特別）
  • Ｂ型肝炎治療Up to date  [招待講演]
    萩原 智
    姫路肝疾患フォーラム 2020年12月 口頭発表（招待・特別） ホテルモントレ姫路, 兵庫
  • B型肝炎最新治療～長期治療を見据えた核酸アナログ選択～  [招待講演]
    萩原 智
    South Osaka Liver Summit 2019年12月 口頭発表（一般） ホテルモントレグラスミア大阪, 大阪
  • 基調講演「長期目標から考えるHBV治療選択について」  [招待講演]
    萩原 智
    HBV Lecture Meeting 2019年12月 口頭発表（基調） ホテル日航大阪, 大阪
  • C型肝炎治療の最新情報  [招待講演]
    萩原 智
    C型肝炎と肝癌の最新治療 2019年11月 口頭発表（一般） あべのハルカス, 大阪
  • アテゾリズマブによる肝機能障害に対して血漿交換を施行した一例  [招待講演]
    萩原 智
    第39回南大阪肝疾患研究会 2019年10月 口頭発表（一般） ホテルアゴーラリージェンシー堺, 大阪
  • 新時代の肝炎治療～肝炎、肝がんの実臨床～  [招待講演]
    萩原 智
    肝炎インターネット講演会 2019年09月 公開講演，セミナー，チュートリアル，講習，講義等
  • 基調講演「B型肝炎の新規治療戦略～TAFの実臨床経験を踏まえて～」  [招待講演]
    萩原 智
    HBV Expert Meeting in Gifu 2019年08月 口頭発表（基調） 都ホテル岐阜長良川
  • 招待講演「B型肝炎の新規治療戦略-長期治療を考慮した薬剤選択-」  [招待講演]
    萩原 智
    第5回多摩リバーカンファレンス 2019年06月 口頭発表（招待・特別） パレスホテル立川, 東京
  • B型肝炎の新規治療戦略-長期治療を考慮した薬剤選択-  [招待講演]
    萩原 智
    第4回関西肝疾患フォーラム 2019年05月 口頭発表（一般） 帝国ホテル大阪, 大阪
  • ランチョンセミナー31「肝炎治療へのアプローチを考察する～Real World Dataが示す実際～」  [招待講演]
    萩原 智
    第105回日本消化器病学会総会 2019年05月 その他 ANAクラウンプラザホテル金沢, 石川
  • B型肝炎の新規治療戦略-ベムリディの実臨床経験を踏まえて-」  [招待講演]
    萩原 智
    Liver Science Meeting in 高松 2019年04月 口頭発表（招待・特別） ホテルパールガーデン, 香川
  • B型肝炎の新規治療戦略  [招待講演]
    萩原 智
    第15回 Kinki Liver Club 2019年03月 口頭発表（招待・特別）
  • B型肝炎の新規治療戦略 ～ ベムリディの実臨床経験を踏まえて～  [招待講演]
    萩原 智
    G-STATION Lecture ベムリディ特別番組 2019年03月 口頭発表（招待・特別） ホテルアゴーラリージェンシー堺
  • ここまで来た！C型肝炎治療～患者の病態に合わせた治療薬の選択と今後の課題～  [招待講演]
    萩原 智
    第40回日本病院薬剤師会近畿学術大会ランチョンセミナー 2019年01月 口頭発表（招待・特別）
  • DAA治療によるベネフィットー発癌・再発抑制の検討ー  [招待講演]
    萩原 智
    アッヴィ肝炎フォーラム～マヴィレット1周年記念講演会～ 2019年01月 口頭発表（招待・特別）
  • B型肝炎の新規治療戦略 ～ ベムリディの実臨床経験を踏まえて～  [招待講演]
    萩原 智
    Hepatitis Expert Meeting 2018年12月 口頭発表（招待・特別） 阪急インターナショナル
  • B型肝炎の新規治療戦略 ～ ベムリディの実臨床経験を踏まえて～  [招待講演]
    萩原 智
    ウイルス性肝炎学術講演会 2018年11月 口頭発表（招待・特別） ハイアットリージェンシー京都
  • ウイルス性肝炎治療のup-to-date～G/P療法の最新治療成績もふまえて～  [招待講演]
    萩原 智
    Web Live-Seminar 2018年11月 口頭発表（招待・特別）
  • ウイルス性肝炎治療のup-to-date  [招待講演]
    萩原 智
    伊賀医師会学術講演会 2018年11月 口頭発表（招待・特別）
  • 多様な患者ニーズに応える慢性肝炎治療  [通常講演]
    萩原 智
    JDDW2018 KOBE サテライトシンポジウム80 2018年11月 シンポジウム・ワークショップパネル（公募）
  • 当院におけるTAFの有効性・安全性の検討  [招待講演]
    萩原 智
    第2回大阪和歌山消化器疾患カンファレンス 2018年09月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺
  • ウイルス性肝炎の最新治療  [招待講演]
    萩原 智
    第14回Interactive Medical Conference 2018年09月 口頭発表（招待・特別）
  • 特別講演「ウイルス性肝炎の最新治療」  [招待講演]
    萩原 智
    堺市医師会内科医会学術講演会 2018年08月 口頭発表（招待・特別）
  • テノホビルアラフェナミドの初期使用経験について  [通常講演]
    萩原 智; 西田直生志; 工藤正俊
    第60回京都肝疾患懇話会 2018年07月 口頭発表（一般） 京都ホテルオークラ, 京都
  • ウイルス性肝炎の最新情報  [招待講演]
    萩原 智
    肝炎・消化器疾患連携セミナー 2018年06月 公開講演，セミナー，チュートリアル，講習，講義等 市立岸和田市民病院, 大阪
  • IFNフリー治療を臨床で活かす ～有効性と忍容性を考慮に入れた治療～  [招待講演]
    萩原 智
    第54回日本肝臓学会総会ランチョンセミナー 2018年06月 口頭発表（招待・特別）
  • B型肝炎治療のup-to-date  [招待講演]
    萩原 智
    肝炎診療連携セミナー 2018年05月 口頭発表（招待・特別）
  • テノホビルアラフェナミドの初期使用経験について  [通常講演]
    萩原 智
    第3階関西肝疾患フォーラム 2018年05月 口頭発表（一般） 帝国ホテル大阪, 大阪
  • ベムリディ（TAF）の臨床的意義 ‐自験例を踏まえて‐  [招待講演]
    萩原 智
    第104回日本消化器病学会総会 ランチョンセミナー15 2018年04月 口頭発表（招待・特別） 京王プラザホテル
  • B型肝炎治療のup-to-date  [通常講演]
    萩原 智
    Hepatitis Forum 2018年03月 口頭発表（一般）
  • 当院におけるC型肝炎治療の成績  [招待講演]
    萩原 智
    第14回Kinki Liver Club 2018年03月 口頭発表（招待・特別）
  • ウイルス性肝炎治療Up to date  [招待講演]
    萩原 智
    第5回住吉消化器ネットワークセミナー 2018年03月 口頭発表（招待・特別）
  • 実臨床におけるVemlidy（TAF）の有効性・安全性の検討 ～ETVからの切り替えについて～  [招待講演]
    萩原 智
    ベムリディ発売1周年記念講演会 in Osaka 2018年01月 口頭発表（招待・特別） 帝国ホテル大阪
  • C型肝炎治療のUp to date  [招待講演]
    萩原 智
    大阪狭山市医師会学術講演会 2017年12月 口頭発表（招待・特別） 旧狭山美原医療保健センター2階大会議室
  • B型肝炎治療のUp to date  [招待講演]
    萩原 智
    大阪和歌山消化器疾患カンファレンス 2017年11月 口頭発表（招待・特別） アバローム紀の国
  • ハーボニー配合錠の心・腎・肝機能への影響  [招待講演]
    萩原 智
    G-STATION WEB講演会 2017年09月 口頭発表（招待・特別） ホテルアゴーラリージェンシー堺
  • 実臨床におけるエレルサ®/グラジナ®の使用成績  [招待講演]
    萩原 智
    肝炎インターネット講演会 2017年08月 口頭発表（招待・特別）
  • 特別講演「C型肝炎治療のピットフォール」  [招待講演]
    萩原 智
    倉敷肝炎ネットワークセミナー 2017年07月 口頭発表（招待・特別） 倉敷中央病院総合保険管理センター古久賀ホール, 岡山
  • Naiveに対する各DAA治療不成功例の特徴  [招待講演]
    萩原 智
    XIMENCY発売記念講演会 1st Announcement 2017年07月 口頭発表（招待・特別） 東京プリンスホテル, 東京
  • C型肝炎治療のピットフォール～より安全に確実にSVRを目指すために～  [招待講演]
    萩原 智
    G-STATION-Lecture-, WEB講演会 2017年07月 口頭発表（招待・特別）
  • C型肝炎治療のピットフォール  [招待講演]
    萩原 智
    Smart Life Symposium in 多治見 2017年07月 口頭発表（招待・特別） オースタット国際ホテル多治見, 滋賀
  • STAT3制御分子に注目した肝細胞癌のソラフェニブ治療効果予測の可能性. プレナリーセッション1  [通常講演]
    櫻井俊治; 工藤正俊; 有住忠明; 田北雅弘; 矢田典久; 萩原 智; 南 康範; 依田 広; 上嶋一臣; 西田直生志
    第16回日本肝がん分子標的治療研究会 2017年06月 シンポジウム・ワークショップパネル（公募） ルネッサンスリゾートナルト, 徳島
  • DAA投与におけるSVR後のAFP及びALT異常値と関連する臨床背景の検討  [通常講演]
    河野匡志; 西田直生志; 南 知宏; 千品寛和; 有住忠晃; 田北雅弘; 依田 広; 矢田典久; 南 康範; 萩原 智; 上嶋一臣; 工藤正俊
    第53回日本肝臓学会総会 2017年06月 口頭発表（一般） 広島国際会議場, 広島
  • C型肝炎について病気や新しい治療をテーマにお届けします  [招待講演]
    萩原 智
    高岡美樹のべっぴんラジオ,ラジオ大阪 2017年06月 メディア報道等
  • 当院におけるDAAs治療成績  [招待講演]
    萩原 智
    第13回Kinki Liver Club 2017年03月 口頭発表（招待・特別） スイスホテル南海大阪, 大阪
  • 特別講演「当院におけるウイルス性肝炎診療」  [招待講演]
    萩原 智
    泉州消化器病談話会 2017年03月 口頭発表（招待・特別） 市立岸和田市民病院, 大阪
  • 特別講演「当院におけるウイルス性肝炎治療」  [招待講演]
    萩原 智
    阪南肝炎セミナー 2017年03月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺, 大阪
  • 当院におけるDAAs治療成績  [招待講演]
    萩原 智
    エレルサ®・グラジナ®発売記念講演会in南大阪 2017年02月 口頭発表（招待・特別） シェラトン都ホテル大阪, 大阪
  • 特別講演「肝臓病と採血データの見方」  [招待講演]
    萩原 智
    日本肝臓学会主催平成28年度「肝がん撲滅運動」 2017年01月 口頭発表（招待・特別） ビッグ・アイ, 大阪
  • Locked Nucleic Acidsを用いた血清中マイクロRNA定量とソラフェニブ治療に対する反応予測  [通常講演]
    西田直生志; 岩西美奈; 南 知宏; 千品寛和; 河野匡志; 有住忠晃; 田北雅弘; 矢田典久; 依田 広; 萩原 智; 南 康範; 上嶋一臣; 工藤正俊
    第15回日本肝がん分子標的治療研究会 2017年01月 口頭発表（一般） イイノホール＆カンファレンスセンター, 東京
  • 癌遺伝子ガンキリンは炎症細胞でのSTAT3を活性化することで大腸発癌を促進する  [通常講演]
    櫻井俊治; 工藤正俊; 渡邊智裕; 樫田博史; 西田直生志; 米田頼晃; 永井知行; 萩原 智
    第2回G-PLUS 2016年12月 口頭発表（一般） ホテルイースト21東京, 東京
  • 特別講演「新しい肝炎治療時代の臨床検査―肝炎ウイルスマーカーの意義を再検討する―」  [招待講演]
    萩原 智
    大阪府医師会医学会臨床検査シリーズ 2016年12月 口頭発表（招待・特別） 大阪府医師会館, 大阪
  • 特別講演「整形外科医が知っておくべきB型・C型肝炎最新治療」  [招待講演]
    萩原 智
    Joint operation seminar～整形外科・消化器疾患について～ 2016年12月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺, 大阪
  • エンテカビルとPEG-IFNα2a/2b 48週併用療法の効果および治療効果予測因子の検討. ワークショップ9「B型肝炎治療のアップデート」  [通常講演]
    萩原 智; 西田直生志; 工藤正俊
    第20回日本肝臓学会大会, 第58回日本消化器病学会大会, 第92回日本消化器内視鏡学会総会, 第14回日本消化器外科学会大会, 第54回日本消化器がん検診学会大会(JDDW 2016) 2016年11月 シンポジウム・ワークショップパネル（公募） 神戸コンベンションセンター, 兵庫
  • Combination therapy with peginterferon and entecavir for persistent viral suppression in patients with chronic hepatitis B  [通常講演]
    Hagiwara S; Nishida N; Kudo M
    23rd International Symposium on Hepatitis C Virus and Related Viruses (HCV2016) 2016年10月 口頭発表（一般） Kyoto International Conference Center
  • 特別講演「当院におけるウイルス性肝疾患診療」  [招待講演]
    萩原 智
    伊都医師会学術講演会 2016年10月 口頭発表（招待・特別） ラポール橋本商工会館, 和歌山
  • 特別講演「HCV感染透析患者の最新治療」  [招待講演]
    萩原 智
    阪南HCV連携セミナー 2016年09月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺, 大阪
  • 特別講演「B型肝炎と言われたら」  [招待講演]
    萩原 智
    近畿大学医学部附属病院肝疾患診療連携拠点病院事業肝臓病教室 2016年08月 口頭発表（招待・特別） 近畿大学医学部附属病院PET棟3階大会議室, 大阪
  • 特別講演「当院における肝疾患診療」  [招待講演]
    萩原 智
    Liver Disease Meeting 2016年07月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺, 大阪
  • NASH関連肝発癌における線維化進展と遺伝子変化. ワークショップ2「非ウイルス性肝細胞癌の病態と分類」  [通常講演]
    萩原 智; 西田直生志; 工藤正俊
    第52回日本肝癌研究会 2016年07月 シンポジウム・ワークショップパネル（公募） 虎ノ門ヒルズフォーラム, 東京
  • 当院におけるDrug eluting bead (DEB)-TACEの現況  [通常講演]
    田北雅弘; 南 知宏; 千品寛和; 有住忠晃; 矢田典久; 萩原 智; 南 康範; 依田 広; 上嶋一臣; 西田直生志; 任 誠雲; 柳生行伸; 松木 充; 鶴崎正勝; 村上卓道; 工藤正俊
    第16回関西肝血流動態・機能イメージ研究会 2016年06月 口頭発表（一般） オーバルホール, 大阪
  • 特別講演「化学療法施行時のB型肝炎の再活性化-対策と現状-」  [招待講演]
    萩原 智
    第3回阪奈血液疾患治療セミナー 2016年06月 口頭発表（招待・特別） スイスホテル南海大阪, 大阪
  • C型肝炎に対する当院でのDAAs治療成績  [招待講演]
    萩原 智
    第1回関西肝疾患フォーラム 2016年06月 口頭発表（招待・特別） 帝国ホテル大阪, 大阪
  • 特別講演「当院における肝疾患診療‐トルバプタン治療成績も含めて‐」  [招待講演]
    萩原 智
    第2回北・中河内患者のQOLを考える会 2016年06月 口頭発表（招待・特別） ザ・リッツカールトン大阪, 大阪
  • トルバプタンにおける初期、および遅発性効果予測因子の検討  [通常講演]
    萩原 智; 千品寛和; 工藤正俊
    第102回日本消化器病学会総会 2016年04月 口頭発表（一般） 京王プラザホテル, 東京
  • ラジオ波焼灼術後のバブルによる高エコー域を壊死部とみなして良いか？  [通常講演]
    南 康範; 岩西美奈; 南 知宏; 千品寛和; 河野匡志; 有住忠晃; 田北雅弘; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第29回日本腹部造影エコー・ドプラ診断研究会 2016年04月 口頭発表（一般） 宮崎市エムアールティ・ミック, 北九州
  • NASH関連肝発癌における線維化進展と遺伝子変化  [招待講演]
    萩原 智
    Kansai Liver Club 2016 2016年04月 口頭発表（招待・特別） 太閤園, 大阪
  • 特別講演「C型慢性肝炎の最新治療」  [招待講演]
    萩原 智
    CHC Expert Meeting 2016年03月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺, 大阪
  • 特別講演「肝細胞癌治療の最新知見」  [招待講演]
    萩原 智
    CHC Expert Meeting 2016年03月 口頭発表（招待・特別） ホテル・アゴーラリージェンシー堺, 大阪
  • B型肝炎の最先端  [招待講演]
    萩原 智
    平成27年度「肝がん撲滅運動」 2016年02月 口頭発表（招待・特別） 堺商工会議所, 大阪
  • 若年男性に発症した肝細胞腺腫の悪性転化の一例  [通常講演]
    南 知宏; 萩原 智; 岩西美奈; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 南 康範; 依田 広; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第104回例会 2016年02月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 自己免疫性溶血性貧血を合併した自己免疫性肝炎の一例  [通常講演]
    岩西美奈; 依田 広; 高島耕太; 南 知宏; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 南 康範; 上嶋一臣; 西田直生志; 工藤正俊; 平瀬主税; 前西 修; 筑後孝章
    日本消化器病学会近畿支部第104回例会 2016年02月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 当院でのダクラタスビル/アスナプレビル併用療法の検討  [通常講演]
    千品寛和; 萩原 智; 岩西美奈; 南 知宏; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 依田 広; 南 康範; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第104回例会 2016年02月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 座長; Freshman Session3「肝臓」  [招待講演]
    萩原 智
    日本消化器病学会近畿支部第104回例会 2016年02月 その他 大阪国際交流センター, 大阪
  • 特別講演「当院におけるウイルス性肝炎診療」  [招待講演]
    萩原 智
    第20回奈良肝臓ミーティング 2016年02月 口頭発表（招待・特別） 橿原ロイヤルホテル, 奈良
  • 特別講演「C型肝炎の最新治療」  [招待講演]
    萩原 智
    羽曳野市医師会学術講演会 2015年12月 口頭発表（招待・特別） 羽曳野市立保健センター, 大阪
  • 肝細胞癌に対してUS-US fusionを用いたラジオ波焼灼術  [通常講演]
    南 知宏; 南 康範; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第19回日本肝臓学会大会 2015年10月 口頭発表（一般） グランドプリンスホテル高輪, 東京
  • 転移性肝癌に対してUS-US fusionを用いたラジオ波焼灼術  [通常講演]
    南 知宏; 南 康範; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第57回日本消化器病学会大会 2015年10月 口頭発表（一般） グランドプリンスホテル高輪, 東京
  • 転移性肝癌に対するUS-US fusionを用いたラジオ波焼灼術  [通常講演]
    南 知宏; 南 康範; 岩西美奈; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 依田 広; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第103回例会 2015年09月 口頭発表（一般） 大阪国際交流センター, 大阪
  • トルバプタンの治療効果における予測因子の検討  [通常講演]
    千品寛和; 萩原 智; 岩西美奈; 南 知宏; 河野匡志; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 南 康範; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第103回例会 2015年09月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 慢性下痢を主訴としたC型慢性肝炎関連クリオグロブリン血症の一例  [通常講演]
    足立哲平; 岡元寿樹; 河野匡志; 田中梨絵; 山田光成; 峯 宏昌; 永井知行; 朝隈 豊; 米田頼晃; 岡崎能久; 萩原 智; 櫻井俊治; 松井繁長; 樫田博史; 工藤正俊; 野崎祐史; 松村 到; 石井道治
    日本消化器病学会近畿支部第103回例会 2015年09月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 著明な肝機能障害を呈した骨髄性ポルフィリン症の一例  [通常講演]
    青山真吾; 萩原 智; 岩西美奈; 南 知宏; 千品寛和; 河野匡志; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 南 康範; 依田 広; 上嶋一臣; 櫻井俊治; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第103回例会 2015年09月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 固形がんにおける化学療法施行時のB型肝炎ウイルス再活性化の多施設共同前向き観察研究. シンポジウム1「ウイルス性肝炎診療の最前線」  [通常講演]
    萩原 智; 池田公史; 溝上雅史
    日本消化器病学会近畿支部第103回例会 2015年09月 シンポジウム・ワークショップパネル（公募） 大阪国際交流センター, 大阪
  • B型肝炎の最新治療、肝発がんの抑制  [招待講演]
    萩原 智
    B型肝炎医療講演＆訴訟説明会 2015年09月 口頭発表（招待・特別） 栂文化会館, 大阪
  • B型肝炎について  [招待講演]
    萩原 智
    平成27年度肝臓病教室 2015年09月 口頭発表（招待・特別） 近畿大学医学部附属病院, 大阪
  • 肝性浮腫におけるトルバプタンの使用経験（内科の立場から）  [招待講演]
    萩原 智
    肝臓フォーラムin Osaka-肝硬変合併症をとらえた診療への取り組み- 2015年07月 口頭発表（招待・特別） ウェスティンホテル大阪, 大阪
  • 肝細胞癌に対してUS-US fusionを用いたラジオ波焼灼術. ビデオセッション1「RFAの推奨手技」  [通常講演]
    南 康範; 南 知宏; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第51回日本肝癌研究会 2015年07月 口頭発表（一般） 神戸国際会議場, 兵庫
  • 上腸間膜静脈血栓症による急性腸管虚血に対しTIPSを施行した一例  [通常講演]
    沼本勲男; 鶴﨑正勝; 柳生行伸; 渡口真史; 山川美帆; 任 誠雲; 松木 充; 村上卓道; 萩原 智; 工藤正俊; 吉藤竹仁; 船内正憲
    第59回関西Interventional Radiology研究会 2015年06月 口頭発表（一般） ホテルエルセラーン大阪, 大阪
  • 固形がんにおける化学療法施行時のB型肝炎ウイルス再活性化-各施設共同前向き観察研究  [招待講演]
    萩原 智
    第17回関西B型肝炎研究会 2015年06月 口頭発表（招待・特別） ホテルモントレグラスミア, 大阪
  • 若年男性に発症したHCAの一例  [招待講演]
    萩原 智
    第59回大阪肝穿刺生検治療研究会 2015年06月 口頭発表（招待・特別） ホテルグランヴィア大阪, 大阪
  • ウイルス性肝炎の最新治療  [招待講演]
    萩原 智
    富田林肝胆膵治療研究会 2015年06月 口頭発表（招待・特別） 富田林医師会館, 大阪
  • 転移性肝癌に対してUS-US fusionを用いたラジオ波焼灼術  [通常講演]
    南 知宏; 南 康範; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第51回日本肝臓学会総会 2015年05月 口頭発表（一般） 鶴屋東館, 熊本
  • intermediate stageの肝細胞癌に対してTACE不応後のTACE継続とソラフェニブの検討  [通常講演]
    有住忠晃; 上嶋一臣; 南 知宏; 千品寛和; 河野匡志; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 南 康範; 櫻井俊治; 西田直生志; 工藤正俊
    第51回日本肝臓学会総会 2015年05月 口頭発表（一般） 鶴屋東館, 熊本
  • 固形がんにおける化学療法施行時のB型肝炎ウイルス再活性化の多施設共同前向き観察研究. シンポジウム2「B型肝炎に対する治療戦略と今後の展開」  [通常講演]
    萩原 智; 池田公史; 溝上雅史
    第51回日本肝臓学会総会 2015年05月 シンポジウム・ワークショップパネル（公募） 熊本ホテルキャッスル, 熊本
  • 変異型HBx遺伝子の肝発癌促進における分子機序の解明. ワークショップ4「肝病態を反映する新たなバイオマーカーの探索」  [通常講演]
    萩原 智; 西田直生志; 工藤正俊
    第51回日本肝臓学会総会 2015年05月 シンポジウム・ワークショップパネル（公募） 熊本ホテルキャッスル, 熊本
  • DAAsを用いたC型肝炎治療  [招待講演]
    萩原 智
    河内Hepatitis Conference-専門医が考えるB型・C型肝炎の治療について- 2015年05月 口頭発表（招待・特別） セントレジスホテル大阪, 大阪
  • 発癌抑制を目指したB型肝炎治療  [招待講演]
    萩原 智
    第12回Kinki Liver Clubバニプレビル学術講演会 2015年04月 口頭発表（招待・特別） スイスホテル南海大阪, 大阪
  • ウイルス性肝炎の最新治療  [招待講演]
    萩原 智
    平成27年4月泉佐野泉南医師会学術講演会 2015年04月 口頭発表（招待・特別） ホテル日航関西空港, 大阪
  • 転移性肝癌に対してUS-US fusionを用いたラジオ波焼灼術  [通常講演]
    南 知宏; 南 康範; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第28回日本腹部造影エコー・ドプラ診断研究会 2015年04月 口頭発表（一般） 札幌医科大学, 北海道
  • Drug freeを目指したエンテカビルとPEG-IFN α2a/2b 48週併用療法の効果について  [招待講演]
    萩原 智
    Kansai Liver Club 2015 2015年04月 口頭発表（招待・特別） 太閤園, 大阪
  • Plain cone-beam CTによる肝動脈塞栓術の早期治療効果予測  [通常講演]
    南 康範; 南 知宏; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊; 柳生行伸; 鶴崎正勝; 村上卓道
    第17回関西肝癌局所療法研究会 2015年03月 口頭発表（一般） 阪急電鉄本社ビル, 大阪
  • 当院における肝細胞癌に対するDEB-TACEの治療成績  [通常講演]
    鶴崎正勝; 渡口真史; 柳生行伸; 沼本勲男; 朝戸信行; 山川美帆; 任 誠雲; 松木 充; 村上卓道; 田北雅弘; 北井 聡; 井上達夫; 萩原 智; 南 康範; 上嶋一臣; 工藤正俊
    第17回関西肝癌局所療法研究会 2015年03月 口頭発表（一般） 阪急電鉄本社ビル, 大阪
  • 慢性リンパ性白血病の発症を契機にB型肝炎の再活性化から急性肝不全を来し急速な転帰を辿った一例  [通常講演]
    渡部由佳子; 萩原 智; 南 知宏; 河野匡志; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 南 康範; 櫻井俊治; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第102回例会 2015年02月 口頭発表（一般） 京都テルサ, 京都
  • 当院における肝細胞癌に対するディーシービーズ®を用いたDEB-TACEの治療成績  [通常講演]
    渡口真史; 鶴崎正勝; 柳生行伸; 沼本勲男; 朝戸信行; 山川美帆; 任 誠雲; 松木 充; 村上卓道; 井上達夫; 萩原 智; 南 康範; 上嶋一臣; 工藤正俊
    第21回肝血流動態・機能イメージ研究会 2015年02月 口頭発表（一般） 東京ビッグサイト「国際会議場」, 東京
  • 高齢者の進行肝細胞癌に対する当院でのソラフェニブ治療の成績  [通常講演]
    有住忠晃; 上嶋一臣; 南 知宏; 千品寛和; 河野匡志; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 南 康範; 櫻井俊治; 西田直生志; 工藤正俊
    第11回日本肝がん分子標的治療研究会 2015年01月 口頭発表（一般） 海運クラブ, 東京
  • ダクラタスビル・アスナプレビル併用療法を用いたHCVの治療戦略  [招待講演]
    萩原 智
    南大阪HCV治療懇話会 2014年12月 口頭発表（招待・特別） アゴーラ・リージェンシー堺, 大阪
  • Pathological feature, oxidative DNA damage and epigenetic alteration of tumor suppressor genes in nonalcoholic fatty liver disease  [通常講演]
    Nishida N; Yada N; Chishina H; Arizumi T; Takita M; Kitai S; Inoue T; Hagiwara S; Minami Y; Ueshima K; Sakurai T; Kudo M
    65th Annual Meeting, American Association for the Study of Liver Diseases (AASLD2014) 2014年11月 口頭発表（一般） Boston, USA
  • B-modeで描出困難な肝癌に対するFusion imaging+造影USガイドでのラジオ波焼灼術  [通常講演]
    南 知宏; 南 康範; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 井上達夫; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    第22回日本消化器関連学会週間JDDW2014（第88回日本消化器内視鏡学会総会, 第56回日本消化器病学会大会, 第18回日本肝臓学会大会, 第12回日本消化器外科学会大会, 第52回日本消化器がん検診学会大会） 2014年10月 口頭発表（一般） 神戸国際展示場・ポートピアホテル・神戸国際会議場, 兵庫
  • 甲状腺クリーゼを契機に急性肝不全を発症した1例  [通常講演]
    山本貴子; 萩原 智; 千品寛和; 河野匡志; 有住忠晃; 田北雅弘; 北井 聡; 井上達夫; 矢田典久; 南 康範; 櫻井俊治; 上嶋一臣; 西田直生志; 工藤正俊; 庭野史丸; 池上博司
    日本消化器病学会近畿支部第101回例会 2014年10月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 当院におけるマイクロバルーン閉塞下肝動脈化学塞栓療法（B-TACE）導入後の検討  [通常講演]
    千品寛和; 田北雅弘; 有住忠晃; 北井 聡; 井上達夫; 矢田典久; 南 康範; 萩原 智; 上嶋一臣; 西田直生志; 朝戸信行; 任 誠雲; 柳生行伸; 松木 充; 鶴﨑正勝; 村上卓道; 工藤正俊
    第14回関西肝血流動態・機能イメージ研究会 2014年07月 口頭発表（一般） オーバルホール, 大阪
  • 当院における肝細胞癌に対するディーシービーズ®を用いたTACEの初期経験  [通常講演]
    渡口真史; 鶴﨑正勝; 柳生行伸; 沼本勲男; 朝戸信行; 山川美帆; 任 誠雲; 松木 充; 村上卓道; 井上達夫; 萩原 智; 南 康範; 上嶋一臣; 工藤正俊
    第14回肝血流動態・機能イメージ研究会 2014年07月 口頭発表（一般） オーバルホール, 大阪
  • ソラフェニブ投与にてPD判定であった進行肝細胞癌患者の検討  [通常講演]
    有住忠晃; 上嶋一臣; 千品寛和; 田北雅弘; 北井 聡; 井上達夫; 矢田典久; 萩原 智; 南 康範; 櫻井俊治; 西田直生志; 工藤正俊
    第10回日本肝がん分子標的治療研究会 2014年06月 口頭発表（一般） 淡路夢舞台国際会議場, 兵庫
  • ヒト肝発癌における酸化ストレスとエピゲノム変異の関連. パネルディスカッション2「ゲノム・エピゲノム解析に基づく肝癌診療の将来展望」  [通常講演]
    萩原 智; 西田直生志; 工藤正俊
    第50回日本肝癌研究会 2014年06月 シンポジウム・ワークショップパネル（公募） 国立京都国際会館, 京都
  • 超音波エラストグラフィによる非アルコール性脂肪性肝疾患患者の意識改革  [通常講演]
    矢田典久; 萩原 智; 工藤正俊
    第100回日本消化器病学会総会 2014年04月 口頭発表（一般） 東京国際フォーラム, 東京
  • B-modeで描出困難な肝癌に対するFusion image+造影USガイドでのラジオ波焼灼術の有用性  [通常講演]
    南 知宏; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 井上達夫; 南 康範; 上嶋一臣; 西田直生志; 工藤正俊
    第27回日本腹部造影エコー・ドプラ診断研究会 2014年04月 口頭発表（一般） はまぎんホールヴィアマーレ, 横浜
  • EOB-MRIと造影超音波検査による乏血性結節の多血化因子の検討  [通常講演]
    井上達夫; 兵頭朋子; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 村上卓道; 工藤正俊
    第27回日本腹部造影エコー・ドプラ診断研究会 2014年04月 口頭発表（一般） はまぎんホールヴィアマーレ, 横浜
  • Plain cone-beam CTによる肝動脈塞栓術の定量的治療効果予測  [通常講演]
    南 康範; 南 知宏; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 井上達夫; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊; 柳生行伸; 村上卓道
    第100回日本消化器病学会総会 2014年04月 口頭発表（一般） 東京国際フォーラム, 東京
  • TS-1+ Interferon併用療法が奏効した巨大な肝細胞癌の一例  [通常講演]
    南 知宏; 南 康範; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 井上達夫; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊
    日本消化器病学会近畿支部第100回例会 2014年02月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 座長「Freshman Session 2」  [招待講演]
    萩原 智
    日本消化器病学会近畿支部第100回例会 2014年02月 その他 大阪国際交流センター, 大阪
  • plain cone-beam CTによる肝動脈塞栓術の定量的治療効果予測  [通常講演]
    南 康範; 南 知宏; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 井上達夫; 萩原 智; 上嶋一臣; 西田直生志; 工藤正俊; 柳生行伸; 村上卓道
    第20回肝血流動態・機能イメージ研究会 2014年02月 口頭発表（一般） 大阪国際交流センター「大ホール」, 大阪
  • EOB-MRIと造影超音波検査により乏血性結節の多血化因子の検討  [通常講演]
    井上達夫; 兵頭朋子; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 上嶋一臣; 西田直生志; 村上卓道; 工藤正俊
    第20回肝血流動態・機能イメージ研究会 2014年02月 口頭発表（一般） 大阪国際交流センター「大ホール」, 大阪
  • TACE不応の進行肝細胞癌に対するソラフェニブ開始時期の検討.  [通常講演]
    有住 忠晃; 上嶋 一臣; 千品 寛和; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊
    第9回日本肝がん分子標的治療研究会 2014年01月 海運クラブ, 東京 第9回日本肝がん分子標的治療研究会
  • 血便を契機に発見された上行結腸非上皮性巨大腫瘤の2例  [通常講演]
    沼本勲男; 朝隈 豊; 岡元寿樹; 山田光成; 千品寛和; 足立哲平; 高山政樹; 峯 宏昌; 永井知行; 川崎正憲; 櫻井俊治; 松井繁長; 樫田博史; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 潰瘍性大腸炎に膵胆管合流異常症を合併した1例  [通常講演]
    東 千尋; 山雄健太郎; 田中梨絵; 大本俊介; 門阪薫平; 鎌田 研; 宮田 剛; 今井 元; 坂本洋城; 北野雅之; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • walled-off necrosisの術前の管理においてメタリックステントによるドレナージが有用であった  [通常講演]
    中田有紀; 北野雅之; 大本俊介; 門阪薫平; 宮田 剛; 鎌田 研; 山雄健太郎; 今井 元; 坂本洋城; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 食欲不振を契機に発見された巨大脾腫瘍の一例  [通常講演]
    吉川恵輔; 奥田英之; 秦 康倫; 木下大輔; 清水昌子; 岸谷 譲; 永田嘉昭; 川崎俊彦; 太田善夫; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 胃Inverted hamartomatous polypの一例  [通常講演]
    尾崎信人; 河野匡志; 丸山康典; 松本 望; 高場雄久; 奥村直己; 山本典雄; 冨田崇文; 梅原康湖; 谷池聡子; 森村正嗣; 米田 円; 山田 哲; 辻 直子; 落合 健; 前倉俊治; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • コーラ溶解法と結石粉砕術で内視鏡的摘出した胃十二指腸動脈瘤の一例  [通常講演]
    田中梨絵; 永井知行; 千品寛和; 山田光成; 足立哲平; 高山政樹; 峯 宏昌; 川崎正憲; 朝隈 豊; 松井繁長; 樫田博史; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 陥凹を伴ったSessile serrated adenoma/polyp（SSA/P）の1例  [通常講演]
    千品寛和; 朝隈 豊; 南 知宏; 岡元寿樹; 山田光成; 田中梨絵; 足立哲平; 峯 宏昌; 高山政樹; 永井知行; 川崎正憲; 櫻井俊治; 松井繁長; 樫田博史; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 潰瘍性大腸炎の加療中に壊疽性膿皮症および下肢深部静脈血栓症を合併した1例  [通常講演]
    松本 望; 尾崎信人; 河野匡志; 丸山康典; 高場雄久; 奥村直己; 山本典雄; 冨田崇文; 梅原康湖; 谷池聡子; 森村正嗣; 米田 円; 山田 哲; 辻 直子; 遠藤英樹; 落合 健; 前倉俊治; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 消化管病変を合併したHenoch-Schonlein紫斑病（HSP）の一例  [通常講演]
    南 知宏; 松井繁長; 岡元寿樹; 足立哲平; 高山政樹; 峯 宏昌; 永井知行; 川崎正憲; 朝隈 豊; 櫻井俊治; 樫田博史; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 造影ハーモニックEUS（CH-EUS）による膵腫瘤性病変の血流の定量化の試み  [通常講演]
    大本俊介; 北野雅之; 門阪薫平; 宮田 剛; 鎌田 研; 山雄健太郎; 今井 元; 坂本洋城; 工藤正俊
    日本消化器内視鏡学会近畿支部第91回支部例会 2013年11月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 造影ハーモニックEUS（CH-EUS）における膵腫瘍の血流評価の有用性について  [通常講演]
    大本俊介; 田中梨絵; 門阪薫平; 鎌田 研; 宮田 剛; 山雄健太郎; 今井 元; 坂本洋城; 北野雅之; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • Acoustic structure quantificationによるfocal spared areaの描出の試み  [通常講演]
    前川 清; 横川美加; 辻 裕美子; 前野知子; 市島真由美; 塩見香織; 矢野雅彦; 井上達夫; 南 康範; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • Fly thruによるPV Shuntの描出  [通常講演]
    前川 清; 横川美加; 辻 裕美子; 前野知子; 市島真由美; 塩見香織; 井上達夫; 南 康範; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • ソナゾイド造影を施行した小腸腫瘍の1例  [通常講演]
    横川美加; 辻 裕美子; 前野知子; 市島真由美; 塩見香織; 前川 清; 南 康範; 樫田博史; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • 造影ハーモニックEUSにおける消化器系疾患の鑑別および悪性度診断  [通常講演]
    大本俊介; 北野雅之; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • Fly thruによる胆嚢（胆石・ポリープ）の描出について  [通常講演]
    辻 裕美子; 横川美加; 前野知子; 市島真由美; 塩見香織; 前川 清; 井上達夫; 南 康範; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • 急速な増大を認めた後腹膜嚢胞性腫瘤の一例  [通常講演]
    前野知子; 横川美加; 辻 裕美子; 市島真由美; 塩見香織; 前川 清; 樫田博史; 工藤正俊
    日本超音波医学会第40回関西地方会学術集会 2013年11月 口頭発表（一般） 大阪国際会議場, 大阪
  • HBs抗原消失を目指したエンテカビルとPEG-IFN48週併用療法の効果について  [通常講演]
    萩原 智; 西田 直生志; 工藤 正俊
    第15回葵肝臓研究会 2013年11月 メルパルク京都 第15回葵肝臓研究会
  • Role of oxidative stress and epigenetic alteration on chronic hepatitis C-related human hepatocarcinogenesis  [通常講演]
    西田 直生志; 工藤 正俊; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 上嶋 一臣; Takeshi Nagasaka; Ajay Goel
    The 64th Annual Meeting of the American Association for the Study of Liver Disease (AASLD) 2013年11月 Washington D.C. The 64th Annual Meeting of the American Association for the Study of Liver Disease (AASLD)
  • 肝のう胞に対するオレイン酸モノエタノールアミン注入療法の検討  [通常講演]
    田北 雅弘; 有住 忠晃; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第17回日本肝臓学会大会（第21回日本消化器関連学会週間JDDW2013） 2013年10月 グランドプリンスホテル新高輪, 東京 第17回日本肝臓学会大会（第21回日本消化器関連学会週間JDDW2013）
  • C型肝炎に対する3剤併用療法の高齢者における認容性の検討  [通常講演]
    田北 雅弘; 萩原 智; 工藤 正俊
    第17回日本肝臓学会大会（第21回日本消化器関連学会週間JDDW2013） 2013年10月 グランドプリンスホテル新高輪, 東京 第17回日本肝臓学会大会（第21回日本消化器関連学会週間JDDW2013）
  • 各種超音波エラストグラフィによる肝線維化診断. パネルディスカッション5「非侵襲的肝病態評価法の適応と限界」  [通常講演]
    矢田 典久; 萩原 智; 工藤 正俊
    第55回日本消化器病学会大会（第21回日本消化器関連学会週間JDDW2013） 2013年10月 品川プリンスホテル, 東京 第55回日本消化器病学会大会（第21回日本消化器関連学会週間JDDW2013）
  • Sorafenib treatment for non-hypervascular hepatocellular carcinoma  [通常講演]
    有住 忠晃; 上嶋 一臣; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊
    Seventh Annual Conference International Liver Cancer Association (ILCA) 2013年09月 Washington D.C. Seventh Annual Conference International Liver Cancer Association (ILCA)
  • 慢性C型肝炎に対するテラプレビル3剤併用療法中に結核性リンパ節炎を発症した1例  [通常講演]
    千品 寛和; 井上 達夫; 南 知宏; 岡元 寿樹; 山田 光成; 田中 梨絵; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部第99回例会 2013年09月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第99回例会
  • 急激な肝機能低下をきたしたBudd-Chiari症候群の1例  [通常講演]
    鍵岡 賛典; 萩原 智; 岩西 美奈; 南 知宏; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 南 康範; 上嶋 一臣; 櫻井 俊治; 工藤 正俊
    日本消化器病学会近畿支部第99回例会 2013年09月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第99回例会
  • 急性発症型自己免疫性肝炎の一例  [通常講演]
    岩西 美奈; 萩原 智; 鍵岡 賛典; 南 知宏; 有住 忠晃; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 南 康範; 上嶋 一臣; 櫻井 俊治; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部第99回例会 2013年09月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第99回例会
  • HBs抗原消失を目指したエンテカビルとPEG-IFNα2b 48週併用療法の効果について. シンポジウム「ウイルス性肝炎治療の最前線」  [通常講演]
    萩原 智; 工藤 正俊; 大﨑往夫
    日本消化器病学会近畿支部第99回例会 2013年09月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第99回例会
  • Unique association between global dna hypomethylation and chromosomal alterations in human hepatocellular carcinoma.  [通常講演]
    西田 直生志; 工藤 正俊; 千品 寛和; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 井上 達夫; 南 康範; 上嶋 一臣; 櫻井 俊治; Yokomichi N; Nagasaka T; Goel A
    Seventh Annual Conference International Liver Cancer Asso-ciation(ILCA) 2013年09月 Washington D.C., USA Seventh Annual Conference International Liver Cancer Asso-ciation(ILCA)
  • 肝原発神経内分泌腫瘍の1例  [通常講演]
    田中梨絵; 井上達夫; 千品寛和; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 南 康範; 上嶋一臣; 西田直生志; 工藤正俊; 兵頭朋子; 村上卓道
    第13回関西肝血流動態イメージ研究会 2013年07月 口頭発表（一般） オーバルホール, 大阪
  • 経皮的ラジオ波焼灼術後の穿刺経路焼灼は必要か？: 後出血予防の検討  [通常講演]
    南 康範; 早石 宗右; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊; 鄭 浩柄
    第49回日本肝癌研究会 2013年07月 京王プラザホテル, 東京 第49回日本肝癌研究会
  • 進行肝細胞癌のソラフェニブ治療における腫瘍血流と治療効果との関連. ワークショップ1「分子標的薬の効果予後予測因子から治療法対象を考える」  [通常講演]
    有住 忠晃; 上嶋 一臣; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊
    第8回日本肝がん分子標的治療研究会 2013年06月 和倉温泉「加賀屋」, 石川 第8回日本肝がん分子標的治療研究会
  • Real-time tissue quantification (VTTQ)による自己免疫性肝炎の治療評価  [通常講演]
    矢田 典久; 萩原 智; 工藤 正俊
    日本超音波医学会第86回学術集会 2013年05月 大阪国際会議場, 大阪 日本超音波医学会第86回学術集会
  • 肝血管筋脂肪腫の3例  [通常講演]
    田中 梨絵; 南 康範; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本超音波医学会第86回学術集会 2013年05月 大阪国際会議場, 大阪 日本超音波医学会第86回学術集会
  • Heat shock protein 27 expression is inversely correlated with intraepithelial neoplasia and positively correlated with poor differentiation of gastris cancer.  [通常講演]
    永田 嘉昭; 櫻井 俊治; 高山 政樹; 永井 知行; 川崎 正憲; 朝隈 豊; 萩原 智; 西田 直生志; 松井 繁長; 樫田 博史; 工藤 正俊
    Digestive Disease Week(DDW) 2013 2013年05月 Orlando, USA Digestive Disease Week(DDW) 2013
  • Noninvasive assessment of liver fibrosis by measurement of LF index in patients with chronic viral hepatitis.  [通常講演]
    矢田 典久; 萩原 智; 有住 忠晃; 田北 雅弘; 北井 聡; 井上 達夫; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    Digestive Disease Week(DDW) 2013 2013年05月 Orlando, USA Digestive Disease Week(DDW) 2013
  • 肝原発神経内分泌腫瘍の１例  [通常講演]
    田中梨絵; 井上達夫; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 南 康範; 上嶋一臣; 西田直生志; 樫田博史; 工藤正俊
    第26回日本腹部造影エコーー・ドプラ診断研究会 2013年04月 口頭発表（一般） ウインクあいち, 愛知
  • 肝血管筋脂肪腫の3例  [通常講演]
    田中 梨絵; 上嶋 一臣; 千品 寛和; 有住 忠晃; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 南 康範; 西田 直生志; 工藤 正俊
    第99回日本消化器病学会総会 2013年03月 かごしま県民交流センター, 鹿児島 第99回日本消化器病学会総会
  • HBs抗原消失を目指したエンテカビルとPEG-IFN48週併用療法の高価について  [通常講演]
    萩原 智
    第10回Osaka Liver Collaboration Meeting 2013年02月 口頭発表（招待・特別） ホテル日航大阪, 大阪
  • 腫瘍内出血を呈した肉腫様肝癌の1例  [通常講演]
    千品 寛和; 井上 達夫; 田中 梨絵; 山田 光成; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部第98回例会 2013年02月 神戸ポートピアホテル, 兵庫 日本消化器病学会近畿支部第98回例会
  • PEG-IFNα2a少量長期療法における発癌リスクの検討-IL28B遺伝子多型との関連も含めて-  [通常講演]
    萩原 智
    第34回南大阪肝胆膵研究会 2013年01月 口頭発表（招待・特別） ホテルアゴーラリージェンシー堺, 大阪
  • ソラフェニブ治療におけるJNK活性の重要性-CD133との関連も含めて-  [通常講演]
    萩原 智; 櫻井 俊治; 工藤 正俊
    第7回日本肝がん分子標的治療研究会 2013年01月 じゅうろくプラザ, 岐阜 第7回日本肝がん分子標的治療研究会
  • 腫瘍内出血を認めた肉腫様肝癌の１例  [通常講演]
    千品寛和; 井上達夫; 田中梨絵; 山田光成; 有住忠晃; 田北雅弘; 北井 聡; 矢田典久; 萩原 智; 南 康範; 上嶋一臣; 西田直生志; 工藤正俊; 隈部 力; 中島 収
    第19回肝血流動態イメージ研究会 2013年01月 口頭発表（一般） 東京ビッグサイト「国際会議場」, 東京
  • ソラフェニブ治療におけるJNK活性の重要性-CD133との関連も含めて-  [招待講演]
    萩原 智
    第20回浜名湖シンポジウム 2012年12月 口頭発表（招待・特別） アクトシティ浜松コングレスセンター, 静岡
  • The retrospective study of novel anticancer agent, miriplatin in TACE and TAI for unresectable hepatocellular carcinoma in Japan.  [通常講演]
    永井 知行; 上嶋 一臣; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 西田 直生志; 工藤 正俊
    Asian Pacific Digestive Week (APDW) 2012 2012年12月 ポスター発表 Bangkok, Thailand Asian Pacific Digestive Week (APDW) 2012
  • 肝細胞癌に対するラジオ波焼灼療法の治療効果判定における造影超音波検査の有用性の検討～造影CTとの比較～  [通常講演]
    井上 達夫; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第20回日本消化器関連学会週間JDDW2012 2012年10月 神戸国際展示場, 兵庫 第20回日本消化器関連学会週間JDDW2012
  • 肝嚢胞に対するオレイン酸モノエタノールアミン注入療法の検討  [通常講演]
    田北 雅弘; 井上 達夫; 有住 忠晃; 早石 宗右; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第20回日本消化器関連学会週間JDDW2012 2012年10月 神戸国際展示場, 兵庫 第20回日本消化器関連学会週間JDDW2012
  • 転移性肝癌に対する肝動脈塞栓術とラジオ波焼灼術の併用療法の有用性  [通常講演]
    南 康範; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第48回日本肝癌研究会 2012年07月 石川県立音楽堂, ANAクラウンプラザホテル金沢, 石川 第48回日本肝癌研究会
  • 進行肝細胞癌に対するソラフェニブ投与における投与後の腫瘍濃染の低下の有無と生存期間の検討  [通常講演]
    有住 忠晃; 上嶋 一臣; 早石 宗右; 田北 雅弘; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊
    第48回日本肝癌研究会 2012年07月 石川県立音楽堂, ANAクラウンプラザホテル金沢, 石川 第48回日本肝癌研究会
  • 肝細胞癌に対するラジオ波焼灼療法の治療効果判定における造影超音波検査の有用性～造影CTとの比較～  [通常講演]
    井上 達夫; 有住 忠晃; 早石 宗右; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第48回日本肝癌研究会 2012年07月 石川県立音楽堂, ANAクラウンプラザホテル金沢, 石川 第48回日本肝癌研究会
  • 化学療法施行後にB型肝炎ウイルス再活性化を認めた2例  [招待講演]
    萩原 智
    第14回関西B型肝炎研究会 2012年06月 口頭発表（招待・特別） ガーデンシティクラブ大阪, 大阪
  • IL28BとPEG-IFN/RBV併用療法をうけたHCVジェノタイプ1型高ウイルス量患者の効果との関連について  [通常講演]
    田北 雅弘; 萩原 智; 有住 忠晃; 早石 宗右; 上田 泰輔; 北井 聡; 矢田 典久; 井上 達夫; 南 康範; 上嶋 一臣; 櫻井 俊治; 西田 直生志; 工藤 正俊; 鄭 浩柄
    第48回日本肝臓学会総会 2012年06月 JR金沢駅前もてなしドーム, 金沢 第48回日本肝臓学会総会
  • Drug freeを目指したエンテカビルとPEG-IFNα2b 48週併用療法の効果について. ワークショップ22「B型慢性肝炎に対する抗ウイルス療法の継続と終了をめぐって」  [通常講演]
    萩原 智; 工藤 正俊; 大﨑 往夫
    第48回日本肝臓学会総会 2012年06月 ポルテ金沢, 金沢 第48回日本肝臓学会総会
  • 当院における肝細胞癌分子標的治療の現状. パネルディスカッション「ソラフェニブ治療の実践－多数症例の使用経験を踏まえた治療の実践と問題点の解決を示す―」  [通常講演]
    上嶋 一臣; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊
    第6回日本肝がん分子標的治療研究会 2012年06月 ザ・プリンス箱根, 神奈川 第6回日本肝がん分子標的治療研究会
  • Usefulness of contrast-enhanced ultrasonography to evaluate a post treatment effect of radiofrequentry ablation about hepatocellular carcinoma: comparison with contrast-enhanced CT  [通常講演]
    井上 達夫; 有住 忠晃; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 櫻井 俊治; 上嶋 一臣; 西田 直生志; 工藤 正俊
    Digestive Disease Week(DDW) 2012 2012年05月 San Diego, USA Digestive Disease Week(DDW) 2012
  • The gross classification of hepatocellular carcinoma: usefulness of contrast-enhanced sonography using perfluorocarbon microbubbles (sonazoid)  [通常講演]
    南 康範; 畑中 絹世; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊
    Digestive Disease Week(DDW) 2012 2012年05月 San Diego, USA Digestive Disease Week(DDW) 2012
  • Activation of JNK in the Non-cancerous liver tissue predicts a high risk of recurrence after hepatic resection for hepatocellular carcinoma  [通常講演]
    櫻井 俊治; 萩原 智; 井上 達夫; 上嶋 一臣; 松井 繁長; 西田 直生志; 樫田 博史; 工藤 正俊
    Digestive Disease Week(DDW) 2012 2012年05月 San Diego, USA Digestive Disease Week(DDW) 2012
  • Novel association between global DNA hypomethylation and chromosomal instability phenotype in human hepatocellular carcinoma  [通常講演]
    西田 直生志; 工藤 正俊; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 櫻井 俊治
    Digestive Disease Week(DDW) 2012 2012年05月 San Diego, USA Digestive Disease Week(DDW) 2012
  • 経皮的ラジオ波焼灼術後の後出血予防における穿刺経路焼灼の有効性の検討.  [通常講演]
    早石 宗右; 南 康範; 足立 哲平; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 鄭 浩柄
    第98回日本消化器病学会総会 2012年04月 京王プラザ 第98回日本消化器病学会総会
  • 非上皮性肝悪性腫瘍の3例.  [通常講演]
    足立 哲平; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第98回日本消化器病学会総会 2012年04月 京王プラザ 第98回日本消化器病学会総会
  • 超音波エラストグラフィーによる非アルコール性脂肪性肝炎診断. シンポジウム8「臓器線維化（肝・膵を中心）研究・診療の最前線」  [通常講演]
    矢田 典久; 萩原 智; 工藤 正俊
    第98回日本消化器病学会総会 2012年04月 京王プラザ 第98回日本消化器病学会総会
  • Prognostic impact of EMT-related genes on post-operative prognosis in hepatocellular carcinoma.  [通常講演]
    永井 知行; 荒尾 徳三; 松本 和子; 藤田 至彦; 林 秀敏; 木村 英晴; 萩原 智; 櫻井 俊治; 上嶋 一臣; 土師 誠二; 工藤 正俊; 西尾 和人
    AACR 103rd Annual Meeting 2011 2012年03月 Chicago, USA AACR 103rd Annual Meeting 2011
  • 座長「Freshman Session 肝胆膵」  [招待講演]
    萩原 智
    日本消化器病学会近畿支部第96回例会 2012年01月 その他 大阪国際交流センター, 大阪
  • 「肝炎の診断と治療」  [招待講演]
    萩原 智
    消化器病市民公開講座 最新の消化器の病気のお話 2012年01月 口頭発表（招待・特別） 泉佐野泉の森ホール, 大阪
  • 進行肝細胞癌患者に対する分子標的薬（ソラフェニブ）投与における治療効果判定基準の比較.  [通常講演]
    有住 忠晃; 上嶋 一臣; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 櫻井 俊治; 西田 直生志; 工藤 正俊; 竹田 治彦; 大﨑
    第18回肝血流動態イメージ研究会 2012年01月 神戸ポートピアホテル, 兵庫 第18回肝血流動態イメージ研究会
  • 超音波エラストグラフィーによる非アルコール性脂肪性肝炎診断.  [通常講演]
    矢田 典久; 萩原 智; 工藤 正俊
    第18回肝血流動態イメージ研究会 2012年01月 神戸ポートピアホテル, 兵庫 第18回肝血流動態イメージ研究会
  • 造影エコーによる肝癌肉眼分類の有用性について.  [通常講演]
    早石 宗右; 南 康範; 畑中 絹世; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第18回肝血流動態イメージ研究会 2012年01月 神戸ポートピアホテル, 兵庫 第18回肝血流動態イメージ研究会
  • Interventional radiologyにおける新しい支援画像「FlightPlan」の初期臨床経験.  [通常講演]
    南 康範; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 柳生 行伸; 村上 卓道
    第18回肝血流動態イメージ研究会 2012年01月 神戸ポートピアホテル, 兵庫 第18回肝血流動態イメージ研究会
  • 造影エコーによる肝癌肉眼分類の有用性について.  [通常講演]
    早石 宗右; 南 康範; 畑中 絹世; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 西田 直生志; 工藤 正俊
    日本消化器病学会近畿支部第96回例会 2012年01月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第96回例会
  • 超音波エラストグラフィーは、肝生検の代替になりうるか.  [通常講演]
    矢田 典久; 萩原 智; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 井上 達夫; 南 康範; 上嶋 一臣; 西田 直生志; 工藤 正俊
    第53回大阪肝穿刺生検治療研究会 2011年11月 ホテルグランヴィア大阪, 大阪 第53回大阪肝穿刺生検治療研究会
  • Assessment of hepatobiliary phase Gd-EOB-DTPA-enhanced MRI for HCC and dysplastic nodules and comparison of detection ability versus MDCT.  [通常講演]
    井上 達夫; 工藤 正俊; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 岡田 真広; 兵頭 朋子; 村上 卓道
    The 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) 2011年11月 San Francisco, USA The 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
  • 体外式超音波穿刺用コンベックスプローブEUP-B715の使用経験.  [通常講演]
    矢田 典久; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    日本超音波医学会第38回関西地方会学術集会 2011年11月 大阪国際会議場, 大阪 日本超音波医学会第38回関西地方会学術集会
  • 肝エラストグラフィ -各モダリティ―における測定原理と結果の解釈-. ワークショップ「組織弾性イメージング」  [通常講演]
    矢田 典久; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    日本超音波医学会第38回関西地方会学術集会 2011年11月 大阪国際会議場, 大阪 日本超音波医学会第38回関西地方会学術集会
  • 肝癌に対するラジオ波焼灼療法の治療効果判定 造影USと造影CTの比較検討. パネルディスカッション「造影超音波」  [通常講演]
    井上 達夫; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    日本超音波医学会第38回関西地方会学術集会 2011年11月 大阪国際会議場, 大阪 日本超音波医学会第38回関西地方会学術集会
  • Phase I study of Sorafenib in combination with low-dose cisplatin and fluorouracil intra-arterial infusion chemotherapy.  [通常講演]
    上嶋 一臣; 工藤 正俊; 鄭 浩柄; 萩原 智; 井上 達夫; 矢田 典久; 南 康範; 櫻井 俊治; 田中 正俊; 熊田 卓
    The 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) 2011年11月 San Francisco, USA The 62nd Annual Meeting of the American Association for the Study of Liver Diseases (AASLD)
  • 肝血管肉腫の2例.  [通常講演]
    有住 忠晃; 萩原 智; 大本 俊介; 早石 宗右; 上田 泰輔; 田北 雅弘; 北井 聡; 南 康範; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第19回日本消化器関連学会週間JDDW 2011（第15回日本肝臓学会大会） 2011年10月 福岡国際会議場, 福岡 第19回日本消化器関連学会週間JDDW 2011（第15回日本肝臓学会大会）
  • Impact of TJP-1 and TWIST expression on post-operative prognosis in hepatocellular carcinoma.  [通常講演]
    永井 知行; 荒尾 徳三; 松本 和子; 工藤 可苗; 木村 英晴; 藤田 至彦; 萩原 智; 櫻井 俊治; 上嶋 一臣; 土師 誠二; 工藤 正俊; 西尾 和人
    70th Annual Meeting of the Japanese Cancer Association 2011年10月 Nagoya, Japan 70th Annual Meeting of the Japanese Cancer Association
  • Phase I study of Sorafenib in combination with low-dose cisplatin and flurouracil intra-arterilal infusion chemotherapy.  [通常講演]
    上嶋 一臣; 工藤 正俊; 櫻井 俊治; 鄭 浩柄; 南 康範; 萩原 智; 井上 達夫; 矢田 典久; 北井 聡; 有住 忠晃; 早石 宗右; 田中 正俊; 熊田 卓
    International Liver Cancer Association Fifth Annual Conference (ILCA) 2011 2011年09月 Hong Kong, China International Liver Cancer Association Fifth Annual Conference (ILCA) 2011
  • Interventional radiologyにおける新しい支援画像「FlightPlan」の初期臨床経験.  [通常講演]
    南 康範; 足立 哲平; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 村上 卓道; 柳生 行伸
    日本消化器病学会近畿支部第95回例会 2011年08月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第95回例会
  • 経皮的ラジオ波焼灼術後の後出血予防における穿刺経路焼灼の有効性の検討.  [通常講演]
    早石 宗右; 南 康範; 足立 哲平; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 鄭 浩柄
    日本消化器病学会近畿支部第95回例会 2011年08月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第95回例会
  • 肝細胞癌に対するラジオ波焼灼療法の治療効果判定～造影超音波検査と造影CTの比較検討～.  [通常講演]
    井上 達夫; 畑中 絹世; 有住 忠晃; 早石 宗右; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    日本消化器病学会近畿支部第95回例会 2011年08月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第95回例会
  • 術前診断が困難であった肝血管肉腫の一例.  [通常講演]
    足立 哲平; 早石 宗右; 有住 忠晃; 田北 雅弘; 北井 聡; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊; 土師 誠二; 武本 昌子; 鄭 浩柄
    日本消化器病学会近畿支部第95回例会 2011年08月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第95回例会
  • 肝細胞癌治療におけるJNK活性の重要性-ソラフェニブ治療効果との関連も含めて-. シンポジウム「肝細胞癌に対する分子標的治療の基礎と臨床」  [通常講演]
    萩原 智; 櫻井 俊治; 工藤 正俊
    第47回日本肝癌研究会 2011年07月 シンポジウム・ワークショップパネル（公募） 静岡県コンベンションアーツセンター, 静岡 第47回日本肝癌研究会
  • ソラフェニブによりCRとなった進行肝細胞癌2症例の臨床的特徴について. ワークショップ「ソラフェニブによりRECISTにてCR例の集積から特徴を掴む」  [通常講演]
    上嶋 一臣; 有住 忠晃; 早石 宗右; 北井 聡; 矢田 典久; 萩原 智; 井上 達夫; 南 康範; 櫻井 俊治; 工藤 正俊
    第47回日本肝癌研究会 2011年07月 静岡県コンベンションアーツセンター, 静岡 第47回日本肝癌研究会
  • 肝細胞癌治療におけるJNK活性の重要性-ソラフェニブ治療効果との関連も含めて-.  [通常講演]
    萩原 智; 櫻井 俊治; 工藤 正俊
    第47回日本肝臓学会総会 シンポジウム「テーラーメイド医療時代へ向けた肝癌治療」 2011年06月 ホテルグランパシフィック LE DAIBA, 東京 第47回日本肝臓学会総会 シンポジウム「テーラーメイド医療時代へ向けた肝癌治療」
  • B型慢性肝炎に対するPRG-IFNa2bとエンテカビル48週併用療法の有効性について.  [通常講演]
    萩原 智; 峯 宏昌; 有住 忠晃; 早石 宗右; 上田 泰輔; 田北 雅弘; 畑中 絹世; 北井 聡; 矢田 典久; 井上 達夫; 鄭 浩柄; 櫻井 俊治; 上嶋 一臣; 工藤 正俊; 犬塚 義; 大﨑
    第97回日本消化器病学会総会 2011年05月 京王プラザホテル, 東京 第97回日本消化器病学会総会
  • Expression levels of EMT-related genes in hepatocellular carcinoma.  [通常講演]
    永井 知行; 荒尾 徳三; 松本 和子; 工藤 可苗; 萩原 智; 櫻井 俊治; 上嶋 一臣; 土師 誠二; 工藤 正俊; 西尾 和人
    AACR 102th Annual Meeting 2011 2011年04月 Florida, USA AACR 102th Annual Meeting 2011
  • 講演「肝炎の診断と治療」  [招待講演]
    萩原 智
    第44回日本消化器病学会近畿支部市民公開講座 最新の消化器の病気のお話 2010年11月 口頭発表（招待・特別） 藤井寺パープルホール, 大阪
  • The usefulness of the post-vascular phase of contrast-enhanced ultrasonography with Sonazoid in the evaluation of gross type of hepatocellular carcinoma.  [通常講演]
    畑中 絹世; 鄭 浩柄; 工藤 正俊; 北井 聡; 井上 達夫; 矢田 典久; 萩原 智; 上嶋 一臣
    American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2010 2010年10月 ポスター発表 Massachusetts, USA American Association for the Study of Liver Diseases (AASLD) The Liver Meeting 2010
  • 線維化進行C型肝炎患者における脾摘後のインターフェロン導入における問題点-好中球数の変化について-.  [通常講演]
    鄭 浩柄; 上田 泰輔; 早石 宗右; 田北 雅弘; 北井 聡; 畑中 絹世; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊
    第18回日本消化器関連学会週間（第14回日本肝臓学会大会） 2010年10月 パシフィコ横浜, 神奈川 第18回日本消化器関連学会週間（第14回日本肝臓学会大会）
  • 造影エコーによる肝細胞癌の診断能、Gd-EOB-MRI、Dynamic CTとの比較検討.  [通常講演]
    井上 達夫; 畑中 絹世; 早石 宗右; 上田 泰輔; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第18回日本消化器関連学会週間（第14回日本肝臓学会大会） 2010年10月 パシフィコ横浜, 神奈川 第18回日本消化器関連学会週間（第14回日本肝臓学会大会）
  • 非閉塞性腸管虚血を発症した悪性リンパ腫の一例.  [通常講演]
    宮田 剛; 井上 達夫; 有住 忠晃; 早石 宗右; 上田 泰輔; 辰巳 千栄; 田北 雅弘; 北井 聡; 石川 恵美; 矢田 典久; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第18回日本消化器関連学会週間（第52回日本消化器病学会）, 2010年10月 パシフィコ横浜, 神奈川 第18回日本消化器関連学会週間（第52回日本消化器病学会）,
  • Can Gd-EOB-DTPA-enhanced MRI discriminate between dysplastic nodules and early-to- well-differentiated HCC?  [通常講演]
    井上 達夫; 工藤 正俊; 早石 宗右; 上田 泰輔; 田北 雅弘; 北井 聡; 畑中 絹世; 矢田 典久; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣; 岡田 真広; 熊野 正士; 村上 卓道; 坂元 亨宇
    18th United European Gastroenterology Week (UEGW) 2010 2010年10月 Barcelona, Spain 18th United European Gastroenterology Week (UEGW) 2010
  • Usefulness of hepatocyte phase imaging of Gd-EOB-DTPA-MRI in detecting borderline lesions which are difficult to detect other imaging modalities.  [通常講演]
    井上 達夫; 工藤 正俊; 早石 宗右; 上田 泰輔; 田北 雅弘; 北井 聡; 矢田 典久; 萩原 智; 鄭 浩柄; 上嶋 一臣
    18th United European Gastroenterology Week (UEGW) 2010 2010年10月 Barcelona, Spain 18th United European Gastroenterology Week (UEGW) 2010
  • 発熱、及び軽度の肝機能障害に発症した肝サルコイドーシスの1例.  [通常講演]
    有住 忠晃; 萩原 智; 早石 宗右; 田北 雅弘; 上田 泰輔; 北井 聡; 畑中 絹世; 矢田 典久; 井上 達夫; 鄭 浩柄; 上嶋 一臣; 樫田 博史; 工藤 正俊
    日本消化器病学会近畿支部第93回例会 2010年09月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第93回例会
  • 発癌分子機序に基づく新しい肝がん治療薬の可能性.  [通常講演]
    櫻井 俊治; 萩原 智; 矢田 典久; 井上 達夫; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第2回日本肝がん分子標的治療研究会 2010年06月 大手町サンケイプラザ, 東京 第2回日本肝がん分子標的治療研究会
  • B型肝炎の最新治療  [招待講演]
    萩原 智
    南大阪肝臓病セミナー 2010年03月 口頭発表（招待・特別） スイスホテル南海大阪, 大阪
  • 遊走脾の捻転により脾梗塞をきたした一例.  [通常講演]
    宮田 剛; 鄭 浩柄; 有住 忠晃; 早石 宗右; 田北 雅弘; 上田 泰輔; 辰巳 千栄; 北井 聡; 畑中 絹世; 石川 恵美; 矢田 典久; 井上 達夫; 萩原 智; 上嶋 一臣; 工藤 正俊; 土師 誠二; 山崎 満夫
    日本消化器病学会近畿支部第92回例会 2010年02月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第92回例会
  • 肝機能障害を認めたエルシニア腸炎の一例.  [通常講演]
    足立 哲平; 萩原 智; 有住 忠晃; 峯 宏昌; 宮田 剛; 早石 宗右; 辰巳 千栄; 上田 泰輔; 田北 雅弘; 畑中 絹世; 北井 聡; 石川 恵美; 矢田 典久; 井上 達夫; 鄭 浩柄; 上嶋 一臣; 工藤 正俊; 梅原 泰
    日本消化器病学会近畿支部第92回例会 2010年02月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第92回例会
  • C型慢性肝炎SVR後に悪性リンパ腫を発症した一例.  [通常講演]
    高場 雄久; 宮田 剛; 峯 宏昌; 鎌田 研; 有住 忠晃; 田北 雅弘; 早石 宗右; 永井 知行; 上田 泰輔; 辰巳 千栄; 北井 聡; 畑中 絹世; 矢田 典久; 井上 達夫; 石川 恵美; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    日本消化器病学会近畿支部第92回例会 2010年02月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第92回例会
  • 慢性C型肝炎に対してPEG-IFN+Ribavirin併用療法中にITPを発症した1例.  [通常講演]
    有住 忠晃; 石川 恵美; 宮田 剛; 峯 宏昌; 早石 宗右; 田北 雅弘; 上田 泰輔; 辰巳 千栄; 北井 聡; 畑中 絹世; 矢田 典久; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊; 金井 良高
    日本消化器病学会近畿支部第92回例会 2010年02月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第92回例会
  • 癌幹細胞のマーカーであるCD133は進行肝細胞癌に対するS1+PEG-IFNalpha2b治療における効果予測因子である. シンポジウム「消化器癌化学療法の適応と限界-肝胆膵領域-」  [通常講演]
    萩原 智; 上嶋 一臣; 鄭 浩柄; 工藤 正俊
    日本消化器病学会近畿支部第92回例会 2010年02月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第92回例会
  • The cancer stem cell marker CD133 is a predictor of the effectiveness of S1+PEG-IFN α-2b therapy against advanced hepatocellular carcinoma  [通常講演]
    萩原 智; 工藤 正俊; 上嶋 一臣; 鄭 浩柄; 井上 達夫; 矢田 典久; 北井 聡; 田北 雅弘; 永井 知行; 土師 誠二; 木村 雅友; Ah-Mee Park; 宗像 浩
    The 60th Annual Meeting of the American Association for the study of liver diseases (AASLD) 2009年11月 Boston, USA The 60th Annual Meeting of the American Association for the study of liver diseases (AASLD)
  • Gd-EOB MRIによる肝細胞癌の診断能～造影超音波検査, Dynamic CTとの比較検討.  [通常講演]
    井上 達夫; 畑中 絹世; 早石 宗右; 永井 知行; 田北 雅弘; 上田 泰輔; 高橋 俊介; 北井 聡; 石川 恵美; 矢田 典久; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第45回日本肝臓学会総会 2009年06月 神戸ポートピアホテル, 兵庫 第45回日本肝臓学会総会
  • 特異な経緯をたどったアルコール性肝硬変に合併した肝細胞癌の一例.  [通常講演]
    早石 宗右; 鄭 浩柄; 辰巳 千栄; 永井 知行; 上田 泰輔; 高橋 俊介; 北井 聡; 石川 恵美; 矢田 典久; 井上 達夫; 萩原 智; 南 康範; 上嶋 一臣; 工藤 正俊
    第45回日本肝臓学会総会 2009年06月 神戸ポートピアホテル, 兵庫 第45回日本肝臓学会総会
  • ステロイド未使用の潰瘍性大腸炎に対するサイクロスポリン持続静注と経口タクロリムスの比較検討.  [通常講演]
    梅原 泰; 高山 政樹; 川崎 正憲; 朝隈 豊; 岡田 無文; 松井 繁長; 早石 宗右; 野田 佳寿; 坂本 洋城; 井上 達夫; 石川 恵美; 矢田 典久; 萩原 智; 末冨 洋一郎; 南 康範; 鄭 浩柄; 上嶋 一臣; 北野 雅之; 汐見 幹夫; 工藤 正俊
    第82回日本消化器内視鏡学会近畿地方会 2009年03月 大阪国際交流センター, 大阪 第82回日本消化器内視鏡学会近畿地方会
  • Value of liver parenchymal phase imaging of contrast-enhanced ultrasonography to diagnose the premalignant/borderline lesions and overt HCC  [通常講演]
    Inoue T; Kudo M; Hatanaka K; Takahashi S; Kitai S; Ueda D; Hagiwara S; Minami Y; Chung H; Ueshima K
    16th United Europian Gastroenterology Week(UEGW) 2008年10月 ポスター発表 Vienna, Austria
  • 当院でのステロイド未使用の潰瘍性大腸炎に対する白血球除去療法の治療成績.  [通常講演]
    梅原 泰; 川崎 正憲; 朝隈 豊; 岡田 無文; 市川 勉; 松井 繁長; 今井 元; 野田 佳寿; 坂本 洋城; 石川 恵美; 井上 達夫; 萩原 智; 末冨 洋一郎; 南 康範; 鄭 浩柄; 上嶋 一臣; 北野 雅之; 汐見 幹夫; 工藤 正俊
    第76回日本消化器内視鏡学会総会 2008年10月 グランドプリンスホテル新高輪, 東京 第76回日本消化器内視鏡学会総会
  • Qualitative and quantitative analysis of liver-parenchymal phase contrast-enhanced US with Sonazoid in detecting HCC; Comparison with SPIO-MRI.  [通常講演]
    井上 達夫; 工藤 正俊; 畑中絹世; 前川 清; 高橋 俊介; 北井 聡; 上田 泰輔; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣
    16th United Europian Gastroenterology Week(UEGW) 2008年10月 Vienna, Austria 16th United Europian Gastroenterology Week(UEGW)
  • ソナゾイド造影超音波検査におけるpost vascular phase imagingとSPIO-MRIとの比較  [通常講演]
    井上達夫; 畑中絹世; 上田泰輔; 辰巳千栄; 北井 聡; 高橋俊介; 石川恵美; 萩原 智; 南 康範; 鄭 浩柄; 上嶋一臣; 工藤正俊; 横川美加; 前野知子; 市島真由美; 前川 清
    第12回日本肝臓学会大会 2008年10月 口頭発表（一般） グランドプリンスホテル新高輪, 東京
  • C型慢性肝炎に対するインターフェロン療法著効後に発症した肝細胞癌破裂の1例  [通常講演]
    峯 宏昌; 萩原 智; 早石 宗右; 辰巳 千栄; 上田 泰輔; 高橋 俊介; 北井 聡; 畑中 絹世; 石川 恵美; 井上 達夫; 南 康範; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    日本消化器病学会近畿支部第89回例会 2008年09月 大阪国際交流センター, 大阪 日本消化器病学会近畿支部第89回例会
  • 進行肝細胞癌に対するS-1, ペグインターフェロン併用療法  [通常講演]
    上嶋一臣; 早石宗右; 辰巳千栄; 上田泰輔; 北井 聡; 高橋俊介; 石川恵美; 井上達夫; 萩原 智; 南 康範; 鄭 浩柄; 工藤正俊
    第44回日本肝臓学会総会 2008年06月 口頭発表（一般） 愛媛県県民文化会館, 愛媛
  • 「基礎的検討: PEG-IFN/5FU併用によるアポトーシス誘導機序」, ランチョンセミナー「肝疾患診療におけるPEG-IFN介入治療の役割」  [招待講演]
    萩原 智
    第44回日本肝癌研究会 2008年05月 口頭発表（招待・特別） 大阪国際会議場, 大阪
  • Defect Re-inection imagingの有用性について.  [通常講演]
    畑中 絹世; 南 康範; 北井 聡; 辰巳 千栄; 高橋 俊介; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    日本超音波医学会第81回学術集会 2008年05月 神戸国際会議場, 兵庫 日本超音波医学会第81回学術集会
  • 非B非C肝癌の臨床的特徴: B型関連肝癌・C型関連肝癌との比較.  [通常講演]
    畑中 絹世; 南 康範; 辰巳 千栄; 上田 泰輔; 北井 聡; 高橋 俊介; 石川 恵美; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第44回日本肝癌研究会 2008年05月 大阪国際会議場, 大阪. 第44回日本肝癌研究会
  • Defect Re-injection Testの有用性とRFA治療支援.  [通常講演]
    畑中 絹世; 南 康範; 辰巳 千栄; 上田 泰輔; 北井 聡; 高橋 俊介; 石川 恵美; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    シンポジウム「RFA-STATE of ARTS」, 第44回日本肝癌研究会 2008年05月 大阪. シンポジウム「RFA-STATE of ARTS」, 第44回日本肝癌研究会
  • Defect Re-injection Testの有用性について.  [通常講演]
    畑中 絹世; 北井 聡; 上田 泰輔; 辰巳 千栄; 井上 達夫; 萩原 智; 南 康範; 鄭 浩柄; 上嶋 一臣; 前川 清; 工藤 正俊
    第94回日本消化器病学会総会, 2008年05月 福岡. 第94回日本消化器病学会総会,
  • Sonazoidを用いた造影超音波ガイド下ラジオ波焼灼術の有用性.  [通常講演]
    南 康範; 今井 元; 上田 泰輔; 辰巳 千栄; 北井 聡; 高橋 俊介; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第21回日本腹部造影エコー・ドプラ診断研究会 2008年04月 秋葉原コンベンションホール, 東京. 第21回日本腹部造影エコー・ドプラ診断研究会
  • ステロイド、免疫調節剤使用歴のないサイトメガロウイルス感染を合併した潰瘍性大腸炎の2例  [通常講演]
    梅原 泰; 川崎正憲; 朝隈 豊; 岡田無文; 市川 勉; 松井繁長; 今井 元; 野田佳寿; 坂本洋城; 井上達夫; 石川恵美; 萩原 智; 末冨洋一郎; 南 康範; 鄭 浩柄; 上嶋一臣; 北野雅之; 汐見幹夫; 工藤正俊
    第80回日本消化器内視鏡学会近畿地方会 2008年03月 口頭発表（一般） 大阪国際交流センター, 大阪
  • 高齢発症クローン病に対するTOP-DOWN療法で経時的に粘膜治癒が追えた1例  [通常講演]
    有住忠晃; 梅原 泰; 川崎正憲; 朝隈 豊; 岡田無文; 市川 勉; 松井繁長; 今井 元; 野田佳寿; 坂本洋城; 石川恵美; 井上達夫; 萩原 智; 末冨洋一郎; 南 康範; 鄭 浩柄; 上嶋一臣; 北野雅之; 汐見幹夫; 工藤正俊
    第88回日本消化器病学会近畿支部例会 2008年02月 口頭発表（一般） 大阪国際交流センター, 大阪
  • Defect Re-injection imagingの有用性について.  [通常講演]
    畑中 絹世; 南 康範; 上田 泰輔; 辰巳 千栄; 北井 聡; 高橋 俊介; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第88回日本消化器病学会近畿支部例会 2008年02月 大阪国際交流センター, 大阪. 第88回日本消化器病学会近畿支部例会
  • Sonazoidを用いた造影超音波ガイド下ラジオ波焼灼術の有用性.  [通常講演]
    南 康範; 今井 元; 上田 泰輔; 辰巳 千栄; 北井 聡; 高橋 俊介; 井上 達夫; 萩原 智; 鄭 浩柄; 上嶋 一臣; 工藤 正俊
    第88回日本消化器病学会近畿支部例会 2008年02月 大阪国際交流センター, 大阪 第88回日本消化器病学会近畿支部例会
  • ペグインターフェロンがS-1の抗腫瘍効果を増強したと考えられたHCC肺転移の1例.  [通常講演]
    上嶋 一臣; 今井 元; 辰巳 千栄; 上田 泰輔; 川崎 正憲; 北井 聡; 高橋 俊介; 石川 恵美; 井上 達夫; 萩原 智; 南 康範; 鄭 浩柄; 工藤 正俊
    第45回 大阪肝穿刺生検治療研究会 2007年12月 大阪 第45回 大阪肝穿刺生検治療研究会
  • クローン病に対するインフリキシマブ投与の有効性の検討  [通常講演]
    梅原 泰; 工藤正俊; 仲谷達也; 福田信宏; 永島美樹; 石川恵美; 坂本洋城; 井上達夫; 坂口康浩; 萩原 智; 南 康範; 末冨洋一郎; 小牧孝充; 鄭 浩柄; 上嶋一臣; 松井繁長; 福永豊和; 北野雅之; 汐見幹夫
    第49回日本消化器病学会大会 2007年10月 口頭発表（一般） ポートピアホテル, 神戸
  • B型肝炎ウィルス感染における発癌リスク因子の検討.  [通常講演]
    萩原 智; 工藤 正俊
    第2回大阪肝臓ミーティング-スミフェロン発売20周年記念- 2007年09月 大阪 第2回大阪肝臓ミーティング-スミフェロン発売20周年記念-
  • B型慢性肝炎ウィルス感染における発癌リスク因子の検討  [通常講演]
    萩原 智; 高橋俊介; 北井 聡; 石川恵美; 井上達夫; 南 康範; 鄭 浩柄; 上嶋一臣; 福永豊和; 仲谷達也; 工藤正俊
    第18回南大阪肝疾患研究会 2007年07月 口頭発表（一般） リーガロイヤルホテル堺, 大阪
  • 診断に苦慮し急速な経過をたどった肉腫様肝癌の一例  [通常講演]
    井上達夫; 辰巳千栄; 北井 聡; 高橋俊介; 畑中絹世; 萩原 智; 南 康範; 鄭 浩柄; 上嶋一臣; 福永豊和; 工藤正俊
    第43回日本肝癌研究会 2007年06月 口頭発表（一般） 東京ドームホテル, 東京
  • Regulatory failure of serum prohepcidin levels in patients with hepatitis C  [通常講演]
    Nagashima M; Kudo M; Chung H; Ishikawa E; Hagiwara S; Nakatani T
    DDW (Digestive Disease Week) and the 108th Annual Meeting of the AGA 2007年05月 ポスター発表 Washington, DC
  • B型肝炎ウィルス感染における発癌リスク因子の検討  [通常講演]
    萩原 智; 工藤正俊; 仲谷達也; 鄭 浩柄; 大崎往夫; 山下幸孝; 梶村幸三
    第93回日本消化器病学会総会 2007年04月 口頭発表（一般） 青森市文化会館, 青森
  • Regulatory failure of serum prohepcidin levels in patients with hepatitis C  [通常講演]
    Nagashima M; Kudo M; Chung H; Ishikawa E; Hagiwara S; Nakatani T
    17th APASL Conference 2007年03月 ポスター発表 Kyoto
  • C型肝硬変に伴う肝内びまん性動門脈シャントに対して肝動脈塞栓術およびバルン閉塞下逆行性シャント閉塞術が奏功した一例  [通常講演]
    前川昌平; 鄭 浩柄; 辰巳千栄; 北井 聡; 高橋俊介; 萩原 智; 井上達夫; 南 康範; 上嶋一臣; 福永豊和; 工藤正俊; 堀 信一
    第86回日本消化器病学会近畿支部例会 2007年02月 口頭発表（一般） 京都テルサ, 京都
  • B型肝炎ウイルス感染における発癌リスク因子の検討  [通常講演]
    萩原 智; 仲谷達也; 南 康範; 鄭 浩柄; 上嶋一臣; 福永豊和; 工藤正俊
    第85回日本消化器病学会近畿支部例会 2006年09月 口頭発表（一般） 大阪国際交流センター, 大阪
  • ペグインターフェロン（PEG-IFN）と5-FUの併用によるp53を介する肝細胞癌抑制効果  [通常講演]
    仲谷達也; 福永豊和; 上嶋一臣; 鄭 浩柄; 南 康範; 井上達夫; 坂口康浩; 萩原 智; 工藤正俊
    第47回京都肝疾患懇話会 2006年07月 口頭発表（一般） 京都ホテルオークラ, 京都
  • von Gierke disease（糖尿病I型）に肝細胞癌を合併した一症例  [通常講演]
    鄭 浩柄; 高橋俊介; 萩原 智; 井上達夫; 坂口康浩; 南 康範; 上嶋一臣; 福永豊和; 工藤正俊; 中居拓也
    第42回日本肝癌研究会 2006年07月 口頭発表（一般） 東京ドームホテル, 東京
  • Carcinogenic risk factors in hepatitis B rivus infection  [通常講演]
    Hagiwara S; Nakatani T; Minami Y; Chung H; Ueshima K; Fukunaga T; Kudo M; Munakata H
    41th Annual Meeting of the European Association for the Study of the Liver (EASL) 2006年04月 ポスター発表 Vienna, Austria
  • Comparison of staging systems for hepatocellular carcinoma in Japanese cohort  [通常講演]
    Chung H; Takahashi S; Minami Y; Inoue T; Sakaguchi Y; Hagiwara S; Fukunaga T; Ueshima K; Kudo M
    41th Annual Meeting of the European Association for the Study of the Liver (EASL) 2006年04月 ポスター発表 Vienna, Austria
  • 肝癌の経皮的ラジオ波焼灼術におけるReal-time Virtual Sonographyの有用性について  [通常講演]
    南 康範; 工藤正俊; 鄭 浩柄; 福永豊和; 上嶋一臣; 萩原 智; 坂口康浩; 高橋俊介; 畑中絹代; 井上達夫
    第92回日本消化器病学会総会 2006年04月 口頭発表（一般） リーガロイヤルホテル小倉, 福岡
  • B型肝炎ウイルスキャリアにおけるgenotypeおよびCP/PC変異測定の臨床的意義  [通常講演]
    萩原 智; 工藤正俊
    Bay Area Digestive 2006年03月 口頭発表（一般） 淡路夢舞台, 淡路
  • ポスターセッション「B型肝炎ウイルス（HBV）キャリアにおけるHBV genotype及びCore Promoter (CP)/ Pre core (PC) 変異測定の臨床的意義」  [通常講演]
    萩原 智; 石川恵美; 坂口康浩; 井上達夫; 南 康範; 鄭 浩柄; 上嶋一臣; 福永豊和; 仲谷達也; 工藤正俊
    第13回日本消化器病学会総会（DDW） 2005年10月 ポスター発表 ポートピアホテル, 神戸国際展示場, 神戸国際会議場, 神戸
  • Real-time virtual sonography, an integrated system of computer tomography with ultrasound images: value in radiofrequency ablation guidance  [通常講演]
    Minami Y; Chung H; Inoue T; Hagiwara S; Hatanaka K; Sakaguchi Y; Ueshima K; Fukunaga T; Kudo M
    15th Asian Pacific Association for the Study of the Liver (APASL) 2005年08月 ポスター発表 Bali
  • B型肝炎ウイルスキャリアにおけるgenotype及びcore promoter/pro core変異測定の臨床的意義  [通常講演]
    萩原 智; 石川恵美; 坂口康浩; 井上達夫; 南 康範; 鄭 浩柄; 仲谷達也; 福永豊和; 工藤正俊
    第14回南大阪肝疾患研究会 2005年07月 口頭発表（一般） リーガロイヤルホテル3階「ガーデンコート」, 大阪
  • B型肝炎ウイルスキャリアにおけるgenotype、及びCore Promoter/Pre Core変異測定の臨床的意義  [通常講演]
    萩原 智; 石川恵美; 坂口康浩; 井上達夫; 南 康範; 鄭 浩柄; 仲谷達也; 福永豊和; 工藤正俊
    第7回関西B型肝炎研究会 2005年06月 口頭発表（一般） ガーデンシティクラブ大阪, 大阪
  • 日本肝癌研究会 肝障害度のスコア化による新分類法の提唱. ポスター「肝細胞癌の予後解析1」  [通常講演]
    鄭 浩柄; 井上達夫; 坂口康浩; 萩原 智; 南 康範; 上嶋一臣; 福永豊和; 工藤正俊; 大崎往夫; 春日井博志; 関 寿人; 岡 博子
    第41回日本肝癌研究会 2005年06月 ポスター発表 幕張メッセ国際会議場, 千葉
  • 肝癌の経皮的ラジオ波焼灼術におけるReal-time Virtual Sonographyの有用性について. ビデオセッション「経皮的局所療法(II)」  [通常講演]
    南 康範; 鄭 浩柄; 井上達夫; 坂口康浩; 萩原 智; 畑中絹世; 上嶋一臣; 工藤正俊
    第41回日本肝癌研究会 2005年06月 シンポジウム・ワークショップパネル（公募） 幕張メッセ国際会議場, 千葉
  • 当院における肝細胞癌に対する経皮的ラジオ波治療成績と工夫. パネルディスカッション「より安全で効果的なラジオ波焼灼療法」  [通常講演]
    鄭 浩柄; 井上達夫; 坂口康浩; 萩原 智; 南 康範; 上嶋一臣; 福永豊和; 工藤正俊
    第41回日本肝癌研究会 2005年06月 シンポジウム・ワークショップパネル（公募） 幕張メッセ国際会議場, 千葉
  • 肝細胞癌の分化度診断における造影エコーの有用性  [通常講演]
    井上達夫; 坂口康浩; 萩原 智; 南 康範; 鄭 浩柄; 上嶋一臣; 福永豊和; 前川 清; 工藤正俊
    第78回日本超音波医学会総会 2005年05月 口頭発表（一般） 東京国際フォーラム, 東京
  • 造影エコー法のpostvascular phase imagingとSPIOMRIの比較検討  [通常講演]
    井上達夫; 坂口康浩; 萩原 智; 南 康範; 鄭 浩柄; 上嶋一臣; 福永豊和; 前川 清; 綿井良輔; 粟井和夫; 工藤正俊
    第78回日本超音波医学会総会 2005年05月 口頭発表（一般） 東京国際フォーラム, 東京
  • 当院におけるラジオ波焼灼術の成績と工夫（シンポジウム「安全で確実なラジオ波熱凝固療法施行のために」）  [通常講演]
    鄭 浩柄; 井上達夫; 萩原 智; 南 康範; 上嶋一臣; 福永豊和; 工藤正俊
    第7回関西肝癌局所療法研究会 2005年03月 口頭発表（一般） ホテルグランヴィア大阪, 大阪
  • EUS-FNABが治療方針の決定に有用であった悪性傍神経筋腫の一例  [通常講演]
    坂本洋城; 北野雅之; 末富洋一郎; 井上達夫; 坂口康浩; 梅原 泰; 萩原 智; 福田信宏; 永島美樹; 市川 勉; 畑中絹世; 汐見幹夫; 工藤正俊; 筑後孝章
    第74回日本消化器内視鏡学会近畿地方会 2005年03月 口頭発表（一般） 大阪国際会議場, 大阪
  • 主膵管拡張を契機に診断できたTS1膵癌の一症例  [通常講演]
    坂本洋城; 北野雅之; 末冨洋一郎; 井上達夫; 坂口康浩; 梅原 泰; 萩原 智; 福田信宏; 永島美樹; 市川 勉; 畑中絹世; 汐見幹夫; 工藤正俊; 川辺高史; 中居卓也; 竹山宣典; 筑後孝章
    第74回日本消化器内視鏡学会近畿地方会 2005年03月 口頭発表（一般） 大阪国際会議場, 大阪
  • 肝血管腫が原因と考えられるFocal Sparing 5例の検討  [通常講演]
    井上達夫; 坂口康浩; 萩原 智; 南 康範; 鄭 浩柄; 福永豊和; 前川 清; 工藤正俊
    第11回肝血流動態イメージ研究会 2005年02月 口頭発表（一般） パシフィコ横浜, 横浜
  • 肝細胞癌症例における門脈腫瘍栓出現のrisuk factorについての検討  [通常講演]
    萩原 智; 工藤正俊
    第17回南大阪消化器病懇話会 2004年11月 口頭発表（一般） リーガロイヤルホテル堺, 大阪
  • 肝細胞癌症例における門脈腫瘍栓出現のrisk factorについての検討  [通常講演]
    萩原 智; 工藤正俊
    第8回日本肝臓学会大会（DDW） 2004年10月 口頭発表（一般） 福岡国際会議場, 福岡
  • Evaluation of therapeutic response to gemcitabine in pancreatic cancers: value of contrast-enhanced harmonic ultrasonography  [通常講演]
    Sakamoto H; Kitano M; Suetomi Y; Fukuta N; Inoue T; Sakaguchi Y; Umehara Y; Hagiwara S; Ichikawa T; Hatanaka K; Kudo M
    12th United European Gastroenterology Week (UEGW) 2004年09月 ポスター発表 Prague
  • 肝細胞癌再発抑制を目的としたインターフェロン少量・長期・間欠投与  [通常講演]
    坂口康浩; 鄭 浩柄; 井上達夫; 萩原 智; 石川恵美; 南 康範; 福永豊和; 川崎俊彦; 工藤正俊
    第43回京都肝疾患懇話会 2004年07月 口頭発表（一般） 京都
  • ワークショップ「肝細胞癌に対する経皮的ラジオ波焼灼術の長期治療成績」  [通常講演]
    鄭 浩柄; 石川恵美; 井上達夫; 坂口康浩; 小川 力; 萩原; 智; 南 康範; 福永豊和; 川崎俊彦; 工藤正俊; 土師誠二; 中居卓也
    第40回日本肝癌研究会 2004年06月 シンポジウム・ワークショップパネル（公募） 茨城
  • 造影超音波検査における肝腫瘍のpost-vascular-phaseにおける悪性度評価ーSPIO-MRI、組織学的所見、免疫染色との比較検討ー  [通常講演]
    井上達夫; 周 佩; 坂口康浩; 萩原 智; 南 康範; 鄭 浩柄; 福永豊和; 川崎俊彦; 工藤正俊; 前川 清; 綿井良輔; 粟井和夫; 前西 修
    第40回日本肝臓学会総会 2004年06月 シンポジウム・ワークショップパネル（公募） シェラトングランデトーキョーベイホテル, 千葉
  • 肝細胞癌staging systemの有用性に関する検討  [通常講演]
    鄭 浩柄; 小川 力; 井上達夫; 坂口康浩; 萩原 智; 石川恵美; 南 康範; 福永豊和; 川崎俊彦; 工藤正俊; 大崎往夫
    第40回日本肝臓学会総会 2004年06月 口頭発表（一般） シェラトングランデトーキョーベイホテル, 千葉
  • 肝細胞癌症例における門脈腫瘍栓出現のrisk factorについての検討  [通常講演]
    萩原 智; 石川恵美; 小川 力; 坂口康浩; 井上達夫; 南 康範; 鄭 浩柄; 福永豊和; 川崎俊彦; 工藤正俊
    第40回日本肝臓学会総会 2004年06月 口頭発表（一般） シェラトングランデトーキョーベイホテル, 千葉
  • 肝細胞癌に対するラジオ波焼灼術後のインターフェロン少量・長期・間歇投与の有用性について  [通常講演]
    坂口康浩; 工藤正俊; 川崎俊彦; 福永豊和; 鄭 浩柄; 南 康範; 小川 力; 井上達夫; 萩原 智; 石川恵美
    第40回日本肝癌研究会 2004年06月 口頭発表（一般） 茨城
  • シンポジウム造影超音波検査における肝腫瘍のpost-vascular-phaseにおける悪性度評価組織学的所見との比較検討  [通常講演]
    井上達夫; 周 佩; 坂口康浩; 萩原 智; 南 康範; 鄭 浩柄; 福永豊和; 川崎俊彦; 工藤正俊
    第9回関西超音波造影剤研究会 2004年03月 シンポジウム・ワークショップパネル（公募） 大阪
  • 乏血性膵腫瘍の1例  [通常講演]
    坂本洋城; 北野雅之; 萩原 智; 末富洋一郎; 汐見幹夫; 工藤正俊; 前川 清
    日本超音波医学会第27回関西地方会 2004年02月 口頭発表（一般） 大阪
  • 造影超音波検査が膵癌の胆管ステント内腫瘍進展の診断に有用であった1例  [通常講演]
    坂本康明; 坂本洋城; 北野雅之; 萩原 智; 末富洋一郎; 汐見幹夫; 工藤正俊; 前川 清
    日本超音波医学会第27回関西地方会 2004年02月 口頭発表（一般） 大阪
  • 虚血性大腸炎の経過を体外式超音波法で追えた一例  [通常講演]
    梅原 泰; 末富洋一郎; 福田信宏; 坂本洋城; 坂口康浩; 井上達夫; 小川 力; 萩原 智; 市川 勉; 石川恵美; 鄭 浩柄; 中岡良介; 福永豊和; 南 康範; 仲谷達也; 松井繁長; 川崎俊彦; 北野雅之; 汐見幹夫; 工藤正俊
    第146回大阪腹部超音波研究会 2003年11月 口頭発表（一般） 大阪
  • 超音波Color Doppler Imagingによる胃癌原発巣内の血流評価  [通常講演]
    桑口 愛; 末富洋一郎; 福田信宏; 梅原 泰; 坂本洋城; 坂口康浩; 井上達夫; 小川 力; 萩原 智; 市川 勉; 石川恵美; 鄭 浩柄; 中岡良介; 福永豊和; 南康範; 仲谷達也; 松井繁長; 川崎俊彦; 北野雅之; 汐見幹夫; 工藤正俊
    第146回大阪腹部超音波研究会 2003年11月 口頭発表（一般） 大阪
  • 血流動態より境界病変と考えられる硬変肝内微小結節性病変の予後  [通常講演]
    福永豊和; 工藤正俊; 岡部純弘; 織野彬雄; 汐見幹夫; 川崎俊彦; 北野雅之; 松井繁長; 仲谷達也; 中岡良介; 鄭 浩柄; 南 康範; 末富洋一郎; 福田信宏; 萩原 智; 小川 力; 井上達夫; 梅原 泰; 坂口康浩; 石川恵美
    第7回日本肝臓学会大会 2003年10月 口頭発表（一般） 大阪
  • ゼロタイプI型かる高ウイルス量のC型慢性肝炎に対するIFN-α2b・リバビリン併用療法の効果  [通常講演]
    石川恵美; 工藤正俊; 汐見幹夫; 川崎俊彦; 北野雅之; 松井繁長; 福永豊和; 鄭 浩柄; 中岡良介; 仲谷達也; 南 康範; 末富洋一郎; 福田信宏; 萩原 智; 小川 力; 坂口康浩; 梅原 泰; 井上達夫; 坂本洋城; 豊澤昌子
    第7回日本肝臓学会大会 2003年10月 口頭発表（一般） 大阪
  • 術中内視鏡検査にて放射線性小腸炎による消化管出血と診断できた一例  [通常講演]
    石川恵美; 市川 勉; 豊澤昌子; 坂本洋城; 井上達夫; 梅原 泰; 小川 力; 坂口康浩; 萩原 智; 福田信宏; 末富洋一郎; 南 康範; 吉本理恵; 鄭 浩柄; 中岡良介; 仲谷達也; 福永豊和; 松井繁長; 北野雅之; 川崎俊彦; 汐見幹夫; 工藤正俊
    第71回日本消化器内視鏡学会近畿地方会 2003年10月 口頭発表（一般） 京都
  • 大腸粘膜病変を伴ったWegener肉芽腫の一例  [通常講演]
    梅原 泰; 西尾 健; 坂本洋城; 小川 力; 井上達夫; 坂口康浩; 市川 勉; 豊澤昌子; 萩原 智; 福田信宏; 石川恵美; 末富洋一郎; 南 康範; 仲谷達也; 中岡良介; 鄭 浩柄; 福永豊和; 松井繁長; 北野雅之; 川崎俊彦; 汐見幹夫; 工藤正俊
    第71回日本消化器内視鏡学会近畿地方会 2003年10月 口頭発表（一般） 京都
  • 肝細胞癌に対するラジオ波焼灼療法(RFA)後の腫瘍マーカーの変動とその意義  [通常講演]
    小川 力; 豊澤昌子; 石川恵美; 坂本洋城; 井上達夫; 梅原 泰; 坂口康浩; 萩原 智; 福田信宏; 末富洋一郎; 南 康範; 鄭 浩柄; 中岡良介; 福永豊和; 仲谷達也; 松井繁長; 北野雅之; 川崎俊彦; 汐見幹夫; 工藤正俊
    第45回日本消化器病学会大会 2003年10月 口頭発表（一般） 大阪
  • Angiotensin-II(AT-II)による膵星細胞の膵線維化に及ぼす影響  [通常講演]
    福田信宏; 仲谷達也; 北野雅之; 石川恵美; 坂本洋城; 梅原 泰; 小川 力; 坂口康浩; 萩原 智; 末富洋一郎; 南 康範; 鄭 浩柄; 中岡良介; 松井繁長; 川崎俊彦; 汐見幹夫; 乾 絹世; 工藤正俊
    第45回日本消化器病学会大会 2003年10月 口頭発表（一般） 大阪
  • 十二指腸静脈瘤出血例の臨床的特徴の検討  [通常講演]
    市川 勉; 松井繁長; 石川恵美; 中岡良介; 鄭 浩柄; 末富洋一郎; 坂本洋城; 梅原 泰; 井上達夫; 坂口康浩; 萩原 智; 南 康範; 畑中絹世; 小川 力; 福田信宏; 仲谷達也; 福永豊和; 北野雅之; 川崎俊彦; 汐見幹夫; 工藤正俊
    第79回日本消化器病学会近畿支部例会 2003年09月 口頭発表（一般） 奈良
  • 腹部血管造影にて出血部位を同定できた小腸動静脈奇形の一症例  [通常講演]
    石川恵美; 工藤正俊; 汐見幹夫; 川崎俊彦; 北野雅之; 福永豊和; 松井繁長; 仲谷達也; 中岡良介; 鄭 浩柄; 末富洋一郎; 南 康範; 福田信宏; 坂口康浩; 井上達也; 小川 力; 坂本洋城; 梅原 泰; 萩原 智; 所 忠男; 塩崎 均
    第79回日本消化器病学会近畿支部例会 2003年09月 口頭発表（一般） 奈良
  • 造影ハーモニックイメージを用いた胆嚢隆起性病変の検討  [通常講演]
    井上達夫; 市川 勉; 石川恵美; 坂本洋城; 小川 力; 梅原 泰; 坂口康浩; 福田信宏; 萩原 智; 末富洋一郎; 南 康範; 中岡良介; 鄭 浩柄; 松井繁長; 福永豊和; 北野雅之; 川崎俊彦; 汐見幹夫; 前川 清; 工藤正俊
    第39回日本胆道学会学術集会 2003年09月 口頭発表（一般） 金沢
  • 多血性の過形成結節を認めたアルコール性肝硬変の一例  [通常講演]
    井上達夫; 浅田 卓; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 工藤正俊; 江口真由美; 山本真由美; 遠田由紀; 前川 清; 中島 収; 神代正道
    第6回肝血流動態イメージ研究会 2003年02月 口頭発表（一般） 神戸
  • 右胃静脈環流異常の2症例  [通常講演]
    亀山千晴; 遠田弘一; 井上達夫; 梅原 泰; 浅田 卓; 坂口康浩; 小川 力; 加藤玲明; 時枝数雄; 萩原 智; 中岡良介; 谷池聡子; 松井繁長; 由谷逸朗; 山本健二; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    第71回日本消化器病学会支部例会 1999年09月 口頭発表（一般） 大阪国際交流センター
  • A-Pシャントを伴う肝血管腫のfocal spared areaの成因としての意義  [通常講演]
    遠田弘一; 井上達夫; 梅原 泰; 浅田 卓; 坂口康浩; 小川 力; 加藤玲明; 時枝数雄; 萩原 智; 中岡良介; 谷池聡子; 亀山千晴; 松井繁長; 由谷逸朗; 山本健二; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    第71回日本消化器病学会支部例会 1999年09月 口頭発表（一般） 大阪国際交流センター
  • Fusion 3D法を用いた3次元超音波診断装置の使用経験  [通常講演]
    山本健二; 井上達夫; 梅原 泰; 浅田 卓; 坂口康浩; 小川 力; 加藤玲明; 時枝数雄; 萩原 智; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    第71回日本消化器病学会支部例会 1999年09月 口頭発表（一般） 大阪国際交流センター
  • 遊走脾の1例  [通常講演]
    萩原 智; 谷池聡子; 中岡良介; 亀山千晴; 遠田弘一; 松井繁長; 由谷逸朗; 山本健二; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊; 岩崎拓也; 吉田英樹; 土師誠二; 野村秀明; 大柳治正
    第71回日本消化器病学会支部例会 1999年09月 口頭発表（一般） 大阪国際交流センター
  • 内視鏡的に止血し得た幼児出血性十二指腸潰瘍の1例  [通常講演]
    由谷逸朗; 汐見幹夫; 萩原 智; 中岡良介; 亀山千晴; 谷池聡子; 松井繁長; 山本健二; 上硲俊法; 井上良一; 工藤正俊; 山内勝治; 桑島宏彰
    第71回日本消化器病学会支部例会 1999年09月 口頭発表（一般） 大阪国際交流センター
  • 特異な経過をたどった胃カルチノイドと原発性肝細胞癌の1剖検例  [通常講演]
    中岡良介; 汐見幹夫; 萩原 智; 谷池聡子; 亀山千晴; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 工藤正俊
    第71回日本消化器病学会支部例会 1999年09月 口頭発表（一般） 大阪国際交流センター
  • 超音波上肝左葉欠損と考えられた一例  [通常講演]
    浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • 肝疾患におけるBモード血流表示の有用性  [通常講演]
    前川 清; 山本真由美; 江口真由美; 遠田由紀; 浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 由谷逸朗; 山本健二; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • 多発性血管周皮腫の一例  [通常講演]
    山本真由美; 江口真由美; 遠田由紀; 前川 清; 浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • 重複門脈の一例  [通常講演]
    福田信宏; 浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原智; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • 超音波検査にて診断された遊走脾の一例  [通常講演]
    萩原 智; 浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 福田信宏; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊; 土師誠二; 野村秀明; 大柳治正
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • P-Vシャントに伴うfocal spared areaの一例  [通常講演]
    遠田弘一; 浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • Fusion 3Dによる3次元超音波の有用性について  [通常講演]
    山本健二; 浅田 卓; 井上達夫; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊; 橋本新一; 山形 仁
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • Hypervascularを呈したアルコール性過形成結節の一例  [通常講演]
    井上達夫; 浅田 卓; 梅原 泰; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊; 中島 収; 神代正道
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • 食事負荷によって改善の見られた門脈逆流の一例  [通常講演]
    梅原 泰; 浅田 卓; 井上達夫; 坂口康浩; 加藤玲明; 時枝数雄; 萩原 智; 福田信宏; 山本真由美; 江口真由美; 遠田由紀; 前川 清; 中岡良介; 谷池聡子; 亀山千晴; 遠田弘一; 松井繁長; 山本健二; 由谷逸朗; 上硲俊法; 汐見幹夫; 井上良一; 工藤正俊
    日本超音波医学会第18回関西地方会 1999年09月 口頭発表（一般） 大阪
  • 真性多血症による門脈圧亢進症に対してTIPSを施行した1例  [通常講演]
    松井繁長; 井上良一; 中岡良介; 上硲俊法; 工藤正俊
    第6回日本門脈圧亢進症学会総会 1999年09月 口頭発表（一般） 宇部

MISC

受賞

  • 2022年 日本肝臓学会研究奨励賞
  • 2018年11月 日本肝臓学会 日本肝臓学会冠第3回Gilead Sciences Award
     
    受賞者: 萩原 智
  • 2017年02月 第23回肝血流動態･機能イメージ研究会 板井悠二賞
     
    受賞者: 萩原 智
  • 2013年12月 第21回浜名湖シンポジウム 特別賞（基礎的意義）
     
    受賞者: 萩原 智
  • 2013年06月 第7回日本肝がん分子標的治療研究会 優秀演題賞
     
    受賞者: 萩原 智

共同研究・競争的資金等の研究課題

  • 免疫チェックポイント阻害剤投与に伴う急速な腫瘍増大(HPD)の発症機序の解析
    文部科学省：科学研究費補助金(基盤研究(C))
    研究期間 : 2022年04月 -2024年03月 
    代表者 : 萩原 智
  • 緑茶カテキンEGCGを用いた臓器線維症治療のための基礎的研究
    文部科学省：科学研究費補助金(基盤研究(C))
    研究期間 : 2018年 -2020年 
    代表者 : 吉田 浩二
  • ヘリコバクターピロリ菌の慢性感染からみた慢性炎症性神経疾患の発症機序の解明
    文部科学省：科学研究費補助金(基盤研究(C))
    研究期間 : 2018年 -2020年 
    代表者 : 朴 雅美
  • 肝癌惹起性HBx変異の存在下で形成される腫瘍微小免疫環境の解析
    文部科学省：科学研究費補助金(基盤研究(C))
    研究期間 : 2018年 -2020年 
    代表者 : 萩原 智
  • 非ステロイド性抗炎症薬による小腸粘膜傷害でのGal-3および腸内細菌の役割
    文部科学省：科学研究費補助金(基盤研究(C))
    研究期間 : 2015年 -2017年 
    代表者 : 朴 雅美
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2011年 -2013年 
    代表者 : 吉田 浩二; 杉岡 孝二; 萩原 智
     
    角膜線維芽細胞(keratocyte)はTGF-β刺激を受けると、活性化し、筋線維芽細胞様の形態を示すようになった。また、TGF-β処理によりkeratocyteのインテグリンα11(ITGA11)、α-SMA、fibronectinの発現は亢進した。ITGA11およびcalcium- and integrin-binding protein 1（CIB1）を高発現させた細胞はTGF-βに対する感受性が亢進した。また、緑茶成分epigallocatechin-3-gallate (EGCG)はTGF-βtype IIレセプターに結合し、TGF-βの作用を阻害することが判明した。
  • 日本学術振興会：科学研究費助成事業
    研究期間 : 2008年 -2010年 
    代表者 : 吉田 浩二; 斉藤 昭夫; 萩原 智
     
    transgelinをノックダウンした筋線維芽細胞は活性化が抑制された。また、TGF-βでヒト肺線維芽細胞を刺激したとき、インテグリンα11(ITGA11)の発現が著明に亢進した。calcium and integrin binding protein 1 (CIB1)はITGA11の細胞内ドメインと結合した。TGF-β処理した肺線維芽細胞およびブレオマイシンにより肺線維症を起こしたマウスの肺組織においてCIB1の発現が増加する傾向が見られたことから、CIB1が線維化に関与している可能性が示唆された。
  • 「B型肝炎ウイルス再活性化に関与するウイルス・宿主要因の解明に基づく予防対策法の確立を目指す研究
    日本医療研究開発機構：肝炎等克服緊急対策研究事業
    代表者 : 池田 公史

委員歴

  • 2023年01月 - 現在   日本消化器病学会   学会評議員
  • 2016年12月 - 現在   日本内科学会   近畿支部評議員
  • 2015年01月 - 現在   日本消化器病学会   近畿支部評議員
  • 2014年10月 - 現在   日本肝臓学会   近畿支部評議員

その他のリンク

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