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Tetsuhiro Chiba,1 Atsushi Hiraoka,2 Shigeru Mikami,3 Masami Shinozaki,4 Yukio Osaki,5 Masamichi Obu,6 Takamasa Ohki,7 Naoyuki Mita,8 Dianne Ledesma,8 Nariaki Yoshihara,8 Kathleen Beusterien,9 Kaitlan Amos,9 John FP Bridges,10 Osamu Yokosuka111Department of Gastroenterology and Nephrology, Chiba University Graduate School of Medicine, Chiba, Japan; 2Gastroenterology Center, Ehime Prefectural Central Hospital, Matsuyama, Ehime Prefecture, Japan; 3Department of Internal Medicine, Kikkoman General Hospital, Noda-shi, Chiba Prefecture, Japan; 4Department of Gastroenterology, Numazu City Hospital, Shizuoka, Japan; 5Department of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan; 6Department of Gastroenterology, Kimitsu Chuo Hospital, Kisarazu City, Chiba Prefecture, Japan; 7Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan; 8Market Access, Bayer Yakuhin, Ltd., Tokyo, Japan; 9ORS Health, Washington DC, USA; 10Department of Biomedical Informatics and Department of Surgery, The Ohio State University College of Medicine, Columbus, OH, USA; 11Japan Community Health care Organization Funabashi Central Hospital, Funabashi, Chiba Prefecture, JapanPurpose: This study aimed to evaluate Japanese patient preferences regarding features of intermediate or advanced (Progressed) hepatocellular carcinoma (HCC) treatments: transarterial chemoembolization (TACE), hepatic arterial infusion chemotherapy (HAIC), and oral anti-cancer therapy.Methods: Patients with HCC, recruited from clinical sites and a patient panel in Japan, completed a cross-sectional web-based survey. Preferences were quantified using best–worst scaling, where patients identified the best and worst among 13 treatment features. Direct elicitation was used to identify preference for TACE, HAIC, or oral therapy, including the likelihood of trying each. Additional items asked for the willingness to try an oral medication that delays progression by six months but has an 8% or 21% risk of severe hand-foot skin reaction (HFSR).Results: The sample (N=119; 29 early stage; 90 Progressed) most preferred “oral medication”, “artery branches plugged”, and “prevents formation of new blood vessels”, and least preferred “risk of liver damage” and “risk of catheter-related complications”. Overall, 51%, 40%, and 8% preferred oral therapy, TACE, and HAIC, respectively (p

Abstract Resistance-associated substitutions (RASs) of hepatitis C virus (HCV) affect the efficacy of direct-acting antivirals (DAAs). In this study, we aimed to clarify the susceptibility of the coexistence of nonstructural (NS) 5A Q24K/L28M/R30Q (or R30E)/A92K RASs, which were observed in patients with DAAs re-treatment failure and to consider new therapeutic agents. We used a subgenomic replicon system in which HCV genotype 1B strain 1B-4 was electroporated into OR6c cells derived from HuH-7 cells (Wild-type [WT]). We converted WT genes to NS5A Q24K/L28M/R30Q/A92K or Q24/L28K/R30E/A92K. Compared with the WT, the Q24K/L28M/R30Q/A92K RASs was 36,000-fold resistant to daclatasvir, 440,000-fold resistant to ledipasvir, 6300-fold resistant to velpatasvir, 3100-fold resistant to elbasvir, and 1.8-fold resistant to pibrentasvir. Compared with the WT, the Q24K/L28M/R30E/A92K RASs was 640,000-fold resistant to daclatasvir and ledipasvir, 150,000-fold resistant to velpatasvir, 44,000-fold resistant to elbasvir, and 1500-fold resistant to pibrentasvir. The Q24K/L28M/R30E/A92K RASs was 816.3 times more resistant to pibrentasvir than the Q24K/L28M/R30Q/A92K RASs. Furthermore, a combination of pibrentasvir and sofosbuvir showed therapeutic efficacy against these RASs. Combination regimens may eradicate HCV with NS5A Q24K/L28M/R30E/A92K RASs.

Background: There are many reports on the choice of treatment for and prognosis of left-sided obstructive colorectal cancer; however, few studies have focused on the prognostic factors of left-sided obstructive colorectal cancer. Therefore, we analyzed the prognostic factors using a post hoc analysis of a retrospective multicenter study in Japan. Methods: A total of 301 patients were enrolled in this study to investigate the prognostic factors for relapse-free survival. The relationships between sex, age, decompression for bridge to surgery, depth of invasion, lymph node metastasis, postoperative complications, adjuvant chemotherapy, carcinoembryonic antigen, carbohydrate antigen 19-9, neutrophil-to-lymphocyte ratio, and relapse-free survival were examined. Results: No change in the decompression method, T3 cancer, negative postoperative complications (grades 0–1 of Clavien-Dindo classification), and adjuvant chemotherapy during Stage III indicated a significantly better prognosis in a Cox univariate analysis. Lymph node metastasis was not selected as a prognostic factor. Excluding patients with <12 harvested lymph nodes (possible stage migration), lymph node metastasis was determined as a prognostic factor. In a Cox multivariate analysis, change in the decompression method, depth of invasion, lymph node metastasis (excluding N0 cases with <12 harvested lymph nodes), and adjuvant chemotherapy were prognostic factors. Conclusions: Similar to those in nonobstructive colorectal cancer, depth of invasion and lymph node metastasis were prognostic factors in left-sided obstructive colorectal cancer, and patients with <12 dissected lymph nodes experienced stage migration. Stage migration may result in disadvantages, such as not being able to receive adjuvant chemotherapy. [ABSTRACT FROM AUTHOR]