Faculty Profiles - TAKAKI Akinobu

MISC - TAKAKI Akinobu

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Prospective evaluation of the factors predicting the prognosis of advanced hepatocellular carcinoma (HCC) patients treated with sorafenib.

Takuya Adachi, Kazuhiro Nouso, Koji Miyahara, Chihiro Dohi, Nozomu Wada, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Shinichiro Nakamura, Hidenori Shiraha, Koichi Takaguchi, Shuji Uematsu, Shouta Iwadou, Yoshitaka Takuma, Hiroaki Hagihara, Hiroyuki Takabatake, Akinobu Takaki, Hiroyuki Okada

JOURNAL OF CLINICAL ONCOLOGY 35 2017.5

Dynamic computed tomography is useful for prediction of pathological grade in pancreatic neuroendocrine neoplasm

Shigeru Horiguchi, Hironari Kato, Hidenori Shiraha, Koichiro Tsutsumi, Naoki Yamamoto, Kazuyuki Matsumoto, Takeshi Tomoda, Daisuke Uchida, Yutaka Akimoto, Syou Mizukawa, Takehiro Tanaka, Koichi Ichimura, Akinobu Takaki, Takahito Yagi, Hiroyuki Okada

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 4 ) 925 - 931 2017.4

Language：English Publisher：WILEY

Background and Aim Pathological grading is important in defining the therapeutic strategy in pancreatic neuroendocrine neoplasm (PNEN) but is difficult for unresectable cases. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) is useful in the diagnosis of PNEN, but its usefulness for pathological grading is not well established. No studies have examined the diagnostic ability of dynamic computed tomography (CT) for pathological grading of PNEN. We investigated the usefulness of EUS-FNA and dynamic CT in the diagnosis and pathological grading of PNEN.
Methods In this retrospective study, 39 PNEN patients finally diagnosed via EUS-FNA and/or surgical resection underwent dynamic CT. Pathological samples were diagnosed based on WHO2010; staging was based on the European Neuroendocrine Tumor Society classification. The proportion of the quantification value in the tumor to the pancreatic parenchyma in arterial phase was defined as the CT ratio. Immunohistochemical staining with CD31 was performed to evaluate microvessel density (MVD). We evaluated the relationship between pathological grade, CT ratio, and MVD.
Results By using EUS-FNA, 35 of 39 (90%) cases were diagnosed as PNEN. As for pathological grade, 15 of 35 (43%) cases could be identified correctly. CT ratio could predict pathological Grade 3 disease. The sensitivity, specificity, and diagnostic accuracy were 100%, 94%, and 95%. MVD was significantly correlated with CT ratio (r=0.83, P<0.0001) and pathological grade (P=0.0074).
Conclusions Computed tomography ratio has a relationship with pathological grade in PNEN, which would help decide therapeutic strategy in unresectable cases and cases in which pathological grading is difficult.

DOI： 10.1111/jgh.13594

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肝腫瘤に対する穿刺・治療の進歩穿刺用マイクロコンベックスプローブに求められるもの

中村進一郎, 大西秀樹, 桑木健志, 竹内康人, 白羽英則, 和田望, 安中幸, 能祖一裕, 高木章乃夫, 岡田裕之

超音波医学 44 ( Suppl. ) S260 - S260 2017.4

PREDICTION OF PROGNOSIS: RETREATMENT WITH TACE ON DEMAND IN PATIENTS WITH HCC

Nozomu Wada, Kazuhiro Nouso, Shouta Iwado, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

GASTROENTEROLOGY 152 ( 5 ) S1174 - S1174 2017.4

肝硬変体液貯留に対するトルバプタンの効果予測因子としての酸化ストレスの重要性

足立卓哉, 高木章乃夫, 佐藤秀一, 大山淳史, 下村泰之, 和田望, 竹内康人, 安中幸, 安中哲也, 桑木健志, 大西秀樹, 池田房雄, 中村進一郎, 白羽英則, 岡田裕之

肝臓 58 ( Suppl.1 ) A407 - A407 2017.4

SUBCLINICAL PULMONARY HYPERTENSION IS A STRONG RISK OF POST LIVING DONOR LIVER TRANSPLANTATION SURVIVAL FOR LIVER CIRRHOSIS

Yosuke Saragai, Akinobu Takaki, Yuzo Umeda, Tetsuya Yasunaka, Ryuji Kaku, Kazufumi Nakamura, Takahito Yagi, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Takuya Adachi, Yasuyuki Shimomura, Nozomu Wada, Kenji Kuwaki, Fusao Ikeda, Hideki Onishi, Hidenori Shiraha, Shinichiro Nakamura, Hiroshi Ito, Toshiyoshi Fujiwara, Hiroyuki Okada

GASTROENTEROLOGY 152 ( 5 ) S1122 - S1122 2017.4

非アルコール性脂肪性肝疾患におけるPNPLA3およびTM6SF2遺伝子多型の組織学的検討

岩崎良章, 池田房雄, 中山光, 下村泰之, 和田望, 安中哲也, 高木章乃夫, 岡田裕之

肝臓 58 ( Suppl.1 ) A383 - A383 2017.4

Application of radiofrequency ablation for the treatment of intermediate-stage hepatocellular carcinoma

Kazuhiro Nouso, Kazuya Kariyama, Shinichiro Nakamura, Ayano Oonishi, Akiko Wakuta, Atsushi Oyama, Soichiro Ako, Chihiro Dohi, Nozomu Wada, Yuki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Fusao Ikeda, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 3 ) 695 - 700 2017.3

Language：English Publisher：WILEY

Background and Aim: Transcatheter arterial chemoembolization (TACE) is a standard therapy for the treatment of intermediate-stage hepatocellular carcinoma (HCC). In this study, we tried to elucidate the possibility of using radiofrequency ablation (RFA) as an alternative treatment of intermediate-stage HCC.
Methods: Among 246 patients who were initially diagnosed with intermediate-stage HCC, 76 who were treated with TACE (TACE group) and 91 who were treated with RFA (RFA group) were enrolled in this study. The risk for survival was analyzed with the Cox Proportional Hazard Model, and the survival rates were compared using propensity score matching.
Results: About half (50.6%) of the intermediate-stage HCC patients in the RFA group were diagnosed with Barcelona Clinic Liver Cancer substage-B1 (BCLC-B1) compared with only 19.7% of the patients in the TACE group. Survival of the RFA group was longer than that of TACE group in patients with BCLC-B1 and BCLC-B2. In contrast, no difference between groups was observed in patients with BCLC-B3/4. Multivariate analysis revealed that large tumor size (> 30 mm, hazard ratio = 1.685, P = 0.043), high des-gamma-carboxyprothrombin (> 100 mAU/mL, hazard ratio = 1.920, P = 0.012), and TACE group (hazard ratio = 1.896, P = 0.016) were significant risk factors for survival. Overall 3-year survival of the patients in the RFA group (69.5%) was significantly longer than that of patients in the TACE group (51.5%) after propensity score matching (P = 0.032). No significant adverse events were observed in either group.
Conclusions: RFA was useful for the treatment of less advanced intermediate-stage HCC and could be an alternative to TACE in selected cases.

DOI： 10.1111/jgh.13586

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Early Chimerism After Liver Transplantation Reflects the Clinical Course of Recurrent Hepatitis C

Masashi Utsumi, Akinobu Takaki, Yuzo Umeda, Kazuko Koike, Stephanie C. Napier, Nobukazu Watanabe, Susumu Shinoura, Ryuichi Yoshida, Daisuke Nobuoka, Tetsuya Yasunaka, Takahiro Oto, Motoo Araki, Kazuhide Yamamoto, Toshiyoshi Fujiwara, Takahito Yagi

ANNALS OF TRANSPLANTATION 22 156 - 165 2017.3

Language：English Publisher：INT SCIENTIFIC LITERATURE, INC

Background: Human leukocyte antigen (HLA) mismatch is a characteristic feature of post-orthotopic liver transplantation (OLT) hepatitis C. To investigate the importance of donor HLA-restricted immune cells in post-OLT hepatitis C recurrence, we analyzed the frequency of donor chimerism and the clinical course of post-OLT hepatitis C.
Material/Methods: We analyzed peripheral blood chimerism in 11 HCV-reinfected patients with post-HLA mismatched OLT. Patients were divided into 2 groups: the OLT chronic hepatitis C (CHC) group (n=8), exhibiting active hepatitis C recurrence; and the OLT-persistently normal ALT (PNALT) group (n=3), without active hepatitis. Chimerism was analyzed by flow cytometry using donor-specific anti-HLA antibodies in peripheral blood mononuclear cells from 1-100 days after OLT. Kidney (n=7) and lung (n=7) transplant recipients were also analyzed for comparison. As immune cells from the donor liver might contribute to post-OLT chimerism, the characteristics of perfusates from donor livers (n=10) were analyzed and defined.
Results: Donor-derived cells were frequently observed in liver and lung transplant recipients. The frequency of donor-derived cells from the B cell subset was significantly higher in peripheral blood from OLT-CHC group than in that of the OLT-PNALT group. B cells, however, were not the predominant subset in the perfusates, indicating that inflow of donor-derived cells alone did not cause the chimerism.
Conclusions: Chimerism of B cells is frequent in liver transplant patients with early recurrence of hepatitis C. We propose that monitoring of early chimerism could facilitate early detection of chronic hepatitis C recurrence, although we need more cases to investigate.

DOI： 10.12659/AOT.900494

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Loss of Runt-related transcription factor 3 induces resistance to 5-fluorouracil and cisplatin in hepatocellular carcinoma (vol 35, pg 2576, 2016)

Junro Kataoka, Hidenori Shiraha, Shigeru Horiguchi, Hiroaki Sawahara, Daisuke Uchida, Teruya Nagahara, Masaya Iwamuro, Hiroki Morimoto, Yasuto Takeuchi, Kenji Kuwaki, Hideki Onishi, Shinichiro Nakamura, Akinobu Takaki, Kazuhiro Nouso, Takahito Yagi, Kazuhide Yamamoto, Hiroyuki Okada

ONCOLOGY REPORTS 37 ( 3 ) 1921 - 1921 2017.3

Serum-inducible protein (IP)-10 is a disease progression-related marker for non-alcoholic fatty liver disease

Nozomu Wada, Akinobu Takaki, Fusao Ikeda, Tetsuya Yasunaka, Masahiro Onji, Kazuhiro Nouso, Atsuko Nakatsuka, Jun Wada, Kazuko Koike, Koji Miyahara, Hidenori Shiraha, Kazuhide Yamamoto, Hiroyuki Okada

HEPATOLOGY INTERNATIONAL 11 ( 1 ) 115 - 124 2017.1

Language：English Publisher：SPRINGER

The molecular pathogenesis of non-alcoholic steatohepatitis (NASH) is not well defined. The objective of the present study was to identify disease progression-related cytokines and investigate the molecular pathogenesis of such changes in NASH.
A study population of 20 non-alcoholic fatty liver (NAFL) and 59 NASH patients diagnosed by liver biopsy and 15 healthy volunteers was recruited. The serum pro- and anti-inflammatory cytokines were measured by a multiple enzyme-linked immunosorbent assay. The hepatic mRNA expressions of cytokines were measured by real-time PCR. A monocyte cell line was stimulated with Toll-like receptor (TLR) ligand under a high glucose and insulin condition, and cellular cytokine mRNA expression was quantified.
One group of cytokines was higher in NAFL and NASH than in controls, while another group was higher in NASH than in NAFL and controls. The NASH-specific second group included interleukin (IL)-15 and interferon-gamma-inducible protein (IP)-10. In particular, IP-10 was higher in NAFL than in controls and higher in NASH than in NAFL and controls. The sensitivity to diagnose NASH was 90%, with specificity of 50%. Insulin resistance reflecting a high glucose and insulin condition resulted in higher IP-10 mRNA expression in the monocyte cell line only with concomitant TLR-2 stimulation.
IP-10 is a sensitive marker of the need for liver biopsy. Insulin resistance with bacteria-related TLR-2 stimulation might induce IP-10 production from monocytes. Insulin resistance and intestinal barrier function should be intensively controlled to prevent progression from NAFL to NASH.

DOI： 10.1007/s12072-016-9773-y

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Oxidative stress controlling agents are effective for small intestinal injuries induced by non-steroidal anti-inflammatory drugs

Yoshiyasu Kono, Seiji Kawano, Akinobu Takaki, Yasuyuki Shimomura, Masahiro Onji, Hisashi Ishikawa, Sakuma Takahashi, Joichiro Horii, Sayo Kobayashi, Daisuke Kawai, Kazuhide Yamamoto, Hiroyuki Okada

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 1 ) 136 - 145 2017.1

Language：English Publisher：WILEY-BLACKWELL

Background and AimVideo-capsule endoscopy (VCE) has shown that intestinal ulcers are common in non-steroidal anti-inflammatory drugs (NSAIDs) users, although the mechanisms and management have not been clearly defined. To explore the contribution of oxidative stress and potential of anti-oxidants for NSAIDs-induced intestinal ulcers, we assessed human serum oxidative stress balance and the effect of anti-oxidants using a mouse model.
MethodsA total of 30 NSAIDs users (17 aspirin and 13 non-aspirin users) received VCE. Serum reactive oxygen metabolite (d-ROM) and antioxidative OXY-adsorbent test (OXY) were measured. The indomethacin (IND)-induced mouse intestinal ulcer model was used to assess the effect of anti-oxidants. Eight-week-old mice were divided into four groups; control diet and diet including IND (N group), IND and L-carnitine (NC group), and IND and vitamin E (NE group).
ResultsSerum OXY levels among non-aspirin users were lower in the mucosal injuries positive group than the negative group (P<0.05). In the mouse models, the degree of mucosal injuries was lower in NC and NE than N (P<0.01). Serum d-ROM levels were lower in NC and NE than N (P<0.01), and OXY levels were higher in NC than N and NE (P<0.01). The degeneration of intestinal mitochondria was mild in NC and NE. The serum KC/CXCL-1 level and hepatic expression of the anti-oxidant molecule Gpx4 were lower in NC than N.
ConclusionsNon-aspirin NSAID-induced intestinal ulcers are related to decreased anti-oxidative stress function. Anti-oxidants, especially L-carnitine, are good candidates for intestinal ulcers.

DOI： 10.1111/jgh.13424

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Sufficient management of alert system of positive test results for HBV and HCV infection in electronic medical chart for facilitating hepatological consultation

Yasuyuki Shimomura, Yousuke Fujii, Fusao Ikeda, Tetsuya Yasunaka, Noriko Yamasaki, Ikuko Kasahara, Naomi Inuyama, Michihiro Koyama, Shihoko Namba, Yasuto Takeuchi, Nozomu Wada, Takeshi Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

Acta Hepatologica Japonica 58 ( 8 ) 427 - 434 2017

Language：Japanese Publisher：Japan Society of Hepatology

Alert for positive results of hepatitis tests in electronic medical chart is helpful for management of hepatitis carriers at non-hepatology departments. Further attempts for sufficient hepatological consultations in this alert system, such as explaining the test results to the subjects by mailing notification forms with referral to the hepatologists were adopted. The notification forms were re-mailed to the subjects without the reply in 6 months. Aggregate analysis by reviewing the charts of the subjects confirmed that the rate of hepatological consultation was improved from 49% to 72% with further attempts (p&lt
0.001, the chi-square test). Mailing notification forms with referral to the hepatologists can be helpful for facilitating hepatological consultation in alert system of positive test results for HBV and HCV infection in electronic medical chart.

DOI： 10.2957/kanzo.58.427

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Correction to

Hiromitsu Kumada, Tsunamasa Watanabe, Fumitaka Suzuki, Kenji Ikeda, Ken Sato, Hidenori Toyoda, Masanori Atsukawa, Akio Ido, Akinobu Takaki, Nobuyuki Enomoto, Koji Kato, Katia Alves, Margaret Burroughs,Rebecca Redman, David Pugatch, Tami J. Pilot-Matias, Preethi Krishnan, Rajneet, K. Oberoi, Wangang Xie, Kazuaki Chayama

Journal of Gastroenterology, Gastroenterologia Japonica 873 - 882 2017

Usefulness of the seminars on liver disease at workplace to improve work environment associated with viral hepatitis

Shihoko Namba, Fusao Ikeda, Yasuyuki Shimomura, Naomi Inuyama, Shinnosuke Okubo, Takashi Makita, Yuko Hasegawa, Kenji Iwai, Akiko Hosoba, Rumi Miura, Yosuke Fujii, Tetsuya Yasunaka, Yasuto Takeuchi, Nozomu Wada, Takeshi Kuwaki, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Akinobu Takaki, Hiroyuki Okada

Acta Hepatologica Japonica, Kanzo 58 ( 5 ) 304 - 306 2017

Hepatic and Gastric Involvement in a Case of Systemic Sarcoidosis Presenting with Rupture of Esophageal Varices

Hiroaki Saito, Masayasu Ohmori, Masaya Iwamuro, Takehiro Tanaka, Nozomu Wada, Tetsuya Yasunaka, Akinobu Takaki, Hiroyuki Okada

INTERNAL MEDICINE 56 ( 19 ) 2583 - 2588 2017

Language：English Publisher：JAPAN SOC INTERNAL MEDICINE

A 46-year-old woman presented with massive hematemesis, caused by the rupture of esophageal varices. The laboratory investigations showed pancytopenia, and imaging tests revealed hepatosplenomegaly and ascites. A diagnosis of systemic sarcoidosis was made based on biopsies of the liver, stomach, lungs, heart, and skin. Although fat deposition was predominant, non-caseating granuloma and cirrhotic changes were found in the liver. Non-caseating granuloma was also identified in a biopsy specimen from minute depressions of the gastric folds. This case illustrates the rare involvement of the digestive system in a case of systemic sarcoidosis.

DOI： 10.2169/internalmedicine.8768-16

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A sofosbuvir-based direct-acting antiviral treatment regimen exhibits a strong protective effect against post-liver transplantation chronic hepatitis C recurrence

Atsushi Oyama, Akinobu Takaki, Tetsuya Yasunaka, Takuya Adachi, Fusao Ikeda, Nozomu Wada, Yasuhito Takeuchi, Hideki Onishi, Shinichiro Nakamura, Hidenori Shiraha, Kosei Takagi, Takashi Kuise, Daisuke Nobuoka, Ryuichi Yoshida, Yuzo Umeda, Mari Yoshida, Chisato Arimori, Takahito Yagi, Hiroyuki Okada

Acta Hepatologica Japonica 58 ( 11 ) 599 - 604 2017

Language：Japanese Publisher：Japan Society of Hepatology

The efficacy and safety of anti-hepatitis C virus (HCV. direct-acting antivirals were evaluated in postorthotopic liver transplantation patients. There were 29 patients with HCV genotype 1 and 2 with genotype 2. Of the 29 genotype 1 patients, 5 received daclatasvir (DCV. + asunaprevir (ASV), and 25 received sofosbuvir (SOF. + ledipasvir (LDV), including 1 who had failed DCV + ASV. Both genotype 2 patients received SOF + ribavirin. Four patients with DCV + ASV completed the protocol, and 3 of them achieved a sustained viral re-sponse for 24 weeks (SVR24). All of the patients who received SOF + LDV and SOF + RBV achieved SVR24 with minor adverse events. In post-liver transplantation patients, SOF-based regimens showed highly satisfactory efficacy and safety.

DOI： 10.2957/kanzo.58.599

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Safety and Efficacy of Small Bowel Examination by Capsule Endoscopy for Patients before Liver Transplantation (vol 2017, 8193821, 2017)

Seiji Kawano, Akinobu Takaki, Masaya Iwamuro, Tetsuya Yasunaka, Yoshiyasu Kono, Kou Miura, Toshihiro Inokuchi, Yoshiro Kawahara, Yuzo Umeda, Takahito Yagi, Hiroyuki Okada

BIOMED RESEARCH INTERNATIONAL 2017 406 - 410 2017

The Serum Oxidative/Anti-oxidative Stress Balance Becomes Dysregulated in Patients with Non-alcoholic Steatohepatitis Associated with Hepatocellular Carcinoma

Yasuyuki Shimomura, Akinobu Takaki, Nozomu Wada, Tetsuya Yasunaka, Fusao Ikeda, Takayuki Maruyama, Naofumi Tamaki, Daisuke Uchida, Hideki Onishi, Kenji Kuwaki, Shinichiro Nakamura, Kazuhiro Nouso, Yasuhiro Miyake, Kazuko Koike, Takaaki Tomofuji, Manabu Morita, Kazuhide Yamamoto, Hiroyuki Okada

INTERNAL MEDICINE 56 ( 2 ) 243 - 251 2017

Language：English Publisher：JAPAN SOC INTERNAL MEDICINE

Objective Oxidative stress is associated with the progression of chronic liver disease. Non-alcoholic fatty liver disease (NAFLD) is also an oxidative stress-related disease. However, the oxidative/anti-oxidative balance has not been fully characterized in NAFLD. The objective of the present study was to investigate the balance between oxidative stress and the anti-oxidative activity in NAFLD, including non-alcoholic steatohepatitis (NASH)-related hepatocellular carcinoma (HCC).
Patients We recruited 69 patients with histologically proven NAFLD without HCC (NAFLD; n=58), and with NASH-related HCC (NASH-HCC; n=11). The 58 NAFLD patients included patients with non-alcoholic fatty liver (NAFL; n=14) and NASH (n=44).
Methods The serum levels of reactive oxygen metabolites (ROM) and anti-oxidative markers (OXY) were determined and then used to calculate the oxidative index. The correlations among such factors as ROM, OXY, oxidative index, and clinical characteristics were investigated.
Results In NAFLD, ROM positively correlated with the body mass index (BMI), hemoglobin A1c (HbA1c), C-reactive protein (CRP), and the histological grade or inflammatory scores, while only high HbA1c and CRP levels were significant factors that correlated with a higher ROM according to a multivariate analysis. OXY positively correlated with the platelet counts, albumin, and creatinine levels, while negatively correlating with age. However, it improved after treatment intervention. The oxidative index positively correlated with BMI, CRP, and HbA1c. The NASH-HCC patients exhibited a lower OXY than the NASH patients, probably due to the effects of aging.
Conclusion Oxidative stress correlated with the levels of NASH activity markers, while the anti-oxidative function was preserved in younger patients as well as in patients with a well-preserved liver function. The NASH-HCC patients tended to be older and exhibited a diminished anti-oxidative function.

DOI： 10.2169/internalmedicine.56.7002

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Low-dose FP療法が奏効した切除不能混合型肝癌の1例

加藤小百合, 竹内康人, 和田望, 森元裕貴, 桑木健志, 大西秀樹, 中村進一郎, 白羽英則, 高木章乃夫, 岡田裕之

日本消化器病学会雑誌 113 ( 12 ) 2050 - 2056 2016.12

Language：Japanese Publisher：(一財)日本消化器病学会

症例は50歳代、女性。肝左葉を占める、肝内多発転移・門脈腫瘍塞栓をともなう混合型肝癌と診断された。肝細胞癌成分が有意と判断し、肝細胞癌に準じた化学療法を導入した。Sorafenib・CDDP肝動注療法では病勢と全身状態の悪化を認めたが、Low-dose FP(LFP)療法は奏効を認め、長期生存が得られている。今回LFP療法が、切除不能な混合型肝癌の治療の選択肢としても有効である可能性が示唆された。(著者抄録)

DOI： 10.11405/nisshoshi.113.2050

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