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203. Regional left ventricular contraction abnormality during early systole in patients with angina pectoris. Assessment with radionuclide ventriculography

Author

Shimizu T, Ikezono T, M Ozaki, Matsuda Y, Yuhji Furutani, Kumada T, T Yamagishi, Reizo Kusukawa, and H Yamaoka

Subjects
Male, medicine.medical_specialty, Systole, Heart Ventricles, Radionuclide ventriculography, Angina Pectoris, Coronary artery disease, Internal medicine, medicine, Humans, Myocardial infarction, cardiovascular diseases, Radionuclide Imaging, End-systolic volume, Aged, Ejection fraction, business.industry, Heart, Stroke Volume, Stroke volume, Middle Aged, medicine.disease, Myocardial Contraction, medicine.anatomical_structure, Ventricle, Cardiology, Female, Cardiology and Cardiovascular Medicine, business, Research Article
Abstract

To determine the presence and prevalence of regional contraction abnormalities in patients with angina pectoris, radionuclide ventriculography gated to an electrocardiogram was carried out in 22 control subjects (group 1) and in 22 patients with angina pectoris (group 2) with isolated stenosis of the left anterior descending coronary artery. No patients had had previous myocardial infarctions. A computer program subdivided the left ventricle into four regions at a geometric centre, and time-activity curves (30-40 ms/frame) of the global, septal, apical, and lateral regions were computed. There was no significant difference in the ejection fraction in the global or in any of the regions between the two groups. End systole in each region occurred close to global end systole in both groups. In the global region the percentage stroke volume ejected during the first third of systole was not significantly less in group 2 than in group 1. Regional analysis of the segments perfused by the stenosed vessel showed that the percentage stroke volume ejected during the first third of systole in group 2 was significantly less in the septal region and in the apical region compared with that in group 1. In contrast, in the normally perfused lateral region, there was no significant difference in the percentage stroke volume at the first third of systole between the two groups. This indicates that early contraction abnormalities are present in the region perfused by the stenosed vessel in patients with angina pectoris without previous myocardial infarction. Thus analysing the regional change in left ventricular volume during ejection in patients with coronary artery disease can show localised areas of contraction abnormalities during early systole that are not apparent when ventricular contraction is assessed as a whole.

Published
1984

221. Observation of Electron Bubbles in para-H<INF>2</INF>−D<INF>2</INF> (HD) Mixtures by High-Resolution ESR Spectroscopy

Author

Kumada, T., Mori, S., Kumagai, J., Aratono, Y., and Miyazaki, T.

Abstract

A sharp singlet signal assigned to electron bubbles was observed in γ-irradiated solid para-H2−D2 (HD) mixtures by use of high-resolution ESR spectroscopy. The signal was not observed in pure para-H2 but in the mixtures. This result indicates that the D2 and HD molecules play an important role in the formation of the electron bubbles in para-H2. The electron bubbles decay with a half-lifetime of about 2 h, and the decay rate constant at 4.2 K is very close to that at 2.2 K. This result shows that the electron bubbles migrate in the p-H2 sample via quantum mechanical tunneling.

Published
1999

222. Stabilization of Hydrogen Radical Anions in Solid Hydrogen

Author

Ichikawa, T., Tachikawa, H., Kumagai, J., Kumada, T., and Miyazaki, T.

Abstract

The electron spin resonance g-factor of H2- in γ-irradiated crystalline H2 was found to be not 2.003 but 2.0023. A novel model has been proposed for explaining the formation and stabilization of H2- in crystalline H2. The model assumes H2- to be located at the center of a cavity that has previously been occupied by a trapped electron. The excess electron of H2- is forced to be attached on one H2 in the cavity due to strong repulsive interactions between the excess electron and H2 molecules surrounding the cavity. A quantum-mechanical calculation shows that an electron trapped in the vacancy of crystalline H2 automatically converts to H2- by drawing one of the surrounding H2 molecules into the center of the vacancy.

Published
1997

225. Identification of lenvatinib prognostic index via recursive partitioning analysis in advanced hepatocellular carcinoma

Author

Marianna Silletta, V. Burgio, Gianluca Masi, A. Takata, M.G. Viola, Mario Domenico Rizzato, Kazuto Tajiri, H. Toyoda, M. Scartozzi, Francesca Salani, Syusuke Okamura, Francesco Giuseppe Foschi, Takashi Kumada, G. Astara, I.G. Rapposelli, Fabio Conti, Emiliano Tamburini, Claudia Campani, Kazuhito Kawata, Fabio Marra, A. Forgione, A. Hiraoka, Giovanni Luca Frassineti, R. Tortora, Takuji Torimura, Shigeo Shimose, Masahito Nakano, Masanori Atsukawa, Stefano Cascinu, Andrea Casadei-Gardini, H. Shibata, G.G. Di Costanzo, Caterina Vivaldi, Antonio Pellino, Claudia Angela Maria Fulgenzi, Toshifumi Tada, Eleonora Lai, Fabio Piscaglia, S. Lonardi, Margherita Rimini, Rapposelli, I. G., Shimose, S., Kumada, T., Okamura, S., Hiraoka, A., Di Costanzo, G. G., Marra, F., Tamburini, E., Forgione, A., Foschi, F. G., Silletta, M., Lonardi, S., Masi, G., Scartozzi, M., Nakano, M., Shibata, H., Kawata, K., Pellino, A., Vivaldi, C., Lai, E., Takata, A., Tajiri, K., Toyoda, H., Tortora, R., Campani, C., Viola, M. G., Piscaglia, F., Conti, F., Fulgenzi, C. A. M., Frassineti, G. L., Rizzato, M. D., Salani, F., Astara, G., Torimura, T., Atsukawa, M., Tada, T., Burgio, V., Rimini, M., Cascinu, S., Casadei-Gardini, A., Rapposelli I.G., Shimose S., Kumada T., Okamura S., Hiraoka A., Di Costanzo G.G., Marra F., Tamburini E., Forgione A., Foschi F.G., Silletta M., Lonardi S., Masi G., Scartozzi M., Nakano M., Shibata H., Kawata K., Pellino A., Vivaldi C., Lai E., Takata A., Tajiri K., Toyoda H., Tortora R., Campani C., Viola M.G., Piscaglia F., Conti F., Fulgenzi C.A.M., Frassineti G.L., Rizzato M.D., Salani F., Astara G., Torimura T., Atsukawa M., Tada T., Burgio V., Rimini M., Cascinu S., and Casadei-Gardini A.

Subjects
Oncology, Cancer Research, medicine.medical_specialty, lenvatinib prognostic index, Carcinoma, Hepatocellular, hepatocellular carcinoma, recursive partitioning analysis, Humans, Phenylurea Compounds, Prognosis, Quinolines, Chemoembolization, Therapeutic, Liver Neoplasms, Recursive partitioning, Prognostic score, chemistry.chemical_compound, Internal medicine, medicine, Original Research, business.industry, Carcinoma, Treatment options, Hepatocellular, medicine.disease, chemistry, Hepatocellular carcinoma, Cohort, Chemoembolization, Therapeutic, Medium Risk, Lenvatinib, business
Abstract

Background After the advent of new treatment options for advanced hepatocellular carcinoma (HCC), the identification of prognostic factors is crucial for the selection of the most appropriate therapy for each patient. Patients and methods With the aim to fill this gap, we applied recursive partitioning analysis (RPA) to a cohort of 404 patients treated with lenvatinib. Results The application of RPA resulted in a classification based on five variables that originated a new prognostic score, the lenvatinib prognostic index (LEP) index, identifying three groups: low risk [patients with prognostic nutritional index (PNI) >43.3 and previous trans-arterial chemoembolization (TACE)]; medium risk [patients with PNI >43.3 but without previous TACE and patients with PNI, Highlights • This study shows a new prognostic index (LEP index) for patients undergoing systemic therapy for hepatocellular carcinoma. • LEP index is an easy-to-use tool, based on clinical and laboratory features, that identifies three risk groups. • LEP index may be used to stratify hepatocellular carcinoma patients in order to select the most appropriate treatment.

Published
2021

229. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib

Author

T. Ishikawa, M. Imai, Noritomo Shimada, Kazuya Kariyama, Shinya Fukunishi, Akemi Tsutsui, Masashi Hirooka, Hideki Iwamoto, Norio Itokawa, Atsushi Hiraoka, Tomomi Okubo, Ei Itobayashi, Kazuhito Kawata, Joji Tani, Yoichi Hiasa, Kouji Joko, N. Sakamoto, F. Marra, Taeang Arai, Koichi Takaguchi, Francesco Giuseppe Foschi, Masanori Atsukawa, Yohei Koizumi, Marianna Silletta, Massimo Iavarone, Takuya Nagano, J. Siebler, Stefano Cascinu, T. Sho, Margherita Rimini, S. Shigeo, T. Aoki, L. Aldrighetti, Toshifumi Tada, G. Suda, A. Jefremow, V. Burgio, Takashi Niizeki, Hidenori Toyoda, Gianluca Masi, Sara Lonardi, Kazuto Tajiri, F. Ratti, Shinichiro Nakamura, W. Kang, A. Cucchetti, Takashi Kumada, Raffaella Tortora, E. Tamburini, Kunihiko Tsuji, Satoshi Yasuda, Fabio Piscaglia, Hiroshi Shibata, Kazuhiro Nouso, Giuseppe Cabibbo, K. Ueshima, Hironori Ochi, Andrea Casadei-Gardini, Hideko Ohama, T. Takaaki, M. Kudo, M.J. Goh, Rimini M., Kudo M., Tada T., Shigeo S., Kang W., Suda G., Jefremow A., Burgio V., Iavarone M., Tortora R., Marra F., Lonardi S., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Foschi F.G., Silletta M., Kumada T., Iwamoto H., Aoki T., Goh M.J., Sakamoto N., Siebler J., Hiraoka A., Niizeki T., Ueshima K., Sho T., Atsukawa M., Hirooka M., Tsuji K., Ishikawa T., Takaguchi K., Kariyama K., Itobayashi E., Tajiri K., Shimada N., Shibata H., Ochi H., Yasuda S., Toyoda H., Fukunishi S., Ohama H., Kawata K., Tani J., Nakamura S., Nouso K., Tsutsui A., Nagano T., Takaaki T., Itokawa N., Okubo T., Arai T., Imai M., Joko K., Koizumi Y., Hiasa Y., Cucchetti A., Ratti F., Aldrighetti L., Cascinu S., Casadei-Gardini A., Rimini, M., Kudo, M., Tada, T., Shigeo, S., Kang, W., Suda, G., Jefremow, A., Burgio, V., Iavarone, M., Tortora, R., Marra, F., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Foschi, F. G., Silletta, M., Kumada, T., Iwamoto, H., Aoki, T., Goh, M. J., Sakamoto, N., Siebler, J., Hiraoka, A., Niizeki, T., Ueshima, K., Sho, T., Atsukawa, M., Hirooka, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Takaaki, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Cucchetti, A., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.

Subjects
Oncology, Phenylurea Compound, atezolizumab, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Quinoline, lenvatinib, bevacizumab, chemistry.chemical_compound, Liver disease, Retrospective Studie, Non-alcoholic Fatty Liver Disease, Internal medicine, Medicine, Humans, nonalcoholic steatohepatitis, Original Research, Retrospective Studies, Univariate analysis, Settore MED/12 - Gastroenterologia, Performance status, business.industry, Phenylurea Compounds, Hazard ratio, Liver Neoplasms, Retrospective cohort study, Hepatitis C, hepatocellular carcinoma, medicine.disease, Prognosis, digestive system diseases, advanced hepatocarcinoma, hepatitis C, immunotherapy, sorafenib, chemistry, Liver Neoplasm, Hepatocellular carcinoma, nonalcoholic steatohepatiti, Quinolines, business, Lenvatinib, Human
Abstract

Background Hepatocellular carcinoma (HCC) treatment remains a big challenge in the field of oncology. The liver disease (viral or not viral) underlying HCC turned out to be crucial in determining the biologic behavior of the tumor, including its response to treatment. The aim of this analysis was to investigate the role of the etiology of the underlying liver disease in survival outcomes. Patients and methods We conducted a multicenter retrospective study on a large cohort of patients treated with lenvatinib as first-line therapy for advanced HCC from both Eastern and Western institutions. Univariate and multivariate analyses were performed. Results Among the 1232 lenvatinib-treated HCC patients, 453 (36.8%) were hepatitis C virus positive, 268 hepatitis B virus positive (21.8%), 236 nonalcoholic steatohepatitis (NASH) correlate (19.2%) and 275 had other etiologies (22.3%). The median progression-free survival (mPFS) was 6.2 months [95% confidence interval (CI) 5.9-6.7 months] and the median overall survival (mOS) was 15.8 months (95% CI 14.9-17.2 months). In the univariate analysis for OS NASH-HCC was associated with longer mOS [22.2 versus 15.1 months; hazard ratio (HR) 0.69; 95% CI 0.56-0.85; P = 0.0006]. In the univariate analysis for PFS NASH-HCC was associated with longer mPFS (7.5 versus 6.5 months; HR 0.84; 95% CI 0.71-0.99; P = 0.0436). The multivariate analysis confirmed NASH-HCC (HR 0.64; 95% CI 0.48-0.86; P = 0.0028) as an independent prognostic factor for OS, along with albumin–bilirubin (ALBI) grade, extrahepatic spread, neutrophil-to-lymphocyte ratio, portal vein thrombosis, Eastern Cooperative Oncology Group (ECOG) performance status and alpha-fetoprotein. An interaction test was performed between sorafenib and lenvatinib cohorts and the results highlighted the positive predictive role of NASH in favor of the lenvatinib arm (P = 0.0047). Conclusion NASH has been identified as an independent prognostic factor in a large cohort of patients with advanced HCC treated with lenvatinib, thereby suggesting the role of the etiology in the selection of patients for tyrosine kinase treatment. If validated, this result could provide new insights useful to improve the management of these patients., Highlights • Evidence supported the idea that etiology could sustain a crucial role in biological behavior. • NASH constitutes one of the more important risk factors for hepatocarcinoma, and its incidence is increasing very fast. • We performed an analysis in patients treated with lenvatinib as the first-line therapy. • NASH was found to be an independent prognostic factor.

Published
2021

230. Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: An inverse probability of treatment weighting analysis

Author

Andrea Casadei‐Gardini, Mario Scartozzi, Toshifumi Tada, Changhoon Yoo, Shigeo Shimose, Gianluca Masi, Sara Lonardi, Luca Giovanni Frassineti, Silvestris Nicola, Fabio Piscaglia, Takashi Kumada, Hyung‐Don Kim, Hironori Koga, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Yeonghak Bang, Masanori Atsukawa, Takuji Torimura, Kunihiko Tsuj, Ei Itobayashi, Hidenori Toyoda, Shinya Fukunishi, Lorenza Rimassa, Margherita Rimini, Stefano Cascinu, Alessandro Cucchetti, Shinichiro Nakamura, Kojiro Michitaka, Norio Itokawa, Korenobu Hayama, Masashi Hirooka, Yohei Koizumi, Yoichi Hiasa, Toru Ishikawa, Michitaka Imai, Koichi Takaguchi, Akemi Tsutsui, Takuya Nagano, Kazuya Kariyama, Kazuhiro Nouso, Kazuto Tajiri, Noritomo Shimada, Hiroshi Shibata, Hironori Ochi, Kouji Joko, Satoshi Yasuda, Hideko Ohama, Kazuhito Kawata, Casadei-Gardini A., Scartozzi M., Tada T., Yoo C., Shimose S., Masi G., Lonardi S., Frassineti L.G., Nicola S., Piscaglia F., Kumada T., Kim H.-D., Koga H., Vivaldi C., Solda C., Hiraoka A., Bang Y., Atsukawa M., Torimura T., Tsuj K., Itobayashi E., Toyoda H., Fukunishi S., Rimassa L., Rimini M., Cascinu S., Cucchetti A., Nakamura S., Michitaka K., Itokawa N., Hayama K., Hirooka M., Koizumi Y., Hiasa Y., Ishikawa T., Imai M., Takaguchi K., Tsutsui A., Nagano T., Kariyama K., Nouso K., Tajiri K., Shimada N., Shibata H., Ochi H., Joko K., Yasuda S., Ohama H., Kawata K., Casadei-Gardini, A., Scartozzi, M., Tada, T., Yoo, C., Shimose, S., Masi, G., Lonardi, S., Frassineti, L. G., Nicola, S., Piscaglia, F., Kumada, T., Kim, H. -D., Koga, H., Vivaldi, C., Solda, C., Hiraoka, A., Bang, Y., Atsukawa, M., Torimura, T., Tsuj, K., Itobayashi, E., Toyoda, H., Fukunishi, S., Rimassa, L., Rimini, M., Cascinu, S., Cucchetti, A., Nakamura, S., Michitaka, K., Itokawa, N., Hayama, K., Hirooka, M., Koizumi, Y., Hiasa, Y., Ishikawa, T., Imai, M., Takaguchi, K., Tsutsui, A., Nagano, T., Kariyama, K., Nouso, K., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Joko, K., Yasuda, S., Ohama, H., and Kawata, K.

Subjects
Sorafenib, Oncology, medicine.medical_specialty, Carcinoma, Hepatocellular, Antineoplastic Agents, lenvatinib, survival, trans-arterial chemoembolization, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, law, Internal medicine, medicine, Clinical endpoint, performance status, Humans, Adverse effect, Probability, Hepatology, Performance status, business.industry, Phenylurea Compounds, Carcinoma, Liver Neoplasms, Hepatocellular, medicine.disease, extrahepatic disease, sorafenib, Quinolines, chemistry, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Cohort, 030211 gastroenterology & hepatology, Lenvatinib, business, medicine.drug, performance statu
Abstract

Purpose Data from common clinical practice were used to generate balanced cohorts of patients receiving either sorafenib or lenvatinib, for unresectable hepatocellular carcinoma, with the final aim to investigate their declared equivalence. Methods Clinical features of lenvatinib and sorafenib 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 and occurrence of adverse events was the secondary. Results The analysis included 385 patients who received lenvatinib, and 555 patients who received sorafenib. In the unadjusted cohort, lenvatinib did not show a survival advantage over sorafenib (HR: 0.85, 95% CI 0.70-1.02). After IPTW adjustment, lenvatinib still not returned a survival advantage over sorafenib (HR: 0.82, 95% CI: 0.62-1.07) even in presence of balanced baseline characteristics. Lenvatinib provided longer survival than sorafenib in patients previously submitted to TACE (HR: 0.69), with PS of 0 (HR: 0.73) or without extrahepatic disease (HR: 0.69). Conclusion Present results confirmed randomized controlled trial in the real-life setting, but also suggests that in earlier stages some benefit can be expected.

Published
2021

231. Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib

Author

Joji Tani, Noritomo Shimada, Taeang Arai, Massimo Iavarone, Valentina Burgio, Koichi Takaguchi, Masanori Atsukawa, Marianna Silletta, Hideko Ohama, Takaaki Tanaka, Hironori Koga, Masashi Hirooka, Emiliano Tamburini, Stefano Cascinu, Ei Itobayashi, Luca Aldrighetti, Gianluca Masi, Takashi Kumada, Kazuhito Kawata, Yoichi Hiasa, Toshifumi Tada, Atsushi Hiraoka, Raffaella Tortora, Shinichiro Nakamura, Kouji Joko, Takuji Torimura, Sara Lonardi, Takuya Nagano, Hironori Ochi, Ilario Giovanni Rapposelli, Francesco Giuseppe Foschi, Akemi Tsutsui, Hideki Iwamoto, Shigeo Shimose, Satoshi Yasuda, Tomomi Okubo, Hiroshi Shibata, Takashi Niizeki, Hidenori Toyoda, Giuseppe Cabibbo, Margherita Rimini, Toru Ishikawa, Shinya Fukunishi, Claudia Campani, Kazuya Kariyama, Kazuto Tajiri, Kunihiko Tsuji, Fabio Piscaglia, Andrea Casadei-Gardini, Kazuhiro Nouso, Yohei Koizumi, Francesca Ratti, Norio Itokawa, Michitaka Imai, Rapposelli I.G., Tada T., Shimose S., Burgio V., Kumada T., Iwamoto H., Hiraoka A., Niizeki T., Atsukawa M., Koga H., Hirooka M., Torimura T., Iavarone M., Tortora R., Campani C., Lonardi S., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Giuseppe Foschi F., Silletta M., Tsuji K., Ishikawa T., Takaguchi K., Kariyama K., Itobayashi E., Tajiri K., Shimada N., Shibata H., Ochi H., Yasuda S., Toyoda H., Fukunishi S., Ohama H., Kawata K., Tani J., Nakamura S., Nouso K., Tsutsui A., Nagano T., Tanaka T., Itokawa N., Okubo T., Arai T., Imai M., Joko K., Koizumi Y., Hiasa Y., Rimini M., Ratti F., Aldrighetti L., Cascinu S., Casadei-Gardini A., Rapposelli, I. G., Tada, T., Shimose, S., Burgio, V., Kumada, T., Iwamoto, H., Hiraoka, A., Niizeki, T., Atsukawa, M., Koga, H., Hirooka, M., Torimura, T., Iavarone, M., Tortora, R., Campani, C., Lonardi, S., Tamburini, E., Piscaglia, F., Masi, G., Cabibbo, G., Giuseppe Foschi, F., Silletta, M., Tsuji, K., Ishikawa, T., Takaguchi, K., Kariyama, K., Itobayashi, E., Tajiri, K., Shimada, N., Shibata, H., Ochi, H., Yasuda, S., Toyoda, H., Fukunishi, S., Ohama, H., Kawata, K., Tani, J., Nakamura, S., Nouso, K., Tsutsui, A., Nagano, T., Tanaka, T., Itokawa, N., Okubo, T., Arai, T., Imai, M., Joko, K., Koizumi, Y., Hiasa, Y., Rimini, M., Ratti, F., Aldrighetti, L., Cascinu, S., and Casadei-Gardini, A.

Subjects
Phenylurea Compound, medicine.medical_specialty, Carcinoma, Hepatocellular, Multivariate analysis, predictive factors, adverse event, lenvatinib, Gastroenterology, predictive factor, chemistry.chemical_compound, Quality of life, Internal medicine, medicine, Humans, Adverse effect, Retrospective Studies, adverse events, hepatocellular carcinoma, Settore MED/12 - Gastroenterologia, Hepatology, business.industry, Phenylurea Compounds, Liver Neoplasms, Hazard ratio, medicine.disease, Confidence interval, Discontinuation, chemistry, Liver Neoplasm, Hepatocellular carcinoma, Quality of Life, Quinolines, Lenvatinib, business
Abstract

Background and Aim: Lenvatinib is a standard of care option in first-line therapy of advanced hepatocellular carcinoma (HCC). In the present study, we aim to identify, in patients with HCC treated with lenvatinib, a possible association between occurrence and grading of adverse events (AEs) and outcome. Methods: We performed a retrospective analysis of 606 Japanese and Italian patients treated with lenvatinib in first-line setting and investigated the possible correlation between the onset of AEs, toxicity grade (G) and outcome measures such as overall survival (OS) and progression-free survival (PFS). Results: The appearance of arterial hypertension G≥2 independently predicted prolonged OS [hazard ratio (HR) 0.66, 95% confidence interval (CI) 0.46–0.93, P=.0188], whereas decreased appetite G≥2 independently predicted decreased OS (HR 1.70, 95% CI 1.25–2.32, P=.0007) by multivariate analysis. Appearance of hand-foot skin reaction independently predicted prolonged PFS (HR 0.72, 95% CI 0.56–0.93, P=.0149), whereas decreased appetite G≥2 predicted decreased PFS (HR 1.36, 95% CI 1.04–1.77, P=.0277). Conclusions: Our main findings are that the occurrence of arterial hypertension G≥2 is a predictor of longer survival, whereas decreased appetite G≥2 predicts for a poor prognosis. A careful management of AEs under lenvatinib treatment for HCC is required, to improve patients’ quality of life, minimize the need for treatment discontinuation and achieve optimal outcome.

Published
2021

235. Pressure effect to chemical reaction, hydrogen isotope recombination reactions in liquid helium at cryogenic temperature — Part II.

Author

Iguchi, K., Aratono, Y., Kumada, T., and Okuno, K.

Subjects
*CHEMICAL reactions, *LIQUID helium, *RADIOCHEMICAL analysis, *SUPERFLUIDITY, *TRITIUM
Abstract

Behavior of the hydrogen isotope in recombination reactions, H+H→H2 H+T→HT and T+T→T2 under pressurized conditions at 1.6 K were investigated using liquid helium as cryogenic reaction media by radiochemical methods. Pressure effects were observed in changes of isotope ratio HT/T2. It became clearer that the balance of changes in bubble energy effective mass associated with energy and chemical potential contributed to the recombination reactions through bubble states. It was suggested that bubble radius was decreased significantly at higher pressure. [ABSTRACT FROM AUTHOR]

Published
2009
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236. Pressure effect in hydrogen isotope recombination reactions in liquid helium at cryogenic temperature.

Author

Iguchi, K., Aratono, Y., Kumada, T., and Okuno, K.

Subjects
*HYDROGEN isotopes, *LIQUID helium, *LOW temperature engineering, *CHEMICAL reactions, *CHEMICAL processes
Abstract

The behavior of recombinations of H+H→H2, H+T→HT and T+T→T2 in liquid helium at cryogenic temperature of 1.6 K was investigated under pressurized condition using radiochemical methods. It was found that the isotope ratios of H2, HT and T2 were changed with the pressure. The changes will contribute to the bubble formation, chemical potential and the effective masses of H and T. This work is a preliminary information to carry out chemical reactions in liquid helium. [ABSTRACT FROM AUTHOR]

Published
2008
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238. Measurement of thermal conductivity of buffer materials and evaluation of existing correlations predicting it

Author

Ould-Lahoucine, C., Sakashita, H., and Kumada, T.

Subjects
*BENTONITE, *SILICA sand, *SEMICONDUCTORS
Abstract

The paper concerns the measurement of thermal conductivity of buffer materials and the evaluation of existing correlations predicting their thermal conductivities. A thermistor probe method developed by the authors was used to measure the thermal conductivity of bentonite and mixtures of bentonite and silica-sand with different densities, water contents, and sand volume. The present and existing thermal conductivity data were compared with various existing correlations. As a result, it is found that the correlation proposed by Sakashita and Kumada provides the most accurate predictions for the thermal conductivity of bentonite. For the bentonite silica-sand mixtures, the correlation of Bruggeman predicts the thermal conductivity with sufficient accuracy. The correlation of Fricke is also a good correlation to predict the thermal conductivity of mixtures of bentonite and silica-sand, provided the real shape of sand particles is simulated as a spheroid. [Copyright &y& Elsevier]

Published
2002
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239. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis

Author

M. Rimini, L. Rimassa, K. Ueshima, V. Burgio, S. Shigeo, T. Tada, G. Suda, C. Yoo, J. Cheon, D.J. Pinato, S. Lonardi, M. Scartozzi, M. Iavarone, G.G. Di Costanzo, F. Marra, C. Soldà, E. Tamburini, F. Piscaglia, G. Masi, G. Cabibbo, F.G. Foschi, M. Silletta, T. Pressiani, N. Nishida, H. Iwamoto, N. Sakamoto, B.-Y. Ryoo, H.J. Chon, F. Claudia, T. Niizeki, T. Sho, B. Kang, A. D’Alessio, T. Kumada, A. Hiraoka, M. Hirooka, K. Kariyama, J. Tani, M. Atsukawa, K. Takaguchi, E. Itobayashi, S. Fukunishi, K. Tsuji, T. Ishikawa, K. Tajiri, H. Ochi, S. Yasuda, H. Toyoda, C. Ogawa, T. Nishimur, T. Hatanaka, S. Kakizaki, N. Shimada, K. Kawata, T. Tanaka, H. Ohama, K. Nouso, A. Morishita, A. Tsutsui, T. Nagano, N. Itokawa, T. Okubo, T. Arai, M. Imai, A. Naganuma, Y. Koizumi, S. Nakamura, K. Joko, H. Iijima, Y. Hiasa, F. Pedica, F. De Cobelli, F. Ratti, L. Aldrighetti, M. Kudo, S. Cascinu, A. Casadei-Gardini, M Rimini , L Rimassa, K Ueshima, V Burgio, S Shigeo, T Tada, G Suda, C Yoo, J Cheon, D J Pinato, S Lonardi, M Scartozzi, M Iavarone, G G Di Costanzo, F Marra, C Soldà, E Tamburini, F Piscaglia, G Masi, G Cabibbo, F G Foschi, M Silletta, T Pressiani, N Nishida, H Iwamoto, N Sakamoto, B-Y Ryoo, H J Chon, F Claudia, T Niizeki, T Sho, B Kang, A D'Alessio, T Kumada, A Hiraoka, M Hirooka, K Kariyama, J Tani, M Atsukawa, K Takaguchi, E Itobayashi, S Fukunishi, K Tsuji, T Ishikawa, K Tajiri, H Ochi, S Yasuda, H Toyoda, C Ogawa, T Nishimur, T Hatanaka, S Kakizaki, N Shimada, K Kawata , T Tanaka, H Ohama, K Nouso, A Morishita, A Tsutsui, T Nagano, N Itokawa, T Okubo, T Arai, M Imai, A Naganuma, Y Koizumi, S Nakamura, K Joko, H Iijima, Y Hiasa, F Pedica, F De Cobelli, F Ratti, L Aldrighetti, M Kudo, S Cascinu, A Casadei-Gardini, Rimini M., Rimassa L., Ueshima K., Burgio V., Shigeo S., Tada T., Suda G., Yoo C., Cheon J., Pinato D.J., Lonardi S., Scartozzi M., Iavarone M., Di Costanzo G.G., Marra F., Solda C., Tamburini E., Piscaglia F., Masi G., Cabibbo G., Foschi F.G., Silletta M., Pressiani T., Nishida N., Iwamoto H., Sakamoto N., Ryoo B.-Y., Chon H.J., Claudia F., Niizeki T., Sho T., Kang B., D'Alessio A., Kumada T., Hiraoka A., Hirooka M., Kariyama K., Tani J., Atsukawa M., Takaguchi K., Itobayashi E., Fukunishi S., Tsuji K., Ishikawa T., Tajiri K., Ochi H., Yasuda S., Toyoda H., Ogawa C., Nishimur T., Hatanaka T., Kakizaki S., Shimada N., Kawata K., Tanaka T., Ohama H., Nouso K., Morishita A., Tsutsui A., Nagano T., Itokawa N., Okubo T., Arai T., Imai M., Naganuma A., Koizumi Y., Nakamura S., Joko K., Iijima H., Hiasa Y., Pedica F., De Cobelli F., Ratti F., Alrighetti L., Kudo M., Cascinu S., and Casadei-Gardini A.

Subjects
atezolizumab, Cancer Research, Settore MED/12 - Gastroenterologia, Oncology, sorafenib, NAFLD, NASH, advanced HCC, advanced HCC, NASH, NAFLD, lenvatinib, sorafenib, atezolizumab, bevacizumab, lenvatinib, bevacizumab
Abstract

Background: A growing body of evidence suggests that non-viral hepatocellular carcinoma (HCC) might benefit less from immunotherapy. Materials and methods: We carried out a retrospective analysis of prospectively collected data from consecutive patients with non-viral advanced HCC, treated with atezolizumab plus bevacizumab, lenvatinib, or sorafenib, in 36 centers in 4 countries (Italy, Japan, Republic of Korea, and UK). The primary endpoint was overall survival (OS) with atezolizumab plus bevacizumab versus lenvatinib. Secondary endpoints were progression-free survival (PFS) with atezolizumab plus bevacizumab versus lenvatinib, and OS and PFS with atezolizumab plus bevacizumab versus sorafenib. For the primary and secondary endpoints, we carried out the analysis on the whole population first, and then we divided the cohort into two groups: non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) population and non-NAFLD/NASH population. Results: One hundred and ninety patients received atezolizumab plus bevacizumab, 569 patients received lenvatinib, and 210 patients received sorafenib. In the whole population, multivariate analysis showed that treatment with lenvatinib was associated with a longer OS [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.44-0.95; P = 0.0268] and PFS (HR 0.67; 95% CI 0.51-0.86; P = 0.002) compared to atezolizumab plus bevacizumab. In the NAFLD/NASH population, multivariate analysis confirmed that lenvatinib treatment was associated with a longer OS (HR 0.46; 95% CI 0.26-0.84; P = 0.0110) and PFS (HR 0.55; 95% CI 0.38-0.82; P = 0.031) compared to atezolizumab plus bevacizumab. In the subgroup of non-NAFLD/NASH patients, no difference in OS or PFS was observed between patients treated with lenvatinib and those treated with atezolizumab plus bevacizumab. All these results were confirmed following propensity score matching analysis. By comparing patients receiving atezolizumab plus bevacizumab versus sorafenib, no statistically significant difference in survival was observed. Conclusions: The present analysis conducted on a large number of advanced non-viral HCC patients showed for the first time that treatment with lenvatinib is associated with a significant survival benefit compared to atezolizumab plus bevacizumab, in particular in patients with NAFLD/NASH-related HCC.

Published
2022

240. Differences in background characteristics of patients with chronic hepatitis C who achieved sustained virologic response with interferon-free versus interferon-based therapy and the risk of developing hepatocellular carcinoma after eradication of hepatitis C virus in Japan

Author

Toyoda, H., Tada, T., Takaguchi, K., Senoh, T., Shimada, N., Hiraoka, A., Michitaka, K., Ishikawa, T., and Kumada, T.

Subjects
*HEPATITIS C treatment, *CANCER risk factors, *LIVER cancer, *THERAPEUTIC use of interferons, *IMMUNE response
Abstract

We compared the background characteristics of patients with chronic hepatitis C who achieved eradication of hepatitis C virus ( HCV), that is sustained virologic response ( SVR), with interferon ( IFN)-based versus IFN-free antiviral therapy in Japan. In addition, we used a previously reported risk assessment model to compare the incidence of hepatocellular carcinoma ( HCC) after SVR by treatment type. Pretreatment characteristics of 1533 patients who achieved SVR with IFN-based therapy and 1086 patients with IFN-free therapy from five institutions across Japan were compared. The risk of HCC after SVR was assessed based on pretreatment characteristics, and the incidence of HCC after SVR was estimated in both groups. Age and serum alpha-fetoprotein levels were higher, platelet count was lower, and liver fibrosis was more advanced in patients who achieved SVR with IFN-free therapy compared with IFN-based therapy. The incidence of HCC after SVR in the IFN-free group was estimated to be more than twofold higher than in the IFN-based therapy group (7.29% vs. 3.09%, and 6.23% vs. 3.01% when excluding patients who have underwent curative treatment for HCC). There are large differences in pretreatment characteristics between patients who achieved SVR with IFN-based and IFN-free therapies in Japan, which are associated with differential risk of HCC after SVR. These differences can influence the incidence of HCC after SVR and should be taken into consideration when comparing IFN-based and IFN-free therapies in terms of hepatocarcinogenesis suppression with HCV eradication. [ABSTRACT FROM AUTHOR]

Published
2017
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241. Is Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma Superior Even to Lenvatinib? A Matching-Adjusted Indirect Comparison

Author

Takashi Kumada, Stefano Cascinu, Andrea Casadei-Gardini, Alessandro Cucchetti, Takashi Niizeki, Shigeo Shimose, Toshifumi Tada, Casadei-Gardini, A., Tada, T., Shimose, S., Kumada, T., Niizeki, T., Cascinu, S., and Cucchetti, A.

Subjects
0301 basic medicine, Oncology, Sorafenib, Male, Cancer Research, medicine.medical_specialty, Carcinoma, Hepatocellular, Bevacizumab, Antibodies, Monoclonal, Humanized, law.invention, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Randomized controlled trial, Atezolizumab, law, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Pharmacology (medical), business.industry, Phenylurea Compounds, Hazard ratio, Liver Neoplasms, Survival Analysis, Confidence interval, 030104 developmental biology, chemistry, 030220 oncology & carcinogenesis, Number needed to treat, Quinolines, Female, Lenvatinib, business, medicine.drug
Abstract

Background: Atezolizumab plus bevacizumab showed superior progression-free and overall survival compared to sorafenib in the IMbrave150 trial. It would therefore be useful to compare the efficacy of lenvatinib and that of atezolizumab plus bevacizumab to determine if a benefit of one therapy against the other exists. Objective: The aim of the present report was to apply a matching-adjusted indirect comparison (MAIC) to individual participant data (IPD) from patients treated with lenvatinib outside of randomized trials, to aggregate results derived from the IMbrave150 trial. Patients and methods: Data from 455 patients who received lenvatinib as first-line systemic therapy for unresectable HCC represented the present IPD. Data inclusion were adapted to those reported in the IMbrave150 trial. Results: Overall survival on atezolizumab plus bevacizumab proved to be superior to lenvatinib (log-rank: 0.001) with a hazard ratio of 0.59 (95% confidence interval 0.46–0.75). The number needed to treat ranged between seven in the first 12 months and five at the 15th month. Conclusions: The present MAIC highlights that the combination of atezolizumab plus bevacizumab is superior to lenvatinib. However, updated data or sub-analyses of the IMbrave150 trial would provide more robust estimates for such a treatment comparison.

Published
2021

242. Biomarker-based prognosis in hepatocellular carcinoma: validation and extension of the BALAD model.

Author

Fox, R, Berhane, S, Teng, M, Cox, T, Tada, T, Toyoda, H, Kumada, T, Kagebayashi, C, Satomura, S, and Johnson, P J

Subjects
*BIOMARKERS, *LIVER cancer, *POLYNOMIALS, *REGRESSION analysis, *HAZARD function (Statistics), *PROGNOSIS
Abstract

Background:The Japanese 'BALAD' model offers the first objective, biomarker-based, tool for assessment of prognosis in hepatocellular carcinoma, but relies on dichotomisation of the constituent data, has not been externally validated, and cannot be applied to the individual patients.Methods:In this Japanese/UK collaboration, we replicated the original BALAD model on a UK cohort and then built a new model, BALAD-2, on the original raw Japanese data using variables in their continuous form. Regression analyses using flexible parametric models with fractional polynomials enabled fitting of appropriate baseline hazard functions and functional form of covariates. The resulting models were validated in the respective cohorts to measure the predictive performance.Results:The key prognostic features were confirmed to be Bilirubin and Albumin together with the serological cancer biomarkers, AFP-L3, AFP, and DCP. With appropriate recalibration, the model offered clinically relevant discrimination of prognosis in both the Japanese and UK data sets and accurately predicted patient-level survival.Conclusions:The original BALAD model has been validated in an international setting. The refined BALAD-2 model permits estimation of patient-level survival in UK and Japanese cohorts. [ABSTRACT FROM AUTHOR]

Published
2014
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245. A Phase II Multi-Center Study of Triple Therapy with Paclitaxel, S-1 and Cisplatin in Patients with Advanced Gastric Cancer.

Author

Iwase, H., Shimada, M., Tsuzuki, T., Ina, K., Sugihara, M., Haruta, J., Shinoda, M., Kumada, T., and Goto, H.

Subjects
*PACLITAXEL, *ALKALOIDS, *ANTINEOPLASTIC agents, *METASTASIS, *CISPLATIN, *GASTROINTESTINAL diseases
Abstract

Objectives: To carry out a phase II multi-center study on the efficacy and safety of triple combination therapy with paclitaxel, S-1, and cisplatin in patients with unresectable/metastatic gastric cancer. Methods: A total of 63 patients from 8 institutions were included in this study. Paclitaxel (160 mg/m2) was administered by infusion for 3 h on the first day. S-1 (70 mg/m2/day) was administered orally for 14 consecutive days from the first day. Cisplatin (60 mg/m2) was administered intravenously over 24 h on day 14 of every 28-day cycle. Results: All 63 patients were assessed for clinical efficacy and safety. A total of 259 cycles of treatment were administered (median 4, range 1-10). Grade 3-4 toxicities included neutropenia in 30.2%, thrombocytopenia in 12.7%, and anemia in 11.1%. There was no grade 3-4 non-hematological toxicity or treatment-related death. Complete response was observed in 6 patients and partial response in 34 patients. The overall response rate was 63.5%. The median progression-free survival and response duration were 8.0 and 8.8 months, respectively, and median survival time was 15 months. Conclusions: Triple combination therapy with paclitaxel, S-1, and cisplatin showed promising safety and efficacy profiles with the potential to become a standard regimen for unresectable/metastatic gastric cancer. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2011
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246. Mutations in the core and NS5A region of hepatitis C virus genotype 1b and correlation with response to pegylated-interferon-alpha 2b and ribavirin combination therapy.

Author

Hayashi, K., Katano, Y., Ishigami, M., Itoh, A., Hirooka, Y., Nakano, I., Urano, F., Yoshioka, K., Toyoda, H., Kumada, T., and Goto, H.

Subjects
*HEPATITIS C virus, *VIRAL genetics, *INTERFERONS, *RIBAVIRIN, *COMBINATION drug therapy, *AMINO acids, *MULTIVARIATE analysis, *STATISTICAL correlation
Abstract

Mutations in two regions of hepatitis C virus (HCV) have been implicated in influencing response to interferon (IFN) therapy. Substitutions in the NS5A region of HCV have been associated with response to IFN therapy, and this region has been known as the IFN sensitivity-determining region (ISDR). The mutations in the core region of HCV have also been reported to predict IFN response. The aim of this study was to investigate whether amino acid substitutions in the core region and ISDR among patients with HCV genotype 1b affect the response to IFN therapy. A total of 213 patients who completed IFN treatment were randomly selected. All patients received pegylated-IFN-alpha 2b once each week, plus oral ribavirin daily for 48 weeks. Of the 213 patients, 117 (54.9%) showed early virologic response (EVR), with HCV-negativity, at 12 weeks. Factors related to EVR on multivariate analysis were non-Gln70 and Leu91 in the core region, and ISDR mutant-type. One hundred and two (47.9%) showed a sustained virologic response (SVR). SVR occurred more frequently in patients without Gln70 (55.4%) than in those with Gln70 (21.3%) ( P < 0.0001). SVR was achieved in 43.6% of patients with wild-type ISDR and 62.5% of patients with mutant-type ( P = 0.0227). Of the 34 patients who simultaneously had non-Gln70 and mutant-type ISDR, 26 (76.5%) achieved SVR. Factors related to SVR on multivariate analysis were non-Gln70 and ISDR mutant-type. In conclusion, amino acid substitutions in the core region and ISDR were useful for predicting the response to IFN in patients with HCV genotype 1b. [ABSTRACT FROM AUTHOR]

Published
2011
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247. The Influence of Node-Fibril Morphology on Healing of High-Porosity Expanded Polytetrafluoroethylene Grafts.

Author

Miura, H., Yasuda, K., Shimada, T., Hazama, K., Katoh, H., Watanabe, S., Okuda, Y., Kumada, T., and Nishibe, T.

Subjects
*POLYTEF, *VASCULAR grafts, *CAROTID artery surgery, *SCANNING electron microscopy, *CELL proliferation, *POROSITY
Abstract

Purpose: To manufacture high-porosity expanded polytetrafluoroethylene (ePTFE) vascular grafts with the same internodal distance but different node-fibril morphology, and to evaluate their biologic behaviors in a canine carotid artery implantation model. Materials and Methods: Several types of high-porosity ePTFE vascular grafts with the same inside diameter (4 mm) and wall thickness (650 μm) were manufactured under different heating, stretching conditions. The luminal surface and cross section of the grafts were photographed by scanning electron microscopy and the node-fibril structure was examined. Two typical types of high-porosity ePTFE vascular grafts were then selected and proceeded to an animal study. The test grafts were explanted after an interval of 12 weeks and subjected to histomorphometric analyses. Results: The following two types of high-porosity ePTFE vascular grafts were selected; one had a through-pore structure extending from the outer to the inner surface and the other had a random-node architecture with tortuous path channels extending from the outer to the inner surface. The histomorphometric analyses of thrombus-free surface, thickness of pseudointima, cellular ingrowth, capillary ingrowth, and cellular proliferation revealed no significant differences between the grafts. Conclusion: In high-porosity ePTFE vascular grafts, graft healing enhanced by transmural tissue ingrowth may be not largely dependent on node-fibril morphology. This knowledge will be helpful to design a new type of high-porosity ePTFE vascular grafts available for clinical use.Copyright © 2002 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Published
2002
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