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1. Efficacy of Atezolizumab Plus Bevacizumab–Transcatheter Arterial Chemoembolization Sequential Therapy for Patients with Intermediate-Stage Hepatocellular Carcinoma

Author

Etsuko Moriyama, Shigeo Shimose, Takashi Niizeki, Hideki Iwamoto, Masatoshi Tanaka, Tomotake Shirono, Yu Noda, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, and Takumi Kawaguchi

Subjects
atezolizumab plus bevacizumab, hepatocellular carcinoma, TACE, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

This retrospective study aimed to evaluate the impact of atezolizumab plus bevacizumab–transcatheter arterial chemoembolization (TACE) sequential therapy in unresectable hepatocellular carcinoma (HCC), especially in patients with intermediate-stage HCC. A total of 212 patients were enrolled and categorized into the Atez/Bev-TACE sequential therapy (n = 23) or Atez/Bev monotherapy group (n = 189) between 2020 and 2024. Of these, patients with intermediate-stage HCC were categorized into the Atez/Bev-TACE sequential (n = 18) or Atez/Bev monotherapy group (n = 91). The best objective response rate, disease control rate, and median progression-free survival (PFS) after TACE were 73.9%, 82.6%, and 6.1 months, respectively. The PFS after TACE was significantly higher in the Atez/Bev sequential therapy group than in the no-Atez/Bev-administration group after TACE (6.9 months vs. 5.0 months, p = 0.025). The median overall survival (OS) was significantly higher in the Atez/Bev-TACE sequential therapy group than in the Atez/Bev monotherapy group for intermediate-stage HCC (34.9 months vs. 17.8 months; p = 0.016). Independent factors associated with OS were low alpha-fetoprotein levels, modified albumin–bilirubin 1 or 2a levels, and Atez/Bev-TACE sequential therapy. Atez/Bev-TACE sequential therapy improved prognosis compared with Atez/Bev monotherapy in patients with intermediate-stage HCC. Moreover, Atez/Bev should be readministered after TACE.

Published
2024
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2. Impact of metformin, statin, aspirin and insulin on the prognosis of uHCC patients receiving first line Lenvatinib or Atezolizumab plus Bevacizumab

Author

Margherita Rimini, Margarida Montes, Elisabeth Amadeo, Francesco Vitiello, Masatoshi Kudo, Toshifumi Tada, Goki Suda, Shigeo Shimose, Sara Lonardi, Fabian Finkelmeier, Francesca Salani, Lorenzo Antonuzzo, Fabio Marra, Massimo Iavarone, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Rodolfo Sacco, Ilario Giovanni Rapposelli, Mario Scartozzi, Pella Nicoletta, Luca Aldrighetti, Mara Persano, Silvia Camera, Federico Rossari, Silvia Foti, Takashi Kumada, Atsushi Hiraoka, Hideki Iwamoto, Mario Domenico Rizzato, Vera Himmelsbach, Gianluca Masi, Mattia Corradi, Ciro Celsa, Conti Fabio, Giovanni Luca Frassineti, Stefano Cascinu, Andrea Casadei-Gardini, and Jose Presa

Subjects
Advanced HCC, Atezolizumab, Bevacizumab, Lenvatinib BMI, Medicine, Science
Abstract

Abstract Recently, in Hepatocellular carcinoma (HCC) setting, the use of metformin has been associated to a trend toward worse response rate, overall survival and progression free survival in patients who received immunotherapy. The study population included individuals from both Eastern and Western regions with a confirmed diagnosis of HCC and receiving first line treatment with Atezolizumab plus bevacizumab or Lenvatinib. Univariate and multivariate analyses were performed by Cox proportional. For the analysis, patients were stratified based on their use of concomitant medication or not. At the time of database lock, 319 deaths were observed: 209 in the Lenvatinib cohort, 110 in the Atezolizumab plus bevacizumab cohort. In the Atezolizumab plus Bevacizumab arm, 50 (16.5%) patients were on chronic metformin use. At the univariate analysis for OS, patients who used metformin showed significantly shorter OS compared to patients who did not use metformin (HR 1.9, 95% CI 1.1–3.2). Multivariate analysis confirmed that patients in metformin group had significantly shorter OS compared to patients in no-metformin group (HR 1.9; 95% CI 1.1–3.1). At the univariate analysis for PFS, patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.6, 95% CI 1.0–2.6). Multivariate analysis confirmed that patients in metformin group had significantly shorter PFS compared to patients in no-metformin group (HR 1.7; 95% CI 1.1–2.7; p = 0.0147). No differences were reported in terms of ORR and DCR between patients in metformin group and those in no-metformin group. In the Lenvatinib cohort, 65 (15%) patients were recorded to chronically use metformin. No statistically significant differences in terms of both OS and PFS were found between patients in metformin group and patients in no-metformin group. This analysis unveils a negative prognostic role associated with metformin use specifically within the Atezolizumab plus Bevacizumab group.

Published
2024
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5. Disease etiology impact on outcomes of hepatocellular carcinoma patients treated with atezolizumab plus bevacizumab: a real-world, multicenter study

Author

Federico Rossari, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Mara Persano, Silvia Foti, Silvia Camera, Bernardo Stefanini, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini, and Margherita Rimini

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post-hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizumab plus bevacizumab is equally effective in viral and non-viral patients. Methods We retrospectively analyzed 885 HCC patients treated with first-line A + B from multiple centers from Eastern and Western countries, 53.9% having viral and 46.1% non-viral etiology. Baseline clinical and laboratory characteristics were analyzed with uni- and multi-variate models to explore potential differences on overall survival (OS), time to progression (TTP), disease control rates based on etiology and to identify putative prognostic factors in etiology subgroups. Treatment toxicities and access to second-line treatments and outcomes were also reported and compared between etiologies. Results Overall, no statistically significant differences were found in OS (mOS: viral 15.9 months; non-viral 16.3 months), TTP (mTTP: viral 8.3 months; non-viral 7.2 months), and disease control rates (DCR: viral 78.1%; non-viral 80.8%) based on etiology. Prognostic factors of survival and progression were mainly shared between viral and non-viral etiologies, including alpha-fetoprotein, aspartate transaminase, neutrophil-to-lymphocyte ratio (NLR) and ALBI score. Exploratory analyses highlighted a possible stronger association of immunological factors, i.e. NLR and eosinophil count, to treatment outcomes in viral patients. The toxicity profile, the access to and type of second-line treatments and their outcome in terms of OS almost overlap in the two etiology subgroups. Conclusion Atezolizumab plus bevacizumab efficacy does not vary according to underlying etiology of HCC in a multicenter, real-world population, matching recent post-hoc findings from the IMbrave-150 trial. Preliminary analyses suggest that some prognostic factors differ between viral and non-viral patients, potentially due to biological and immunological differences. Prospective and comparative trials stratifying by etiology are warranted to validate these findings and guide clinical practice.

Published
2024
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6. Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma in the era of chemo-diversity

Author

Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Takashi Niizeki, and Takumi Kawaguchi

Subjects
hepatocellular carcinoma, hepatic arterial infusion chemotherapy, molecular targeted agents, new fp, locoregional treatment, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Recently, treatments for unresectable hepatocellular carcinoma (HCC) have undergone remarkable development. Various systemic chemotherapy drugs have been approved and are recommended by clinical guidelines worldwide. Although systemic treatments are effective and contribute to prolonged patient survival, their effects are unsatisfactory for some specific tumor conditions, such as macrovascular invasion. Hepatic arterial infusion chemotherapy (HAIC) is a traditional treatment for advanced HCC. As yet, there is no worldwide consensus recommending HAIC because no high-quality clinical trials have demonstrated its survival benefit. However, clinical evidence is gradually accumulating that shows its survival benefit, and it is recognized as an effective locoregional treatment for advanced HCC. Several HAIC regimens have been reported, including cisplatin monotherapy, cisplatin plus 5-fluorouracil (low-dose FP), lipiodol-suspended FP, and an oxaliplatin-based regimen. We have entered an era of chemo-diversity in the treatment of advanced HCC. This review aimed to clarify the relevance of HAIC in the era of chemo-diversity. We propose a multidisciplinary therapeutic strategy combining locoregional HAIC treatment with sequential drug therapy, with the aim of becoming cancer-free through conversion therapy.

Published
2023
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7. The impact of curative conversion therapy aimed at a cancer‐free state in patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Author

Shigeo Shimose, Hideki Iwamoto, Tomotake Shirono, Masatoshi Tanaka, Takashi Niizeki, Masahiko Kajiwara, Satoshi Itano, Yoichi Yano, Satoru Matsugaki, Etsuko Moriyama, Yu Noda, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, and Takumi Kawaguchi

Subjects
atezolizumab plus bevacizumab, conversion therapy, hepatocellular carcinoma, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background and Aims We aimed to validate the predictive factors for tumor response and the prognostic impact of conversion therapy aimed at cancer‐ and drug‐free states in patients with unresectable hepatocellular carcinoma (u‐HCC) undergoing atezolizumab plus bevacizumab (Atez/Bev) therapy. Methods This retrospective study enrolled 156 patients who were Child‐Pugh class A with u‐HCC treated using Atez/Beva. The profile of objective response was investigated using decision‐tree analysis. Progression‐free, recurrence‐free, and overall survival were assessed. Results The progression‐free and overall survival were 6.1 and 18.0 months, respectively. Objective response and disease control rates were 32.0% and 84.0%, respectively. Decision‐tree analysis revealed that neutrophil‐to‐lymphocyte ratio (NLR)

Published
2023
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8. Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Japanese perspective

Author

Hironori Koga, Hideki Iwamoto, Hiroyuki Suzuki, Shigeo Shimose, Masahito Nakano, and Takumi Kawaguchi

Subjects
bclc staging, radiofrequency ablation, transcatheter arterial chemoembolization, molecular-targeted agents, immune checkpoint inhibitors, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Striking advances in systemic therapy for unresectable advanced hepatocellular carcinoma (HCC) have improved the average prognosis of patients with HCC. As a result, the guidelines for the treatment of HCC have changed significantly. However, various issues have emerged in clinical practice. First, there is no established biomarker that can predict response to systemic therapy. Second, there is no established treatment regimen after primary systemic therapy, including combined immunotherapy. Third, there is no established treatment regimen for intermediate-stage HCC. These points make the current guidelines ambiguous. In this review, we present the Japanese guidelines for the diagnosis and treatment of HCC based on the latest evidence; introduce various efforts mainly in Japanese real-life practice to update these guidelines; and present our perspectives on future guidelines.

Published
2023
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9. Tumor‐derived insulin‐like growth factor‐binding protein‐1 contributes to resistance of hepatocellular carcinoma to tyrosine kinase inhibitors

Author

Hiroyuki Suzuki, Hideki Iwamoto, Takahiro Seki, Toru Nakamura, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Yasuko Imamura, Takashi Niizeki, Masahito Nakano, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Miwa Sakai, Kazutoyo Morita, Masamichi Nakayama, Tomoharu Yoshizumi, Ryoko Kuromatsu, Hirohisa Yano, Yihai Cao, Hironori Koga, and Takuji Torimura

Subjects
hepatocellular carcinoma, hypoxia, IGFBP‐1, lenvatinib, molecular targeting, resistance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Antiangiogenic tyrosine kinase inhibitors (TKIs) provide one of the few therapeutic options for effective treatment of hepatocellular carcinoma (HCC). However, patients with HCC often develop resistance toward antiangiogenic TKIs, and the underlying mechanisms are not understood. The aim of this study was to determine the mechanisms underlying antiangiogenic TKI resistance in HCC. Methods We used an unbiased proteomic approach to define proteins that were responsible for the resistance to antiangiogenic TKIs in HCC patients. We evaluated the prognosis, therapeutic response, and serum insulin‐like growth factor‐binding protein‐1 (IGFBP‐1) levels of 31 lenvatinib‐treated HCC patients. Based on the array of results, a retrospective clinical study and preclinical experiments using mouse and human hepatoma cells were conducted. Additionally, in vivo genetic and pharmacological gain‐ and loss‐of‐function experiments were performed. Results In the patient cohort, IGFBP‐1 was identified as the signaling molecule with the highest expression that was inversely associated with overall survival. Mechanistically, antiangiogenic TKI treatment markedly elevated tumor IGFBP‐1 levels via the hypoxia‐hypoxia inducible factor signaling. IGFBP‐1 stimulated angiogenesis through activation of the integrin α5β1‐focal adhesion kinase pathway. Consequently, loss of IGFBP‐1 and integrin α5β1 by genetic and pharmacological approaches re‐sensitized HCC to lenvatinib treatment. Conclusions Together, our data shed light on mechanisms underlying acquired resistance of HCC to antiangiogenic TKIs. Antiangiogenic TKIs induced an increase of tumor IGFBP‐1, which promoted angiogenesis through activating the IGFBP‐1‐integrin α5β1 pathway. These data bolster the application of a new therapeutic concept by combining antiangiogenic TKIs with IGFBP‐1 inhibitors.

Published
2023
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10. Deterioration of liver function and aging disturb sequential systemic therapy for unresectable hepatocellular carcinoma

Author

Shigeo Shimose, Atsushi Hiraoka, Masatoshi Tanaka, Hideki Iwamoto, Takaaki Tanaka, Kazunori Noguchi, Hajime Aino, Taizo Yamaguchi, Satoshi Itano, Hideya Suga, Takashi Niizeki, Etsuko Moriyama, Tomotake Shirono, Yu Noda, Naoki Kamachi, Shusuke Okamura, Masahito Nakano, Takumi Kawaguchi, Ryoko Kuromatsu, Hironori Koga, and Takuji Torimura

Subjects
Medicine, Science
Abstract

Abstract This study aimed to investigate the clinical characteristics of patients with unresectable hepatocellular carcinoma (HCC), who were eligible for sequential systemic therapy. We evaluated 365 patients with HCC who underwent systemic therapy after 2017. The overall survival (OS) was 13.7 months, 19.2 months, and 35.6 months in the first-line, second-line, and third-line or later therapy groups, respectively. Multivariate analysis revealed that the modified-albumin-bilirubin (m-ALBI) grade, macrovascular invasion, extrahepatic spread, discontinuation due to adverse events (AEs), and sequential therapy were independent factors for OS. At the end of each therapy, the ALBI score was significantly worse among patients with discontinuation due to AEs than among those without. The conversion rate to second-line and third-line therapy among patients with discontinuation due to AEs was significantly lower than that among patients without (30.4% vs. 69.2%, p

Published
2022
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11. Durable complete response is achieved by balloon‐occluded transcatheter arterial chemoembolization for hepatocellular carcinoma

Author

Tomotake Shirono, Hideki Iwamoto, Takashi Niizeki, Shigeo Shimose, Akira Kajiwara, Hiroyuki Suzuki, Naoki Kamachi, Yu Noda, Shusuke Okamura, Masahito Nakano, Ryoko Kuromatsu, Kenta Murotani, Hironori Koga, and Takuji Torimura

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract In 2013 and 2014, the development of microcatheters with balloons for the 4‐Fr system and new embolization materials provided various options for transarterial chemoembolization (TACE), expanding the range of treatment strategies. At our hospital, balloon‐occluded TACE (B‐TACE), conventional TACE (C‐TACE), and drug‐eluting bead TACE (DEB‐TACE) have been actively performed for hepatocellular carcinoma (HCC). This study compared the local recurrence‐free (LRF) periods of nodules with complete necrosis (TE4) obtained using each treatment method by extracting the nodules evaluated as complete response by the modified Response Evaluation Criteria in Solid Tumors. We performed 580 TACE procedures between June 2013 and April 2019. Among them, 58 HCC nodules in 43 patients, 33 nodules in 30 patients, and 45 nodules in 25 patients were evaluated as having complete necrosis after C‐TACE, DEB‐TACE, and B‐TACE, respectively. The time to local recurrence for each nodule was defined as the LRF period, and the quality of TE4 for each TACE was examined. Factors related to overall survival and the LRF period were determined by univariate and multivariate analyses, and overall survival and the LRF period were analyzed using the Kaplan–Meier method. Multivariate analysis of the LRF period showed that B‐TACE was an independent factor. The median LRF periods were 39.3, 13, and 9.1 months for B‐TACE, C‐TACE, and DEB‐TACE, respectively. Moreover, B‐TACE had a significantly longer LRF period than C‐TACE and DEB‐TACE. Conclusion: There was no significant difference between C‐TACE and DEB‐TACE. The LRF period of nodules with TE4 was the longest with B‐TACE, suggesting that B‐TACE should be used to achieve a radical cure in patients with HCC.

Published
2022
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13. Incidence and predictors of esophagogastric varices bleeding in patients with hepatocellular carcinoma in lenvatinib

Author

Massimo Iavarone, Eleonora Alimenti, Toshifumi Tada, Shigeo Shimose, Goki Suda, Changhoon Yoo, Caterina Soldà, Fabio Piscaglia, Giulia Tosetti, Fabio Marra, Caterina Vivaldi, Fabio Conti, Marta Schirripa, Hideki Iwamoto, Takuya Sho, So Heun Lee, Mario Domenico Rizzato, Matteo Tonnini, Margherita Rimini, Claudia Campani, Gianluca Masi, Francesco Foschi, Mariangela Bruccoleri, Takumi Kawaguchi, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Shinya Fukunishi, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Takeshi Hatanaka, Satoru Kakizaki, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Atsushi Naganuma, Andrea Casadei-Gardini, and Pietro Lampertico

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use maybe limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods: In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy (UGE) available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence and risk factors for the presence of EGV and high risk EGV at baseline, impact of EGV bleeding on patients’ survival. Results: 535 patients were enrolled in the study [median age 72 years, 78% male, 63% viral aetiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis (nPVT), 56% BCLC-C]: 234 had EGV (44%): 70 (30%) at high-risk and 59 on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high risk EGV (HR 6.94, 95% CI 2.23-21.57, p=0.001). In these patients the 12-month risk was 17%. High risk varices were independently associated with Child-Pugh B score (OR 2.12; 95%CI 1.08-4.17, p=0.03), nPVT (OR 2.54; 95%CI 1.40-4.61, p=0.002) and platelets

Published
2023
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14. DNA Methylation in Noncancerous Liver Tissues as Biomarker for Multicentric Occurrence of Hepatitis C Virus–Related Hepatocellular Carcinoma

Author

Hiroyuki Suzuki, Hideki Iwamoto, Ken Yamamoto, Mai Tsukaguchi, Toru Nakamura, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Takashi Niizeki, Shusuke Okamura, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Ryoko Kuromatsu, Toru Hisaka, Hirohisa Yano, Hironori Koga, and Takuji Torimura

Subjects
Hepatocellular Carcinoma, DNA Methylation, Hepatitis C Virus, Multicentric Occurrence, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Background and Aims: Hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) progresses with a highly multicentric occurrence (MO) even after radical hepatectomy. Despite several efforts to clarify the pathogenesis of MO, the underlying molecular mechanism remains elusive. The aim of this study was to evaluate alterations in DNA methylation in noncancerous liver tissues in the MO of HCC. Methods: A total of 203 patients with HCV-related HCC who underwent radical hepatectomy at our hospital between January 2008 and January 2012 were recruited. We defined a group of nonearly recurrence of HCC (NR) for ≥3 years after radical hepatectomy and a group of early recurrence of HCC (ER) with MO within 2 years after radical hepatectomy. Results: Three patients each were selected in the NR and ER groups in the first set, and 13 patients in the NR group and 17 patients in the ER group were selected in the second set. Genome-wide DNA methylation profiles were obtained from noncancerous liver tissues using a Human Methylation 450 BeadChip, and the differences between the groups were analyzed for each set. After excluding single nucleotide polymorphism-associated methylation sites and low-call sites, 401,282 sites were assessed using a generalized linear model without any adjustments. Nine gene regions, APBB1P, CLSTN3, DLG5, IRX5, OAS1, SOX12, SNX19, TENM2, and TRIM54, exhibiting a significant difference (P < .001) in DNA methylation levels were identified in the common direction between the 2 analysis sets. Conclusion: Alterations in DNA methylation of 9 genes in noncancerous liver tissues appear to be involved in MO after radical hepatectomy for HCV-related HCC.

Published
2022
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15. First‐line sorafenib sequential therapy and liver disease etiology for unresectable hepatocellular carcinoma using inverse probability weighting: A multicenter retrospective study

Author

Shigeo Shimose, Atsushi Hiraoka, Masahito Nakano, Hideki Iwamoto, Masatoshi Tanaka, Takaaki Tanaka, Kazunori Noguchi, Hajime Aino, Kei Ogata, Masahiko Kajiwara, Satoshi Itano, Yoshinori Yokokura, Taizo Yamaguchi, Hiroshi Kawano, Norito Matsukuma, Hideya Suga, Takashi Niizeki, Tomotake Shirono, Yu Noda, Naoki Kamachi, Shusuke Okamura, Takumi Kawaguchi, Hironori Koga, and Takuji Torimura

Subjects
carcinoma, hepatocellular, nonalcoholic steatohepatitis, sequential therapy, sorafenib, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background and Aims Sequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC. Methods We evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2). Results Overall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. Conclusions Sequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

Published
2021
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17. Usefulness of a novel transarterial chemoinfusion plus external‐beam radiation therapy for advanced hepatocellular carcinoma with tumor thrombi in the inferior vena cava and right atrium: Case study

Author

Tomotake Shirono, Hironori Koga, Takashi Niizeki, Hiroaki Nagamatsu, Hideki Iwamoto, Shigeo Shimose, Masahito Nakano, Shusuke Okamura, Yu Noda, Naoki Kamachi, Ryoko Kuromatsu, Etsuyo Ogo, and Takuji Torimura

Subjects
cardiac invasion, hepatic arterial infusion chemoembolization, oncologic emergency, sorafenib, tumor thrombus, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Invasion beyond inferior vena cava (IVC) to right atrium (RA) is a rare complication in patients with advanced hepatocellular carcinoma (HCC), and results in fatal oncologic emergencies, including pulmonary embolism and right heart failure. Aim As there is no gold standard treatment for unresectable HCC with tumor thrombi involving IVC and RA, we considered it valuable to assess safety and efficacy of a combination of hepatic arterial infusion chemoembolization (HAIC) therapy and external‐beam radiation therapy (EBRT). Methods and results The “New FP” was chosen as the HAIC therapy, in which the enhanced permeation and retention effect was achieved using a cisplatin‐Lipiodol suspension combined with continuous infusion of 5‐fluorouracil (5‐FU). Sixteen patients with HCC with tumor thrombi in IVC, RA, and pulmonary arteries were enrolled. modified response evaluation criteria in solid tumors‐based evaluation of response to the combination treatment was as follows: complete response, 6.2% (1 patient); partial response, 81.3% (13 patients); stable disease, 12.5% (2 patients); progressive disease, 0%. The median overall survival time (MST) was 19.0 months. Notably, MST of patients receiving sequential sorafenib monotherapy (39.0 months) was significantly longer than that of the rest (15.3 months). Conclusion The combination of New FP and EBRT is an efficacious treatment option for unresectable HCC involving IVC and RA, complicated with pulmonary embolism. Sequential administration of molecular‐targeted drugs may prolong survival in such patients.

Published
2022
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18. Case Report: Exacerbation of varices following atezolizumab plus bevacizumab treatment of hepatocellular carcinoma: A case series and literature review

Author

Hiroyuki Suzuki, Hideki Iwamoto, Shigeo Shimose, Takashi Niizeki, Tomotake Shirono, Yu Noda, Naoki Kamachi, Taizo Yamaguchi, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, and Takumi Kawaguchi

Subjects
atezolizumab, bevacizumab, hepatocellular carcinoma, gastrointestinal hemorrhage, portal hypertension, varices, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Recently, a combined regimen of atezolizumab and bevacizumab (AB) treatment has been approved as a first-line treatment in patients with advanced hepatocellular carcinoma (HCC), contributing to prolonged survival. However, we often encounter cases where treatment must be discontinued due to the occurrence of adverse events. One of these events, which is often fatal, is gastrointestinal bleeding. To clarify the clinical effects of gastrointestinal bleeding after AB treatment, we evaluated patients with HCC who were treated with AB at our institution. Of the 105 patients, five treated with AB developed gastrointestinal bleeding, necessitating treatment discontinuation. Additionally, we encountered two cases where exacerbation of varicose veins was observed, and AB therapy could be continued by preventive treatment of varices. In conclusion, an appropriate follow-up is required during treatment with AB to prevent possible exacerbation of varicose veins.

Published
2022
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19. REal life study of LEnVAtiNib therapy for HepAtocellular carcinoma: RELEVANT study

Author

Andrea Casadei-Gardini, Margherita Rimini, Masatoshi Kudo, Shigeo Shimose, Toshifumi Tada, Goki Suda, Myung Ji Goh, Andre Jefremow, Mario Scartozzi, Giuseppe Cabibbo, Claudia Campani, Emiliano Tamburini, Francesco Tovoli, Kazuomi Ueshima, Tomoko Aoki, Hideki Iwamoto, Takuji Torimura, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Ei Itobayashi, Hidenori Toyoda, Naoya Sakamoto, Takuya Sho, Wonseok Kang, Jürgen Siebler, Markus Friedrich Neurath, Valentina Burgio, and Stefano Cascinu

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Introduction: In the REFLECT trial, lenvatinib was found to be non-inferior compared to sorafenib in terms of Overall Survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world, and to identify clinical factors that could be significantly associated with survival outcomes. Methods: The study population derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included Western and Eastern populations from 23 centres in five countries. Results: We included 1325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3 and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH related aetiology was independently associated with good prognosis. Median progression free survival was 6.3 months. Multivariate analysis for Progression Free survival revealed that NAFLD/NASH, BCLC, NLR and AST as independent prognostic factors for progression free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited that the appearance of decreased appetite Grade ≥ 2 versus Grade 0-1 as an independent prognostic factor for worse Progression Free Survival. 924 patients on 1325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over two-months from the beginning of second line treatment. From first line therapy the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months) and best supportive care (10.8 months). Conclusions: Our study confirms in a large and global population of patients with advanced HCC not candidate to locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.

Published
2022
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20. Primary Treatment with Molecular‐Targeted Agents for Hepatocellular Carcinoma: A Propensity Score‐matching Analysis

Author

Masahito Nakano, Ryoko Kuromatsu, Takashi Niizeki, Shusuke Okamura, Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Hironori Koga, Takuji Torimura, and The Kurume Liver Cancer Study Group of Japan

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Sorafenib and lenvatinib, as molecular‐targeted agents, constitute effective primary treatment options for advanced hepatocellular carcinoma (HCC). However, the choice of optimal primary treatment agent remains controversial. Here, we aimed to assess the respective outcomes between these agents as primary treatment in patients with advanced HCC through use of propensity score–matching analysis (PSMA). We enrolled 670 consecutive patients who were diagnosed with advanced HCC and received sorafenib (n = 524) or lenvatinib (n = 146) as the primary treatment among 18 participating institutions between May 2009 and October 2019. To reduce confounding, we used PSMA regarding seven variables related to advanced HCC prognosis, resulting in the selection of 292 patients (n = 146 for each agent). Following PSMA, no significant difference was observed in the outcome of overall survival time between patients treated with sorafenib or lenvatinib (median survival time 15.3 or 14.9 months, respectively; P = 0.2358). Patients treated with lenvatinib exhibited significantly greater therapeutic effects (response rate: 5% and 31%; disease control rate: 46% and 69% for sorafenib and lenvatinib, respectively; P

Published
2020
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21. Evaluating the therapeutic effect of lenvatinib against advanced hepatocellular carcinoma by measuring blood flow changes using contrast‐enhanced ultrasound

Author

Naoki Kamachi, Masahito Nakano, Shusuke Okamura, Takashi Niizeki, Hideki Iwamoto, Shigeo Shimose, Tomotake Shirono, Yu Noda, Ryoko Kuromatsu, Hironori Koga, and Takuji Torimura

Subjects
early stage, modified RECIST, peak intensity, renal function, time curve analysis, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background The antitumor effect of a drug is considered to be associated with a decrease in tumor blood flow. Aims We investigated whether the efficacy of lenvatinib (LEN) could be accurately assessed by measuring blood flow in hepatocellular carcinoma (HCC) during early treatment stages. Methods and results Blood flow changes and treatment results of 19 patients who underwent contrast‐enhanced ultrasound (CEUS), before and after LEN administration, in Kurume University Hospital from July 2018 to June 2020 were examined. Blood flow was evaluated after the intravenous administration of perflubutane (0.015 ml/kg). The vascular phase was photographed and used as RAW data, and time‐intensity curve analysis was used to obtain the region of interest (ROI) on the entire tumor nodule and quantify tumor blood flow. The evaluation was performed before and 1 and 4 weeks after LEN administration. Mean ± standard deviation (SD) values of the brightness of blood flow in the background liver before and 1 and 4 weeks after LEN administration were 2.84 × 10−4 ± 2.94 × 10−4, 3.07 × 10−4 ± 3.79 × 10−4, and 10.0 × 10−4 ± 20.8 × 10−4 dB, respectively. Blood flow in the background liver did not significantly decrease at 1 and 4 weeks compared with that before treatment. Mean ± SD values of the brightness of blood flow in HCC before and 1 and 4 weeks after administration were 3.49 × 10−3 ± 4.58 × 10−3, 1.16 × 10−3 ± 1.57 × 10−3, and 6.39 × 10−3 ± 22.8 × 10−3 dB, respectively. Blood flow in HCC after 1 week was significantly lower than that before administration (p = .0192). The therapeutic effects were significantly higher in the group with ≥50% blood flow reduction in HCC at 1 week after administration (p = .0038) and the group with reduced blood flow in HCC at 4 weeks after administration (p = .0051) than those before administration. Conclusion Early blood flow evaluation by CEUS may be useful in predicting the therapeutic effect of LEN for unresectable advanced HCC.

Published
2022
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22. Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments

Author

Hiroyuki Suzuki, Hideki Iwamoto, Masahito Nakano, Toru Nakamura, Atsutaka Masuda, Takahiko Sakaue, Toshimitsu Tanaka, Dan Nakano, Ryoko Kuromatsu, Takashi Niizeki, Shusuke Okamura, Shigeo Shimose, Tomotake Shirono, Yu Noda, Naoki Kamachi, Hirohisa Yano, Atsushi Kawaguchi, Hironori Koga, and Takuji Torimura

Subjects
Hepatocellular carcinoma, Combination chemotherapy, Sorafenib, Metronomic chemotherapy, S-1, STAM mouse, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Objective: Although sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib. Methods: Antitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015. Results: In mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p

Published
2021
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23. Blunt splenic injury in a child with situs inversus totalis treated with transcatheter arterial embolization

Author

Naoki Hashizume, Kimio Asagiri, Naoko Komatsuzaki, Suguru Fukahori, Shinji Ishii, Nobuyuki Saikusa, Naruki Higashidate, Motomu Yoshida, Saki Sakamoto, Hirotomo Nakahara, Yoshihiko Konoike, Kojiro Nagai, Shigeo Shimose, Takashi Niizeki, and Minoru Yagi

Subjects
Splenic injury, Situs inversus, Transcatheter arterial embolization, Pediatrics, RJ1-570, Surgery, RD1-811
Abstract

We report the first case of blunt splenic rupture in a child with situs inversus totalis treated with transcatheter arterial embolization (TAE). A 12-year-old girl fell roughly 4 feet onto the pavement while riding her bicycle. Contrast-enhanced computed tomography revealed situs inversus totalis, a massive hemorrhage in the abdominal cavity, and a ruptured spleen with extravasation. Arteriography showed that the internal organs were located opposite their normal positioning. TAE was carried out with gelfoam and a micro coils at the branch of the upper lobe of the splenic artery. TAE is effective for blunt splenic injury with extravasation in a child with situs inversus. In TAE, there is no technical difference about situs inversus excepted mirror image of abdominal vascular formation.

Published
2016
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24. Inhibition of hypoxia-inducible factor via upregulation of von Hippel-Lindau protein induces âangiogenic switch offâ in a hepatoma mouse model

Author

Hideki Iwamoto, Toru Nakamura, Hironori Koga, Jesus Izaguirre-Carbonell, Shinji Kamisuki, Fumio Sugawara, Mitsuhiko Abe, Kazuki Iwabata, Yu Ikezono, Takahiko Sakaue, Atsutaka Masuda, Hirohisa Yano, Keisuke Ohta, Masahito Nakano, Shigeo Shimose, Tomotake Shirono, and Takuji Torimura

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

âAngiogenic switch offâ is one of the ideal therapeutic concepts in the treatment of cancer. However, the specific molecules which can induce âangiogenic switch offâ in tumor have not been identified yet. In this study, we focused on von Hippel-Lindau protein (pVHL) in hepatocellular carcinoma (HCC) and investigated the effects of sulfoquinovosyl-acylpropanediol (SQAP), a novel synthetic sulfoglycolipid, for HCC. We examined mutation ratio of VHL gene in HCC using 30 HCC samples and we treated the HCC-implanted mice with SQAP. Thirty clinical samples showed no VHL genetic mutation in HCC. SQAP significantly inhibited tumor growth by inhibiting angiogenesis in a hepatoma mouse model. SQAP induced tumor âangiogenic switch offâ by decreasing hypoxia-inducible factor (HIF)-1, 2α protein via pVHL upregulation. pVHL upregulation decreased HIFα protein levels through different multiple mechanisms: (i) increasing pVHL-dependent HIFα protein degradation; (ii) decreasing HIFα synthesis with decrease of NF-κB expression; and (iii) decrease of tumor hypoxia by vascular normalization. We confirmed these antitumor effects of SQAP by the loss-of-function experiments. We found that SQAP directly bound to and inhibited transglutaminase 2. This study provides evidence that upregulation of tumor pVHL is a promising target, which can induce âangiogenic switch offâ in HCC.

Published
2015
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26. Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?

Author

Margherita Rimini, Mara Persano, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Fabio Piscaglia, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Lorenza Rimassa, Mario Scartozzi, Stefano Cascinu, and Andrea Casadei-Gardini

Subjects
Cancer Research, Oncology, Pharmacology (medical)
Published
2023
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27. Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments

Author

Persano, Mara, primary, Rimini, Margherita, additional, Tada, Toshifumi, additional, Suda, Goki, additional, Shigeo, Shimose, additional, Kudo, Masatoshi, additional, Cheon, Jaekyung, additional, Finkelmeier, Fabian, additional, Presa, José, additional, Masi, Gianluca, additional, Yoo, Changhoon, additional, Lonardi, Sara, additional, Piscaglia, Fabio, additional, Iavarone, Massimo, additional, Di Costanzo, Giuseppe, additional, Marra, Fabio, additional, Cabibbo, Giuseppe, additional, Foschi, Francesco, additional, Siletta, Marianna, additional, Cascinu, Stefano, additional, Scartozzi, Mario, additional, and Gardini, Andrea Casadei, additional

Published
2023
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28. Survival outcomes from Atezolizumab plus Bevacizumab versus Lenvatinib versus Sorafenib in Child Pugh B unresectable hepatocellular carcinoma patients

Author

Rimini, Margherita, primary, Persano, Mara, additional, Tada, Toshifumi, additional, Suda, Goki, additional, Shigeo, Shimose, additional, Kudo, Masatoshi, additional, Cheon, Jaekyung, additional, Finkelmeier, Fabian, additional, Lim, Ho Yeong, additional, Presa, José, additional, Lonardi, Sara, additional, Piscaglia, Fabio, additional, Chon, Hong Jae, additional, Masi, Gianluca, additional, Scartozzi, Mario, additional, Cascinu, Stefano, additional, and Casadei-Gardini, Andrea, additional

Published
2023
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29. Incidence and risk factors of esophagogastric varices bleeding in patients with advanced hepatocellular carcinoma treated with lenvatinib

Author

Iavarone, Massimo, primary, Alimenti, Eleonora, additional, Tada, Toshifumi, additional, Shigeo, Shimose, additional, Suda, Goki, additional, Yoo, Changhoon, additional, Soldà, Caterina, additional, Piscaglia, Fabio, additional, Gardini, Andrea Casadei, additional, Marra, Fabio, additional, Vivaldi, Caterina, additional, Conti, Fabio, additional, Schirripa, Marta, additional, Iwamoto, Hideki, additional, Sho, Takuya, additional, Leo, So Heun, additional, Rizzato, Mario Domenico, additional, Tonnini, Matteo, additional, Rimini, Margherita, additional, Campani, Claudia, additional, Masi, Gianluca, additional, Foschi, Francesco, additional, Bruccoleri, Mariangela, additional, Kawaguchi, Takumi, additional, Kumada, Takashi, additional, Hiraoka, Atsushi, additional, Atsukawa, Masanori, additional, Fukunishi, Shinya, additional, Ishikawa, Toru, additional, Tajiri, Kazuto, additional, Ochi, Hironori, additional, Yasuda, Satoshi, additional, Toyoda, Hidenori, additional, Hatanaka, Takeshi, additional, Kakizaki, Satoru, additional, Kawata, Kazuhito, additional, Tada, Faujimasa, additional, Ohama, Hideko, additional, Itokawa, Norio, additional, Okubo, Tomomi, additional, Arai, Taeang, additional, Imai, Michitaka, additional, Naganuma, Atsushi, additional, Tosetti, Giulia, additional, and Lampertico, Pietro, additional

Published
2023
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30. Significance of ramucirumab following atezolizumab plus bevacizumab therapy for hepatocellular carcinoma using real‐world data

Author

Shigeo Shimose, Rie Sugimoto, Atsushi Hiraoka, Masatoshi Tanaka, Hideki Iwamoto, Yuki Tanaka, Fujimasa Tada, Hideko Ohama, Takashi Niizeki, Tomotake Shirono, Etsuko Moriyama, Yu Noda, Naoki Kamachi, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, and Takumi Kawaguchi

Subjects
Infectious Diseases, Hepatology
Abstract

Few studies have reported the efficacy and safety of ramucirumab (RAM) after atezolizumab plus bevacizumab (Atezo/Beva) treatment and the overall associated outcomes. Thus, we aimed to evaluate the therapeutic effects and safety of RAM post-treatment with Atezo/Beva.This retrospective study enrolled 46 patients with unresectable hepatocellular carcinoma who were treated with RAM. The patients were classified into the RAM administered following Atezo/Beva failure (n = 12) or RAM administered following other drug failure (n = 34) groups. Progression-free survival (PFS), overall survival (OS), and adverse event (AE) rates were assessed.There were significant differences in the objective response rates and disease control rates between the RAM administered following Atezo/Beva and RAM administered following others groups (objective response rate 33.3%. vs. 0.0%, p = 0.001; disease control rate 83.3% vs. 32.3, p = 0.001). Although there was no significant difference in the OS rates, the median PFS rates in the RAM administered following Atezo/Beva group was significantly higher than in the RAM administered following others group (PFS 3.9 months. vs. 1.9 months, p = 0.047). The AE rates were comparable between the two groups; ascites was the most common AE (45.6%). Using decision tree analysis, the presence of splenomegaly and body mass index (BMI) 19.8 were the first and second splitting variables for RAM-related ascites, respectively.The therapeutic effect of RAM increased in patients with Atezo/Beva failure. Patients with splenomegaly and low BMI should be monitored for ascites during RAM treatment.

Published
2022
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31. Comparison of Efficacy and Safety of Atezolizumab Plus Bevacizumab and Lenvatinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: A Propensity Score Matching Analysis

Author

Takashi Niizeki, Takayuki Tokunaga, Yuko Takami, Yoshiyuki Wada, Masaru Harada, Michihiko Shibata, Kazuhiko Nakao, Ryu Sasaki, Fumihito Hirai, Satoshi Shakado, Tomoharu Yoshizumi, Shinji Itoh, Hiroshi Yatsuhashi, Shigemune Bekki, Akio Ido, Seiichi Mawatari, Koichi Honda, Rie Sugimoto, Takeshi Senju, Hirokazu Takahashi, Takuya Kuwashiro, Tatsuji Maeshiro, Makoto Nakamuta, Yoshifusa Aratake, Tsutomu Yamashita, Yuichiro Otsuka, Shuichi Matsumoto, Tetsuro Sohda, Shigeo Shimose, Kenta Murotani, and Yasuhito Tanaka

Subjects
Bevacizumab, Cancer Research, Carcinoma, Hepatocellular, Oncology, Liver Neoplasms, Humans, Pharmacology (medical), Propensity Score, Retrospective Studies
Abstract

A comparison between atezolizumab plus bevacizumab (ATEZO/BEVA) and lenvatinib (LEN) for the treatment of hepatocellular carcinoma (HCC) remains unclear.This study aimed to compare the therapeutic effects and safety of ATEZO/BEVA and LEN as first-line therapies for HCC.This study was a retrospective analysis of 810 patients with HCC who underwent ATEZO/BEVA (n = 186) or LEN (n = 624) as first-line systemic therapy between March 2018 to March 2022 at 14 facilities. After propensity score matching, 304 patients (ATEZO/BEVA group: n = 152; LEN group: n = 152) were analyzed.After propensity score matching, although there was no significant difference in objective response rates (ORRs) between the ATEZO/BEVA and LEN groups (ORR 44.8% vs. 46.7%, p = 0.644), the median progression-free survival (PFS) and median overall survival (OS) in the ATEZO/BEVA group were significantly higher than those in the LEN group (median PFS: 8.3 months vs. 6.0 months, p = 0.005; median OS: not reached vs. 20.2 months, p = 0.039). The rates of appetite loss, fatigue, and proteinuria of grade 3 or higher in the ATEZO/BEVA group were lower than those in the LEN group. However, the rate of bleeding of grade 3 or higher in the ATEZO/BEVA group was higher than that in the LEN group. The conversion rate was higher in the ATEZO/BEVA group than that in the LEN group (8.6% vs. 1.9%, p = 0.007).ATEZO/BEVA showed superiority to LEN in terms of prognosis and conversion rate as first-line therapy. Moreover, ATEZO/BEVA had a lower rate of severe adverse events, except for bleeding, than LEN.

Published
2022
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32. Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study

Author

Mara Persano, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, Lorenza Rimassa, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Takumi Kawaguchi, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Fabio Piscaglia, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Massimo Iavarone, Giovanni Di Costanzo, Fabio Marra, Mario Scartozzi, Emiliano Tamburini, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Antonella Cammarota, Valentina Burgio, Stefano Cascinu, Andrea Casadei-Gardini, and Mara Persano, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, Lorenza Rimassa, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Takumi Kawaguchi, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Fabio Piscaglia, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Massimo Iavarone, Giovanni Di Costanzo, Fabio Marra, Mario Scartozzi, Emiliano Tamburini, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Antonella Cammarota, Valentina Burgio, Stefano Cascinu, Andrea Casadei-Gardini

Subjects
Cancer Research, Settore MED/12 - Gastroenterologia, Lenvatinib, Oncology, Advanced HCC, Atezolizumab plus bevacizumab, First-line therapy, General Medicine
Abstract

Purpose: The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting. Methods: Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea). Results: 1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not reached in both arms, but the result from univariate Cox regression model showed 62% reduction of death risk for patients treated with atezolizumab plus bevacizumab (p = 0.05). In all multivariate analyses, treatment arm was not found to be an independent factor conditioning OS. Comparing ORR achieved in the two arms, there was a statistically significant difference in favor of lenvatinib compared to atezolizumab plus bevacizumab in all subgroups except for Eastern patients, Child-Pugh B patients, presence of portal vein thrombosis, α-feto-protein ≥ 400 ng/mL, presence of extrahepatic disease, albumin-bilirubin (ALBI) grade 2, and no previous locoregional procedures. Conclusion: Lenvatinib achieves higher ORR in all patient subgroups. Patients who achieve CR with atezolizumab plus bevacizumab can achieve OS so far never recorded in HCC patients. This study did not highlight any factors that could identify patient subgroups capable of obtaining CR.

Published
2022

33. Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients

Author

Margherita Rimini, Mara Persano, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Francesca Salani, Sara Lonardi, Fabio Piscaglia, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Marta Schirripa, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Mario Scartozzi, Stefano Cascinu, and Andrea Casadei-Gardini

Subjects
Cancer Research, Oncology, General Medicine
Published
2023
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34. Role of the prognostic nutritional index in predicting survival in advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab

Author

Margherita Rimini, Mara Persano, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa Ramos, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Bernardo Stefanini, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Angelo Della Corte, Francesca Ratti, Francesco De Cobelli, Luca Aldrighetti, Mario Scartozzi, Stefano Cascinu, and Andrea Casadei-Gardini

Subjects
Cancer Research, Oncology, General Medicine
Abstract

Introduction: The prognostic nutritional index (PNI) is a multiparametric score introduced by Onodera based on the blood levels of lymphocytes and albumin in patients with gastrointestinal neoplasms. Regarding hepatocellular carcinoma (HCC), its prognostic role has been demonstrated in patients treated with sorafenib and lenvatinib. The aim of this real-world study is to investigate the association between clinical outcomes and PNI in patients being treated with atezolizumab plus bevacizumab. Methods: The overall cohort of this multicentric study included 871 consecutive HCC patients from 4 countries treated with atezolizumab plus bevacizumab in first-line therapy. The PNI was calculated as follows: 10 × serum albumin concentration (g/dL) + 0.005 × peripheral lymphocyte count (number/mm3). Results: For only 773 patients, data regarding lymphocyte counts and albumin levels were available, so only these patients were included in the final analysis. The cut-off point of the PNI was determined to be 41 by receiver operating characteristic (ROC) analysis. 268 patients (34.7%) were categorized as the PNI-low group, while the remaining 505 (65.3%) patients as the PNI-high group. At the univariate analysis, high PNI was associated with longer overall survival (OS) (22.5 vs. 10.1 months, HR 0.34, p < 0.01) and progression-free survival (PFS) (8.7 vs. 5.8 months, HR 0.63, p < 0.01) compared to patients with low PNI. At the multivariate analysis, high versus low PNI resulted as an independent prognostic factor for OS (HR 0.49 , p < 0.01) and PFS (HR 0.82, p = 0.01). There was no difference in objective response rate (ORR) between the two groups (high 26.1% vs. low 19.8%, p = 0.09), while disease control rate (DCR) was significantly higher in the PNI-high group (76.8% vs. 66.4%, p = 0.01). Conclusion: PNI is an independent prognostic factor for OS and PFS in HCC patients on first-line treatment with atezolizumab plus bevacizumab.

Published
2023
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35. First‐line sorafenib sequential therapy and liver disease etiology for unresectable hepatocellular carcinoma using inverse probability weighting: A multicenter retrospective study

Author

Masahiko Kajiwara, Hironori Koga, Takumi Kawaguchi, Taizo Yamaguchi, Hideya Suga, Yu Noda, Shusuke Okamura, Masatoshi Tanaka, Atsushi Hiraoka, Takaaki Tanaka, Takuji Torimura, Tomotake Shirono, Naoki Kamachi, Hiroshi Kawano, Masahito Nakano, Takashi Niizeki, Satoshi Itano, Shigeo Shimose, Kazunori Noguchi, Yoshinori Yokokura, Hajime Aino, Kei Ogata, Hideki Iwamoto, and Norito Matsukuma

Subjects
Adult, Male, Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, carcinoma, Gastroenterology, Liver disease, hepatocellular, Japan, Non-alcoholic Fatty Liver Disease, Internal medicine, Nonalcoholic fatty liver disease, Carcinoma, medicine, Humans, Radiology, Nuclear Medicine and imaging, nonalcoholic steatohepatitis, Research Articles, RC254-282, Aged, Retrospective Studies, Aged, 80 and over, Hepatitis, sequential therapy, business.industry, Liver Neoplasms, Clinical Cancer Research, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Retrospective cohort study, Middle Aged, medicine.disease, Progression-Free Survival, digestive system diseases, Oncology, Hepatocellular carcinoma, Etiology, Female, sorafenib, business, Research Article, medicine.drug
Abstract

Background and Aims Sequential therapy with molecular‐targeted agents (MTAs) is considered effective for unresectable hepatocellular carcinoma (HCC) patients. This study purposed to evaluate the efficacy of sequential therapy with sorafenib (SORA) as a first‐line therapy and to investigate the therapeutic impact of SORA in nonalcoholic fatty liver disease (NAFLD) or nonalcoholic steato hepatitis (NASH)‐related HCC. Methods We evaluated 504 HCC patients treated with SORA (Study‐1). The times of administration for sorafenib from 2009 to 2015, 2016 to 2017, and 2018 and later were defined as the early‐, mid‐, and late‐term periods, respectively. Among them, 180 HCC patients treated with SORA in addition to MTAs in the mid‐ and late‐term periods were divided into groups based on disease etiology (NAFLD or NASH [n = 37] and viral or alcohol [n = 143]), and outcomes were compared after inverse probability weighting (IPW) (Study‐2). Results Overall survival (OS) of HCC patients who received sequential MTA therapy after first‐line SORA was significantly longer. The median survival times (MST) were 12.6 versus 17.6 versus 17.4 months in the early‐term group, mid‐term group, and the later‐time group (early vs. mid, p = 0.014, early vs. later. p = 0.045), respectively. (Study‐1). In Study‐2, there was no significant differences in OS between the Virus/alcohol group and the NAFLD/NASH group in patients who received sequential therapy (MST was 23.4 and 27.0 months p = 0.173, respectively). The NAFLD or NASH, female sex, albumin‐bilirubin (ALBI) grade 2b, and major Vp (Vp3/Vp4) were significant factors for OS treated with SORA. Conclusions Sequential therapy with SORA as the first‐line treatment improved the prognosis of unresectable HCC patients and was effective regardless of HCC etiology., Sequential therapy with SORA as the first‐line treatment prolonged the prognosis of unresectable HCC patients and was effective regardless of HCC etiology.

Published
2021
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36. Impact of branched-chain amino acids and frailty on the management of lenvatinib-related fatigue in patients with hepatocellular carcinoma

Author

Sachiyo Yoshio, Takuji Torimura, Shunji Koya, Takashi Niizeki, Shigeo Shimose, Takumi Kawaguchi, Hiroo Matsuse, and Keisuke Hirota

Subjects
Antineoplastic Agents, lenvatinib, frailty, RC799-869, chemistry.chemical_compound, medicine, Humans, In patient, Letter to the Editor, Molecular Biology, carcinoma, hepatocellular, chemistry.chemical_classification, Hepatology, business.industry, Phenylurea Compounds, Liver Neoplasms, Diseases of the digestive system. Gastroenterology, medicine.disease, Amino acid, chemistry, amino acids, branched-chain, Hepatocellular carcinoma, Quinolines, Cancer research, fatigue, Lenvatinib, business
Published
2021

37. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population

Author

Andrea Casadei-Gardini, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, Lorenza Rimassa, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Fabio Piscaglia, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Massimo Iavarone, Giovanni Di Costanzo, Fabio Marra, Mario Scartozzi, Emiliano Tamburini, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Mara Persano, Angelo Della Corte, Francesca Ratti, Francesco De Cobelli, Luca Aldrighetti, Stefano Cascinu, and Alessandro Cucchetti

Subjects
Cancer Research, Oncology
Abstract

Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomised controlled trial. We conducted a retrospective multi-centre study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario.Clinical features of lenvatinib and atezolizumab plus bevacizumab patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival (OS) was the primary end-point.The analysis included 1341 patients who received lenvatinib, and 864 patients who received atezolizumab plus bevacizumab. After IPTW adjustment, atezolizumab plus bevacizumab did not show a survival advantage over lenvatinib HR 0.97 (p = 0.739). OS was prolonged by atezolizumab plus bevacizumab over lenvatinib in viral patients (HR: 0.76; p = 0.024). Conversely, OS was prolonged by lenvatinib in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (HR: 1.88; p = 0.014). In the IPTW-adjusted population, atezolizumab plus bevacizumab provided better safety profile for most of the recorded adverse events.Our study did not identify any meaningful difference in OS between atezolizumab plus bevacizumab and lenvatinib. Although some hints are provided suggesting that patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease might benefit more from lenvatinib therapy and patients with viral aetiology more from atezolizumab plus bevacizumab.

Published
2022

38. Association between Adverse Events and Prognosis in Patients with Hepatocellular Carcinoma Treated with Atezolizumab Plus Bevacizumab: A Multicenter Retrospective Study

Author

Shigeo Shimose, Hideki Iwamoto, Masatoshi Tanaka, Takashi Niizeki, Masahiko Kajiwara, Satoshi Itano, Etsuko Moriyama, Tomotake Shirono, Yu Noda, Naoki Kamachi, Masahito Nakano, Ryoko Kuromatsu, Hironori Koga, and Takumi Kawaguchi

Subjects
Cancer Research, Oncology, adverse events, overall survival, hepatocellular carcinoma, progression-free survival
Abstract

This study aimed to evaluate the correlation between adverse events (AEs) and overall survival (OS) in patients with unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab (atezo/beva). This was a multicenter study in which 130 patients were enrolled. Hypertension and skin disorders had a significant correlation with longer survival (median survival time (MST): not reached vs. 14.3 months and not reached vs. 14.8 months, p = 0.001 and p = 0.047, respectively). In contrast, liver injuries were significantly correlated with shorter survival (MST: 14.7 months vs. not reached, p = 0.036), and the median development time was 21 days. In a logistic regression analysis, fatigue ≥ grade 2, liver injury ≥ grade 3, and modified albumin–bilirubin grade 2b were identified as independent factors for discontinuation due to AEs. The OS in the no discontinuation due to AE group was significantly longer than that in the discontinuation due to AEs group (MST not reached vs. 11.2 months, p = 0.001). We concluded that the development of liver injury was a negative factor for OS and that we should be vigilant in monitoring AE during atezo/beva treatments.

Published
2022

39. Multimolecular-Targeted Agents for Intermediate-Stage Hepatocellular Carcinoma Influence Time to Stage Progression and Overall Survival

Author

Naoki Kamachi, Masahito Nakano, Takashi Niizeki, Takumi Kawaguchi, Takuji Torimura, Shigeo Shimose, Hironori Koga, Yu Noda, Ryoko Kuromatsu, Masatoshi Tanaka, Tomotake Shirono, Shusuke Okamura, Hideki Iwamoto, and Akira Kajiwara

Subjects
Adult, Male, Oncology, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Multivariate analysis, Antineoplastic Agents, Kaplan-Meier Estimate, Intermediate stage, Refractory, Internal medicine, medicine, Overall survival, Humans, In patient, Chemoembolization, Therapeutic, Stage (cooking), Propensity Score, Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, business.industry, Phenylurea Compounds, Liver Neoplasms, General Medicine, Middle Aged, Sorafenib, medicine.disease, Combined Modality Therapy, Survival Rate, Treatment Outcome, Hepatocellular carcinoma, Propensity score matching, Disease Progression, Quinolines, Female, business, Follow-Up Studies
Abstract

Background & Aims: Intermediate hepatocellular carcinoma (HCC) treatment has become complicated due to the development of various molecular-targeted agents (MTAs). We aimed to determine whether the administration of MTAs in patients with intermediate-stage HCC contributed to the prevention of progression to an advanced stage. Methods: We enrolled and retrospectively examined 289 patients with Child-Pugh class A who had been diagnosed with intermediate-stage HCC and underwent initial trans-arterial chemoembolization (TACE). Patients were classified into 2 groups: a group in which MTAs were administered to patients whose condition was refractory to TACE (n = 65) and a group in which MTAs were not administered (n = 65) at intermediate-stage HCC after propensity score matching (PSM). Time to stage progression (TTSP) and overall survival (OS) were calculated using the Kaplan-Meier method and analyzed using a log-rank test after PSM. Results: TTSP and OS of the group with MTA administration were significantly longer than those of the group without MTA administration (TTSP: 36.4 vs. 17.9 months, p < 0.001; median survival time [MST]: 44.6 vs. 26.6 months, p = 0.001). Within the up-to-seven criteria and administration of MTAs at the intermediate-stage HCC were identified as independent factors for TTSP and OS in the multivariate analysis. TTSP and OS in the era of the multi-MTA group were significantly longer than those in the era of the mono-MTA group (TTSP: 44.8 vs. 27.4 months, p = 0.01; MST: 53.4 vs. 33.3 months, p = 0.01). Conclusion: The administration of MTAs in patients with intermediate-stage HCC contributes to the prevention of stage progression and prolongs OS.

Published
2021
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40. Hepatitis C Virus Elimination Using Direct Acting Antivirals after the Radical Cure of Hepatocellular Carcinoma Suppresses the Recurrence of the Cancer

Author

Ryoko Kuromatsu, Tatsuya Ide, Shusuke Okamura, Yu Noda, Naoki Kamachi, Masahito Nakano, Tomotake Shirono, Shigeo Shimose, Hideki Iwamoto, Reiichiro Kuwahara, Teruko Arinaga-Hino, Takashi Niizeki, Yuki Zaizen, Hiroshi Takaki, Miki Shirachi, Hironori Koga, and Takuji Torimura

Subjects
Cancer Research, Oncology, digestive system diseases, hepatocellular carcinoma, hepatitis C virus, direct-acting antiviral, recurrence, radiofrequency ablation, hepatic resection, propensity score matching
Abstract

It remains unclear whether hepatocellular carcinoma (HCC) recurrence in hepatitis C virus (HCV)-infected patients can be suppressed by the elimination of the virus using direct-acting antivirals (DAAs) after radical HCC treatment. We evaluated the sustained inhibitory effect of DAAs on HCC recurrence after curative treatment. This multicenter retrospective study included 190 HCV-positive patients after radical treatment for early-stage HCC. Patients were classified into the DAA treatment group (n = 70) and the non-DAA treatment group (n = 120) after HCC treatment. After propensity score matching (PSM), 112 patients were assessed for first and second recurrences using the Kaplan–Meier method and analyzed using a log-rank test. The first recurrence rates at 1 and 3 years were 3.6% and 42.1% in the DAA treatment group and 21.7% and 61.9% in the non-DAA treatment group, respectively (p = 0.0026). Among 85 patients who received radical treatment, the second recurrence rate at 3 years was 2.2% in the DAA treatment group and 33.9% in the non-DAA treatment group (p = 0.0128). In HCV-positive patients with early-stage HCC, the first and second recurrences were suppressed by DAA therapy after radical treatment, suggesting that the inhibitory effect of DAA therapy on HCC recurrence was sustained.

Published
2022
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42. Validation of the easy-to-use lenvatinib prognostic index to predict prognosis in advanced hepatocellular carcinoma patients treated with lenvatinib

Author

Margherita Rimini, Wonseok Kang, Valentina Burgio, Mara Persano, Tamoko Aoki, Shigeo Shimose, Toshifumi Tada, Takashi Kumada, Takuya Sho, Eleonora Lai, Ciro Celsa, Claudia Campani, Matteo Tonnini, Emiliano Tamburini, Atsushi Hiraoka, Koichi Takaguchi, Naoshi Nishida, Hideki Iwamoto, Ei Itobayashi, Kunihiko Tsuji, Naoya Sakamoto, Toru Ishikawa, Hidenori Toyoda, Masatoshi Kudo, Takumi Kawaguchi, Takeshi Hatanaka, Kazugiro Nouso, Goki Suda, Giuseppe Cabibbo, Fabio Marra, Angelo Della Corte, Francesca Ratti, Federica Pedica, Francesco De Cobelli, Luca Aldrighetti, Mario Scartozzi, Stefano Cascinu, Andrea Casadei‐Gardini, Rimini, Margherita, Kang, Wonseok, Burgio, Valentina, Persano, Mara, Aoki, Tamoko, Shimose, Shigeo, Tada, Toshifumi, Kumada, Takashi, Sho, Takuya, Lai, Eleonora, Celsa, Ciro, Campani, Claudia, Tonnini, Matteo, Tamburini, Emiliano, Hiraoka, Atsushi, Takaguchi, Koichi, Nishida, Naoshi, Iwamoto, Hideki, Itobayashi, Ei, Tsuji, Kunihiko, Sakamoto, Naoya, Ishikawa, Toru, Toyoda, Hidenori, Kudo, Masatoshi, Kawaguchi, Takumi, Hatanaka, Takeshi, Nouso, Kazugiro, Suda, Goki, Cabibbo, Giuseppe, Marra, Fabio, Della Corte, Angelo, Ratti, Francesca, Pedica, Federica, De Cobelli, Francesco, Aldrighetti, Luca, Scartozzi, Mario, Cascinu, Stefano, and Casadei-Gardini, Andrea

Subjects
Infectious Diseases, Hepatology, prognostic factors, hepatocellular carcinoma, lenvatinib
Abstract

Aim The identification of new prognostic factors able to stratify hepatocellular carcinoma patients candidate to first-line therapy is urgent. In the present work we validated the prognostic value of the lenvatinib prognostic index. Methods Data of Eastern and Western patients treated with lenvatinib as first-line for Barcelona Clinic Liver Cancer stage B or C hepatocellular carcinoma were recollected. The lenvatinib prognostic index was composed by three classes of risk according with our previous study. The "low risk" group includes patients with prognostic nutritional index (PNI) >43.3 and with previous transarterial chemoembolization. The "medium risk" group includes patients with PNI >43.3, but without previous transarterial chemoembolization and patients with PNI

Published
2022

43. Global multi-stakeholder endorsement of the MAFLD definition

Author

Nahum Méndez-Sánchez, Elisabetta Bugianesi, Robert G Gish, Frank Lammert, Herbert Tilg, Mindie H Nguyen, Shiv K Sarin, Núria Fabrellas, Shira Zelber-Sagi, Jian-Gao Fan, Gamal Shiha, Giovanni Targher, Ming-Hua Zheng, Wah-Kheong Chan, Shlomo Vinker, Takumi Kawaguchi, Laurent Castera, Yusuf Yilmaz, Marko Korenjak, C Wendy Spearman, Mehmet Ungan, Melissa Palmer, Mortada El-Shabrawi, Hans-Juergen Gruss, Jean-François Dufour, Anil Dhawan, Heiner Wedemeyer, Jacob George, Luca Valenti, Yasser Fouad, Manuel Romero‐Gomez, Mohammed Eslam, Maria Lorena Abate, Bahaa Abbas, Ahmed Amr Abbassy, Waleed Abd El Ghany, Amira Abd Elkhalek, Emad Abd ElMajeed, Mohammad Abdalgaber, Mohamed AbdAllah, Marwa Abdallah, Nourhan Abdallah, Shereen Abdelaleem, Yasser Abdelghani, Wael Abdelghany, Safaa Mohamed Abdelhalim, Wafaa Abdelhamid, Nehal Abdelhamid, Nadia A. Abdelkader, Elsayed Abdelkreem, Aly Mohamed Abdelmohsen, Awny Ali Abdelrahman, Sherief M Abd-elsalam, Doaa Abdeltawab, Abdulbaset Abduh, Nada Abdulhakam, Maheeba Abdulla, Navid Abedpoor, Ludovico Abenavoli, Fredrik Åberg, Omala Ablack, Mostafa Abo elftouh, Yousry Esam-Eldin Abo-Amer, Ashraf Aboubkr, Alaa Aboud, Amr M. Abouelnaga, Galal A. Aboufarrag, Ashraf Aboutaleb, Leticia Abundis, Gupse Adalı, Enrique Adames, Leon Adams, Danjuma Adda, Noor Adel, Nada Adel, Muhammad Adel Sayed, Taiba Jibril Afaa, Nawal Afredj, Gulnara Aghayeva, Alessio Aghemo, Carlos A. Aguilar-Salinas, Golo Ahlenstiel, Walid Ahmady, Wafaa Ahmed, Amira Ahmed, Samah Nasser Ahmed, Heba Mostafa Ahmed, Rasha Ahmed, Elmar Aigner, Mesut Akarsu, Maisam Akroush, Umit Akyuz, Mamun Al Mahtab, Tahani Al Qadiri, Yusriya Al Rawahi, Razzaq AL rubaee, Muna Al Saffar, Shahinul Alam, Zaid Al-Ani, Agustín Albillos, Mohamed Alboraie, Said Al-Busafi, Mohamed Al-Emam, Jawaher Alharthi, Kareem Ali, Basma Abdelmoez Ali, Mohammad Ali, Raja Affendi Raja Ali, Anna Alisi, Ali Raad AL-Khafaji, Maryam Alkhatry, Rocio Aller, Yahya Almansoury, Khalid Al-Naamani, Alaa Alnakeeb, Anna Alonso, Saleh A. Alqahtani, Leina Alrabadi, Khalid Alswat, Mahir Altaher, Turki Altamimi, Jose Altamirano, Mario R. Alvares-da-Silva, Elsragy Adel M. Aly, Amgad Alzahaby, Ahmed Alzamzamy, Keisuke Amano, Maysa A. Amer, Mona A. Amin, Sayed A. Amin, Ashraf A. Amir, Javier Ampuero, Noha Anas, Pietro Andreone, Soa Fy Andriamandimby, Mahmoud Anees, Peltec Angela, Manal Antonios, Wael Arafat, Jose Moreno Araya, Juan Armendariz-Borunda, Matthew J. Armstrong, Hassan Ashktorab, Patricia Aspichueta, Fathia Assal, Mira Atef, Dina Attia, Hoda Atwa, Reham Awad, Mohyeldeen Abd Elaziz Awad, Sally Awny, Obafemi Awolowo, Yaw Asante Awuku, Ibrahim Ayada, Than Than Aye, Sherif Ayman, Hedy Ayman, Hesham Ayoub, Hosny M. Azmy, Romiro P. Babaran, Omneya Badreldin, Ahmed Badry, İbrahim Halil Bahçecioğlu, Amira Bahour, Jiajia Bai, Yasemin Balaban, Muthuswamy Balasubramanyam, Khaled Bamakhrama, Jesus M Banales, Babu Bangaru, Jianfeng Bao, Jorge Suazo Barahona, Salma Barakat, Sandra Maria Barbalho, Bikwa Barbra, Beatriz Barranco, Francisco Barrera, Ulrich Baumann, Shamardan Bazeed, Eva Bech, Aourarh Benayad, Andreas Benesic, David Bernstein, Fernando Bessone, Susie Birney, Cyrille Bisseye, Martin Blake, Bilal Bobat, Leonilde Bonfrate, Dmitry S Bordin, Francisco Bosques-Padilla, Jerome Boursier, Boushab Mohamed Boushab, David Bowen, Patricia Medina Bravo, Paul N Brennan, Bisi Bright, Ilse Broekaert, Xabier Buque, Diego Burgos-Santamaría, Julio Burman, Luca Busetto, Chris D. Byrne, Patricia Anne I. Cabral-Prodigalidad, Guillermo Cabrera-Alvarez, Wei Cai, Francesca Cainelli, Ali Riza Caliskan, Ali Canbay, Ana Cano-Contreras, Hai-Xia Cao, Zhujun Cao, Andres Carrion, Francesca Carubbi, Teresa Casanovas, Marlen Ivón Castellanos Fernández, Jin Chai, Siew Pheng Chan, Phunchai Charatcharoenwitthaya, Norberto Chavez-Tapia, Kazuaki Chayama, Jinjun Chen, Lin Chen, Zhong-Wei Chen, Huiting Chen, Sui-Dan Chen, Qiang Chen, Yaxi Chen, Gang Chen, En-Quang Chen, Fei Chen, Pei-Jer Chen, Robert Cheng, Wendy Cheng, Jack Tan Wei Chieh, Imad Chokr, Evangelos Cholongitas, Ashok Choudhury, Abhijit Chowdhury, Evaristus Sunday Chukwudike, Stefano Ciardullo, Michelle Clayton, Karine Clement, Marie Michelle Cloa, Cecilia Coccia, Cristina Collazos, Massimo Colombo, Arif Mansur Cosar, Helma Pinchemel Cotrim, Joris Couillerot, Alioune Coulibaly, Gonzalo Crespo, Javier Crespo, Maria Cruells, Ian Homer Y. Cua, Hesham K. Dabbous, George N Dalekos, Patricia D'Alia, Li Dan, Viet Hang Dao, Mostafa Darwish, Christian Datz, Milagros B Davalos-Moscol, Heba Dawoud, Blanca Olaechea de Careaga, Robert de Knegt, Victor de Ledinghen, Janaka de Silva, Nabil Debzi, Marie Decraecker, Elvira Del Pozo, Teresa C Delgado, Manuel Delgado-Blanco, Łukasz Dembiński, Adilson Depina, Moutaz Derbala, Hailemichael Desalegn, Christèle Desbois-Mouthon, Mahmoud Desoky, Anouk Dev, Agostino Di Ciaula, Moisés Diago, Ibrahima Diallo, Luis Antonio Díaz, Melisa Dirchwolf, Paola Dongiovanni, Andrriy Dorofeyev, Xiaoguang Dou, Mark W. Douglas, Michael Doulberis, Cecil K. Dovia, Adam Doyle, Ivana Dragojević, Joost PH Drenth, Xuefei Duan, Audrius Dulskas, Dan L Dumitrascu, Oliver Duncan, Vincent Dusabejambo, Rev. Shem N.A. Dwawhi, Sho Eiketsu, Doaa El Amrousy, Ahmed El Deeb, Ghada El Deriny, Hesham Salah El Din, Salwa El Kamshishy, Mohamed El Kassas, Maissa El Raziky, Osama A Elagamy, Wafaa Elakel, Dina Elalfy, Hanaa Elaraby, Heba ElAwady, Reda Elbadawy, Hanaa Hassan Eldash, Manal S. Eldefrawy, Carol Lezama Elecharri, Amel Elfaramawy, Mohammed Elfatih, Mahmoud Elfiky, Mohamed Elgamsy, Mohamed Elgendy, Mohamed A. El-Guindi, Nagi Elhussieny, Ahmed Maher Eliwa, Zeineb Elkabbany, Hesham El-Khayat, Nehal M. El-Koofy, Alaa Elmetwalli, Amr Elrabat, Fathiya El-Raey, Fatma Elrashdy, Medhat Elsahhar, Esraa M. Elsaid, Shimaa Elsayed, Hany Elsayed, Aly Elsayed, Amr M. Elsayed, Hamdy Elsayed, Magdy El-Serafy, Ahmed M. Elsharkawy, Reem Yehia Elsheemy, Eman Elsayed Elshemy, Sara Elsherbini, Naglaa Eltoukhy, Reda Elwakil, Ola Emad, Shaimaa Emad, Mohamed Embabi, Ilkay Ergenç, Tatiana Ermolova, Gamal Esmat, Doaa M. Esmat, Enrique Carrera Estupiñan, Said Ettair, Tcaciuc Eugen, Mohammed Ezz-Eldin, Lidia Patricia Valdivieso Falcón, Yu-Chen Fan, Samah Fandari, Mahmoud Farag, Taghreed Mohamed Farahat, Eman M. Fares, Michael Fares, Eduardo Fassio, Hayam Fathy, Dina Fathy, Wael Fathy, Soheir Fayed, Dan Feng, Gong Feng, Miguel Fernández-Bermejo, Cristina Targa Ferreira, Javier Díaz Ferrer, Alastair Forbes, Rabab Fouad, Hanan M. Fouad, Tove Frisch, Hideki Fujii, Shuhei Fukunaga, Shinya Fukunishi, Hacer Fulya, Masato Furuhashi, Yasmine Gaber, Augusto Jose G. Galang, Jacqueline Cordova Gallardo, Rocío Galloso, Mahmoud Gamal, Reham Gamal, Hadeel Gamal, Jian Gan, Anar Ganbold, Xin Gao, George Garas, Tony Garba, Miren García-Cortes, Carmelo García-Monzón, Javier García-Samaniego, Amalia Gastaldelli, Manuel Gatica, Elizabeth Gatley, Tamar Gegeshidze, Bin Geng, Hasmik Ghazinyan, Salma Ghoneem, Luca Giacomelli, Gianluigi Giannelli, Edoardo G. Giannini, Matthew Giefer, Pere Ginès, Marcos Girala, Pablo J Giraudi, George Boon-Bee Goh, Ahmed Ali Gomaa, Benbingdi Gong, Dina Hilda C. Gonzales, Humberto C. Gonzalez, Maria Saraí Gonzalez-Huezo, Isabel Graupera, Ivica Grgurevic, Henning Grønbæk, Xuelian Gu, Lin Guan, Ibrahima Gueye, Alice Nanelin Guingané, Ozen Oz Gul, Cuma Bulent Gul, Qing Guo, Pramendra Prasad Gupta, Ahmet Gurakar, Juan Carlos Restrepo Gutierrez, Ghada Habib, Azaa Hafez, Emilia Hagman, Eman Halawa, Osama Hamdy, Abd Elkhalek Hamed, Dina H. Hamed, Saeed Hamid, Waseem Hamoudi, Yu Han, James Haridy, Hanan Haridy, David C H Harris Harris, Michael Hart, Fuad Hasan, Almoutaz Hashim, Israa Hassan, Ayman Hassan, Essam Ali Hassan, Adel Ahmed Hassan, Magda Shehata Hassan, Fetouh Hassanin, Alshymaa Hassnine, John Willy Haukeland, Amr Ismael M. Hawal, Jinfan He, Qiong He, Yong He, Fang-Ping He, Mona Hegazy, Adham Hegazy, Osama Henegil, Nelia Hernández, Manuel Hernández-Guerra, Fatima Higuera-de-la-Tijera, Ibrahim Hindy, Keisuke Hirota, Lee Chi Ho, Alexander Hodge, Mohamed Hosny, Xin Hou, Jiao-Feng Huang, Yan Huang, Zhifeng Huang, Yuan Huang, Ang Huang, Xiao-Ping Huang, Sheng Hui-ping, Bela Hunyady, Mennatallah A. Hussein, Osama Hussein, Shahinaz Mahmoud Hussien, Luis Ibáñez-Samaniego, Jamal Ibdah, Luqman Ibrahim, Miada Ibrahim, Ibrahim Ibrahim, Maria E. Icaza-Chávez, Sahar Idelbi, Ramazan Idilman Idilman, Mayumi Ikeda, Giuseppe Indolfi, Federica Invernizzi, Iram Irshad, Hasan Mohamed Ali Isa, Natacha Jreige Iskandar, Abdulrahman Ismaiel, Mariam Ismail, Zulkifli Ismail, Faisal Ismail, Hideki Iwamoto, Kathryn Jack, Rachael Jacob, Fuad Jafarov, Wasim Jafri, Helen Jahshan, Prasun K Jalal, Ligita Jancoriene, Martin Janicko, Hiruni Jayasena, Meryem Jefferies, Vivekanand Jha, Fanpu Ji, Yaqiu Ji, Jidong Jia, Changtao Jiang, Ni Jiang, Zong-zhe Jiang, Xing Jin, Yi Jin, Xu Jing, Qian Jingyu, Maia Jinjolava, FX Himawan Haryanto Jong, Alina Jucov, Ibecheole Julius, Mona Kaddah, Yoshihiro Kamada, Abobakr kamal, Enas Mohamed Kamal, Ashraf Sayed Kamel, Jia-Horng Kao, Maja Karin, Thomas Karlas, Mohammad Kashwaa, Leolin Katsidzira, Eda Kaya, M.Azzam Kayasseh, Bernadette Keenan, Caglayan Keklikkiran, William Keml, Deia K. Khalaf, Rofida Khalefa, Sherin Khamis, Doaa Khater, Hamed khattab, Anatoly Khavkin, Olga Khlynova, Nabil Khmis, Nazarii Kobyliak, Apostolos Koffas, Kazuhiko Koike, Kenneth Y.Y. Kok, Tomas Koller, Narcisse Patrice Komas, Nataliya V. Korochanskaya, Yannoula Koulla, Shunji Koya, Colleen Kraft, Bledar Kraja, Marcin Krawczyk, Mohammad Shafi Kuchay, Anand V Kulkarni, Ashish Kumar, Manoj Kumar, Sulaiman Lakoh, Philip Lam, Ling Lan, Naomi F. Lange, Kamran Bagheri Lankarani, Nicolas Lanthier, Kateryna Lapshyna, Sameh A. Lashen, Konang Nguieguia Justine Laure, Leonid Lazebnik, Didier Lebrec, Samuel S. Lee, Way Seah Lee, Yeong Yeh Lee, Diana Julie Leeming, Nathalie Carvalho Leite, Roberto Leon, Cosmas Rinaldi Adithya Lesmana, Junfeng Li, Qiong Li, Jun Li, Yang-Yang Li, Yufang Li, Lei Li, Min Li, Yiling li, Huiqing Liang, Tang Lijuan, Seng Gee Lim, Lee-Ling Lim, Shumei Lin, Han-Chieh Lin, Rita Lin, Rania Lithy, Yaru Liu, Yuanyuan Liu, Xin Liu, Wen-Yue Liu, Shourong Liu, Ken Liu, Tian Liu, Amedeo Lonardo, Mariana Bravo López, Eva López-Benages, Patricio Lopez-Jaramillo, Huimin Lu, Lun Gen Lu, Yan Lu, John Lubel, Rashid Lui, Iulianna Lupasco, Elena Luzina, Xiao-Hui Lv, Kate Lynch, Hong-Lei Ma, Mariana Verdelho Machado, Nonso Maduka, Katerina Madzharova, Russellini Magdaong, Sanjiv Mahadeva, Amel Mahfouz, Nik Ritza Kosai Nik Mahmood, Eman Mahmoud, Mohamed Mahrous, Rakhi Maiwall, Ammar Majeed, Avik Majumdar, Loey Mak, Madiha M Maklouf, Reza Malekzadeh, Claudia Mandato, Alessandra Mangia, Jake Mann, Hala Hussien Mansour, Abdellah Mansouri, Alessandro Mantovani, Jun qian Mao, Flor Maramag, Giulio Marchesini, Claude Marcus, Rui António Rocha Tato Marinho, Maria L Martinez-Chantar, Antonieta A. Soares Martins, Rana Marwan, Karen Frances Mason, Ghadeer Masoud, Mohamed Naguib Massoud, Maria Amalia Matamoros, Rosa Martín Mateos, Asmaa Mawed, Jean Claude Mbanya, Charles Mbendi, Lone McColaugh, Duncan McLeod, Juan Francisco Rivera Medina, Ahmed Megahed, Mai Mehrez, Iqbal Memon, Shahin Merat, Randy Mercado, Ahmed Mesbah, Taoufik Meskini, Mayada Metwally, Rasha Metwaly, Lei Miao, Eileen Micah, Luca Miele, Vladimir Milivojevic, Tamara Milovanovic, Yvonne L. Mina, Milan Mishkovik, Amal Mishriki, Tim Mitchell, Alshaimaa Mohamed, Mona Mohamed, Sofain Mohamed, Shady Mohammed, Ahmed Mohammed, Viswanathan Mohan, Sara Mohie, Aalaa Mokhtar, Reham Moniem, Mabel Segura Montilla, Jose Antonio Orozco Morales, María María Sánchez Morata, Jose Maria Moreno-Planas, Silvia Morise, Sherif Mosaad, Mohamed Moselhy, Alaa Mohamed Mostafa, Ebraheem Mostafa, Nezha Mouane, Nasser Mousa, Hamdy Mahfouz Moustafa, Abeer Msherif, Kate Muller, Christopher Munoz, Ana Beatriz Muñoz-Urribarri, Omar Alfaro Murillo, Feisul Idzwan Mustapha, Emir Muzurović, Yehia Nabil, Shaymaa Nafady, Ayu Nagamatsu, Atsushi Nakajima, Dan Nakano, Yuemin Nan, Fabio Nascimbeni, Mirella S. Naseef, Nagwa Nashat, Taran Natalia, Francesco Negro, Alexander V. Nersesov, Manuela Neuman, Masolwa Ng'wanasayi, Yan Ni, Amanda Nicoll, Takashi Niizeki, Dafina Nikolova, Wang Ningning, Madunil Niriella, K.A Nogoibaeva, Rozeena Nordien, Catherine O Sullivan, James O'Beirne, Solomon Obekpa, Ponsiano Ocama, Missiani Ochwoto, Michael Promise Ogolodom, Olusegun Ojo, Nana Okrostsvaridze, Claudia P. Oliveira, Raul Contreras Omaña, Omneya M. Omar, Hanaa Omar, Mabroka Omar, Salma Omran, Reham Omran, Marian Muse Osman, Nevin Owise, Theobald Owusu-Ansah, P. Martín Padilla- Machaca, Sirish Palle, Ziyan Pan, Xiao-Yan Pan, Qiuwei Pan, Apostolis Papaefthymiou, Feliciano Chanana Paquissi, Gabriella Par, Arit Parkash, Diana Payawal, Kevork M. Peltekian, Xuebin Peng, Liang Peng, Ying Peng, Rahul Pengoria, Martina Perez, José Luis Pérez, Norma Marlene Pérez, Marcello Persico, Mário Guimarães Pessoa, Salvatore Petta, Mathew Philip, Maria Corina Plaz Torres, Naveen Polavarapu, Jaime Poniachik, Piero Portincasa, Chunwen Pu, Tuğrul Pürnak, Edhie Purwanto, Xiaolong Qi, Xingshun Qi, Zibing Qian, Zhao Qiang, Zengpei Qiao, Liang Qiao, Alberto Queiroz, Atoosa Rabiee, Manal Radwan, Alain Marcel Rahetilahy, Yasmin Ramadan, Dina Ramadan, Anis Safura Ramli, Grant A. Ramm, Ao Ran, Ivan Rankovic, Huiying RAO, Sara Raouf, Sayantan Ray, Nancy Reau, Ahmed Refaat, Thomas Reiberger, Jose M Remes-Troche, Eira Cerda Reyes, Ben Richardson, Ezequiel Ridruejo, Sergio Riestra Jimenez, Ibrahim Rizk, Stuart Roberts, Juan Pablo Roblero, Jorge Alberto Prado Robles, Don Rockey, Manuel Rodríguez, Heriberto Rodríguez Hernández, Eva Román, Fernando Gomes Romeiro, Stefano Romeo, Jose Miguel Rosales-Zabal, Georgina R. Roshdi, Natalia Rosso, Andres Ruf, Patricia Cordero Ruiz, Nelia R. Runes, Andrea Ruzzenente, Marno Ryan, Ahmed Saad, Eman BE Sabbagh, Meriam Sabbah, Shimaa Saber, Reham Sabrey, Ramy Sabry, Maysaa Abdallah Saeed, Dina Said, Ebada M Said, Mohammad Amin Sakr, Yara Salah, Rabab Maamoun Salama, Asmaa Salama, Hussein Saleh, Ahmed Saleh, Ahmed Salem, Ahmed Thabet Salem, Alkassoum Salifou, Aso Faeq Salih, Abdallah Salman, Hanen Samouda, Faisal Sanai, Juan Francisco Sánchez-Ávila, Lakshumanan Sanker, Tomoya Sano, Miquel Sanz, Tobokalova Saparbu, Rohit Sawhney, Fatma Sayed, Sayed A. Sayed, Ashraf Othman Sayed, Manar Sayed, Giada Sebastiani, Laura Secadas, Khawaja Qamaruddin Sediqi, Sameh Seif, Nady Semida, Ebubekir Şenateş, Elena Daniela Serban, Lawrence Serfaty, Wai-Kay Seto, Ikram Sghaier, Min Sha, Hamada M. Shabaan, Lobna Shalaby, Inass Shaltout, Ala I. Sharara, Vishal Sharma, Isaac Thom Shawa, Ahmed Shawkat, Nehal Shawky, Osama Shehata, Sinead Sheils, Abate Bane Shewaye, Guojun Shi, Junping Shi, Shigeo Shimose, Tomotake Shirono, Lan Shou, Ananta Shrestha, Guanghou Shui, William Sievert, Solveig Sigurdardottir, Mostafa Mohamed Sira, Riyadh Siradj, Cecilia Sison, Linda Smyth, Reham Soliman, Jose D Sollano, Roger Sombie, Mark Sonderup, Siddharth Sood, German Soriano, Catherine A M Stedman, Oksana Stefanyuk, Davor Štimac, Simone Strasser, Pavel Strnad, Katherine Stuart, Wen Su, Minghua Su, Yoshio Sumida, Shuji Sumie, Dan-Qin Sun, Jing Sun, Hiroyuki Suzuki, Gianluca Svegliati-Baroni, Mohamed Osman Swar, S. TAHARBOUCHT, Zenab Taher, Saori Takamura, Lin Tan, Soek-Siam Tan, Tawesak Tanwandee, Sara Tarek, Ghelimici Tatiana, Federica Tavaglione, Gina Y. Tecson, Hoi-Poh Tee, Rolf Teschke, Mostafa Tharwat, Vo Duy Thong, Mark Thursz, Tulari Tine, Claudio Tiribelli, Ieva Tolmane, Jing Tong, Marco Tongo, Mamdouh Torkie, Aldo Torre, Esther A Torres, Meri Trajkovska, Sombat Treeprasertsuk, Tsubasa Tsutsumi, Thomas Tu, Josep A. Tur, Dilara Turan, Svetlana Turcan, Svetlana Turkina, Engin Tutar, Christian Tzeuton, Rose Ugiagbe, Ahmet Uygun, Michele Vacca, Pietro Vajro, David Van der Poorten, Laurens A. Van Kleef, Eliza Vashakidze, Carlos Moctezuma Velazquez, Mirtha Infante Velazquez, Sandro Vento, Veronique Verhoeven, Umberto Vespasiani-Gentilucci, Shireene Ratna Vethakkan, Josep Vilaseca, Libor Vítek, Ance Volkanovska, Michael Wallace, Wang Wan, Yan Wang, Ying Wang, Xiaolin Wang, Xuemei Wang, Chengyan Wang, Chunjiong Wang, Mingjie Wang, Pelden Wangchuk, Martin Weltman, MaryFrances White, Johannes Wiegand, Mohamed-Naguib Wifi, Alan Wigg, Markus Wilhelmi, Remon William, Henning Wittenburg, Shengjie Wu, Abdu Mohammed Wubeneh, Hongping Xia, Jian Xiao, Xiao Xiao, Wang Xiaofeng, Wanyuan Xiong, Liang Xu, Jie Xu, Weiguo Xu, Jing-Hang Xu, Keshu Xu, Yumin Xu, Shi-Hao Xu, Meng Xu, Aimin Xu, Chengfu Xu, Hongmei Yan, Jingyi Yang, Rui-Xu Yang, Yating Yang, Qinhe Yang, Naibin Yang, Jia Yao, Justine Yara, Serkan Yaraş, Nimet Yılmaz, Ramy Younes, Huda younes, Sona Young, Farah Youssef, Yanyan Yu, Ming-Lung Yu, Jing Yuan, Zhang Yue, Man-Fung Yuen, Wang Yun, Nonka Yurukova, Serag Zakaria, Samy Zaky, Maia Zaldastanishvili, Rodrigo Zapata, Nazanin Zare, Enver Zerem, Nema Zeriban, Xu Zeshuai, Huijie Zhang, Xuemei Zhang, Yupei Zhang, Wen-Hua Zhang, Xuchen Zhang, Yon-ping Zhang, Yuexin Zhang, Zhan-qing Zhang, Jingmin Zhao, Rong-Rong Zhao, Hongwei Zhao, Chao Zheng, Yijie Zheng, Ruidan Zheng, Tian-Lei Zheng, Kenneth Zheng, Xi Qiao Zhou, Yongjian Zhou, Yu-Jie Zhou, Hong Zhou, Ling Zhou, Yongning Zhou, Long dong Zhu, Yong Fen Zhu, Yueyong Zhu, Pei-Wu Zhu, Ebtesam Ziada, David Ziring, Li Ziyi, Shanshan Zou, Zhengsheng Zou, Huaibin Zou, Roberto Zuart Ruiz, UCL - (SLuc) Service de gastro-entérologie, UCL - SSS/IREC/GAEN - Pôle d'Hépato-gastro-entérologie, Mendez-Sanchez, N, Bugianesi, E, Gish, R, Lammert, F, Tilg, H, Nguyen, M, Sarin, S, Fabrellas, N, Zelber-Sagi, S, Fan, J, Shiha, G, Targher, G, Zheng, M, Chan, W, Vinker, S, Kawaguchi, T, Castera, L, Yilmaz, Y, Korenjak, M, Spearman, C, Ungan, M, Palmer, M, El-Shabrawi, M, Gruss, H, Dufour, J, Dhawan, A, Wedemeyer, H, George, J, Valenti, L, Fouad, Y, Romero-Gomez, M, Eslam, M, Abate, M, Abbas, B, Abbassy, A, Abd El Ghany, W, Abd Elkhalek, A, Abd ElMajeed, E, Abdalgaber, M, Abdallah, M, Abdallah, N, Abdelaleem, S, Abdelghani, Y, Abdelghany, W, Abdelhalim, S, Abdelhamid, W, Abdelhamid, N, Abdelkader, N, Abdelkreem, E, Abdelmohsen, A, Abdelrahman, A, Abd-elsalam, S, Abdeltawab, D, Abduh, A, Abdulhakam, N, Abdulla, M, Abedpoor, N, Abenavoli, L, Aberg, F, Ablack, O, Abo elftouh, M, Abo-Amer, Y, Aboubkr, A, Aboud, A, Abouelnaga, A, Aboufarrag, G, Aboutaleb, A, Abundis, L, Adali, G, Adames, E, Adams, L, Adda, D, Adel, N, Adel Sayed, M, Afaa, T, Afredj, N, Aghayeva, G, Aghemo, A, Aguilar-Salinas, C, Ahlenstiel, G, Ahmady, W, Ahmed, W, Ahmed, A, Ahmed, S, Ahmed, H, Ahmed, R, Aigner, E, Akarsu, M, Akroush, M, Akyuz, U, Al Mahtab, M, Al Qadiri, T, Al Rawahi, Y, AL rubaee, R, Al Saffar, M, Alam, S, Al-Ani, Z, Albillos, A, Alboraie, M, Al-Busafi, S, Al-Emam, M, Alharthi, J, Ali, K, Ali, B, Ali, M, Ali, R, Alisi, A, AL-Khafaji, A, Alkhatry, M, Aller, R, Almansoury, Y, Al-Naamani, K, Alnakeeb, A, Alonso, A, Alqahtani, S, Alrabadi, L, Alswat, K, Altaher, M, Altamimi, T, Altamirano, J, Alvares-da-Silva, M, Aly, E, Alzahaby, A, Alzamzamy, A, Amano, K, Amer, M, Amin, M, Amin, S, Amir, A, Ampuero, J, Anas, N, Andreone, P, Andriamandimby, S, Anees, M, Angela, P, Antonios, M, Arafat, W, Araya, J, Armendariz-Borunda, J, Armstrong, M, Ashktorab, H, Aspichueta, P, Assal, F, Atef, M, Attia, D, Atwa, H, Awad, R, Awad, M, Awny, S, Awolowo, O, Awuku, Y, Ayada, I, Aye, T, Ayman, S, Ayman, H, Ayoub, H, Azmy, H, Babaran, R, Badreldin, O, Badry, A, Bahcecioglu, I, Bahour, A, Bai, J, Balaban, Y, Balasubramanyam, M, Bamakhrama, K, Banales, J, Bangaru, B, Bao, J, Barahona, J, Barakat, S, Barbalho, S, Barbra, B, Barranco, B, Barrera, F, Baumann, U, Bazeed, S, Bech, E, Benayad, A, Benesic, A, Bernstein, D, Bessone, F, Birney, S, Bisseye, C, Blake, M, Bobat, B, Bonfrate, L, Bordin, D, Bosques-Padilla, F, Boursier, J, Boushab, B, Bowen, D, Bravo, P, Brennan, P, Bright, B, Broekaert, I, Buque, X, Burgos-Santamaria, D, Burman, J, Busetto, L, Byrne, C, Cabral-Prodigalidad, P, Cabrera-Alvarez, G, Cai, W, Cainelli, F, Caliskan, A, Canbay, A, Cano-Contreras, A, Cao, H, Cao, Z, Carrion, A, Carubbi, F, Casanovas, T, Castellanos Fernandez, M, Chai, J, Chan, S, Charatcharoenwitthaya, P, Chavez-Tapia, N, Chayama, K, Chen, J, Chen, L, Chen, Z, Chen, H, Chen, S, Chen, Q, Chen, Y, Chen, G, Chen, E, Chen, F, Chen, P, Cheng, R, Cheng, W, Chieh, J, Chokr, I, Cholongitas, E, Choudhury, A, Chowdhury, A, Chukwudike, E, Ciardullo, S, Clayton, M, Clement, K, Cloa, M, Coccia, C, Collazos, C, Colombo, M, Cosar, A, Cotrim, H, Couillerot, J, Coulibaly, A, Crespo, G, Crespo, J, Cruells, M, Cua, I, Dabbous, H, Dalekos, G, D'Alia, P, Dan, L, Dao, V, Darwish, M, Datz, C, Davalos-Moscol, M, Dawoud, H, de Careaga, B, de Knegt, R, de Ledinghen, V, de Silva, J, Debzi, N, Decraecker, M, Del Pozo, E, Delgado, T, Delgado-Blanco, M, Dembinski, L, Depina, A, Derbala, M, Desalegn, H, Desbois-Mouthon, C, Desoky, M, Dev, A, Di Ciaula, A, Diago, M, Diallo, I, Diaz, L, Dirchwolf, M, Dongiovanni, P, Dorofeyev, A, Dou, X, Douglas, M, Doulberis, M, Dovia, C, Doyle, A, Dragojevic, I, Drenth, J, Duan, X, Dulskas, A, Dumitrascu, D, Duncan, O, Dusabejambo, V, Dwawhi, R, Eiketsu, S, El Amrousy, D, El Deeb, A, El Deriny, G, El Din, H, El Kamshishy, S, El Kassas, M, El Raziky, M, Elagamy, O, Elakel, W, Elalfy, D, Elaraby, H, Elawady, H, Elbadawy, R, Eldash, H, Eldefrawy, M, Elecharri, C, Elfaramawy, A, Elfatih, M, Elfiky, M, Elgamsy, M, Elgendy, M, El-Guindi, M, Elhussieny, N, Eliwa, A, Elkabbany, Z, El-Khayat, H, El-Koofy, N, Elmetwalli, A, Elrabat, A, El-Raey, F, Elrashdy, F, Elsahhar, M, Elsaid, E, Elsayed, S, Elsayed, H, Elsayed, A, El-Serafy, M, Elsharkawy, A, Elsheemy, R, Elshemy, E, Elsherbini, S, Eltoukhy, N, Elwakil, R, Emad, O, Emad, S, Embabi, M, Ergenc, I, Ermolova, T, Esmat, G, Esmat, D, Estupinan, E, Ettair, S, Eugen, T, Ezz-Eldin, M, Falcon, L, Fan, Y, Fandari, S, Farag, M, Farahat, T, Fares, E, Fares, M, Fassio, E, Fathy, H, Fathy, D, Fathy, W, Fayed, S, Feng, D, Feng, G, Fernandez-Bermejo, M, Ferreira, C, Ferrer, J, Forbes, A, Fouad, R, Fouad, H, Frisch, T, Fujii, H, Fukunaga, S, Fukunishi, S, Fulya, H, Furuhashi, M, Gaber, Y, Galang, A, Gallardo, J, Galloso, R, Gamal, M, Gamal, R, Gamal, H, Gan, J, Ganbold, A, Gao, X, Garas, G, Garba, T, Garcia-Cortes, M, Garcia-Monzon, C, Garcia-Samaniego, J, Gastaldelli, A, Gatica, M, Gatley, E, Gegeshidze, T, Geng, B, Ghazinyan, H, Ghoneem, S, Giacomelli, L, Giannelli, G, Giannini, E, Giefer, M, Gines, P, Girala, M, Giraudi, P, Goh, G, Gomaa, A, Gong, B, Gonzales, D, Gonzalez, H, Gonzalez-Huezo, M, Graupera, I, Grgurevic, I, Gronbaek, H, Gu, X, Guan, L, Gueye, I, Guingane, A, Gul, O, Gul, C, Guo, Q, Gupta, P, Gurakar, A, Gutierrez, J, Habib, G, Hafez, A, Hagman, E, Halawa, E, Hamdy, O, Hamed, A, Hamed, D, Hamid, S, Hamoudi, W, Han, Y, Haridy, J, Haridy, H, Harris, D, Hart, M, Hasan, F, Hashim, A, Hassan, I, Hassan, A, Hassan, E, Hassan, M, Hassanin, F, Hassnine, A, Haukeland, J, Hawal, A, He, J, He, Q, He, Y, He, F, Hegazy, M, Hegazy, A, Henegil, O, Hernandez, N, Hernandez-Guerra, M, Higuera-de-la-Tijera, F, Hindy, I, Hirota, K, Ho, L, Hodge, A, Hosny, M, Hou, X, Huang, J, Huang, Y, Huang, Z, Huang, A, Huang, X, Hui-ping, S, Hunyady, B, Hussein, M, Hussein, O, Hussien, S, Ibanez-Samaniego, L, Ibdah, J, Ibrahim, L, Ibrahim, M, Ibrahim, I, Icaza-Chavez, M, Idelbi, S, Idilman, R, Ikeda, M, Indolfi, G, Invernizzi, F, Irshad, I, Isa, H, Iskandar, N, Ismaiel, A, Ismail, M, Ismail, Z, Ismail, F, Iwamoto, H, Jack, K, Jacob, R, Jafarov, F, Jafri, W, Jahshan, H, Jalal, P, Jancoriene, L, Janicko, M, Jayasena, H, Jefferies, M, Jha, V, Ji, F, Ji, Y, Jia, J, Jiang, C, Jiang, N, Jiang, Z, Jin, X, Jin, Y, Jing, X, Jingyu, Q, Jinjolava, M, Jong, F, Jucov, A, Julius, I, Kaddah, M, Kamada, Y, Kamal, A, Kamal, E, Kamel, A, Kao, J, Karin, M, Karlas, T, Kashwaa, M, Katsidzira, L, Kaya, E, Kayasseh, M, Keenan, B, Keklikkiran, C, Keml, W, Khalaf, D, Khalefa, R, Khamis, S, Khater, D, Khattab, H, Khavkin, A, Khlynova, O, Khmis, N, Kobyliak, N, Koffas, A, Koike, K, Kok, K, Koller, T, Komas, N, Korochanskaya, N, Koulla, Y, Koya, S, Kraft, C, Kraja, B, Krawczyk, M, Kuchay, M, Kulkarni, A, Kumar, A, Kumar, M, Lakoh, S, Lam, P, Lan, L, Lange, N, Lankarani, K, Lanthier, N, Lapshyna, K, Lashen, S, Laure, K, Lazebnik, L, Lebrec, D, Lee, S, Lee, W, Lee, Y, Leeming, D, Leite, N, Leon, R, Lesmana, C, Li, J, Li, Q, Li, Y, Li, L, Li, M, Liang, H, Lijuan, T, Lim, S, Lim, L, Lin, S, Lin, H, Lin, R, Lithy, R, Liu, Y, Liu, X, Liu, W, Liu, S, Liu, K, Liu, T, Lonardo, A, Lopez, M, Lopez-Benages, E, Lopez-Jaramillo, P, Lu, H, Lu, L, Lu, Y, Lubel, J, Lui, R, Lupasco, I, Luzina, E, Lv, X, Lynch, K, Ma, H, Machado, M, Maduka, N, Madzharova, K, Magdaong, R, Mahadeva, S, Mahfouz, A, Mahmood, N, Mahmoud, E, Mahrous, M, Maiwall, R, Majeed, A, Majumdar, A, Mak, L, Maklouf, M, Malekzadeh, R, Mandato, C, Mangia, A, Mann, J, Mansour, H, Mansouri, A, Mantovani, A, Mao, J, Maramag, F, Marchesini, G, Marcus, C, Marinho, R, Martinez-Chantar, M, Martins, A, Marwan, R, Mason, K, Masoud, G, Massoud, M, Matamoros, M, Mateos, R, Mawed, A, Mbanya, J, Mbendi, C, Mccolaugh, L, Mcleod, D, Medina, J, Megahed, A, Mehrez, M, Memon, I, Merat, S, Mercado, R, Mesbah, A, Meskini, T, Metwally, M, Metwaly, R, Miao, L, Micah, E, Miele, L, Milivojevic, V, Milovanovic, T, Mina, Y, Mishkovik, M, Mishriki, A, Mitchell, T, Mohamed, A, Mohamed, M, Mohamed, S, Mohammed, S, Mohammed, A, Mohan, V, Mohie, S, Mokhtar, A, Moniem, R, Montilla, M, Morales, J, Morata, M, Moreno-Planas, J, Morise, S, Mosaad, S, Moselhy, M, Mostafa, A, Mostafa, E, Mouane, N, Mousa, N, Moustafa, H, Msherif, A, Muller, K, Munoz, C, Munoz-Urribarri, A, Murillo, O, Mustapha, F, Muzurovic, E, Nabil, Y, Nafady, S, Nagamatsu, A, Nakajima, A, Nakano, D, Nan, Y, Nascimbeni, F, Naseef, M, Nashat, N, Natalia, T, Negro, F, Nersesov, A, Neuman, M, Ng'Wanasayi, M, Ni, Y, Nicoll, A, Niizeki, T, Nikolova, D, Ningning, W, Niriella, M, Nogoibaeva, K, Nordien, R, O Sullivan, C, O'Beirne, J, Obekpa, S, Ocama, P, Ochwoto, M, Ogolodom, M, Ojo, O, Okrostsvaridze, N, Oliveira, C, Omana, R, Omar, O, Omar, H, Omar, M, Omran, S, Omran, R, Osman, M, Owise, N, Owusu-Ansah, T, Padilla- Machaca, P, Palle, S, Pan, Z, Pan, X, Pan, Q, Papaefthymiou, A, Paquissi, F, Par, G, Parkash, A, Payawal, D, Peltekian, K, Peng, X, Peng, L, Peng, Y, Pengoria, R, Perez, M, Perez, J, Perez, N, Persico, M, Pessoa, M, Petta, S, Philip, M, Plaz Torres, M, Polavarapu, N, Poniachik, J, Portincasa, P, Pu, C, Purnak, T, Purwanto, E, Qi, X, Qian, Z, Qiang, Z, Qiao, Z, Qiao, L, Queiroz, A, Rabiee, A, Radwan, M, Rahetilahy, A, Ramadan, Y, Ramadan, D, Ramli, A, Ramm, G, Ran, A, Rankovic, I, Rao, H, Raouf, S, Ray, S, Reau, N, Refaat, A, Reiberger, T, Remes-Troche, J, Reyes, E, Richardson, B, Ridruejo, E, Riestra Jimenez, S, Rizk, I, Roberts, S, Roblero, J, Robles, J, Rockey, D, Rodriguez, M, Rodriguez Hernandez, H, Roman, E, Romeiro, F, Romeo, S, Rosales-Zabal, J, Roshdi, G, Rosso, N, Ruf, A, Ruiz, P, Runes, N, Ruzzenente, A, Ryan, M, Saad, A, Sabbagh, E, Sabbah, M, Saber, S, Sabrey, R, Sabry, R, Saeed, M, Said, D, Said, E, Sakr, M, Salah, Y, Salama, R, Salama, A, Saleh, H, Saleh, A, Salem, A, Salifou, A, Salih, A, Salman, A, Samouda, H, Sanai, F, Sanchez-Avila, J, Sanker, L, Sano, T, Sanz, M, Saparbu, T, Sawhney, R, Sayed, F, Sayed, S, Sayed, A, Sayed, M, Sebastiani, G, Secadas, L, Sediqi, K, Seif, S, Semida, N, Senates, E, Serban, E, Serfaty, L, Seto, W, Sghaier, I, Sha, M, Shabaan, H, Shalaby, L, Shaltout, I, Sharara, A, Sharma, V, Shawa, I, Shawkat, A, Shawky, N, Shehata, O, Sheils, S, Shewaye, A, Shi, G, Shi, J, Shimose, S, Shirono, T, Shou, L, Shrestha, A, Shui, G, Sievert, W, Sigurdardottir, S, Sira, M, Siradj, R, Sison, C, Smyth, L, Soliman, R, Sollano, J, Sombie, R, Sonderup, M, Sood, S, Soriano, G, Stedman, C, Stefanyuk, O, Stimac, D, Strasser, S, Strnad, P, Stuart, K, Su, W, Su, M, Sumida, Y, Sumie, S, Sun, D, Sun, J, Suzuki, H, Svegliati-Baroni, G, Swar, M, Taharboucht, S, Taher, Z, Takamura, S, Tan, L, Tan, S, Tanwandee, T, Tarek, S, Tatiana, G, Tavaglione, F, Tecson, G, Tee, H, Teschke, R, Tharwat, M, Thong, V, Thursz, M, Tine, T, Tiribelli, C, Tolmane, I, Tong, J, Tongo, M, Torkie, M, Torre, A, Torres, E, Trajkovska, M, Treeprasertsuk, S, Tsutsumi, T, Tu, T, Tur, J, Turan, D, Turcan, S, Turkina, S, Tutar, E, Tzeuton, C, Ugiagbe, R, Uygun, A, Vacca, M, Vajro, P, Van der Poorten, D, Van Kleef, L, Vashakidze, E, Velazquez, C, Velazquez, M, Vento, S, Verhoeven, V, Vespasiani-Gentilucci, U, Vethakkan, S, Vilaseca, J, Vitek, L, Volkanovska, A, Wallace, M, Wan, W, Wang, Y, Wang, X, Wang, C, Wang, M, Wangchuk, P, Weltman, M, White, M, Wiegand, J, Wifi, M, Wigg, A, Wilhelmi, M, William, R, Wittenburg, H, Wu, S, Wubeneh, A, Xia, H, Xiao, J, Xiao, X, Xiaofeng, W, Xiong, W, Xu, L, Xu, J, Xu, W, Xu, K, Xu, Y, Xu, S, Xu, M, Xu, A, Xu, C, Yan, H, Yang, J, Yang, R, Yang, Y, Yang, Q, Yang, N, Yao, J, Yara, J, Yaras, S, Yilmaz, N, Younes, R, Younes, H, Young, S, Youssef, F, Yu, Y, Yu, M, Yuan, J, Yue, Z, Yuen, M, Yun, W, Yurukova, N, Zakaria, S, Zaky, S, Zaldastanishvili, M, Zapata, R, Zare, N, Zerem, E, Zeriban, N, Zeshuai, X, Zhang, H, Zhang, X, Zhang, Y, Zhang, W, Zhang, Z, Zhao, J, Zhao, R, Zhao, H, Zheng, C, Zheng, Y, Zheng, R, Zheng, T, Zheng, K, Zhou, X, Zhou, Y, Zhou, H, Zhou, L, Zhu, L, Zhu, Y, Zhu, P, Ziada, E, Ziring, D, Ziyi, L, Zou, S, Zou, Z, Zou, H, Zuart Ruiz, R, and Global Multi-Stakeholder Consensus on the Redefinition of Fatty Liver Disease

Subjects
Renal disorders Radboud Institute for Molecular Life Sciences [Radboudumc 11], Hepatology, Non-alcoholic Fatty Liver Disease, NAFLD, consensu, Gastroenterology, MAFLD, definition, Humans, MAFLD, NAFLD, Human medicine
Abstract

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Published
2022
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44. Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: A large, real-life, worldwide population

Author

Margherita Rimini, Andrea Casadei-Gardini, Mara Persano, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Lorenza Rimassa, Josè Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Mario Scartozzi, Valentina Burgio, Stefano Cascinu, and Alessandro Cucchetti

Subjects
Cancer Research, Oncology
Abstract

579 Background: Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomized controlled trial. We conducted a retrospective multi-center study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario. Methods: Clinical features of lenvatinib and atezolizumab plus bevacizumab patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival was the primary endpoint. Results: The analysis included 1,341 patients who received lenvatinib, and 864 patients who received atezolizumab plus bevacizumab. After IPTW adjustment, atezolizumab plus bevacizumab did not show a survival advantage over lenvatinib HR 0.97 (p=0.739). OS was prolonged by atezolizumab plus bevacizumab over lenvatinib in viral patients (HR: 0.76; p=0.024). Conversely, OS was prolonged by lenvatinib in patients with NASH/NAFLD (HR: 1.88; p=0.014). In the IPTW-adjusted population, atezolizumab plus bevacizumab provided better safety profile for most of the recorded adverse events. Conclusions: Our study did not identify any meaningful difference in overall survival between atezolizumab plus bevacizumab and lenvatinib. Although some hints are provided suggesting that patients with NASH/NAFLD might benefit more from lenvatinib therapy and patients with viral etiology more from atezolizumab plus bevacizumab.

Published
2023
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45. Association between contrast enhancement on contrast-enhanced CT and lenvatinib effectiveness in hepatocellular carcinoma

Author

Ryoko Kuromatsu, Takuji Torimura, Hideki Iwamoto, Yu Noda, Tomotake Shirono, Shusuke Okamura, Shigeo Shimose, Naoki Kamachi, Masahito Nakano, Takashi Niizeki, and Hironori Koga

Subjects
Cancer Research, Contrast enhancement, Enhanced ct, business.industry, media_common.quotation_subject, Cancer, computed tomography, Articles, hepatocellular carcinoma, lenvatinib, medicine.disease, chemistry.chemical_compound, Oncology, chemistry, Hepatocellular carcinoma, medicine, Contrast (vision), prognosis, Nuclear medicine, business, Lenvatinib, histological differentiation, media_common
Abstract

The aim of the present study was to investigate whether the degree of contrast enhancement on contrast-enhanced (CE)-CT can predict the prognosis of patients with hepatocellular carcinoma (HCC) treated with lenvatinib (LEN). A total of 67 consecutive patients with LEN-treated HCC were retrospectively analysed. In the pretreatment CE-CT, the CT values were measured using a region of interest within the main nodule and the liver parenchyma in the arterial phase, and the macroscopic degree of contrast enhancement of the tumour area was quantified by calculating the enhancement ratio (ER) of the liver parenchyma. The associations of pretreatment ER with progression-free survival (PFS) and overall survival (OS) were then investigated. There were 20, 27 and 20 patients in the ER ≥1.5, 1.0≤ ER

Published
2021

46. Efficacy and tolerability of Sorafenib plus metronomic chemotherapy S-1 for advanced hepatocellular carcinoma in preclinical and clinical assessments

Author

Atsutaka Masuda, Shigeo Shimose, Hirohisa Yano, Hideki Iwamoto, Hiroyuki Suzuki, Takuji Torimura, Toru Nakamura, Toshimitsu Tanaka, Yu Noda, Ryoko Kuromatsu, Hironori Koga, Tomotake Shirono, Dan Nakano, Shusuke Okamura, Takahiko Sakaue, Naoki Kamachi, Atsushi Kawaguchi, Masahito Nakano, and Takashi Niizeki

Subjects
Sorafenib, Oncology, Cancer Research, medicine.medical_specialty, Hepatocellular carcinoma, MTD, Maximum Tolerated Dose, Hb, Hemoglobin, MTA, Molecular Targeted Agent, Combination chemotherapy, Internal medicine, medicine, AE, Adverse Event, MC, Metronomic Chemotherapy, Adverse effect, neoplasms, PDGF, Platelet-Derived Growth Factor, RC254-282, Original Research, STAM mouse, MVD, Micro Vessel Density, VEGF, Vascular Endothelial Growth Factor, business.industry, Metronomic chemotherapy, Therapeutic effect, WBC, White Blood Cell, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, S-1, LC, Liver Cirrhosis, medicine.disease, Metronomic Chemotherapy, digestive system diseases, NASH, Non-Alcoholic Steato Hepatitis, OS, Overall Survival, Tolerability, Toxicity, VT, Vehicle Treatment, HCC, Hepatocellular Carcinoma, business, PCNA, Proliferating Cell Nuclear Antigen, medicine.drug
Abstract

Highlight • Sorafenib plus MC S-1 chemotherapy can be safely used in patients with advanced HCC. • Combination of the metronomic chemotherapy enhanced anti-angiogenic effects, leading a stronger tumor hypoxic environment. • Strong intra tumoral hypoxia increased tumor cell apoptosis and reduced tumor cells proliferation., Objective Although sorafenib, a molecular targeted agent, has survival benefits for advanced hepatocellular carcinoma (HCC) patients, its disease control rate remains limited. To explore the potential for augmenting its antitumor effect, we assessed the preclinical and clinical efficacy and tolerability of S-1 metronomic chemotherapy (MC) plus sorafenib. Methods Antitumor effects and toxicity of this combination were tested with HAK-1B xenograft and spontaneous HCC mouse models, and a prospective pilot study was performed to compare therapeutic effects and safety between sorafenib plus MC S-1 for 12 advanced HCC cases and the historical control of 363 sorafenib-treated advanced HCC patients at our hospital from July 2011 to June 2015. Results In mice, the combination chemotherapy enhanced anti-angiogenic effects, resulting in a stronger tumor hypoxic environment and increased tumor cell apoptosis. Clinically, the objective response rate of the combination chemotherapy was higher than that of sorafenib mono therapy (16.7%; 2/12 vs 5.2%; 19/363, p

Published
2021

47. Robust Effect of Hepatic Arterial Infusion Chemotherapy and Radiation Therapy on Hepatocellular Carcinoma Arising from Fontan-associated Liver Disease

Author

Ryoko Kuromatsu, Takuji Torimura, Naoki Kamachi, Naohisa Mizukami, Yoshinao Kinjyo, Masahito Nakano, Shusuke Okamura, Hiroyuki Suzuki, Yusuke Koteda, Takashi Niizeki, Hironori Koga, Kenji Suda, Satoshi Ota, Tomotake Shirono, Hirohisa Yano, Shigeo Shimose, Akira Kajiwara, Hideki Iwamoto, Yu Noda, Makoto Koda, and Jun Akiba

Subjects
Adult, Male, medicine.medical_specialty, Necrosis, Carcinoma, Hepatocellular, medicine.medical_treatment, Autopsy, Fontan Procedure, Gastroenterology, Fontan procedure, Lesion, Liver disease, Postoperative Complications, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, Internal Medicine, medicine, Humans, Infusions, Intra-Arterial, neoplasms, Cisplatin, business.industry, Liver Neoplasms, General Medicine, medicine.disease, digestive system diseases, Radiation therapy, Hepatocellular carcinoma, Fluorouracil, medicine.symptom, business, medicine.drug
Abstract

Fontan-associated liver disease (FALD) caused by long-term systemic venous congestion following the Fontan procedure may eventually lead to hepatocellular carcinoma (HCC). Treatment strategies for HCC due to FALD (FALD-HCC) remain unclear. We herein report a 35-year-old man with FALD-HCC that was well controlled by 3 cycles of continuous infusion of 5-fluorouracil and low-dose cisplatin (low-dose FP therapy) combined with 60 Gy of radiation therapy. However, the patient ultimately died of extrahepatic metastases. A pathological autopsy revealed more than 90% necrosis in the primary HCC lesion. This case suggests that low-dose FP therapy might be effective in FALD-HCC.

Published
2021

48. Hepatic Arterial Infusion Chemotherapy with Cisplatin Versus Sorafenib for Intrahepatic Advanced Hepatocellular Carcinoma: A Propensity Score-Matched Analysis

Author

Mika Nakazaki, Shigeo Shimose, Kazuta Fukumori, Kotaro Kuwaki, Kota Takaki, Yuki Zaizen, Shusuke Okamura, Ryoko Kuromatsu, Sohei Yoshimura, Tomotake Shirono, Masaru Fukahori, Takuji Torimura, Yoichi Yano, Yu Noda, Naoki Kamachi, Masahito Nakano, Takashi Niizeki, Hideki Iwamoto, Hironori Koga, and Takahiko Sakaue

Subjects
Sorafenib, Cancer Research, medicine.medical_specialty, hepatic arterial infusion chemotherapy, cisplatin, propensity score-matched analysis, Gastroenterology, Article, Internal medicine, Hepatic arterial infusion chemotherapy, medicine, Overall survival, risk factors, neoplasms, RC254-282, oncology_oncogenics, Cisplatin, business.industry, Significant difference, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, medicine.disease, digestive system diseases, Oncology, Hepatocellular carcinoma, Propensity score matching, sorafenib, multikinase inhibitor, business, Median survival, medicine.drug
Abstract

Given that the outcome of hepatic arterial infusion chemotherapy (HAIC) with cisplatin for intrahepatic advanced hepatocellular carcinoma (HCC) is unclear, we aimed to compare prognostic factors for overall survival (OS) following HAIC with cisplatin versus sorafenib for intrahepatic advanced HCC using propensity score-matched analysis. We enrolled 331 patients with intrahepatic advanced HCC who received HAIC with cisplatin (n = 88) or sorafenib (n = 243) between June 2006 and March 2020. No significant difference was observed in OS between HAIC with cisplatin and sorafenib cohorts (median survival time [MST]: 14.0 vs. 12.3 months, p = 0.0721). To reduce confounding effects, 166 patients were selected using propensity score-matched analysis (n = 83 for each treatment). HAIC with cisplatin significantly prolonged OS compared with sorafenib (MST: 15.6 vs. 11.0 months, p = 0.0157). Following stratification according to the Child-Pugh classification, for patients with class A (MST: 24.0 vs. 15.0 months, p = 0.0145), HAIC with cisplatin rather than sorafenib significantly prolonged OS. Our findings suggest that HAIC with cisplatin demonstrates longer prognostic effects than sorafenib in intrahepatic advanced HCC.

Published
2021
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49. Clinical Importance of Regimens in Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma with Macrovascular Invasion

Author

Ryoko Kuromatsu, Yu Noda, Hideki Iwamoto, Shusuke Okamura, Shigeo Shimose, Suzuki Hiroyuki, Naoki Kamachi, Takuji Torimura, Masahito Nakano, Takashi Niizeki, Tomotake Shirono, Miwa Sakai, and Hironori Koga

Subjects
Cancer Research, medicine.medical_specialty, New FP, hepatic arterial infusion chemotherapy, Gastroenterology, Article, Vascular invasion, Internal medicine, Hepatic arterial infusion chemotherapy, medicine, vascular invasion, Objective response, RC254-282, Cisplatin, low dose FP, business.industry, Therapeutic effect, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hepatocellular carcinoma, medicine.disease, digestive system diseases, Regimen, Oncology, Hepatocellular carcinoma, Lipiodol, macrovascular invasion, business, medicine.drug
Abstract

Macroscopic vascular invasion (MVI) is a poor prognostic factor in hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in MVI-HCC. However, it is not clear which regimens are suitable for HAIC. In this study, we aimed to compare the therapeutic effects between New FP (a fine-powder cisplatin suspended with lipiodol plus 5-fluorouracil) and low dose FP (LFP/cisplatin plus 5-fluorouracil) in the treatment of MVI-HCC patients with Child–Pugh class A. New FP is a regimen that consists of a fine-powder cisplatin suspended with lipiodol and 5-fluorouracil. Fifty-one patients were treated with LFP, and 99 patients were New FP. We compared the therapeutic effects of LFP and New FP and assessed factors that associated with the therapeutic effects. The median survival and progression-free survival times of LFP and New FP were 16.1/24.7 and 5.4/8.8 months, respectively (p &lt, 0.05, p &lt, 0.05). The complete response (29％) and objective response rate (76%) of New FP were significantly higher than those of LFP (p &lt, 0.001, p &lt, 0.01). Factors associated with better therapeutic response were better ALBI-grade and New FP treatment choice. New FP is a more powerful regimen than LFP in HAIC for MVI-HCC. New FP represents a recommended HAIC regimen for the treatment of patients with MVI-HCC.

Published
2021

50. Usefulness of a novel transarterial chemoinfusion plus external-beam radiation therapy for advanced hepatocellular carcinoma with tumor thrombi in the inferior vena cava and right atrium: Case study

Author

Ryoko Kuromatsu, Tomotake Shirono, Takuji Torimura, Naoki Kamachi, Hironori Koga, Masahito Nakano, Takashi Niizeki, Hideki Iwamoto, Etsuyo Ogo, Yu Noda, Shusuke Okamura, Hiroaki Nagamatsu, and Shigeo Shimose

Subjects
Sorafenib, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, medicine.medical_treatment, Vena Cava, Inferior, Inferior vena cava, Hepatic arterial infusion, medicine, Humans, Heart Atria, business.industry, Liver Neoplasms, medicine.disease, Pulmonary embolism, Radiation therapy, Oncology, medicine.vein, Response Evaluation Criteria in Solid Tumors, Hepatocellular carcinoma, cardiovascular system, Radiology, Fluorouracil, business, Pulmonary Embolism, Progressive disease, medicine.drug
Abstract

Background Invasion beyond inferior vena cava (IVC) to right atrium (RA) is a rare complication in patients with advanced hepatocellular carcinoma (HCC), and results in fatal oncologic emergencies, including pulmonary embolism and right heart failure. Aim As there is no gold standard treatment for unresectable HCC with tumor thrombi involving IVC and RA, we considered it valuable to assess safety and efficacy of a combination of hepatic arterial infusion chemoembolization (HAIC) therapy and external-beam radiation therapy (EBRT). Methods and results The "New FP" was chosen as the HAIC therapy, in which the enhanced permeation and retention effect was achieved using a cisplatin-Lipiodol suspension combined with continuous infusion of 5-fluorouracil (5-FU). Sixteen patients with HCC with tumor thrombi in IVC, RA, and pulmonary arteries were enrolled. modified response evaluation criteria in solid tumors-based evaluation of response to the combination treatment was as follows: complete response, 6.2% (1 patient); partial response, 81.3% (13 patients); stable disease, 12.5% (2 patients); progressive disease, 0%. The median overall survival time (MST) was 19.0 months. Notably, MST of patients receiving sequential sorafenib monotherapy (39.0 months) was significantly longer than that of the rest (15.3 months). Conclusion The combination of New FP and EBRT is an efficacious treatment option for unresectable HCC involving IVC and RA, complicated with pulmonary embolism. Sequential administration of molecular-targeted drugs may prolong survival in such patients.

Published
2021

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