Faculty Profiles - TAKAKI Akinobu

Papers - TAKAKI Akinobu

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Gastric peroral endoscopic myo-neurotomy as less-invasive bariatric surgery in porcine models: an experimental study

Kenta Hamada, Yasushi Yamasaki, Akinobu Takaki, Takehiro Tanaka, Hiroyuki Okada

iGIE 3 ( 3 ) 358 - 365 2024.9

Publishing type：Research paper (scientific journal)

Background and Aims: Obesity is a global health problem, and less-invasive treatments are warranted. We developed a novel endoscopic intervention named peroral endoscopic myo-neurotomy (POEM-N) that is performed at the greater curvature of the gastric antrum as a bariatric/metabolic procedure and assessed its feasibility using porcine models. Methods: Six live pigs were divided into 3 groups of 2: POEM-N with a high-fat diet (HFD) (POEM-N group); sham procedure with HFD (HF-control group); and sham procedure with normal diet (N-control group). All pigs were fed the diets for 2 weeks, underwent POEM-N or sham procedure, and were observed for 2 weeks after the procedure. The primary outcome was the safety and feasibility of POEM-N. Adverse events and histology of the area after POEM-N were evaluated to assess the procedure's safety and feasibility. Secondary outcomes were changes in body weight and glycolipid levels. Results: There was no severe worsening of vital signs during or after the POEM-N procedure. All pigs were well and food intake was good, with no delayed adverse events. Excessive storage of dietary residue, deformity of the gastric antrum, and fold concentration were observed after POEM-N, as expected. Histologic examination revealed hypertrophic regeneration of Auerbach's plexus, which regulates gastric peristalsis, in both POEM-N pigs. After the procedure, HFD-induced weight gain in the POEM-N pigs slowed, and the increase in serum and liver cholesterol levels was suppressed. Conclusions: We applied POEM-N as a bariatric/metabolic procedure and showed its safety and feasibility using porcine models.

DOI： 10.1016/j.igie.2024.06.002

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Response to the letter: "Predictive factors for transition to conversion therapy in HCC using atezolizumab plus bevacizumab". International journal

Tatsuya Kikuchi, Yasuto Takeuchi, Kazuhiro Nouso, Kazuya Kariyama, Kenji Kuwaki, Junichi Toshimori, Shota Iwado, Akio Moriya, Hiroaki Hagihara, Hiroyuki Takabatake, Toshifumi Tada, Tetsuya Yasunaka, Masahiro Sakata, Masahiko Sue, Nozomi Miyake, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki, Motoyuki Otsuka

Liver international : official journal of the International Association for the Study of the Liver 44 ( 7 ) 1736 - 1737 2024.7

Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab. International journal

Liver international : official journal of the International Association for the Study of the Liver 44 ( 6 ) 1456 - 1463 2024.6

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

DOI： 10.1111/liv.15907

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Impact of Nutritional Status on Neutrophil-to-Lymphocyte Ratio as a Predictor of Efficacy and Adverse Events of Immune Check-Point Inhibitors. International journal

Masahiko Sue, Yasuto Takeuchi, Shoichiro Hirata, Akinobu Takaki, Motoyuki Otsuka

Cancers 16 ( 10 ) 2024.5

Language：English Publishing type：Research paper (scientific journal)

The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained.

DOI： 10.3390/cancers16101811

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肝細胞癌の病態解明のためのトランスレーショナルリサーチ血清抗PD1自己抗体高値はアテゾリズマブ/ベバシズマブ治療予後不良の予測因子となる

高木章乃夫, 松本和幸, 佐々木裕貴, 須江真彦, 足立卓哉, 和田望, 竹内康人, 大西秀樹, 白羽英則, 大塚基之

日本消化器病学会雑誌 121 ( 臨増総会 ) A236 - A236 2024.3

Anti-PD-1 Autoantibody Predicts Survival of Patients With Hepatocellular Carcinoma Receiving Atezolizumab/Bevacizumab

Yuki Sasaki, Kazuyuki Matsumoto, Akinobu Takaki, Takuya Adachi, Masahiro Takahara, Keita Ozato, Yasuto Takeuchi, Masahiko Sue, Nozomi Miyake, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Takashi Oda, Koichiro Tsutsumi, Kazuhiro Nouso, Kazuya Kariyama, Hiroaki Hagihara, Akio Moriya, Motoyuki Otsuka

Gastro Hep Advances 3 ( 8 ) 1138 - 1147 2024.1

Publishing type：Research paper (scientific journal)

Background and Aims: Methods for predicting therapeutic response to immune checkpoint inhibitors in cancer therapy are in high demand. In patients with advanced hepatocellular carcinoma (HCC), atezolizumab (anti-programmed cell death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor) combination therapy (Atezo/Bev therapy) is a first-line treatment. However, no reliable biomarkers are currently available to predict its efficacy. Here, we examined serum anti-PD-1 autoantibody levels as candidate biomarkers. Methods: We prospectively enrolled 63 patients with advanced HCC who received Atezo/Bev therapy. Serum anti-PD-1 autoantibody levels were measured before treatment using an indirect enzyme-linked immunosorbent assay. The correlation between the titers and response to therapy was statistically examined. Results: Serum anti-PD-1 autoantibody levels were not significantly associated with the treatment response in any patient. However, when examining only patients who received the Atezo/Bev as their first-line therapy, higher anti-PD-1 autoantibody levels were significantly associated with worse overall survival rates. The titer was an independent risk factor for poor prognosis (odds ratio [OR] = 7.8, P = .013), in addition to a higher neutrophil-to-lymphocyte ratio (OR = 7.1, P = .009) and lower albumin levels (OR = 14.2, P = .003). Conclusion: Serum anti-PD-1 autoantibody levels correlated with the overall survival rate in patients who received Atezo/Bev as first-line therapy. Serum anti-PD-1 autoantibody levels may serve as new biomarkers for predicting the efficacy of immune checkpoint inhibitors in patients with HCC.

DOI： 10.1016/j.gastha.2024.07.018

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Detection of hepatocellular carcinoma during Fontan-associated liver disease follow-up: a report of three cases

Hideki Onishi, Norihisa Toh, Teiji Akagi, Kenji Baba, Yasuhiro Kotani, Akinobu Takaki, Shingo Kasahara, Hiroshi Ito

Clinical Journal of Gastroenterology 2023.11

The prediction of early progressive disease in patients with hepatocellular carcinoma receiving atezolizumab plus bevacizumab. International journal

Yasuto Takeuchi, Kazuhiro Nouso, Shin-Ichi Fujioka, Kazuya Kariyama, Haruhiko Kobashi, Shuji Uematsu, Akio Moriya, Hiroaki Hagihara, Hiroyuki Takabatake, Shinichiro Nakamura, Kazuhisa Yabushita, Tatsuya Kikuchi, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Hideki Onishi, Hidenori Shiraha, Akinobu Takaki

Cancer medicine 12 ( 17 ) 17559 - 17568 2023.8

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND AND AIMS: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first-line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real-world clinical practice. METHODS: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e-PD; PD within 9 weeks) and analyzed the risk factors for e-PD. RESULTS: There were 47 patients (25.5%) diagnosed as e-PD. Patients with e-PD had a worse performance status (PS) and albumin-bilirubin (ALBI) and Child-Pugh (C-P) scores and a significantly higher rate of a systemic therapy than those with non-e-PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9-10, p < 0.001), ALBI score ≥-2.30 (OR = 2.1, 95% CI = 1.0-4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4-6.4, p = 0.0038) were significant and independent determinants of e-PD. When examining the liver function trends in e-PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001). CONCLUSIONS: The liver function and systemic therapy are useful predictors of e-PD in HCC patients treated with atezolizumab plus bevacizumab in real-world clinical practice.

DOI： 10.1002/cam4.6369

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Disease Progression-Related Markers for Aged Non-Alcoholic Fatty Liver Disease Patients.

Kosaku Morimoto, Yasuto Takeuchi, Akinobu Takaki, Nozomu Wada, Atsushi Oyama, Takuya Adachi, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada

Acta medica Okayama 77 ( 4 ) 377 - 385 2023.8

Language：English Publishing type：Research paper (scientific journal)

Liver fibrosis is an important phenomenon in non-alcoholic fatty liver disease (NAFLD) progression. Standard markers reflecting liver fibrosis, including the FIB-4 index, increase with age. This study aimed to identify fibrosis progression-related markers that are diagnostically beneficial even in aged individuals. Serum levels of pro- and anti-inflammatory cytokines were measured by multiple enzyme-linked immunosorbent assay. Two standard NAFLD or fibrosis progression-related markers - the FIB-4 index and APRI score - were analyzed along with cytokine levels to define the best approach to discriminate advanced fibrosis. Ninety-eight NAFLD patients were enrolled: 59 and 39 patients with fibrosis stages 1-2 and 3-4 respectively. In addition to the FIB-4 index and APRI score, the following factors showed significant differences between stages 1-2 and stages 3-4 in a multivariate analysis: platelet counts, IP-10, and RANTES. The fibrosis stage, FIB-4, APRI, PDGF-BB, and RANTES were related to the prognosis. In aged patients, IP-10, GM-CSF, and RANTES differed between stages 1-2 and stages 3-4. FIB-4 and APRI were beneficial for their correlation with fibrosis. However, to stratify either young or elderly advanced fibrosis patients, and to identify patients likely to have a bad outcome, RANTES was the best marker.

DOI： 10.18926/AMO/65748

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Oxidative stress-related markers as prognostic factors for patients with primary sclerosing cholangitis in Japan. International journal

Atsushi Oyama, Akinobu Takaki, Takuya Adachi, Nozomu Wada, Yasuto Takeuchi, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada, Motoyuki Otsuka

Hepatology international 17 ( 5 ) 1215 - 1224 2023.7

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/PURPOSE: Primary sclerosing cholangitis (PSC) is a rare chronic liver disease. The mechanisms and prediction of PSC progression are unclear. Recent investigations have shown that general conditions, such as oxidative stress, affect the course of chronic diseases. We investigated the clinical course and oxidative stress-related condition of PSC to determine prognostic factors. METHODS: We recruited 58 patients with PSC (mean age; 37.4 years, mean observation period; 1382 days) who visited our department from 2003 to 2021. Clinical characteristics were investigated to define prognostic factors. Oxidative stress status was evaluated using two types of markers: an oxidative stress marker (serum reactive oxygen metabolite; dROM) and an antioxidant marker (serum OXY adsorbent test; OXY). RESULTS: The revised Mayo risk, Child-Pugh, model for end-stage liver disease-sodium (MELD-Na) scores or fibrosis-related FIB-4 index significantly predicted poor overall survival. High intestinal immunoglobulin A (IgA) levels predicted poor survival. Among patients with high and intermediate revised Mayo risk scores, those with physiologically high dROM levels showed better survival than those with lower dROM levels. In this population, dROM was negatively correlated with AST and IgA, which are both correlated with survival. CONCLUSIONS: High and intermediate revised Mayo risk score group predicted a poor clinical course in PSC. Additionally, the Child-Pugh score, MELD-Na score, FIB-4 index, and serum IgA were significantly correlated with survival. In patients with high and intermediate revised Mayo risk scores, physiologically high oxidative stress status correlated with low IgA levels and a good prognosis.

DOI： 10.1007/s12072-023-10557-2

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肝生検により診断された播種性bacillus Calmette-Guerin(BCG)症の1例

伊木道子, 竹内康人, 須江真彦, 三宅望, 足立卓哉, 和田望, 大西秀樹, 白羽秀則, 高木章乃夫, 大塚基之

日本消化器病学会中国支部例会プログラム・抄録集 119回 62 - 62 2023.6

【肝胆膵領域におけるアルコール医学の新潮流】アルコール性肝障害の臨床研究における新知見アルコール性肝障害における肝移植の現状

高木章乃夫, 竹内康人, 八木孝仁, 大塚基之

肝胆膵 86 ( 4 ) 523 - 528 2023.4

肝硬変の成因と病態の推移当院における肝硬変の成因と病態の推移

足立卓哉, 高木章乃夫, 大山淳史, 和田望, 竹内康人, 大西秀樹, 白羽英則

肝臓 64 ( Suppl.1 ) A266 - A266 2023.4

肝癌における非薬物療法の最前線(手術,焼灼,TACE,放射線治療) 肝細胞癌の集学的治療における放射線治療の役割

大西秀樹, 竹内康人, 高木章乃夫

肝臓 64 ( Suppl.1 ) A172 - A172 2023.4

肝硬変の成因と病態の推移当院における肝硬変の成因と病態の推移

足立卓哉, 高木章乃夫, 大山淳史, 和田望, 竹内康人, 大西秀樹, 白羽英則

肝臓 64 ( Suppl.1 ) A266 - A266 2023.4

当院における免疫チェックポイント阻害薬による免疫有害事象の臨床的特徴についての検討肝障害を中心に

須江真彦, 竹内康人, 大山淳史, 足立卓哉, 大西秀樹, 白羽英則, 高木章乃夫

日本消化器病学会雑誌 120 ( 臨増総会 ) A272 - A272 2023.3

膵癌化学療法における血中自己抗体を用いた治療効果予測の可能性

松本和幸, 高木章乃夫, 高原政宏, 小幡泰介, 藤井佑樹, 山崎辰洋, 内田大輔, 堀口繁, 堤康一郎, 加藤博也

日本消化器病学会雑誌 120 ( 臨増総会 ) A292 - A292 2023.3

急性肝炎が遷延し,死亡に至ったE型肝炎の一例

安中哲也, 高木章乃夫, 大山淳史, 足立卓哉, 和田望, 坂田雅浩, 白羽英則, 岡田裕之

肝臓 64 ( 2 ) 101 - 101 2023.2

History of Transcatheter Arterial Chemoembolization Predicts the Efficacy of Hepatic Arterial Infusion Chemotherapy in Hepatocellular Carcinoma Patients.

Hideki Onishi, Kazuhiro Nouso, Akinobu Takaki, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Yasuto Takeuchi, Hidenori Shiraha, Hiroyuki Okada

Acta medica Okayama 76 ( 6 ) 695 - 703 2022.12

Language：English Publishing type：Research paper (scientific journal)

This study sought to identify factors that are predictive of a therapeutic response to hepatic arterial infusion chemotherapy (HAIC) by focusing on the number of prior transcatheter arterial chemoembolization (TACE) sessions. To determine the parameters predicting a good response to HAIC, we retrospectively analyzed 170 patients with hepatocellular carcinoma (HCC) who received HAIC regimens comprising low-dose cisplatin combined with 5-fluorouracil (LFP) or cisplatin (CDDP) for the first time. In both the LFP and CDDP regimens, the response rates were significantly lower in patients with three or more prior TACE sessions than in those with two or fewer prior TACE sessions (LFP 57% versus 28%; p=0.01, CDDP 27% versus 6%; p=0.01). Multivariable logistic regression analysis revealed that the number of prior TACE sessions (≥ 3) was significantly associated with non-responder status (odds ratio 4.17, 95% Confidence Interval (CI) 1.76-9.86) in addition to the HAIC regimen. Multivariable analysis using the Cox proportional hazards model revealed that a larger number of prior TACE sessions (≥ 3) was a significant risk factor for survival (hazard ratio 1.60, 95% CI 1.12-2.29) in addition to Child-Pugh class, serum alpha-fetoprotein concentration, and maximum diameter of HCC. HCC patients who receive fewer prior TACE sessions (≤ 2) were found to be better responders to HAIC.

DOI： 10.18926/AMO/64120

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Pathogenesis of Severe Liver Injury in Patients with Anorexia Nervosa: A Report of Two Cases and a Literature Review.

Masahiro Sakata, Akinobu Takaki, Atsushi Oyama, Takuya Adachi, Nozomu Wada, Yasuto Takeuchi, Tetsuya Yasunaka, Hideki Onishi, Hidenori Shiraha, Hiroyuki Okada

The Kurume medical journal 67 ( 2.3 ) 121 - 129 2022.11

Language：English Publishing type：Research paper (scientific journal)

Anorexia nervosa (AN) can cause severe protein energy malnutrition and the consequent development of various organ disorders. AN is known to cause hepatic complications. We report two cases of starvation and refeeding-induced liver injury in patients with AN, and review the literature on the hepatic complications of AN. Acute liver injury can be induced by both starvation and refeeding, although the underlying pathomechanisms and management of liver injury differ between these two conditions. Clinicians should carefully identify the clinical features to ensure an accurate diagnosis and appropriate management of these conditions.

DOI： 10.2739/kurumemedj.MS6723011

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Papers - TAKAKI Akinobu