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MATSUURA Takanori
Graduate School of Medicine / Faculty of Medical Sciences
Assistant Professor

Researcher basic information

■ Research Areas
  • Life sciences / Gastroenterology

Research activity information

■ Paper
  • Shohei Komatsu, Toshifumi Tada, Nobuaki Ishihara, Masaki Omori, Takanori Matsuura, Eisuke Ueshima, Keitaro Sofue, Yoshimi Fujishima, Jun Ishida, Masahiro Kido, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Yoshihide Nanno, Hiroaki Yanagimoto, Yuzo Kodama, Takumi Fukumoto
    Mar. 2026, World Journal of Surgery
    Scientific journal

  • Nobuaki Ishihara, Shohei Komatsu, Toshifumi Tada, Takanori Matsuura, Eisuke Ueshima, Keitaro Sofue, Masaki Omori, Masahiro Kido, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Kentaro Tai, Toshihiko Yoshida, Keisuke Arai, Hiroaki Yanagimoto, Yuzo Kodama, Takamichi Murakami, Takumi Fukumoto
    Mar. 2026, Hepatology Research
    Scientific journal

  • Tatsuya Sakane, Toshifumi Tada, Takanori Matsuura
    Feb. 2026, Hepatology Research
    Scientific journal

  • Masaki Omori, Shohei Komatsu, Toshifumi Tada, Nobuaki Ishihara, Takanori Matsuura, Eisuke Ueshima, Yoshimi Fujishima, Jun Ishihda, Masahiro Kido, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Hiroaki Yanagimoto, Keitaro Sofue, Yuzo Kodama, Takumi Fukumoto
    BACKGROUND: This study evaluated how lesion location affects treatment response and prognosis in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN) or immune checkpoint inhibitors (ICIs; atezolizumab/bevacizumab or durvalumab/tremelimumab). Considering tumor microenvironment and heterogeneity, we analyzed lesion-specific responses to optimize therapy. METHODS: In this retrospective study, lesion-specific responses were assessed for intrahepatic lesions (IHLs), lung, lymph node, intra-abdominal, and other lesions; bone metastases were excluded due to evaluation limitations. Responses were measured using a modified size-based RECIST 1.1 method. Lesion-specific objective response rate (ORR) and disease control rate (DCR) were compared between LEN and ICI groups. RESULTS: ORR for IHLs was higher with ICIs than LEN (16.3 % vs. 3.5 %, P = 0.002). No significant differences were observed for lung, lymph node, or intra-abdominal lesions; adrenal metastases showed no response in either group. Subgroup analysis indicated better ORR and DCR for lung lesions treated with ICIs and lymph node lesions treated with LEN in patients without IHLs versus those with IHLs. CONCLUSIONS: ICIs achieved higher ORR in IHLs than LEN, with no significant differences for metastatic lesions. The presence of IHLs may influence distant lesion response, and therapeutic efficacy varies with treatment regimen.
    Nov. 2025, HPB : the official journal of the International Hepato Pancreato Biliary Association, English, International magazine
    Scientific journal

  • Shohei Komatsu, Toshifumi Tada, Kazuki Terashima, Nobuaki Ishihara, Masaki Omori, Takanori Matsuura, Eisuke Ueshima, Keitaro Sofue, Yuzo Kodama, Takumi Fukumoto
    Oct. 2025, World Journal of Surgery
    Scientific journal

  • Hideko Ohama, Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Tanaka, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Atsushi Naganuma, Hisashi Kosaka, Tomomitsu Matono, Hidekatsu Kuroda, Yutaka Yata, Hiroki Nishikawa, Michitaka Imai, Tomoko Aoki, Hironori Ochi, Hideyuki Tamai, Shohei Komatsu, Fujimasa Tada, Shinichiro Nakamura, Yoshiko Nakamura, Teruki Miyake, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Akemi Tsutsui, Takuya Nagano, Kazunari Tanaka, Takanori Matsuura, Yuichi Koshiyama, Yuki Kanayama, Hidenao Noritake, Hirayuki Enomoto, Kosuke Matsui, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada
    BACKGROUND: Immune-mediated adverse events (imAEs) are a significant concern in patients with unresectable hepatocellular carcinoma (uHCC) undergoing combination immunotherapy with durvalumab and tremelimumab (Dur/Tre). This study aimed to investigate the potential association of risk factors, particularly nutrition and immune markers, associated with the development of imAEs. METHODS: Between November 2022 and December 2024, 312 patients with uHCC treated with Dur/Tre were enrolled and retrospectively analyzed. Clinical characteristics, inflammatory markers, and nutritional indices (Geriatric Nutritional Risk Index [GNRI], body mass index, Prognostic Nutritional Index-Onodera, C-reactive protein-to-albumin ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio) were evaluated to identify predictors for imAE development. RESULTS: The imAEs occurred in 122 patients (39.1%), most commonly affecting dermatological, gastrointestinal, and endocrine systems. On multivariate analysis, only normal GNRI (≥ 98) was independently associated with a higher incidence of imAE (odds ratio: 1.99, 95% confidence interval: 1.05-3.79, P = 0.036). Patients with GNRI ≥ 98 also showed better overall survival (OS) than those with GNRI < 98 (not reached vs. 12.5 months, P < 0.001). Among patients who developed imAEs, no significant differences were observed in the imAE types or high-dose steroid use between the GNRI ≥ 98 group (n = 66) and the GNRI < 98 group (n = 56) (40.9% vs. 58.9%, P = 0.069). CONCLUSIONS: Normal GNRI status (≥ 98) was associated with an increased risk of imAE development and improved OS in patients with uHCC receiving Dur/Tre therapy. GNRI may be a useful clinical factor for identifying patients at higher risk of developing imAEs.
    Aug. 2025, Journal of gastroenterology, English, Domestic magazine
    Scientific journal

  • Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hidenao Noritake, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Kosuke Matsui, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo
    AIM: To evaluate the safety and efficacy of durvalumab plus tremelimumab (Dur/Tre) in older adults with unresectable hepatocellular carcinoma (HCC). METHODS: A total of 345 patients with HCC who received Dur/Tre were included in this study. Using propensity score matching, we compared outcomes between older (aged ≥ 75 years; n = 120) and younger individuals (n = 120). RESULTS: The median progression-free survival (PFS) was 3.3 months in the older group and 4.5 months in the younger group (p = 0.271). The median overall survival (OS) was 17.0 months in older individuals and 19.2 months in younger individuals (p = 0.598). No statistically significant differences were observed in the therapeutic response between the two groups (p = 0.264). Additionally, the incidence of immune-mediated adverse events (AEs) did not differ significantly between older and younger individuals. Multivariate analyses revealed that age group (older vs. younger) was not an independent prognostic factor for PFS (p = 0.250) or OS (p = 0.489). In a subgroup analysis stratifying older individuals into three age categories (75-79, 80-84, and ≥ 85 years), no significant differences were observed in the cumulative OS or PFS across the subgroups (p = 0.308 and 0.783). Similarly, the incidence of immune-mediated AEs did not differ significantly among the age categories. CONCLUSIONS: Dur/Tre appears to be a safe and effective treatment option for patients with HCC, regardless of age. Dur/Tre appears to be a safe and effective treatment option for patients with unresectable HCC, regardless of age.
    Aug. 2025, Hepatology research : the official journal of the Japan Society of Hepatology, English, International magazine
    Scientific journal

  • Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Kosuke Matsui, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo
    BACKGROUND AND AIMS: To assess the outcomes of patients with hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atezo/Bev), categorised by oncological resectability criteria, which reflect tumour burden and extent of disease. METHODS: A cohort of 467 HCC patients who received Atezo/Bev was enrolled. Patients were classified into two groups based on oncological resectability criteria: BR (borderline resectable) 1 (n = 153) and BR2 (n = 314). RESULTS: The median progression-free survival (PFS) was 9.0 months in the BR1 group and 6.8 months in the BR2 group (p = 0.014). Multivariable analysis identified the following independent prognostic factors for PFS: age ≥ 75 years (hazard ratio [HR], 1.309), albumin-bilirubin (ALBI) grade ≥ 2 (HR, 1.494), neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (HR, 1.289), α-fetoprotein ≥ 100 ng/mL (HR, 1.523) and BR2 classification (HR, 1.360). The median overall survival (OS) was 25.3 months in the BR1 group and 22.3 months in the BR2 group (p = 0.048). Multivariable analysis identified the following independent prognostic factors for OS: age ≥ 75 years (HR, 1.522), ALBI grade ≥ 2 (HR, 2.411), NLR ≥ 3 (HR, 1.635), α-fetoprotein ≥ 100 ng/mL (HR, 1.530) and BR2 classification (HR, 1.421). When oncological resectability factors (tumour number and size, vascular invasion and extrahepatic spread) were incorporated into the multivariable analysis, major vascular invasion emerged as a significant predictor of both PFS (HR, 3.188) and OS (HR, 2.650). CONCLUSIONS: In patients with HCC characterised by limited resectability undergoing Atezo/Bev, vascular invasion, in addition to liver function, is a critical prognostic determinant of tumour progression.
    Aug. 2025, Liver international : official journal of the International Association for the Study of the Liver, 45(8) (8), e70217, English, International magazine
    Scientific journal

  • Takanori Matsuura, Masatoshi Abe, Yoshiyuki Harada, Masahiro Kido, Hajime Nagahara, Yuzo Kodama, Yoshihide Ueda, Eiji Hara, Hirohiko Niioka, Tomonori Matsumoto
    Jul. 2025, Communications Medicine
    Scientific journal

  • Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo
    AIM: To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). METHODS: A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted. Additionally, hazard ratio (HR) spline curve analysis was used to determine the optimal NLR cut-off values for predicting overall survival (OS). RESULTS: The median progression-free survival (PFS) was 3.5 months (95% confidence interval [CI]: 2.7-4.4), whereas the median OS was not reached (95% CI: 12.1 months-not reached). Multivariate analysis demonstrated that treatment with Dur/Tre as a second-line therapy or beyond was independently associated with worse PFS (HR: 1.819; 95% CI: 1.230-2.688; p = 0.003). Furthermore, an NLR of ≥ 2.56 was identified as an independent predictor of reduced OS (HR: 1.919; 95% CI: 1.033-3.566; p = 0.039). The median OS was not reached (95% CI: 12.3 months-not reached) in patients with an NLR of < 2.56, compared with 12.1 months (95% CI: 9.0 months-not reached) in those with an NLR of ≥ 2.56 (p = 0.016). A Sankey diagram illustrating post-treatment outcomes revealed that a significantly larger proportion of patients with high NLRs did not proceed to subsequent therapies but instead received best supportive care (p = 0.046). Spline curve analysis showed that an NLR range of approximately 2.3-3.0 represents an appropriate cut-off for predicting OS. CONCLUSIONS: The NLR is a significant prognostic biomarker for OS in patients with HCC treated with Dur/Tre.
    Jun. 2025, Hepatology research : the official journal of the Japan Society of Hepatology, English, International magazine
    Scientific journal

  • Shohei Komatsu, Toshifumi Tada, Takashi Nishimura, Motofumi Tanaka, Atsushi Takebe, Saeko Kushida, Yoshimi Fujishima, Nobuaki Ishihara, Takanori Matsuura, Ikuo Nakamura, Taro Okazaki, Masahiro Tsuda, Jun Ishida, Ippei Matsumoto, Seiko Hirono, Hirayuki Enomoto, Yuzo Kodama, Takumi Fukumoto
    INTRODUCTION: Oncological resectability criteria for hepatocellular carcinoma have been defined (resectable [R]/borderline resectable 1 [BR1]/borderline resectable 2 [BR2]); however, their validation is necessary. METHODS: A total of 1,469 patients who underwent hepatectomy and 525 patients who received systemic chemotherapy, including lenvatinib, atezolizumab plus bevacizumab, and durvalumab plus tremelimumab, as first-line treatment were analyzed. RESULTS: In the BR1 group, the median survival times (MSTs) of patients who underwent hepatectomy and systemic chemotherapy were 52.7 and 34.6 months, respectively, without a significant difference (p = 0.075). In the propensity score matching (PSM) analysis of the BR1 group, the MSTs of hepatectomy and systemic chemotherapy were 42.4 and 35.1 months, respectively, without a significant difference (p = 0.772). Hepatitis virus infection, modified albumin-bilirubin (mALBI) grade 2b + 3, and the presence of extrahepatic metastasis were identified as poor prognostic factors for hepatectomy, whereas mALBI grade 2b + 3 was the only poor prognostic factor for systemic chemotherapy. In the BR2 group, the MSTs of hepatectomy and systemic chemotherapy were 20.1 and 19.5 months, respectively, with significantly better survival for hepatectomy than for systemic chemotherapy (p = 0.017). In the PSM analysis of the BR2 group, the MSTs of hepatectomy and systemic chemotherapy were 20.1 and 21.0 months, respectively, without a significant difference (p = 0.375). Serum alpha-fetoprotein levels≥100, intrahepatic tumor number ≥6, and the presence of extrahepatic metastasis were identified as poor prognostic factors for hepatectomy, whereas female, serum alpha-fetoprotein levels ≥100, mALBI grade 2b + 3, intrahepatic maximal tumor size >5 cm, and the presence of extrahepatic metastasis were identified as poor prognostic factors for systemic chemotherapy. CONCLUSION: In the PSM analysis, no significant differences were observed between the BR1 and BR2 groups for hepatectomy and systemic chemotherapy. The intrahepatic tumor number for hepatectomy and the intrahepatic maximal tumor size for systemic chemotherapy are significant risk factors for BR2 patients, highlighting the characteristics of each treatment and the potential for selecting the optimal modality.
    Jun. 2025, Liver cancer, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Jun Kitadai, Toshifumi Tada, Takanori Matsuura, Mayumi Ehara, Tatsuya Sakane, Miki Kawano, Yuta Inoue, Shoji Tamura, Aya Horai, Yuuki Shiomi, Yoshihiko Yano, Yuzo Kodama
    AIMS: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; however, they are associated with ICI-induced liver injury (ICI-LI), which manifests as hepatocellular, mixed, or cholestatic patterns with variable treatment responses. This study aimed to develop and validate a predictive model to identify ICI-LI type using clinical data available at ICI initiation. METHODS: A retrospective analysis of 297 patients with ICI-LI was conducted. Baseline clinical data were analyzed using univariate and multivariate logistic regression to predict ICI-LI types in the training and validation cohorts. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariate analysis in the training cohort identified male sex (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.57-7.06, p = 0.002), serum albumin levels (OR: 0.42, 95% CI: 0.19-0.91, p = 0.027), and serum alanine aminotransferase (ALT) levels (OR: 0.97, 95% CI: 0.94-0.99, p = 0.015) as significant predictors, along with ICI regimen types selected using the Akaike information criterion. The logistic regression model, expressed as p = 1/{1 + (-(5.02 + 1.20 × (sex [F:0, M:1])) - 0.87 × albumin [g/dL] - 0.03 × ALT [U/L] - 0.9 × (drug [non-anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) related regimen:0, anti-CTLA-4 related regimen:1]))}, achieved an area under the ROC (AUROC) of 0.73 (95% CI: 0.63-0.82) in the training cohort. At a cut-off of 0.86, the sensitivity was 60.3%, specificity 74.4%, positive predictive value 92.3%, and negative predictive value 26.9%. In the validation cohort, the AUROC was 0.752 (95% CI: 0.476-1.00). CONCLUSION: This predictive model demonstrates its utility in classifying ICI-LI types.
    Apr. 2025, JGH open : an open access journal of gastroenterology and hepatology, 9(4) (4), e70147, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Eisuke Ueshima, Keitaro Sofue, Shohei Komatsu, Nobuaki Ishihara, Masato Komatsu, Akihiro Umeno, Kentaro Nishiuchi, Ryohei Kozuki, Takeru Yamaguchi, Takanori Matsuura, Toshifumi Tada, Takamichi Murakami
    Background/Objectives: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). Methods: We performed immunohistochemical staining with CD3+ and CD8+ antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). Results: HCCs with peritumoral enhancement in the arterial phase (p < 0.001) and rim APHE (p = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase (p = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature (p < 0.001). Conclusions: We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy.
    Mar. 2025, Cancers, 17(6) (6), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Shohei Komatsu, Yoshihiko Yano, Kazuki Terashima, Yoshimi Fujishima, Jun Ishida, Nobuaki Ishihara, Takanori Matsuura, Tomoaki Okimoto, Yuzo Kodama, Takumi Fukumoto
    PURPOSE: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the first-order or main trunk/contralateral branches (Vp3/4) is poor. The present study aimed to clarify the real-world data of atezolizumab plus bevacizumab treatment (Ate/bev) for HCC patients with Vp3/4 PVTT. METHODS: The subjects of this study were 22 consecutive HCC patients with Vp3/4 PVTT, who were treated with Ate/bev. Survival rates and radiological responses were evaluated based on the modified albumin-bilirubin (mALBI) grade [mALBI 1 + 2a (1/2a) versus 2b + 3 (2b/3)] using the modified Response Evaluation Criteria in Solid Tumors. RESULTS: The median survival time of the 22 patients was 15.0 months, with 1- and 2-year survival rates of 62.7% and 49.3%, respectively. The objective response (OR) rates of patients with mALBI 1/2a and 2b/3 were 91.7% (11/12) and 10.0% (1/10), respectively, with a significant difference (p < 0.001). The 2-year survival rates of patients with mALBI 1/2a and 2b/3 were 78.6% and 20.0%, respectively, with a significant difference (p = 0.0041). CONCLUSION: Ate/bev was effective for treating HCC patients with Vp3/4 PVTT. OR rate and MST were favorable, particularly for patients with preserved liver function (mALBI 1/2a), suggesting its great potential for the treatment of HCC in patients with Vp3/4 PVTT.
    Feb. 2025, Surgery today, 55(7) (7), 900 - 908, English, Domestic magazine
    Scientific journal

  • Yuta Inoue, Yoshihiko Yano, Saeko Kushida, Seiya Hirohata, Seitetsu Yoon, Eiichiro Yasutomi, Hirotaka Hirano, Soo Ki Kim, Ryutaro Yoshida, Yoshihide Ueda, Kenji Momose, Hiroki Hayashi, Takuo Kado, Katsuhisa Nishi, Hidenori Tanaka, Tomomitsu Matono, Atsushi Yamamoto, Hiroshi Tei, Chiharu Nishioka, Yosuke Yagi, Shoji Tamura, Tatsuya Sakane, Mayumi Ehara, Miki Kawano, Jun Kitadai, Takanori Matsuura, Yuuki Shiomi, Shohei Komatsu, Takumi Fukumoto, Toshifumi Tada, Yuzo Kodama
    BACKGROUND AND AIMS: Tremelimumab plus durvalumab (Dur/Tre) combination therapy is now a first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Because systemic therapy is not effective in some patients, it is clinically important to identify factors that could predict the response to treatment at an early stage. We investigated the factors associated with the response to Dur/Tre for advanced HCC in a clinical setting. METHODS: Seventy patients (median age 74 years; 61 men) who received Dur/Tre between March 2023 and September 2024 were analyzed. We examined the factors associated with the treatment response, including pretreatment factors and factors early in treatment. RESULTS: The median treatment duration was 77.5 (interquartile range [IQR] 28-187) days. The overall response and disease control rates were 25.8% and 58.1%, respectively. The median (IQR) progression-free survival (PFS) and overall survival (OS) were 82 (61-133) and 415 (337-NA) days, respectively. Multivariable analysis revealed that higher absolute lymphocyte count (ALC) and lower des-γ-carboxyprothrombin (DCP) levels were significantly associated with PFS. Receiver operating characteristic curve analysis showed that the cutoff value for ALC after 4 weeks of treatment in relation to clinical efficacy was 1125/mm3. A log-rank test using the Kaplan-Meier method showed that OS was significantly longer in patients with ALC above the cutoff and in patients whose DCP levels decreased after starting treatment. CONCLUSION: Higher ALC and lower DCP levels after treatment initiation were associated with the clinical efficacy of Dur/Tre for advanced HCC.
    Feb. 2025, JGH open : an open access journal of gastroenterology and hepatology, 9(2) (2), e70123, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Nobuaki Ishihara, Shohei Komatsu, Yoshihiko Yano, Yoshimi Fujishima, Jun Ishida, Masahiro Kido, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Toshihiko Yoshida, Kentaro Tai, Keisuke Arai, Hiroaki Yanagimoto, Hirochika Toyama, Takanori Matsuura, Toshifumi Tada, Yuzo Kodama, Takumi Fukumoto
    BACKGROUND/AIM: Atezolizumab plus bevacizumab (AteBev) is widely used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, evidence regarding the optimal drug sequence following AteBev treatment is limited. This study aimed to compare the treatment outcomes between tyrosine kinase inhibitors (TKIs) and durvalumab plus tremelimumab (DurTre) following AteBev treatment. PATIENTS AND METHODS: Overall, 134 consecutive patients who received AteBev for advanced HCC were enrolled in this study. Treatment outcomes were retrospectively compared between TKIs (AteBev→TKI group) and DurTre (AteBev→DurTre group). RESULTS: The AteBev→TKI and Ate→DurTre groups included 46 and 7 patients, respectively. The AteBev→TKI group had significantly longer median progression-free survival after second-line treatment (3.6 vs. 0.94 months, p<0.001). The disease control rate was significantly higher in the AteBev→TKI group (p=0.020). The serum alpha-fetoprotein levels significantly decreased at one month in the AteBev→TKI group (0.909 vs. 1.435, p=0.035), whereas the albumin-bilirubin score significantly decreased at one month in the AteBev→TKI group (0.875 vs. 0.952, p=0.017). Each group reported no new unmanageable adverse events. CONCLUSION: TKIs may be a more optimal drug sequence than DurTre after AteBev treatment from an oncological perspective. TKIs following AteBev treatment require careful monitoring for deteriorating liver function.
    International Institute of Anticancer Research, Jan. 2025, Anticancer research, 45(1) (1), 251 - 260, English, International magazine
    Scientific journal

  • Takanori Ito, Yasuto Takeuchi, Kazuyuki Mizuno, Michitaka Imai, Yoko Yoshimaru, Kazumichi Abe, Masanori Abe, Takanori Matsuura, Masataka Yokode, Masahiro Shiokawa, Yuzo Kodama, Mina Komuta, Kenichi Harada, Atsushi Tanaka
    With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI-induced liver injury) as an immune-related adverse event has become a major concern in clinical practice. Because severe cases of liver injury require administration of corticosteroids, a comprehensive evaluation is crucial, including clinical course, blood and imaging tests, and if necessary, pathological examination through liver biopsy. As with liver injury induced by other drugs, classification of injury type by R-value is useful in deciding treatment strategies for ICI-induced liver injury. Histologically, the most representative feature is an acute hepatitis-like hepatocellular injury, characterized by diffuse lobular inflammation accompanied by CD8-positive T lymphocytes. Another condition that can cause liver injury during ICI treatment is cholangitis accompanied by non-obstructive bile duct dilatation and bile duct wall thickening. Many cases of ICI-induced cholangitis are classified as non-hepatocellular injury type, and they have been reported to respond poorly to corticosteroids. It is essential that gastroenterologists/hepatologists and doctors in various departments work in cooperation to develop a system that achieves early diagnosis and appropriate treatment of ICI-induced liver injury.
    Aug. 2024, Hepatology research : the official journal of the Japan Society of Hepatology, 54(8) (8), 719 - 726, English, International magazine
    Scientific journal

  • Miki Kawano, Yoshihiko Yano, Atsushi Yamamoto, Eiichiro Yasutomi, Yuta Inoue, Jun Kitadai, Ryutaro Yoshida, Takanori Matsuura, Yuuki Shiomi, Yoshihide Ueda, Yuzo Kodama
    Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan-Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI.
    Apr. 2024, Diagnostics (Basel, Switzerland), 14(8) (8), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Yoshihiko Yano, Itsuko Sato, Takamitsu Imanishi, Ryutaro Yoshida, Takanori Matsuura, Yoshihide Ueda, Yuzo Kodama
    Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.
    Mar. 2024, Diagnostics (Basel, Switzerland), 14(7) (7), English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Takanori Matsuura, Yoshihide Ueda, Yoshiyuki Harada, Kazuki Hayashi, Kisara Horisaka, Yoshihiko Yano, Shinichi So, Masahiro Kido, Takumi Fukumoto, Yuzo Kodama, Eiji Hara, Tomonori Matsumoto
    BACKGROUND: Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs. METHODS: The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells. RESULTS: Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination. CONCLUSIONS: Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.
    Oct. 2023, British journal of cancer, 129(8) (8), 1251 - 1260, English, International magazine
    Scientific journal

  • Fumiaki Kawara, Takanori Matsuura, Kodai Yamanaka, Chiharu Nishioka
    Aug. 2023, Internal medicine (Tokyo, Japan), 62(15) (15), 2285 - 2286, English, Domestic magazine
    Scientific journal

  • Yoshihiko Yano, Atsushi Yamamoto, Takuya Mimura, Saeko Kushida, Seiya Hirohata, Seitetsu Yoon, Hirotaka Hirano, Soo Ki Kim, Yuri Hatazawa, Kenji Momose, Hiroki Hayashi, Takuo Kado, Katsuhisa Nishi, Hidenori Tanaka, Takanori Matsuura, Ryutaro Yoshida, Naoki Asaji, Eiichiro Yasutomi, Yuuki Shiomi, Akihiro Minami, Shohei Komatsu, Takumi Fukumoto, Yoshihide Ueda, Yuzo Kodama
    BACKGROUND AND AIM: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). METHODS: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. RESULTS: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin-bilirubin (ALBI) grade and low level of des-gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log-rank tests with the Kaplan-Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. CONCLUSION: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.
    Jul. 2023, JGH open : an open access journal of gastroenterology and hepatology, 7(7) (7), 476 - 481, English, International magazine
    Scientific journal
    Link to Kobe Univ. Repository (Kernel)

  • Fumiaki Kawara, Akihiro Minami, Kazuya Hara, Kodai Yamanaka, Takanori Matsuura, Mitsuko Mimura, Chiharu Nishioka
    Nov. 2022, Endoscopy, 54(11) (11), E662-E663, English, International magazine
    Scientific journal

  • Yoshihiko Yano, Atsushi Yamamoto, Akihiro Minami, Kenji Momose, Takuya Mimura, Soo Ki Kim, Hiroki Hayashi, Takuo Kado, Hirotaka Hirano, Seiya Hirohata, Seitetsu Yoon, Katsuhisa Nishi, Hiroshi Tei, Hidenori Tanaka, Sachiko Oouchi, Takanori Matsuura, Eiichiro Yasutomi, Yuri Hatazawa, Yuuki Shiomi, Yoshihide Ueda, Yuzo Kodama
    BACKGROUND AND AIM: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. METHODS: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. RESULTS: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan-Meier analysis revealed no significant differences in progression-free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). CONCLUSION: The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.
    Jun. 2022, JGH open : an open access journal of gastroenterology and hepatology, 6(6) (6), 427 - 433, English, International magazine
    Scientific journal

■ Lectures, oral presentations, etc.
  • Potential role of Geriatric Nutritional Risk Index as a risk factor for immune-mediated adverse events during durvalumab plus tremelimumab therapy in unresectable hepatocellular carcinoma.
    Hideko Ohama, Atsushi Hiraoka, Toshifumi Tada, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Tanaka, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Atsushi Naganuma, Hisashi Kosaka, Tomomitsu Matono, Hidekatsu Kuroda, Yutaka Yata, Hiroki Nishikawa, Michitaka Imai, Tomoko Aoki, Hironori Ochi, Hideyuki Tamai, Shohei Komatsu, Fujimasa Tada, Shinichiro Nakamura, Yoshiko Nakamura, Teruki Miyake, Osamu Yoshida, Kazuhiro Nouso, Asahiro Morishita, Norio Itokawa, Tomomi Okubo, Taeang Arai, Akemi Tsutsui, Takuya Nagano, Kazunari Tanaka, Takanori Matsuura, Yuichi Koshiyama, Yuki Kanayama, Hidenao Noritake, Hirayuki Enomoto, Kosuke Matsui, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo, Takashi Kumada
    Journal of gastroenterology, Aug. 2025, English, BACKGROUND: Immune-mediated adverse events (imAEs) are a significant concern in patients with unresectable hepatocellular carcinoma (uHCC) undergoing combination immunotherapy with durvalumab and tremelimumab (Dur/Tre). This study aimed to investigate the potential association of risk factors, particularly nutrition and immune markers, associated with the development of imAEs. METHODS: Between November 2022 and December 2024, 312 patients with uHCC treated with Dur/Tre were enrolled and retrospectively analyzed. Clinical characteristics, inflammatory markers, and nutritional indices (Geriatric Nutritional Risk Index [GNRI], body mass index, Prognostic Nutritional Index-Onodera, C-reactive protein-to-albumin ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio) were evaluated to identify predictors for imAE development. RESULTS: The imAEs occurred in 122 patients (39.1%), most commonly affecting dermatological, gastrointestinal, and endocrine systems. On multivariate analysis, only normal GNRI (≥ 98) was independently associated with a higher incidence of imAE (odds ratio: 1.99, 95% confidence interval: 1.05-3.79, P = 0.036). Patients with GNRI ≥ 98 also showed better overall survival (OS) than those with GNRI < 98 (not reached vs. 12.5 months, P < 0.001). Among patients who developed imAEs, no significant differences were observed in the imAE types or high-dose steroid use between the GNRI ≥ 98 group (n = 66) and the GNRI < 98 group (n = 56) (40.9% vs. 58.9%, P = 0.069). CONCLUSIONS: Normal GNRI status (≥ 98) was associated with an increased risk of imAE development and improved OS in patients with uHCC receiving Dur/Tre therapy. GNRI may be a useful clinical factor for identifying patients at higher risk of developing imAEs.

  • Utilizing the Conversion Concept Based on Disease Status Following Atezolizumab Plus Bevacizumab Treatment for Hepatocellular Carcinoma
    Shohei Komatsu, Toshifumi Tada, Kazuki Terashima, Nobuaki Ishihara, Masaki Omori, Takanori Matsuura, Eisuke Ueshima, Keitaro Sofue, Yuzo Kodama, Takumi Fukumoto
    World Journal of Surgery, Aug. 2025

  • Safety and Efficacy of Durvalumab Plus Tremelimumab in Older Individuals With Unresectable Hepatocellular Carcinoma: A Multicenter Analysis.
    Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hidenao Noritake, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Kosuke Matsui, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo
    Hepatology research : the official journal of the Japan Society of Hepatology, Aug. 2025, English, AIM: To evaluate the safety and efficacy of durvalumab plus tremelimumab (Dur/Tre) in older adults with unresectable hepatocellular carcinoma (HCC). METHODS: A total of 345 patients with HCC who received Dur/Tre were included in this study. Using propensity score matching, we compared outcomes between older (aged ≥ 75 years; n = 120) and younger individuals (n = 120). RESULTS: The median progression-free survival (PFS) was 3.3 months in the older group and 4.5 months in the younger group (p = 0.271). The median overall survival (OS) was 17.0 months in older individuals and 19.2 months in younger individuals (p = 0.598). No statistically significant differences were observed in the therapeutic response between the two groups (p = 0.264). Additionally, the incidence of immune-mediated adverse events (AEs) did not differ significantly between older and younger individuals. Multivariate analyses revealed that age group (older vs. younger) was not an independent prognostic factor for PFS (p = 0.250) or OS (p = 0.489). In a subgroup analysis stratifying older individuals into three age categories (75-79, 80-84, and ≥ 85 years), no significant differences were observed in the cumulative OS or PFS across the subgroups (p = 0.308 and 0.783). Similarly, the incidence of immune-mediated AEs did not differ significantly among the age categories. CONCLUSIONS: Dur/Tre appears to be a safe and effective treatment option for patients with HCC, regardless of age. Dur/Tre appears to be a safe and effective treatment option for patients with unresectable HCC, regardless of age.

  • Vascular Invasion Within the Resectability Criteria Is a Prognostic Factor in Patients Treated With Atezolizumab and Bevacizumab.
    Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Kosuke Matsui, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo
    Liver international : official journal of the International Association for the Study of the Liver, Aug. 2025, English, BACKGROUND AND AIMS: To assess the outcomes of patients with hepatocellular carcinoma (HCC) who were treated with atezolizumab plus bevacizumab (Atezo/Bev), categorised by oncological resectability criteria, which reflect tumour burden and extent of disease. METHODS: A cohort of 467 HCC patients who received Atezo/Bev was enrolled. Patients were classified into two groups based on oncological resectability criteria: BR (borderline resectable) 1 (n = 153) and BR2 (n = 314). RESULTS: The median progression-free survival (PFS) was 9.0 months in the BR1 group and 6.8 months in the BR2 group (p = 0.014). Multivariable analysis identified the following independent prognostic factors for PFS: age ≥ 75 years (hazard ratio [HR], 1.309), albumin-bilirubin (ALBI) grade ≥ 2 (HR, 1.494), neutrophil-to-lymphocyte ratio (NLR) ≥ 3 (HR, 1.289), α-fetoprotein ≥ 100 ng/mL (HR, 1.523) and BR2 classification (HR, 1.360). The median overall survival (OS) was 25.3 months in the BR1 group and 22.3 months in the BR2 group (p = 0.048). Multivariable analysis identified the following independent prognostic factors for OS: age ≥ 75 years (HR, 1.522), ALBI grade ≥ 2 (HR, 2.411), NLR ≥ 3 (HR, 1.635), α-fetoprotein ≥ 100 ng/mL (HR, 1.530) and BR2 classification (HR, 1.421). When oncological resectability factors (tumour number and size, vascular invasion and extrahepatic spread) were incorporated into the multivariable analysis, major vascular invasion emerged as a significant predictor of both PFS (HR, 3.188) and OS (HR, 2.650). CONCLUSIONS: In patients with HCC characterised by limited resectability undergoing Atezo/Bev, vascular invasion, in addition to liver function, is a critical prognostic determinant of tumour progression.

  • Selective identification of polyploid hepatocellular carcinomas with poor prognosis by artificial intelligence-based pathological image recognition
    Takanori Matsuura, Masatoshi Abe, Yoshiyuki Harada, Masahiro Kido, Hajime Nagahara, Yuzo Kodama, Yoshihide Ueda, Eiji Hara, Hirohiko Niioka, Tomonori Matsumoto
    Communications Medicine, Jul. 2025

  • Neutrophil-Lymphocyte Ratio Predicts Overall Survival in Patients With HCC Treated With Durvalumab Plus Tremelimumab.
    Tomomitsu Matono, Toshifumi Tada, Takashi Kumada, Atsushi Hiraoka, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Hiroki Nishikawa, Kazunari Tanaka, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Yuichi Koshiyama, Hidenori Toyoda, Chikara Ogawa, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Hideko Ohama, Fujimasa Tada, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Takashi Nishimura, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Tomoko Aoki, Hidekatsu Kuroda, Yutaka Yata, Hideyuki Tamai, Takanori Matsuura, Shohei Komatsu, Yoshihide Ueda, Yoshiko Nakamura, Osamu Yoshida, Shinichiro Nakamura, Hirayuki Enomoto, Masaki Kaibori, Takumi Fukumoto, Yoichi Hiasa, Masatoshi Kudo
    Hepatology research : the official journal of the Japan Society of Hepatology, Jun. 2025, English, AIM: To investigate the prognostic impact of the neutrophil-to-lymphocyte ratio (NLR) on outcomes in patients with hepatocellular carcinoma (HCC) treated with durvalumab plus tremelimumab (Dur/Tre). METHODS: A total of 182 patients with HCC who received Dur/Tre were included in the analysis. Univariate and multivariate survival analyses were conducted. Additionally, hazard ratio (HR) spline curve analysis was used to determine the optimal NLR cut-off values for predicting overall survival (OS). RESULTS: The median progression-free survival (PFS) was 3.5 months (95% confidence interval [CI]: 2.7-4.4), whereas the median OS was not reached (95% CI: 12.1 months-not reached). Multivariate analysis demonstrated that treatment with Dur/Tre as a second-line therapy or beyond was independently associated with worse PFS (HR: 1.819; 95% CI: 1.230-2.688; p = 0.003). Furthermore, an NLR of ≥ 2.56 was identified as an independent predictor of reduced OS (HR: 1.919; 95% CI: 1.033-3.566; p = 0.039). The median OS was not reached (95% CI: 12.3 months-not reached) in patients with an NLR of < 2.56, compared with 12.1 months (95% CI: 9.0 months-not reached) in those with an NLR of ≥ 2.56 (p = 0.016). A Sankey diagram illustrating post-treatment outcomes revealed that a significantly larger proportion of patients with high NLRs did not proceed to subsequent therapies but instead received best supportive care (p = 0.046). Spline curve analysis showed that an NLR range of approximately 2.3-3.0 represents an appropriate cut-off for predicting OS. CONCLUSIONS: The NLR is a significant prognostic biomarker for OS in patients with HCC treated with Dur/Tre.

  • Prognosis of Hepatectomy versus Systemic Chemotherapy Based on Oncological Resectability Criteria for Borderline Resectable Hepatocellular Carcinoma.
    Shohei Komatsu, Toshifumi Tada, Takashi Nishimura, Motofumi Tanaka, Atsushi Takebe, Saeko Kushida, Yoshimi Fujishima, Nobuaki Ishihara, Takanori Matsuura, Ikuo Nakamura, Taro Okazaki, Masahiro Tsuda, Jun Ishida, Ippei Matsumoto, Seiko Hirono, Hirayuki Enomoto, Yuzo Kodama, Takumi Fukumoto
    Liver cancer, Jun. 2025, English, INTRODUCTION: Oncological resectability criteria for hepatocellular carcinoma have been defined (resectable [R]/borderline resectable 1 [BR1]/borderline resectable 2 [BR2]); however, their validation is necessary. METHODS: A total of 1,469 patients who underwent hepatectomy and 525 patients who received systemic chemotherapy, including lenvatinib, atezolizumab plus bevacizumab, and durvalumab plus tremelimumab, as first-line treatment were analyzed. RESULTS: In the BR1 group, the median survival times (MSTs) of patients who underwent hepatectomy and systemic chemotherapy were 52.7 and 34.6 months, respectively, without a significant difference (p = 0.075). In the propensity score matching (PSM) analysis of the BR1 group, the MSTs of hepatectomy and systemic chemotherapy were 42.4 and 35.1 months, respectively, without a significant difference (p = 0.772). Hepatitis virus infection, modified albumin-bilirubin (mALBI) grade 2b + 3, and the presence of extrahepatic metastasis were identified as poor prognostic factors for hepatectomy, whereas mALBI grade 2b + 3 was the only poor prognostic factor for systemic chemotherapy. In the BR2 group, the MSTs of hepatectomy and systemic chemotherapy were 20.1 and 19.5 months, respectively, with significantly better survival for hepatectomy than for systemic chemotherapy (p = 0.017). In the PSM analysis of the BR2 group, the MSTs of hepatectomy and systemic chemotherapy were 20.1 and 21.0 months, respectively, without a significant difference (p = 0.375). Serum alpha-fetoprotein levels≥100, intrahepatic tumor number ≥6, and the presence of extrahepatic metastasis were identified as poor prognostic factors for hepatectomy, whereas female, serum alpha-fetoprotein levels ≥100, mALBI grade 2b + 3, intrahepatic maximal tumor size >5 cm, and the presence of extrahepatic metastasis were identified as poor prognostic factors for systemic chemotherapy. CONCLUSION: In the PSM analysis, no significant differences were observed between the BR1 and BR2 groups for hepatectomy and systemic chemotherapy. The intrahepatic tumor number for hepatectomy and the intrahepatic maximal tumor size for systemic chemotherapy are significant risk factors for BR2 patients, highlighting the characteristics of each treatment and the potential for selecting the optimal modality.

  • Development of a Predictive Model for Classifying Immune Checkpoint Inhibitor-Induced Liver Injury Types.
    Jun Kitadai, Toshifumi Tada, Takanori Matsuura, Mayumi Ehara, Tatsuya Sakane, Miki Kawano, Yuta Inoue, Shoji Tamura, Aya Horai, Yuuki Shiomi, Yoshihiko Yano, Yuzo Kodama
    JGH open : an open access journal of gastroenterology and hepatology, Apr. 2025, English, AIMS: Immune checkpoint inhibitors (ICIs) have transformed cancer therapy; however, they are associated with ICI-induced liver injury (ICI-LI), which manifests as hepatocellular, mixed, or cholestatic patterns with variable treatment responses. This study aimed to develop and validate a predictive model to identify ICI-LI type using clinical data available at ICI initiation. METHODS: A retrospective analysis of 297 patients with ICI-LI was conducted. Baseline clinical data were analyzed using univariate and multivariate logistic regression to predict ICI-LI types in the training and validation cohorts. A predictive model was developed and validated using receiver operating characteristic (ROC) curve analysis. RESULTS: Multivariate analysis in the training cohort identified male sex (odds ratio [OR]: 3.33, 95% confidence interval [CI]: 1.57-7.06, p = 0.002), serum albumin levels (OR: 0.42, 95% CI: 0.19-0.91, p = 0.027), and serum alanine aminotransferase (ALT) levels (OR: 0.97, 95% CI: 0.94-0.99, p = 0.015) as significant predictors, along with ICI regimen types selected using the Akaike information criterion. The logistic regression model, expressed as p = 1/{1 + (-(5.02 + 1.20 × (sex [F:0, M:1])) - 0.87 × albumin [g/dL] - 0.03 × ALT [U/L] - 0.9 × (drug [non-anti-cytotoxic T lymphocyte antigen 4 (CTLA-4) related regimen:0, anti-CTLA-4 related regimen:1]))}, achieved an area under the ROC (AUROC) of 0.73 (95% CI: 0.63-0.82) in the training cohort. At a cut-off of 0.86, the sensitivity was 60.3%, specificity 74.4%, positive predictive value 92.3%, and negative predictive value 26.9%. In the validation cohort, the AUROC was 0.752 (95% CI: 0.476-1.00). CONCLUSION: This predictive model demonstrates its utility in classifying ICI-LI types.

  • Immunoscore Predicted by Dynamic Contrast-Enhanced Computed Tomography Can Be a Non-Invasive Biomarker for Immunotherapy Susceptibility of Hepatocellular Carcinoma.
    Eisuke Ueshima, Keitaro Sofue, Shohei Komatsu, Nobuaki Ishihara, Masato Komatsu, Akihiro Umeno, Kentaro Nishiuchi, Ryohei Kozuki, Takeru Yamaguchi, Takanori Matsuura, Toshifumi Tada, Takamichi Murakami
    Cancers, Mar. 2025, English, Background/Objectives: Although immunotherapy is the primary treatment option for intermediate-stage hepatocellular carcinoma (HCC), its efficacy varies. This study aimed to identify non-invasive imaging biomarkers predictive of the immunoscore linked to dynamic contrast-enhanced computed tomography (CECT). Methods: We performed immunohistochemical staining with CD3+ and CD8+ antibodies and counted the positive cells in the invasive margin (IM) and central tumor (CT), converting them to an immunoscore of 0 to 4 points. We assessed the dynamic CECT findings obtained from 96 patients who underwent hepatectomy for HCC and evaluated the relationship between dynamic CECT findings and immunoscores. For validation, we assessed the treatment effects on 81 nodules using the Response Evaluation Criteria in Solid Tumors in another cohort of 41 patients who received combined immunotherapy with atezolizumab and bevacizumab (n = 27) and durvalumab and tremelizumab (n = 14). Results: HCCs with peritumoral enhancement in the arterial phase (p < 0.001) and rim APHE (p = 0.009) were associated with the immunoscore in univariate linear regression analysis and peritumoral enhancement in the arterial phase (p = 0.004) in multivariate linear regression analysis. The time to nodular progression in HCCs with peritumoral enhancement in the arterial phase was significantly longer than that in HCCs without this feature (p < 0.001). Conclusions: We identified HCCs with peritumoral enhancement in the arterial phase as a noninvasive imaging biomarker to predict immune-inflamed HCC with a high immunoscore tendency. These HCCs were most likely to respond to combined immunotherapy.

  • The potential efficacy of atezolizumab plus bevacizumab treatment for hepatocellular carcinoma patients with macroscopic portal vein tumor thrombus.
    Shohei Komatsu, Yoshihiko Yano, Kazuki Terashima, Yoshimi Fujishima, Jun Ishida, Nobuaki Ishihara, Takanori Matsuura, Tomoaki Okimoto, Yuzo Kodama, Takumi Fukumoto
    Surgery today, Feb. 2025, English, PURPOSE: The prognosis of patients with hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT) in the first-order or main trunk/contralateral branches (Vp3/4) is poor. The present study aimed to clarify the real-world data of atezolizumab plus bevacizumab treatment (Ate/bev) for HCC patients with Vp3/4 PVTT. METHODS: The subjects of this study were 22 consecutive HCC patients with Vp3/4 PVTT, who were treated with Ate/bev. Survival rates and radiological responses were evaluated based on the modified albumin-bilirubin (mALBI) grade [mALBI 1 + 2a (1/2a) versus 2b + 3 (2b/3)] using the modified Response Evaluation Criteria in Solid Tumors. RESULTS: The median survival time of the 22 patients was 15.0 months, with 1- and 2-year survival rates of 62.7% and 49.3%, respectively. The objective response (OR) rates of patients with mALBI 1/2a and 2b/3 were 91.7% (11/12) and 10.0% (1/10), respectively, with a significant difference (p < 0.001). The 2-year survival rates of patients with mALBI 1/2a and 2b/3 were 78.6% and 20.0%, respectively, with a significant difference (p = 0.0041). CONCLUSION: Ate/bev was effective for treating HCC patients with Vp3/4 PVTT. OR rate and MST were favorable, particularly for patients with preserved liver function (mALBI 1/2a), suggesting its great potential for the treatment of HCC in patients with Vp3/4 PVTT.

  • Higher Absolute Lymphocyte Counts and Lower Des-γ-Carboxyprothrombin Levels After Treatment Initiation Are Associated With the Clinical Efficacy of Tremelimumab Plus Durvalumab Combination Therapy for Hepatocellular Carcinoma.
    Yuta Inoue, Yoshihiko Yano, Saeko Kushida, Seiya Hirohata, Seitetsu Yoon, Eiichiro Yasutomi, Hirotaka Hirano, Soo Ki Kim, Ryutaro Yoshida, Yoshihide Ueda, Kenji Momose, Hiroki Hayashi, Takuo Kado, Katsuhisa Nishi, Hidenori Tanaka, Tomomitsu Matono, Atsushi Yamamoto, Hiroshi Tei, Chiharu Nishioka, Yosuke Yagi, Shoji Tamura, Tatsuya Sakane, Mayumi Ehara, Miki Kawano, Jun Kitadai, Takanori Matsuura, Yuuki Shiomi, Shohei Komatsu, Takumi Fukumoto, Toshifumi Tada, Yuzo Kodama
    JGH open : an open access journal of gastroenterology and hepatology, Feb. 2025, English, BACKGROUND AND AIMS: Tremelimumab plus durvalumab (Dur/Tre) combination therapy is now a first-line systemic therapy for advanced hepatocellular carcinoma (HCC). Because systemic therapy is not effective in some patients, it is clinically important to identify factors that could predict the response to treatment at an early stage. We investigated the factors associated with the response to Dur/Tre for advanced HCC in a clinical setting. METHODS: Seventy patients (median age 74 years; 61 men) who received Dur/Tre between March 2023 and September 2024 were analyzed. We examined the factors associated with the treatment response, including pretreatment factors and factors early in treatment. RESULTS: The median treatment duration was 77.5 (interquartile range [IQR] 28-187) days. The overall response and disease control rates were 25.8% and 58.1%, respectively. The median (IQR) progression-free survival (PFS) and overall survival (OS) were 82 (61-133) and 415 (337-NA) days, respectively. Multivariable analysis revealed that higher absolute lymphocyte count (ALC) and lower des-γ-carboxyprothrombin (DCP) levels were significantly associated with PFS. Receiver operating characteristic curve analysis showed that the cutoff value for ALC after 4 weeks of treatment in relation to clinical efficacy was 1125/mm3. A log-rank test using the Kaplan-Meier method showed that OS was significantly longer in patients with ALC above the cutoff and in patients whose DCP levels decreased after starting treatment. CONCLUSION: Higher ALC and lower DCP levels after treatment initiation were associated with the clinical efficacy of Dur/Tre for advanced HCC.

  • Treatment Outcomes of Tyrosine Kinase Inhibitors and Durvalumab Plus Tremelimumab After Atezolizumab Plus Bevacizumab for Hepatocellular Carcinoma.
    Nobuaki Ishihara, Shohei Komatsu, Yoshihiko Yano, Yoshimi Fujishima, Jun Ishida, Masahiro Kido, Hidetoshi Gon, Kenji Fukushima, Takeshi Urade, Toshihiko Yoshida, Kentaro Tai, Keisuke Arai, Hiroaki Yanagimoto, Hirochika Toyama, Takanori Matsuura, Toshifumi Tada, Yuzo Kodama, Takumi Fukumoto
    Anticancer research, Jan. 2025, English, International Institute of Anticancer Research, BACKGROUND/AIM: Atezolizumab plus bevacizumab (AteBev) is widely used as a first-line treatment for advanced hepatocellular carcinoma (HCC). However, evidence regarding the optimal drug sequence following AteBev treatment is limited. This study aimed to compare the treatment outcomes between tyrosine kinase inhibitors (TKIs) and durvalumab plus tremelimumab (DurTre) following AteBev treatment. PATIENTS AND METHODS: Overall, 134 consecutive patients who received AteBev for advanced HCC were enrolled in this study. Treatment outcomes were retrospectively compared between TKIs (AteBev→TKI group) and DurTre (AteBev→DurTre group). RESULTS: The AteBev→TKI and Ate→DurTre groups included 46 and 7 patients, respectively. The AteBev→TKI group had significantly longer median progression-free survival after second-line treatment (3.6 vs. 0.94 months, p<0.001). The disease control rate was significantly higher in the AteBev→TKI group (p=0.020). The serum alpha-fetoprotein levels significantly decreased at one month in the AteBev→TKI group (0.909 vs. 1.435, p=0.035), whereas the albumin-bilirubin score significantly decreased at one month in the AteBev→TKI group (0.875 vs. 0.952, p=0.017). Each group reported no new unmanageable adverse events. CONCLUSION: TKIs may be a more optimal drug sequence than DurTre after AteBev treatment from an oncological perspective. TKIs following AteBev treatment require careful monitoring for deteriorating liver function.

  • Diagnostic guide for immune checkpoint inhibitor-induced liver injury.
    Takanori Ito, Yasuto Takeuchi, Kazuyuki Mizuno, Michitaka Imai, Yoko Yoshimaru, Kazumichi Abe, Masanori Abe, Takanori Matsuura, Masataka Yokode, Masahiro Shiokawa, Yuzo Kodama, Mina Komuta, Kenichi Harada, Atsushi Tanaka
    Hepatology research : the official journal of the Japan Society of Hepatology, Aug. 2024, English, With the widespread use of immune checkpoint inhibitors (ICIs), liver injury (ICI-induced liver injury) as an immune-related adverse event has become a major concern in clinical practice. Because severe cases of liver injury require administration of corticosteroids, a comprehensive evaluation is crucial, including clinical course, blood and imaging tests, and if necessary, pathological examination through liver biopsy. As with liver injury induced by other drugs, classification of injury type by R-value is useful in deciding treatment strategies for ICI-induced liver injury. Histologically, the most representative feature is an acute hepatitis-like hepatocellular injury, characterized by diffuse lobular inflammation accompanied by CD8-positive T lymphocytes. Another condition that can cause liver injury during ICI treatment is cholangitis accompanied by non-obstructive bile duct dilatation and bile duct wall thickening. Many cases of ICI-induced cholangitis are classified as non-hepatocellular injury type, and they have been reported to respond poorly to corticosteroids. It is essential that gastroenterologists/hepatologists and doctors in various departments work in cooperation to develop a system that achieves early diagnosis and appropriate treatment of ICI-induced liver injury.

  • Risk Factors for Immune Checkpoint Inhibitor-Induced Liver Injury and the Significance of Liver Biopsy.
    Miki Kawano, Yoshihiko Yano, Atsushi Yamamoto, Eiichiro Yasutomi, Yuta Inoue, Jun Kitadai, Ryutaro Yoshida, Takanori Matsuura, Yuuki Shiomi, Yoshihide Ueda, Yuzo Kodama
    Diagnostics (Basel, Switzerland), Apr. 2024, English, Immune checkpoint inhibitor (ICI)-induced liver injury (LI) is a common adverse event, but the clinical characteristics based on the classification of hepatocellular injury and cholestatic types are not fully evaluated. This study aims to analyze risk factors and histological findings in relation to the classification of ICI-induced LI. In total, 254 ICI-induced LI patients among 1086 treated with ICIs between September 2014 and March 2022 were classified according to the diagnostic criteria for drug-induced LI (DILI), and their risk factors and outcomes were evaluated. Kaplan-Meier analyses showed that overall survival in patients with hepatocellular-injury-type LI was significantly longer than others (p < 0.05). Regarding pre-treatment factors, the lymphocyte count was significantly higher in patients with ICI-induced LI, especially in hepatocellular-injury-type LI. Gamma glutamyl transferase (γGTP) and alkaline phosphatase (ALP) were also significantly lower in patients with ICI-induced LI (p < 0.05). Multivariate analyses revealed that malignant melanoma, high lymphocyte count, and low ALP levels were extracted as factors contributing to hepatocellular-injury-type LI. The histological findings among 37 patients diagnosed as ICI-induced LI via liver biopsy also revealed that the spotty/focal necrosis was significantly frequent in hepatocellular-injury-type LI, whereas ductular reactions were frequently observed in cholestatic-type LI. It is suggested that the histological inflammation pattern in patients with LI is closely correlated with the type of DILI.

  • Clinical Significance and Remaining Issues of Anti-HBc Antibody and HBV Core-Related Antigen.
    Yoshihiko Yano, Itsuko Sato, Takamitsu Imanishi, Ryutaro Yoshida, Takanori Matsuura, Yoshihide Ueda, Yuzo Kodama
    Diagnostics (Basel, Switzerland), Mar. 2024, English, Currently, hepatitis B virus (HBV) core antibody (anti-HBc antibody) and HBV core-related antigen (HBcrAg) are widely used as serum markers for diagnosis based on the HBV core region. This review focused on anti-HBc antibodies and HBcrAg and aimed to summarize the clinical significance of currently used assay systems and the issues involved. While anti-HBc is very significant for clinical diagnosis, the clinical significance of quantitative assay of anti-HBc antibody has been reevaluated with improvements in diagnostic performance, including its association with clinical stage and prediction of carcinogenesis and reactivation. In addition, concerning the new HBcrAg, a high-sensitivity assay method has recently been established, and its diagnostic significance, including the prediction of reactivation, is being reevaluated. On the other hand, the quantitative level of anti-HBc antibody expressed in different units among assay systems complicates the interpretation of the results. However, it is difficult to standardize assay systems as they vary in advantages, and caution is needed in interpreting the assay results. In conclusion, with the development of highly sensitive HBcrAg and anti-HBc antibody, a rapid and sensitive detection assay system has been developed and used in clinical practice. In the future, it is hoped that a global standard will be created based on the many clinical findings.

  • Histological diagnosis of polyploidy discriminates an aggressive subset of hepatocellular carcinomas with poor prognosis.
    Takanori Matsuura, Yoshihide Ueda, Yoshiyuki Harada, Kazuki Hayashi, Kisara Horisaka, Yoshihiko Yano, Shinichi So, Masahiro Kido, Takumi Fukumoto, Yuzo Kodama, Eiji Hara, Tomonori Matsumoto
    British journal of cancer, Oct. 2023, English, BACKGROUND: Although genome duplication, or polyploidization, is believed to drive cancer evolution and affect tumor features, its significance in hepatocellular carcinoma (HCC) is unclear. We aimed to determine the characteristics of polyploid HCCs by evaluating chromosome duplication and to discover surrogate markers to discriminate polyploid HCCs. METHODS: The ploidy in human HCC was assessed by fluorescence in situ hybridization for multiple chromosomes. Clinicopathological and expression features were compared between polyploid and near-diploid HCCs. Markers indicating polyploid HCC were explored by transcriptome analysis of cultured HCC cells. RESULTS: Polyploidy was detected in 36% (20/56) of HCCs and discriminated an aggressive subset of HCC that typically showed high serum alpha-fetoprotein, poor differentiation, and poor prognosis compared to near-diploid HCCs. Molecular subtyping revealed that polyploid HCCs highly expressed alpha-fetoprotein but did not necessarily show progenitor features. Histological examination revealed abundant polyploid giant cancer cells (PGCCs) with a distinct appearance and frequent macrotrabecular-massive architecture in polyploid HCCs. Notably, the abundance of PGCCs and overexpression of ubiquitin-conjugating enzymes 2C indicated polyploidy in HCC and efficiently predicted poor prognosis in combination. CONCLUSIONS: Histological diagnosis of polyploidy using surrogate markers discriminates an aggressive subset of HCC, apart from known HCC subgroups, and predict poor prognosis in HCC.

  • A Case of Duodenal Edema-related Undiagnosed Hereditary Angioedema.
    Fumiaki Kawara, Takanori Matsuura, Kodai Yamanaka, Chiharu Nishioka
    Internal medicine (Tokyo, Japan), Aug. 2023, English

  • Factors associated with the response to atezolizumab/bevacizumab combination therapy for hepatocellular carcinoma.
    Yoshihiko Yano, Atsushi Yamamoto, Takuya Mimura, Saeko Kushida, Seiya Hirohata, Seitetsu Yoon, Hirotaka Hirano, Soo Ki Kim, Yuri Hatazawa, Kenji Momose, Hiroki Hayashi, Takuo Kado, Katsuhisa Nishi, Hidenori Tanaka, Takanori Matsuura, Ryutaro Yoshida, Naoki Asaji, Eiichiro Yasutomi, Yuuki Shiomi, Akihiro Minami, Shohei Komatsu, Takumi Fukumoto, Yoshihide Ueda, Yuzo Kodama
    JGH open : an open access journal of gastroenterology and hepatology, Jul. 2023, English, BACKGROUND AND AIM: The purpose of this study was to analyze factors associated with the overall survival (OS) of atezolizumab/bevacizumab combination therapy for advanced hepatocellular carcinoma (aHCC). We also assessed the OS of patients with ineffective therapy and those who discontinued treatment owing to adverse events (AEs). METHODS: This retrospective multicenter study involved 139 patients with aHCC who received atezolizumab/bevacizumab combination therapy between November 2020 and September 2022. RESULTS: The median duration of treatment was 136.5 days, and the median observation period was 316 days. The overall response rate was 40%, and the disease control rate was 78% according to mRECIST criteria. Grade ≥2 AEs occurred in 63 patients (43%) and led to treatment discontinuation in 16 patients. Multivariate analysis revealed that treatment response and occurrence of grade ≥2 AEs after therapy, as well as low level of albumin-bilirubin (ALBI) grade and low level of des-gamma carboxy prothrombin (DCP) before therapy, were extracted as factors that contributed to OS. Log-rank tests with the Kaplan-Meier method showed significant differences in OS among these factors. The OS of patients who discontinued owing to AEs was significantly shorter than that of other patients. CONCLUSION: Not only factors before therapy but also treatment response and the appearance of AEs are involved in OS for atezolizumab/bevacizumab combination therapy. Although the development of AEs also contributed to OS, appropriate management of AEs is important to avoid discontinuing treatment with this combination.

  • Endoscopic closure of cecal fistula using purse-string suture after plombage with polyglycolic acid sheets and fibrin glue.
    Fumiaki Kawara, Akihiro Minami, Kazuya Hara, Kodai Yamanaka, Takanori Matsuura, Mitsuko Mimura, Chiharu Nishioka
    Endoscopy, Nov. 2022, English

  • Significance of post-progression therapy after tyrosine kinase inhibitors for advanced hepatocellular carcinoma.
    Yoshihiko Yano, Atsushi Yamamoto, Akihiro Minami, Kenji Momose, Takuya Mimura, Soo Ki Kim, Hiroki Hayashi, Takuo Kado, Hirotaka Hirano, Seiya Hirohata, Seitetsu Yoon, Katsuhisa Nishi, Hiroshi Tei, Hidenori Tanaka, Sachiko Oouchi, Takanori Matsuura, Eiichiro Yasutomi, Yuri Hatazawa, Yuuki Shiomi, Yoshihide Ueda, Yuzo Kodama
    JGH open : an open access journal of gastroenterology and hepatology, Jun. 2022, English, BACKGROUND AND AIM: Molecular-targeted therapies such as sorafenib and lenvatinib have long been used as first-line treatment for advanced hepatocellular carcinoma (aHCC). However, adverse events or limited therapeutic effects may necessitate the change to another therapeutic option, known as post-progression therapy. To investigate the significance of post-progression therapy, we analyzed the outcomes of aHCC patients following first-line molecular-targeted therapy in a real-world study. METHODS: This retrospective, multicenter study involved patients with aHCC who received sorafenib or lenvatinib as first-line therapy between January 2011 and September 2021. RESULTS: In total, 513 patients were analyzed: 309 treated with sorafenib and 204 with lenvatinib. The overall response and disease control rates were 15 and 50%, respectively, in the sorafenib group and 30 and 75%, respectively, in the lenvatinib group (P < 0.001). Kaplan-Meier analysis revealed no significant differences in progression-free survival and overall survival (OS) between the two treatments. Multivariate analysis revealed that fibrosis-4 index, disease control rate, post-progression therapy, and use of an immune checkpoint inhibitor (ICI) were significantly associated with OS. OS was significantly longer in patients who received post-progression therapy than in those who did not (log-rank P < 0.001). Most patients who received an ICI as post-progression therapy had previously received lenvatinib. Among lenvatinib-treated patients, OS was significantly longer in patients who received an ICI than in patients received another or no post-progression therapy (P = 0.004). CONCLUSION: The introduction of newer drugs for post-progression therapy is expected to prolong survival. ICI-based regimens appear to be effective after lenvatinib.

■ Research Themes
  • 消化器指定難病と免疫関連有害事象に共通する自己免疫機構の解明およびその臨床応用
    児玉 裕三, 渡邉 大輔, 増田 充弘, 松浦 敬憲
    日本学術振興会, 科学研究費助成事業, 基盤研究(B), 神戸大学, 01 Apr. 2025 - 31 Mar. 2028

  • 癌細胞の多倍体化に着目した、肝内胆管癌の予後不良バイオマーカーの探索
    松浦 敬憲
    日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 01 Apr. 2025 - 31 Mar. 2028

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