367 results on '"Nouso K"'
Search Results
2. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
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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.
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- 2021
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3. Novel REIC/Dkk-3-encoding adenoviral vector as a promising therapeutic agent for pancreatic cancer
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Sawahara, H, Shiraha, H, Uchida, D, Kato, H, Nagahara, T, Iwamuro, M, Kataoka, J, Horiguchi, S, Watanabe, M, Sakaguchi, M, Takaki, A, Nouso, K, Nasu, Y, Kumon, H, and Okada, H
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- 2016
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4. 937P Multicenter phase II trial of lenvatinib plus hepatic intra-arterial infusion chemotherapy with cisplatin for advanced hepatocellular carcinoma: LEOPARD
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Ikeda, M., primary, Yamashita, T., additional, Ogasawara, S., additional, Kudo, M., additional, Inaba, Y., additional, Morimoto, M., additional, Tsuchiya, K., additional, Shimizu, S., additional, Kojima, Y., additional, Hiraoka, A., additional, Nouso, K., additional, Aikata, H., additional, Numata, K., additional, Sato, T., additional, Okusaka, T., additional, and Furuse, J., additional
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- 2021
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5. Effect of oral zinc in hepatic encephalopathy remains unclear: authorsʼ reply
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Takuma, Y., Nouso, K., Makino, Y., Hayashi, M., and Takahashi, H.
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- 2010
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6. Clinical trial: oral zinc in hepatic encephalopathy
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Takuma, Y., Nouso, K., Makino, Y., Hayashi, M., and Takahashi, H.
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- 2010
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7. Preoperative estimation of remnant hepatic function using fusion images obtained by 99mTc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography
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Yumoto, Y., Yagi, T., Sato, S., Nouso, K., Kobayashi, Y., Ohmoto, M., Yumoto, E., Nagaya, I., and Nakatsukasa, H.
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- 2010
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8. Evolution of prognostic factors in hepatocellular carcinoma in Japan
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NOUSO, K., KOBAYASHI, Y., NAKAMURA, S., KOBAYASHI, S., TOSHIMORI, J., KUWAKI, K., HAGIHARA, H., ONISHI, H., MIYAKE, Y., IKEDA, F., SHIRAHA, H., TAKAKI, A., IWASAKI, Y., KOBASHI, H., and YAMAMOTO, K.
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- 2010
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9. Serum interferon-gamma-inducing factor/IL-18 levels in primary biliary cirrhosis
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Yamano, T., Higashi, T., Nouso, K., Nakatsukasa, H., Kariyama, K., Yumoto, E., Kobayashi, Y., Yamamoto, K., Iwagaki, H., Yagi, T., Tanimoto, T., Kurimoto, M., Tanaka, N., and Tsuji, T.
- Published
- 2000
10. Estimation of remnant liver function before hepatectomy using 99mTc-GSA and prognosis of patients after hepatectomy.
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Yumoto, Y, Mitani, K, Higashi, T, Yagi, T, Hiraki, Y, Kurokawa, T, Hanafusa, T, Nakatsukasa, H, Nouso, K, Kobayashi, K, Kariyama, K, Ohmoto, M, and Tsuji, T
- Published
- 2000
11. Safety and Efficacy of Radiofrequency Ablation with Artificial Ascites for Hepatocellular Carcinoma
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Nishimura, M., Nouso, K., Kazuya Kariyama, Wakuta, A., Kishida, M., Wada, N., Higashr, T., and Yamamoto, K.
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Adult ,Male ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Ascites ,hepatocellular carcinoma ,Middle Aged ,Catheter Ablation ,Humans ,Female ,radiofrequency ablation ,Neoplasm Recurrence, Local ,artificial ascites ,Aged - Abstract
The artificial ascites technique is often used during radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) treatment because it prevents visceral damage and improves visualization by minimizing interference of the lungs and mesentery. This study determined the efficacy and safety of RFA using the artificial ascites technique in HCC patients. We examined 188 HCC patients who were treated by RFA and fulfilled the Milan criteria. Treatment outcomes (complete ablation rate, local recurrence rate, complication rate, liver function including total bilirubin level, alanine aminotransferase level, albumin level, and prothrombin time) were compared among patients divided into 3 groups based on the volume of artificial ascites injected:Group I (n = 86), no artificial ascites injected;Group II (n = 35),1,000 ml artificial ascites injected;and Group III (n = 67),1,000 ml artificial ascites injected. No significant difference was observed in complete ablation or local recurrence rates among the 3 groups, or in the extent of liver function damage after RFA. Artificial ascites disappeared within 7 days; additional diuretics were needed only in 5 (all from Group III) of 102 patients. No serious complications such as intestinal perforation or intraperitoneal bleeding were observed. Thus, we found that artificial ascites injection during RFA is effective and safe, and can be used to prevent major procedural complications.
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- 2012
12. Liver Sarcoidosis with Unique MRI Images Using Gadolinium Ethoxybenzyl Diethylenetriamine Pentaacetic Acid
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Wada, N., Nouso, K., Kazuya Kariyama, Wakuta, A., Kishida, M., Nishimura, M., and Higashi, T.
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Gadolinium DTPA ,Sarcoidosis ,Liver Diseases ,Ursodeoxycholic Acid ,liver sarcoidosis ,Humans ,Female ,gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB) ,Middle Aged ,Tomography, X-Ray Computed ,Magnetic Resonance Imaging ,ursodeoxycholic acid (UDCA) - Abstract
Sarcoidosis is a systemic disease characterized by the formation of non-caseating granulomas in multiple organs. In the diagnosis of sarcoidosis, imaging modalities such as ultrasonography, computed tomography (CT) and magnetic resonance imaging (MRI) are useful;however, there are few reports of MRI imaging using gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB) MRI. A 46-year-old Japanese female with suspected pulmonary sarcoidosis was admitted to our hospital because low-density mottles in the liver were observed incidentally by chest CT. The low-density mottles were not enhanced at the arterial phase or portal phase by abdominal CT and MRI, and decreased uptake was observed in the hepatobiliary phase of Gd-EOB MRI. No hematological disorder was observed except for a slight increase of biliary enzymes. The lesion was diagnosed as liver sarcoidosis by the liver biopsy. Since the patient refused steroid therapy, we prescribed ursodeoxycholic acid (UDCA). 600mg/day. The serum levels of biliary enzymes were normalized and the abdominal CT findings gradually improved after the initiation of UDCA medication. Gd-EOB MRI showed unique hypointense areas in the liver at the hepatobiliary phase, which might be useful in the diagnosis of liver sarcoidosis.
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- 2015
13. Prognostic model for hepatocellular carcinoma with time-dependent factors
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Kuwaki, K., Nouso, K., Kobayashi, Y., Nakamura, S., Yoichi M. Ito, Iwadou, S., Hagihara, H., Yasunaka, T., Toshimori, J., Miyatake, H., Miyoshi, K., Onishi, H., Miyake, Y., Shoji, B., Takaki, A., Shiraha, H., Iwasaki, Y., Kobashi, H., and Yamamoto, K.
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Adult ,Aged, 80 and over ,Male ,Carcinoma, Hepatocellular ,Time Factors ,Liver Neoplasms ,hepatocellular carcinoma ,Middle Aged ,Prognosis ,Survival Analysis ,Young Adult ,Humans ,Female ,Aged ,Follow-Up Studies ,Proportional Hazards Models - Abstract
The purpose of this study was to build a prognostic model of hepatocellular carcinoma (HCC) using time-dependent covariates to re-evaluate the prognosis at any stage of the disease. The subjects were consecutive HCC patients who were treated at our institute between 1995 and 2007. We constructed time-fixed and time-dependent prognostic models with a training group (n=336) and compared the prognostic abilities between conventional Cancer of the Liver Italian Program (CLIP) scores, Japan Integrated Staging (JIS) scores, an Okuda classification, and our prognostic models in the testing group (n=227) with the c-index. The time-dependent prognostic model consisted of main tumor size, tumor number, portal vein invasion, distant metastasis, alpha-fetoprotein, des-gamma-carboxy prothrombin (DCP), bilirubin, and albumin and the weighted scores were set for each factor depending on the hazard ratio for the prognosis. The prognostic index was determined by summing the scores. The c-index values for the CLIP scores, JIS scores, Okuda classification, and our time-dependent model were 0.741, 0.727, 0.609, and 0.870, respectively. These results indicate that our time-dependent model can estimate the prognosis of HCC more precisely than traditional time-fixed models and can be used to re-predict the prognosis of HCC.
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- 2011
14. Droplet digital PCR measurement of HER2 in patients with gastric cancer
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Kinugasa, H, primary, Nouso, K, additional, Tanaka, T, additional, Miyahara, K, additional, Morimoto, Y, additional, Dohi, C, additional, Matsubara, T, additional, Okada, H, additional, and Yamamoto, K, additional
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- 2015
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15. Cellular distribution of 92-kd type IV collagenase/gelatinase B in human hepatocellular carcinoma
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Ashida, K., Nakatsukasa, H., Higashi, T., Ohguchi, S., Hino, N., Nouso, K., Urabe, Y., Yoshida, K., Kinugasa, N., and Tsuji, T.
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Adult ,Male ,Carcinoma, Hepatocellular ,Liver Neoplasms ,Middle Aged ,Immunohistochemistry ,Liver ,Matrix Metalloproteinase 9 ,Organ Specificity ,Humans ,Female ,Collagenases ,RNA, Messenger ,In Situ Hybridization ,Research Article ,Aged - Abstract
To examine the possible involvement of gelatinase B in human hepatocellular carcinoma (HCC), cellular localization of transcripts and protein of gelatinase B were studied by using in situ hybridization and immunohistochemistry. Transcripts for gelatinase B were observed in tumor cells in 22 cases of 27 HCCs and also in dysplastic nodules. However, there was no significant difference in the expression among histological grades of HCC. The expression was mostly homogeneous, but the intensity varied with the nodules. Of 13 cases with capsular invasion, 12 expressed gelatinase B, whereas 10 of 14 without capsular invasion did (P < 0.05). Gelatinase B transcripts were commonly observed in the sinusoidal cells of the hepatic lobules, in mesenchymal cells both in fibrous capsules and around the necrosis, and also in some undefined cells of the portal tracts of noncancerous liver. Localization of gelatinase B protein was mostly similar to but sometimes different from that of the transcripts in cancer nodules. In conclusion, the expression of gelatinase B appears to be an important characteristic of malignant transformation of hepatocytes. The findings suggest that gelatinase B synthesized by cancer cells plays an important role in the growth and invasion of HCC by degrading surrounding extracellular matrices.
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- 1996
16. 727 LONG-TERM EFFICACY AND IMPACT ON HEPATOCELLULAR CARCINOMA DEVELOPMENT OF NUCLEOSIDE ANALOGUE TREATMENT WITH LAMIVUDINE AND ENTECAVIR FOR CHRONIC HEPATITIS B AND CIRRHOSIS
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Kobashi, H., primary, Miyake, Y., additional, Ikeda, F., additional, Yasunaka, T., additional, Nishino, K., additional, Moriya, A., additional, Kubota, J.-I., additional, Nakamura, S., additional, Takaki, A., additional, Nouso, K., additional, Yamada, G., additional, and Yamamoto, K., additional
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- 2011
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17. Prognostic factors and treatment effects for hepatocellular carcinoma in Child C cirrhosis
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Nouso, K, primary, Ito, Y M, additional, Kuwaki, K, additional, Kobayashi, Y, additional, Nakamura, S, additional, Ohashi, Y, additional, and Yamamoto, K, additional
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- 2008
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18. Expression of telomerase-associated protein 1 and telomerase reverse transcriptase in hepatocellular carcinoma
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Toshikuni, N, primary, Nouso, K, additional, Higashi, T, additional, Nakatsukasa, H, additional, Onishi, T, additional, Kaneyoshi, T, additional, Kobayashi, Y, additional, Kariyama, K, additional, Yamamoto, K, additional, and Tsuji, T, additional
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- 2000
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19. Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma.
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Miyahara, K, Nouso, K, Morimoto, Y, Takeuchi, Y, Hagihara, H, Kuwaki, K, Onishi, H, Ikeda, F, Miyake, Y, Nakamura, S, Shiraha, H, Takaki, A, Honda, M, Kaneko, S, Sato, T, Sato, S, Obi, S, Iwadou, S, Kobayashi, Y, and Takaguchi, K
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VASCULAR endothelial growth factors , *CYTOKINES , *ANGIOPOIETIN-2 , *FOLLISTATIN , *GRANULOCYTE colony stimulating factor receptor , *COHORT analysis - Abstract
Background:We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.Methods:In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).Results:Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21-2.81), and OS (HR, 1.95; 95% CI, 1.21-3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30-3.06) and OS (HR, 1.94; 95% CI, 1.19-3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.Conclusion:High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib. [ABSTRACT FROM AUTHOR]
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- 2013
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20. Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan.
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Nouso, K, Miyahara, K, Uchida, D, Kuwaki, K, Izumi, N, Omata, M, Ichida, T, Kudo, M, Ku, Y, Kokudo, N, Sakamoto, M, Nakashima, O, Takayama, T, Matsui, O, Matsuyama, Y, Yamamoto, K, and Liver Cancer Study Group of Japan
- Abstract
Background: The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear.Methods: The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy.Results: A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41-0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001).Conclusion: For advanced HCC, HAIC is considered to be an effective treatment. [ABSTRACT FROM AUTHOR]- Published
- 2013
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21. Expression of MAGE-1 and -3 genes and gene products in human hepatocellular carcinoma
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Kariyama, K, primary, Higashi, T, additional, Kobayashi, Y, additional, Nouso, K, additional, Nakatsukasa, H, additional, Yamano, T, additional, Ishizaki, M, additional, Kaneyoshi, T, additional, Toshikuni, N, additional, Ohnishi, T, additional, Fujiwara, K, additional, Nakayama, E, additional, Terracciano, L, additional, Spagnoli, G C, additional, and Tsuji, T, additional
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- 1999
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22. Expression of membrane cofactor protein (MCP, CD46) in human liver diseases
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Kinugasa, N, primary, Higashi, T, additional, Nouso, K, additional, Nakatsukasa, H, additional, Kobayashi, Y, additional, Ishizaki, M, additional, Toshikuni, N, additional, Yoshida, K, additional, Uematsu, S, additional, and Tsuji, T, additional
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- 1999
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23. Telomere length in human liver diseases
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URABE, Y, primary, NOUSO, K, additional, HIGASHI, T, additional, NAKATSUKASA, H, additional, HINO, N, additional, ASHIDA, K, additional, KINUGASA, N, additional, YOSHIDA, K, additional, UEMATSU, S, additional, and TSUJI, T, additional
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- 1997
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24. Cellular distribution of transcripts for tissue inhibitor of metalloproteinases 1 and 2 in human hepatocellular carcinomas
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Nakatsukasa, H, primary, Ashida, K, additional, Higashi, T, additional, Ohguchi, S, additional, Tsuboi, S, additional, Hino, N, additional, Nouso, K, additional, Urabe, Y, additional, Kinugasa, N, additional, Yoshida, K, additional, Uematsu, S, additional, Ishizaki, M, additional, Kobayashi, Y, additional, and Tsuji, T, additional
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- 1996
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25. Preoperative estimation of remnant hepatic function using fusion images obtained by 99mTc-labelled galactosyl-human serum albumin liver scintigraphy and computed tomography.
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Yumoto, Y., Yagi, T., Sato, S., Nouso, K., Kobayashi, Y., Ohmoto, M., Yumoto, E., Nagaya, I., and Nakatsukasa, H.
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GLYCOSPHINGOLIPIDS ,LIVER failure ,TUMORS ,LIVER tumors ,LIVER surgery - Abstract
The article focuses on a study which examined the role of hepatic asialoglycoprotein receptor (ASGP-R) analysis in the preoperative estimation of remnant liver function in liver surgery. The study included 101 patients who are undergoing hepatic resection for liver tumors. It concluded that combined receptor concentration and the amount of hepatic receptor in liver remnant can be used to evaluate the risk of postoperative liver failure.
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- 2010
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26. The formation of capsule and septum in human hepatocellular carcinoma.
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Ishizaki, Masahiko, Ashida, Kozo, Higashi, Toshihiro, Nakatsukasa, Harushige, Kaneyoshi, Toshihiko, Fujiwara, Keishi, Nouso, Kazuhiro, Kobayashi, Yoshiyuki, Uemura, Masayuki, Nakamura, Shinichiro, Tsuji, Takao, Ishizaki, M, Ashida, K, Higashi, T, Nakatsukasa, H, Kaneyoshi, T, Fujiwara, K, Nouso, K, Kobayashi, Y, and Uemura, M
- Abstract
The formation of fibrous capsule around the cancer nodule and of the septum in the tumor is frequently observed with the development of hepatocellular carcinoma (HCC). We aimed to clarify how the capsule and septum were formed during the growth of HCC. Liver samples surgically resected from 25 patients with HCC were studied with in situ hybridization for type-I, -III, and -IV procollagen. Type-I and -III procollagen-expressing cells, mostly alpha-smooth muscle actin (SMA)-positive, were increased in the fibrous capsule and in the septum between HCC nodules. These cells were also found at the invasion front of HCC and around the necrotic cancer tissues. Type-IV procollagen gene expression was mainly observed in mesenchymal cells localized in both HCCs and non-cancerous liver. Cancer cells or hepatocytes did not express any of these procollagen genes. The present study reveals that the capsule and septum are mainly formed by alpha-SMA-positive mesenchymal cells at the interface between two different tissues (e.g., cancer nodule vs non-cancerous liver or another cancer nodule). The wound healing occurs even in HCC. The capsule formation may result from interaction between tumor and host liver and interfere the growth and invasion of HCC. [ABSTRACT FROM AUTHOR]
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- 2001
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27. Reduced expression of insulin-like growth factor binding protein-3 and its promoter hypermethylation in human hepatocellular carcinoma
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Hanafusa, T., Yumoto, Y., Nouso, K., Nakatsukasa, H., Onishi, T., Fujikawa, T., Taniyama, M., Nakamura, S., Uemura, M., and Takuma, Y.
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- 2002
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28. Expression of MAGE, GAGE and BAGE genes in human liver diseases: utility as molecular markers for hepatocellular carcinoma
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Kobayashi, Y., Higashi, T., Nouso, K., Nakatsukasa, H., Ishizaki, M., Kaneyoshi, T., Toshikuni, N., Kariyama, K., Nakayama, E., and Tsuji, T.
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- 2000
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29. Recombinant mouse cytochromes P1-450 and P3-450: enzymatic characterization of the hemoprotein expressed in human cells infected with recombinant vaccinia virus
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Nouso, K., Narayana Battula, Thorgeirsson, S. S., Higashi, T., and Tsuji, T.
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Recombination, Genetic ,DNA, Complementary ,Gene Expression ,7-Alkoxycoumarin O-Dealkylase ,cytochrome P-450 ,Recombinant Proteins ,vaccinia virus ,Mice ,Cytochrome P-450 Enzyme System ,kinetics ,Cytochrome P-450 CYP1A1 ,Vaccinia ,Animals ,Humans ,Tissue Distribution ,Oxidoreductases ,HeLa Cells - Abstract
We expressed mouse cytochrome P1-450 and P3-450 using recombinant vaccinia virus gene expression system in HeLa cells that were devoid of significant basal levels of P-450. HeLa cells were infected with the recombinant vaccinia virus containing either mouse cytochrome P1-450 or P3-450 cDNA, and the cell lysates were analyzed for the kinetics of P-450 enzyme activity and protein expression at the same time. 7-Ethoxycoumarin O-deethylase and ethoxyresorufin O-deethylase activities were measured as an expression of the cytochrome P-450 enzyme activities. Both cell lines began to express these enzyme activities as early as 12h after infection. The activities increased linearly up to the 24 h time point, and were kept for 36 h. Western immunoblot analysis showed that these cytochrome P-450 proteins were detected at 16 h and reached maximum quantity at 24 h after infection. These data showed a good correlation between cytochrome P-450 enzyme activity and protein concentration throughout the process of P-450 gene expression by vaccinia virus vector, suggesting a complete formation of cytochrome P-450 holoenzyme from the early stage of the protein expression.
30. Apoptosis and proliferation of human hepatocellular carcinoma
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Hino, N., Higashi, T., Nouso, K., Nakatsukasa, H., and Tsuji, T.
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Cell proliferation -- Physiological aspects ,Cell death -- Physiological aspects ,Liver cancer -- Development and progression ,Health ,Physiological aspects ,Development and progression - Abstract
According to the authors' abstract of an article published in Liver, 'To investigate the contribution of apoptosis, a major mechanism of cell death, in the growth of hepatocellular carcinoma, we [...]
- Published
- 1996
31. Loss of runt-related transcription factor 3 expression leads hepatocellular carcinoma cells to escape apoptosis
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Nakamura Shinichiro, Takaki Akinobu, Hagihara Hiroaki, Toshimori Junichi, Ohnishi Hideki, Kuwaki Kenji, Uemura Masayuki, Takaoka Nobuyuki, Iwamuro Masaya, Horiguchi Shigeru, Matsubara Minoru, Tanaka Shigetomi, Nishina Shin-ichi, Shiraha Hidenori, Nakanishi Yutaka, Kobayashi Yoshiyuki, Nouso Kazuhiro, Yagi Takahito, and Yamamoto Kazuhide
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Runt-related transcription factor 3 (RUNX3) is known as a tumor suppressor gene for gastric cancer and other cancers, this gene may be involved in the development of hepatocellular carcinoma (HCC). Methods RUNX3 expression was analyzed by immunoblot and immunohistochemistry in HCC cells and tissues, respectively. Hep3B cells, lacking endogenous RUNX3, were introduced with RUNX3 constructs. Cell proliferation was measured using the MTT assay and apoptosis was evaluated using DAPI staining. Apoptosis signaling was assessed by immunoblot analysis. Results RUNX3 protein expression was frequently inactivated in the HCC cell lines (91%) and tissues (90%). RUNX3 expression inhibited 90 ± 8% of cell growth at 72 h in serum starved Hep3B cells. Forty-eight hour serum starvation-induced apoptosis and the percentage of apoptotic cells reached 31 ± 4% and 4 ± 1% in RUNX3-expressing Hep3B and control cells, respectively. Apoptotic activity was increased by Bim expression and caspase-3 and caspase-9 activation. Conclusion RUNX3 expression enhanced serum starvation-induced apoptosis in HCC cell lines. RUNX3 is deleted or weakly expressed in HCC, which leads to tumorigenesis by escaping apoptosis.
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- 2011
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32. Twist expression promotes migration and invasion in hepatocellular carcinoma
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Kobayashi Yoshiyuki, Nakamura Shinichiro, Takaki Akinobu, Uemura Masayuki, Nakanishi Yutaka, Nishina Shinichi, Tanaka Shigetomi, Ueda Naoki, Takaoka Nobuyuki, Fujikawa Tatsuya, Shiraha Hidenori, Matsuo Noriyuki, Nouso Kazuhiro, Yagi Takahito, and Yamamoto Kazuhide
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Twist, a transcription factor of the basic helix-loop-helix class, is reported to regulate cancer metastasis. It is known to induce epithelial-mesenchymal transition (EMT). In this study, we evaluated the expression of twist and its effect on cell migration in hepatocellular carcinoma (HCC). Methods We examined twist expression using immunohistochemistry in 20 tissue samples of hepatocellular carcinoma, and assessed twist expression in HCC cell lines by RT-PCR and Western blot analysis. Ectopic twist expression was created by introducing a twist construct in the twist-negative HCC cell lines. Endogenous twist expression was blocked by twist siRNA in the twist-positive HCC cell lines. We studied EMT related markers, E-cadherin, Vimentin, and N-cadherin by Western blot analysis. Cell proliferation was measured by MTT assay, and cell migration was measured by in vitro wound healing assay. We used immunofluorescent vinculin staining to visualize focal adhesion. Results We detected strong and intermediate twist expression in 7 of 20 tumor samples, and no significant twist expression was found in the tumor-free resection margins. In addition, we detected twist expression in HLE, HLF, and SK-Hep1 cells, but not in PLC/RPF/5, HepG2, and Huh7 cells. Ectopic twist-expressing cells demonstrated enhanced cell motility, but twist expression did not affect cell proliferation. Twist expression induced epithelial-mesenchymal transition together with related morphologic changes. Focal adhesion contact was reduced significantly in ectopic twist-expressing cells. Twist-siRNA-treated HLE, HLF, and SK-Hep1 cells demonstrated a reduction in cell migration by 50, 40 and 18%, respectively. Conclusion Twist induces migratory effect on hepatocellular carcinoma by causing epithelial-mesenchymal transition.
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- 2009
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33. Functional promoter upstream p53 regulatory sequence of IGFBP3 that is silenced by tumor specific methylation
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Yumoto Eichiro, Iwasaki Yoshiaki, Nouso Kazuhiro, Shiraha Hidenori, Shinji Toshiyuki, Hanafusa Tadashi, Ono Toshiro, and Koide Norio
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Abstract Background Insulin-like growth factor binding protein (IGFBP)-3 functions as a carrier of insulin-like growth factors (IGFs) in circulation and a mediator of the growth suppression signal in cells. There are two reported p53 regulatory regions in the IGFBP3 gene; one upstream of the promoter and one intronic. We previously reported a hot spot of promoter hypermethylation of IGFBP-3 in human hepatocellular carcinomas and derivative cell lines. As the hot spot locates at the putative upstream p53 consensus sequences, these p53 consensus sequences are really functional is a question to be answered. Methods In this study, we examined the p53 consensus sequences upstream of the IGFBP-3 promoter for the p53 induced expression of IGFBP-3. Deletion, mutagenesis, and methylation constructs of IGFBP-3 promoter were assessed in the human hepatoblastoma cell line HepG2 for promoter activity. Results Deletions and mutations of these sequences completely abolished the expression of IGFBP-3 in the presence of p53 overexpression. In vitro methylation of these p53 consensus sequences also suppressed IGFBP-3 expression. In contrast, the expression of IGFBP-3 was not affected in the absence of p53 overexpression. Further, we observed by electrophoresis mobility shift assay that p53 binding to the promoter region was diminished when methylated. Conclusion From these observations, we conclude that four out of eleven p53 consensus sequences upstream of the IGFBP-3 promoter are essential for the p53 induced expression of IGFBP-3, and hypermethylation of these sequences selectively suppresses p53 induced IGFBP-3 expression in HepG2 cells.
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- 2005
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34. Telomere length in human liver diseases
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Urabe, Y, Nouso, K, Higashi, T, Nakatsukasa, H, Hino, N, Ashida, K, Kinugasa, N, Yoshida, K, Uematsu, S, and Tsuji, T
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- 1997
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35. Effect of 3-methylcholanthrene induction on the distribution and DNA adduction of 2-amino-3-methylimidazo[4,5-ƒ]quinoline (IQ) in F344 rats
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Snyderwine, E.G., Nouso, K., and Schut, H.A.J.
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- 1993
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36. Nonalcoholic steatohepatitis in hepatocarcinoma: new insights about its prognostic role in patients treated with lenvatinib
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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.
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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.
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- 2021
37. Lenvatinib versus sorafenib in first-line treatment of unresectable hepatocellular carcinoma: An inverse probability of treatment weighting analysis
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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.
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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.
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- 2021
38. Adverse events as potential predictive factors of activity in patients with advanced hepatocellular carcinoma treated with lenvatinib
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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.
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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.
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- 2021
39. Effect of 3-methylcholanthrene induction on the distribution and DNA adduction of 2-amino-3-methylimidazo[4,5,-f]quinoline (IQ) in F344 rats
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Snyderwine, E. G., Nouso, K., and Schut, H. A. J.
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- 1993
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40. Atezolizumab plus bevacizumab versus lenvatinib or sorafenib in non-viral unresectable hepatocellular carcinoma: an international propensity score matching analysis
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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.
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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.
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- 2022
41. P-464 The secretion of procathepsin B and changes in its sugar moiety in cultured hepatoma cells
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Liu, L, Higashi, T, Uematsu, S, Yoshida, K, Kinugasa, N, Urabe, Y, Ashida, K, Hino, N, Nouso, K, Nakatsukasa, H, and Tsuji, T
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- 1995
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42. P-447 Localization of 92KD gelatinase (MMP9) gene transcripts in human hepatocellular carcinoma
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Ashida, K, Nakatsukasa, H, Higashi, T, Hino, N, Nouso, K, Urabe, Y, Yoshida, K, Kinugasa, N, Uematsu, S, and Tsuji, T
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- 1995
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43. Factors affecting an increase in spleen volume and association of spleen volume variation with the clinical outcomes of atezolizumab and bevacizumab treatment for hepatocellular carcinoma: A retrospective analysis.
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Hatanaka T, Saito N, Kakizaki S, Hiraoka A, Tada T, Kariyama K, Tani J, Takaguchi K, Itobayashi E, Ishikawa T, Toyoda H, Kawata K, Naganuma A, Yata Y, Ohama H, Matono T, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Nakamura S, and Kumada T
- Abstract
Introduction: Gastrointestinal varices rupture is considered to be prone to occur during atezolizumab and bevacizumab (Atez/Bev) treatment. This study aimed to investigate predictive factors affecting the increase in spleen volume (SpV) and the association of SpV variation with the clinical outcomes of Atez/Bev., Methods: A total of 164 HCC patients were included in this retrospective multicenter study. We measured SpV based on CT scans obtained before treatment and at evaluations. We used the inverse probability of treatment weight to address the imbalance between patient characteristics., Results: The median pretreatment SpV was 184 (130-257) cm3 and the median SpV variation was 27 (9-60) cm3. An increase in the SpV was observed in 140 patients (85.4%). Age <74 years (p = 0.03), mALBI grade 2b or 3 (p = 0.03), and pretreatment SpV ≥184 cm3 (p < 0.001) were significantly associated with increased SpV. There were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with SpV variation <25 cm3 and those with SpV variation ≥25 cm3 in the crude (p=0.3 and 0.7) and IPTW-weighted cohorts (p = 0.08 and 0.8, respectively). Regarding pretreatment SpV, there were no significant differences in PFS or OS between patients with and without pretreatment spleen enlargement in the crude (both p = 0.3) and IPTW-weighted cohort (p = 0.6 and 0.3, respectively)., Conclusion: Caution is warranted to detect the aggravation of portal hypertension when administering Atez/Bev to young patients or patients with an impaired liver function or pretreatment spleen enlargement. The impact of spleen modulation by Atez/Bev appears to be limited on clinical efficacy., (S. Karger AG, Basel.)
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- 2024
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44. Increased Oxidative Stress and Decreased Citrulline in Blood Associated with Severe Novel Coronavirus Pneumonia in Adult Patients.
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Tsuge M, Ichihara E, Hasegawa K, Kudo K, Tanimoto Y, Nouso K, Oda N, Mitsumune S, Kimura G, Yamada H, Takata I, Mitsuhashi T, Taniguchi A, Tsukahara K, Aokage T, Hagiya H, Toyooka S, Tsukahara H, and Maeda Y
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- Humans, Male, Female, Middle Aged, Aged, Adult, SARS-CoV-2, Nitric Oxide blood, Nitric Oxide metabolism, Prospective Studies, Citrulline blood, COVID-19 blood, COVID-19 virology, Oxidative Stress, Biomarkers blood
- Abstract
This study investigated the correlation between oxidative stress and blood amino acids associated with nitric oxide metabolism in adult patients with coronavirus disease (COVID-19) pneumonia. Clinical data and serum samples were prospectively collected from 100 adult patients hospitalized for COVID-19 between July 2020 and August 2021. Patients with COVID-19 were categorized into three groups for analysis based on lung infiltrates, oxygen inhalation upon admission, and the initiation of oxygen therapy after admission. Blood data, oxidative stress-related biomarkers, and serum amino acid levels upon admission were compared in these groups. Patients with lung infiltrations requiring oxygen therapy upon admission or starting oxygen post-admission exhibited higher serum levels of hydroperoxides and lower levels of citrulline compared to the control group. No remarkable differences were observed in nitrite/nitrate, asymmetric dimethylarginine, and arginine levels. Serum citrulline levels correlated significantly with serum lactate dehydrogenase and C-reactive protein levels. A significant negative correlation was found between serum levels of citrulline and hydroperoxides. Levels of hydroperoxides decreased, and citrulline levels increased during the recovery period compared to admission. Patients with COVID-19 with extensive pneumonia or poor oxygenation showed increased oxidative stress and reduced citrulline levels in the blood compared to those with fewer pulmonary complications. These findings suggest that combined oxidative stress and abnormal citrulline metabolism may play a role in the pathogenesis of COVID-19 pneumonia.
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- 2024
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45. Identification of risk groups for advanced liver fibrosis in the general population using the Fibrosis-3 index.
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Kariyama K, Kawanaka M, Nouso K, Wakuta A, Shiota S, Kurisu A, Sugiyama A, Akita T, Kumada T, and Tanaka J
- Abstract
Background and Aim: We conducted a study using the Fibrosis-3 (FIB-3) index, which is the established age-independent index of fibrosis in nonviral liver disease and addresses the limitations of the FIB-4 index in older age group, to assess the liver fibrosis risk among diverse demographic groups in the general population., Methods: We analyzed 31 327 individuals who underwent health examinations between 2013 and 2020 and investigated the distribution of the FIB-3 index by age group. In addition, we examined the age distribution of the FIB-3 index stratified by background factors, such as sex, body mass index (BMI), alcohol consumption habits, and the presence or absence of fatty liver., Results: In terms of age-specific distribution, the FIB-3 index remained below 1.5 in >90% of cases until the age of 50 years but exceeded 1.5 beyond the age of 50 years, in approximately 30% among those aged 70 years. Notably, the FIB-3 index above 31 years old was significantly higher in men than in women. Among the different BMI categories, individuals with BMI < 18.5 exhibited the highest prevalence of fibrosis. Habitual drinkers had a higher proportion with FIB-3. index ≥1.5, and some had FIB-3 index ≥2.5, raising the suspicion of advanced hepatic fibrosis. No distinct association was identified between the FIB-3 index and the presence of fatty liver., Conclusions: The FIB-3 index was useful for identifying cases of advancing hepatic fibrosis in a health checkup population. Liver fibrosis progresses with age in the general population, especially among men, those with low BMI, and habitual drinkers., (© 2024 The Author(s). JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)
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- 2024
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46. A smartphone app-based intervention combined with face-to-face sessions for alcohol dependence at internal medicine clinics: A randomized controlled trial.
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Miyake N, So R, Kariyama K, Itagaki Y, Yamagishi T, Wakuta A, Nishimura M, Murakami S, Ogawa M, Takebayashi Y, Sunami T, Yumoto Y, Ito M, Maesato H, Matsushita S, and Nouso K
- Abstract
Background: Addressing the limited access to treatments for alcohol dependence, we developed ALM-002, a therapeutic application to be "prescribed" for non-abstinence-oriented treatment in internal medicine settings. Our objective was to preliminarily assess the efficacy and safety of ALM-002., Methods: In a multicenter, open-label randomized controlled trial, participants aged ≥20 with alcohol dependence and daily alcohol consumption exceeding 60 g for men and 40 g for women, without severe complications, were randomly assigned to either the intervention group using ALM-002 or the treatment-as-usual control group. Participant in both groups received individual face-to-face sessions by physicians at weeks 0, 4, 8, and 12. The primary endpoint was the change in heavy drinking days (HDDs) from week 0 to week 12. A mixed model for repeated measures was employed., Results: We enrolled 43 participants: 22 in the intervention group and 21 in the control group. A significant reduction in HDDs every 4 weeks from week 0 to week 12 was observed, with a between-group difference of -6.99 days (95% CI: -12.4 to -1.6 days, standardized mean difference: -0.80)., Conclusions: These results indicate the potential of ALM-002 as a viable treatment for alcohol dependence. Further studies are needed to evaluate the clinical potential of ALM-002., Competing Interests: Declaration of competing interest RS reports personal fees from CureApp, Inc., during the conduct of the study; grants from Osake-no-Kagaku Foundation, grants from The Mental Health Okamoto Memorial Foundation, grants from Kobayashi Magobe Memorial Medical Foundation, personal fees from Otsuka Pharmaceutical Co., Ltd., personal fees from Nippon Shinyaku Co., Ltd., personal fees from Takeda Pharmaceutical Co., Ltd., outside the submitted work; In addition, RS has a patent JP2022049590A, US20220084673A1 pending, a patent JP2022178215A pending, a patent JP2022070086 pending, and a patent JP2023074128A pending. YI, TY received a research funding from CureApp Inc. outside the submitted work. SMa and KN received personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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47. Outcomes of patients with hepatocellular carcinoma treated with atezolizumab plus bevacizumab in real-world clinical practice who met or did not meet the inclusion criteria for the phase 3 IMbrave150 trial.
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Tada T, Kumada T, Hiraoka A, Hirooka M, Kariyama K, Tani J, Atsukawa M, Takaguchi K, Itobayashi E, Fukunishi S, Nishikawa H, Tsuji K, Ishikawa T, Tajiri K, Koshiyama Y, Toyoda H, Ogawa C, Hatanaka T, Kakizaki S, Kawata K, Ohama H, Tada F, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Arai T, Nishimura T, Imai M, Kosaka H, Naganuma A, Matono T, Aoki T, Kuroda H, Yata Y, Koizumi Y, Nakamura S, Enomoto H, Kaibori M, Hiasa Y, and Kudo M
- Subjects
- Humans, Male, Female, Middle Aged, Aged, Treatment Outcome, Progression-Free Survival, Adult, Liver Neoplasms drug therapy, Liver Neoplasms mortality, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular mortality, Bevacizumab therapeutic use, Antibodies, Monoclonal, Humanized therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Abstract
Background: Atezolizumab plus bevacizumab (Atezo/Bev) is frequently selected as the primary systemic therapy for hepatocellular carcinoma (HCC)., Aims: To investigate the outcomes of patients with HCC treated with Atezo/Bev in a real-world setting based on whether they met the inclusion criteria for the phase 3 IMbrave150 trial., Methods: A total of 936 patients were enrolled. There were 404 patients who met the inclusion criteria of the phase 3 IMbrave150 trial (IMbrave150 group) and 532 who did not (non-IMbrave150 group)., Results: Median progression-free survival (PFS) in the IMbrave150 and non-IMbrave150 groups was 7.4 months and 5.6 months (p = 0.002). Multivariable analysis revealed that non-B, non-C HCC aetiology (hazard ratio [HR], 1.173), α-fetoprotein ≥100 ng/mL (HR, 1.472), Barcelona Clinic Liver Cancer stage ≥ C (HR, 1.318), and modified albumin-bilirubin (mALBI) grade 2b or 3 (HR, 1.476) are independently associated with PFS. Median overall survival (OS) in the IMbrave150 and non-Imbrave150 groups was 26.5 and 18.8 months (p < 0.001). Multivariable analysis revealed that Eastern Cooperative Oncology Group performance status ≥2 (HR, 1.986), α-fetoprotein ≥100 ng/mL (HR, 1.481), and mALBI grade 2b or 3 (HR, 2.037) are independently associated with OS. In subgroup analysis, there were no significant differences in PFS or OS between these groups among patients with mALBI grade 1 or 2a., Conclusions: Patients who are treated with Atezo/Bev and meet the inclusion criteria for the phase 3 IMbrave150 trial, as well as those who do not meet the inclusion criteria but have good liver function, have a good prognosis for survival., (© 2024 John Wiley & Sons Ltd.)
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- 2024
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48. Prevalence of hazardous drinking and suspected alcohol dependence in Japanese primary care settings.
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So R, Kariyama K, Oyamada S, Matsushita S, Nishimura H, Tezuka Y, Sunami T, Furukawa TA, Kawaguchi M, Kobashi H, Nishina S, Otsuka Y, Tsujimoto Y, Horie Y, Yoshiji H, Yuzuriha T, and Nouso K
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- Humans, Male, Adult, Female, Middle Aged, Japan epidemiology, Cross-Sectional Studies, Aged, Prevalence, Young Adult, Alcohol Drinking epidemiology, East Asian People, Alcoholism epidemiology, Primary Health Care statistics & numerical data
- Abstract
Objective: We aimed to assess the prevalence of hazardous drinking and potential alcohol dependence among Japanese primary care patients, and their readiness to change and awareness of others' concerns., Methods: From July to August 2023, we conducted a multi-site cross-sectional study as a screening survey for participants in a cluster randomized controlled trial. The trial included outpatients aged 20-74 from primary care clinics. Using the Alcohol Use Disorders Identification Test (AUDIT) alongside a self-administered questionnaire, we evaluated the prevalence of hazardous drinking and suspected alcohol dependence, patients' readiness to change, and their awareness of others' concerns., Results: Among the 1388 participants from 18 clinics, 22% (95% confidence interval (CI): 20% to 24%) were identified as engaging in hazardous drinking or suspected of being alcohol dependent. As the AUDIT scores increased, so did their readiness to change. However, only 22% (95%CI: 16% to 28%) of those with scores ranging from 8 to 14 reported that others, including physicians, had expressed concerns about their drinking during the past year. For those with scores of 15 or higher, the figure was 74%., Conclusions: This study underscores the need for universal or high-risk alcohol screening and brief intervention in Japanese primary care settings. Trial registry UMIN-CTR (https://www.umin.ac.jp/ctr/) (UMIN000051388)., Competing Interests: Declaration of competing interest RS and HN were employees of CureApp, Inc. during the conduct of the study. RS reports grants from Osake-no-Kagaku Foundation, grants from The Mental Health Okamoto Memorial Foundation, grants from Kobayashi Magobe Memorial Medical Foundation, personal fees from Otsuka Pharmaceutical Co., Ltd., Nippon Shinyaku Co., Ltd., Takeda Pharmaceutical Co., Ltd., and Sumitomo Pharma Co., Ltd. outside the submitted work; In addition, RS has a patent JP2022049590A, US20220084673A1 pending, a patent JP2022178215A pending, a patent JP2022070086 pending, and a patent JP2023074128A pending. TAF reports personal fees from Boehringer-Ingelheim, Daiichi Sankyo, DT Axis, Kyoto University Original, Shionogi, SONY and UpToDate, and a grant from DT Axis and Shionogi, outside the submitted work; In addition, TAF has patents 2020–548,587 and 2022–082495 pending, and intellectual properties for Kokoro-app licensed to Mitsubishi-Tanabe. YH and HY report personal fees from Otsuka Pharmaceutical and Cure App Inc. outside the submitted work. SM has received a research grant from Asahi Quality & Innovations, Ltd. and has received speaker's honoraria from EA Pharma, Otsuka Pharmaceutical, Yoshitomi Yakuhin, Eisai, Nippon Shinyaku, Otsuka Pharmaceutical and MSD, and personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work within the past three years. YT reports personal fees from Otsuka Pharmaceutical Co., MSD K.K. TY reports personal fees from Otsuka Pharmaceutical, Cure App Inc., and Nippon Shinyaku Co., Ltd. outside the submitted work. KN received personal fees for coordinating a pivotal study from Cure App Inc. outside the submitted work. Other authors report no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)
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- 2024
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49. Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.
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Persano M, Rimini M, Tada T, Suda G, Shimose S, Kudo M, Rossari F, Yoo C, Cheon J, Finkelmeier F, Lim HY, Presa J, Masi G, Bergamo F, Amadeo E, Vitiello F, Kumada T, Sakamoto N, Iwamoto H, Aoki T, Chon HJ, Himmelsbach V, Iavarone MA, Cabibbo G, Montes M, Foschi FG, Vivaldi C, Soldà C, Sho T, Niizeki T, Nishida N, Steup C, Bruccoleri M, 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, Nishimura T, Hatanaka T, Kakizaki S, Shimada N, Kawata K, Hiraoka A, Tada F, Ohama H, Nouso K, Morishita A, Tsutsui A, Nagano T, Itokawa N, Okubo T, Imai M, Kosaka H, Naganuma A, Koizumi Y, Nakamura S, Kaibori M, Iijima H, Hiasa Y, Foti S, Camera S, Piscaglia F, Scartozzi M, Cascinu S, and Casadei-Gardini A
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- Humans, Male, Female, Retrospective Studies, Aged, Middle Aged, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Antineoplastic Combined Chemotherapy Protocols pharmacology, Aged, 80 and over, Adult, Prognosis, Bevacizumab therapeutic use, Bevacizumab pharmacology, Antibodies, Monoclonal, Humanized therapeutic use, Antibodies, Monoclonal, Humanized pharmacology, Antibodies, Monoclonal, Humanized adverse effects, Liver Neoplasms drug therapy, Liver Neoplasms pathology, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology
- Abstract
Background: In the context of patients with hepatocellular carcinoma (HCC) treated with systemic therapy, the correlation between the appearance of adverse events (AEs) and reported efficacy outcomes is well-known and widely investigated. From other pathological settings, we are aware of the prognostic and predictive value of the occurrence of immune-related AEs in patients treated with immune-checkpoint inhibitors., Objective: This retrospective multicenter real-world study aims to investigate the potential prognostic value of AEs in patients with HCC treated with atezolizumab plus bevacizumab in the first-line setting., Patients and Methods: The study population consisted of 823 patients from five countries (Italy, Germany, Portugal, Japan, and the Republic of Korea)., Results: Of the patients, 73.3% presented at least one AE during the study period. The most common AEs were proteinuria (29.6%), arterial hypertension (27.2%), and fatigue (26.0%). In all, 17.3% of the AEs were grade (G) 3. One death due to bleeding was reported. The multivariate analysis confirmed the appearance of decreased appetite G < 2 [versus G ≥ 2; hazard ratio (HR) 0.60; 95% confidence interval (CI) 0.13-0.90; p < 0.01] and immunotoxicity G < 2 (versus G ≥ 2; HR: 0.70; 95% CI 0.24-0.99; p = 0.04) as independent prognostic factors for overall survival, and the appearance of decreased appetite G < 2 (versus G ≥ 2; HR: 0.73; 95% CI 0.43-0.95; p = 0.01), diarrhea (yes versus no; HR: 0.57, 95% CI 0.38-0.85; p = 0.01), fatigue (yes versus no; HR: 0.82, 95% CI 0.65-0.95; p < 0.01), arterial hypertension G < 2 (versus G ≥ 2; HR: 0.68, 95% CI 0.52-0.87; p < 0.01), and proteinuria (yes versus no; HR: 0.79, 95% CI 0.64-0.98; p = 0.03) as independent prognostic factors for progression-free survival., Conclusions: As demonstrated for other therapies, there is also a correlation between the occurrence of AEs and outcomes for patients with HCC for the combination of atezolizumab plus bevacizumab., (© 2024. The Author(s).)
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- 2024
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50. Response to the letter: "Predictive factors for transition to conversion therapy in HCC using atezolizumab plus bevacizumab".
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Kikuchi T, Takeuchi Y, Nouso K, Kariyama K, Kuwaki K, Toshimori J, Iwado S, Moriya A, Hagihara H, Takabatake H, Tada T, Yasunaka T, Sakata M, Sue M, Miyake N, Adachi T, Wada N, Onishi H, Shiraha H, Takaki A, and Otsuka M
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- Humans, Bevacizumab therapeutic use, Bevacizumab administration & dosage, Antibodies, Monoclonal, Humanized therapeutic use, Liver Neoplasms drug therapy, Carcinoma, Hepatocellular drug therapy, Antineoplastic Combined Chemotherapy Protocols therapeutic use
- Published
- 2024
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