Papers

• Relationship between daily physical activity and muscle cramping in elderly liver cirrhosis patients―A multicenter study
  Atsushi Hiraoka, Tadashi Namisaki, Masato Nakai, Nagisa Hara, Hirokazu Takahashi, Yuichiro Eguchi, Hideko Ohama, Fujimasa Tada, Naoya Sakamoto, Hitoshi Yoshiji
  INTERNAL MEDICINE, 29 Mar. 2025
  English, Scientific journal
• Relationship between daily physical activity and muscle cramping in elderly liver cirrhosis patients-A multicenter study.
  Atsushi Hiraoka, Tadashi Namisaki, Masato Nakai, Nagisa Hara, Hirokazu Takahashi, Yuichiro Eguchi, Hideko Ohama, Fujimasa Tada, Naoya Sakamoto, Hitoshi Yoshiji
  Internal medicine (Tokyo, Japan), 29 Mar. 2025, [Domestic magazines]
  English, Scientific journal, Introduction Sarcopenia is a common secondary muscle-related complication observed in patients with chronic liver disease (CLD), along with muscle cramping. The present study aimed to assess the daily activity levels to explore the relationship between the number of steps taken and muscle cramping in patients with cirrhosis (LC) in Japan. Methods Fifty patients were enrolled (male 25, Child-Pugh A, B=42:8). Daily steps were recorded over six months using a pedometer, and seasonal sub-analyses were performed. Sarcopenia was diagnosed in accordance with the guidelines of the Japan Society of Hepatology. Results The median number of steps per day was 3,881, with no significant seasonal differences. Muscle cramping, reduced handgrip strength and sarcopenia were noted in 66.0%, 34.0% and 23.9% of the patients, respectively. However, no significant relationships were found between muscle cramping, handgrip strength, and the average number of steps per day. Although no significant differences in daily steps were noted in the comparisons of patients with varying degrees of hepatic function or the sarcopenia status, those with muscle cramping had a worse modified ALBI grade (≥2b) than those without (42.4% vs. 5.9%, P=0.009). The median average number of steps per day was not significantly different between the patients with and without muscle cramping (3,673 vs. 4,775, P=0.292). Conclusions The present study revealed that the average number of steps per day in LC patients is low. Although no significant relationship between daily activity and muscle cramping was observed, the establishment of appropriate intervention strategies to maintain daily activity and prevent sarcopenia progression is urgently required.
• Panniculitis of the Lower Extremities Caused by Acute Deterioration of Autoimmune Pancreatitis
  Soichiro Oda, Masaki Kuwatani, Shoya Shiratori, Hiroki Yonemura, Syunichiro Nozawa, Ryo Sugiura, Kazumichi Kawakubo, Kazuki Watanabe, Mika Watanabe, Naoya Sakamoto
  Journal of Gastroenterology and Hepatology, Wiley, 09 Mar. 2025
  Scientific journal, ABSTRACT
  
  A 73‐year‐old female with type 1 autoimmune pancreatitis (AIP) presented with painful erythema on her lower extremities and elevated serum pancreatic enzyme levels. Her CT images revealed focal enlargement of the pancreatic tail with an increased density of the surrounding fatty tissue. Based on serum and CT findings, she was diagnosed as having acute deterioration of AIP. Skin biopsy of erythema revealed fat necrosis with ghost cells, calcification, and inflammatory infiltration, consistent with pancreatic panniculitis. Increasing the prednisolone dose to 25 mg/day promptly ameliorated her symptoms and normalized her enzyme levels.
  
  Pancreatic panniculitis is a rare complication of pancreatitis characterized by painful subcutaneous nodules and fat necrosis. Although it has been reported in association with conditions such as pancreatic cancer and chronic pancreatitis, its occurrence in AIP has not been documented. This case highlights pancreatic panniculitis as a potential complication of AIP for the first time.
• Elevated A2F bisect N-glycans of serum IgA reflect progression of liver fibrosis in patients with MASLD.
  Hisatoshi Hanamatsu, Goki Suda, Masatsugu Ohara, Koji Ogawa, Nobuharu Tamaki, Hayato Hikita, Hiroaki Haga, Shinya Maekawa, Masaya Sugiyama, Tatsuhiko Kakisaka, Masato Nakai, Takuya Sho, Nobuaki Miura, Masayuki Kurosaki, Yasuhiro Asahina, Akinobu Taketomi, Yoshiyuki Ueno, Tetsuo Takehara, Takashi Nishikaze, Jun-Ichi Furukawa, Naoya Sakamoto
  Journal of gastroenterology, 24 Jan. 2025, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Advanced liver fibrosis in cases of metabolic dysfunction-associated steatotic liver disease (MASLD) leads to cirrhosis and hepatocellular carcinoma. The current gold standard for liver fibrosis is invasive liver biopsy. Therefore, a less invasive biomarker that accurately reflects the stage of liver fibrosis is highly desirable. METHODS: This study enrolled 269 patients with liver biopsy-proven MASLD. Patients were divided into three groups (F0/1 (n = 41/85), F2 (n = 47), and F3/4 (n = 72/24)) according to fibrosis stage. We performed serum N-glycomics and identified glycan biomarker for fibrosis stage. Moreover, we explored the carrier proteins and developed a sandwich ELISA to measure N-glycosylation changes of carrier protein. RESULTS: Comprehensive N-glycomic analysis revealed significant changes in the expression of A2F bisect and its precursors as fibrosis progressed. The sum of neutral N-glycans carrying bisecting GlcNAc and core Fuc (neutral sum) had a better diagnostic performance to evaluate advanced liver fibrosis (AUC = 0.804) than conventional parameters (FIB4 index, aspartate aminotransferase-to-alanine aminotransferase ratio (AAR), and serum level of Mac-2-binding protein glycol isomer (M2BPGi). The combination of the neutral sum and FIB4 index enhanced diagnostic performance (AUC = 0.840). IgM, IgA, and complement C3 were identified as carrier proteins with A2F bisect N-glycan. A sandwich ELISA based on N-glycans carrying bisecting GlcNAc and IgA showed similar diagnostic performance than the neutral sum. CONCLUSIONS: A2F bisect N-glycan and its precursors are promising candidate biomarkers for advanced fibrosis in MASLD patients. Analysis of these glycan alterations on IgA may have the potential to serve as a novel ELISA diagnostic tool for MASLD in routine clinical practice. CLINICAL TRIAL NUMBER: UMIN000030720.
• Subcutaneous adipose tissue radiodensity as a predictor of poor prognosis in advanced biliary tract cancer
  Ryo Sugiura, Yasuyuki Kawamoto, Masaki Kuwatani, Kazumichi Kawakubo, Kazuaki Harada, Masatsugu Ohara, Hiroki Yonemura, Shunichiro Nozawa, Naoya Sakamoto
  Journal of Hepato-Biliary-Pancreatic Sciences, Wiley, 08 Jan. 2025
  Scientific journal, Abstract
  
  Background
  
  High subcutaneous adipose tissue radiodensity (SATr), an indirect surrogate marker of adipose tissue quality, was associated with poor prognosis in various cancers. The present study aimed to assess the association of SATr with survival outcomes in patients with advanced biliary tract cancer (BTC).
  
  Methods
  
  This retrospective, single‐center study included patients with unresectable or recurrent BTC who underwent chemotherapy/chemoradiotherapy. Overall survival (OS) and progression‐free survival (PFS) were assessed using the log‐rank test and the Cox proportional hazards model according to the SATr status.
  
  Results
  
  The study cohort included 234 patients, including 38 and 196 patients with high and non‐high SATr, respectively. The median OS durations were 10.5 and 17.4 months (HR = 1.72, 95% CI: 1.19–2.49, p < .01) and the median PFS durations were 4.9 and 8.0 months (HR = 1.52, 95% CI: 1.05–2.20, p = .03) in patients with high and non‐high SATr, respectively. By multivariate analysis, high SATr, neutrophil/lymphocyte ratio >5, modified Glasgow prognostic score 1–2, and serum carcinoembryonic antigen >5.0 ng/mL were predictors for OS (HR, 1.66, 2.42, 2.00, and 1.56, respectively; p < .05). By multivariate analysis, metastatic disease status, high SATr, neutrophil/lymphocyte ratio >5, and modified Glasgow prognostic score 1–2 were independent risk factors for worse PFS (HR, 1.56, 1.56, 1.81, and 1.57, respectively; p < .05).
  
  Conclusions
  
  High SATr was associated with risk of tumor progression and poor prognosis in patients with advanced BTC treated by palliative chemotherapy/chemoradiotherapy.
• Letter: Positivity of High-Sensitivity HBsAg Test Was Significantly Associated With Poorer Prognosis in Patients With Non-HBV-Related HCC-Authors' Reply.
  Naohiro Yasuura, Goki Suda, Masatsugu Ohara, Naoya Sakamoto
  Alimentary pharmacology & therapeutics, 60, 11-12, 1647, 1649, Dec. 2024, [International Magazine]
  English
• Association of proteinuria with improved prognosis in unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab, and the predictive role of serum vascular endothelial growth factor D levels: A multicenter retrospective study.
  Zijian Yang, Goki Suda, Takuya Sho, Osamu Maehara, Masatsugu Ohara, Tomoka Yoda, Qingjie Fu, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Takashi Kitagataya, Naoki Kawagishi, Masato Nakai, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Yoshiya Yamamoto, Masaru Baba, Ren Yamada, Tomoe Kobayashi, Minhu Chen, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 25 Nov. 2024, [International Magazine]
  English, Scientific journal, AIM: Atezolizumab/bevacizumab is a first-line therapy for unresectable hepatocellular carcinoma (HCC). Among several adverse events, grade ≥2 proteinuria is considered a significant adverse event that may cause bevacizumab interruption. Studies have shown that proteinuria might predict improved prognosis, although data are scarce and the association remains controversial, and the mechanisms and predictive factors remain unclear. We aimed to clarify these. METHODS: In this multicenter retrospective study, we screened patients with HCC treated with atezolizumab/bevacizumab. The prognostic impact of grade ≥2 proteinuria was examined in patients with proper clinical data and preserved serum for growth factor analysis. For biomarker analysis predicting proteinuria, baseline serum vascular endothelial growth factor (VEGF)-A, VEGF-C, and VEGF-D levels were analyzed. RESULTS: This study included 75 patients, and 32 (42.7%) experienced grade ≥2 proteinuria. No significant differences were observed between those with or without proteinuria, except for aspartate transaminase and alanine transaminase levels. Time-dependent Cox proportional hazards analysis revealed that grade ≥2 proteinuria was significantly associated with better prognosis (hazard ratio 0.221; 95% confidence interval 0.082-0.592; p = 0.003). In biomarker analysis, low baseline serum VEGF-C and VEGF-D levels were significantly associated with proteinuria, and multivariate analysis demonstrated that baseline serum VEGF-D level was significantly associated with grade ≥2 proteinuria (hazard ratio 0.101; 95% confidence interval 0.029-0.357; p < 0.001). CONCLUSIONS: Grade ≥2 proteinuria in patients with unresectable HCC treated with atezolizumab/bevacizumab indicates a better prognosis, and baseline serum VEGF-D levels can help predict its occurrence. These findings can help in managing adverse events and prognosis in advanced HCC treated with atezolizumab/bevacizumab.
• Lenvatinib versus sorafenib second-line therapy in patients with hepatocellular carcinoma progressed to atezolizumab plus bevacizumab: a retrospective real-world study.
  Mara Persano, Andrea Casadei-Gardini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Federico Rossari, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Alberto Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Mariangela Bruccoleri, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Luigi Mascia, Silvia Foti, Silvia Camera, Fabio Piscaglia, Mario Scartozzi, Stefano Cascinu, Margherita Rimini
  Oncology, 1, 27, 11 Oct. 2024, [International Magazine]
  English, Scientific journal, INTRODUCTION: the most frequently used first-line treatment in patients with advanced hepatocellular carcinoma (HCC) is atezolizumab plus bevacizumab. Upon progression after this treatment, the standard of care in many countries is sorafenib, due to the lack of reimbursement for other drugs. Several randomized trials are currently underway to clarify the best second-line therapy in patients with HCC. This real-world study aims to compare outcomes reached by lenvatinib and sorafenib second-line therapy in this setting. METHODS: the overall cohort included 891 patients with HCC from 5 countries treated with atezolizumab plus bevacizumab in first-line setting between October 2018 and April 2022. At data cut-off (May 2022), 41.5% of patients were continuing first-line treatment, 5.5% were lost at follow up, and 53.0% of patients had progressive disease after first-line therapy. 51.5% of patients with progressive disease received a second-line treatment, while 48.5% didn't receive any subsequent therapy. Between patients receiving second-line treatment, 11.1% patients underwent transarterial chemoembolization, 21.0% received sorafenib, 35.4% underwent lenvatinib, and 32.5% were treated with other drugs. RESULTS: lenvatinib second-line subgroup achieved a median overall survival (mOS) of 18.9 months, significative longer (p = 0.01; HR: 2.24) compared to sorafenib subgroup that reached a mOS of 14.3 months. The multivariate analysis highlighted Albumin-Bilirubin 1 grade [p < 0.01; hazard ratio (HR): 5.23] and lenvatinib second-line therapy (p = 0.01; HR: 2.18) as positive prognostic factors for OS. The forest plot highlighted a positive trend in terms of OS in favor of patients treated with lenvatinib second-line regardless of baseline characteristics before first-line therapy. CONCLUSION: these results suggest that, in patients with HCC progressed to first-line atezolizumab plus bevacizumab, lenvatinib second-line therapy is associated to an improved survival compared to sorafenib.
• Disease Etiology Impact on Outcomes of Hepatocellular Carcinoma Patients Treated with Atezolizumab plus Bevacizumab: A Real-World, Multicenter Study.
  Federico Rossari, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Mara Persano, Silvia Foti, Silvia Camera, Bernardo Stefanini, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini, Margherita Rimini
  Liver cancer, 13, 5, 522, 536, Oct. 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, INTRODUCTION: The impact of etiology on response to immunotherapy in advanced hepatocellular carcinoma (HCC) is being debated, with contrasting findings between early and recent post hoc analyses of IMbrave-150 and metanalyses of clinical trials of PD-1/PD-L1 blockers. As a results, it is not clear whether the first-line systemic treatment atezolizumab plus bevacizumab (A + B) is equally effective in viral and nonviral patients. METHODS: We retrospectively analyzed 885 HCC patients treated with the first-line A + B from multiple centers from Eastern and Western countries, 53.9% having viral and 46.1% nonviral etiology. Baseline clinical and laboratory characteristics were analyzed with uni- and multivariate models to explore potential differences on overall survival (OS), time-to-progression (TTP), disease control rates (DCRs) based on etiology and to identify putative prognostic factors in etiology subgroups. Treatment toxicities and access to the second-line treatments and outcomes were also reported and compared between etiologies. RESULTS: Overall, no statistically significant differences were found in median OS (mOS: viral 15.9 months; nonviral 16.3 months), TTP (mTTP: viral 8.3 months; nonviral 7.2 months), and DCRs (viral 78.1%; nonviral 80.8%) based on etiology. Prognostic factors of survival and progression were mainly shared between viral and nonviral etiologies, including alpha-fetoprotein, aspartate transaminase, neutrophil-to-lymphocyte ratio (NLR) and ALBI score. Exploratory analyses highlighted a possible stronger association of immunological factors, i.e., NLR and eosinophil count, to treatment outcomes in viral patients. The toxicity profile, the access to and type of the second-line treatments and their outcome in terms of OS almost overlap in the two etiology subgroups. CONCLUSION: Atezolizumab plus bevacizumab efficacy does not vary according to underlying etiology of HCC in a multicenter, real-world population, matching recent post hoc findings from the IMbrave-150 trial. Preliminary analyses suggest that some prognostic factors differ between viral and nonviral patients, potentially due to biological and immunological differences. Prospective and comparative trials stratifying by etiology are warranted to validate these findings and guide clinical practice.
• Positivity of high-sensitivity HBsAg test, not previous HBV infection, indicates poor prognosis in patients with non-HBV-related HCC.
  Naohiro Yasuura, Goki Suda, Masatsugu Ohara, Akimitsu Meno, Takuya Sho, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Tomoya Saitou, Masaya Sugiyama, Takasuke Fukuhara, Masaru Baba, Takashi Kitagataya, Naoki Kawagishi, Masato Nakai, Mitsuteru Natsuizaka, Koji Ogawa, Akinobu Taketomi, Naoya Sakamoto
  Alimentary pharmacology & therapeutics, 04 Sep. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND AND AIMS: The prognostic impact of previous-HBV-infection (pHBV) in non-HBV-related hepatocellular carcinoma (non-HBV-related-HCC) and the prevalence, characteristics and significance of recently developed high-sensitivity HBs antigen positivity (hHBsAg+) in these patients remain unclear. We aimed to close these gaps. METHODS: We retrospectively screened patients with newly diagnosed non-HBV-related-HCC (standard HBsAg-test negative) at Hokkaido University. Patients with complete clinical information and preserved serum for hHBsAg+ were included. We evaluated the prevalence, characteristics and prognostic impact of pHBV and hHBsAg+ in non-HBV-related-HCC. RESULTS: A total of 401 non-HBV-related-HCC patients were included (288 with pHBV/113 without pHBV). In non-HBV-related-HCC, pHBV did not affect overall survival (OS). Among non-HBV-related-HCC patients with pHBV, 11.8% (34/288) were hHBsAg+ and had more advanced stages of HCC, higher AFP levels, higher vascular invasion rates, and significantly shorter OS than others (OS: 19.3 vs. 61.4 months, p = 0.012). Comparison of OS among non-HBV-related-HCC patients without pHBV (group 1), those with pHBV and without hHBsAg+ (group 2), and those with pHBV and hHBsAg+ (group 3) revealed significantly shorter OS in group 3 (19.3, 56.6 and 66.4 months in groups 1, 2 and 3, respectively; p = 0.036). Multivariate Cox regression indicated that compared with group 1, only group 3 was significantly and independently associated with shorter OS (HR: 2.044, p = 0.011). Subgroup analysis revealed that this association was particularly evident in non-HBV-related-HCC patients with non-B-non-C aetiology and advanced HCC. CONCLUSIONS: In non-HBV-related-HCC patients, hHBsAg+, not pHBV, is significantly and independently associated with poor prognosis.
• Efficacy and Safety of Durvalumab/Tremelimumab in Unresectable Hepatocellular Carcinoma as Immune Checkpoint Inhibitor Rechallenge Following Atezolizumab/Bevacizumab Treatment.
  Takuya Sho, Goki Suda, Masatsugu Ohara, Risako Kohya, Takashi Sasaki, Sonoe Yoshida, Shunichi Hosoda, Koji Ogawa, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Masaru Baba, Yoshiya Yamamoto, Yoko Tsukuda, Takashi Meguro, Ren Yamada, Tomoe Kobayashi, Tomofumi Takagi, Naoya Sakamoto
  Targeted oncology, 19, 5, 769, 778, Sep. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND: While guidelines recommend immune checkpoint inhibitor (ICI) rechallenge as second-line therapy for unresectable hepatocellular carcinoma (HCC), data supporting this remain limited, particularly regarding a standard regimen for first- and second-line treatments. Tremelimumab/durvalumab was recently approved but data on ICI rechallenge are lacking. OBJECTIVES: The purpose of this study was to evaluate the early efficacy and safety of tremelimumab/durvalumab for HCC as an ICI rechallenge following initial ICI therapy with atezolizumab/bevacizumab. PATIENTS AND METHODS: This multicenter retrospective study included patients with HCC who underwent treatment with tremelimumab/durvalumab, with relevant available clinical information. We evaluated the safety and efficacy of tremelimumab/durvalumab as ICI rechallenge following initial treatment with atezolizumab/bevacizumab. We analyzed the outcomes in patients who underwent tremelimumab/durvalumab as an ICI rechallenge and those who received tremelimumab/durvalumab as their initial ICI therapy RESULT: A total of 45 patients treated with tremelimumab/durvalumab were included, with 55.6% (25/45) undergoing ICI rechallenge. The objective-response and disease-control rates in patients who underwent ICI rechallenge were 14.3% (3/21) and 47.6% (10/21), respectively, similar to those in patients initially treated with tremelimumab/durvalumab. All patients (n = 3) who experienced the best response to progressive disease (PD) with initial atezolizumab/bevacizumab experienced PD during ICI rechallenge. The incidence rates of adverse events were similar between patient groups treated with tremelimumab/durvalumab as ICI rechallenge and initial ICI. Among patients experiencing immune-related adverse events (irAEs) with atezolizumab/bevacizumab, 75% (3/4) encountered similar irAEs during ICI rechallenge. CONCLUSION: Early safety and efficacy profiles of durvalumab/tremelimumab as ICI rechallenge are satisfactory.
• 悪性肝門部胆道閉塞に対する初期ドレナージとしての内視鏡的胆道内ステント留置術と内視鏡的経鼻胆道ドレナージ術の比較(Comparison of endoscopic biliary inside stenting with endoscopic nasobiliary drainage as the initial drainage for malignant hilar biliary obstruction)　　　　　　　　　　　　　　　
  杉浦 諒, 桑谷 将城, 坂本 直哉
  胆道, 38, 3, 383, 383, (一社)日本胆道学会, Sep. 2024
  English
• 胆道癌患者における術前骨格筋量減少の危険因子解析　　　　　　　　　　　　　　　
  杉浦 諒, 桑谷 将城, 坂本 直哉, 小田 総一郎, 白鳥 翔也, 野澤 俊一郎, 米村 洋輝, 川久保 和道
  胆道, 38, 3, 461, 461, (一社)日本胆道学会, Sep. 2024
  Japanese
• 膵IPMN長期経過観察例の評価 IPMN患者における骨格筋量減少の膵発癌に与える影響
  小田 総一郎, 川久保 和道, 白鳥 翔也, 野澤 俊一郎, 米村 洋輝, 岸 法磨, 杉浦 諒, 桑谷 将城, 坂本 直哉
  膵臓, 39, 3, A308, A308, (一社)日本膵臓学会, Jul. 2024
  Japanese
• Preoperative risk factors for skeletal muscle mass loss in patients with biliary tract cancer
  Ryo Sugiura, Masaki Kuwatani, Kazumichi Kawakubo, Kazuma Kishi, Hiroki Yonemura, Shunichiro Nozawa, Masatsugu Ohara, Takehiro Noji, Satoshi Hirano, Naoya Sakamoto
  Journal of Hepato-Biliary-Pancreatic Sciences, Wiley, 06 Jun. 2024
  Scientific journal, Abstract
  
  Background
  
  Endoscopic retrograde cholangiography (ERC)‐related procedures, usually performed before biliary tract cancer (BTC) surgery, are associated with increased risk for various complications, which can cause sarcopenia. No study has previously elucidated the relationship between preoperative ERC‐related procedures and sarcopenia/skeletal muscle mass loss.
  
  Methods
  
  Patients with BTC who underwent radical surgical resection following ERC‐related procedures were included. Skeletal muscle mass was evaluated using the psoas muscle mass index (PMI), which was determined using computed tomography images, and the change in PMI before the initial pre‐ERC and surgery (ΔPMI) was calculated. Risk factors for advanced skeletal muscle mass loss, defined as a large ΔPMI, were evaluated.
  
  Results
  
  The study cohort included 90 patients with a median age of 72 (interquartile range, 65–75) years. The median PMI pre‐ERC and surgery was 4.40 and 4.15 cm²/m², respectively (p < .01). The median ΔPMI was −6.2% (interquartile range, −10.9% to 0.5%). By multivariate analysis, post‐ERC pancreatitis and cholangitis before surgery were independent predictive factors for large PMI loss (odds ratio, 4.57 and 3.18, respectively; p = .03 and p = .02, respectively).
  
  Conclusions
  
  Skeletal muscle mass decreases preoperatively in most patients with BTC undergoing ERC. Post‐ERC pancreatitis and cholangitis before surgery were independent risk factors for large skeletal muscle mass loss.
• Proteomic analysis of serum extracellular vesicles reveals Fibulin-3 as a new marker predicting liver-related events in MASLD.
  Sadatsugu Sakane, Hayato Hikita, Kumiko Shirai, Tatsuya Sakamoto, Ryohei Narumi, Jun Adachi, Naruyasu Kakita, Yukinori Yamada, Hidenori Toyoda, Hirokazu Takahashi, Goki Suda, Machiko Kai, Yuki Tahata, Ryotaro Sakamori, Shusuke Kumazaki, Kenji Fukumoto, Yuta Myojin, Kazuhiro Murai, Takahiro Kodama, Tomohide Tatsumi, Takeshi Tomonaga, Naoya Sakamoto, Eiichi Morii, Tetsuo Takehara
  Hepatology communications, 8, 6, 01 Jun. 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: There is a need for novel noninvasive markers for metabolic dysfunction-associated steatotic liver disease (MASLD) to stratify patients at high risk for liver-related events including liver cancer and decompensation. In the present study, we used proteomic analysis of proteins in extracellular vesicles (EVs) to identify new biomarkers that change with fibrosis progression and can predict the development of liver-related events. METHODS: We analyzed serum EVs from 50 patients with MASLD assessed for liver fibrosis by biopsy and identified proteins that altered with advanced fibrosis. A further evaluation was conducted on another cohort of 463 patients with MASLD with biopsy. RESULTS: Eight candidate proteins were identified by proteomic analysis of serum EVs. Among them, serum levels of Fibulin-3, Fibulin-1, and Ficolin 1 correlated with their EV levels. In addition, serum Fibulin-3 and serum Fibulin-1 levels changed significantly with advanced fibrosis. Using another cohort with biopsy, we found that the serum Fibulin-3 concentration was significantly greater in those with advanced fibrosis but that the serum Fibulin-1 concentration was not significantly different. Multivariate Cox proportional hazards analysis revealed that a higher Fibrosis-4 (FIB-4) index and higher serum Fibulin-3 concentration were independent risk factors for liver-related events. When the cutoff value for the serum Fibulin-3 concentration was 6.0 µg/mL according to the Youden index of AUROCs, patients with high serum Fibulin-3 significantly more frequently developed liver-related events than did other patients. Validation using another cohort of 226 patients with clinically diagnosed MASLD confirmed that high serum Fibulin-3 levels are associated with a greater frequency of liver-related events. CONCLUSIONS: Serum Fibulin-3 was identified as a biomarker for predicting liver-related events in patients with MASLD.
• GGT1 is a SNP eQTL gene involved in STAT3 activation and associated with the development of Post-ERCP pancreatitis.
  Ryutaro Furukawa, Masaki Kuwatani, Jing-Jing Jiang, Yuki Tanaka, Rie Hasebe, Kaoru Murakami, Kumiko Tanaka, Noriyuki Hirata, Izuru Ohki, Ikuko Takahashi, Takeshi Yamasaki, Yuta Shinohara, Shunichiro Nozawa, Shintaro Hojyo, Shimpei I Kubota, Shigeru Hashimoto, Satoshi Hirano, Naoya Sakamoto, Masaaki Murakami
  Scientific reports, 14, 1, 12224, 12224, 28 May 2024, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Post-ERCP pancreatitis (PEP) is an acute pancreatitis caused by endoscopic-retrograde-cholangiopancreatography (ERCP). About 10% of patients develop PEP after ERCP. Here we show that gamma-glutamyltransferase 1 (GGT1)-SNP rs5751901 is an eQTL in pancreatic cells associated with PEP and a positive regulator of the IL-6 amplifier. More PEP patients had the GGT1 SNP rs5751901 risk allele (C) than that of non-PEP patients at Hokkaido University Hospital. Additionally, GGT1 expression and IL-6 amplifier activation were increased in PEP pancreas samples with the risk allele. A mechanistic analysis showed that IL-6-mediated STAT3 nuclear translocation and STAT3 phosphorylation were suppressed in GGT1-deficient cells. Furthermore, GGT1 directly associated with gp130, the signal-transducer of IL-6. Importantly, GGT1-deficiency suppressed inflammation development in a STAT3/NF-κB-dependent disease model. Thus, the risk allele of GGT1-SNP rs5751901 is involved in the pathogenesis of PEP via IL-6 amplifier activation. Therefore, the GGT1-STAT3 axis in pancreas may be a prognosis marker and therapeutic target for PEP.
• 末梢血幹細胞移植前後で発症し,再活性化が疑われた急性E型肝炎の1例　　　　　　　　　　　　　　　
  久保 彰則, 小川 浩司, 得地 祐匡, 重沢 拓, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 石田 勢津子, 坂本 直哉
  肝臓, 65, 5, 259, 259, (一社)日本肝臓学会, May 2024
  Japanese
• Impact of body mass index on the prognosis of unresectable HCC patients receiving first-line Lenvatinib or atezolizumab plus bevacizumab.
  Margherita Rimini, Bernardo Stefanini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Fabian Finkelmeier, Changhoon Yoo, José Presa, Elisabeth Amadeo, Virginia Genovesi, Maria Caterina De Grandis, Massimo Iavarone, Fabio Marra, Francesco Foschi, Emiliano Tamburini, Federico Rossari, Francesco Vitiello, Linda Bartalini, Caterina Soldà, Francesco Tovoli, Caterina Vivaldi, Sara Lonardi, Marianna Silletta, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Vera Himmelsbach, Margarida Montes, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Mara Persano, Silvia Camera, Silvia Foti, Luca Aldrighetti, Stefano Cascinu, Andrea Casadei-Gardini, Fabio Piscaglia
  Liver international : official journal of the International Association for the Study of the Liver, 44, 5, 1108, 1125, May 2024, [International Magazine]
  English, Scientific journal, INTRODUCTION: Overweight is a negative prognostic factor in the general population in the long term. However, the role of body mass index (BMI) in the short-mid term in advanced tumours is unclear. The present analysis investigates the role of BMI weight classes in a large sample of patients affected by HCC and receiving atezolizumab plus bevacizumab or lenvatinib as first-line treatment. METHODS AND MATERIAL: The cohort included consecutive patients affected by BCLC-c and BCLC-B HCC patients from a multicenter international study group who received atezolizumab plus bevacizumab or lenvatinib as first-line therapy. Population was stratified according to the BMI in under-, over- and normal-weight according to the conventional thresholds. The primary objective of the study was to evaluate the prognostic and predictive impact of BMI in patients affected by advanced or intermediate HCC. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analysed with log-rank tests. RESULTS: 1292 consecutive patients with HCC were analysed. 466 (36%) patients were treated with lenvatinib and 826 (64%) patients were treated with atezolizumab plus bevacizumab. In the atezolizumab plus bevacizumab arm, 510 (62%) patients were normal-weight, 52 (6%) underweight and 264 (32%) overweight. At the univariate analysis for OS, underweight patients had significantly shorter OS compared to normal-weight patients, whereas no differences were found between normal-weight versus overweight. Multivariate analysis confirmed that underweight patients had significantly shorter OS compared to normal-weight patients (HR: 1.7; 95% CI: 1.0-2.8; p = .0323). In the lenvatinib arm, 26 patients (5.6%) were categorized as underweight, 256 (54.9%) as normal-weight, and 184 (39.5%) as overweight. At the univariate analysis for OS, no significant differences were found between normal-weight versus underweight and between normal-weight versus overweight, which was confirmed at multivariate analysis. CONCLUSION: Our analysis highlighted a prognostic role of BMI in a cohort of patients with advanced HCC who received atezolizumab plus bevacizumab, while no prognostic role for low BMI was apparent in patients who received lenvatinib.
• Adverse Events as Potential Predictive Factors of Activity in Patients with Advanced HCC Treated with Atezolizumab Plus Bevacizumab.
  Mara Persano, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Federico Rossari, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Alberto Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Mariangela Bruccoleri, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Silvia Foti, Silvia Camera, Fabio Piscaglia, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini
  Targeted oncology, 30 Apr. 2024, [International Magazine]
  English, Scientific journal, 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.
• 膵管狭窄/拡張に対する内視鏡的逆行性膵管造影下ブラシ細胞診と連続膵液細胞診の診断能の比較　　　　　　　　　　　　　　　
  杉浦 諒, 桑谷 将城, 坂本 直哉
  Gastroenterological Endoscopy, 66, Suppl.1, 1016, 1016, (一社)日本消化器内視鏡学会, Apr. 2024
  Japanese
• 膵癌早期診断の試み 十二指腸液中のメタボローム解析による膵良悪性疾患の鑑別
  岸 法磨, 桑谷 将城, 小田 総一郎, 白鳥 翔也, 米村 洋輝, 野澤 俊一郎, 杉浦 諒, 川久保 和道, 坂本 直哉
  日本消化器病学会雑誌, 121, 臨増総会, A221, A221, (一財)日本消化器病学会, Mar. 2024
  Japanese
• 食道胃静脈瘤に対し経皮経脾静脈瘤塞栓術を施行した1例　　　　　　　　　　　　　　　
  保浦 直弘, 大原 正嗣, めの 晃光, 甲谷 理紗子, 佐々木 貴志, 吉田 苑永, 細田 峻一, 北潟谷 隆, 中井 正人, 荘 拓也, 須田 剛生, 小川 浩司, 阿保 大介, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 134回・128回, 46, 46, 日本消化器病学会-北海道支部, Mar. 2024
  Japanese
• Surveillance esophagogastroduodenoscopy using linked color imaging and narrow-band imaging: A multicenter randomized controlled trial.
  Marina Kubo, Shoko Ono, Osamu Dohi, Hayato Fukui, Takuto Hikichi, Tsunetaka Kato, Momoko Tsuda, Mio Matsumoto, Sosuke Kato, Rieko Mukai, Nobuaki Yagi, Ryo Takagi, Naoya Sakamoto, Mototsugu Kato
  Journal of gastroenterology and hepatology, 25 Feb. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: There has been no report on a direct comparison between linked color imaging (LCI) and second-generation narrow-band imaging (2G-NBI) for surveillance of epithelial neoplasms in the upper gastrointestinal tract (UGIT). The aim of this study was to verify the superiority of LCI to 2G-NBI for surveillance esophagogastroduodenoscopy and to clarify how each endoscopic system should be used. METHODS: This study was conducted as an open-label, two-arm-parallel (1:1), multicenter, randomized controlled trial at six institutions. Patients aged 20-85 years with a treatment history of epithelial neoplasms in the UGIT were recruited. Patients were assigned to a 2G-NBI group and an LCI group, and esophagogastroduodenoscopy was performed with primary image-enhanced endoscopy followed by white light imaging (WLI). The primary endpoint was the detection rate of one or more epithelial neoplasms in the primary image-enhanced endoscopy. A WLI-detected epithelial neoplasm was defined as a lesion that was detected in only WLI. RESULTS: A total of 372 patients in the 2G-NBI group and 378 patients in the LCI group were analyzed. Epithelial neoplasms in the UGIT were detected by 2G-NBI in 18 patients (4.6%) and were detected by LCI in 20 patients (5.3%) (P = 0.87). WLI-detected epithelial neoplasms were in 11 patients in the 2G-NBI group (3.0%) and in 1 patient in the LCI group (0.27%) (P = 0.003). CONCLUSIONS: Linked color imaging did not show superiority to 2G-NBI for the detection of epithelial neoplasms. Also, the percentage of WLI-detected epithelial neoplasms in primary NBI was significantly higher than that in primary LCI.
• Safety and Efficacy of Lenvatinib in Very Old Patients with Unresectable Hepatocellular Carcinoma.
  Silvia Camera, Margherita Rimini, Federico Rossari, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Francesca Salani, Mariarosaria Marseglia, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Sara Lonardi, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Mara Persano, Silvia Foti, Fabio Piscaglia, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini
  Targeted oncology, 19, 1, 29, 39, 22 Jan. 2024, [International Magazine]
  English, Scientific journal, BACKGROUND: Data concerning the use of lenvatinib in very old patients (≥ 80 years) are limited, although the incidence of hepatocellular carcinoma (HCC) in this patient population is constantly increasing. OBJECTIVE: This analysis aimed to evaluate the efficacy and safety of lenvatinib in a large cohort of very old patients (≥ 80 years) with unresectable HCC. PATIENTS AND METHODS: The study was conducted on a cohort of 1325 patients from 46 centers in four Western and Eastern countries (Italy, Germany, Japan, and the Republic of Korea) who were undergoing first-line treatment with lenvatinib between July 2010 and February 2022. Patients were stratified according to age as very old (≥ 80 years) and not very old (< 80 years). RESULTS: The median overall survival (OS) was 15.7 months for patients < 80 years old and 18.4 months for patients ≥ 80 years old [hazard ratio (HR) = 1.02, 95% confidence interval (CI) 0.84-1.25, p = 0.8281]. Median progression free survival (PFS) was 6.3 months for patients < 80 years old and 6.5 months for patients ≥ 80 years old (HR = 1.07, 95% CI 0.91-1.25, p = 0.3954). No differences between the two study groups were found in terms of disease control rate (DCR; 80.8% versus 78.8%; p = 0.44) and response rate (RR; 38.2% versus 37.9%; p = 0.88). Patients < 80 years old experienced significantly more hand-foot skin reaction (HFSR) grade ≥ 2 and decreased appetite grade ≥ 2. Conversely, patients ≥ 80 years old experienced significantly more fatigue grade ≥ 2. In the very old group, parameters associated with prognosis were AFP, albumin-bilirubin (ALBI) grade, Barcelona Clinic Liver Cancer (BCLC), and Child-Pugh score. BCLC stage was the only independent predictor of overall survival (OS; HR = 1.59, 95% CI 1.11-2.29, p = 0.01115). CONCLUSIONS: Our study highlights the same efficacy and safety of lenvatinib between very old and not very old patients.
• 【チーム医療で取り組む肝胆膵疾患の栄養マネジメント】肝胆膵疾患に最適な栄養アセスメント法とは　　　　　　　　　　　　　　　
  中井 正人, 大原 正嗣, 坂本 直哉
  肝胆膵, 88, 1, 7, 13, (株)アークメディア, Jan. 2024
  Japanese
• α-FAtE: A new predictive score of response to atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma.
  Federico Rossari, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Changhoon Yoo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Francesca Bergamo, Elisabeth Amadeo, Francesco Vitiello, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Massimo Iavarone, Giuseppe Cabibbo, Margarida Montes, Francesco Giuseppe Foschi, Caterina Vivaldi, Caterina Soldà, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Atsushi Hiraoka, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Mara Persano, Valentina Burgio, Fabio Piscaglia, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini, Margherita Rimini
  International journal of cancer, 23 Nov. 2023, [International Magazine]
  English, Scientific journal, Atezolizumab plus bevacizumab (AB) and lenvatinib can be alternatively used as first-line systemic treatment of unresectable hepatocellular carcinoma (HCC). However, no direct comparison of the two regimens has been performed in randomized clinical trials, making the identification of baseline differential predictors of response of major relevance to tailor the best therapeutic option to each patient. Baseline clinical and laboratory characteristics of real-world AB-treated HCC patients were analyzed in uni- and multivariate analyses to find potential prognostic factors of overall survival (OS). Significant variables were incorporated in a composite score (α-FAtE) and it was tested for specificity and sensitivity in receiver operating characteristic (ROC) curve and in multivariate analysis for OS. The score was applied in uni- and multivariate analyses for OS of a comparable lenvatinib-treated HCC population. Finally, comparison between treatments was performed in patients with low and high α-FAtE scores and predictivity estimated by interaction analysis. Time-to-progression (TTP) was a secondary endpoint. OS of AB-treated HCC patients was statistically longer in those with α-fetoprotein <400 ng/mL (HR 0.62, p = .0407), alkaline phosphatase (ALP) <125 IU/L (HR 0.52, p = .0189) and eosinophil count ≥70/μL (HR 0.46, p = .0013). The α-FAtE score was generated by the sum of single points attributed to each variable among the above reported. In ROC curve analysis, superior sensitivity and specificity were achieved by the score compared to individual variables (AUC 0.794, p < .02). Patients with high score had longer OS (HR 0.44, p = .0009) and TTP (HR 0.34, p < .0001) compared to low score if treated with AB, but not with lenvatinib. Overall, AB was superior to lenvatinib in high score patients (HR 0.55, p = .0043) and inferior in low score ones (HR 1.75, p = .0227). At interaction test, low α-FAtE score resulted as negative predictive factor of response to AB (p = .0004). In conclusion, α-FAtE is a novel prognostic and predictive score of response to first-line AB for HCC patients that, if validated in prospective studies, could drive therapeutic choice between lenvatinib and AB.
• 胸部食道がん化学放射線療法における重症放射線食道炎に関する後方視的研究
  原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 結城 敏志, 坂本 直哉, 川本 泰之, 小松 嘉人, 打浪 雄介, 田口 大志, 加藤 徳雄, 青山 英史
  北海道医学雑誌, 98, 2, 139, 140, 北海道医学会, Nov. 2023
  Japanese
• 【胆膵の画像・内視鏡診断の進歩-早期診断と正確な診断のために】閉塞性黄疸に対する内視鏡的診断アプローチ EUS/ERCP
  桑谷 将城, 米村 洋輝, 野澤 俊一郎, 岸 法磨, 杉浦 諒, 川久保 和道, 坂本 直哉
  臨床消化器内科, 38, 13, 1625, 1631, (株)日本メディカルセンター, Nov. 2023
  Japanese
• Application of polyglycolic acid sheets and basic fibroblast growth factor to prevent esophageal stricture after endoscopic submucosal dissection in pigs.
  Yusuke Nishimura, Masayoshi Ono, Naoto Okubo, Takayuki Sone, Masayuki Higashino, Shogo Matsumoto, Marina Kubo, Keiko Yamamoto, Shoko Ono, Shunsuke Ohnishi, Naoya Sakamoto
  Journal of gastroenterology, 58, 11, 1094, 1104, Nov. 2023, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Endoscopic submucosal dissection (ESD) has been the first-line treatment for early-stage esophageal cancer. However, it often causes postoperative stricture in cases requiring wide dissection. Basic fibroblast growth factor (bFGF) reportedly has anti-scarring effects during cutaneous wound healing. We hypothesized that suppressing myofibroblast activation will prevent stricture after esophageal ESD. METHODS: We resected a complete porcine esophagus circumference section by ESD. To investigate the preventive effect of bFGF on esophageal stricture formation after ESD, we endoscopically applied bFGF-soaked poly-glycolic acid (PGA) sheets onto the wound bed after ESD and fixed them by spraying fibrin glue (PGA + bFGF group), PGA sheets alone onto the wound bed and fixed them by spraying fibrin glue (PGA group), or nothing (control group). After removing the esophagus on day 22, we evaluated the mucosal constriction rate. RESULTS: Compared with those in the control group, esophageal stricture was significantly reduced in the PGA + bFGF group, and the areas stained with α-SMA and calponin-1 antibodies were significantly inhibited in the PGA + bFGF and PGA groups. The thickness of the fibrous layer in the PGA + bFGF group was uniform compared to that of the other groups. Thus, PGA + bFGF inhibited the development of unregulated fibroblasts in the acute phase, leading to uniform wound healing. CONCLUSIONS: Stenosis after esophageal ESD is related to fibrosis in the acute phase. Administration of PGA and bFGF suppresses myofibroblast activation in the acute phase, thereby preventing esophageal constriction in pigs.
• 胸部食道がん化学放射線療法における重症放射線食道炎に関する後方視的研究
  原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 結城 敏志, 坂本 直哉, 川本 泰之, 小松 嘉人, 打浪 雄介, 田口 大志, 加藤 徳雄, 青山 英史
  北海道医学雑誌, 98, 2, 139, 140, 北海道医学会, Nov. 2023
  Japanese
• 【薬物療法によって変貌する肝細胞癌治療:2023 Update】Advanced stage肝細胞癌 Phase 3 HIMALAYA試験の結果とその解釈　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 北潟谷 隆, 大原 正嗣, 中井 正人, 小川 浩司, 坂本 直哉
  肝胆膵, 87, 4, 439, 446, (株)アークメディア, Oct. 2023
  Japanese
• IMbrave150基準外進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療効果と肝予備能変化　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 大原 正嗣, 中井 正人, 小川 浩司, 出水 孝章, 目黒 高志, 中村 晃久, 高木 智史, 馬場 英, 古家 乾, 鈴木 和治, 山本 義也, 伊藤 淳, 山田 錬, 宮城島 拓人, 坂本 直哉
  肝胆膵, 87, 4, 508, 509, (株)アークメディア, Oct. 2023
  Japanese
• 北海道における肝炎医療コーディネーター養成研修会の実施状況の変遷に関する検討　　　　　　　　　　　　　　　
  大原 正嗣, 小川 浩司, 長谷川 智子, 櫻井 菜々子, 中井 正人, 荘 拓也, 須田 剛生, 坂本 直哉
  肝臓, 64, Suppl.3, A808, A808, (一社)日本肝臓学会, Oct. 2023
  Japanese
• IMbrave150基準外症例におけるアテゾリズマブ+ベバシズマブ併用療法の生存に寄与する因子の検討 多施設共同研究
  荘 拓也, 須田 剛生, 大原 正嗣, 中井 正人, 小川 浩司, 出水 孝章, 目黒 高志, 中村 晃久, 高木 智史, 馬場 英, 古家 乾, 山本 義也, 伊藤 淳, 山田 錬, 宮城島 拓人, 坂本 直哉
  日本消化器病学会雑誌, 120, 臨増大会, A813, A813, (一財)日本消化器病学会, Oct. 2023
  Japanese
• 【薬物療法によって変貌する肝細胞癌治療:2023 Update】Advanced stage肝細胞癌 Phase 3 HIMALAYA試験の結果とその解釈　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 北潟谷 隆, 大原 正嗣, 中井 正人, 小川 浩司, 坂本 直哉
  肝胆膵, 87, 4, 439, 446, (株)アークメディア, Oct. 2023
  Japanese
• IMbrave150基準外進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療効果と肝予備能変化　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 大原 正嗣, 中井 正人, 小川 浩司, 出水 孝章, 目黒 高志, 中村 晃久, 高木 智史, 馬場 英, 古家 乾, 鈴木 和治, 山本 義也, 伊藤 淳, 山田 錬, 宮城島 拓人, 坂本 直哉
  肝胆膵, 87, 4, 508, 509, (株)アークメディア, Oct. 2023
  Japanese
• Albumin-Bilirubin Grade Analyses of Atezolizumab plus Bevacizumab versus Sorafenib in Patients with Unresectable Hepatocellular Carcinoma: A Post Hoc Analysis of the Phase III IMbrave150 Study.
  Masatoshi Kudo, Richard S Finn, Ann-Lii Cheng, Andrew X Zhu, Michel Ducreux, Peter R Galle, Naoya Sakamoto, Naoya Kato, Michitaka Nakano, Jing Jia, Arndt Vogel
  Liver cancer, 12, 5, 479, 493, Oct. 2023, [International Magazine]
  English, Scientific journal, INTRODUCTION: Atezolizumab + bevacizumab showed survival benefit in patients with unresectable hepatocellular carcinoma (HCC) versus sorafenib in the Phase III IMbrave150 study. This exploratory analysis examined the prognostic impact of a baseline albumin-bilirubin (ALBI) score. METHODS: Patients with treatment-naïve unresectable HCC, ≥1 measurable untreated lesion, and Child-Pugh class A liver function were randomized 2:1 to receive atezolizumab 1,200 mg + bevacizumab 15 mg/kg every 3 weeks or sorafenib 400 mg twice daily. Overall survival (OS) and progression-free survival (PFS) were assessed in the intention-to-treat population by ALBI/modified (m)ALBI grade. Time to deterioration (TTD; defined as time to 0.5-point increase from the baseline ALBI score over 2 visits or death) of liver function and safety were investigated. RESULTS: Of 501 enrolled patients, 336 were randomized to receive atezolizumab + bevacizumab (ALBI grade [G] 1: n = 191; G2: n = 144 [mALBI G2a: n = 72, G2b: n = 72]; missing ALBI grade: n = 1) and 165 to sorafenib (ALBI G1: n = 87; G2: n = 78 [mALBI G2a: n = 37; G2b: n = 41]). Median follow-up was 15.6 months. OS and PFS improved with atezolizumab + bevacizumab versus sorafenib in patients with ALBI G1 (OS HR: 0.50 [95% CI: 0.35, 0.72]; PFS HR: 0.61 [95% CI: 0.45, 0.82]). In patients with ALBI G2 or mALBI G2a or G2b, PFS was numerically longer with atezolizumab + bevacizumab versus sorafenib, but no OS benefit was seen. Median TTD in the intention-to-treat population was 10.2 months (95% CI: 8.0, 11.0) with atezolizumab + bevacizumab versus 8.6 months (95% CI: 6.2, 11.8) with sorafenib (HR: 0.82 [95% CI: 0.65, 1.03]). Safety profiles of atezolizumab and bevacizumab were consistent with previous analyses, regardless of ALBI grade. CONCLUSION: ALBI grade appeared to be prognostic for outcomes with both atezolizumab + bevacizumab and sorafenib treatment in patients with HCC. Atezolizumab + bevacizumab preserved liver function for a numerically longer duration than sorafenib.
• 肝肺症候群を合併したBudd-Chiari症候群の1例　　　　　　　　　　　　　　　
  保浦 直弘, 目野 晃光, 甲谷 理紗子, 佐々木 貴志, 細田 峻一, 吉田 苑永, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 小川 浩司, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 133回・127回, 40, 40, 日本消化器病学会-北海道支部, Sep. 2023
  Japanese
• 腹腔鏡下横隔膜縫合術、腹腔静脈シャント術により体液コントロールされた肝硬変の1例　　　　　　　　　　　　　　　
  目野 晃光, 小川 浩司, 保浦 直弘, 甲谷 理紗子, 佐々木 貴志, 細田 峻一, 吉田 苑永, 得地 祐匡, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 坂本 直哉, 武藤 潤
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 133回・127回, 40, 40, 日本消化器病学会-北海道支部, Sep. 2023
  Japanese
• 消化器癌に対する免疫療法の現状と課題 非切除肝細胞癌患者における複合的がん免疫療法における治療後獲得薬剤耐性化に伴ってみられる血清増殖因子変化の検討　　　　　　　　　　　　　　　
  須田 剛生, 大原 正嗣, 坂本 直哉
  肝臓, 64, Suppl.2, A558, A558, (一社)日本肝臓学会, Sep. 2023
  Japanese
• 肝癌患者におけるマニュアルトレース法による筋肉量と皮下脂肪CT値評価の有用性の検討　　　　　　　　　　　　　　　
  大原 正嗣, 須田 剛生, 佐々木 貴志, 甲谷 理紗子, 細田 峻一, 吉田 苑永, 得地 祐匡, 中井 正人, 荘 拓也, 小川 浩司, 坂本 直哉
  肝臓, 64, Suppl.2, A644, A644, (一社)日本肝臓学会, Sep. 2023
  Japanese
• Metabolomics of Duodenal Juice for Biliary Tract Cancer Diagnosis
  Kazuma Kishi, Masaki Kuwatani, Yuki Ohnishi, Yasuhiro Kumaki, Hiroyuki Kumeta, Hajime Hirata, Yunosuke Takishin, Ryutaro Furukawa, Kosuke Nagai, Hiroki Yonemura, Shunichiro Nozawa, Ryo Sugiura, Kazumichi Kawakubo, Tomoyasu Aizawa, Naoya Sakamoto
  Cancers, 15, 17, 4370, 4370, MDPI AG, 01 Sep. 2023
  Scientific journal, The poor prognosis of malignant biliary diseases is partially caused by their difficult early diagnosis. Therefore, many patients are only diagnosed at advanced stages. This study aimed to improve diagnosis by clarifying the differences in the duodenal juice metabolomes of benign and malignant biliary diseases. From October 2021 to January 2023, duodenal juice was obtained from 67 patients with suspected biliary diseases who required endoscopic ultrasonography and endoscopic retrograde cholangiography for diagnosis/treatment. The samples metabolomes were analyzed via nuclear magnet resonance spectroscopy using an 800-MHz spectrometer. Metabolomes of malignant and benign diseases were then compared, and multivariate analysis was performed to determine the relevant factors for malignancy/benignancy. For benignancy, no significant predictors were observed. For malignancy, acetone was a significant predictor, with higher concentrations in the malignant group than in the benign group. Regarding the receiver operating characteristic curve analysis for biliary tract carcinoma diagnosis, the predictive value of acetone in duodenal juice was comparable with serum CA19-9 levels (area under the curve: 0.7330 vs. 0.691, p = 0.697). In conclusion, duodenal juice metabolomics is a feasible method that is available for differential diagnosis in the biliary disease field.
• Sequential therapies after atezolizumab plus bevacizumab or lenvatinib first-line treatments in hepatocellular carcinoma patients.
  Mara Persano, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Takashi Niizeki, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Bernardo Stefanini, Atsushi Hiraoka, Takuya Sho, Naoshi Nishida, Christoph Steup, Massimo Iavarone, Giovanni Di Costanzo, Fabio Marra, Emiliano Tamburini, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Claudia Campani, Elisabeth Amadeo, Federico Rossari, Valentina Burgio, Stefano Cascinu, Mario Scartozzi, Andrea Casadei-Gardini
  European journal of cancer (Oxford, England : 1990), 189, 112933, 112933, Aug. 2023, [International Magazine]
  English, Scientific journal, INTRODUCTION: The aim of this retrospective proof-of-concept study was to compare different second-line treatments for patients with hepatocellular carcinoma and progressive disease (PD) after first-line lenvatinib or atezolizumab plus bevacizumab. MATERIALS AND METHODS: A total of 1381 patients had PD at first-line therapy. 917 patients received lenvatinib as first-line treatment, and 464 patients atezolizumab plus bevacizumab as first-line. RESULTS: 49.6% of PD patients received a second-line therapy without any statistical difference in overall survival (OS) between lenvatinib (20.6months) and atezolizumab plus bevacizumab first-line (15.7months; p = 0.12; hazard ratio [HR]= 0.80). After lenvatinib first-line, there wasn't any statistical difference between second-line therapy subgroups (p = 0.27; sorafenib HR: 1; immunotherapy HR: 0.69; other therapies HR: 0.85). Patients who underwent trans-arterial chemo-embolization (TACE) had a significative longer OS than patients who received sorafenib (24.7 versus 15.8months, p < 0.01; HR=0.64). After atezolizumab plus bevacizumab first-line, there was a statistical difference between second-line therapy subgroups (p < 0.01; sorafenib HR: 1; lenvatinib HR: 0.50; cabozantinib HR: 1.29; other therapies HR: 0.54). Patients who received lenvatinib (17.0months) and those who underwent TACE (15.9months) had a significative longer OS than patients treated with sorafenib (14.2months; respectively, p = 0.01; HR=0.45, and p < 0.05; HR=0.46). CONCLUSION: Approximately half of patients receiving first-line lenvatinib or atezolizumab plus bevacizumab access second-line treatment. Our data suggest that in patients progressed to atezolizumab plus bevacizumab, the systemic therapy able to achieve the longest survival is lenvatinib, while in patients progressed to lenvatinib, the systemic therapy able to achieve the longest survival is immunotherapy.
• Promising Highly Targeted Therapies for Cholangiocarcinoma: A Review and Future Perspectives.
  Masaki Kuwatani, Naoya Sakamoto
  Cancers, 15, 14, 20 Jul. 2023, [International Magazine]
  English, Scientific journal, To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. Similarly, "staphylococcal enterotoxin A-MUC1 antibody" and "anti-GPC1 antibody-monomethyl auristatin F" conjugates showed anticancer activity. PDT is effective in areas where appropriate photosensitizers and light coexist. Its mechanism involves photosensitizer excitation and subsequent reactive oxygen species production in cancer cells upon irradiation. Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer. Currently, new forms of photosensitizers with nanotechnology and novel irradiation catheters are being developed. PIT is the most novel anti-cancer therapy developed in 2011 that selectively kills targeted cancer cells using a unique photosensitizer called "IR700" conjugated with an antibody specific for cancer cells. PIT is currently in the early stages of development for identifying appropriate CCA cell targets and irradiation devices. Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.
• Novel endoscopic management of gastroenterological anastomosis leakage by injecting gel-forming solutions: an experimental animal study.
  Yusuke Watanabe, Keiko Yamamoto, Zijian Yang, Haruna Tsuchibora, Masakazu Fujii, Masayoshi Ono, Shoko Ono, Takayuki Kurokawa, Naoya Sakamoto
  Surgical endoscopy, 19 Jul. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: Anastomotic leakage (AL) after gastrointestinal surgery remains a challenging complication that requires surgical or non-surgical treatment. Although various therapeutic endoscopic techniques are available, no definitive interventions exist. We developed a therapeutic endoscopic submucosal injection method using novel gel-forming mixed solutions to close AL and evaluated the elasticity of the developed hydrogel. The safety and efficacy of the injection method were explored in porcine AL models. METHODS: We developed a novel gel-forming solution, and the formed gel lasted approximately one week within the gastrointestinal wall. An indentation test evaluated the elasticity of the novel hydrogel. After the confirmation of AL on porcine anterior gastric walls, sodium alginate was endoscopically injected into the submucosal layer around the leakage site circularly, followed by a calcium lactate/chitosan-based solution. After that, the outcomes data were collected, and histopathological effectiveness was evaluated. RESULTS: The increased sodium alginate elasticity with the addition of calcium lactate/chitosan-based solution facilitated long-lasting gel formation. Four pigs with AL underwent this intervention consecutively. Each endoscopic injection was completed in less than 5 min. No significant complications were observed for 3 weeks after the intervention. All AL sites were macroscopically healed. Histopathologic findings at 3 weeks showed that the wall defect was filled with collagen fibers that had grown around the site of the muscle layer tear. No tissue necrosis was observed. CONCLUSION: This preclinical study demonstrated that the therapeutic injection method for gastroenterological AL using gel-forming solutions could be an alternative endoscopic treatment, especially in patients with severe conditions or comorbidities. The optimal target of this treatment is small size and early AL without poor blood flow or intense hypertrophic scar lesions.
• 【ウイルス性肝炎学2023-最新の病態・診断・治療情報-】B型肝炎 日本におけるB型肝炎の疫学 国際比較
  小川 浩司, 大原 正嗣, 坂本 直哉
  日本臨床, 81, 増刊7 ウイルス性肝炎学2023, 203, 208, (株)日本臨床社, Jul. 2023
  Japanese
• Neutrophil gelatinase-associated lipocalin predicts the efficacy of tolvaptan for ascites in patients with liver cirrhosis.
  Masato Nakai, Kenichi Morikawa, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Masatsugu Ohara, Takuya Sho, Goki Suda, Koji Ogawa, Naoya Sakamoto
  Journal of gastroenterology, 58, 7, 656, 667, Jul. 2023, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Acute kidney injury (AKI) is associated with liver cirrhosis (LC), water retention, diuretics to treat water retention, and a poor prognosis. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) reportedly predicts a poor prognosis in decompensated LC. This study investigated the usefulness of uNGAL in predicting the short- and long-term effects of tolvaptan (TVP) and the incidence of AKI post-TVP administration. METHODS: Of the LC cases with water retention, 86 with available pre-treatment uNGAL were analyzed. A short-term response was defined as weight loss of ≥ 1.5 kg within the first week; a long-term response was defined as a short-term response without early recurrence. The uNGAL usefulness in predicting the short- and long-term effects of TVP and AKI incidence post-TVP administration was investigated. RESULTS: Short-term effects of TVP were observed in 52 patients. Of these, 15 patients had an early recurrence. In multivariate analysis, significant short-term predictive factors were C-reactive protein (CRP) < 1.4 mg/dl, uNa/K ratio ≥ 3.51, and uNGAL < 50.2 ng/ml. Patients were classified according to these three cut-off values, with short-term response rates of 92.9%, 68.8%, 26.7%, and 0% for 0, 1, 2, and 3 points, respectively. CRP < 0.94 mg/dl and uNGAL < 50.2 ng/ml were significant factors for predicting the long-term response of TVP. The AKI incidence post-TVP was 8.1% (n = 7) and was significantly higher among those with uNGAL ≥ 38.1 ng/mL. CONCLUSION: uNGAL is a useful predictor of the short- and long-term efficacy of TVP and can be useful in predicting AKI incidence post-TVP administration.
• Potential Correlation between Changes in Serum FGF21 Levels and Lenvatinib-Induced Appetite Loss in Patients with Unresectable Hepatocellular Carcinoma.
  Risako Kohya, Goki Suda, Masatsugu Ohara, Takashi Sasaki, Tomoka Yoda, Naofumi Sakurai, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  Cancers, 15, 12, 20 Jun. 2023, [International Magazine]
  English, Scientific journal, Lenvatinib, used for unresectable hepatocellular carcinoma (HCC), causes appetite loss, but the underlying mechanisms, clinical impact, and predictive factors have been unclear. The endocrine factor FGF21 modulates appetite and is involved in cachexia. We evaluated the association between FGF21 level changes during lenvatinib treatment for unresectable HCC and appetite loss. Sixty-three eligible unresectable HCC patients who started lenvatinib treatment between 2018 and 2021 were included. We analyzed FGF21 levels at baseline; 1, 2, and 4 weeks after lenvatinib initiation, and before the onset of appetite loss. Grade ≥ 2 lenvatinib-induced appetite loss led to liver functional reserve deterioration at disease progression and a poor prognosis. Baseline characteristics and serum FGF21 levels were similar between patients with and without appetite loss. However, the serum FGF21 change rate increased significantly at 4 weeks post-lenvatinib initiation in patients with grade ≥ 2 appetite loss, as compared to those without appetite loss. Similar significant increases in the serum FGF21 level change rate were observed prior to grade ≥ 2 appetite loss onset. This suggests that changes in FGF21 levels can be used to predict patients with a greater risk of marked appetite loss and provides insights into the mechanisms underlying lenvatinib-induced appetite loss in patients with HCC.
• Recent prevalence and characteristics of patients with hepatitis delta virus in Hokkaido, Japan.
  Takashi Sasaki, Goki Suda, Masatsugu Ohara, Shunichi Hosoda, Naoki Kawagishi, Risako Kohya, Tomoka Yoda, Osamu Maehara, Shunsuke Ohnishi, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Sho Komukai, Koji Ogawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 18 Jun. 2023, [International Magazine]
  English, Scientific journal, AIM: Although hepatitis delta virus (HDV) coinfection with hepatitis B virus (HBV) is a global health concern, the global prevalence of HDV infections remains unknown due to insufficient data in many countries. In Japan, HDV prevalence has not been updated for over 20 years. We aimed to investigate the recent prevalence of HDV infections in Japan. METHODS: We screened 1264 consecutive patients with HBV infection at Hokkaido University Hospital between 2006 and 2022. Patients' serums were preserved and subsequently tested for HDV antibody (immunoglobulin-G). Available clinical information was collected and analyzed. We compared the changes in liver fibrosis using the Fibrosis-4 (FIB-4) index between propensity-matched patients with and without the evidence of anti-HDV antibodies and corrected for baseline FIB-4 index, nucleoside/nucleotide analog treatment, alcohol intake, sex, HIV coinfection, liver cirrhosis, and age. RESULTS: After excluding patients without properly stored serums and those lacking appropriate clinical information, 601 patients with HBV were included. Of these, 1.7% of patients had detectable anti-HDV antibodies. Patients with anti-HDV antibody serum positivity had a significantly higher prevalence of liver cirrhosis, significantly lower prothrombin time, and a higher prevalence of HIV coinfection than those who demonstrated serum anti-HDV antibody negativity. A propensity-matched longitudinal analysis revealed that liver fibrosis (FIB-4 index) progressed more rapidly in patients with positive results for anti-HDV antibody tests. CONCLUSIONS: The recent prevalence of HDV infections in Japanese patients with HBV was 1.7% (10/601). These patients experienced rapid liver fibrosis progression, highlighting the importance of routine HDV testing.
• 【超高齢社会における肝胆膵疾患診療】高齢者における肝硬変治療　　　　　　　　　　　　　　　
  中井 正人, 吉田 苑永, 坂本 直哉
  肝胆膵, 86, 6, 697, 702, (株)アークメディア, Jun. 2023
  Japanese
• 【肝疾患-診療のチェックポイント2023】(第I部)診断のチェックポイント(第5章) 肝疾患鑑別診断のチェックポイント 肝炎ウイルス以外のウイルス性肝障害が疑われるとき
  大原 正嗣, 須田 剛生, 坂本 直哉
  臨床消化器内科, 38, 7, 807, 811, (株)日本メディカルセンター, Jun. 2023
  Japanese
• 眼科外来への肝炎医療コーディネーターの配置による肝炎ウイルス陽性者対策の推進
  大原 正嗣, 小川 浩司, 長谷川 智子, 新明 康弘, 坂本 直哉, 是永 匡紹
  肝臓, 64, 6, 289, 291, (一社)日本肝臓学会, Jun. 2023
  Japanese, 当院肝疾患相談センターでは、院内非専門診療科での肝炎ウイルス陽性者(陽性者)の肝臓専門医(消化器内科)への紹介対策として、電子カルテアラートシステムによる陽性者対応を行っているが、アラートが通知された後に、必ずしも肝臓専門医への紹介や問診に至らず、未対応のままの患者が存在していることが判明した。そこで、院内非専門診療科で陽性者数が最も多かった眼科の外来看護師3名を肝炎医療コーディネーター(肝Co)として新たに養成・配置し、令和2年から要対応者には肝Coが個別対応を行っている。今回、肝Co配置前後(平成31年～令和3年)の眼科における陽性者数(B型肝炎ウイルス、C型肝炎ウイルス合算)、紹介率、要対応率の推移について検討、報告した。その結果、陽性者数は、39名(平成31年)、29名(令和2年)、30名(令和3年)で、紹介率は、肝Coの介入(肝Coが設置された令和2年は、平成31年まで遡って対応)により、アラート通知による平成31年の18.0%が25.6%まで改善し、以後、令和2年27.6%、令和3年26.7%と推移している。未対応者の指標となる要対応率については、アラート通知のみの28.2%(平成31年)、34.5%(令和2年)、20.0%(令和3年)が、肝Coの介入により2.6%(平成31年)、3.4%(令和2年)、6.7%(令和3年)と大幅に低下、改善した。
• Low Baseline CXCL9 Predicts Early Progressive Disease in Unresectable HCC with Atezolizumab Plus Bevacizumab Treatment.
  Shunichi Hosoda, Goki Suda, Takuya Sho, Koji Ogawa, Megumi Kimura, Zijian Yang, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto
  Liver cancer, 12, 2, 156, 170, Jun. 2023, [International Magazine]
  English, Scientific journal, INTRODUCTION: Atezolizumab plus bevacizumab treatment is highly effective in patients with unresectable hepatocellular carcinoma (HCC). However, progressive disease (PD) occurs in approximately 20% of HCC patients treated with atezolizumab plus bevacizumab, resulting in a poor prognosis. Thus, the prediction and early detection of HCC is crucial. METHODS: Patients with unresectable HCC treated with atezolizumab plus bevacizumab and had baseline preserved serum (n = 68) were screened and classified according to their PD, 6 weeks after treatment initiation (early PD; n = 13). Of these, 4 patients each with and without early PD were selected for cytokine array and genetic analyses. The identified factors were validated in the validated cohort (n = 60) and evaluated in patients treated with lenvatinib. RESULTS: No significant differences were observed in the genetic alterations in circulating tumor DNA. Cytokine array data revealed that baseline MIG (CXCL9), ENA-78, and RANTES differed substantially between patients with and without early PD. Subsequent analysis in the validation cohort revealed that baseline CXCL9 was significantly lower in patients with early PD than that in patients without early PD, and the best cut-off value of serum CXCL9 to predict early PD was 333 pg/mL (sensitivity: 0.600, specificity: 0.923, AUC = 0.75). In patients with lower serum CXCL9 (<333 pg/mL), 35.3% (12/34) experienced early PD with atezolizumab plus bevacizumab, while progression-free survival (PFS) was significantly shorter relative to that in patients without (median PFS, 126 days vs. 227 days; HR: 2.41, 95% CI: 1.22-4.80, p = 0.0084). While patients with objective response to lenvatinib had significantly lower CXCL9 levels compared with those of patients without. CONCLUSION: Baseline low serum CXCL9 (<333 pg/mL) levels may predict early PD in patients with unresectable HCC treated with atezolizumab plus bevacizumab.
• Significance of Shear Wave Dispersion Slope Values Before Versus After Biliary Drainage in Patients With Obstructive Jaundice
  Ryo Sugiura, Masaki Kuwatani, Mutsumi Nishida, Megumi Satoh, Kazumichi Kawakubo, Shin Kato, Koji Hirata, Masahito Nakajima, Hajime Hirata, Yunosuke Takishin, Naoya Sakamoto
  Ultrasound Quarterly, Publish Ahead of Print, Ovid Technologies (Wolters Kluwer Health), 22 May 2023
  Scientific journal
• Quantitative diagnostic algorithm using endocytoscopy for superficial nonampullary duodenal epithelial tumors.
  Marina Kubo, Shoko Ono, Isao Yokota, Shogo Matsumoto, Yusuke Nishimura, Masayoshi Ono, Keiko Yamamoto, Naoya Sakamoto
  Journal of gastroenterology and hepatology, 38, 9, 1496, 1502, 02 May 2023, [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Optical biopsy using endocytoscopy for superficial nonampullary duodenal epithelial tumors (SNADETs) is practical; however, a diagnostic algorithm has not been established. The aim of this study was to determine correlations of endocytoscopic findings of SNADETs with histology using computer analysis and to establish an algorithm. METHODS: Endocytoscopic images and histological images of duodenal lesions from 70 patients were retrospectively collected. The numbers of glands and densely stained areas with methylene blue (DSMs) per 1 mm2 and the percentage of DSMs per screen in endocytoscopy were determined. Moreover, correlations in DSMs and glands between endocytoscopy and histological images were analyzed. Histopathological diagnoses were assessed according to the revised Vienna classification. The primary outcome was correlation between the number of glands in endocytoscopy and that in histology. Finally, a diagnostic algorithm for endoscopic intervention of SNADETs with a statistical program command was established. RESULTS: The number of glands in endocytoscopic images was correlated with that in histopathological images (ρ 0.64, P < 0.001). There were significant differences in the mean number of glands between category 4/5 and category 3 (P = 0.03) and the mean percentage of DSMs between category 4/5 and category 1 (P < 0.001). When the cutoffs for the number of glands and percentage of DSMs were set at 47 per 1 mm2 and 20.8% in one screen, respectively, the area under the ROC curve was 0.89. CONCLUSIONS: Endocytoscopic images of SNADETs reflect histopathological atypia, and computer analysis provides a practical diagnostic algorithm for endoscopic intervention.
• Improvement of detection sensitivity of upper gastrointestinal epithelial neoplasia in linked color imaging based on data of eye tracking.
  Masayuki Higashino, Shoko Ono, Shogo Matsumoto, Marina Kubo, Naohiro Yasuura, Shuhei Hayasaka, Ikko Tanaka, Yoshihiko Shimoda, Yusuke Nishimura, Masayoshi Ono, Keiko Yamamoto, Yuji Ono, Naoya Sakamoto
  Journal of gastroenterology and hepatology, 38, 5, 710, 715, May 2023, [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Linked color imaging (LCI) is useful for screening in the gastrointestinal tract; however, its true clinical benefit has not been determined. The aim of this study was to determine the objective advantage of LCI for detection of upper gastrointestinal neoplasms. METHODS: Nine endoscopists, including three novices, three trainees, and three experts, prospectively performed eye tracking. From 30 cases of esophageal or gastric neoplasm and 30 normal cases without neoplasms, a total of 120 images, including 60 pair images of white light imaging (WLI) and LCI taken at the same positions and angles, were randomly shown for 10 s. The sensitivity of tumor detection as a primary endpoint was evaluated and sensitivities by organ, size, and visual gaze pattern were also assessed. Color differences (ΔE using CIE1976 [L*a*b*]) between lesions and surrounding mucosa were measured and compared with detectability. RESULTS: A total of 1080 experiments were completed. The sensitivities of tumor detection in WLI and LCI were 53.7% (50.1-56.8%) and 68.1% (64.8-70.8%), respectively (P = 0.002). LCI provided higher sensitivity than WLI for the novice and trainee groups (novice: 42.2% [WLI] vs 65.6% [LCI], P = 0.003; trainee: 54.4% vs 70.0%, P = 0.045). No significant correlations were found between sensitivity and visual gaze patterns. LCI significantly increased ΔE, and the diagnostic accuracy with WLI depended on ΔE. CONCLUSIONS: In conclusion, LCI significantly improved sensitivity in the detection of epithelial neoplasia and enabled epithelial neoplasia detection that is not possible with the small color difference in WLI. (UMIN000047944).
• 肝疾患におけるサルコペニア診断と栄養・運動介入の課題 マニュアルトレース法による筋肉量評価及び皮下脂肪CT値と肝疾患患者の予後の検討　　　　　　　　　　　　　　　
  大原 正嗣, 須田 剛生, 坂本 直哉
  肝臓, 64, Suppl.1, A231, A231, (一社)日本肝臓学会, Apr. 2023
  Japanese
• A病院における肝炎検査陽性者拾い上げの取り組み 眼科・整形外科外来との協働　　　　　　　　　　　　　　　
  長谷川 智子, 小川 浩司, 大原 正嗣, 櫻井 菜々子, 中野 政子, 坂本 直哉
  肝臓, 64, Suppl.1, A281, A281, (一社)日本肝臓学会, Apr. 2023
  Japanese
• Clinical significance of dispersion imaging by shear wave elastography in the treatment and diagnosis of pancreatic cancer.
  Yunosuke Takishin, Masaki Kuwatani, Mutsumi Nishida, Tomoko Mitsuhashi, Kazuma Kishi, Kosuke Nagai, Ryutaro Furukawa, Hajime Hirata, Koji Hirata, Shin Kato, Kazumichi Kawakubo, Naoya Sakamoto
  Journal of gastroenterology and hepatology, 38, 4, 656, 663, Apr. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Recently, dispersion imaging by shear wave elastography has been developed to visualize a tissue viscosity-related factor by measuring the dispersion slope. However, clinical significance of dispersion imaging in the field of pancreatic cancer is unknown. This study aimed to investigate the clinical significance of dispersion imaging in the treatment and diagnosis of pancreatic cancer. METHODS: We measured shear wave dispersion slope (SWD) (m/s/kHz) and shear wave elasticity (SWE) (kPa) in patients with pancreatic ductal adenocarcinoma (PDA). The primary endpoint was the relationship between the changes in SWD and SWE values before and after chemotherapy and the response to chemotherapy. Secondary endpoints included SWD and SWE values in relation to differences between PDA and non-PDA sites and histopathological scores of stroma, inflammation, fibrosis, and necrosis in endoscopic ultrasound-guided fine-needle aspiration specimens. RESULTS: Fifty-six patients were included, 30 of whom underwent chemotherapy. There was no relationship between the changes of SWD and SWE values and chemotherapy responses. In 56 patients, the median SWD value was 12.20 m/s/kHz (interquartile range [IQR]: 10.88-13.61) at PDA sites and 13.57 m/s/kHz (IQR: 12.28-16.20) at non-PDA sites (P = 0.005). The median SWE value was 8.18 kPa (IQR: 7.00-9.74) at PDA sites and 6.14 kPa (IQR: 5.40-6.77) at non-PDA sites (P < 0.001). Histopathological evaluation revealed that inflammation scores were correlated with SWD values (rs  = 0.42, P < 0.001). CONCLUSIONS: Dispersion imaging in pancreatic cancer would be useful for diagnosis and assessing inflammation.
• Effects of activation of an alcohol metabolic gene, cigarette smoking, and alcohol intake on the incidence of metachronous gastric cancer in patients who underwent endoscopic resection for gastric cancer: A multicenter retrospective pilot study
  Satoshi Abiko, Yuichi Shimizu, Marin Ishikawa, Masaki Inoue, Katsuma Nakajima, Risako Kohya, Koji Hirata, Kazuharu Suzuki, Ryo Sugiura, Shuichi Miyamoto, Kenji Kinoshita, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Takuto Miyagishima, Naoya Sakamoto
  JGH Open, Wiley, 31 Mar. 2023
  Scientific journal
• Survival outcomes from atezolizumab plus bevacizumab versus Lenvatinib in Child Pugh B unresectable hepatocellular carcinoma patients.
  Margherita Rimini, Mara Persano, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Francesca Salani, Sara Lonardi, Fabio Piscaglia, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Marta Schirripa, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini
  Journal of cancer research and clinical oncology, 149, 10, 7565, 7577, 28 Mar. 2023, [Peer-reviewed], [International Magazine]
  English, Scientific journal, INTRODUCTION: The best first-line treatment for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class B remains unknown. The aim of the present study was to perform a real-world analysis on a large sample of patients with unresectable HCC with CP B treated with atezolizumab plus bevacizumab Vs Lenvatinib. METHODS: The study population included patients affected by advanced (BCLC-C) or intermediate (BCLC-B) HCC patients not suitable for locoregional therapies from both the Western and Eastern world (Italy, Germany, Republic of Korea and Japan), who received atezolizumab plus bevacizumab or Lenvatinib as first-line treatment. All the study population presented a CP class of B. The primary endpoint of the study was the overall survival (OS) of CP B patients treated with Lenvatinib compared to atezolizumab plus bevacizumab. Survival curves were estimated using the product-limit method of Kaplan-Meier. The role of stratification factors was analyzed with log-rank tests. Finally, an interaction test was performed for the main baseline clinical characteristics. RESULTS: 217 CP B HCC patients were enrolled in the study: 65 (30%) received atezolizumab plus bevacizumab, and 152 (70%) received lenvatinib. The mOS for patients receiving Lenvatinib was 13.8 months (95% CI: 11.6-16.0), compared to 8.2 months (95% CI 6.3-10.2) for patients receiving atezolizumab plus bevacizumab as first-line treatment (atezolizumab plus bevacizumab Vs Lenvatinib: HR 1.9, 95% CI 1.2-3.0, p = 0.0050). No statistically significant differences were highlighted in terms of mPFS. The multivariate analysis confirmed that patients receiving Lenvatinib as first-line treatment have a significantly longer OS compared to patients receiving atezolizumab plus bevacizumab (HR 2.01; 95% CI 1.29-3.25, p = 0.0023). By evaluating the cohort of patients who received atezolizumab plus bevacizumab, we found that Child B patients with ECOG PS 0, or BCLC B stage or ALBI grade 1 were those who had benefited from the treatment thus showing survival outcomes no significantly different compared to those receiving Lenvatinib. CONCLUSION: The present study suggests for the first time a major benefit from Lenvatinib compared to atezolizumab plus bevacizumab in a large cohort of patients with CP B class HCC.
• Hepatitis C virus eradication by direct-acting antivirals causes a simultaneous increase in the prevalence of fatty liver and hyper low-density lipoprotein cholesterolemia without an increase in body weight.
  Yoshimasa Tokuchi, Goki Suda, Naoki Kawagishi, Masatsugu Ohara, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Osamu Maehara, Shunsuke Ohnishi, Akinori Kubo, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Takashi Kitagataya, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 53, 7, 595, 606, 21 Mar. 2023, [International Magazine]
  English, Scientific journal, AIM: Hepatitis C virus (HCV) infection has been reported to cause liver steatosis. Thus, eradicating HCV with direct-acting antivirals (DAAs) is expected to reduce liver steatosis. We aimed to clarify long-term changes in the prevalence of fatty liver and hyper-low-density lipoprotein (LDL) cholesterolemia and their associations in patients who achieve successful HCV eradication using DAAs. METHODS: This retrospective study included patients with HCV who achieved sustained virologic response after interferon-free DAA and analyzed the changes in the prevalence of fatty liver diagnosed with controlled attenuation parameter (CAP), hyper-LDL cholesterolemia, and their relationships at baseline (n = 100) and 24 weeks (SVR24, n = 100), 96 weeks (SVR96, n = 100), and 144 weeks (SVR144, n = 90) after DAA. RESULTS: In 100 participants, the prevalence of fatty liver (19% vs. 32%, p = 0.0349) and hyper-LDL cholesterolemia (6% vs. 15%, p = 0.0379) significantly increased without changes in body weight at SVR96. Median total cholesterol, low-density lipoprotein cholesterol (LDL-C), and small-dense-LDL (sdLDL) levels and CAP values were significantly greater at SVR24, SVR96, and SVR144 than at baseline. Baseline CAP values and changes in CAP values were significantly negatively correlated at every observation point: r = -0.5305, p < 0.0001 at SVR24; r = -0.3617, p = 0.0005 at SVR96; and r = -0.4735, p < 0.0001 at SVR144. A similar relationship was observed in cholesterol levels. Unlike at baseline, CAP values were significantly positively correlated with LDL-C and sdLDL-C levels at all observation points after DAAs. CONCLUSIONS: Direct-acting antivirals may cause an increased prevalence of fatty liver accompanying hyper-LDL cholesterolemia without increased body weight. As post-SVR liver steatosis could cause HCC, careful follow-up may be required.
• Real-World Data for Atezolizumab Plus Bevacizumab in Unresectable Hepatocellular Carcinoma: How Does Adherence to the IMbrave150 Trial Inclusion Criteria Impact Prognosis?
  Margherita Rimini, Mara Persano, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Fabio Piscaglia, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Lorenza Rimassa, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini
  Targeted oncology, 18, 2, 221, 233, 15 Mar. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: Atezolizumab plus bevacizumab has recently been approved as a new first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). OBJECTIVE: We performed a real-world study to evaluate the impact of the IMbrave150 trial inclusion criteria on the safety and efficacy of treatment outside of clinical trials. METHODS: We analyzed patients treated with atezolizumab plus bevacizumab for unresectable HCC from four different countries. No specific inclusion and exclusion criteria were applied, except for the absence of previous systemic therapies for HCC. The entire population was split into two groups according to concordance with the inclusion criteria as reported in the IMbrave150 trial in 'IMbrave150-in' and 'IMbrave150-out' patients, and safety and efficacy in the two groups of patients were evaluated. RESULTS: Overall, 766 patients were included in the analysis: 561/766 (73%) in the 'IMbrave150-in' group and 205/766 (27%) in the 'IMbrave150-out' group. Median overall survival (OS) and median progression-free survival (PFS) were 16.3 versus 14.3 months (hazard ratio [HR] 0.48, 95% confidence interval [CI] 0.35-0.65; p < 0.0001] and 8.3 versus 6.0 months (HR 0.79, 95% CI 0.63-0.99; p = 0.0431) in 'IMbrave150-in' and 'IMbrave150-out' patients, respectively. Multivariate analysis confirmed that patients included in the 'IMbrave150-in' group had significantly longer OS compared with patients included in the 'IMbrave150-out' group (HR 0.76, 95% CI 0.47-0.97; p = 0.0195). In 'IMbrave150-in' patients, the albumin-bilirubin (ALBI) grade was not associated with OS, whereas in 'IMbrave150-out' patients, those with ALBI grade 1 reported a significant benefit in terms of OS compared with those with ALBI grade 2 (16.7 vs. 5.9 months; HR 4.40, 95% CI 2.40-8.08; p > 0.0001). No statistically significant differences were reported in the 'IMbrave150-in' and 'IMbrave150-out' groups in terms of safety profile. CONCLUSION: Adherence to the IMbrave150 trial inclusion criteria favorably impacts the prognosis of patients receiving atezolizumab plus bevacizumab. Among patients who did not meet the IMbrave150 inclusion criteria, those with ALBI grade 1 could benefit from the treatment.
• 肝細胞腺腫との鑑別が困難であった限局性結節性過形成の1例　　　　　　　　　　　　　　　
  吉田 苑永, 小川 浩司, 佐々木 貴志, 甲谷 理紗子, 細田 峻一, 久保 彰則, 得地 祐匡, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 132回・126回, 42, 42, 日本消化器病学会-北海道支部, Mar. 2023
  Japanese
• BCLCステージB2肝癌に対してアテゾリズマブ+ベバシズマブ併用療法と焼灼療法にてCancer Freeが得られた1症例　　　　　　　　　　　　　　　
  細田 峻一, 荘 拓也, 佐々木 貴志, 甲谷 理紗子, 吉田 苑永, 得地 祐匡, 大原 正嗣, 中井 正人, 須田 剛生, 小川 浩司, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 132回・126回, 46, 46, 日本消化器病学会-北海道支部, Mar. 2023
  Japanese
• BavenoVI分類とYerdel分類を用いた肝疾患に伴う門脈血栓症に対するアンチトロンビンIII製剤の治療効果の検討
  中井 正人, 小川 浩司, 佐々木 貴志, 甲谷 理紗子, 吉田 苑永, 細田 俊一, 得地 祐匡, 北潟谷 隆, 大原 正嗣, 荘 拓也, 須田 剛生, 坂本 直哉
  日本消化器病学会雑誌, 120, 臨増総会, A417, A417, (一財)日本消化器病学会, Mar. 2023
  Japanese
• Prediction Model with HLA-A*33:03 Reveals Number of Days to Develop Liver Cancer from Blood Test.
  Nao Nishida, Jun Ohashi, Goki Suda, Takehiro Chiyoda, Nobuharu Tamaki, Takahiro Tomiyama, Sachiko Ogasawara, Masaya Sugiyama, Yosuke Kawai, Seik-Soon Khor, Masao Nagasaki, Akihiro Fujimoto, Takayo Tsuchiura, Miyuki Ishikawa, Koichi Matsuda, Hirohisa Yano, Tomoharu Yoshizumi, Namiki Izumi, Kiyoshi Hasegawa, Naoya Sakamoto, Masashi Mizokami, Katsushi Tokunaga
  International journal of molecular sciences, 24, 5, 01 Mar. 2023, [International Magazine]
  English, Scientific journal, The development of liver cancer in patients with hepatitis B is a major problem, and several models have been reported to predict the development of liver cancer. However, no predictive model involving human genetic factors has been reported to date. For the items incorporated in the prediction model reported so far, we selected items that were significant in predicting liver carcinogenesis in Japanese patients with hepatitis B and constructed a prediction model of liver carcinogenesis by the Cox proportional hazard model with the addition of Human Leukocyte Antigen (HLA) genotypes. The model, which included four items-sex, age at the time of examination, alpha-fetoprotein level (log10AFP) and presence or absence of HLA-A*33:03-revealed an area under the receiver operating characteristic curve (AUROC) of 0.862 for HCC prediction within 1 year and an AUROC of 0.863 within 3 years. A 1000 repeated validation test resulted in a C-index of 0.75 or higher, or sensitivity of 0.70 or higher, indicating that this predictive model can distinguish those at high risk of developing liver cancer within a few years with high accuracy. The prediction model constructed in this study, which can distinguish between chronic hepatitis B patients who develop hepatocellular carcinoma (HCC) early and those who develop HCC late or not, is clinically meaningful.
• Novel usage of one nasobiliary drainage tube for cholecystitis with cholangitis from external to internal drainage.
  Kazuma Kishi, Masaki Kuwatani, Naoya Sakamoto
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 20 Feb. 2023, [International Magazine]
  English, Scientific journal
• Correlation of UGT1A1 Gene Polymorphisms or Prior Irinotecan Treatment and Treatment Outcomes of Nanoliposomal-Irinotecan plus 5-Fluorouracil/Leucovorin for Pancreatic Ductal Adenocarcinoma: A Multicenter, Retrospective Cohort Study (HGCSG2101).
  Kazuaki Harada, Takahiro Yamamura, Osamu Muto, Michio Nakamura, Susumu Sogabe, Kentaro Sawada, Shintaro Nakano, Masataka Yagisawa, Tetsuhito Muranaka, Masayoshi Dazai, Miki Tateyama, Yoshimitsu Kobayashi, Sosuke Kato, Kazuteru Hatanaka, Yasuyuki Kawamoto, Satoshi Yuki, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
  Journal of clinical medicine, 12, 4, 17 Feb. 2023, [International Magazine]
  English, Scientific journal, The effects of UGT1A1 gene polymorphisms or prior irinotecan treatment on treatment outcomes of nanoliposomal-irinotecan plus 5-fluorouracil/leucovorin (nal-IRI+5-FU/LV) in patients with unresectable pancreatic ductal adenocarcinoma (PDAC) are not established. This multicenter, retrospective cohort study compared treatment outcomes in patients with UGT1A1*1/*1 and those with UGT1A1*1/*6 or *1/*28 genotypes. We also analyzed the impact of prior irinotecan treatment on survival outcomes in 54 patients treated with nal-IRI+5-FU/LV. Comparable effectiveness was found regardless of the UGT1A1 genotypes. While no significant differences were found, grade ≥3 neutropenia and febrile neutropenia were more frequent in patients with UGT1A1*1/*6 or *1/*28 than in those with UGT1A1*1/*1 genotypes (grade ≥3 neutropenia, 50.0% vs. 30.8%, p = 0.24; febrile neutropenia, 9.1% vs. 0.0%, p = 0.20, respectively). No significant difference in progression-free survival (PFS) and overall survival (OS) was observed between irinotecan-naïve-patients and other patients. However, irinotecan-resistant patients showed significantly shorter PFS (hazard ratio (HR) 2.83, p = 0.017) and OS (HR 2.58, p = 0.033) than other patients. Our study indicated that patients with UGT1A1*1/*6 or *1/*28 may be prone to neutropenia, though further study is needed. The survival benefit of nal-IRI+5-FU/LV could be maintained in patients without disease progression after irinotecan therapy.
• Changes in Serum Growth Factors during Resistance to Atezolizumab Plus Bevacizumab Treatment in Patients with Unresectable Hepatocellular Carcinoma.
  Zijian Yang, Goki Suda, Osamu Maehara, Masatsugu Ohara, Tomoka Yoda, Takashi Sasaki, Risako Kohya, Sonoe Yoshida, Shunichi Hosoda, Yoshimasa Tokuchi, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  Cancers, 15, 3, 18 Jan. 2023, [International Magazine]
  English, Scientific journal, The possible mechanisms of resistance to atezolizumab/bevacizumab for unresectable HCC, and the subsequent response to these therapies, remain underexplored. The sequential changes in serum growth factors, including VEGF-A, VEGF-C, VEGF-D, ANG-2, FGF-19, HGF, and EGF during atezolizumab/bevacizumab for unresectable HCC were evaluated in 46 patients. Patients who experienced PD after CR, PR, or SD to atezolizumab/bevacizumab were evaluated. A total of 4, 9, 19, and 14 patients showed CR, PR, SD, and PD, respectively. Of 32 patients with disease control, 28 experienced PD after CR, PR, or SD with atezolizumab/bevacizumab. Baseline growth factor levels were similar between patients with or without disease control and those with or without an objective response. Growth factor changes between the baseline and the best overall response points (BOR) for patients with disease control showed that FGF-19 significantly increased and ANG2 significantly decreased at the BOR. Growth factor changes between the BOR and the PD point in 28 patients who experienced PD after disease control showed that VEGF-D and ANG2 significantly increased at the PD point compared with that at the BOR. Summarily, increased serum VEGF-D and ANG-2 levels might contribute to developing resistance to atezolizumab/bevacizumab for unresectable HCC and might be target molecules in subsequent salvage therapies.
• Serum Angiopoietin-2 Predicts the Occurrence and Recurrence of Hepatocellular Carcinoma after Direct-Acting Antiviral Therapy for Hepatitis C.
  Naoki Kawagishi, Goki Suda, Yoshiya Yamamoto, Masaru Baba, Ken Furuya, Osamu Maehara, Shunsuke Ohnishi, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Yoshimasa Tokuchi, Takashi Kitagataya, Masatsugu Ohara, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  Viruses, 15, 1, 07 Jan. 2023, [International Magazine]
  English, Scientific journal, Progressive liver fibrosis after anti-HCV treatment is a risk factor for HCC. Angiopoietin-2 (Ang2) is associated with non-regression of liver fibrosis after direct-acting antiviral (DAA). This study evaluated the predictive value of serum Ang2 levels for HCC occurrence or recurrence after DAA administration. In this retrospective study, 310 HCV-infected patients treated with DAAs in 2014-2020 were screened and evaluated for HCC occurrence or recurrence every three-six months. Multivariate Cox regression analysis revealed that age ≥ 75 years (HR: 2.92, 95% CI: 1.34-6.33; p = 0.007) and baseline Ang2 level ≥ 464 pg/mL (HR: 2.75, 95% CI: 1.18-6.37; p = 0.019) were significantly associated with HCC occurrence after DAA therapy. A high or low risk of HCC after DAA therapy could be distinguished by the combination of age and baseline Ang2 level. The cumulative incidences of de-novo HCC at two and four years were 0.8% and 3.8% in the low-risk group and 22.6% and 27.1% in the high-risk group, respectively. Baseline Ang2 level ≥ 402 pg/mL was significantly associated with HCC recurrence in patients who achieved sustained virological response with DAAs (HR: 3.68). In conclusion, serum Ang2 levels can predict HCC occurrence and recurrence after successful HCV eradication by DAAs.
• Prophylactic tenofovir alafenamide for hepatitis B virus reactivation and reactivation-related hepatitis.
  Goki Suda, Masaru Baba, Yoshiya Yamamoto, Takuya Sho, Koji Ogawa, Megumi Kimura, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Qingjie Fu, Zijian Yang, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Tomoe Kobayashi, Izumi Tsunematsu, Naoya Sakamoto
  Journal of medical virology, 95, 2, e28452, 04 Jan. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND: No prospective study on the efficacy of tenofovir alafenamide (TAF), a novel tenofovir prodrug, in preventing HBV reactivation has yet been reported. METHODS: This multicenter prospective study enrolled HBV-carriers who received TAF to prevent HBV reactivation before antitumor or immunosuppressive therapy, and patients with resolved HBV infection who experienced HBV-reactivation and received TAF to prevent HBV reactivation-related hepatitis. The efficacy of prophylactic TAF in preventing HBV reactivation and HBV reactivation-related hepatitis was evaluated at 6 and 12 months after initiating TAF. RESULTS: Overall, 110 patients were administered TAF to prevent HBV reactivation or HBV reactivation-related hepatitis. Three patients died owing to primary disease, whereas one patient was transferred to another hospital within 6 months after initiating TAF. Seven patients died due to primary disease, and five patients were transferred to another hospital within 12 months after initiating TAF. Therefore, 106 and 94 (77 patients with HBV infection, 17 with previous-HBV infection) patients were evaluated at 6 and 12 months after initiating TAF, respectively. No patient experienced HBV reactivation, HBV reactivation-related hepatitis, or treatment discontinuation due to HBV reactivation or adverse events of TAF after 6 and 12 months. CONCLUSION: TAF could effectively prevent HBV reactivation and HBV reactivation-related hepatitis. This article is protected by copyright. All rights reserved.
• Anti-epidermal growth factor receptor treatment for patients with NeoRAS wild-type metastatic colorectal cancer: a case report of two cases.
  Kazuaki Harada, Satoshi Yuki, Yasuyuki Kawamoto, Takeaki Nakamura, Shiho Kaneko, Koichi Ishida, Naoya Sakamoto, Yoshito Komatsu
  Therapeutic advances in medical oncology, 15, 17588359231216090, 17588359231216090, 2023, [International Magazine]
  English, The NeoRAS phenomenon is defined as the conversion of tumor RAS status from mutant-type (MT) to wild-type (WT) after systemic chemotherapy in metastatic colorectal cancer (mCRC). Cetuximab, an anti-epidermal growth factor receptor (EGFR) antibody, is effective in patients with RAS WT mCRC but ineffective in those with RAS MT mCRC; however, its outcome in patients with NeoRAS WT mCRC is unclear. Herein, we report two cases of NeoRAS WT mCRC that responded clinically to anti-EGFR treatment. The first was a 40-year-old man with synchronous peritoneal metastatic rectosigmoid cancer. The first RAS testing on tumor tissue revealed a KRAS G12C mutation, which was converted to RAS WT after two lines of chemotherapy, as assessed by liquid biopsy. After initiating irinotecan plus cetuximab treatment, a computed tomography (CT) scan revealed that malignant ascites had resolved. The treatment was discontinued after 4 months because of disease progression. The second was a 68-year-old male patient with synchronous liver metastasis from sigmoid colon cancer. The KRAS G12D mutation, initially detected in tumor tissue, was not detected by liquid biopsy after six lines of chemotherapy. Cetuximab monotherapy was initiated, and the liver metastases shrank significantly. The patient continued cetuximab monotherapy for 8 months without disease progression. Our cases demonstrate the efficacy of anti-EGFR therapy for NeoRAS WT mCRC and highlight the importance of capturing the gene mutation profile throughout the clinical course for optimal treatment selection.
• Characteristics and usefulness of transabdominal ultrasonography in immune-mediated colitis.
  Kensuke Sakurai, Takehiko Katsurada, Mutsumi Nishida, Satomi Omotehara, Shinya Fukushima, Shinsuke Otagiri, Kazunori Nagashima, Reizo Onishi, Ryo Takagi, Yoshito Komatsu, Naoya Sakamoto
  Intestinal research, 21, 1, 126, 136, Jan. 2023, [International Magazine]
  English, Scientific journal, BACKGROUND/AIMS: The usefulness of ultrasonography (US) in diseases of the gastrointestinal tract has been reported recently. This prospective study aimed to determine the features of US findings in immune-mediated colitis (IMC), an adverse event induced by immune checkpoint inhibitor, and examine the correlation between US findings, colonoscopy (CS) findings, and severity of colitis. METHODS: We studied patients examined using CS and US upon suspicion of IMC in Hokkaido University Hospital between April 2018 and February 2021. Endoscopic findings of IMC were assessed using the Ulcerative Colitis Endoscopic Index of Severity (UCEIS). The severity of US findings in IMC was evaluated using US grade, which is the ultrasonographic grading scale in ulcerative colitis. Bowel wall thickness and the intensity of the color Doppler signal were also analyzed. Severity of colitis was evaluated using Common Terminology Criteria for Adverse Events (CTCAE) grade version 5. RESULTS: Fourteen patients with IMC were enrolled. The US findings were bowel wall thickening, loss of stratification, ulceration and increased blood flow signal. The US grade was moderately correlated with the UCEIS (r=0.687, p=0.009) and CTCAE grade (r=0.628, p=0.035). Bowel wall thickness and UCEIS (r=0.628, p=0.020), as well as color Doppler signal grade and CTCAE grade (r=0.724, p=0.008), were significantly correlated. CONCLUSIONS: US findings in IMC were mainly similar to those of ulcerative colitis, but there were some findings that were characteristic only of IMC. Significant correlation was found between US findings, CS findings, and severity of colitis. Hence, US could be useful for the evaluation of IMC.
• Coexistence of muscle atrophy and high subcutaneous adipose tissue radiodensity predicts poor prognosis in hepatocellular carcinoma.
  Masatsugu Ohara, Goki Suda, Risako Kohya, Takashi Sasaki, Tomoka Yoda, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Osamu Maehara, Shunsuke Ohnishi, Yoshimasa Tokuchi, Takashi Kitagataya, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  Frontiers in nutrition, 10, 1272728, 1272728, 2023, [International Magazine]
  English, Scientific journal, INTRODUCTION: We aimed to assess the prognostic implications of muscle atrophy and high subcutaneous adipose tissue (SAT) radiodensity in patients with hepatocellular carcinoma (HCC). METHODS: In this retrospective study, muscle atrophy was assessed using the psoas muscle index (PMI) obtained from computed tomography. SAT radiodensity was evaluated based on radiodensity measurements. Survival and multivariate analyses were performed to identify factors associated with prognosis. The impact of muscle atrophy and high SAT radiodensity on prognosis was determined through survival analysis. RESULTS: A total of 201 patients (median age: 71 years; 76.6% male) with HCC were included. Liver cirrhosis was observed in 72.6% of patients, and the predominant Child-Pugh grade was A (77.1%). A total of 33.3% of patients exhibited muscle atrophy based on PMI values, whereas 12.9% had high SAT radiodensity. Kaplan-Meier survival analysis demonstrated that patients with muscle atrophy had significantly poorer prognosis than those without muscle atrophy. Patients with high SAT radiodensity had a significantly worse prognosis than those without it. Muscle atrophy, high SAT radiodensity, the Barcelona Clinic Liver Cancer class B, C, or D, and Child-Pugh score ≥ 6 were significantly associated with overall survival. Further classification of patients into four groups based on the presence or absence of muscle atrophy and high SAT radiodensity revealed that patients with both muscle atrophy and high SAT radiodensity had the poorest prognosis. CONCLUSION: Muscle atrophy and high SAT radiodensity are significantly associated with poor prognosis in patients with HCC. Identifying this high-risk subgroup may facilitate the implementation of targeted interventions, including nutritional therapy and exercise, to potentially improve clinical outcomes.
• Simultaneous determination of heparan sulfate, chondroitin/dermatan sulfates, and hyaluronan glycosaminoglycan disaccharides by high-performance liquid chromatography using a reverse-phase column with adamantyl groups.
  Hisatoshi Hanamatsu, Satoshi Makino, Masatsugu Ohara, Goki Suda, Ikuko Yokota, Shoko Nishihara, Naoya Sakamoto, Jun-Ichi Furukawa
  Journal of chromatography. A, 1689, 463748, 463748, 23 Dec. 2022, [International Magazine]
  English, Scientific journal, Glycosaminoglycans (GAGs), which are one of the major components of proteoglycans, play a pivotal role in physiological processes such as signal transduction, cell adhesion, growth, and differentiation. Characterization of GAGs is challenging due to the tremendous structural diversity of heteropolysaccharides with numerous sulfate or carboxyl groups. In this present study, we examined the analysis of 2-aminobenzamide (2-AB) labeled GAG disaccharides by high-performance liquid chromatography (HPLC) using a reverse-phase (RP)-column with adamantyl groups. Under the analytical conditions, 17 types of 2-AB labeled GAG disaccharides derived from heparan sulfate, chondroitin/dermatan sulfates, and hyaluronan were sequentially separated in a single analysis. The analysis time was fast with high retention time reproducibility. Moreover, the RP-HPLC column with adamantyl groups allowed the quantification of GAGs in various biological samples, such as serum, cultured cells, and culture medium.
• Clinical outcomes with atezolizumab plus bevacizumab or lenvatinib in patients with hepatocellular carcinoma: a multicenter real-world study.
  Mara Persano, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, Lorenza Rimassa, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Takumi Kawaguchi, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Fabio Piscaglia, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Massimo Iavarone, Giovanni Di Costanzo, Fabio Marra, Mario Scartozzi, Emiliano Tamburini, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Antonella Cammarota, Valentina Burgio, Stefano Cascinu, Andrea Casadei-Gardini
  Journal of cancer research and clinical oncology, 13 Dec. 2022, [International Magazine]
  English, Scientific journal, PURPOSE: The purpose of this study is to compare response rates of lenvatinib and atezolizumab plus bevacizumab, in first-line real-world setting. METHODS: Overall cohort included Western and Eastern hepatocellular carcinoma (HCC) patient populations from 46 centres in 4 countries (Italy, Germany, Japan, and Republic of Korea). RESULTS: 1312 patients were treated with lenvatinib, and 823 patients were treated with atezolizumab plus bevacizumab. Objective response rate (ORR) was 38.6% for patients receiving lenvatinib, and 27.3% for patients receiving atezolizumab plus bevacizumab (p < 0.01; odds ratio 0.60). For patients who achieved complete response (CR), overall survival (OS) was not reached in both arms, but the result from univariate Cox regression model showed 62% reduction of death risk for patients treated with atezolizumab plus bevacizumab (p = 0.05). In all multivariate analyses, treatment arm was not found to be an independent factor conditioning OS. Comparing ORR achieved in the two arms, there was a statistically significant difference in favor of lenvatinib compared to atezolizumab plus bevacizumab in all subgroups except for Eastern patients, Child-Pugh B patients, presence of portal vein thrombosis, α-feto-protein ≥ 400 ng/mL, presence of extrahepatic disease, albumin-bilirubin (ALBI) grade 2, and no previous locoregional procedures. CONCLUSION: Lenvatinib achieves higher ORR in all patient subgroups. Patients who achieve CR with atezolizumab plus bevacizumab can achieve OS so far never recorded in HCC patients. This study did not highlight any factors that could identify patient subgroups capable of obtaining CR.
• Real Life Study of Lenvatinib Therapy for Hepatocellular Carcinoma: RELEVANT Study.
  Andrea Casadei-Gardini, Margherita Rimini, Masatoshi Kudo, Shigeo Shimose, Toshifumi Tada, Goki Suda, Myung Ji Goh, Andre Jefremow, Mario Scartozzi, Giuseppe Cabibbo, Claudia Campani, Emiliano Tamburini, Francesco Tovoli, Kazuomi Ueshima, Tomoko Aoki, Hideki Iwamoto, Takuji Torimura, Takashi Kumada, Atsushi Hiraoka, Masanori Atsukawa, Ei Itobayashi, Hidenori Toyoda, Naoya Sakamoto, Takuya Sho, Wonseok Kang, Jürgen Siebler, Markus Friedrich Neurath, Valentina Burgio, Stefano Cascinu
  Liver cancer, 11, 6, 527, 539, Dec. 2022, [International Magazine]
  English, Scientific journal, INTRODUCTION: In the REFLECT trial, lenvatinib was found to be noninferior compared to sorafenib in terms of overall survival. Here, we analyze the effects of lenvatinib in the real-life experience of several centers across the world and identify clinical factors that could be significantly associated with survival outcomes. METHODS: The study population was derived from retrospectively collected data of HCC patients treated with lenvatinib. The overall cohort included western and eastern populations from 23 center in five countries. RESULTS: We included 1,325 patients with HCC and treated with lenvatinib in our analysis. Median OS was 16.1 months. Overall response rate was 38.5%. Multivariate analysis for OS highlighted that HBsAg positive, NLR >3, and AST >38 were independently associated with poor prognosis in all models. Conversely, NAFLD/NASH-related etiology was independently associated with good prognosis. Median progression-free survival was 6.3 months. Multivariate analysis for progression-free survival revealed that NAFLD/NASH, BCLC, NLR, and AST were independent prognostic factors for progression-free survival. A proportion of 75.2% of patients suffered from at least one adverse effect during the study period. Multivariate analysis exhibited the appearance of decreased appetite grade ≥2 versus grade 0-1 as an independent prognostic factor for worse progression-free survival. 924 patients of 1,325 progressed during lenvatinib (69.7%), and 827 of them had a follow-up over 2 months from the beginning of second-line treatment. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy (47.0 months), followed by TACE (24.7 months), ramucirumab (21.2 months), sorafenib (15.7 months), regorafenib (12.7 months), and best supportive care (10.8 months). CONCLUSIONS: Our study confirms in a large and global population of patients with advanced HCC, not candidates for locoregional treatment the OS reported in the registration study and a high response rate with lenvatinib.
• Atezolizumab plus bevacizumab versus lenvatinib for unresectable hepatocellular carcinoma: a large real-life worldwide population.
  Andrea Casadei-Gardini, Margherita Rimini, Toshifumi Tada, Goki Suda, Shigeo Shimose, Masatoshi Kudo, Jaekyung Cheon, Fabian Finkelmeier, Ho Yeong Lim, Lorenza Rimassa, José Presa, Gianluca Masi, Changhoon Yoo, Sara Lonardi, Francesco Tovoli, Takashi Kumada, Naoya Sakamoto, Hideki Iwamoto, Tomoko Aoki, Hong Jae Chon, Vera Himmelsbach, Tiziana Pressiani, Margarida Montes, Caterina Vivaldi, Caterina Soldà, Fabio Piscaglia, Atsushi Hiraoka, Takuya Sho, Takashi Niizeki, Naoshi Nishida, Christoph Steup, Massimo Iavarone, Giovanni Di Costanzo, Fabio Marra, Mario Scartozzi, Emiliano Tamburini, Giuseppe Cabibbo, Francesco Giuseppe Foschi, Marianna Silletta, Masashi Hirooka, Kazuya Kariyama, Joji Tani, Masanori Atsukawa, Koichi Takaguchi, Ei Itobayashi, Shinya Fukunishi, Kunihiko Tsuji, Toru Ishikawa, Kazuto Tajiri, Hironori Ochi, Satoshi Yasuda, Hidenori Toyoda, Chikara Ogawa, Takashi Nishimura, Takeshi Hatanaka, Satoru Kakizaki, Noritomo Shimada, Kazuhito Kawata, Fujimasa Tada, Hideko Ohama, Kazuhiro Nouso, Asahiro Morishita, Akemi Tsutsui, Takuya Nagano, Norio Itokawa, Tomomi Okubo, Taeang Arai, Michitaka Imai, Hisashi Kosaka, Atsushi Naganuma, Yohei Koizumi, Shinichiro Nakamura, Masaki Kaibori, Hiroko Iijima, Yoichi Hiasa, Valentina Burgio, Mara Persano, Angelo Della Corte, Francesca Ratti, Francesco De Cobelli, Luca Aldrighetti, Stefano Cascinu, Alessandro Cucchetti
  European journal of cancer (Oxford, England : 1990), 180, 9, 20, 25 Nov. 2022, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIMS: Atezolizumab plus bevacizumab and lenvatinib have not been compared in a randomised controlled trial. We conducted a retrospective multi-centre study to compare the clinical efficacy and safety of lenvatinib and atezolizumab with bevacizumab as a first-line treatment for patients with unresectable HCC in the real-world scenario. METHODS: Clinical features of lenvatinib and atezolizumab plus bevacizumab patients were balanced through inverse probability of treatment weighting (IPTW) methodology, which weights patients' characteristics and measured outcomes of each patient in both treatment arms. Overall survival (OS) was the primary end-point. RESULTS: The analysis included 1341 patients who received lenvatinib, and 864 patients who received atezolizumab plus bevacizumab. After IPTW adjustment, atezolizumab plus bevacizumab did not show a survival advantage over lenvatinib HR 0.97 (p = 0.739). OS was prolonged by atezolizumab plus bevacizumab over lenvatinib in viral patients (HR: 0.76; p = 0.024). Conversely, OS was prolonged by lenvatinib in patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease (HR: 1.88; p = 0.014). In the IPTW-adjusted population, atezolizumab plus bevacizumab provided better safety profile for most of the recorded adverse events. CONCLUSION: Our study did not identify any meaningful difference in OS between atezolizumab plus bevacizumab and lenvatinib. Although some hints are provided suggesting that patients with non-alcoholic steatohepatitis/non-alcoholic fatty liver disease might benefit more from lenvatinib therapy and patients with viral aetiology more from atezolizumab plus bevacizumab.
• Genetic Analyses of Cell-Free DNA in Pancreatic Juice or Bile for Diagnosing Pancreatic Duct and Biliary Tract Strictures
  Kosuke Nagai, Masaki Kuwatani, Koji Hirata, Goki Suda, Hajime Hirata, Yunosuke Takishin, Ryutaro Furukawa, Kazuma Kishi, Hiroki Yonemura, Shunichiro Nozawa, Ryo Sugiura, Kazumichi Kawakubo, Naoya Sakamoto
  Diagnostics, 12, 11, 2704, 2704, MDPI AG, 05 Nov. 2022
  Scientific journal, Poor prognosis of pancreaticobiliary malignancies is attributed to intrinsic biological aggressiveness and the lack of reliable methods for early diagnosis. This study aimed to evaluate the feasibility and availability of pancreatic juice- and bile-derived cell-free DNA (cfDNA) for diagnosing pancreaticobiliary strictures. From October 2020 to February 2022, pancreatic juice or bile was obtained from 50 patients with pancreaticobiliary strictures during endoscopic retrograde cholangiopancreatography. cfDNAs extracted from the samples were analyzed using next-generation sequencing and a cancer gene panel. The obtained cfDNAs, genetic data and clinical information were analyzed for diagnosis. cfDNA concentrations in pancreatic juice were higher in the intraductal papillary mucinous neoplasm group than in the other groups, whereas those in bile were similar in all groups. In pancreatic juice, the sensitivity, specificity and positive and negative predictive values of cfDNA analyses were 33%, 100%, 100% and 71.4%, respectively, whereas those of cytological analyses were 0%, 100%, 0% and 62.5%, respectively. In bile, those of cell-free DNA analyses were 53%, 75%, 89.5% and 28.6%, respectively, whereas those of cytological analyses were 19%, 100%, 100% and 16%, respectively. In conclusion, pancreatic juice- and bile-derived cfDNA is a novel liquid biopsy tool that can diagnose pancreaticobiliary strictures.
• Incidence of post-transplant hepatitis B virus reactivation with the use of kidneys from donors with resolved hepatitis B virus infection.
  Ren Yamada, Kenichi Morikawa, Kiyohiko Hotta, Daiki Iwami, Tatsu Tanabe, Sachiyo Murai, Nobuo Shinohara, Sonoe Yoshida, Shunichi Hosoda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Megumi Kimura, Koji Yamamoto, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  Journal of viral hepatitis, 29, 11, 976, 985, Nov. 2022, [International Magazine]
  English, Scientific journal, Donors with resolved hepatitis B virus (HBV) infection may be a solution for the organ shortage for kidney transplantation (KT). The purpose of this study was to clarify the current state of HBV markers after KT from donors with resolved HBV infection to HBV naïve recipients and the rate of HBV reactivation in recipients with resolved HBV infection. Furthermore, we investigated HBV covalently closed circular DNA (cccDNA) in transplanted organs from donors with resolved HBV infection and the capability of HBV replication in kidney cell lines. We retrospectively analysed the HBV status of 340 consecutive donors and recipients who underwent KT in a single centre. We prospectively measured cccDNA by real-time polymerase chain reaction in kidney biopsy specimens of 32 donors with resolved HBV infection. HBV reactivation was found in three recipients with resolved HBV infection (4.8%, 3/63) after KT. We analysed 45 cases of transplantation from donors with resolved HBV infection to HBV-naive recipients. One case (2.2%, 1/45) became seropositive for hepatitis B core antibody (anti-HBc) and in another case (2.2%, 1/45), HBV-DNA was detected qualitatively in an HBV naive recipient with a donor with resolved HBV infection. In the latter case, cccDNA was measured in the donor kidney during KT. HBV replication was observed in kidney cell lines with HBV plasmid transfection. In conclusion, the risk of reactivation in anti-HBc-positive donors is relatively low. However, post-transplant HBV monitoring should be conducted in all at-risk cases.
• Serum IL-1β predicts de novo hepatitis B virus reactivation during direct-acting antiviral therapy for hepatitis C, not during anti-cancer/immunosuppressive therapy
  Naoki Kawagishi, Goki Suda, Ryotaro Sakamori, Takeshi Matsui, Masahiro Onozawa, Zijian Yang, Sonoe Yoshida, Masatsugu Ohara, Megumi Kimura, Akinori Kubo, Osamu Maehara, Qingjie Fu, Shunichi Hosoda, Yoshimasa Tokuchi, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Hajime Sakai, Shunsuke Ohnishi, Masaru Baba, Tetsuo Takehara, Naoya Sakamoto
  Scientific Reports, 12, 1, Springer Science and Business Media LLC, 07 Oct. 2022
  Scientific journal, Abstract
  
  De novo hepatitis B virus (HBV) reactivation occurs during direct-acting antiviral (DAA) treatment in hepatitis C virus (HCV)-infected patients with resolved HBV infection. We evaluated the predictive factors, mechanical insight, and differences of cytokine levels during anti-cancer/immunosuppressive and DAA. Eleven, 35, and 19 HCV-infected patients with previous HBV infection with HBV reactivation during DAA treatment, previous HBV infection without HBV reactivation during DAA treatment, and without HBV infection resolution receiving DAA treatment, respectively, were enrolled. Clinical data and baseline cytokine levels were analyzed. Low baseline serum interleukin (IL)-1β levels predicted de novo HBV reactivation during DAA treatment (odds ratio: 47.6, 95% confidence interval: 6.94–333.3). HCV-infected patients with the IL-1β gene single nucleotide polymorphism rs16944 AA allele had significantly higher IL-1β levels; no HCV-infected patient with the IL-1β AA allele experienced HBV reactivation during DAA treatment. Compared to HCV-infected patients with HBV infection resolution, non-HCV infected patients with or without HBV reactivation during anti-cancer/immunosuppressive therapy or bone marrow transplantation had remarkably lower baseline IL-1β levels. Low IL-1β levels were not associated with HBV reactivation. IL-1β levels before DAA for HCV-infected patients with resolved HBV infection could predict HBV reactivation during DAA treatment.
• 肝疾患病態解明のための細胞生物学的アプローチ 肝細胞癌幹細胞維持機構の解析　　　　　　　　　　　　　　　
  須田 剛生, 大原 正嗣, 坂本 直哉
  肝臓, 63, Suppl.3, A691, A691, (一社)日本肝臓学会, Oct. 2022
  Japanese
• 【進化する肝細胞癌の薬物療法:2022 update】免疫療法の基礎と臨床 免疫療法(単剤・複合療法)の効果は肝細胞癌のetiologyと関係するか　　　　　　　　　　　　　　　
  小川 浩司, 大原 正嗣, 中井 正人, 荘 拓也, 須田 剛生, 坂本 直哉
  肝胆膵, 85, 3, 393, 398, (株)アークメディア, Sep. 2022
  Japanese
• 切除不能進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の治療効果と肝予備能変化　　　　　　　　　　　　　　　
  荘 拓也, 出水 孝章, 目黒 高志, 中村 晃久, 上林 実, 高木 智史, 馬場 英, 古家 乾, 鈴木 和治, 山本 義也, 伊藤 淳, 山田 錬, 宮城島 拓人, 須田 剛生, 大原 正嗣, 中井 正人, 小川 浩司, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 39, 39, 日本消化器病学会-北海道支部, Sep. 2022
  Japanese
• 肝血管筋脂肪腫の1切除例　　　　　　　　　　　　　　　
  佐々木 貴志, 甲谷 理紗子, 細田 峻一, 吉田 苑永, 得地 祐匡, 久保 彰則, 大原 正嗣, 須田 剛生, 中井 正人, 荘 拓也, 小川 浩司, 坂本 直哉, 相山 健, 武冨 紹信, 岡崎 ななせ, 松野 吉宏
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 40, 40, 日本消化器病学会-北海道支部, Sep. 2022
  Japanese
• 日本人肥満2型糖尿病における腹腔鏡下スリーブ状胃切除術が脂肪肝と膵β細胞機能に及ぼす効果 前向きコホート研究　　　　　　　　　　　　　　　
  大江 悠希, 中村 昭伸, 曹 圭龍, 高瀬 崇宏, 小川 浩司, 海老原 裕磨, 吉川 仁人, 西田 睦, 宮 愛香, 野本 博司, 亀田 啓, 荘 拓也, 須田 剛生, 倉島 庸, 阿保 大介, 工藤 與亮, 坂本 直哉, 平野 聡, 渥美 達也, 三好 秀明
  糖尿病合併症, 36, Suppl.1, 172, 172, (一社)日本糖尿病合併症学会, Sep. 2022
  Japanese
• 内科・外科による消化器病共同診療の現況と展望 当院における潰瘍性大腸炎に対する手術成績　　　　　　　　　　　　　　　
  吉田 雅, 本間 重紀, 市川 伸樹, 藤好 直, 柴田 賢吾, 松井 博紀, 桂田 武彦, 桜井 健介, 福島 新弥, 青山 慶哉, 坂本 直哉, 武冨 紹信
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 26, 26, 日本消化器病学会-北海道支部, Sep. 2022
  Japanese
• 内科・外科による消化器病共同診療の現況と展望 局所進行直腸癌における術前FOLFOX療法の有効性の検討(RNAC01試験)の解釈とその発展　　　　　　　　　　　　　　　
  藤好 直, 本間 重紀, 市川 伸樹, 結城 敏志, 川本 泰之, 原田 一顕, 吉田 雅, 柴田 賢吾, 松井 博紀, 小松 嘉人, 坂本 直哉, 武冨 紹信
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 26, 26, 日本消化器病学会-北海道支部, Sep. 2022
  Japanese
• 内科・外科による消化器病共同診療の現況と展望 当科における切除可能境界膵癌に対する術前治療の現状　　　　　　　　　　　　　　　
  原田 一顕, 中村 赳晶, 渡辺 亮介, 山村 貴洋, 川本 泰之, 結城 敏志, 桑谷 将城, 田口 大志, 加藤 徳雄, 浅野 賢道, 中村 透, 平野 聡, 小松 嘉人, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 131回・125回, 28, 28, 日本消化器病学会-北海道支部, Sep. 2022
  Japanese
• 肝硬変体液貯留に対するトルバプタン投与症例における尿NGAL測定の有用性　　　　　　　　　　　　　　　
  中井 正人, 森川 賢一, 吉田 苑永, 細田 峻一, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 大原 正嗣, 荘 拓也, 須田 剛生, 小川 浩司, 坂本 直哉
  肝臓, 63, Suppl.2, A592, A592, (一社)日本肝臓学会, Sep. 2022
  Japanese
• Assessment of postoperative common bile duct stones after endoscopic extraction and subsequent cholecystectomy
  Ryo Sugiura, Hideaki Nakamura, Shoichi Horita, Takashi Meguro, Kiyotaka Sasaki, Hidetoshi Kagaya, Tatsuya Yoshida, Hironori Aoki, Takayuki Morita, Miyoshi Fujita, Eiji Tamoto, Masayuki Fukushima, Yoshitomo Ashitate, Takashi Ueno, Akio Tsutaho, Masaki Kuwatani, Naoya Sakamoto
  Surgical Endoscopy, 36, 9, 6535, 6542, Springer Science and Business Media LLC, Sep. 2022
  Scientific journal
• No increased risk of hepatocellular carcinoma after eradication of hepatitis C virus by direct-acting antivirals, compared with interferon-based therapy.
  Masaaki Korenaga, Kazumoto Murata, Namiki Izumi, Nobuharu Tamaki, Osamu Yokosuka, Tetsuo Takehara, Naoya Sakamoto, Goki Suda, Shuhei Nishiguchi, Hirayuki Enomoto, Fusao Ikeda, Mikio Yanase, Hidenori Toyoda, Takuya Genda, Takeji Umemura, Hiroshi Yatsuhashi, Kazumi Yamasaki, Tatsuya Ide, Nobuo Toda, Tatsuo Kanda, Kazushige Nirei, Yoshiyuki Ueno, Hiroaki Haga, Yoichi Nishigaki, Kunio Nakane, Masao Omata, Hitoshi Mochizuki, Yoshihiko Aoki, Masatoshi Imamura, Tatsuya Kanto, Masashi Mizokami
  Global health & medicine, 4, 4, 216, 224, 31 Aug. 2022, [Domestic magazines]
  English, Scientific journal, It is well-known that sustained virological response (SVR) by interferon (IFN)-based therapy against hepatitis C virus (HCV) infection reduced the incidence of hepatocellular carcinoma (HCC). However, whether IFN-free direct-acting antivirals reduce the risk of HCC is controversial. Therefore, this study aims to compare the incidence of HCC after the achievement of SVR between sofosbuvir combined with ledipasvir (SOF/LDV) and simeprevir with pegylated interferon plus ribavirin (Sim+IFN). Japanese patients with HCV infection (genotype 1) who achieved SVR between January 2013 and December 2014 by SOF/LDV (NCT01975675, n = 320) or Sim+IFN (000015933, n = 289) therapy in two nationwide, multicenter, phase III studies were prospectively monitored for the development of HCC by ultrasonography for 5 years after the end of treatment (EOT). No HCC was detected before the treatment. HCC was detected in 9 and 7 patients in the SOF/LDV and the Sim+IFN group in 5 years, respectively. The cumulative incidences of HCC rates 1, 3, and 5 years after EOT were similar between the two groups (1.5%, 2.7%, and 3.2% for the SOF/LDV and 1.8%, 2.8%, and 3.0% for the Sim+IFN group, respectively). No HCC was developed 3.5 years after EOT. Interestingly, a retrospective careful review of imaging taken before therapy revealed hepatic nodules in 50% of HCC patients, suggesting HCC was pre-existed before therapy. In conclusion, we could not find any differences in the incidence of HCC after the HCV eradication between the two therapeutic regimens, suggesting no enhancement of HCC development by DAA.
• Usefulness of ultrasonography and elastography in diagnosing oxaliplatin-induced sinusoidal obstruction syndrome.
  Rika Saito, Yasuyuki Kawamoto, Mutsumi Nishida, Takahito Iwai, Yasuka Kikuchi, Isao Yokota, Ryo Takagi, Takahiro Yamamura, Ken Ito, Kazuaki Harada, Satoshi Yuki, Yoshito Komatsu, Naoya Sakamoto
  International journal of clinical oncology, 27, 11, 1780, 1790, 30 Aug. 2022, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Sinusoidal obstruction syndrome (SOS) refers to liver injury caused by hematopoietic stem cell transplantation (HSCT) and anticancer drugs including oxaliplatin. Increased splenic volume (SV) on computed tomography (CT) indicates oxaliplatin-induced SOS. Similarly, ultrasonography and liver stiffness measurement (LSM) by shear-wave elastography (SWE) can help diagnose SOS after HSCT; however, their usefulness for diagnosing oxaliplatin-induced SOS remains unclear. We investigated the usefulness of the Hokkaido ultrasonography-based scoring system with 10 ultrasonographic parameters (HokUS-10) and SWE in diagnosing oxaliplatin-induced SOS early. METHODS: In this prospective observational study, ultrasonography and SWE were performed before and at 2, 4, and 6 months after oxaliplatin-based chemotherapy. HokUS-10 was used for assessment. CT volumetry of the SV was performed in clinical practice, and an SV increase ≥ 30% was considered the diagnostic indicator of oxaliplatin-induced SOS. We assessed whether HokUS-10 and SWE can lead to an early detection of oxaliplatin-induced SOS before an increased SV on CT. RESULTS: Of the 30 enrolled patients with gastrointestinal cancers, 12 (40.0%) with an SV increase  ≥ 30% on CT were diagnosed with SOS. The HokUS-10 score was not correlated with an SV increase ≥ 30% (r = 0.18). The change in rate of three HokUS-10 parameters were correlated with an SV increase ≥ 30% (r = 0.32-0.41). The change in rate of LSM by SWE was correlated with an SV increase  ≥ 30% (r = 0.40). CONCLUSIONS: The usefulness of HokUS-10 score was not demonstrated; however, some HokUS-10 parameters and SWE could be useful for the early diagnosis of oxaliplatin-induced SOS.
• Efficacy and Effect on Liver Functional Reserve of Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma in Patients Who Do Not Meet Eligibility Criteria of IMbrave150
  Takuya Sho, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Koji Ogawa, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Zijian Yang, Megumi Kimura, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Tomofumi Takagi, Jun Ito, Tomoe Kobayashi, Takuto Miyagishima, Naoya Sakamoto
  Cancers, 14, 16, 3938, 3938, MDPI AG, 15 Aug. 2022
  Scientific journal, The IMbrave150 trial demonstrated the high efficacy and safety of atezolizumab and bevacizumab for unresectable hepatocellular carcinoma (HCC). In this multicenter study, the efficacy of this combination and its effect on liver functional reserve were evaluated in patients not meeting the eligibility criteria of IMbrave150. Of 115 patients with unresectable HCC treated with atezolizumab and bevacizumab between October 2020 and January 2022, 72 did not meet the eligibility criteria of IMbrave150, most frequently due to a history of systemic therapy (60/72), platelet counts < 75 × 109/L (7/72), Child-Pugh B (9/72), and 2+ proteinuria (8/72). Atezolizumab and bevacizumab therapy was equally effective for patients who did or did not meet the eligibility criteria (PFS, 6.5 vs. 6.9 months, p = 0.765), consistent with subgroup analyses of histories of systemic therapy, platelet counts, Child-Pugh, and proteinuria. Baseline ALBI scores were worse in patients who did not meet the criteria than in those who did and significantly worsened after treatment initiation in patients not meeting the criteria (baseline vs. 12 weeks; 2.35 ± 0.43 vs. −2.18 ± 0.54; p = 0.007). Accordingly, atezolizumab plus bevacizumab was effective for patients not meeting the eligibility criteria of IMbrave150, although careful monitoring for changes in liver functional reserve is needed.
• VALIDATION OF THE EASY-TO-USE LENVATINIB PROGNOSTIC (LEP) INDEX TO PREDICT PROGNOSIS IN ADVANCED HEPATOCELLULAR CARCINOMA PATIENTS TREATED WITH LENVATINIB.
  Margherita Rimini, Wonseok Kang, Valentina Burgio, Mara Persano, Tamoko Aoki, Shigeo Shimose, Toshifumi Tada, Takashi Kumada, Takuya Sho, Eleonora Lai, Ciro Celsa, Claudia Campani, Matteo Tonnini, Emiliano Tamburini, Atsushi Hiraoka, Koichi Takaguchi, Naoshi Nishida, Hideki Iwamoto, Ei Itobayashi, Kunihiko Tsuji, Naoya Sakamoto, Toru Ishikawa, Hidenori Toyoda, Masatoshi Kudo, Takumi Kawaguchi, Takeshi Hatanaka, Kazugiro Nouso, Goki Suda, Giuseppe Cabibbo, Fabio Marra, Angelo Della Corte, Francesca Ratti, Federica Pedica, Francesco De Cobelli, Luca Aldrighetti, Mario Scartozzi, Stefano Cascinu, Andrea Casadei-Gardini
  Hepatology research : the official journal of the Japan Society of Hepatology, 12 Aug. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: The identification of new prognostic factors able to stratify HCC patients candidate to first line therapy is an urgent. In the present work we validated the prognostic value of the LEP index. MATHERIALS AND METHODS: Data of Eastern and Western patients treated with lenvatinib as first-line for BCLC stage B or C HCC were recollected. LEP index was composed by three class of risk according with our previously study. The 'low risk'group includes patients with PNI >43.3 and with previous TACE. The 'medium risk' group includes patients with PNI >43.3 but without previous TACE and patients with PNI <43.3, ALBI grade 1 and BCLC-B. The 'high risk'group includes patients with PNI <43.3, ALBI grade 2 and patients with PNI <43.3, ALBI grade 1 and BCLC-C. RESULTS: 717 patients were included. Median OS was 20.7 months (95% CI 16.1-51.6) in patients with low risk (n = 223), 16.7 months (95% CI 13.3-47.0) in medium risk (n = 264) and 10.7 months (95% CI 9.3-12.2) in high risk (n = 230) [HR 1, 1.29 and 1.92 respectively; p < 0.0001]. Median PFS was 7.3 months (95% CI 6.3-46.5) in patients with low risk, 6.4 months (95% CI 5.3-8.0) in medium and 4.9 months (95% CI 4.3-5.5) in high risk [HR 1, 1.07, 1.47 respectively; p = 0.0009]. CONCLUSION: The LEP index confirms its prognostic value on an external cohort of HCC patients treated with Lenvatinib. This article is protected by copyright. All rights reserved.
• Long-term changes in aberrant DNA methylation and gastritis after Helicobacter pylori eradication focused on metachronous gastric cancer.
  Ikko Tanaka, Shoko Ono, Yoshiyuki Watanabe, Hiroyuki Yamamoto, Ritsuko Oikawa, Shogo Matsumoto, Marina Kubo, Yusuke Nishimura, Yoshihiko Shimoda, Masayoshi Ono, Keiko Yamamoto, Naoya Sakamoto
  Helicobacter, e12915, 08 Aug. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: A persistently high methylation level in gastric mucosa after Helicobacter pylori (H. pylori) eradication is presumed to be a risk for metachronous gastric cancer (MGC); however, long-term changes in aberrant DNA methylation and histological gastritis have been unclear. Our aim was to examine changes in DNA methylation and histological gastritis according to the occurrence of MGC. METHODS: Subjects were classified into three groups: 25 patients in whom MGCs occurred after the initial endoscopic resection (ER) for early gastric cancer and H. pylori eradication (MGC group), 17 patients in whom MGC did not occur for more than 5 years after the initial ER and H. pylori eradication (non-MGC group) and 29 patients without a history of gastric cancer who succeeded in eradication more than 5 years ago (HP group). Aberrance of DNA methylation in three genes (miR-124a-3, EMX1, NKX6-1) and histological score of atrophy and intestinal metaplasia (IM) were evaluated using biopsy samples before and more than a mean of 5 years after H. pylori eradication. Also, the mean Z-score was calculated using Z-score values of the three genes. RESULTS: The methylation level of miR-124a-3 in the HP group and non-MGC group and that of EMX1 in the HP group significantly decreased in the long term after eradication. In the MGC group, H. pylori eradication did not improve aberrant methylation, and the mean Z-score significantly increased. There were significant positive correlations between methylation levels in miR-124a-3 and EMX1 and histological findings after eradication. CONCLUSIONS: A persistently high methylation level after H. pylori eradication reflected precancerous mucosal conditions and led to long-term MGC.
• Phase II Study of Ramucirumab Plus Irinotecan Combination Therapy as Second-Line Treatment in Patients with Advanced Gastric Cancer: HGCSG1603.
  Yasuyuki Kawamoto, Satoshi Yuki, Kentaro Sawada, Michio Nakamura, Osamu Muto, Susumu Sogabe, Yoshiaki Shindo, Atsushi Ishiguro, Atsushi Sato, Yasushi Tsuji, Masayoshi Dazai, Hiroyuki Okuda, Takashi Meguro, Kazuaki Harada, Mari Sekiguchi, Kazufumi Okada, Yoichi M Ito, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
  The oncologist, 27, 8, e642-e649, 05 Aug. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: Ramucirumab is a human IgG1 monoclonal vascular endothelial growth factor receptor-2 antibody that inhibits tumor cell growth and affects the tumor cell microenvironment. We assessed the efficacy and safety of ramucirumab plus irinotecan combination therapy as second-line treatment in patients with previously treated advanced gastric cancer. MATERIALS AND METHODS: Patients with advanced gastric cancer refractory or intolerant to primary chemotherapy were included. Ramucirumab 8 mg/kg plus irinotecan 150 mg/m2 combination therapy was administered every 2 weeks. The primary endpoint was progression-free survival rate at 6 months and secondary endpoints were overall survival, progression-free survival, response rate, safety, and dose intensity for each drug. RESULTS: Thirty-five patients were enrolled between January 2018 and September 2019. The progression-free survival rate at 6 months was 26.5% [95%CI, 13.2%-41.8%, P = .1353)]. Median progression-free and overall survivals were 4.2 months (95%CI, 2.5-5.4 months) and 9.6 months (95%CI, 6.4-16.6 months), respectively. The overall response rate was 25.9% (95%CI, 11.1-36.3%) and disease control rate was 85.2% (95%CI, 66.3-95.8%). Grade ≥3 adverse events that occurred in >10% of patients included neutropenia, leucopenia, anemia, anorexia, and febrile neutropenia. No death or new safety signals with a causal relation to the study treatment were observed. CONCLUSION: Although the primary endpoint was not achieved statistically, combination therapy of ramucirumab plus irinotecan showed anticancer activity and a manageable safety profile for second-line treatment of patients with advanced gastric cancer.
• 本邦における腹腔鏡下スリーブ状胃切除術後の骨密度変化と関連因子 前向きコホート研究　　　　　　　　　　　　　　　
  大江 悠希, 曹 圭龍, 小川 浩司, 海老原 裕磨, 宮 愛香, 野本 博司, 亀田 啓, 中村 昭伸, 坂本 直哉, 平野 聡, 渥美 達也, 三好 秀明
  日本骨粗鬆症学会雑誌, 8, Suppl.1, 158, 158, (一社)日本骨粗鬆症学会, Aug. 2022
  Japanese
• Pre-sarcopenia and Mac-2 binding protein glycosylation isomer as predictors of recurrence and prognosis of early-stage hepatocellular carcinoma.
  Masato Nakai, Kenichi Morikawa, Shunichi Hosoda, Sonoe Yoshida, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Masatsugu Ohara, Takuya Sho, Goki Suda, Koji Ogawa, Naoya Sakamoto
  World journal of hepatology, 14, 7, 1480, 1494, 27 Jul. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: The Mac-2 binding protein glycosylation isomer (M2BPGi), a fibrosis marker in various liver diseases, is reportedly a prognostic marker in patients with hepatocellular carcinoma (HCC) who underwent hepatectomy. AIM: To evaluate whether the M2BPGi value, M2BP, and pre-sarcopenia before radiofrequency ablation (RFA) could be useful recurrence and prognostic markers in patients with early-stage HCC. METHODS: In total, 160 patients with early-stage primary HCC treated with RFA were separately analyzed as hepatitis C virus (HCV)-positive and HCV-negative. Factors contributing to recurrence and liver-related death, including M2BP, M2BPGi, and skeletal muscle mass index, were statistically analyzed. Eighty-three patients were HCV-positive and 77 were HCV-negative. RESULTS: In HCV-positive patients, only des-γ-carboxy-prothrombin ≥ 23 mAU/mL was a significant poor prognostic factor affecting survival after RFA. In HCV-negative patients, M2BPGi ≥ 1.86 cutoff index was significantly associated with tumor recurrence, while M2BP was not. M2BPGi ≥ 1.86 cutoff index (hazard ratio, 4.89; 95% confidence interval: 1.97-12.18; P < 0.001) and pre-sarcopenia (hazard ratio, 3.34, 95% confidence interval: 1.19-9.37; P = 0.022) were independent significant poor prognostic factors in HCV-negative patients. CONCLUSION: In HCV-negative patients with primary HCC treated with RFA, lower M2BPGi contributed to a lower tumor recurrence rate and longer survival period. Pre-sarcopenia contributed to the poor prognosis independently in HCV-negative patients. These factors might be useful recurrence and prognostic markers for early-stage primary HCC.
• 特集 胆道･膵疾患を診る-早期診断･早期治療のために 胆膵実地診療のコツ 閉塞性黄疸のドレナージ,何を考える?
  桒谷 将城, 岸 法磨, 永井 孝輔, 川久保 和道, 坂本 直哉
  内科, 130, 1, 41, 46, 南江堂, 01 Jul. 2022
• Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon-lambda 3 induction in chronic hepatitis B patients.
  Machiko Umemura, Koji Ogawa, Kenichi Morikawa, Akinori Kubo, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Tomoe Shimazaki, Megumi Kimura, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Kota Ono, Kazumoto Murata, Masaya Sugiyama, Masashi Mizokami, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 52, 7, 586, 596, Jul. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND & AIMS: Benefits of nucleos(t)ide analogs (NAs) on hepatitis B surface antigen (HBsAg) reduction and interferon-lambda3 (IFN-λ3) induction are still not known. This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN-λ3 levels in chronic hepatitis B (CHB) patients. METHODS: A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN-λ3 levels among patients receiving ETV and ADV/TDF were measured before the initiation of therapy and 1, 3, and 5 years post-therapy. RESULTS: The change (mean ± standard deviation) in serum HBsAg levels from baseline to year five was -0.38 ± 0.46 and -0.84 ± 0.64 log10 IU/ml in ETV and ADV/TDF groups, respectively (p = 0.0004). Higher serum IFN-λ3 levels were observed in ADV/TDF group compared with ETV group during treatment (p < 0.001). Serum IFN-λ3 levels showed negative correlation with HBsAg reduction in ADV/TDF group (r = -0.386, p = 0.038) at week 48. Nucleotide analogs (ADV/TDF) treatment has associated factors with -0.3 log HBsAg decline at 1 year, -0.5 log HBsAg decline at 3 years, and -0.8 log HBsAg decline at 5 years after NAs treatment on multivariate analysis. CONCLUSIONS: Nucleotide analog (ADV/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN-λ3 induction.
• Small-molecule inhibitor cocktail promotes the proliferation of pre-existing liver progenitor cells.
  Qingjie Fu, Shunsuke Ohnishi, Goki Suda, Naoya Sakamoto
  Stem cell reports, 17, 7, 1589, 1603, 13 Jun. 2022, [International Magazine]
  English, Scientific journal, A recent study showed that a cocktail of three small molecules, Y-27632, A83-01, and CHIR99021 (YAC), converts mature hepatocytes (MHs) into proliferative bipotent cells that can be induced into MHs and cholangiocytes in rats. However, when we reproduced these experiments, it was found that bipotent cells may be derived from resident liver progenitor cells (LPCs), whose proliferative activity was promoted by YAC. A simple and efficient sorting scheme was also developed in this study to harvest high-purity and high-yield LPCs. The inducible bipotency of purified LPCs was verified; in addition, they were found to spontaneously differentiate into hepatocytes and cholangiocytes due to changes in proliferative status even without induction. Moreover, during the differentiation process, some hepatocytes spontaneously reconverted to LPCs under certain conditions, such as the release of contact inhibition. These findings may improve our understanding of LPCs and provide a cell source for regenerative medicine.
• Analysis of the Pancreatic Cancer Microbiome Using Endoscopic Ultrasound–Guided Fine-Needle Aspiration–Derived Samples
  Shintaro Nakano, Yasuyuki Kawamoto, Yoshito Komatsu, Rika Saito, Ken Ito, Takahiro Yamamura, Kazuaki Harada, Satoshi Yuki, Kazumichi Kawakubo, Ryo Sugiura, Shin Kato, Koji Hirata, Hajime Hirata, Masahito Nakajima, Ryutaro Furukawa, Yunosuke Takishin, Kousuke Nagai, Isao Yokota, Keisuke H. Ota, Shinji Nakaoka, Masaki Kuwatani, Naoya Sakamoto
  Pancreas, Publish Ahead of Print, 4, 351, 357, Ovid Technologies (Wolters Kluwer Health), 13 Jun. 2022
  Scientific journal
• 【臓器線維化へのアプローチ-肝臓・膵臓のアンチエイジングを見据えて-】臓器線維化治療のニューウェーブ　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 坂本 直哉
  アンチ・エイジング医学, 18, 3, 182, 185, (株)メディカルレビュー社, Jun. 2022
  Japanese
• Multicenter, prospective, observational study of chemotherapy-induced dysgeusia in gastrointestinal cancer.
  Ken Ito, Satoshi Yuki, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Kazuaki Harada, Shintaro Nakano, Rika Saito, Takayuki Ando, Kentaro Sawada, Masataka Yagisawa, Atsushi Ishiguro, Masayoshi Dazai, Ichiro Iwanaga, Kazuteru Hatanaka, Atsushi Sato, Ryusuke Matsumoto, Yoshiaki Shindo, Miki Tateyama, Tetsuhito Muranaka, Masaki Katagiri, Isao Yokota, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
  Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer, 30, 6, 5351, 5359, Jun. 2022, [International Magazine]
  English, Scientific journal, PURPOSE: Dysgeusia is an adverse event caused by chemotherapy. Although retrospective studies have shown zinc administration improves dysgeusia, there have been no prospective studies. The present study examined effects of zinc therapy on dysgeusia in patients with gastrointestinal cancer. METHODS: This multicenter, prospective, observational study enrolled patients with dysgeusia during chemotherapy treatment. Patients received no intervention (control), polaprezinc p.o., or zinc acetate hydrate p.o., and serum zinc levels were measured at 0 (baseline), 6, and 12 weeks. Dysgeusia was assessed using CTCAE v5.0 and subjective total taste acuity (STTA) criteria using questionnaires at baseline and 12 weeks. RESULTS: From February 2020 to June 2021, 180 patients were enrolled from 17 institutes. There were no differences in mean baseline serum zinc levels among the groups (67.3, 66.6, and 67.5 μg/dL in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. P = 0.846). The changes in mean serum zinc levels after 12 weeks were - 3.8, + 14.3, and + 46.6 μg/dL, and the efficacy rates of dysgeusia were 33.3%, 36.8%, and 34.6% using CTCAE and 33.3%, 52.6%, 32.7% using STTA in the no intervention, polaprezinc, and zinc acetate hydrate groups, respectively. The STTA scores improved in all groups, with significant improvement observed in the polaprezinc group compared with the no intervention group (P = 0.045). CONCLUSION: There was no significant correlation between the degree of serum zinc elevation and improvement in dysgeusia, suggesting that polaprezinc, but not zinc acetate hydrate, was effective in improving chemotherapy-induced dysgeusia. TRIAL REGISTRATION: UMIN000039653. Date of registration: March 2, 2020.
• Optical biopsy for esophageal squamous cell neoplasia by using endocytoscopy.
  Yoshihiko Shimoda, Yuichi Shimizu, Hiroaki Takahashi, Satoshi Okahara, Takakazu Miyake, Shin Ichihara, Ikko Tanaka, Masaki Inoue, Sayoko Kinowaki, Masayoshi Ono, Keiko Yamamoto, Shoko Ono, Naoya Sakamoto
  BMC gastroenterology, 22, 1, 259, 259, 21 May 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: Endocytoscopy (ECS) enables microscopic observation in vivo for the gastrointestinal mucosa; however, there has been no prospective study in which the diagnostic accuracy of ECS for lesions that have not yet undergone histological diagnosis was evaluated. We conducted a surveillance study for patients in a high-risk group of esophageal squamous cell carcinoma (ESCC) and evaluated the in vivo histological diagnostic accuracy of ECS. METHODS: This study was a multicenter prospective study. We enrolled 197 patients in the study between September 1, 2019 and November 30, 2020. The patients first underwent white light imaging and narrow band imaging, and ultra-high magnifying observation was performed if there was a lesion suspected to be an esophageal tumor. Endoscopic submucosal dissection (ESD) was later performed for lesions that were diagnosed to be ESCC by ECS without biopsy. We evaluated the diagnostic accuracy of ECS for esophageal tumorous lesions. RESULTS: ESD was performed for 37 patients (41 lesions) who were diagnosed as having ESCC by ECS, and all of them were histopathologically diagnosed as having ESCC. The sensitivity [95% confidence interval (CI)] was 97.6% (87.7-99.7%), specificity (95% CI) was 100% (92.7-100%), diagnostic accuracy (95% CI) was 98.9% (94.0-99.8%), positive predictive value (PPV) (95% CI) was 100% (91.4-100%) and negative predictive value (NPV) (95% CI) was 98.0% (89.5-99.7%). CONCLUSIONS: ECS has a high diagnostic accuracy and there were no false positives in cases diagnosed and resected as ESCC. Optical biopsy by using ECS for esophageal lesions that are suspected to be tumorous is considered to be sufficient in clinical practice.
• Study protocol of the HGCSG1803: a phase II multicentre, non-randomised, single-arm, prospective trial of combination chemotherapy with oxaliplatin, irinotecan and S-1 (OX-IRIS) as first-line treatment for metastatic or relapsed pancreatic cancer.
  Shintaro Nakano, Yasuyuki Kawamoto, Satoshi Yuki, Kazuaki Harada, Takuto Miyagishima, Susumu Sogabe, Masayoshi Dazai, Atsushi Sato, Atsushi Ishiguro, Michio Nakamura, Shinya Kajiura, Yasuo Takahashi, Miki Tateyama, Kazuteru Hatanaka, Yasushi Tsuji, Takahide Sasaki, Yoshiaki Shindo, Tomoe Kobayashi, Isao Yokota, Naoya Sakamoto, Yuh Sakata, Yoshito Komatsu
  BMJ open, 12, 5, e048833, 09 May 2022, [International Magazine]
  English, Scientific journal, INTRODUCTION: Combination chemotherapy with oxaliplatin, irinotecan, fluorouracil and leucovorin (FOLFIRINOX) has become one of the standard treatments for metastatic pancreatic cancer. However, the use of FOLFIRINOX requires prolonged infusion. Therefore, we planned to develop a new combination chemotherapy regimen with oxaliplatin, irinotecan and S-1 (OX-IRIS) for advanced pancreatic cancer. In the phase Ⅰ study that was conducted previously, the safety and recommended dose of OX-IRIS were assessed. In this study, we will evaluate the efficacy and safety of OX-IRIS. METHODS AND ANALYSIS: The HGCSG1803 study started as a multicentre, non-randomised, single-arm, prospective, phase II study in December 2019. Eligible subjects were patients with untreated metastatic or relapsed pancreatic cancer. OX-IRIS is administered as follows: 30 min infusion of antiemetic; 2-hour infusion of oxaliplatin (65 mg/m2); 1.5-hour infusion of irinotecan (100 mg/m2) on day 1 and 15 of each 4-week cycle; and oral S-1 (40 mg/m2) twice daily from after dinner on day one to after breakfast on day 15, followed by a 14-day rest, to be repeated every 2 weeks until disease progression, unacceptable toxicity or patient refusal. The primary endpoint is response rate. The secondary endpoints are overall and progression-free survival, safety and dose for each drug. Using a binomial test, a sample size of 40 patients was set with a threshold value of 10% and expected value of 30%. Registration of 40 cases is planned from 18 institutions in Japan. ETHICS AND DISSEMINATION: All the procedures will be conducted in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Declaration of Helsinki of 1964 and its later versions. All the patients will receive written information about the trial and will provide informed consent before enrolment. This trial was approved by the Hokkaido University Certified Review Board (approval No: 018-037). TRIAL REGISTRATION NUMBER: jRCTs011190008.
• Phase II Study of Continued Trastuzumab Plus Irinotecan in Patients with HER2-positive Gastric Cancer Previously Treated with Trastuzumab (HGCSG 1201).
  Yasuyuki Kawamoto, Satoshi Yuki, Takashi Meguro, Kazuteru Hatanaka, Minoru Uebayashi, Michio Nakamura, Hiroyuki Okuda, Ichiro Iwanaga, Takashi Kato, Shintaro Nakano, Atsushi Sato, Kazuaki Harada, Koji Oba, Yuh Sakata, Naoya Sakamoto, Yoshito Komatsu
  The oncologist, 27, 5, 340-e374, 06 May 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: The efficacy of irinotecan plus continuous trastuzumab beyond progression in patients with gastric cancer previously treated with trastuzumab plus standard first-line chemotherapy has not been reported. METHODS: Patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer who were previously treated with trastuzumab received trastuzumab every 3 weeks and irinotecan every 2 weeks. The primary endpoint was the overall response rate (ORR), and the secondary endpoints included progression-free survival (PFS), 6-month survival rates, safety, and subgroup analysis by HER2 status. RESULTS: Sixteen patients were enrolled in a 3-year pre-planned registration period. This study was prematurely closed due to poor patient accrual. The ORR and disease control rate were 6.7% (95% CI, 0.2-32.0) and 53.3% (95% CI, 26.6-78.7). The median PFS and overall survival (OS) were 2.4 months (95% CI, 0.0-5.2) and 9.7 months (95% CI, 8.2-11.2), respectively. The most frequently reported grades 3-4 adverse events were neutropenia (40%), anemia (27%), anorexia (33%), and fatigue (33%). CONCLUSION: With only 16 patients enrolled, the present study has very low power to detect any clinical benefit of trastuzumab plus irinotecan beyond disease progression in patients with HER2-positive advanced gastric cancer who previously received trastuzumab.Trial Identifier: UMIN000007636.
• Case Report: Hereditary Fibrosing Poikiloderma With Tendon Contractures, Myopathy, and Pulmonary Fibrosis (POIKTMP) Presenting With Liver Cirrhosis and Steroid-Responsive Interstitial Pneumonia
  Michiko Takimoto-Sato, Toshinari Miyauchi, Masaru Suzuki, Hideyuki Ujiie, Toshifumi Nomura, Tomoo Ikari, Tomohiko Nakamura, Kei Takahashi, Machiko Matsumoto-Sasaki, Hirokazu Kimura, Hiroki Kimura, Yuichiro Matsui, Takashi Kitagataya, Ren Yamada, Kazuharu Suzuki, Akihisa Nakamura, Masato Nakai, Takuya Sho, Koji Ogawa, Naoya Sakamoto, Naoko Yamaguchi, Noriyuki Otsuka, Utano Tomaru, Satoshi Konno
  Frontiers in Genetics, 13, Frontiers Media SA, 05 May 2022
  Scientific journal, Background: Hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP) is an extremely rare disease caused by mutations in FAM111B, and only approximately 30 cases have been reported worldwide. Some patients develop interstitial pneumonia, which may lead to progressive pulmonary fibrosis and poor prognosis. However, no effective treatment for interstitial pneumonia associated with POIKTMP has been reported. Here, we report an autopsy case of POIKTMP, wherein interstitial pneumonia was improved by corticosteroids.
  
  Case Presentation: A 44-year-old Japanese man was referred to our hospital due to poikiloderma, hypotrichosis, and interstitial pneumonia. He developed progressive poikiloderma and muscle weakness since infancy. He also had tendon contractures, short stature, liver cirrhosis, and interstitial pneumonia. Mutation analysis of FAM111B revealed a novel and de novo heterozygous missense mutation, c.1886T &gt; G (p(Phe629Cys)), through which we were able to diagnose the patient with POIKTMP. 3 years after the POIKTMP diagnosis, interstitial pneumonia had worsened. After 2 weeks of administrating 40 mg/day of prednisolone, his symptoms and lung shadows improved. However, he subsequently developed severe hepatic encephalopathy and eventually died of respiratory failure due to bacterial pneumonia and pulmonary edema. Autopsy revealed an unclassifiable pattern of interstitial pneumonia, as well as the presence of fibrosis and fatty degeneration in several organs, including the liver, kidney, skeletal muscle, heart, pancreas, and thyroid.
  
  Conclusions: We report a case of POIKTMP in which interstitial pneumonia was improved by corticosteroids, suggesting that corticosteroids could be an option for the treatment of interstitial pneumonia associated with this disease.
• Promising Genomic Testing for Biliary Tract Cancer Using Endoscopic Ultrasound-Guided Fine-Needle Aspiration/Biopsy Specimens.
  Masaki Kuwatani, Kazumichi Kawakubo, Naoya Sakamoto
  Diagnostics (Basel, Switzerland), 12, 4, 05 Apr. 2022, [International Magazine]
  English, Scientific journal, The undesired prognosis of biliary tract cancer is mainly attributed to the difficult detection of cancer lesions, including intraepithelial neoplasia and no standard examination for screening. In addition, pathological diagnosis of biliary stricture, whether it is malignant or benign, is not so easy, because of difficult optimal sampling by forceps biopsy and brush cytology, although various devices and methods for pathological diagnosis have been reported. Furthermore, we have to be careful about post-endoscopic retrograde cholangiography pancreatitis when we approach the biliary tract lesion via a transpapillary route. In order to improve the diagnostic accuracy, there have been several studies that indicate the feasibility and efficacy of genomic analysis for accurate diagnosis of biliary tract cancer by using pathological specimens, including endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/FNB) samples. For efficient and precision medicine for patients with biliary tract cancer, future diagnosis and treatment should also be based on molecular and genetic analyses. In this article, we review and summarize the past knowledge and cutting edge of genomic testing for biliary tract cancer, using EUS-FNA/FNB specimens, and indicate some ingenuities in sample processing to promote effective clinical practice and future perspectives.
• ウイルス肝炎研究-ウイルスゲノム・ホストゲノム・免疫 腎臓移植後のB型肝炎ウイルス再活性化の検討　　　　　　　　　　　　　　　
  山田 錬, 森川 賢一, 坂本 直哉
  肝臓, 63, Suppl.1, A108, A108, (一社)日本肝臓学会, Apr. 2022
  Japanese
• 日本人肥満2型糖尿病における腹腔鏡下スリーブ状胃切除術が脂肪肝に及ぼす効果 前向きコホート研究　　　　　　　　　　　　　　　
  大江 悠希, 高瀬 崇宏, 曹 圭龍, 小川 浩司, 海老原 裕磨, 吉川 仁人, 西田 睦, 宮 愛香, 野本 博司, 亀田 啓, 荘 拓也, 須田 剛生, 中村 昭伸, 倉島 庸, 阿保 大介, 工藤 與亮, 坂本 直哉, 平野 聡, 渥美 達也, 三好 秀明
  糖尿病, 65, Suppl.1, S, 139, (一社)日本糖尿病学会, Apr. 2022
  Japanese
• 非アルコール性脂肪肝炎、非代償性肝硬変のhigh MELD例に実施した脳死肝移植の一例　　　　　　　　　　　　　　　
  中村 恒星, 後藤 了一, 巖築 慶一, 川村 典生, 渡辺 正明, 森川 賢一, 小川 浩司, 坂本 直哉, 嶋村 剛, 武冨 紹信
  日本外科学会定期学術集会抄録集, 122回, RS, 2, (一社)日本外科学会, Apr. 2022
  Japanese
• Artificial intelligence (AI) models for the ultrasonographic diagnosis of liver tumors and comparison of diagnostic accuracies between AI and human experts.
  Naoshi Nishida, Makoto Yamakawa, Tsuyoshi Shiina, Yoshito Mekada, Mutsumi Nishida, Naoya Sakamoto, Takashi Nishimura, Hiroko Iijima, Toshiko Hirai, Ken Takahashi, Masaya Sato, Ryosuke Tateishi, Masahiro Ogawa, Hideaki Mori, Masayuki Kitano, Hidenori Toyoda, Chikara Ogawa, Masatoshi Kudo
  Journal of gastroenterology, 57, 4, 309, 321, Apr. 2022, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Ultrasonography (US) is widely used for the diagnosis of liver tumors. However, the accuracy of the diagnosis largely depends on the visual perception of humans. Hence, we aimed to construct artificial intelligence (AI) models for the diagnosis of liver tumors in US. METHODS: We constructed three AI models based on still B-mode images: model-1 using 24,675 images, model-2 using 57,145 images, and model-3 using 70,950 images. A convolutional neural network was used to train the US images. The four-class liver tumor discrimination by AI, namely, cysts, hemangiomas, hepatocellular carcinoma, and metastatic tumors, was examined. The accuracy of the AI diagnosis was evaluated using tenfold cross-validation. The diagnostic performances of the AI models and human experts were also compared using an independent test cohort of video images. RESULTS: The diagnostic accuracies of model-1, model-2, and model-3 in the four tumor types are 86.8%, 91.0%, and 91.1%, whereas those for malignant tumor are 91.3%, 94.3%, and 94.3%, respectively. In the independent comparison of the AIs and physicians, the percentages of correct diagnoses (accuracies) by the AIs are 80.0%, 81.8%, and 89.1% in model-1, model-2, and model-3, respectively. Meanwhile, the median percentages of correct diagnoses are 67.3% (range 63.6%-69.1%) and 47.3% (45.5%-47.3%) by human experts and non-experts, respectively. CONCLUSION:  The performance of the AI models surpassed that of human experts in the four-class discrimination and benign and malignant discrimination of liver tumors. Thus, the AI models can help prevent human errors in US diagnosis.
• Image findings of malignant lymphoma of the gallbladder
  Kuwatani Masaki, Takishin Yunosuke, Mitsuhashi Tomoko, Sakamoto Naoya
  Tando, 36, 1, 82, 90, Japan Biliary Association, 31 Mar. 2022
  Japanese
• Overestimated Renal Function in Patients with Liver Cirrhosis Predicts Poor Prognosis.
  Sonoe Yoshida, Goki Suda, Masatsugu Ohara, Megumi Kimura, Zijian Yang, Osamu Maehara, Qingjie Fu, Shunichi Hosoda, Kubo Akinori, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 52, 7, 603, 613, 30 Mar. 2022, [International Magazine]
  English, Scientific journal, AIM: A high prevalence of overestimated renal function in patients with liver cirrhosis (LC) has been reported; nonetheless, its impact on prognosis remains unclear. We aimed to evaluate the impact of overestimated renal function on prognosis in patients with LC. METHODS: An overestimated renal function was defined as a >20% increase in the creatinine-based estimated glomerular filtration rate (eGFR), compared with cystatin C-based eGFR. LC patients with conserved serum, who were evaluated for muscle atrophy and had proper clinical information were included, and their prognostic factors were analyzed. RESULTS: A total of 215 consecutive patients with LC were included. The prevalence of overestimated renal function was 29.8% (64/215). Kaplan-Meier survival analysis revealed that patients with overestimated renal function had a poorer prognosis than those without overestimated renal function (hazard ratio [HR]: 2.217 95% confidence interval [CI]: 1.290-3.810; P=0.001). Subgroup analysis showed that overestimated renal function was a significant prognostic factor, irrespective of sex and the presence of hepatocellular carcinoma (HCC). Multivariate Cox regression analyses revealed that overestimated renal function was a significant and independent factor predictive of poor prognosis in the entire cohort (HR: 2.050; 95% CI: 1.041-4.037; P=0.038) and in subgroups classified by Child-Pugh class A (HR: 2.131; 95% CI: 1.019-4.458; P=0.044), Model for End-Stage Liver Disease score <9 (HR: 2.303; 95% CI: 1.038-5.109; P=0.04), and presence of HCC (HR: 2.290; 95% CI: 1.128-4.651; P=0.022). CONCLUSION: Overestimated renal function is a significant and independent prognostic factor in patients with LC. This article is protected by copyright. All rights reserved.
• Bleeding After Gastric Endoscopic Submucosal Dissection Focused on Management of Xa Inhibitors.
  Shoko Ono, Masahiro Ieko, Ikko Tanaka, Yoshihiko Shimoda, Masayoshi Ono, Keiko Yamamoto, Naoya Sakamoto
  Journal of gastric cancer, 22, 1, 47, 55, Mar. 2022, [International Magazine]
  English, Scientific journal, PURPOSE: The use of direct oral Xa inhibitors (DXaIs) to prevent venothrombotic events is increasing. However, gastrointestinal bleeding, including that related to endoscopic resection, is a concern. In this study, we evaluated bleeding and coagulation times during the perioperative period of gastric endoscopic submucosal dissection (ESD). MATERIALS AND METHODS: Patients who consecutively underwent gastric ESD from August 2016 to December 2018 were analyzed. Bleeding rates were compared among the 3 groups (antiplatelet, DXaIs, and control). DXaI administration was discontinued on the day of the procedure. Prothrombin time (PT), activated partial thromboplastin time, and the ratio of inhibited thrombin generation (RITG), which was based on dilute PT, were determined before and after ESD. RESULTS: During the study period, 265 gastric ESDs were performed in 239 patients, where 23 and 50 patients received DXaIs and antiplatelets, respectively. Delayed bleeding occurred in 17 patients (7.4%) and 21 lesions (7.1%). The bleeding rate in the DXaI group was significantly higher than that in the other groups (30.4%, P<0.01), and the adjusted odds ratio of bleeding was 5.7 (95% confidence interval, 1.4-23.7; P=0.016). In patients using DXaIs, there was a significant (P=0.046) difference in the median RITG between bleeding cases (18.6%) and non-bleeding cases (3.8%). CONCLUSIONS: A one-day cessation of DXaIs was related to a high incidence of bleeding after gastric ESD, and monitoring of residual coagulation activity at trough levels might enable the predicted risk of delayed bleeding in patients using DXaIs.
• 個別化医療を見据えた消化器診療の現状 超音波内視鏡下穿刺吸引法で得られた検体を用いた膵腫瘍内細菌叢の検討　　　　　　　　　　　　　　　
  中野 真太郎, 川本 泰之, 小松 嘉人, 伊藤 憲, 原田 一顕, 結城 敏志, 川久保 和道, 杉浦 諒, 加藤 新, 平田 幸司, 平田 甫, 中島 正人, 古川 龍太郎, 滝新 悠之介, 永井 孝輔, 横田 勲, 太田 圭祐, 中岡 慎治, 桑谷 将城, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 130回・124回, 36, 36, 日本消化器病学会-北海道支部, Mar. 2022
  Japanese
• 再活性化が疑われた急性E型肝炎の1例　　　　　　　　　　　　　　　
  久保 彰則, 小川 浩司, 吉田 苑永, 細田 峻一, 得地 祐匡, 山田 錬, 北潟谷 隆, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 石田 勢津子, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 130回・124回, 55, 55, 日本消化器病学会-北海道支部, Mar. 2022
  Japanese
• 若年女性に見られた肝細胞腺腫症の1例　　　　　　　　　　　　　　　
  北潟谷 隆, 吉田 苑永, 細田 俊一, 久保 彰則, 得地 祐匡, 山田 錬, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉, 高桑 恵美, 中島 収
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 130回・124回, 56, 56, 日本消化器病学会-北海道支部, Mar. 2022
  Japanese
• 肝癌に対する新世代マイクロ波凝固療法の治療成績　　　　　　　　　　　　　　　
  中井 正人, 吉田 苑永, 細田 峻一, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 130回・124回, 70, 70, 日本消化器病学会-北海道支部, Mar. 2022
  Japanese
• The potential of soluble CD14 in discriminating nonalcoholic steatohepatitis from nonalcoholic fatty liver disease.
  Akihisa Nakamura, Koji Yamamoto, Rei Takeda, Ren Yamada, Akinori Kubo, Kenichi Morikawa, Sayaka Ando, Tomoe Shimazaki, Takaaki Izumi, Machiko Umemura, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Megumi Kimura, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Toshiro Sugiyama, Hiroshi Takeda, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 52, 6, 508, 521, 07 Feb. 2022, [International Magazine]
  English, Scientific journal, BACKGROUND AND AIMS: Although various noninvasive markers and prediction formulas for nonalcoholic steatohepatitis (NASH) have been reported, they are of value only in the diagnosis of the advanced fibrosis stage of NASH. In this study, we evaluated soluble CD14 (sCD14) as a diagnostic marker for discriminating NASH from nonalcoholic fatty liver disease (NAFLD) using an animal model and clinical specimens. METHODS: Serum sCD14 levels were measured in samples derived from mice with diet-induced NASH and patients using an enzyme-linked immunosorbent assay. Our cohort enrolled 126 patients with liver needle biopsy-proven NAFLD. RESULTS: The intestinal defense mechanism in NASH model mice was altered as a consequence of the unique gut environment. Elevated serum levels of sCD14 were observed in mice with diet-induced NASH, and the condition of the liver was exacerbated as a result of exposure to gut-derived endotoxin. We confirmed that the serum sCD14 levels in NAFL patients significantly differed from those in NASH patients. The area under the curve for distinguishing between NAFL and NASH was 0.891. Moreover, we found that serum sCD14 levels were weakly correlated with the inflammation grade based on the NAFLD activity score (NAS), the grade of fibrosis according to the Brunt fibrosis classification, and a positive correlation with the grade of ballooning based on NAS in patients with NAFLD. CONCLUSION: sCD14 could be a useful pathophysiological marker and diagnostic adjunct distinguishing NASH from NAFLD. The use of sCD14 may allow the screening and identification of high-risk groups for NASH development and support early therapeutic interventions.
• 腎移植後のB型肝炎ウイルス(HBV)再活性化の検討　　　　　　　　　　　　　　　
  堀田 記世彦, 山田 錬, 森川 賢一, 田邉 起, 坂本 直哉, 篠原 信雄
  日本臨床腎移植学会プログラム・抄録集, 55回, 260, 260, (一社)日本臨床腎移植学会, Feb. 2022
  Japanese
• Prediction of hepatocellular carcinoma using age and liver stiffness on transient elastography after hepatitis C virus eradication.
  Masato Nakai, Yoshiya Yamamoto, Masaru Baba, Goki Suda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Ken Furuya, Naoya Sakamoto
  Scientific reports, 12, 1, 1449, 1449, 27 Jan. 2022, [International Magazine]
  English, Scientific journal, Liver stiffness measurement (LSM) is a useful tool for assessing advanced liver fibrosis, an important risk factor for hepatocellular carcinoma (HCC) following hepatitis C (HCV) eradication. This study aimed to clarify the non-invasive factors associated with HCC following sustained virological response (SVR) and to identify the low-risk group. 567 patients without history of HCC who achieved SVR at 24 weeks (SVR24) after IFN-free treatment were retrospectively analyzed. The cumulative incidence of HCC and the risk factors were examined using pre-treatment and SVR24 data. The median observation period was 50.2 months. Thirty cases of HCC were observed, and the 4-year cumulative incidence of HCC was 5.9%. In multivariate analysis, significant pre-treatment factors were age ≥ 71 years (hazard ratio [HR]: 3.402) and LSM ≥ 9.2 kPa (HR: 6.328); SVR24 factors were age ≥ 71 years (HR: 2.689) and LSM ≥ 8.4 kPa (HR: 6.642). In cases with age < 71 years and LSM < 8.4 kPa at the time of SVR24, the 4-year cumulative incidence of HCC was as low as 1.1%. Both pre-treatment LSM (≥ 9.2 kPa) and SVR24 LSM (≥ 8.4 kPa) and age (≥ 71 years) are useful in predicting the risk of HCC after SVR with IFN-free treatment. Identification of low-risk individuals may improve the efficiency of follow-up.
• Changes in Serum Growth Factors during Lenvatinib Predict the Post Progressive Survival in Patients with Unresectable Hepatocellular Carcinoma.
  Zijian Yang, Goki Suda, Osamu Maehara, Masatsugu Ohara, Sonoe Yoshida, Shunichi Hosoda, Megumi Kimura, Akinori Kubo, Yoshimasa Tokuchi, Qingjie Fu, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  Cancers, 14, 1, 04 Jan. 2022, [International Magazine]
  English, Scientific journal, Serum growth factor changes and their effect on prognosis during lenvatinib for unresectable hepatocellular carcinoma (HCC) remain underexplored. The sequential changes in serum growth factors during lenvatinib for unresectable HCC were evaluated in 58 patients using complete clinical data, and preserved serum was used to investigate changes in FGF-19, ANG-2, HGF, VEGF, and EGF. Patients with a complete response (CR), partial response (PR), and stable disease (SD) were evaluated for growth factor changes between the best response and progressive disease (PD) points, classified based on these changes, and evaluated by post progression survival (PPS). A total of 8, 24, 18, and 8 patients showed CR, PR, SD, and PD, respectively. Multivariate analysis revealed that age, relative dose intensity, and baseline ANG-2 were significantly associated with treatment response. Growth factor changes between the best response and PD points revealed that patients could be classified into four groups based on the EGF, ANG-2, and HGF changes. Although patient characteristics at baseline and PD, their response to lenvatinib, and PFS were similar among those groups, patients with an increase in all growth factors had significantly shorter PPS (median PPS was 553, 323, and 316 versus 173 days in groups 1-4 p = 0.032). We revealed that the evaluation of the changes in growth factors during lenvatinib could predict PPS.
• 【肝硬変症の診断治療の最新知見】肝硬変に対する次世代治療法 薬剤・再生療法の開発・治験状況
  小川 浩司, 中井 正人, 坂本 直哉
  日本内科学会雑誌, 111, 1, 74, 81, (一社)日本内科学会, Jan. 2022
  Japanese
• Study protocol for HGCSG1801: A multicenter, prospective, phase II trial of second-line FOLFIRI plus aflibercept in patients with metastatic colorectal cancer refractory to anti-EGFR antibodies.
  Hiroshi Nakatsumi, Yoshito Komatsu, Tetsuhito Muranaka, Satoshi Yuki, Yasuyuki Kawamoto, Kazuaki Harada, Masayoshi Dazai, Miki Tateyama, Yusuke Sasaki, Takuto Miyagishima, Yasushi Tsuji, Masaki Katagiri, Michio Nakamura, Susumu Sogabe, Kazuteru Hatanaka, Takashi Meguro, Tomoe Kobayashi, Atsushi Ishiguro, Osamu Muto, Yoshiaki Shindo, Masahito Kotaka, Takayuki Ando, Ryo Takagi, Naoya Sakamoto, Yu Sakata
  Frontiers in oncology, 12, 939425, 939425, 2022, [International Magazine]
  English, Scientific journal, BACKGROUND: The first-line chemotherapy for patients with RAS and BRAF wild-type metastatic colorectal cancer (mCRC) commonly involves cytotoxic regimens, such as FOLFOX and FOLFIRI, combined with epidermal growth factor receptor (EGFR) antibodies. When progression occurs following anti-EGFR antibody-combined chemotherapy, anti-angiogenic inhibitors can be used as second-line treatment. Although randomized controlled trials have shown that anti-angiogenic inhibitors [bevacizumab, ramucirumab, and aflibercept (AFL)] carry survival benefit when combined with FOLFIRI as second-line chemotherapy, such trials did not provide data on patients with mCRC refractory to anti-EGFR antibody-combined chemotherapy. Therefore, our group planned a multicenter, nonrandomized, single-arm, prospective, phase II study to investigate the safety and efficacy of FOLFIRI plus AFL as a second-line chemotherapy for patients with mCRC refractory to oxaliplatin-based chemotherapy combined with anti-EGFR antibodies. METHODS: FOLFIRI (irinotecan 180 mg/m2, l-leucovorin 200 mg/m2, bolus 5-FU 400 mg/m2, and infusional 5-FU 2400 mg/m2/46 h) and AFL (4 mg/kg) will be administered every 2 weeks until progression or unacceptable toxicities occur. The primary endpoint will be the 6-month progression-free survival (PFS) rate, whereas the secondary endpoints will include overall survival, PFS, response rate, disease control rate, adverse events, and relative dose intensity for each drug. A sample size of 41 participants will be required. This study will be sponsored by the Non-Profit Organization Hokkaido Gastrointestinal Cancer Study Group and will be supported by a grant from Sanofi. DISCUSSION: There is only an observational study reporting data on FOLFIRI plus AFL for patients with mCRC who previously received anti-EGFR antibodies; therefore, a prospective clinical trial is needed. This study will prospectively evaluate the efficacy and safety of FOLFIRI plus AFL in patients with mCRC who are resistant to anti-EGFR antibodies and have limited data. Moreover, this study will reveal predictive biomarkers for AFL-based chemotherapy. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials, jRCTs011190006. Registered 19 November, 2019, https://jrct.niph.go.jp/latest-detail/jRCTs011190006.
• Efficacy of rifaximin against covert hepatic encephalopathy and hyperammonemia in Japanese patients.
  Masato Nakai, Goki Suda, Koji Ogawa, Sonoe Yoshida, Shunichi Hosoda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Masatsugu Ohara, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
  PloS one, 17, 7, e0270786, 2022, [International Magazine]
  English, Scientific journal, Covert hepatic encephalopathy (CHE) impairs patient quality of life and occurs in approximately 30% of liver cirrhosis (LC) cases. Japanese clinical practice guidelines recommend rifaximin to treat overt HE (OHE). However, the usefulness of rifaximin against CHE is not thoroughly investigated in Japanese patients. We aimed to investigate the efficacy of rifaximin against hyperammonemia and CHE in Japan. We observed 102 patients with HE showing hyperammonemia secondary to LC and examined various biochemical and behavioral parameters following rifaximin treatment. CHE was diagnosed when the patients exhibited two or more abnormal neuropsychological test (NPT) scores but did not indicate OHE symptoms. In the 102 cases, a significant therapeutic effect of rifaximin on hyperammonemia was observed from 2 to 48 weeks after starting treatment. Excluding 10 patients diagnosed with OHE upon starting rifaximin treatment, 12 of the 92 remaining patients (11.8%) transitioned to OHE within 1 year. The 1 year cumulative OHE transition rate was 14.5%. Among the 24 patients with CHE diagnosed by the NPT for whom NPT results could be evaluated at 4 and 12 weeks after starting treatment, 10 (41.6%) had recovered from CHE at 12 weeks. When the factors contributing to recovery from CHE were examined by multivariate analysis, an ammonia level <129 μg/dL was a significant factor. Rifaximin was thus significantly effective against both hyperammonemia and CHE in Japanese patients.
• Effect of switching from tenofovir disoproxil fumarate to tenofovir alafenamide on lipid profiles in patients with hepatitis B.
  Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Satoshi Abiko, Kenji Kinoshita, Shuichi Miyamoto, Ryo Sugiura, Megumi Kimura, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  PloS one, 17, 1, e0261760, 2022, [International Magazine]
  English, Scientific journal, For long-term treatment of hepatitis B virus (HBV) infection, switching from tenofovir-disoproxil-fumarate (TDF) to tenofovir-alafenamide (TAF) may prevent renal dysfunction and bone loss. However, the precise effects of this switch on the blood lipid profile remain to be clarified. This is an important issue as TDF is known to have effects on both low- and high-density lipids. Therefore, our retrospective multi-center study aimed to evaluate the effects of switching from TDF to TAF on the lipid profile of patients with HBV infection. Samples were obtained prior to the switch from TDF to TAF and at 6-12 months after TAF initiation. In some cases, additional samples obtained pre- and post-TDF administration were available for analysis. Serum cholesterol levels, including oxidized-low-density lipoprotein (LDL) and non-high-density lipoprotein-cholesterol (HDL-c), and the rate of dyslipidemia, according to the NCEP-ATP III lipid risk classification, were analyzed. The data from 69 patients were analyzed, including 33 patients with pre- and post-TDF-initiation serum samples. Total cholesterol (T-chol), HDL-c, LDL-c, non-HDL-c, and oxidized LDL levels increased significantly after switching to TAF. With regard to sequential changes pre- to post-TAF, TDF was associated with significantly lower serum T-chol, HDL-c, and oxidized LDL-c levels, with T-chol, HDL-c, LDL-c, and oxidized LDL-c levels increasing significantly after the switch. The switch from TDF to TAF was also associated with an increase in the rate of dyslipidemia, from 33% to 39%, with an increase in the rate of severe dyslipidemia of 1.4% and 5.8%, based on T-chol and LDL-c levels. Of note, no cases of severe dyslipidemia were detected pre-TAF treatment. As oxidized LDL-c and non-HDL-c are strongly associated with atherosclerosis development, careful monitoring of lipid is needed after switching from TDF to TAF in this clinical population.
• Prospect of lenvatinib for unresectable hepatocellular carcinoma in the new era of systemic chemotherapy.
  Takuya Sho, Kenichi Morikawa, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Mugumi Kimura, Masato Nakai, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  World journal of gastrointestinal oncology, 13, 12, 2076, 2087, 15 Dec. 2021, [International Magazine]
  English, Scientific journal, The phase III clinical trial of the novel molecular targeted agent (MTA) lenvatinib for patients with advanced hepatocellular carcinoma (HCC) (REFLECT trial) found that lenvatinib was non-inferior to sorafenib in overall survival. Recently, the efficacy of multiple MTAs, including lenvatinib, in practice has been reported, and therapeutic strategies for Barcelona Clinic Liver Cancer (BCLC) intermediate stage HCC are undergoing major changes. Based on these results, lenvatinib could be recommended for patients with transcatheter arterial chemoembolization (TACE)-refractory, ALBI grade 1, within the up-to-seven criteria in the BCLC intermediate stage. Lenvatinib provides a more favorable outcome than TACE, even in cases with large or multinodular HCC beyond the up-to-seven criteria with Child-Pugh grade A. When patients meet the definitions of TACE-refractory or TACE-unsuitable, switching to systemic chemotherapy, including lenvatinib, is for favorable for preserving liver function. If initial treatment, including MTA, has a significant therapeutic effect and downstaging of HCC is obtained, additional TACE or surgical resection should be considered. Lenvatinib also has a therapeutic effect for poorly differentiated type and non-simple nodular type HCC thanks to the survival-prolonging effect of this drug. Furthermore, a significant therapeutic effect is expected in tumors with more than 50% liver involvement or main portal vein invasion, which have traditionally been considered to have a poor prognosis in patients. This suggests that at the start of lenvatinib treatment, HCC patients with ALBI grade 1 may be able to maintain liver functional reserve.
• Possible correlation between increased serum free carnitine levels and increased skeletal muscle mass following HCV eradication by direct acting antivirals
  Yoshimasa Tokuchi, Goki Suda, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Akinori Kubo, Sonoe Yoshida, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Masatsugu Ohara, Ren Yamada, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  Scientific Reports, 11, 1, Springer Science and Business Media LLC, Dec. 2021
  Scientific journal, We aimed to evaluate factors associated with changes in skeletal muscle mass in hepatitis C virus (HCV)-infected patients after treatment with direct-acting antivirals (DAAs). Consecutive HCV-infected patients after treatment with DAA were recruited into the study. Patients who achieved sustained virological response (SVR); and had complete clinical information, preserved serum samples at baseline and SVR48, and skeletal muscle mass evaluations based on the psoas muscle mass index (PMI) on computed tomography at baseline and ≥ 12 months were included. Altogether, 70.7% of patients (41/58) showed increased PMI after DAA therapy, and mean relative PMI was significantly higher after DAA therapy than at baseline. There were no significant associations between baseline clinical factors routinely examined in clinical practice and increased PMI. Among factors reported to be associated with skeletal muscle loss in patients with chronic liver disease, serum zinc levels and total and free carnitine levels increased significantly after DAA therapy and only changes in serum free carnitine levels were significantly associated with an increased PMI (r = 0305, P = 0.020). In conclusion, increased skeletal muscle mass after successful HCV eradication by DAAs was significantly associated with increased serum-free carnitine levels. l-carnitine supplementation may be beneficial in patients with low skeletal muscle mass after DAA.
• Eradication of Helicobacter pylori may improve dyspepsia in the elderly for the long term.
  Ikko Tanaka, Shoko Ono, Yoshihiko Shimoda, Masaki Inoue, Sayoko Kinowaki, Momoko Tsuda, Masayoshi Ono, Keiko Yamamoto, Yuichi Shimizu, Mototsugu Kato, Naoya Sakamoto
  BMC gastroenterology, 21, 1, 445, 445, 25 Nov. 2021, [International Magazine]
  English, Scientific journal, BACKGROUND: Therapy for eradication of Helicobacter pylori (H. pylori) improves symptoms of H. pylori-associated dyspepsia (HPD), but the effects of eradication in elderly patients are unclear. The aim of our study was to investigate dyspepsia symptoms and long-term effects of eradication in elderly patients. METHODS: This retrospective study included 496 patients who received H. pylori eradication therapy. The patients were divided into a group of elderly patients (group E: ≧ 65 years old) and a group of non-elderly patients (group N: < 65 years old). Abdominal symptoms were evaluated using a questionnaire about abdominal symptoms before eradication and after eradication (1-2 months and more than one year). Dyspepsia was defined as a score of 4 points or more for at least one of 4 items (postprandial fullness, early satiety, epigastric pain, and hunger pain). Improvement of symptoms was defined on the basis of changes in Global Overall Systems scores. RESULTS: There were no differences in abdominal symptoms before eradication between the two groups. Successful eradication improved symptoms in patients with dyspepsia within 2 months (in 75.6% (56/74) of the patients in group N and in 64.5% (20/31) of the patients in group E). The questionnaire showed that 80% (32/40) of the patients in group N and 60% (12/20) of the patients in group E had long-term relief of dyspepsia. The scores for abdominal symptoms in group E continued to improve for a mean period of 54.8 months after eradication. CONCLUSIONS: Eradication of H. pylori age-independently improved dyspepsia symptoms for the long term.
• 特集 肝不全･肝硬変に対する再生療法-最先端の今 4.開発中の肝再生医療(7)肝星細胞に対するビタミンAを介した肝線維化改善療法の開発
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  臨床消化器内科, 36, 13, 1690, 1694, 日本メディカルセンター, 20 Nov. 2021
• 治療法の再整理とアップデートのために 専門家による私の治療 C型肝炎
  森川 賢一, 坂本 直哉
  日本医事新報, 5092, 40, 40, (株)日本医事新報社, Nov. 2021
  Japanese
• Evaluation of the risk of metachronous multiple squamous cell carcinoma of the head and neck after transoral surgery based on the genetic polymorphisms of alcohol dehydrogenase 1B and aldehyde dehydrogenase 2.
  Masaki Inoue, Yuichi Shimizu, Masanobu Taniguchi, Yuki Kimura, Hiroto Furuhashi, Akira Dobashi, Takashi Ikeya, Kenichi Goda, Masayuki Kato, Mototsugu Kato, Naoya Sakamoto, Akihito Watanabe
  Carcinogenesis, 42, 10, 1232, 1238, 26 Oct. 2021, [International Magazine]
  English, Scientific journal, Patients with superficial head and neck squamous cell carcinoma (HNSCC) can be completely treated by techniques of transoral surgery (TOS). The aim of this study was to evaluate the risk of metachronous multiple HNSCC arising after TOS based on alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase 2 (ALDH2). We registered patients who underwent TOS for superficial HNSCC. Buccal cell samples were obtained by using a cotton swab to examine two single nucleotide polymorphisms in ADH1B and ALDH2 genotyping. We used Cox proportional hazards models to examine the risk of metachronous HNSCC. A total of 198 patients who underwent TOS for HNSCC were evaluated. In multivariate analysis, risks for second HNSCC were ADH1B*1/*1 [hazard ratio (HR), 1.88; 95% confidence interval (CI), 1.11-3.19; P = 0.02], ALDH2*1/*2 (HR, 2.11; 95% CI, 1.00-5.16; P = 0.048) and alcohol consumption before TOS (HR, 1.17; 95% CI, 1.06-1.27; P = 0.01). The 5-year incidence rates of second primary HNSCC in the temperance group and the non-temperance group were 20.8 and 46.5%, respectively (HR, 0.54; 95% CI, 0.31-0.92; P = 0.02). Cumulative development rates of third HNSCC in the temperance group and non-temperance group at 10 years were 11.3 and 36.1%, respectively (HR, 0.19; 95% CI, 0.03-0.65; P = 0.006). ADH1B*1/*1, ALDH2*1/*2 and moderate or heavy alcohol consumption before treatment are independent risk factors of metachronous HNSCC. Since it was shown that temperance decreased the incidences of second and third metachronous HNSCC, advice to discontinue alcohol drinking is necessary.
• 【肝胆膵疾患におけるバイオマーカーの意義を探る】肝疾患のバイオマーカー NASHにおける新規糖鎖バイオマーカー(AAT-A3F)　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 83, 4, 527, 533, (株)アークメディア, Oct. 2021
  Japanese
• HGCSG2101 実臨床における進行膵癌に対するnal/IRI+5-FU/LVの治療成績　　　　　　　　　　　　　　　
  山村 貴洋, 原田 一顕, 曽我部 進, 澤田 憲太郎, 八木澤 允貴, 中野 真太郎, 太宰 昌佳, 舘山 美樹, 伊藤 憲, 斎藤 里佳, 川本 泰之, 結城 敏志, 坂本 直哉, 坂田 優, 小松 嘉人
  日本癌治療学会学術集会抄録集, 59回, O43, 2, (一社)日本癌治療学会, Oct. 2021
  English
• Endoscopic treatment for hepaticojejunostomy anastomotic stricture: Advantages and disadvantages of balloon dilatation with stenting.
  Masaki Kuwatani, Naoya Sakamoto
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 29 Sep. 2021, [International Magazine]
  English
• The TLR4-TRIF-type 1 IFN-IFN-γ pathway is crucial for gastric MALT lymphoma formation after Helicobacter suis infection.
  Koji Yamamoto, Yasuyuki Kondo, Shunsuke Ohnishi, Masaru Yoshida, Toshiro Sugiyama, Naoya Sakamoto
  iScience, 24, 9, 103064, 103064, 24 Sep. 2021, [International Magazine]
  English, Scientific journal, Helicobacter suis, a zoonotic infection-related bacterium, can induce gastric mucosa-associated lymphoid tissue (MALT) lymphoma in humans and animals. Recently, we reported that the formation of gastric MALT lymphoma after H. suis infection is induced by interferon (IFN)-γ activation. Here, we revealed that activation of the Toll-like receptor (TLR) 4-Toll/IL-1 receptor domain-containing adapter-inducing interferon-β (TRIF) pathway after H. suis infection is associated with the production of type 1 IFNs (IFN-α, IFN-β) by gastric epithelial cells. Additionally, these type 1 IFNs interact with type 1 IFN receptors on gastric B cells, facilitating the secretion of IFN-γ and the activation of which is enhanced by positive feedback regulation in B cells. These results suggest that the TLR4-TRIF-type 1 IFN-IFN-γ pathway is crucial in the development of gastric MALT lymphoma after H. suis infection and may, therefore, represent a therapeutic target for the prevention of this condition.
• Immunoglobulin G4-related cholecystitis mimicking gallbladder cancer diagnosed by EUS-guided biopsy.
  Kosuke Nagai, Masaki Kuwatani, Yunosuke Takishin, Ryutaro Furukawa, Hajime Hirata, Kazumichi Kawakubo, Tomoko Mitsuhashi, Naoya Sakamoto
  Endoscopic ultrasound, 03 Sep. 2021, [International Magazine]
  English, Scientific journal
• 当院における切除不能肝細胞癌に対するAtezolizumab+Bevacizumab併用療法の使用経験　　　　　　　　　　　　　　　
  吉田 苑永, 荘 拓也, 久保 彰則, 得地 祐匡, 細田 峻一, 北潟谷 隆, 山田 錬, 中井 正人, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 129回・123回, 40, 40, 日本消化器病学会-北海道支部, Sep. 2021
  Japanese
• Lenvatinib加療後にCRに至りconversion surgeryを施行した肝内多発転移を伴う肝細胞癌の1例　　　　　　　　　　　　　　　
  細田 峻一, 中井 正人, 吉田 苑永, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉, 岡崎 ななせ, 大塚 拓也, 三橋 智子
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 129回・123回, 42, 42, 日本消化器病学会-北海道支部, Sep. 2021
  Japanese
• Transient elastographyによるLSMと年齢を用いたSVR後肝発癌低リスク群の囲い込み　　　　　　　　　　　　　　　
  中井 正人, 山本 義也, 馬場 英, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 重沢 拓, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 古家 乾, 坂本 直哉
  肝臓, 62, Suppl.2, A543, A543, (一社)日本肝臓学会, Sep. 2021
  Japanese
• 除不能進行肝細胞癌に対するアテゾリズマブ+ベバシズマブ併用療法の初期治療経験:多施設共同研究　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 久保 彰則, 北潟谷 隆, 山田 錬, 重沢 拓, 中井 正人, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 62, Suppl.2, A550, A550, (一社)日本肝臓学会, Sep. 2021
  Japanese
• 巨大大腸腫瘍ESD後の狭窄に対するバルーン拡張で穿孔をきたした1例　　　　　　　　　　　　　　　
  西村 友佑, 大野 正芳, 松本 将吾, 久保 茉理奈, 霜田 佳彦, 田中 一光, 山本 桂子, 小野 尚子, 市川 伸樹, 本間 重紀, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 129回・123回, 62, 62, 日本消化器病学会-北海道支部, Sep. 2021
  Japanese
• 肝細胞癌において血清中表皮型脂肪酸結合タンパク質は組織中発現レベルとは独立した予後不良因子である　　　　　　　　　　　　　　　
  大平 将史, 横尾 英樹, 小川 浩司, 深井 原, 神山 俊哉, 坂本 直哉, 武冨 紹信
  日本癌学会総会記事, 80回, [J14, 4], (一社)日本癌学会, Sep. 2021
  English
• クローン病の予後予測について経腹的超音波検査を用いた後方視的検討　　　　　　　　　　　　　　　
  福島 新弥, 西田 睦, 桜井 健介, 表原 里実, 桂田 武彦, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 129回・123回, 59, 59, 日本消化器病学会-北海道支部, Sep. 2021
  Japanese
• Genomic profiling of intestinal/mixed-type superficial non-ampullary duodenal epithelial tumors.
  Shuichi Miyamoto, Goki Suda, Marin Ishikawa, Hideyuki Hayashi, Satoshi Nimura, Yoshihiro Matsuno, Ryo Mori, Shigeki Tanishima, Takahiko Kudo, Tomofumi Takagi, Yoshiya Yamamoto, Shoko Ono, Yuichi Shimizu, Naoya Sakamoto
  JGH open : an open access journal of gastroenterology and hepatology, 5, 9, 1071, 1077, Sep. 2021, [International Magazine]
  English, Scientific journal, Background and Aim: The mechanism underlying carcinogenesis and the genomic features of superficial non-ampullary duodenal epithelial tumors (SNADETs) have not been elucidated in detail. In this study, we examined the genomic features of incipient SNADETs, such as small lesions resected via endoscopic treatment, using next-generation sequencing (NGS). Methods: Twenty consecutive patients who underwent endoscopic treatment for SNADETs of less than 20 mm between January and December 2017 were enrolled. Targeted genomic sequencing was performed through NGS using a panel of 160 cancer-related genes. Furthermore, the alteration/mutation frequencies in SNADETs were examined. Results: The maximum size of the SNADETs examined in this study was 12 mm in diameter. Five SNADETs were classified as low-grade dysplasia (LGD) tumors, while 14 SNADETs were classified as high-grade dysplasia tumors. Only one carcinoma in situ was detected. NGS data for 16 samples were obtained. APC alterations were detected in 81% of samples (13/16). KRAS, BRAF, and TP53 alterations were detected in 25% (4/16), 18.8% (3/16), and 6.3% (1/16) of cases, respectively. Conclusion: We detected APC alterations in most small SNADETs resected via endoscopic treatment, from LGD to carcinoma samples. Even in SNADETs classified as small LGD exhibited KRAS and BRAF alterations.
• Early response and safety of atezolizumab plus bevacizumab for unresectable hepatocellular carcinoma in patients who do not meet IMbrave150 eligibility criteria.
  Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Osamu Maehara, Shunsuke Ohnishi, Taku Shigesawa, Akihisa Nakamura, Ren Yamada, Masatsugu Ohara, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Kazuharu Suzuki, Takaaki Izumi, Takashi Meguro, Katsumi Terashita, Jun Ito, Takuto Miyagishima, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 51, 9, 979, 989, Sep. 2021, [International Magazine]
  English, Scientific journal, AIM: A clinical trial (IMbrave150) indicated the efficacy and safety of atezolizumab plus bevacizumab for patients with unresectable hepatocellular carcinoma (HCC). In this study, we evaluated this therapeutic combination in a real-world setting, with a focus on patients who did not meet the IMbrave150 eligibility criteria. METHODS: In this multicenter study, patients with unresectable HCC treated with atezolizumab plus bevacizumab between October 2020 and May 2021 were screened. In patients who did not meet IMbrave150 eligibility criteria, treatment responses and safety at 6 and 12 weeks were evaluated. RESULTS: Atezolizumab plus bevacizumab was initiated in 64 patients, including 46 patients (71.9%) who did not meet IMbrave150 eligibility criteria. Most of these patients had a history of systemic therapy (44/46). The objective response rate and disease control rate observed using Response Evaluation Criteria in Solid Tumors 1.1 were 5.2% and 82.8% at 6 weeks and 10.0% and 84.0% at 12 weeks, respectively; these rates were similar between patients who met and did not meet the IMbrave150 criteria. Ten patients experienced progressive disease (PD) at 6 weeks. Portal vein tumor thrombosis was significantly associated with PD (p = 0.039); none of the 15 patients with hepatitis B virus-related HCC experienced PD (p = 0.050). The most common adverse events of grade 3 or higher were aspartate aminotransferase elevation (n = 8, 13.8%) and the safety profile was similar between patients who met and did not meet the IMbrave150 criteria. CONCLUSION: Most patients treated with atezolizumab plus bevacizumab did not meet the IMbrave150 criteria; however, the combination therapy showed good safety and efficacy at the early treatment phase.
• 【ここまできた肝細胞癌の薬物療法:2021 update】免疫療法の動向 アテゾリズマブ+ベバシズマブによるCR例の特徴
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 83, 2, 259, 263, (株)アークメディア, Aug. 2021
  Japanese
• 診断に苦慮した悪性リンパ腫による胆道狭窄の一剖検例
  平田 幸司, 中島 克磨, 鈴木 和治, 宮本 秀一, 木下 賢治, 安孫子 怜史, 畑中 一映, 山本 義也, 成瀬 宏仁, 桑谷 将城, 坂本 直哉, 岡崎 ななせ, 谷川 聖, 田中 伸哉
  胆道, 35, 3, 514, 514, (一社)日本胆道学会, Aug. 2021
  Japanese
• 診断・治療に難渋した症例～round table discussion 反復する急性膵炎と膵周囲液体貯留を認めたpancreatic fistulaの1例
  平田 甫, 桑谷 将城, 永井 孝輔, 瀧新 悠之介, 古川 龍太郎, 坂本 直哉, 浅野 賢道, 平野 聡, 三橋 智子
  膵臓, 36, 3, A257, A257, (一社)日本膵臓学会, Aug. 2021
  Japanese
• 著明な隆起を伴った下咽頭上皮内癌の1例　　　　　　　　　　　　　　　
  西村 友佑, 清水 勇一, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 小野 尚子, 三橋 智子, 鈴木 崇祥, 坂本 直哉
  耳鼻咽喉科展望, 64, 4, 255, 256, 耳鼻咽喉科展望会, Aug. 2021
  Japanese
• 【ここまできた肝細胞癌の薬物療法:2021 update】免疫療法の動向 アテゾリズマブ+ベバシズマブによるCR例の特徴　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 83, 2, 259, 263, (株)アークメディア, Aug. 2021
  Japanese
• Clinical and Image Characteristics of IgG4-Related Sclerosing Cholecystitis.
  Masaki Kuwatani, Naoya Sakamoto
  Diagnostics (Basel, Switzerland), 11, 8, 28 Jul. 2021, [International Magazine]
  English, Scientific journal, Since autoimmune pancreatitis (AIP) was established as a new disease entity, sclerosing change with abundant immunoglobulin-4 (IgG4)-positive plasma cells, storiform fibrosis, and obliterative phlebitis are main pathological features in IgG4-related diseases. Regarding IgG4-related sclerosing cholecystitis (IgG4-CC), which is occasionally associated with AIP cases and is rarely isolated, there are no diagnostic criteria and insufficient perceptions of the image findings. Although there have been some reports on IgG4-CC, differentiation between IgG4-CC and gallbladder cancer is very difficult in some cases with a localized lesion. In this review, we especially focused on image findings of IgG4-CC and summarized its image features for diagnostic assistance. The ultrasonography and CT findings of IgG4-CC could be classified into diffuse and localized types. Based on these findings, the presence of wall thickening with an intact or smooth mucosal layer, followed by a homogenously thickened outer layer, would be a helpful morphological finding to distinguish IgG4-CC from gallbladder cancer.
• Characteristics and Lenvatinib Treatment Response of Unresectable Hepatocellular Carcinoma with Iso-High Intensity in the Hepatobiliary Phase of EOB-MRI.
  Akinori Kubo, Goki Suda, Megumi Kimura, Osamu Maehara, Yoshimasa Tokuchi, Takashi Kitagataya, Masatsugu Ohara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  Cancers, 13, 14, 20 Jul. 2021, [International Magazine]
  English, Scientific journal, In hepatocellular carcinoma (HCC), CTNNB-1 mutations, which cause resistance to immune checkpoint inhibitors, are associated with HCC with iso-high intensity in the hepatobiliary phase of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) in resectable HCC; however, analyses on unresectable HCC are lacking. This study analyzed the prevalence, characteristics, response to lenvatinib, and CTNNB-1 mutation frequency in unresectable HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI. In 52 patients with unresectable HCC treated with lenvatinib, the prevalence of iso-high intensity in the hepatobiliary phase of EOB-MRI was 13%. All patients had multiple HCCs, and 3 patients had multiple HCCs with iso-high intensity in the hepatobiliary phase of EOB-MRI. Lenvatinib response to progression-free survival and overall survival were similar between patients with or without iso-high intensity in the hepatobiliary phase of EOB-MRI. Seven patients (three and four patients who had unresectable HCC with or without iso-high intensity in the hepatobiliary phase of EOB-MRI, respectively) underwent genetic analyses. Among these, two (67%, 2/3) who had HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI carried a CTNNB-1 mutation, while all four patients who had HCC without iso-high intensity in the hepatobiliary phase of EOB-MRI did not carry the CTNNB-1 mutation. This study's findings have clinical implications for the detection and treatment of HCC with iso-high intensity in the hepatobiliary phase of EOB-MRI.
• Frequency and Characteristics of Overestimated Renal Function in Japanese Patients with Chronic Liver Disease and Its Relation to Sarcopenia.
  Sonoe Yoshida, Goki Suda, Masatsugu Ohara, Qingjie Fu, Zijian Yang, Shunichi Hosoda, Megumi Kimura, Kubo Akinori, Yoshimasa Tokuchi, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Osamu Maehara, Shunsuke Ohnishi, Naoya Sakamoto
  Nutrients, 13, 7, 14 Jul. 2021, [International Magazine]
  English, Scientific journal, Renal dysfunction and sarcopenia are important prognostic factors in patients with chronic liver disease (CLD). Muscle atrophy can cause the overestimation of renal function based on serum creatinine. However, the frequency of overestimated renal function in Japanese patients with CLD and its relationship with sarcopenia are unclear. In present study, we evaluated the frequency of overestimated renal function, defined as a >20% higher eGFR using creatinine than using cystatin C, in 307 patients with CLD as well as its relationship with indicators of sarcopenia. In total, 24.8% of patients had overestimated renal function. In a multivariate regression analysis, liver cirrhosis (p = 0.004) and psoas muscle mass index (p = 0.049) were significantly associated with overestimated renal function. Loss of skeletal muscle mass was significantly more frequent in both male and female patients with overestimated renal function than without. In males, the loss of muscle strength and rate of sarcopenia, defined as loss of muscle mass and strength, were significantly higher in patients with than without overestimated renal function. The high frequency of overestimated renal function in Japanese patients suggests that indicators of renal function should be carefully considered; furthermore, monitoring and interventions for both renal function and sarcopenia are needed in patients with CLD.
• Trial protocol: a randomised controlled trial to verify the non-inferiority of a partially covered self-expandable metal stent to an uncovered self-expandable metal stent for biliary drainage during neoadjuvant therapy in patients with pancreatic cancer with obstructive jaundice (PUN-NAC trial).
  Masaki Kuwatani, Kazumichi Kawakubo, Kazuya Sugimori, Hiroyuki Inoue, Hideki Kamada, Hirotoshi Ishiwatari, Shin Kato, Takuji Iwashita, Makoto Yoshida, Shinichi Hashimoto, Masahiro Itonaga, Yusuke Mizukami, Yusuke Nomura, Akio Katanuma, Naoya Sakamoto
  BMJ open, 11, 7, e045698, 08 Jul. 2021, [International Magazine]
  English, Scientific journal, INTRODUCTION: Neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy (NAC/NACRT) for resectable/borderline resectable pancreatic cancers was recently performed to improve clinical outcomes and led to good results, although it remains controversial whether NAC/NACRT is beneficial for resectable pancreatic cancer. A few recent studies revealed longer patency and lower cost related to the stent occlusion of a metal stent than those of a plastic stent during NAC/NACRT. It also remains controversial which type of self-expandable metal stent (SEMS) is the most suitable for patients with resectable/borderline resectable pancreatic cancer during NAC/NACRT: an uncovered SEMS (USEMS), a fully covered SEMS (FCSEMS) or a partially covered SEMS (PCSEMS). So far, two randomised controlled trials indicated that a USEMS and an FCSEMS were similar in preoperative stent dysfunction and adverse event rate. Thus, we aimed to verify the non-inferiority of a PCSEMS to a USEMS in this multicentre randomised controlled trial. METHODS AND ANALYSIS: We designed a multicentre randomised controlled trial, for which we will recruit 100 patients with resectable/borderline resectable pancreatic cancer and distal biliary obstruction scheduled for NAC/NACRT from 13 high-volume institutions. Patients will be randomly allocated to the PCSEMS group or USEMS group. The primary outcome measure is the preoperative biliary event rate. Data will be analysed after completion of the study. We will calculate the 95% CIs of the incidence of preoperative biliary events in each group and analyse whether the difference between them is within the non-inferiority margin (10%). ETHICS AND DISSEMINATION: This study has been approved by the institutional review board of Hokkaido University Hospital. The results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. TRIAL REGISTRATION NUMBER: UMIN000041737; jRCT1012200002.
• 【ガイドライン2020から読み解くNAFLD/NASH】診断 NAFLD/NASHの超音波診断
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 83, 1, 67, 73, (株)アークメディア, Jul. 2021
  Japanese
• 特集 消化器ステント術のすべて II. 臓器別各論 4. 胆･膵 2)術前胆道ドレナージにおけるステント留置-適応と臨床成績
  桒谷 将城, 永井 孝輔, 平田 甫, 瀧新 悠之介, 古川 龍太郎, 川久保 和道, 坂本 直哉, 平野 聡
  外科, 83, 8, 917, 927, 南江堂, 01 Jul. 2021
• 【ガイドライン2020から読み解くNAFLD/NASH】診断 NAFLD/NASHの超音波診断　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 83, 1, 67, 73, (株)アークメディア, Jul. 2021
  Japanese
• Schlafen 11 predicts response to platinum-based chemotherapy in gastric cancers.
  Tsuyoshi Takashima, Daiki Taniyama, Naoya Sakamoto, Maika Yasumoto, Ryuichi Asai, Takuya Hattori, Ririno Honma, Pham Quoc Thang, Shoichi Ukai, Ryota Maruyama, Kenji Harada, Kazuya Kuraoka, Kazuaki Tanabe, Atsuo T Sasaki, Hideki Ohdan, Eiichi Morii, Junko Murai, Wataru Yasui
  British journal of cancer, 125, 1, 65, 77, Jul. 2021, [International Magazine]
  English, Scientific journal, BACKGROUND: Although unresectable or recurrent gastric cancers (GC) are frequently treated with platinum-based chemotherapy, response to treatment remains unpredictable. Because Schlafen 11 (SLFN11) is recently identified as a critical determinant of platinum sensitivity, we investigated the potential clinical utility of SLFN11 in the treatment of GC. METHODS: We analysed the correlation between SLFN11 expression and overall survival in 169 GC patients by our established immunohistochemical approach. The impact of SLFN11 expression on the response to platinum and transition of SLFN11 expression upon long-term treatment with platinum were examined using GC cell lines and organoids. RESULTS: GC patients with high-SLFN11 expression exhibited significantly better survival than those with low-SLFN11 expression, and the significance increased when we selected patients treated with platinum-based chemotherapy. Knockout of SLFN11 and reactivation of SLFN11 in GC cells conferred resistance and sensitivity to platinum, respectively. In GC cells and organoids, long-term treatment with oxaliplatin suppressed SLFN11 expression while imparting drug resistance. The acquired resistance to oxaliplatin was reversed by reactivation of SLFN11 with epigenetic modifying drugs. CONCLUSIONS: This is the first report revealing definitive clinical implications of SLFN11 in the treatment of GC patients and providing novel strategies for the drug selection based on SLFN11 expression.
• FGFR2 maintains cancer cell differentiation via AKT signaling in esophageal squamous cell carcinoma.
  Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Taku Shigesawa, Gouki Kanbe, Megumi Kimura, Masaya Sugiyama, Masashi Mizokami, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Seiji Naganuma, Naoto Okubo, Shunsuke Ohnishi, Hiroshi Takeda, Naoya Sakamoto
  Cancer biology & therapy, 22, 5-6, 372, 380, 03 Jun. 2021, [International Magazine]
  English, Scientific journal, Fibroblast growth factors (FGFs) and their receptors (FGFRs) are important for signaling to maintain cancer stem-like cells (CSCs) in esophageal squamous cell carcinoma (ESCC). However, which FGF receptor, 1, 2, 3, 4, and L1, is essential or whether FGFRs have distinct different roles in ESCC-CSCs is still in question. This study shows that FGFR2, particularly the IIIb isoform, is highly expressed in non-CSCs. Non-CSCs have an epithelial phenotype, and such cells are more differentiated in ESCC. Further, FGFR2 induces keratinocyte differentiation through AKT but not MAPK signaling and diminishes CSC populations. Conversely, knockdown of FGFR2 induces epithelial-mesenchymal transition (EMT) and enriches CSC populations in ESCC. Finally, data analysis using The Cancer Genome Atlas (TCGA) dataset shows that expression of FGFR2 significantly correlated with cancer cell differentiation in clinical ESCC samples. The present study shows that each FGFR has a distinct role and FGFR2-AKT signaling is a key driver of keratinocyte differentiation in ESCC. Activation of FGFR2-AKT signaling could be a future therapeutic option targeting CSC in ESCC.
• Prognostic Value and Molecular Landscape of HER2 Low-Expressing Metastatic Colorectal Cancer.
  Masataka Yagisawa, Kentaro Sawada, Yoshiaki Nakamura, Satoshi Fujii, Satoshi Yuki, Yoshito Komatsu, Takayuki Yoshino, Naoya Sakamoto, Hiroya Taniguchi
  Clinical colorectal cancer, 20, 2, 113, 120, Jun. 2021, [International Magazine]
  English, Scientific journal, BACKGROUND: The prognostic value and molecular landscape of human epidermal growth factor receptor 2 (HER2) low-expressing (HER2-L) metastatic colorectal cancer (mCRC) remain unclear. PATIENTS AND METHODS: This study enrolled patients with mCRC who had undergone surgical resection of primary tumor. Using the specimen, we evaluated HER2 expression by immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positivity was defined as follows: HER2 positivity (HER2-Pos) as IHC 3 + or IHC 2+/FISH positive, HER2-L as IHC 2+/FISH negative or IHC 1+, and HER2 negativity (HER2-Neg) as IHC 0+. Gene alterations were determined by next-generation sequencing. RESULTS: Between 2005 and 2015, a total of 370 patients were analyzed, comprising 15 patients (4%) with HER2-Pos, 21 (6%) with HER2-L, and 334 (90%) with HER2-Neg disease. The clinicopathologic characteristics among groups had no differences. HER2-L had a significantly higher proportion of coaltered RAS mutation than HER2-Pos (P = .037). With a median follow-up of 101.8 months, HER2-L had a significantly better median overall survival than HER2-Pos (P = .029) (18.2 months in HER2-Pos vs. 33.3 in HER2-L vs. 27.9 in HER2-Neg). In 58 patients harboring wild-type RAS and receiving anti-EGFR antibody therapy, HER2-L had a better median progression-free survival tendency than HER2-Pos, with 2.2 months in HER2-Pos, 7.8 in HER2-L, and 5.1 in HER2-Neg (P = .036). CONCLUSION: HER2-L mCRC showed a better prognosis than HER2-Pos mCRC, and it is similar to HER2-Neg mCRC. Hence, HER2-L mCRC might have different biologic behavior in terms of prognostic value and molecular landscape of mCRC, suggesting the possibility of implementation of HER2-guided clinical development against HER2-expressing mCRC.
• Experiment on endoscopic balloon dilation for esophageal stenosis after endoscopic submucosal dissection in pigs.
  Sayoko Kinowaki, Yuichi Shimizu, Masayoshi Ono, Yang ZiJian, Ikko Tanaka, Yoshihiko Shimoda, Masaki Inoue, Marin Ishikawa, Keiko Yamamoto, Shoko Ono, Shunsuke Ohnishi, Naoya Sakamoto
  Journal of gastroenterology, 56, 6, 527, 536, Jun. 2021, [Domestic magazines]
  English, Scientific journal, BACKGROUND AND AIM: Endoscopic balloon dilation (EBD) is effective for esophageal stenosis caused by ESD. However, an efficient EBD method has not been established. We, therefore, conducted EBD experiments on porcine esophageal stenosis models. METHODS: Study 1: in dilation models (day 22 after ESD), the thickness of the outer muscle layer (as an index of the extension effect) and the area of muscle fiber bundle necrosis in the inner muscle layer (as an index of thermal damage) were evaluated. Study 2: in restenosis models (day 43 after ESD), the thickness of the fibrous plexus (as an index of restenosis) was evaluated. In total, 12 porcine models were created. RESULTS: Study 1: the thickness of the outer muscle layer was 1243 ± 322 μm in surrounding locations and it was 803 ± 145 μm beneath the laceration (p = 0.005). In cases of muscular layer injury, the area of necrosis was 15,500 ± 10400 μm2 in surrounding locations and it was 40,200 ± 12900 μm2 at the laceration site (p < 0.001). Study 2: the thickness of the fibrous plexus was 1359 ± 196 μm in surrounding locations and it was 1322 ± 136 μm2 in the laceration scar site (p = 0.74). CONCLUSION: Since thermal damage persists until the completion of stenosis, EBD in the initial stage should be carefully performed. An extension effect was observed only at the laceration site and it later returned to a status similar to that of surrounding locations. Additional intervention would be required for preventing restenosis.
• A Phase I Trial of Oxaliplatin, Irinotecan, and S-1 Combination Therapy (OX-IRIS) as Chemotherapy for Unresectable Pancreatic Cancer (HGCSG 1403).
  Yasuyuki Kawamoto, Hiroshi Nakatsumi, Kazuaki Harada, Tetsuhito Muranaka, Atsushi Ishiguro, Yoshimitsu Kobayashi, Hideyuki Hayashi, Satoshi Yuki, Kentaro Sawada, Masataka Yagisawa, Shintar Nakano, Naoya Sakamoto, Yoshito Komatsu
  The oncologist, 26, 10, e1675-e1682, 28 May 2021, [International Magazine]
  English, Scientific journal, LESSONS LEARNED: Because S-1 is orally administered, OX-IRIS does not necessitate the continuous infusion of 5-FU and is more convenient. The recommended dose of OX-IRIS was determined to be level - 1 (oxaliplatin, 65 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), which has manageable safety and promising anticancer activities. BACKGROUND: OX-IRIS is a new combination therapy of oxaliplatin, irinotecan, and S-1 for unresectable pancreatic ductal adenocarcinoma (PDAC), which may be beneficial because S-1 is administered orally and continuous infusion of 5-fluorouracil (5-FU) is not needed. METHODS: Patients who had not received prior therapy for unresectable PDAC were enrolled. Adenocarcinoma or adenosquamous histology was required. Oxaliplatin and irinotecan were administered on days 1 and 15; S-1 was administered orally twice a day on days 1-14, followed by 14 days of rest (one cycle). Primary endpoints were dose-limiting toxicity (DLT) and maximum tolerated dose (MTD). Secondary endpoints were safety, overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). RESULTS: In level 0 (oxaliplatin, 85 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), two of five patients experienced DLT. In level - 1 (oxaliplatin, 65 mg/m2 ; irinotecan, 100 mg/m2 ; S-1, 80 mg/m2 ), DLT could not be evaluated in two of eight patients because one cycle was not completed; one of the remaining six patients experienced DLT. Anemia, thrombocytopenia, fatigue, nausea, anorexia, diarrhea, and peripheral sensory neuropathy were seen frequently in levels 0 and - 1. ORR was 30% in levels 0 and - 1. Median progression-free survival and median overall survival were 4.1 months (95% confidence interval [CI], 0.0-8.9 months) and 13.7 months (95% CI, 4.8-22.6 months), respectively. CONCLUSION: MTD of OX-IRIS therapy was estimated to be level 0, and the recommended dose (RD) for future trial was level - 1.
• Comprehensive Glycomic Approach Reveals Novel Low-Molecular-Weight Blood Group-Specific Glycans in Serum and Cerebrospinal Fluid.
  Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Ikuko Yokota, Megumi Hirayama, Tomohiro Ando, Hiroyuki Kobayashi, Shunsuke Ohnishi, Nobuaki Miura, Kazue Okada, Shota Sakai, Kohei Yuyama, Yasuyuki Igarashi, Makoto Ito, Yasuro Shinohara, Naoya Sakamoto
  Journal of proteome research, 20, 5, 2812, 2822, 07 May 2021, [International Magazine]
  English, Scientific journal, ABO blood antigens on the human red blood cell membrane as well as different cells in various human tissues have been thoroughly studied. Anti-A and -B antibodies of IgM are present in serum/plasma, but blood group-specific glyco-antigens have not been extensively described. In this study, we performed comprehensive and quantitative serum glycomic analyses of various glycoconjugates and free oligosaccharides in all blood groups. Our comprehensive glycomic approach revealed that blood group-specific antigens in serum/plasma are predominantly present on glycosphingolipids on lipoproteins rather than glycoproteins. Expression of the ABO antigens on glycosphingolipids depends not only on blood type but also on secretor status. Blood group-specific glycans in serum/plasma were classified as type I, whereas those on RBCs had different structures including hexose and hexosamine residues. Analysis of free oligosaccharides revealed that low-molecular-weight blood group-specific glycans, commonly containing lacto-N-difucotetraose, were expressed in serum/plasma according to blood group. Furthermore, comprehensive glycomic analysis in human cerebrospinal fluid showed that many kinds of free oligosaccharides were highly expressed, and low-molecular-weight blood group-specific glycans, which existed in plasma from the same individuals, were present. Our findings provide the first evidence for low-molecular-weight blood group-specific glycans in both serum/plasma and cerebrospinal fluid.
• Very urgent endoscopic retrograde cholangiopancreatography is associated with early discharge in patients with non-severe acute cholangitis.
  Ryo Sugiura, Hirohito Naruse, Yoshiya Yamamoto, Kazuteru Hatanaka, Kenji Kinoshita, Satoshi Abiko, Shuichi Miyamoto, Kazuharu Suzuki, Masayuki Higashino, Risako Kohya, Naoya Sakamoto
  Revista espanola de enfermedades digestivas : organo oficial de la Sociedad Espanola de Patologia Digestiva, 114, 3, 133, 139, 05 May 2021, [International Magazine]
  English, Scientific journal, BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is a first-line procedure for biliary drainage in patients with acute cholangitis, and no study focused very urgent ERCP within several hours of hospital arrival. We aimed to elucidate the utility of very urgent ERCP for non-severe acute cholangitis. METHODS: This retrospective observational study included patients with non-severe acute cholangitis who underwent ERCP between April 2011 and June 2020 in the study institution. Patients were stratified into three groups based on the time to ERCP after hospital arrival: very urgent (≤3hours), urgent (3-24hours), and elective (>24hours). The primary outcome was length of hospital stay (LOS). RESULTS: In the study cohort of 291 patients, including 168 males (57.7%), with a median age of 76 (interquartile range, 70-83) years, 47, 196, and 48 patients underwent very urgent, urgent, and elective ERCP, respectively. The median LOSs in the very urgent, urgent, and elective groups were 12, 14, and, 15 days, respectively (Kaplan-Meier method). A shorter LOS was associated with earlier ERCP (log-rank trend test, P=0.04). The rates of readmission within 30 days of discharge and adverse events were not significantly different among the three groups. By multivariate analysis, very urgent ERCP was associated with a significantly earlier discharge than urgent and elective ERCP (HR 0.71, P=0.04 and HR 0.47, P<0.01, respectively). In addition, age≥75years, pancreatitis, albumin≤2.8g/dL, and two or more ERCP procedures were associated with significantly longer LOS (HRs <1, P<0.05). CONCLUSIONS: Very urgent ERCP for non-severe acute cholangitis was associated with early discharge.
• Possible reasons for the regrettable results of patency of an inside stent in endoscopic transpapillary biliary stenting.
  Masaki Kuwatani, Kazumichi Kawakubo, Naoya Sakamoto
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 04 May 2021, [International Magazine]
  English, Scientific journal, Endoscopic biliary decompression is a minimally invasive procedure for cholestasis since the first endoscopic retrograde cholangiopancreatography-guided biliary stenting performed by Soehendra and Reynders-Frederix. Among the endoscopic biliary decompression, endoscopic transpapillary biliary stenting (EBS), is a mainstream choice and presently has two methods of placement: stenting above the sphincter of Oddi (SO) (suprapapillary) and stenting across the SO (transpapillary). Stent patency is the most important concern for patients, endoscopists and physicians because it can affect both the life prognosis and treatment schedule of patients. Biliary stent occlusion can occur because of several factors. Among them, direct food impaction, biofilm formation, and sludge formation play important roles and are presumed to be theoretically overcome by EBS above the SO. Thus, EBS above the SO is expected to result in a longer patency than EBS across the SO. In the literature, there have been six comparative studies on EBS for distal biliary obstruction in which the stent was placed above or across the SO, including two randomized controlled trials (RCTs) with negative results of stenting above the SO. With respect to EBS for hilar biliary obstruction, there have been no RCTs, whereas four retrospective comparative studies with negative results and four retrospective comparative studies showing positive results of stenting above the SO have been reported. In this review, we focused on EBS above and across the SO, and summarized the positive and negative results of the two types of stenting to promote effective clinical practice and to provide a basis for future studies.
• Recent advances in the treatment of hepatitis C virus infection for special populations and remaining problems.
  Goki Suda, Naoya Sakamoto
  Journal of gastroenterology and hepatology, 36, 5, 1152, 1158, May 2021, [International Magazine]
  English, Scientific journal, Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis, hepatocellular carcinoma (HCC), and liver transplantation (LT). The rate of HCV infection is high in patients on hemodialysis and in patients infected with human immunodeficiency virus (HIV). In liver transplant patients with HCV infection, recurrent HCV infection of the transplanted liver is universal and results in rapid liver fibrosis progression. In patients with HCV/HIV coinfection as well, liver fibrosis advances rapidly. Thus, there is an urgent need for prompt HCV infection treatment in these special populations (i.e. HIV/HCV coinfection, HCV infection after LT, and dialysis patients). Interferon (IFN)-based therapy for HCV infection could not achieve a high rate of sustained viral response and could cause severe adverse events in the aforementioned special populations. Direct-acting antivirals (DAAs) have recently been developed, and clinical trials have shown that IFN-free DAA-based therapies are associated with a significantly better safety and therapeutic profile than IFN-based therapies. However, the majority of the initial DAA trials excluded special populations; thus, the efficacy and safety of IFN-free DAA-based therapy in special populations remained to be clearly established. Although recent clinical trials and clinical studies have shown the high efficacy and safety of this therapy even in special populations, several unresolved problems, including emergence of resistance-associated variants after failure to respond to DAAs and HCC occurrence after DAA therapy, still exist. Hence, in this review, we discuss the recent advances in anti-HCV therapy for special populations and the remaining problems regarding this therapy.
• Changes in the estimated renal function after hepatitis C virus eradication with direct-acting antiviral agents: Impact of changes in skeletal muscle mass.
  Yoshimasa Tokuchi, Goki Suda, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Masatsugu Ohara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Journal of viral hepatitis, 28, 5, 755, 763, May 2021, [International Magazine]
  English, Scientific journal, Hepatitis C virus (HCV) infection can cause renal dysfunction, expected to improve upon HCV eradication. However, adverse effects of HCV eradication using direct-acting antiviral agents (DAAs) on renal function have been recently reported. This retrospective study aimed to evaluate renal function with glomerular filtration rate (eGFR) estimated using creatinine (eGFRcre) and cystatin C (eGFRcys). Complete clinical information and preserved serum samples were collected from 207 patients with HCV infection treated with interferon-free DAA at baseline and SVR48 (SVR48). Patients who underwent paired computed tomography (CT) at baseline and ≥12 months after DAA were evaluated for changes in skeletal muscle mass using the psoas muscle mass index (PMI). eGFRcre significantly worsened at SVR48, while eGFRcys was similar at baseline and SVR48. At baseline, eGFRcre was significantly higher than eGFRcys; eGFRcre and eGFRcys were similar at SVR48. Multivariate analysis revealed that the presence of liver cirrhosis and low-albumin level, as well as cirrhosis and age, was significantly associated with the overestimation of renal function by eGFRcre at baseline and SVR48, respectively. In the 57 patients who underwent paired CT at baseline and ≥12 months after DAA, relative values of PMI significantly increased after DAA. After DAA, in patients with increased PMI (65% 37/57), eGFRcre significantly worsened but did not change in patients without increased PMI. eGFRcre significantly worsened after DAAs; however, this might not reflect accurate changes in renal function, partially because of changes in skeletal muscle mass. eGFRcys did not change after DAAs, and it is a potential alternative to eGFRcre.
• Applicability of APRI and FIB-4 as a transition indicator of liver fibrosis in patients with chronic viral hepatitis.
  Jun Itakura, Masayuki Kurosaki, Hiroko Setoyama, Tetsuro Simakami, Noriko Oza, Masaaki Korenaga, Motohiko Tanaka, Takuji Torimura, Naoya Sakamoto, Nobuyuki Enomoto, Yoshiyuki Ueno, Norifumi Kawada, Shuichi Kaneko, Shuhei Nishiguchi, Kazuaki Chayama, Junko Tanaka, Namiki Izumi, Tatsuya Kanto
  Journal of gastroenterology, 56, 5, 470, 478, May 2021, [Domestic magazines]
  English, Scientific journal, BACKGROUND AND AIMS: The usefulness of APRI or FIB-4 is well established as a non-invasive liver fibrosis marker at a point of diagnosis in patients with chronic liver disease. However, their applicability for the monitoring of progression of liver fibrosis over time is yet to be determined. We aimed to clarify the feasibility of APRI and FIB-4 for the longitudinal evaluation of liver fibrosis in patients with chronic hepatitis B and C. METHODS: This is a multi-center retrospective and prospective cohort study, enrolling 1029 patients with HCV and 384 patients with HBV who were histologically diagnosed by liver biopsy. The observation period of retrospective and prospective study was 14 and 12 years, respectively. The APRI and FIB-4 were traced back in cases of histologically diagnosed cirrhosis, and those were prospectively analyzed after biopsy in cases diagnosed as F3 of METAVIR score, respectively. RESULTS: The averaged APRI and FIB-4 exhibited time-dependent increase in the retrospective study of hepatitis C patients (increase by 0.09/year in APRI and 0.29/year in FIB-4). In the prospective study of untreated hepatitis C patients, such increases were 0.14/year in APRI and 0.40/year in FIB-4, respectively. Neither the average of APRI nor FIB-4 showed a specific tendency with hepatitis B patients and treatment-experienced hepatitis C patients. CONCLUSION: The APRI and FIB-4 may serve as a transition indicator of liver fibrosis in anti-viral treatment-naïve patients with chronic hepatitis C.
• Spiral stent placement for bile leakage after hepatobiliary surgery.
  Yunosuke Takishin, Masaki Kuwatani, Naoya Sakamoto
  Endoscopy, 28 Apr. 2021, [International Magazine]
  English, Scientific journal
• Baseline elevated serum angiopoietin-2 predicts long-term non-regression of liver fibrosis after direct-acting antiviral therapy for hepatitis C.
  Naoki Kawagishi, Goki Suda, Megumi Kimura, Osamu Maehara, Ren Yamada, Yoshimasa Tokuchi, Akinori Kubo, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Masatsugu Ohara, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Naoya Sakamoto
  Scientific reports, 11, 1, 9207, 9207, 28 Apr. 2021, [International Magazine]
  English, Scientific journal, We previously revealed that Angiopoietin-2 (Ang2) predicts non-regression of liver fibrosis based on liver stiffness measurement (LSM) at 24 weeks after anti-hepatitis C virus (HCV) treatment. In this study, we extended the observational period to 96 weeks to investigate the factors associated with non-regression after treatment with direct-acting-antivirals (DAAs). Patients treated with DAAs who underwent transient elastography at baseline and 24 and 96 weeks after DAA therapy were included. Baseline and post-treatment serum Ang2 levels were measured. Liver fibrosis stages were defined based on LSM. Multivariate regression was used to evaluate factors associated with non-regression of liver fibrosis between various time points. In total, 110 patients were included. Of these, 11% showed non-regression of LSM-based fibrosis stage at 96 weeks after DAA therapy. In multivariate analysis, advanced liver fibrosis stage and high baseline Ang2 levels were significantly associated with non-regression at 96 weeks. In patients with advanced liver fibrosis (F3/4), baseline Ang2 levels were associated with non-regression of liver fibrosis stage. Between SVR24 and SVR96, post-treatment Ang2 levels and controlled attenuation parameter values at SVR24 were significantly associated with non-regression of liver fibrosis stage in patients with F3/4. Thus, serum Ang2 levels are an important target for monitoring and therapy.
• Successful treatment by on-demand glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in patients with diffuse large B-cell lymphoma: a case report.
  Machiko Umemura, Goki Suda, Shihori Tsukamoto, Ko Ebata, Shinjiro Takahash, Takashi Sasaki, Sae Nakajima, Koji Hirata, Mariko Ozasa, Masatoshi Takano, Masaki Katagiri, Naoya Sakamoto
  BMC infectious diseases, 21, 1, 389, 389, 27 Apr. 2021, [International Magazine]
  English, Scientific journal, BACKGROUND: In patients with hepatitis C virus (HCV) and malignant lymphoma, hepatitis C flare during R-CHOP can result in discontinuation of treatment. However, appropriate therapeutic strategies for managing hepatitis C flare during R-CHOP have not been established, and this issue is complicated by conflicting results regarding the use of direct-acting antivirals in patients with uncontrolled malignancies. CASE PRESENTATION: We report the first case of effective and safe treatment with on-demand 8-week glecaprevir and pibrentasvir for hepatitis C flare during R-CHOP in a patient with diffuse large B-cell lymphoma (DLBCL). The patient completed five additional courses of R-CHOP without hepatic toxicity. A complete response of DLBCL and a sustained virological response were observed at 24 weeks after glecaprevir and pibrentasvir completion. CONCLUSION: On-demand, direct-acting antivirals could be a novel strategy for managing hepatitis C flare during R-CHOP.
• Chronic Diarrhea as the Presenting Feature of Amyloidosis with Multiple Myeloma: A Case Report Diagnosed by a Myocardial Biopsy.
  Shinsuke Otagiri, Sae Nakajima, Takehiko Katsurada, Kensuke Sakurai, Kana Yamanashi, Takahide Ara, Emi Takakuwa, Tomoko Mitsuhashi, Naoya Sakamoto
  Internal medicine (Tokyo, Japan), 60, 8, 1197, 1203, 15 Apr. 2021, [Domestic magazines]
  English, Scientific journal, A 73-year-old woman with a history of diarrhea for one year and other various symptoms was admitted to our hospital. Gastrointestinal endoscopy that included enteroscopy with multiple biopsies was performed. However, no significant findings were observed. Electrocardiography showed low voltage in all limb leads, and an echocardiogram showed thickened cardiac walls with granular sparkling pattern. A myocardial biopsy revealed amyloidosis, and a bone marrow biopsy showed multiple myeloma. This case suggests that we should suspect the possibility of amyloidosis in a patient with diarrhea and various symptoms involving multiple organ systems. Additionally, electrocardiograms and echocardiograms should be performed even when gastrointestinal biopsies reveal negative results.
• Asymptomatic Choledocholithiasis that Causes a Dilemma between Treatment and Observation.
  Masaki Kuwatani, Naoya Sakamoto
  JMA journal, 4, 2, 176, 177, 15 Apr. 2021, [Domestic magazines]
  English
• IL28B遺伝子多型の発見から臨床応用 : 臨床応用
  須田 剛生, 小川 浩司, 坂本 直哉
  Kanzo, 62, 4, 209, 211, The Japan Society of Hepatology, 01 Apr. 2021
  Japanese
• 【実地医家のためのNAFLD/NASH診療のポイント】実地医家のためのNAFLD/NASH診療のポイント 我が国における脂肪性肝疾患(NAFLD/NASH)の現状　　　　　　　　　　　　　　　
  坂本 直哉, 森川 賢一
  Vita, 38, 2, 2, 7, (株)ビー・エム・エル, Apr. 2021
  Japanese
• 大腸検査における前処置法の工夫 当院における消化管内視鏡検査の鎮静剤使用の現状と課題　　　　　　　　　　　　　　　
  大野 正芳, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 石川 麻倫, 山本 桂子, 小野 尚子, 清水 勇一, 坂本 直哉
  日本大腸検査学会雑誌, 37, 2, 124, 124, 日本大腸検査学会, Apr. 2021
  Japanese
• 食道ESD中の鎮静薬と塩酸ペチジン併用の安全性の後ろ向き検討　　　　　　　　　　　　　　　
  大野 正芳, 清水 勇一, 西村 友佑, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 山本 桂子, 小野 尚子, 坂本 直哉
  Gastroenterological Endoscopy, 63, Suppl.1, 874, 874, (一社)日本消化器内視鏡学会, Apr. 2021
  Japanese
• 超拡大内視鏡観察による表在性非乳頭部十二指腸上分性腫瘍(SNADETs)の内視鏡治療戦略　　　　　　　　　　　　　　　
  久保 茉理奈, 小野 尚子, 西村 友佑, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 63, Suppl.1, 879, 879, (一社)日本消化器内視鏡学会, Apr. 2021
  Japanese
• H.pylori除菌後異時性胃癌症例の臨床病理学的特徴　　　　　　　　　　　　　　　
  田中 一光, 小野 尚子, 坂本 直哉, 西村 友佑, 久保 茉理奈, 霜田 佳彦, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 清水 勇一
  Gastroenterological Endoscopy, 63, Suppl.1, 894, 894, (一社)日本消化器内視鏡学会, Apr. 2021
  Japanese
• 鎮静上部消化管内視鏡検査における術中、術後管理の検討 適切な薬剤使用を目指して　　　　　　　　　　　　　　　
  霜田 佳彦, 大野 正芳, 久保 茉理奈, 西村 友佑, 田中 一光, 井上 雅貴, 木脇 佐代子, 清水 勇一, 山本 桂子, 小野 尚子, 坂本 直哉
  Gastroenterological Endoscopy, 63, Suppl.1, 1015, 1015, (一社)日本消化器内視鏡学会, Apr. 2021
  Japanese
• IBD診療における超音波の有用性 免疫チェックポイント阻害薬誘発性大腸炎における体外式超音波検査の有用性　　　　　　　　　　　　　　　
  桜井 健介, 西田 睦, 表原 里実, 小田切 信介, 長島 一哲, 桂田 武彦, 小松 嘉人, 坂本 直哉
  超音波医学, 48, Suppl., S306, S306, (公社)日本超音波医学会, Apr. 2021
  Japanese
• Functional cureを目指したB型肝炎創薬研究 B型肝炎ウイルス宿主制限因子の回復を目指した創薬戦略　　　　　　　　　　　　　　　
  森川 賢一, 山田 錬, 坂本 直哉
  肝臓, 62, Suppl.1, A89, A89, (一社)日本肝臓学会, Apr. 2021
  Japanese
• 肝疾患移行期医療の現状と問題点 フォンタン術後肝合併症の現状と5年経過からみえてくること　　　　　　　　　　　　　　　
  荘 拓也, 森川 賢一, 坂本 直哉
  肝臓, 62, Suppl.1, A167, A167, (一社)日本肝臓学会, Apr. 2021
  Japanese
• 肝疾患におけるビックデータとAI(人工知能)の臨床応用 肝炎ウイルス複製・病原性と関連する宿主因子のプロテオーム解析　　　　　　　　　　　　　　　
  森川 賢一, 久保 彰則, 坂本 直哉
  肝臓, 62, Suppl.1, A205, A205, (一社)日本肝臓学会, Apr. 2021
  Japanese
• 部分的脾動脈塞栓術(PSE)、バルーン閉塞下逆行性経静脈的塞栓術(B-RTO)の肝予備能、線維化マーカー、予後への影響　　　　　　　　　　　　　　　
  中井 正人, 小川 浩司, 坂本 直哉, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 重沢 拓, 荘 拓也, 須田 剛生, 森川 賢一
  肝臓, 62, Suppl.1, A332, A332, (一社)日本肝臓学会, Apr. 2021
  Japanese
• 肝疾患患者における筋肉量の経時変化の評価はBIA法に比べCT画像を用いた方法が有用である　　　　　　　　　　　　　　　
  大原 正嗣, 須田 剛生, 重沢 拓, 鈴木 和治, 中村 晃久, 川岸 直樹, 中井 正人, 荘 拓也, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 62, Suppl.1, A335, A335, (一社)日本肝臓学会, Apr. 2021
  Japanese
• Endoscopic ultrasonography-guided pancreaticoduodenostomy with a lumen-apposing metal stent to treat main pancreatic duct dilatation.
  Masaki Kuwatani, Kosuke Nagai, Yunosuke Takishin, Ryutaro Furukawa, Hajime Hirata, Kazumichi Kawakubo, Naoya Sakamoto
  Endoscopy, 30 Mar. 2021, [International Magazine]
  English, Scientific journal
• Serum fatty acid-binding protein 5 is a significant factor in hepatocellular carcinoma progression independent of tissue expression level.
  Masafumi Ohira, Hideki Yokoo, Koji Ogawa, Moto Fukai, Toshiya Kamiyama, Naoya Sakamoto, Akinobu Taketomi
  Carcinogenesis, 42, 6, 794, 803, 23 Mar. 2021, [International Magazine]
  English, Scientific journal, Fatty acid-binding protein 5 (FABP5) is highly expressed in hepatocellular carcinoma (HCC) tissues and is related to HCC progression. In this study, we analyzed the potential of serum FABP5 (sFABP5) as a tumor marker in HCC and its clinical significance in HCC progression. We compared the sFABP5 concentration in patients with HCC (HCC group) with that of patients with hepatitis without HCC (hepatitis group). Moreover, we measured the FABP5 expression levels in resected HCC tissues (tFABP5) and analyzed their relationship with sFABP5. We also performed cell-based assays using FABP5 knockout and overexpressing HCC cell lines to analyze the effect of extrinsic FABP5 on HCC cells. We showed that sFABP5 was not a useful tumor marker for HCC, as HCC and sFABP5 were not correlated. However, sFABP5 and tFABP5 significantly correlated with survival after surgery for HCC, while sFABP5 and tFABP5 were independent of each other. In cell-based assays, extrinsic FABP5 was taken up by HCC cell lines and positively affected cell survival under glucose-depleted conditions by complementing the endogenous FABP5 function. In conclusion, sFABP5 had a significant impact on HCC progression irrespective of tFABP5 by augmenting cell viability under glucose-depleted conditions. As tFABP5 and sFABP5 are important factors that are independent of each other in HCC progression, both of them should be considered independently in improving the prognosis of patients with HCC.
• Angiogenic Dreaded Killer: Cholesterol Crystal Embolization.
  Masaki Kuwatani, Naoya Sakamoto
  Internal medicine (Tokyo, Japan), 60, 6, 825, 826, 15 Mar. 2021, [Domestic magazines]
  English, Scientific journal
• Endoscopic Papillectomy for Adenocarcinoma at the Duodenal Papilla- Will it Still Open a Pandora's Box?
  Kuwatani Masaki, Sakamoto Naoya
  Internal medicine (Tokyo, Japan), 60, 16, 2523, 2524, 15 Mar. 2021, [Domestic magazines]
  English, Scientific journal
• A spontaneous rupture of lung metastasis from hepatocellular carcinoma after the introduction of lenvatinib.
  Masayuki Higashino, Ryo Sugiura, Yoshiya Yamamoto, Hirohito Naruse, Naoya Sakamoto
  Journal of gastrointestinal and liver diseases : JGLD, 30, 1, 169, 170, 13 Mar. 2021, [International Magazine]
  English
• 著明な隆起を伴った下咽頭上皮内癌の一例　　　　　　　　　　　　　　　
  西村 友佑, 清水 勇一, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 小野 尚子, 三橋 智子, 鈴木 崇祥, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 47, 47, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 若年発症した食道間葉系腫瘍の1例　　　　　　　　　　　　　　　
  霜田 佳彦, 山本 桂子, 西村 友佑, 久保 茉理奈, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 小野 尚子, 清水 勇一, 村上 壮一, 三橋 智子, 岡田 宏美, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 48, 48, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 若年性ポリポーシス症候群の2例　　　　　　　　　　　　　　　
  西村 友佑, 山本 桂子, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 小野 尚子, 清水 勇一, 三橋 智子, 松野 吉宏, 坂本 直哉
  日本大腸肛門病学会雑誌, 74, 3, 195, 195, (一社)日本大腸肛門病学会, Mar. 2021
  Japanese
• 食道癌 診断と治療のup to date 食道腺癌を含めて 食道胃接合部腺癌における発生母地による臨床病理学的相違　　　　　　　　　　　　　　　
  山本 桂子, 西村 友佑, 久保 茉理奈, 霜田 佳彦, 田中 一光, 木脇 佐代子, 井上 雅貴, 大野 正芳, 小野 尚子, 清水 勇一, 三橋 智子, 高橋 宏明, 山本 義也, 成瀬 宏仁, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 34, 34, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 十二指腸腫瘍-あなたの治療選択は? 当院における表在型非乳頭部上皮性腫瘍に対する内視鏡治療の現状　　　　　　　　　　　　　　　
  大野 正芳, 山本 桂子, 小野 尚子, 清水 勇一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 36, 36, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 悪性貧血と亜急性連合性脊髄変性症を合併した自己免疫性胃炎(多腺性自己免疫症候群3B型)の1例　　　　　　　　　　　　　　　
  菅 彩花, 小野 尚子, 久保 茉理奈, 西村 友佑, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 43, 43, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 脈管侵襲陽性の深達度pT1a早期胃癌の検討　　　　　　　　　　　　　　　
  木脇 佐代子, 小野 尚子, 西村 友佑, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 50, 50, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 内視鏡的に切除した十二指腸下行脚有茎性ポリープの1例　　　　　　　　　　　　　　　
  久保 茉理奈, 小野 尚子, 西村 友佑, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉, 森 康明
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 50, 50, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 胆嚢転移を来した原発性肝細胞癌再発の1例　　　　　　　　　　　　　　　
  得地 祐匡, 須田 剛生, 久保 彰則, 北潟谷 隆, 山田 錬, 重沢 拓, 中井 正人, 荘 拓也, 小川 浩司, 森川 賢一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 57, 57, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 経過観察中に増大傾向がみられ、肝切除術に至った肝原発神経内分泌腫瘍の1例　　　　　　　　　　　　　　　
  久保 彰則, 小川 浩司, 得地 祐匡, 山田 錬, 北潟谷 隆, 重沢 拓, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 58, 58, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• 肝機能障害を契機に診断された肝ヘモクロマトーシスの一例　　　　　　　　　　　　　　　
  吉田 苑永, 中井 正人, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 重沢 拓, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 128回・122回, 67, 67, 日本消化器病学会-北海道支部, Mar. 2021
  Japanese
• KHDRBS3 promotes multi-drug resistance and anchorage-independent growth in colorectal cancer.
  Shoichi Ukai, Naoya Sakamoto, Daiki Taniyama, Kenji Harada, Ririno Honma, Ryota Maruyama, Kazuhito Naka, Takao Hinoi, Yuji Takakura, Wataru Shimizu, Hideki Ohdan, Wataru Yasui
  Cancer science, 112, 3, 1196, 1208, Mar. 2021, [International Magazine]
  English, Scientific journal, 5-Fluorouracil (5-FU) is one of the most frequently used pharmacological agents in the treatment of colorectal cancer (CRC). Resistance to chemotherapy is a major cause of treatment failure of CRC, and it is a well known fact that cancer stem cells play a significant role in the acquisition of drug resistance. In this study, we focused on the KHDRBS3 gene that encodes KH RNA Binding Domain Containing, Signal Transduction Associated 3. We first clarified the relationship between KHDRBS3 and 5-FU resistance. We then observed higher expression levels of KHDRBS3 in KRAS-mutant organoids and cell lines in comparison with KRAS wild-type organoids and cell lines. Immunohistochemical analysis using CRC cases revealed that the prognosis of KHDRBS3-positive patients was significantly worse compared with that of KHDRBS3-negative patients. Univariate and multivariate Cox proportional hazards analyses showed that KHDRBS3 was an independent prognostic factor in patients with CRC. We determined that KHDRBS3 might play a crucial role in the acquisition of stem cell properties, such as drug resistance and spheroid/organoid formation, by regulating CD44 variant expression and the Wnt signaling pathway. In an immunodeficient mouse model, KHDRBS3-positive cells showed efficient tumor formation and formed metastatic lesions in the lungs. These results indicated that KHDRBS3 plays a crucial role in drug resistance and anchorage-independent growth by maintaining stem cell-like features in CRC cells. KHDRBS3 could be a promising candidate marker for predicting chemotherapeutic effect and prognosis in CRC patients.
• Optical effect of spraying l-menthol on gastric intestinal metaplasia visualized by linked color imaging.
  Shoko Ono, Yoshihiko Shimoda, Ikko Tanaka, Sayoko Kinowaki, Masaki Inoue, Masayoshi Ono, Keiko Yamamoto, Yuichi Shimizu, Naoya Sakamoto
  European journal of gastroenterology & hepatology, 33, 3, 358, 363, 01 Mar. 2021, [International Magazine]
  English, Scientific journal, OBJECTIVE: Linked color imaging (LCI) enables noninvasive detection of gastric intestinal metaplasia (GIM) as a lavender color sign (LCS), and there has been a recent report that l-menthol enhanced GIM with LCI. We measured color values of GIM and surrounding mucosa with white light imaging (WLI), LCI and LCI after spraying l-menthol (Mint-LCI) and investigated the effect of l-menthol on gastric mucosa. METHODS: Endoscopic images of the antrum with WLI, LCI and Mint-LCI from 18 patients were prepared. Each of six regions of interest (three points of GIM and three points of surrounding mucosa) was selected for each modality, and CIE1976 (L*a*b*) color space was used to measure the color values. The primary endpoint was color differences (ΔE) between GIM and surrounding mucosa in each modality. RESULTS: For surrounding mucosa, the mean a* value with Mint-LCI was significantly higher than the mean values with WLI and LCI (P < 0.01). The mean b* value of GIM with LCI was significantly lower than that of surrounding mucosa, and spraying l-menthol decreased the b* values of GIM with a change to a deeper lavender color (LCI: 10.0 ± 5.8, Mint-LCI: 3.7 ± 6.1, P < 0.01). However, there was no significant difference in mean ΔE values between LCI and Mint LCI (LCI: 21.1 ± 6.6, Mint-LCI: 22.7 ± 5.4, NS). After spraying l-menthol, the microstructure of GIM changed to translucent and microvessels were obscured. CONCLUSIONS: As shown by LCI, spraying l-menthol optically enhances the color of GIM in the antrum.
• Efficacy of a novel ultra-sharp dilation device for dilating bare metal stent mesh in patients with hilar malignant biliary obstruction.
  Shin Kato, Masaki Kuwatani, Kazumichi Kawakubo, Ryutaro Furukawa, Koji Hirata, Yunosuke Takishin, Hajime Hirata, Naoya Sakamoto
  Scandinavian journal of gastroenterology, 56, 3, 374, 377, Mar. 2021, [International Magazine]
  English, Scientific journal, The placement of additional stents in patients with hilar malignant biliary obstruction can be challenging when a metal stent already exists because occasionally, the catheter and delivery system of the additional stent cannot pass through the mesh of the formerly placed stent. We studied ten consecutive patients with hilar malignant biliary obstruction who underwent mesh dilation using a novel ultra-sharp dilation device (ES dilator) to assess the efficacy and safety of the ES dilator for mesh dilation. Mesh dilation using the ES dilator was successful in eight patients (8/10; 80.0%), which was the same rate as that of patients with pre-dilation using a Soehendra biliary dilation catheter (4/5, 80.0%) and patients without pre-dilation (4/5, 80.0%). In the two patients with dilation failure, the angle of the hilar bile duct branch was too steep to permit the passage of a stiff dilation device. Nonetheless, stent placement was uncomplicated in all mesh-dilated patients (8/8, 100.0%), and no adverse events related to the ES dilator were observed. The efficacy of an ultra-sharp dilation device appears promising for metallic stent mesh dilation, especially in patients where conventional methods are unsuccessful. However, additional data are necessary to confirm our findings.
• Crohn's Disease Activity Evaluation by Transabdominal Ultrasonography: Correlation with Double-Balloon Endoscopy.
  Kana Yamanashi, Takehiko Katsurada, Mutsumi Nishida, Reizo Onishi, Satomi Omotehara, Shinsuke Otagiri, Kensuke Sakurai, Kazunori Nagashima, Kenji Kinoshita, Ryo Takagi, Naoya Sakamoto
  Journal of ultrasound in medicine : official journal of the American Institute of Ultrasound in Medicine, 17 Feb. 2021, [International Magazine]
  English, Scientific journal, OBJECTIVES: Transabdominal ultrasonography (US) has been reported as a useful tool for evaluating Crohn's disease (CD) activity. Endoscopic findings and Crohn's disease activity index (CDAI) are currently considered the gold standard for assessing CD activity. We assessed the correlation between US and double-balloon endoscopy (DBE), and CDAI for evaluating CD activity. METHODS: We analyzed patients with CD undergoing US and DBE within 10 days between the procedures. The intestine was divided into four segments and analyzed by the US scoring system (US-CD) and the simple endoscopic score for Crohn's disease (SES-CD). CDAI was compared with US-CD and SES-CD. Spearman's rank correlation coefficient was used for statistical analysis. RESULTS: Twenty-five patients with CD (11 women, 14 men; mean age 35.4 ± 14.9 years, range 16-65 years) were enrolled. Twenty-four patients received antitumor necrosis factor inhibitor therapy. CDAI was 128.1 (range 36-227). A significant moderate correlation was found between the US-CD and SES-CD in all segments (ρ = .64, P < .01). The US-CD showed a strong correlation with CDAI (ρ = .78, P < .01), whereas the SES-CD showed a moderate correlation (ρ = .55, P < .05). CONCLUSIONS: US-CD and SES-CD showed a moderate correlation for assessing CD activity. US-CD showed a stronger correlation with CDAI than SES-CD, suggesting that US could more accurately evaluate the disease activity.
• Lenvatinib suppresses cancer stem-like cells in HCC by inhibiting FGFR1-3 signaling, but not FGFR4 signaling.
  Taku Shigesawa, Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Megumi Kimura, Tomoe Shimazaki, Koji Yamamoto, Ren Yamada, Takashi Kitagataya, Akihisa Nakamura, Kazuharu Suzuki, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Masaya Sugiyama, Masashi Mizokami, Hiroshi Takeda, Naoya Sakamoto
  Carcinogenesis, 42, 1, 58, 69, 11 Feb. 2021, [Peer-reviewed], [International Magazine]
  English, Scientific journal, In hepatocellular carcinoma (HCC), a subset of cells defined by high CD44 and CD133 expression has been reported to possess cancer stem-like cell (CSC) characteristics and to be associated with a poor prognosis. Since the approval of the multikinase inhibitor, lenvatinib, for patients with unresectable HCC, two such inhibitors (sorafenib and lenvatinib) have been employed as first-line systemic chemotherapeutics for these patients. Based on differences in the kinase-affinity profiles between these two drugs, evidence has suggested that both exert different effects on HCC, although these differences are not fully characterized. In this study, using in vitro and a preclinical in vivo xenograft mouse model, we showed that lenvatinib alone (not sorafenib or the cytotoxic agent, 5-fluorouracil) diminished CD44High/CD133High CSCs in HCC. Furthermore, western blotting and reverse transcriptase-polymerase chain reaction analysis revealed that the expression of fibroblast growth factor receptor (FGFR)-1-4 differed between CD44High/CD133High CSCs and control cells. Analysis of the effects of selective FGFR inhibitors and FGFR small interfering RNAs on CSCs in HCC revealed that lenvatinib diminished CSCs in HCC by inhibiting FGFR1-3 signaling, however, FGFR4 signaling was not impacted. Finally, we showed that FGF2 and FGF19 were involved in maintaining CD44High/CD133High CSCs in HCC, potentially, via FGFR1-3. The findings provide novel mechanistic insights into the effects of lenvatinib on CSCs in HCC and provide clues for developing effective targeted therapies against CSCs in HCC.
• Tenofovir-disoproxil-fumarate modulates lipid metabolism via hepatic CD36/PPAR-alpha activation in hepatitis B virus infection.
  Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Akinobu Nakamura, Hideaki Miyoshi, Megumi Kimura, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Koji Yamamoto, Taku Shigesawa, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  Journal of gastroenterology, 56, 2, 168, 180, Feb. 2021, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Entecavir and tenofovir-disoproxil-fumarate are first-line nucleos(t)ide analogs (NA) for treatment of hepatitis B virus (HBV) infections; however, their long-term administration can impact extrahepatic organs. Herein, we sought to examine the effect of NA on lipid metabolism while also characterizing the associated mechanism. METHODS: A retrospective study was performed on HBV patients administered entecavir or tenofovir-disoproxil-fumarate. Patient clinical information, as well as their preserved serum samples obtained at baseline and 6-12 months after treatment initiation, were analyzed. A 1:1 propensity score matching was applied to the assignment of tenofovir-disoproxil-fumarate or entecavir treatment. Changes in serum cholesterol, including oxidized-LDL, were analyzed. Subsequently, in vitro analysis elucidated the mechanism associated with the effect of NAs on lipid metabolism. RESULTS: Administration of tenofovir-disoproxil-fumarate, not entecavir, to chronic HBV patients, decreased serum cholesterol levels, including non-HDL and oxidized-LDL, which are strongly associated with arteriosclerosis. In vitro analysis revealed that tenofovir-disoproxil-fumarate reduced supernatant cholesterol, and upregulated the scavenger receptor, CD36, in hepatocytes. Meanwhile, silencing of hepatic CD36 increased supernatant cholesterol and negated the cholesterol-reducing effect of tenofovir-disoproxil-fumarate in HepG2-cells. Reporter, microarray, and RT-PCR analyses further revealed that tenofovir-disoproxil-fumarate treatment activates PPAR-α-mediated signaling, and upregulates PPAR-α target genes, including CPT1 and CD36. Alternatively, silencing of PPAR-α reversed the effects of tenofovir-disoproxil-fumarate on CD36. CONCLUSIONS: Tenofovir-disoproxil-fumarate modulates lipid metabolism by upregulating hepatic CD36 via PPAR-α activation. Since dyslipidemia could be associated with arteriosclerosis and hepatocarcinogenesis, these discoveries provide novel insights into anti-HBV therapies, as well as the associated extrahepatic effects of NA.
• Near-infrared photoimmunotherapy (NIR-PIT) on cholangiocarcinoma using a novel catheter device with light emitting diodes.
  Hajime Hirata, Masaki Kuwatani, Kohei Nakajima, Yuki Kodama, Yasuo Yoshikawa, Mikako Ogawa, Naoya Sakamoto
  Cancer science, 112, 2, 828, 838, Feb. 2021, [International Magazine]
  English, Scientific journal, Near-infrared photoimmunotherapy (NIR-PIT) is a novel therapy for cancers that uses NIR light and antibody-photosensitizer (IR700) conjugates. However, it is difficult to deliver NIR light into the bile duct for cholangiocarcinoma (CCA) from the conventional extracorporeal apparatus. Thus, in this study, we developed a dedicated catheter with light emitting diodes (LEDs) that supersedes conventional external irradiation devices; we investigated the therapeutic effect of NIR-PIT for CCA using the novel catheter. The new catheter was designed to be placed in the bile duct and a temperature sensor was attached to the tip of the catheter to avoid thermal burn. An anti-epidermal growth factor receptor (EGFR) antibody, Panitumumab-IR700 conjugate or anti-human epidermal growth factor receptor type 2 (HER2) antibody, Trastuzumab-IR700 conjugate, was used with EGFR- or HER2-expressing cell lines, respectively. The in vitro efficacy of NIR-PIT was confirmed in cultured cells; the capability of the new catheter for NIR-PIT was then tested in a mouse tumor model. NIR-PIT via the developed catheter treated CCA xenografts in mice. NIR-PIT had an effect in Panitumumab-IR700 conjugate- and Trastuzumab-IR700 conjugate-treated CCA cells that depended on the receptor expression level. Tumor growth was significantly suppressed in mice treated with NIR-PIT using the novel catheter compared with controls (P < .01). NIR-PIT was an effective treatment for EGFR- and HER2-expressing CCA cells, and the novel catheter with mounted LEDs was useful for NIR-PIT of CCA.
• Effectiveness of administering zinc acetate hydrate to patients with inflammatory bowel disease and zinc deficiency: a retrospective observational two-center study.
  Kensuke Sakurai, Shigeru Furukawa, Takehiko Katsurada, Shinsuke Otagiri, Kana Yamanashi, Kazunori Nagashima, Reizo Onishi, Keiji Yagisawa, Haruto Nishimura, Takahiro Ito, Atsuo Maemoto, Naoya Sakamoto
  Intestinal research, 22 Jan. 2021, [International Magazine]
  English, Scientific journal, Background/Aims: Inflammatory bowel disease (IBD) patients frequently have zinc deficiency. IBD patients with zinc deficiency have higher risks of IBD-related hospitalization, complications, and requiring surgery. This study aimed to examine the effectiveness of zinc acetate hydrate (ZAH; Nobelzin) in IBD patients with zinc deficiency. Methods: IBD patients with zinc deficiency who received ZAH from March 2017 to April 2020 were registered in this two-center, retrospective, observational study. Changes in serum zinc levels and disease activity (Crohn's Disease Activity Index [CDAI]) before and after ZAH administration were analyzed. Results: Fifty-one patients with Crohn's disease (CD, n = 40) or ulcerative colitis (UC, n = 11) were registered. Median serum zinc level and median CDAI scores significantly improved (55.5-91.0 μg/dL, P< 0.001; 171.5-129, P< 0.001, respectively) in CD patients 4 weeks after starting ZAH administration. Similarly, median serum zinc levels and CDAI scores significantly improved (57.0-81.0 μg/dL, P< 0.001; 177-148, P= 0.012, respectively) 20 weeks after starting ZAH administration. Similar investigations were conducted in groups where no treatment change, other than ZAH administration, was implemented; significant improvements were observed in both serum zinc level and CDAI scores. Median serum zinc levels in UC patients 4 weeks after starting ZAH administration significantly improved from 63.0 to 94.0 μg/dL (P= 0.002), but no significant changes in disease activity were observed. One patient experienced side effects of abdominal discomfort and nausea. Conclusions: ZAH administration is effective in improving zinc deficiency and may contribute to improving disease activity in IBD.
• Effectiveness of red dichromatic imaging for dissection of the submucosal layer when hematoma is encountered.
  Shuichi Miyamoto, Tomohiko R Ohya, Kaori Nishi, Satoshi Abiko, Ryo Sugiura, Yoshiya Yamamoto, Naoya Sakamoto
  Endoscopy, 53, 11, E413-E414, 14 Jan. 2021, [International Magazine]
  English, Scientific journal
• 【肝・胆道系症候群(第3版)-その他の肝・胆道系疾患を含めて-肝臓編(上)】感染症 肝寄生虫症 肝エキノコックス症
  中井 正人, 坂本 直哉
  日本臨床, 別冊, 肝・胆道系症候群I, 63, 68, (株)日本臨床社, Jan. 2021
  Japanese
• 【肝・胆道系症候群(第3版)-その他の肝・胆道系疾患を含めて-肝臓編(上)】血行異常 肝内動静脈短絡(A-V shunt)　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  日本臨床, 別冊, 肝・胆道系症候群I, 303, 306, (株)日本臨床社, Jan. 2021
  Japanese
• Triple-loop clip for the traction-assisted colorectal endoscopic submucosal dissection: multidirectional triple-loop traction method.
  Shuichi Miyamoto, Tomohiko R Ohya, Masayoshi Ono, Naoya Sakamoto
  VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy, 6, 1, 1, 3, Jan. 2021, [International Magazine]
  English, Scientific journal
• Baseline serum angiopoietin-2 and VEGF levels predict the deterioration of the liver functional reserve during lenvatinib treatment for hepatocellular carcinoma.
  Taku Shigesawa, Goki Suda, Megumi Kimura, Osamu Maehara, Yoshimasa Tokuchi, Akinori Kubo, Ren Yamada, Ken Furuya, Masaru Baba, Takashi Kitagataya, Kazuharu Suzuki, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  PloS one, 16, 3, e0247728, 2021, [International Magazine]
  English, Scientific journal, A deteriorated liver functional reserve during systemic therapy for unresectable hepatocellular carcinoma (HCC) causes poor patient outcomes. We aimed to identify predictive factors associated with the deterioration of Child-Pugh score at 8 weeks after lenvatinib initiation. Patients with adequate clinical data and baseline preserved serum samples available were included. Baseline fibroblast growth factor (FGF)19 and 21, angiopoietin (ANG)2, and vascular endothelial growth factor (VEGF) levels were evaluated. Thirty-seven patients were included, and 6, 15, 14, and 2 experienced complete response, partial response, stable disease, and progressive disease, respectively. Twenty-four (65%) and 13 (35%) patients showed a maintained/improved and deteriorated Child-Pugh-score, respectively. While baseline clinical data, treatment response, and laboratory data were similar between these two patient groups, baseline ANG2 and VEGF levels were significantly higher (P = 0.0017) and lower (P = 0.0231), respectively, in patients with deteriorated Child-Pugh score than in those without. Based on receiver operating characteristic curve analysis, cut-off values for ANG2 and VEGF were found to be 3,108 pg/mL and 514.9 pg/mL, respectively. Among patients with low VEGF and high ANG2, 89% (8/9) exhibited a deteriorated Child-Pugh score, whereas none of the patients (0/9) with high VEGF and low ANG2 did. The deterioration of the Child-Pugh score in patients with unresectable HCC who are treated with lenvatinib may be predictable based on combined baseline serum ANG2 and VEGF levels.
• Red dichromatic imaging helps in detecting exposed blood vessels in gastric ulcer induced by endoscopic submucosal dissection.
  Shuichi Miyamoto, Ryo Sugiura, Satoshi Abiko, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Naoya Sakamoto
  Endoscopy, 53, 11, E403-E404, 17 Dec. 2020, [International Magazine]
  English, Scientific journal
• Molecular biological analysis of 5-FU-resistant gastric cancer organoids; KHDRBS3 contributes to the attainment of features of cancer stem cell.
  Shoichi Ukai, Ririno Honma, Naoya Sakamoto, Yusuke Yamamoto, Quoc Thang Pham, Kenji Harada, Tsuyoshi Takashima, Daiki Taniyama, Ryuichi Asai, Kaho Fukada, Kazuhito Naka, Kazuaki Tanabe, Hideki Ohdan, Wataru Yasui
  Oncogene, 39, 50, 7265, 7278, Dec. 2020, [International Magazine]
  English, Scientific journal, 5-FU is one of the key drugs in the treatment of gastric cancer (GC). Much evidence has shown that cancer stem cells (CSCs) play a key role in the acquisition of drug resistance. The organoid is a novel 3D cell culture system technology that sustains stem-cell-driven formation of near-physiological, self-renewing tissues using specific niche factors in a dish. In this study, we established GC organoids (GCOs) and gradually treated them with higher concentrations of 5-FU. We successfully harvested four 5-FU-resistant GCOs, which were supported by significant changes in the expression of molecules related to 5-FU metabolism. We then performed microarray analysis using three normal gastric organoids and three pairs of 5-FU-resistant and parental GCOs. Through the comparison of expression profiles and further validation, we chose KHDRBS3 as a target gene. We found KHDRBS3 to be an independent prognostic factor in GC patients, especially in GC patients treated with 5-FU chemotherapy. We also determined that KHDRBS3 might play an important role in the acquisition of stem cell-like features, such as multi-drug resistance and organoid formation, by regulating CD44 variant expression. We found KHDRBS3, which is thought to play an important role in the acquisition of characteristics of CSCs in GC, to be a promising candidate marker for predicting therapeutic effect and prognosis in GC patients.
• Durable response without recurrence to Tolvaptan improves long-term survival.
  Masato Nakai, Goki Suda, Akinori Kubo, Yoshimasa Tokuchi, Takashi Kitagataya, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Journal of gastroenterology, 55, 12, 1150, 1161, Dec. 2020, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Decompensated liver cirrhosis patients with refractory ascites or pleural effusion have a poor prognosis. Tolvaptan has been used for treating water retention associated with cirrhosis. However, despite the short-term response, water retention recurrence is still observed in some cases. This study aimed to clarify the water retention recurrence rate and the relationship between long-term response without recurrence and prognosis. METHODS: Altogether, 100 patients with decompensated cirrhosis treated with tolvaptan were retrospectively analyzed. Recurrence was evaluated according to the criteria of the EASL clinical practice guideline. The recurrence rate and prognosis of non-responders, patients with recurrence, and long-term responders were analyzed. The baseline factors related to short-term response, recurrence, and long-term response were also evaluated. RESULTS: Approximately 31.0% of the short-term responders had recurrence. Although there was no significant difference in the prognosis by short-term response (p = 0.07), the long-term responders had a significantly better prognosis than those with recurrence and non-responders (p < 0.01). Low CRP levels and high urinary Na/K ratios were significant factors related to short-term response, and the presence of acute kidney injury was also a factor related to non-response. The low CRP level (relapse: < 1.10 mg/dl, long-term response: < 0.94 mg/dl) was identified as a factor related to recurrence and long-term response. CONCLUSION: The long-term responders without recurrence had a significantly better prognosis. CRP was a useful predictor for long-term response, whereas renal function parameters were useful predictors for short-term response. Inflammation control may be important for long-term response and prognosis in cirrhosis patients with water retention.
• Digital PCR-based plasma cell-free DNA mutation analysis for early-stage pancreatic tumor diagnosis and surveillance.
  Tetsuhiro Okada, Yusuke Mizukami, Yusuke Ono, Hiroki Sato, Akihiro Hayashi, Hidemasa Kawabata, Kazuya Koizumi, Sakue Masuda, Shinichi Teshima, Kuniyuki Takahashi, Akio Katanuma, Yuko Omori, Hirotoshi Iwano, Masataka Yamada, Tomoki Yokochi, Shingo Asahara, Kazumichi Kawakubo, Masaki Kuwatani, Naoya Sakamoto, Katsuro Enomoto, Takuma Goto, Junpei Sasajima, Mikihiro Fujiya, Jun Ueda, Seiji Matsumoto, Kenzui Taniue, Ayumu Sugitani, Hidenori Karasaki, Toshikatsu Okumura
  Journal of gastroenterology, 55, 12, 1183, 1193, Dec. 2020, [Domestic magazines]
  English, Scientific journal, BACKGROUND: Cell-free DNA (cfDNA) shed from tumors into the circulation offers a tool for cancer detection. Here, we evaluated the feasibility of cfDNA measurement and utility of digital PCR (dPCR)-based assays, which reduce subsampling error, for diagnosing pancreatic ductal adenocarcinoma (PDA) and surveillance of intraductal papillary mucinous neoplasm (IPMN). METHODS: We collected plasma from seven institutions for cfDNA measurements. Hot-spot mutations in KRAS and GNAS in the cfDNA from patients with PDA (n = 96), undergoing surveillance for IPMN (n = 112), and normal controls (n = 76) were evaluated using pre-amplification dPCR. RESULTS: Upon Qubit measurement and copy number assessment of hemoglobin-subunit (HBB) and mitochondrially encoded NADH:ubiquinone oxidoreductase core subunit 1 (MT-ND1) in plasma cfDNA, HBB offered the best resolution between patients with PDA relative to healthy subjects [area under the curve (AUC) 0.862], whereas MT-ND1 revealed significant differences between IPMN and controls (AUC 0.851). DPCR utilizing pre-amplification cfDNA afforded accurate tumor-derived mutant KRAS detection in plasma in resectable PDA (AUC 0.861-0.876) and improved post-resection recurrence prediction [hazard ratio (HR) 3.179, 95% confidence interval (CI) 1.025-9.859] over that for the marker CA19-9 (HR 1.464; 95% CI 0.674-3.181). Capturing KRAS and GNAS could also provide genetic evidence in patients with IPMN-associated PDA and undergoing pancreatic surveillance. CONCLUSIONS: Plasma cfDNA quantification by distinct measurements is useful to predict tumor burden. Through appropriate methods, dPCR-mediated mutation detection in patients with localized PDA and IPMN likely to progress to invasive carcinoma is feasible and complements conventional biomarkers.
• Immune checkpoint inhibitor-induced enteritis assessed using capsule endoscopy.
  Shinsuke Otagiri, Takehiko Katsurada, Kana Yamanashi, Kensuke Sakurai, Michiko T Sato, Jun Sakakibara-Konishi, Naoya Sakamoto
  JGH open : an open access journal of gastroenterology and hepatology, 4, 6, 1231, 1232, Dec. 2020, [International Magazine]
  English, Scientific journal, We performed capsule endoscopy for a patient with immune checkpoint inhibitor-induced enteritis and found multiple erosions or small ulcers in the small intestine. No reports demonstrated the effectiveness of capsule endoscopy for immune checkpoint inhibitor-induced gastrointestinal adverse events, and our case suggests that capsule endoscopy may be useful to evaluate immune checkpoint inhibitor-induced enteritis.
• クローン病活動性評価の超音波検査とダブルバルーン内視鏡検査との相関の検討　　　　　　　　　　　　　　　
  山梨 香菜, 桂田 武彦, 西田 睦, 大西 礼造, 表原 里実, 桜井 健介, 小田切 信介, 木下 賢治, 長島 一哲, 坂本 直哉
  超音波医学, 47, Suppl., S317, S317, (公社)日本超音波医学会, Nov. 2020
  Japanese
• 【肝細胞癌治療のパラダイムチェンジ-進化する薬物療法2020 Update Part II-(分子標的治療)】カボザンチニブ CELESTIAL試験の総括とサブ解析　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 81, 5, 986, 992, (株)アークメディア, Nov. 2020
  Japanese
• Synchronous multiple needle tract seedings of the gastric wall after EUS-guided fine-needle biopsy for pancreatic cancer.
  Shuhei Hayasaka, Ryo Sugiura, Yoshiya Yamamoto, Hirohito Naruse, Naoya Sakamoto
  Gastrointestinal endoscopy, 92, 5, 1126, 1127, Nov. 2020, [International Magazine]
  English, Scientific journal
• Risk factors for dysfunction of preoperative endoscopic biliary drainage for malignant hilar biliary obstruction.
  Ryo Sugiura, Masaki Kuwatani, Shin Kato, Kazumichi Kawakubo, Hirofumi Kamachi, Akinobu Taketomi, Takehiro Noji, Keisuke Okamura, Satoshi Hirano, Naoya Sakamoto
  Journal of hepato-biliary-pancreatic sciences, 27, 11, 851, 859, Nov. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: Few studies have focused on the risk factors for dysfunction of endoscopic biliary drainage (EBD) in preoperative patients with malignant hilar biliary obstruction (MHBO). METHODS: We searched the database between February 2011 and December 2018 and identified patients with MHBO who underwent radical operation. The rate of dysfunction of the initial EBD, risk factors for dysfunction of the initial EBD and survival after surgery were retrospectively evaluated. RESULTS: We analyzed a total of 131 patients [95 males (72.5%); mean age, 69.5 (±7.3) years; Bismuth-Corlette classification (BC) I/II/IIIa/IIIb/IV, 50/26/22/17/16; hilar cholangiocarcinoma/gall bladder cancer, 115/16]. Dysfunction of the initial EBD occurred in 28 patients (21.4%). The cumulative incidences of dysfunction of the initial EBD in all patients were 18.4%, 38.2% and 47.0% at 30, 60 and 90 days, respectively (Kaplan-Meier method). The rate of dysfunction of the initial EBD increased in patients with BC-IV (P = .03). Multivariate analysis showed that BC-IV and pre-EBD cholangitis were significantly associated with the occurrence of dysfunction of the initial EBD. Survival rates were not significantly different according to the initial biliary drainage methods and presence/absence of the initial EBD dysfunction. CONCLUSIONS: Dysfunction of the initial EBD frequently occurs in patients with the BC-IV and those with pre-EBD cholangitis.
• Relationships of early esophageal cancer with human papillomavirus and alcohol metabolism.
  Masaki Inoue, Yuichi Shimizu, Marin Ishikawa, Satoshi Abiko, Yoshihiko Shimoda, Ikko Tanaka, Sayoko Kinowaki, Masayoshi Ono, Keiko Yamamoto, Shoko Ono, Naoya Sakamoto
  World journal of gastroenterology, 26, 39, 6047, 6056, 21 Oct. 2020, [International Magazine]
  English, Scientific journal, BACKGROUND: It is well known that an alcohol consumption habit together with inactive heterozygous aldehyde dehydrogenase-2 (ALDH2) is an important risk factor for the development of esophageal squamous cell carcinoma (ESCC). It remains controversial whether human papillomavirus (HPV) infection contributes to the occurrence/development of ESCC. There has been no study in which the relationship between ESCC and HPV in addition to alcohol dehydrogenase-1B (ADH1B) and ALDH2 genotypes was evaluated. AIM: To evaluate relationships between HPV infection and development of esophageal cancer, particularly early esophageal cancer, based on ADH1B/ALDH2 polymorphisms. METHODS: We conducted an exploratory retrospective study using new specimens, and we enrolled 145 patients who underwent endoscopic resection for superficial ESCC and had been observed for more than two years by both physical examination and endoscopic examination in Hokkaido University Hospital. Saliva was collected to analyze genetic polymorphisms of ADH1B/ALDH2. We performed in situ hybridization for resected specimens to detect HPV by using an HPV type 16/18 probe. RESULTS: HPV was detected in 15 (10.3%) of the 145 patients with ESCC. HPV-positive rates in inactive ALDH2*1/*2 and ALDH2*1/*1 + *2/*2 were 10.8% and 9.8%, respectively (P = 1.00). HPV-positive rates in slow-metabolizing ADH1B*1/*1 and ADH1B*1/*2 + *2/*2 were 12.0% and 10.0%, respectively (P = 0.72). HPV-positive rates in the heavy or moderate alcohol consumption group and the light or rare consumption group were 11.1% and 8.7%, respectively (P = 0.68). HPV-positive rates in the heavy smoking group and the light or no smoking group were 11.8% and 8.3%, respectively (P = 0.59). The 3-year incidence rates of secondary ESCC or head and neck cancer after initial treatment in the HPV-positive and HPV-negative groups were 14.4% and 21.4% (P = 0.22), respectively. CONCLUSION: In the present situation, HPV status is considered to be less important than other risk factors, such as alcohol consumption, smoking habit, ADH1B/ALDH2 polymorphisms, and HPV status would therefore have no effect on ESCC risk management.
• In vivo optical cellular diagnosis for uterine cervical or vaginal intraepithelial neoplasia using flexible gastrointestinal endocytoscopy -a prospective pilot study.
  Shoko Ono, Ayako Nozaki, Kana Matsuda, Emi Takakuwa, Naoya Sakamoto, Hidemichi Watari
  BMC cancer, 20, 1, 955, 955, 02 Oct. 2020, [International Magazine]
  English, Scientific journal, BACKGROUUND: For patients with any kind of atypical squamous intraepithelial lesion of the uterine cervix or vagina, colposcopy and punch biopsy are common procedures for histological determination following cytology. However, colposcopy-guided biopsy does not provide a high level of diagnostic accuracy. The aim of this study was to determine the usefulness of optical biopsy in vivo using endocytoscopy compared with conventional procedures using colposcopy. METHODS: Between May 2018 and March 2019, patients who were scheduled for cervical conization or mapping biopsies of the vagina were prospectively enrolled. Endocytoscopy was performed by senior endoscopists prior to scheduled procedures, and endocytoscopic images and biopsy samples were taken from the most prominent site and surrounding area of the cervical or vaginal lesions. The collection process of images was randomized and anonymous, and three doctors separately evaluated the images according to the ECA classification. ECA 4 and 5 are indicative of endoscopic malignancy. The primary endpoint was diagnostic accuracy (benign or malignant: cervical intraepithelial neoplasia (CIN) 3 or vaginal intraepithelial neoplasia (VAIN) 3 or worse) of cell images at the most prominent site in each patient. RESULTS: A total of 28 consecutive patients were enrolled. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of endocytoscopic images were 95.0% (84.8-98.6%), 87.5% (61.9-96.5%), 95.0% (84.8-98.6%), 87.5% (61.9-96.5%) and 92.9% (78.2-98.0%), respectively. Inter-observer agreement among three reviewers was 0.78 (0.08-9.88, P < 0.01). On the other hand, the accuracy of colposcopy-guided biopsy was 74.1% (64.0-84.0%). CONCLUSIONS: Optical cell diagnosis of cervical or vaginal intraepithelial neoplasia using endocytoscopy provides a high level of diagnostic accuracy. TRIAL REGISTRATION: The study was registered with the UMIN database (ID: 000031712 ). UMIN000031712 . Registered 16 March 2017.
• 主膵管多発狭窄を呈した膵管上皮内病変の1例　　　　　　　　　　　　　　　
  佐々木 貴志, 桑谷 将城, 三橋 智子, 浅野 賢道, 中村 透, 平野 聡, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 68, 68, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 慢性関節リウマチに対する免疫抑制療法中に重篤な小腸出血を来した1例　　　　　　　　　　　　　　　
  田中 一光, 小野 尚子, 西村 友佑, 久保 茉理奈, 霜田 佳彦, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉, 市川 伸樹, 吉田 雅, 本間 重紀, 杉野 弘和, 岡田 宏美
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 60, 60, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 高度貧血の原因となった胃の過形成性ポリープに対し、プロトンポンプ阻害薬の内服中止が著効した1例　　　　　　　　　　　　　　　
  西村 友佑, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 小野 尚子, 清水 勇一, 清水 亜衣, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 53, 53, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 高度貧血をきたした回腸Pyogenic granulomaに対しEMRを施行した1例　　　　　　　　　　　　　　　
  張 辛寒, 小野 尚子, 西村 友佑, 久保 茉理奈, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 清水 勇一, 清水 亜衣, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 60, 60, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 炎症性腸疾患に対する腹部超音波検査の有用性　　　　　　　　　　　　　　　
  桂田 武彦, 小田切 信介, 桜井 健介, 木下 賢治, 山梨 香菜, 大西 礼造, 長島 一哲, 西田 睦, 表原 里実, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 48, 48, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• Oxaliplatinによる類洞閉塞症候群の診断における腹部超音波検査の有用性の検討　　　　　　　　　　　　　　　
  斎藤 里佳, 西田 睦, 岩井 孝仁, 菊池 穏香, 吉野 裕紀, 横田 勲, 高木 諒, 川本 泰之, 山村 貴洋, 伊藤 憲, 中野 真太郎, 原田 一顕, 結城 敏志, 小松 嘉人, 坂本 直哉
  日本癌治療学会学術集会抄録集, 58回, P, 178, (一社)日本癌治療学会, Oct. 2020
  English
• 消化管間質腫瘍(GIST)におけるレゴラフェニブ治療と骨格筋量の変化に関する検討　　　　　　　　　　　　　　　
  伊藤 憲, 原田 一顕, 川本 泰之, 中積 宏之, 中野 真太郎, 斎藤 里佳, 山村 貴洋, 結城 敏志, 小松 嘉人, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 62, 62, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 消化器癌の化学療法で味覚異常を発症した症例の多施設共同医師主導前向き観察研究　　　　　　　　　　　　　　　
  伊藤 憲, 結城 敏志, 中積 宏之, 安藤 孝将, 太宰 昌佳, 畑中 一映, 宮城島 拓人, 久居 弘幸, 石黒 敦, 植田 亮, 佐々木 尚英, 進藤 吉明, 坂本 直哉, 坂田 優, 小松 嘉人
  日本癌治療学会学術集会抄録集, 58回, P, 180, (一社)日本癌治療学会, Oct. 2020
  English
• 当院における門脈血栓症に対するアンチトロンビンIII製剤の使用成績　　　　　　　　　　　　　　　
  北潟谷 隆, 小川 浩司, 山田 錬, 重沢 拓, 鈴木 和治, 中村 晃久, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 44, 44, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• ソホスブビル/ベルパタスビル投与によりSVR12が得られたC型非代償性肝硬変の1例　　　　　　　　　　　　　　　
  山田 錬, 小川 浩司, 北潟谷 隆, 重沢 拓, 鈴木 和治, 中村 晃久, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  日本消化器病学会北海道支部例会・日本消化器内視鏡学会北海道支部例会プログラム・抄録集, 127回・121回, 45, 45, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 超音波内視鏡下瘻孔形成術における先端鋭拡張専用カテーテルと通電拡張カテーテルの有用性の比較　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 平田 甫, 瀧新 悠之介, 平田 幸司, 古川 龍太郎, 坂本 直哉
  Gastroenterological Endoscopy, 62, Suppl.2, 2172, 2172, (一社)日本消化器内視鏡学会, Oct. 2020
  Japanese
• 【肝細胞癌治療のパラダイムチェンジ-進化する薬物療法2020 Update Part I-(免疫療法)】免疫チェックポイント阻害剤による単剤治療 進行肝細胞癌に対するニボルマブ第III相試験(CheckMate 459試験)のUpdate results　　　　　　　　　　　　　　　
  小川 浩司, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝胆膵, 81, 4, 651, 657, (株)アークメディア, Oct. 2020
  Japanese
• 肝性脳症〜わが国における現状と課題〜 肝性脳症の疫学　　　　　　　　　　　　　　　
  中井 正人, 小川 浩司, 久保 彰則, 得地 祐匡, 北潟谷 隆, 山田 錬, 重沢 拓, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  日本門脈圧亢進症学会雑誌, 26, 3, 75, 75, (一社)日本門脈圧亢進症学会, Oct. 2020
  Japanese
• 胃閉塞を来した若年性ポリポーシスの1例　　　　　　　　　　　　　　　
  霜田 佳彦, 山本 桂子, 田中 一光, 井上 雅貴, 木脇 佐代子, 石川 麻倫, 大野 正芳, 高橋 正和, 森 康明, 中川 学, 中川 宗一, 小野 尚子, 清水 勇一, 倉島 庸, 今本 鉄平, 松野 吉宏, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 127回, 53, 53, 日本消化器病学会-北海道支部, Oct. 2020
  Japanese
• 頭頸部癌放射線照射後遺残、異時性多発癌に対する内視鏡治療成績　　　　　　　　　　　　　　　
  井上 雅貴, 清水 勇一, 霜田 佳彦, 田中 一光, 木脇 佐代子, 石川 麻倫, 大野 正芳, 山本 桂子, 小野 尚子, 本間 明宏, 坂本 直哉
  Gastroenterological Endoscopy, 62, Suppl.2, 2127, 2127, (一社)日本消化器内視鏡学会, Oct. 2020
  Japanese
• 子宮頸部・腟上皮内腫瘍における生体内細胞観察の診断能に関する検討 超拡大内視鏡は有用か　　　　　　　　　　　　　　　
  小野 尚子, 松田 可奈, 石川 麻倫, 大野 正芳, 木脇 佐代子, 霜田 佳彦, 田中 一行, 井上 雅貴, 山本 桂子, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 62, Suppl.2, 2165, 2165, (一社)日本消化器内視鏡学会, Oct. 2020
  Japanese
• 食道ESD中の鎮静薬と塩酸ペチジン併用の後ろ向き検討　　　　　　　　　　　　　　　
  大野 正芳, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 石川 麻倫, 山本 桂子, 小野 尚子, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 62, Suppl.2, 2199, 2199, (一社)日本消化器内視鏡学会, Oct. 2020
  Japanese
• Impact of single-heterozygous UGT1A1 on the clinical outcomes of irinotecan monotherapy after fluoropyrimidine and platinum-based combination therapy for gastric cancer: a multicenter retrospective study.
  Shintaro Nakano, Satoshi Yuki, Yasuyuki Kawamoto, Hiroshi Nakatsumi, Takayuki Ando, Shinya Kajiura, Ayumu Yoshikawa, Kazuaki Harada, Kazuteru Hatanaka, Aya Tanimoto, Atsushi Ishiguro, Takuya Honda, Masayoshi Dazai, Takahide Sasaki, Naoya Sakamoto, Yoshito Komatsu
  International journal of clinical oncology, 25, 10, 1800, 1806, Oct. 2020, [Domestic magazines]
  English, Scientific journal, BACKGROUND: It is unclear whether the UGT1A1 status, single heterozygous (SH) or wild type (WT), is associated with the efficacy and toxicity of irinotecan monotherapy in advanced gastric cancer (AGC). We investigated the association between clinical outcomes (efficacy and safety) and UGT1A1 status in patients who received irinotecan monotherapy. METHODS: We evaluated AGC patients who received irinotecan monotherapy between January 2011 and December 2017. Efficacy was assessed according to overall survival (OS) and progression-free survival (PFS). Toxicity was graded using the Common Toxicity Criteria for Adverse Events (version 4.0). RESULTS: A total of 100 patients were evaluated (62 and 38 patients with UGT1A1 WT and SH, respectively). In the WT and SH groups, the irinotecan dose was reduced in 19 (30.6%) and 18 (47.2%) patients (p = 0.135), respectively; treatment was delayed due to adverse events (AEs) in 19 (30.6%) and 13 (34.2%) patients (p = 0.826), respectively; the median PFS was 3.15 and 3.25 months (HR, 0.734; 95% CI 0.465-1.158; p = 0.184), respectively; and the median OS was 10.4 and 7.26 months (HR, 1.137; 95% CI 0.752-1.721; p = 0.543), respectively. Severe hematological AEs (Grade ≥ 3) were significantly more frequent in the SH group than in the WT group (63% vs. 36%; p = 0.008), while severe non-hematological AEs was not significantly different (16.0% vs. 6.5%; p = 0.173). CONCLUSION: There was no significant difference in the efficacy of irinotecan monotherapy between UGT1A1 WT and UGT1A1 SH, but UGT1A1 SH was associated with a high frequency of severe hematological toxicity.
• Time-dependent changes in the seroprevalence of COVID-19 in asymptomatic liver disease outpatients in an area in Japan undergoing a second wave of COVID-19.
  Goki Suda, Koji Ogawa, Megumi Kimura, Osamu Maehara, Takashi Kitagataya, Masatsugu Ohara, Yoshimasa Tokuchi, Akinori Kubo, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 50, 10, 1196, 1200, Oct. 2020, [International Magazine]
  English, Scientific journal, AIM: Coronavirus disease 2019 (COVID-19) is a serious public health concern, with unclarified prevalence in Japan. Concomitant liver disease could increase the severity of COVID-19 disease, and chronic liver disease patients sometimes require frequent admission and gastrointestinal endoscopy. Thus, clarifying the prevalence of asymptomatic COVID-19 in outpatients with liver disease is essential for preventing nosocomial infections. We aimed to clarify the time-dependent changes in COVID-19 seroprevalence in liver disease outpatients, who were asymptomatic for COVID-19, in an area of Japan experiencing a second wave of COVID-19. METHODS: We included the preserved sera of 100, 300, and 300 consecutive liver disease outpatients, who were asymptomatic for COVID-19, from May 2019, March 2020, and May 2020, respectively. The sera were analyzed immunochromatographically to detect immunoglobulin G against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (KURABO) and by Elecsys Anti-SARS-CoV-2-assay (Roche Diagnostics). RESULTS: Analysis of 100 cases from May 2019, before COVID-19 became pandemic, revealed that the specificity of immunochromatographic tests and Elecsys were 98% (95% confidence interval [CI], 93-99.8%) and 100% (95% CI, 97-100%), respectively. Analysis of 300 cases from March 2020 revealed a seroprevalence of 0.3% (1/300; 95% CI, 0-1.8%) for COVID-19 by Elecsys Anti-SARS-CoV-2 assay. Analysis of 300 cases from May 2020 revealed a seroprevalence of 0% (0/300; 95% CI, 0-1.0%). CONCLUSIONS: The Elecsys Anti-SARS-CoV-2 assay has high specificity. The cumulative seroprevalence of COVID-19 by the Elecsys Anti-SARS-CoV-2 assay in outpatients with liver disease in Sapporo, who were asymptomatic for COVID-19, was 0.17% (1/600; 95% CI, 0.0-0.9%) until May 2020.
• Baseline angiopoietin-2 and FGF19 levels predict treatment response in patients receiving multikinase inhibitors for hepatocellular carcinoma.
  Taku Shigesawa, Goki Suda, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Ren Yamada, Takashi Kitagataya, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  JGH open : an open access journal of gastroenterology and hepatology, 4, 5, 880, 888, Oct. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Prevalence, clinical course, and predictive factors of immune checkpoint inhibitor monotherapy-associated hepatitis in Japan.
  Takashi Kitagataya, Goki Suda, Kazunori Nagashima, Takehiko Katsurada, Koji Yamamoto, Megumi Kimura, Osamu Maehara, Ren Yamada, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Yoshito Komatsu, Hiroo Hata, Satoshi Takeuchi, Takashige Abe, Jun Sakakibara-Konishi, Takanori Teshima, Akihiro Homma, Naoya Sakamoto
  Journal of gastroenterology and hepatology, 35, 10, 1782, 1788, Oct. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Immune checkpoint inhibitors (ICI) have revolutionized anti-malignancy therapy and thus have been increasingly used. Although ICI may cause immune-related adverse events (irAE) in various organs, including the liver, the prevalence and predictive factors of irAE have not been clarified. METHODS: In this retrospective study, consecutive patients who had malignancies and were treated with ICI without other chemotherapeutic agents at Hokkaido University Hospital between 2014 and 2019 were screened. Patients were excluded if they were < 20 years old and had insufficient clinical data. RESULTS: Of the 233 patients screened, 202 patients met the inclusion criteria and were included in the analysis. The patients were aged 25-92 years, and 60.9% were male. The patients received nivolumab (n = 137), pembrolizumab (n = 45), ipilimumab (n = 17), atezolizumab (n = 2), and avelumab (n = 1). The prevalence of any grade and grade ≥ 3 irAE hepatitis was 8.4% (17/202) and 4.0% (8/202), respectively. irAE hepatitis occurred at a median duration of 42 days in any grade and 36 days in grade ≥ 3 after ICI initiation. The clinical course of grade ≥ 3 irAE hepatitis was generally favorable; however, 50% required corticosteroid treatment and two patients required additional mycophenolate mofetil. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis. CONCLUSIONS: Grade ≥ 3 irAE hepatitis was observed in 4.0% of the patients who were treated with ICI. Female sex and history of ICI treatment were significantly associated with the incidence of grade ≥ 3 irAE hepatitis.
• Association between the use of antibiotics and efficacy of gemcitabine plus nab-paclitaxel in advanced pancreatic cancer.
  Shintaro Nakano, Yoshito Komatsu, Yasuyuki Kawamoto, Rika Saito, Ken Ito, Hiroshi Nakatsumi, Satoshi Yuki, Naoya Sakamoto
  Medicine, 99, 39, e22250, 25 Sep. 2020, [International Magazine]
  English, Scientific journal, It is unclear whether the use of antibiotics is related to the efficacy of gemcitabine plus nab-paclitaxel (GnP). Therefore, we investigated the association between the use of antibiotics and efficacy of GnP.We conducted a retrospective single center study from January 2014 to December 2018 in Hokkaido University Hospital.Ninety-nine patients were eligible for the study. Thirty-seven used antibiotics (U) and 62 did not use antibiotics (NU) during GnP therapy. In the U group, 15 patients used β-lactam antibiotics, 21 used new quinolones, and 1 used carbapenem. The median progression-free survival was 5.8 and 2.7 months (hazards ratio [HR] .602, 95% confidence interval [CI] .391-.928, P = .022) and the median overall survival was 11.0 and 8.4 months (HR .768, 95% CI .491-1.202, P = .248) in the U and not use antibiotics groups, respectively. Antibiotic use (HR .489, 95% CI .287-.832, P = .008) and locally advanced pancreatic cancer (HR 1.808, 95% CI 1.051-3.112, P = .032) were independent prognostic factors for progression-free survival.Antibiotic use was associated with a higher efficacy of GnP, and therefore, it may be employed as a novel treatment strategy.
• HCC既往の無いC型肝炎SVR後の初発肝発癌の囲い込み因子としての肝弾性度の有用性　　　　　　　　　　　　　　　
  中井 正人, 山本 義也, 馬場 英, 古家 乾, 北潟谷 隆, 山田 錬, 重沢 拓, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 61, Suppl.2, A682, A682, (一社)日本肝臓学会, Sep. 2020
  Japanese
• 免疫チェックポイント阻害剤関連肝炎の頻度、予測因子、臨床経過の検討　　　　　　　　　　　　　　　
  北潟谷 隆, 須田 剛生, 中井 正人, 荘 拓也, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 61, Suppl.2, A705, A705, (一社)日本肝臓学会, Sep. 2020
  Japanese
• Clip with thread attachment prior to incision - new strategy for traction-assisted esophageal endoscopic submucosal dissection.
  Shuichi Miyamoto, Tomohiko R Ohya, Masayuki Higashino, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Naoya Sakamoto
  Endoscopy, 52, 9, E328-E329, Sep. 2020, [International Magazine]
  English, Scientific journal
• Treatment of hepatocellular carcinoma during the COVID-19 outbreak: The Working Group report of JAMTT-HCC.
  Masatoshi Kudo, Masayuki Kurosaki, Masafumi Ikeda, Hiroshi Aikata, Atsushi Hiraoka, Takuji Torimura, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 50, 9, 1004, 1014, Sep. 2020, [International Magazine]
  English, Scientific journal, This contingency guide was formulated on the premise that delivering standard treatment for hepatocellular carcinoma (HCC) has come under strain due to the coronavirus (COVID-19) pandemic. Measures required are likely to vary largely across regions and individual institutions, depending on the level of the strain imposed by the pandemic (e.g., number of inpatients infected with COVID-19 and the availability of resources, including personal protective equipment and inpatient beds). In addition, models suggest that the second and third waves of COVID-19 will occur before effective vaccines and medicines become widely available in Japan (expected time, 2-3 years). This guide should serve as a good reference for best practices in the management of HCC, which is in light of the possible risk of impending collapse of the healthcare system due to a surge in COVID-19 infections.
• Plasma Lipid Profiling of Three Types of Drug-Induced Liver Injury in Japanese Patients: A Preliminary Study.
  Kosuke Saito, Tatehiro Kagawa, Keiji Tsuji, Yuji Kumagai, Ken Sato, Shotaro Sakisaka, Naoya Sakamoto, Mitsuhiko Aiso, Shunji Hirose, Nami Mori, Rieko Tanaka, Toshio Uraoka, Kazuhide Takata, Koji Ogawa, Kazuhiko Mori, Motonobu Sato, Takayoshi Nishiya, Kazuhiko Takamatsu, Noriaki Arakawa, Takashi Izumi, Yasuo Ohno, Yoshiro Saito, Hajime Takikawa
  Metabolites, 10, 9, 31 Aug. 2020, [International Magazine]
  English, Scientific journal, Drug-induced liver injury (DILI) is a major adverse event caused by drug treatment, which can be categorized into three types: hepatocellular, mixed, and cholestatic. Although nearly every class of drugs can cause DILI, an overall understanding of lipid profiles in DILI patients is lacking. We used lipidomics to analyze the plasma lipid profiles of patients to understand their hepatic pathophysiology and identify DILI biomarkers. We identified 463 lipids and compared their levels between the acute and recovery phases of the three types of DILI patients. Mixed and cholestatic types demonstrated specific plasma lipid alterations between the phases, but the hepatocellular type did not. Moreover, as specific indicators of mixed-type DILI, levels of several ceramides increased in the acute phase, while those of arachidonic acid-containing ether-linked phosphoglycerolipids decreased. In contrast, as specific indicators of cholestatic-type DILI, levels of palmitic acid-containing saturated or monounsaturated phosphatidylcholines increased in the acute phase, while those of arachidonic acid- or docosahexaenoic acid-containing ether-linked phosphoglycerolipids and phosphatidylinositols decreased. We also identified lipids with a relatively high capacity to discriminate the acute phase from the recovery phase and healthy subjects. These findings may help with understanding the pathophysiology of different DILI types and identify candidate biomarkers.
• 難渋する胆道ドレナージの工夫 肝門部胆管金属ステント留置困難症例におけるES dilatorの有用性(Eligible cases of stent-in-stent placement for malignant hilar biliary obstructions in consideration of endoscopic reintervention)
  滝新 悠之介, 桑谷 将城, 坂本 直哉, 古川 龍太郎, 平田 甫, 平田 幸司, 加藤 新
  胆道, 34, 3, 452, 452, 日本胆道学会, Aug. 2020
  English
• 乳頭膨張型胆管癌と術前診断された胆管上皮内癌の一例
  古川 龍太郎, 桑谷 将城, 三橋 智子, 平田 甫, 瀧新 悠之介, 平田 幸司, 加藤 新, 平野 聡, 坂本 直哉
  胆道, 34, 3, 528, 528, 日本胆道学会, Aug. 2020
  Japanese
• 肝門部金属ステント留置困難例でのESダイレーターを用いたトラブルシューティング　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 坂本 直哉, 平田 甫, 瀧新 悠之介, 平田 幸司, 古川 龍太郎
  Gastroenterological Endoscopy, 62, Suppl.1, 1234, 1234, (一社)日本消化器内視鏡学会, Aug. 2020
  Japanese
• 膵周囲液体貯留に対する超音波内視鏡下ドレナージの有効性と安全性　　　　　　　　　　　　　　　
  古川 龍太郎, 桑谷 将城, 坂本 直哉, 平田 甫, 瀧新 悠之介, 平田 幸司, 加藤 新
  Gastroenterological Endoscopy, 62, Suppl.1, 1312, 1312, (一社)日本消化器内視鏡学会, Aug. 2020
  English
• 高齢者食道ESDの治療成績と予後解析　　　　　　　　　　　　　　　
  霜田 佳彦, 清水 勇一, 坂本 直哉, 石川 麻倫, 田中 一光, 井上 雅貴, 木脇 佐代子, 大野 正芳, 山本 桂子, 小野 尚子
  Gastroenterological Endoscopy, 62, Suppl.1, 1216, 1216, (一社)日本消化器内視鏡学会, Aug. 2020
  Japanese
• 生体ブタ全周性食道ESD施行後のバルーン拡張時の病理組織学的検討　　　　　　　　　　　　　　　
  木脇 佐代子, 清水 勇一, 大西 俊介, 大野 正芳, 楊 子健, 霜田 佳彦, 井上 雅貴, 田中 一光, 石川 麻倫, 山本 桂子, 小野 尚子, 坂本 直哉
  Gastroenterological Endoscopy, 62, Suppl.1, 1320, 1320, (一社)日本消化器内視鏡学会, Aug. 2020
  Japanese
• Acute progressing hepatic angiosarcoma: An autopsy case report.
  Masaki Inoue, Mio Matsumoto, Yusuke Sakuhara, Yasunari Takakuwa, Shinji Yoshii, Nobuaki Akakura, Naoya Sakamoto
  Radiology case reports, 15, 8, 1403, 1407, Aug. 2020, [International Magazine]
  English, A man in his 50s presented with pitting edema of both lower legs and abdominal distension as his chief complaint. His personal medical history and family history were unremarkable, except that he was a heavy drinker consuming 66 g of alcohol per day and a heavy smoker. Blood tests upon admission showed slight hepatic dysfunction, thrombocytopenia, jaundice, hypoalbuminemia, and decreased coagulability. Tumor marker tests showed elevated levels of CA19-9 and PIVKA-II. Contrast-enhanced computed tomography revealed enhancement of multiple masses predominantly in the right lobe of the liver in the early phase, followed by diffuse enhancement of the entire liver in the delayed phase. Hepatic arteriography demonstrated large hemangioma-like lesions corresponding to the masses revealed by computed tomography. That findings seemed to be cotton wool appearance. On magnetic resonance images, there were multiple mass-like lesions that showed homogeneous or heterogeneous low signal intensity on T1-weighted images, and clearly high signal intensity on T2-weighted images. The findings were atypical and no definite diagnosis could be made. Hepatic failure then rapidly worsened, and the patient died on hospital day 20. Autopsy led to the diagnosis of hepatic angiosarcoma.
• Lenvatinib in patients with unresectable hepatocellular carcinoma who do not meet the REFLECT trial eligibility criteria.
  Takuya Sho, Goki Suda, Koji Ogawa, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Jun Ito, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Katsumi Terasita, Tomofumi Takagi, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 50, 8, 966, 977, Aug. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: This study aimed to determine the efficacy and safety of lenvatinib for patients with unresectable hepatocellular carcinoma (HCC) who did not meet REFLECT eligibility criteria (phase 3 clinical trial). METHODS: In this multicenter retrospective study, patients with unresectable HCC treated with lenvatinib between 2018 and 2019 and had adequate clinical data were included. Objective response rate, progression-free-survival (PFS) and safety were evaluated according to meeting or not meeting the REFLECT eligibility criteria and according to the criteria of the REFLECT trial. RESULTS: Of the 105 patients included, 61% (64 of 105) did not meet the REFLECT eligibility criteria. Safety and median PFS of lenvatinib were similar between the patients who did and those who did not meet the criteria. Among the patients who did not meet the criteria, 28, 27, 14, six, seven and five had a history of tyrosine kinase inhibitor (TKI) treatment, Child-Pugh score B, HCC in ≥50% of the liver, reduced platelet count, bile duct invasion and main portal vein invasion, respectively. The efficacy and safety of lenvatinib for patients with or without Child-Pugh-score B or HCC in ≥50% of the liver were similar. Although treatment outcome was not significantly different, patients with TKI treatment history tended to have longer median PFS, whereas those with main portal vein invasion tended to have shorter median PFS. CONCLUSION: Lenvatinib was effective for patients who did not meet the REFLECT inclusion criteria. However, the treatment outcome may vary according to several factors, such as a history of TKI treatment and tumor invasion.
• Gastrointestinal: Endoscopic myotomy for a large rectal tumor with severe fibrosis after treatment of hemorrhoids
  S Miyamoto, J Ito, H Naruse, R Sugiura, Y Yamamoto, K Hatanaka, K Kinoshita, M Higashino, S Hayasaka, N Tsuchida, N Shimoyama, N Sakamoto
  Journal of Gastroenterology and Hepatology, 35, 7, 1097, 1097, Wiley, Jul. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Computed tomography, not bioelectrical impedance analysis, is the proper method for evaluating changes in skeletal muscle mass in liver disease
  Masatsugu Ohara, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  JCSM Rapid Communications, 3, 2, 103, 114, Wiley, Jul. 2020
  Scientific journal
• 進行肝細胞癌に対するREFLECT内/外におけるレンバチニブの治療効果と安全性の検討
  荘 拓也, 須田 剛生, 北潟谷 隆, 山田 錬, 重沢 拓, 鈴木 和治, 中村 晃久, 梅村 真知子, 中井 正人, 森川 賢一, 小川 浩司, 坂本 直哉
  日本消化器病学会雑誌, 117, 臨増総会, A253, A253, (一財)日本消化器病学会, Jul. 2020
  Japanese
• 部分的脾動脈塞栓術(PSE)により肝予備能は改善するか
  中井 正人, 小川 浩司, 北潟谷 隆, 山田 錬, 鈴木 和治, 中村 晃久, 梅村 真知子, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  日本消化器病学会雑誌, 117, 臨増総会, A367, A367, (一財)日本消化器病学会, Jul. 2020
  Japanese
• 慢性膵炎による主膵管高度狭窄に対する経乳頭的通電拡張術の有効性
  加藤 新, 桑谷 将城, 平田 甫, 瀧新 悠之介, 平田 幸司, 古川 龍太郎, 坂本 直哉
  膵臓, 35, 3, A326, A326, (一社)日本膵臓学会, Jul. 2020
  Japanese
• IgG4関連硬化性胆管炎の臨床的特徴とステロイド維持療法の妥当性
  瀧新 悠之介, 桑谷 将城, 古川 龍太郎, 平田 甫, 平田 幸司, 加藤 新, 坂本 直哉
  日本消化器病学会雑誌, 117, 臨増総会, A297, A297, (一財)日本消化器病学会, Jul. 2020
  Japanese
• Helicobacter pylori除菌後SM浸潤癌の臨床病理学的特徴
  山本 桂子, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 石川 麻倫, 大野 正芳, 小野 尚子, 清水 勇一, 坂本 直哉
  日本消化器病学会雑誌, 117, 臨増総会, A306, A306, (一財)日本消化器病学会, Jul. 2020
  Japanese
• 大腸EMRにおける抗凝固薬服用者の周術期管理と出血リスク
  田中 一光, 小野 尚子, 霜田 佳彦, 井上 雅貴, 木脇 佐代子, 石川 麻倫, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉
  日本消化器病学会雑誌, 117, 臨増総会, A361, A361, (一財)日本消化器病学会, Jul. 2020
  Japanese
• Side-by-side placement of fully covered self-expandable metal stents for malignant distal biliary obstruction.
  Koji Hirata, Masaki Kuwatani, Hajime Hirata, Ryo Sugiura, Shin Kato, Naoya Sakamoto
  Clinical journal of gastroenterology, 13, 3, 455, 458, Jun. 2020, [Domestic magazines]
  English, Scientific journal, A covered self-expandable metal stent is an efficient and established tool for solution of biliary obstruction. The use of multiple fully covered self-expandable metal stents (SEMSs) for distal malignant biliary obstruction has never been reported. The first case, a 33-year-old female with pancreatic head cancer had low bifurcation of the hepatic ducts and developed obstructive cholangitis by the first single SEMS. The second case, a-59-year-old female with pancreatic head cancer repeatedly underwent biliary decompression by a single SEMS (10-mm, 12-mm), because placed SEMSs were repeatedly dislocated. For solving these problems, we performed side-by-side placement of covered self-expandable metal stents. Finally, side-by-side placement of SEMSs across the papilla for distal malignant biliary obstruction was feasible and available for the two cases.
• High serum angiopoietin-2 level predicts non-regression of liver stiffness measurement-based liver fibrosis stage after direct-acting antiviral therapy for hepatitis C.
  Naoki Kawagishi, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Ren Yamada, Takashi Kitagataya, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 50, 6, 671, 681, Jun. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: Factors associated with improvement of liver fibrosis after successful hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting antiviral agents (DAAs) have been not clarified well. Angiopoietin-2 (Ang2) is reported to be associated with vascular leak and inflammation observed in patients with advanced liver fibrosis. METHODS: In this retrospective study, patients treated with IFN-free DAAs who underwent transient elastography before and at 24-weeks post-treatment and achieved sustained viral response were enrolled. Baseline serum Ang2 was measured, and its relationship with other clinical factors was analyzed. Liver fibrosis stage was defined based on liver stiffness according to a previous report. Predictive factors for regression of liver fibrosis stage after DAA therapy were evaluated. RESULTS: Overall, 116 patients were analyzed. Baseline serum Ang2 levels were significantly associated with liver stiffness, spleen index, and liver stiffness-based liver fibrosis stage. Moreover, 75% of patients experienced regression of liver fibrosis stage after DAA therapy. Multivariate analysis revealed that advanced liver fibrosis stage and Ang2 levels were significantly associated with regression of liver fibrosis stage after DAA therapy. In patients with advanced liver fibrosis (F3/4), baseline Ang2 level alone could predict regression of liver fibrosis stage. A baseline Ang2 cut-off value (354 pg/ML) could predict regression of liver fibrosis stage after DAA therapy with high accuracy (sensitivity 0.882, specificity 0.733). CONCLUSIONS: Evaluation of serum Ang2 levels before DAA therapy is important. Our results provide a novel mechanistic insight into non-regression of liver stiffness after DAA therapy. Long-term and larger studies are required.
• Analysis of the optimal psoas muscle mass index cut-off values, as measured by computed tomography, for the diagnosis of loss of skeletal muscle mass in Japanese people.
  Masatsugu Ohara, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Tomoe Kobayashi, Minoru Uebayashi, Ryo Takagi, Isao Yokota, Tsuyoshi Shimamura, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 50, 6, 715, 725, Jun. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, This study aimed to determine the optimal psoas muscle mass index (PMI) cut-off values for diagnosis of skeletal muscle mass loss. METHODS: We evaluated PMI in two groups of normal controls: a medical check-up group and a liver donation candidate group. We analyzed two novel PMI cut-off values, one based on the mean - two standard deviations (2SD) and one based on the lower 5%. Skeletal muscle mass index (SMI) evaluations using computed tomography (sliceOmatic; TomoVision) and bioelectrical impedance analysis and PMI evaluation were undertaken simultaneously. We analyzed the correlation between our PMI cut-off values and the Japan Society of Hepatology-defined SMI cut-off values. The prevalence of skeletal muscle mass loss in patients with liver disease was assessed using the novel PMI cut-off values. RESULTS: In 504 normal controls aged ≤50 years, the PMI cut-off values based on mean -2SD and the lower 5% were set at 3.30 cm2 /m2 for men and 1.69 cm2 /m2 for women and 3.74 cm2 /m2 for men and 2.29 cm2 /m2 for women, respectively. The PMI cut-off values based on the lower 5% alone showed that skeletal muscle mass loss increased with age. Furthermore, they correlated well with Japan Society of Hepatology-defined SMI (sliceOmatic) cut-off values and showed a significantly higher prevalence of skeletal muscle mass loss in patients with liver cirrhosis than those without liver cirrhosis. CONCLUSIONS: We propose the following PMI cut-off values: 3.74 cm2 /m2 for male individuals and 2.29 cm2 /m2 for female individuals. These cut-off values can facilitate accurate diagnosis and management of sarcopenia in patients with chronic liver disease.
• JNJ-4178 (adafosbuvir, odalasvir, and simeprevir) in Japanese patients with chronic hepatitis C virus genotype 1 or 2 infection with or without compensated cirrhosis: the Phase IIa OMEGA-3 study.
  Tetsuo Takehara, Kazuaki Chayama, Masayuki Kurosaki, Hiroshi Yatsuhashi, Yasuhito Tanaka, Naoki Hiramatsu, Naoya Sakamoto, Yasuhiro Asahina, Akito Nozaki, Toshikazu Nakano, Yosuke Hagiwara, Hiroko Shimizu, Hiroki Yoshida, Yuhan Huang, Michael Biermer, Leen Vijgen, Norio Hayashi
  Journal of gastroenterology, 55, 6, 640, 652, Springer Science and Business Media LLC, Jun. 2020, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: The efficacy, safety, and pharmacokinetics of the combination of three direct-acting antiviral (DAA) agents (adafosbuvir [also known as AL-335], odalasvir, and simeprevir) were investigated in DAA treatment-naïve Japanese patients with genotype (GT)1 or GT2 chronic hepatitis C virus (HCV) infection, with or without compensated cirrhosis. METHODS: In this Phase IIa, open-label, multicenter study-OMEGA-3 (NCT02993250)-patients received JNJ-4178 (adafosbuvir 800 mg once daily [QD], odalasvir 25 mg QD, and simeprevir 75 mg QD) for 8 (non-cirrhotic patients; Cohort 1) or 12 (cirrhotic patients; Cohort 2) weeks. Patients were followed-up to 24 weeks following the end of treatment (EOT). The primary endpoint was safety, including adverse events (AEs). RESULTS: Overall, 33 patients were enrolled into Cohort 1 (N = 22) or 2 (N = 11) and received combined treatment with JNJ-4178. During the treatment and follow-up phases, a higher percentage of patients in Cohort 2 (81.8%) experienced AEs compared with Cohort 1 (68.2%), but the incidence of treatment-related AEs was similar. Most AEs were mild-to-moderate in severity and no patients discontinued due to an AE. There was one serious AE (cataract) in a patient in Cohort 2, which was not considered related to treatment. All patients achieved sustained virologic response 12 weeks after EOT (SVR12). No incidences of viral relapse were observed during follow-up. CONCLUSIONS: In HCV GT1- and GT2-infected Japanese patients, treatment with JNJ-4178 was well tolerated and resulted in 100% of patients achieving SVR12.
• 【消化管腫瘍の内視鏡診断2020】胃腫瘍性病変の内視鏡診断 リンパ増殖性疾患の診断
  小野 尚子, 田中 一光, 木脇 佐代子, 井上 雅貴, 霜田 佳彦, 大野 正芳, 坂本 直哉, 石川 麻倫, 山本 桂子, 清水 勇一, 清水 亜衣, 松野 吉宏
  胃と腸, 55, 5, 593, 601, (株)医学書院, May 2020
  Japanese
• Histological and magnified endoscopic evaluation of villous atrophy in gastrointestinal graft-versus-host disease.
  Kana Matsuda, Shoko Ono, Ikko Tanaka, Masaki Inoue, Sayoko Kinowaki, Marin Ishikawa, Momoko Tsuda, Keiko Yamamoto, Yuichi Shimizu, Shuichiro Takahashi, Eiko Hayase, Daigo Hashimoto, Takanori Teshima, Naoya Sakamoto
  Annals of hematology, 99, 5, 1121, 1128, May 2020, [International Magazine]
  English, Scientific journal, AIM:  To measure histological villous atrophy and to clarify the diagnostic accuracy of endoscopic villous atrophy in gastrointestinal graft-versus-host disease. METHODS:  Data for patients who underwent upper and/or lower endoscopic examinations after hematopoietic stem cell transplantation were retrospectively collected. In study 1, group A included 56 patients in whom GI-GVHD was histologically confirmed and group B included 60 patients in whom GI-GVHD was not histologically confirmed. Group C included 59 patients before HSCT. The lengths of villi and crypts in the duodenum and terminal ileum were histologically measured. In study 2, the diagnostic accuracies of villous atrophy of the duodenum and of the terminal ileum using magnifying endoscopy were evaluated. RESULTS:  In study 1, the lengths of villi and the villi/crypt (V/C) ratios of the duodenum and terminal ileum in group A were significantly smaller than those in the other groups (p < 0.05). V/C ratio was moderately correlated with clinical severity, histological grades, and endoscopic grades in the terminal ileum. In study 2, the diagnostic accuracies of magnified images for villous atrophy were 83.8% in the duodenum and 94.9% in the terminal ileum. CONCLUSION:  Magnifying endoscopy enables evaluation of villous atrophy and is useful for optical biopsy of GVHD.
• Feasibility of a distal pigtail shaped stent placement above the papilla for biliary obstruction.
  Koji Hirata, Masaki Kuwatani, Naoya Sakamoto
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 32, 4, e73-e74, May 2020, [International Magazine]
  English, Scientific journal
• ストレス応答と肝疾患進展 ストレス応答よりみえてくるB型およびC型肝炎ウイルスの戦略　　　　　　　　　　　　　　　
  森川 賢一, 須田 剛生, 坂本 直哉
  肝臓, 61, Suppl.1, A99, A99, (一社)日本肝臓学会, Apr. 2020
  Japanese
• トルバプタン奏効後の再燃と炎症および尿L-FABP値の関連　　　　　　　　　　　　　　　
  中井 正人, 北潟谷 隆, 山田 錬, 重沢 拓, 鈴木 和治, 中村 晃久, 梅村 真知子, 荘 拓也, 須田 剛生, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 61, Suppl.1, A347, A347, (一社)日本肝臓学会, Apr. 2020
  Japanese
• 大規模健常人データ(肝移植ドナー・検診受験者)を用いた低骨格筋量に対する最適psoas muscle mass index cut-off値検討と肝疾患患者における評価　　　　　　　　　　　　　　　
  須田 剛生, 大原 正嗣, 小川 浩司, 荘 拓也, 中井 正人, 森川 賢一, 坂本 直哉
  肝臓, 61, Suppl.1, A474, A474, (一社)日本肝臓学会, Apr. 2020
  Japanese
• NAFLD患者におけるMRエラストグラフィ診断能の検討　　　　　　　　　　　　　　　
  山田 錬, 小川 浩司, 北潟谷 隆, 重沢 拓, 鈴木 和治, 中村 晃久, 梅村 真知子, 中井 正人, 荘 拓也, 須田 剛生, 森川 賢一, 坂本 直哉
  肝臓, 61, Suppl.1, A495, A495, (一社)日本肝臓学会, Apr. 2020
  Japanese
• 進行肝細胞癌に対するレンバチニブ治療成績からみた適格使用時期の検討 多施設共同研究　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 北潟谷 隆, 山田 錬, 重沢 拓, 鈴木 和治, 梅村 真知子, 中井 正人, 森川 賢一, 小川 浩司, 川岸 直樹, 宮城島 拓人, 馬場 英, 古家 乾, 山本 義也, 小林 智絵, 目黒 高志, 高木 智史, 神山 俊哉, 武冨 紹信, 坂本 直哉
  肝臓, 61, Suppl.1, A334, A334, (一社)日本肝臓学会, Apr. 2020
  Japanese
• Long-term outcomes and risk factors of recurrent biliary obstruction after permanent endoscopic biliary stenting for choledocholithiasis in high-risk patients.
  Ryo Sugiura, Hirohito Naruse, Hiroaki Yamato, Taiki Kudo, Yoshiya Yamamoto, Kazuteru Hatanaka, Jun Ito, Kenji Kinoshita, Shuichi Miyamoto, Masayuki Higashino, Shuhei Hayasaka, Naoya Sakamoto
  Journal of digestive diseases, 21, 4, 246, 251, Apr. 2020, [International Magazine]
  English, Scientific journal, OBJECTIVE: To elucidate the long-term outcomes of permanent endoscopic biliary stenting (EBS) and risk factors for recurrent biliary obstruction (RBO) in high-risk or elderly patients with common bile duct (CBD) stones. METHODS: The electronic database of Hakodate Municipal Hospital was searched to identify elderly or high-risk patients with CBD stones who had undergone permanent EBS using a plastic stent without stone removal and were followed up between April 2011 and May 2019, with no further intervention until symptoms occurred. RESULTS: We analyzed a total of 47 patients, of whom 19 (40.4%) were men, with a median age of 86 years (interquartile range 80-90 years). RBO and death without biliary disease occurred in 14 (29.8%) and 19 (40.4%) patients, respectively. The cumulative RBO rates at 20, 40, and 60 months were 22.1%, 31.8%, and 35.5%, respectively. The median time to RBO was 13.0 and 38.0 months in the group with CBD stone  ≥15 mm and 11-14 mm in diameter, respectively. The cumulative RBO incidence rate in the group with CBD stone ≤10 mm in diameter did not reach 50%. The cumulative RBO incidence rates were significantly different among the three groups based on the CBD stone diameter (competing risk analysis, P < 0.01). Multivariate analysis showed that an increase in CBD stone diameter predicted the increased risk of RBO (hazard ratio 1.26, P = 0.01). CONCLUSIONS: Permanent EBS is a feasible option for high-risk patients with small CBD stones.
• Inutility of endoscopic sphincterotomy to prevent pancreatitis after biliary metal stent placement in the patients without pancreatic duct obstruction.
  Shin Kato, Masaki Kuwatani, Tsuyoshi Hayashi, Kazunori Eto, Michihiro Ono, Nobuyuki Ehira, Hiroaki Yamato, Itsuki Sano, Yoko Taya, Manabu Onodera, Kimitoshi Kubo, Hideyuki Ihara, Hajime Yamazaki, Naoya Sakamoto
  Scandinavian journal of gastroenterology, 55, 4, 503, 508, Apr. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Background: The incidence of post-ERCP pancreatitis (PEP) has been reported to be significantly higher in patients without main pancreatic duct (MPD) obstruction who undergo transpapillary biliary metal stent (MS) placement than in those with ordinary ERCP setting.Objective: To evaluate the benefit of endoscopic sphincterotomy (ES) prior to MS placement in preventing PEP in patients with distal malignant biliary obstruction (MBO) without MPD obstruction.Materials and methods: In total, 160 patients who underwent initial MS placement for MBO were enrolled. Eighty-two patients underwent ES immediately prior to MS placement, whereas 78 underwent MS placement without ES. An inverse probability of treatment weighting method was adopted to adjust the differences of the patients' characteristics. The primary outcome was the incidence of PEP. The secondary outcomes included the incidence of other adverse events (bleeding, cholangitis, perforation and stent dislocation) and time to recurrent biliary obstruction.Results: The incidence of PEP was 26.8% in the ES and 23.1% in the non-ES (unadjusted odds ratio [OR] [95%CI]: 1.22, [0.60-2.51], adjusted OR [95%CI]: 1.23, [0.53-2.81], p = .63). Logistic-regression analysis revealed no factors that could be attributed to the occurrence of PEP. The incidence of other adverse events was not different between the groups. The median time to recurrent biliary obstruction was 131 (2-465) days and 200 (4-864) days in the ES and non-ES, respectively (p = .215).Conclusions: ES prior to MS placement for patients with distal MBO without MPD obstruction does not reduce the incidence of PEP.
• Endoscopic ultrasound‐guided fine‐needle biopsy for definitive diagnosis of malignant peritoneal mesothelioma
  Masayuki Higashino, Ryo Sugiura, Naoya Sakamoto
  Digestive Endoscopy, 32, 3, e40, e42, Wiley, Mar. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Hepatobiliary and Pancreatic: Hemosuccus pancreaticus due to an intraductal papillary mucinous neoplasm: A rare cause of obscure gastrointestinal bleeding
  R Sugiura, K Kinoshita, H Naruse, Y Yamamoto, K Hatanaka, J Ito, S Miyamoto, M Higashino, S Hayasaka, N Tsuchida, K Nakanishi, S Ueki, M Umehara, N Shimoyama, T Mitsuhashi, N Sakamoto
  Journal of Gastroenterology and Hepatology, 35, 3, 363, 363, Wiley, Mar. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• 難治性下痢と多彩な臨床症状を呈した全身性アミロイドーシスの1例　　　　　　　　　　　　　　　
  中島 紗慧, 小田切 信介, 桜井 健介, 山梨 香菜, 荒 隆英, 高桑 恵美, 桂田 武彦, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 70, 70, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• ペムブロリズマブが奏効した高頻度マイクロサテライト不安定性の肝内胆管癌の1例　　　　　　　　　　　　　　　
  斎藤 里佳, 伊藤 憲, 中野 真太郎, 川本 泰之, 中積 宏之, 結城 敏志, 小松 嘉人, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 41, 41, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• 進行膵癌における化学療法施行例の予後因子解析　　　　　　　　　　　　　　　
  中野 真太郎, 小松 嘉人, 斉藤 里佳, 伊藤 憲, 川本 泰之, 中積 宏之, 結城 敏志, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 58, 58, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• 消化器がん内視鏡診断・治療の最前線 胆嚢癌に対する術前胆道ドレナージ 肝門部領域胆管癌との比較検討　　　　　　　　　　　　　　　
  平田 幸司, 桑谷 将城, 加藤 新, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 35, 35, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• 悪性胆道狭窄に対するトリプルルーメンカテーテルの有用性　　　　　　　　　　　　　　　
  平田 甫, 桑谷 将城, 瀧新 悠之介, 古川 龍太郎, 平田 幸司, 加藤 新, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 43, 43, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• 【EUSの現状と将来】治療 胆管挿管困難例に対するRendezvous法
  桑谷 将城, 川久保 和道, 加藤 新, 平田 幸司, 平田 甫, 坂本 直哉
  肝胆膵, 80, 3, 471, 479, (株)アークメディア, Mar. 2020
  Japanese
• 表在型非乳頭部十二指腸上皮性腫瘍の内視鏡所見についての検討　　　　　　　　　　　　　　　
  木脇 佐代子, 小野 尚子, 霜田 佳彦, 井上 雅貴, 田中 一光, 石川 麻倫, 大野 正芳, 山本 桂子, 清水 勇一, 坂本 直哉, 三橋 智子, 松野 吉宏
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 59, 59, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• 表在性非乳頭部十二指腸腫瘍に対するエンドサイトスコピーシステムを用いた分類の検討　　　　　　　　　　　　　　　
  宮本 秀一, 工藤 俊彦, 石川 麻倫, 小野 尚子, 清水 勇一, 土田 直央, 早坂 秀平, 東野 真幸, 杉浦 諒, 木下 賢治, 伊藤 淳, 畑中 一映, 山本 義也, 成瀬 宏仁, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 126回, 73, 73, 日本消化器病学会-北海道支部, Mar. 2020
  Japanese
• 【慢性膵炎診療2020】基礎研究・病態 早期慢性膵炎は慢性膵炎確診・準確診例に移行するのか
  桑谷 将城, 加藤 新, 平田 幸司, 平田 甫, 坂本 直哉
  肝胆膵, 80, 2, 265, 269, (株)アークメディア, Feb. 2020
  Japanese
• Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting
  Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto
  JGH OPEN, 4, 1, 54, 60, Feb. 2020, [Peer-reviewed]
  English, Scientific journal
• Early response and safety of lenvatinib for patients with advanced hepatocellular carcinoma in a real-world setting.
  Takuya Sho, Goki Suda, Koji Ogawa, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Mitsuteru Natsuizaka, Masato Nakai, Kenichi Morikawa, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Takashi Meguro, Akiyoshi Saga, Takuto Miyagishima, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto
  JGH open : an open access journal of gastroenterology and hepatology, 4, 1, 54, 60, Feb. 2020, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin as a non-invasive biomarker for non-alcoholic steatohepatitis: a novel glycobiomarker for non-alcoholic steatohepatitis.
  Koji Ogawa, Takashi Kobayashi, Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Akihisa Nakamura, Kazuharu Suzuki, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Masaru Baba, Ken Furuya, Katsumi Terashita, Tomoe Kobayashi, Manabu Onodera, Takahiro Horimoto, Keisuke Shinada, Seiji Tsunematsu, Izumi Tsunematsu, Takashi Meguro, Tomoko Mitsuhashi, Megumi Hato, Kenichi Higashino, Yasuro Shinohara, Naoya Sakamoto
  Scientific reports, 10, 1, 321, 321, 15 Jan. 2020, [Peer-reviewed], [International Magazine]
  English, Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD) that may lead to liver cirrhosis or hepatocellular carcinoma. Here, we examined the diagnostic utility of tri-antennary tri-sialylated mono-fucosylated glycan of alpha-1 antitrypsin (AAT-A3F), a non-invasive glycobiomarker identified in a previous study of NASH diagnosis. This study included 131 biopsy-proven Japanese patients with NAFLD. We evaluated the utility of AAT-A3F in NASH diagnosis, and conducted genetic analysis to analyse the mechanism of AAT-A3F elevation in NASH. Serum AAT-A3F concentrations were significantly higher in NASH patients than in NAFL patients, and in patients with fibrosis, lobular inflammation, and ballooning. Hepatic FUT6 gene expression was significantly higher in NASH than in NAFL. IL-6 expression levels were significantly higher in NASH than in NAFL and showed a positive correlation with FUT6 expression levels. The serum-AAT-A3F levels strongly correlated with hepatic FUT6 expression levels. AAT-A3F levels increased with fibrosis, pathological inflammation, and ballooning in patients with NAFLD and may be useful for non-invasive diagnosis of NASH from the early stages of fibrosis.
• Up-to-date endoscopic diagnosis and treatment of gastric cancer
  Shoko Ono, Yuji Ono, Naoya Sakamoto
  Journal of Japanese Society of Gastroenterology, 117, 2, 126, 134, Japanese Society of Gastroenterology, 2020
  Japanese, Scientific journal
• Esophagitis in Non-Small Cell Lung Carcinoma Treatment Caused by Pembrolizumab.
  Sonoe Yoshida, Shuichi Miyamoto, Hirohito Naruse, Jun Ito, Kenji Kinosita, Taiki Kudo, Kazuteru Hatanaka, Yoshiya Yamamoto, Naoya Sakamoto
  The American journal of gastroenterology, 115, 1, 13, 13, Jan. 2020, [International Magazine]
  English, Scientific journal
• Accuracies of Endoscopic Diagnosis of Helicobacter pylori-Gastritis: Multicenter Prospective Study Using White Light Imaging and Linked Color Imaging.
  Shoko Ono, Osamu Dohi, Nobuaki Yagi, Yoji Sanomura, Shinji Tanaka, Yuji Naito, Naoya Sakamoto, Mototsugu Kato
  Digestion, 101, 5, 624, 630, 2020, [International Magazine]
  English, Scientific journal, INTRODUCTION: The diagnosis of Helicobacter pylori infection status with white light imaging (WLI) is difficult. We evaluated the accuracies of using WLI and linked color imaging (LCI) for diagnosing H. pylori-active gastritis in a multicenter prospective study setting. METHODS: Patients who underwent esophagogastroduodenoscopy were prospectively included. The image collection process was randomized and anonymous, and the image set included 4 images with WLI or 4 images with LCI in the corpus that 5 reviewers separately evaluated. Active gastritis was defined as positive when there was diffuse redness in WLI and crimson coloring in LCI. The H. pylori infection status was determined by the urea breath test and the serum antibody test. Cases in which both test results were negative but atrophy or intestinal metaplasia was histologically confirmed were defined as past infections. The primary endpoint was the diagnostic accuracies of WLI and LCI, and the secondary endpoint was inter-observer agreement. RESULTS: Data for 127 patients were analyzed. The endoscopic diagnostic accuracy for active gastritis was 79.5 (sensitivity of 84.4 and specificity of 74.6) with WLI and 86.6 (sensitivity of 84.4 and specificity of 88.9) with LCI (p = 0.029). LCI significantly improved the accuracy in patients with past infections over WLI (36.8 in WLI and 78.9 in LCI, p < 0.01). The κ values were 0.59 in WLI and 0.70 in LCI. CONCLUSIONS: LCI is useful for endoscopic diagnosis of H. pylori-active or inactive gastritis, and it is advantageous for patients with past infections of inactive gastritis.
• S-1またはカペシタビンを含む標準治療に不応・不耐の胃癌に対するbolus 5-FU/I-LV療法の多施設共同第II相試験 前治療別の解析　　　　　　　　　　　　　　　
  村中 徹人, 小松 嘉人, 結城 敏志, 中野 真太郎, 澤田 憲太郎, 川本 泰之, 中積 宏之, 原田 一顕, 宮城島 拓人, 畑中 一映, 太宰 昌佳, 植田 亮, 笹木 祐介, 辻 靖, 西本 尚樹, 坂田 優, 坂本 直哉
  日本消化管学会雑誌, 4, Suppl., 262, 262, (一社)日本消化管学会, Jan. 2020
  Japanese
• FGFR阻害剤およびMEK阻害剤は食道扁平上皮癌(ESCC)がん幹細胞を減少させる　　　　　　　　　　　　　　　
  前原 経, 夏井坂 光輝, 須田 剛生, 大西 俊介, 坂本 直哉, 武田 宏司
  日本消化管学会雑誌, 4, Suppl., 301, 301, (一社)日本消化管学会, Jan. 2020
  Japanese
• Detection of early adenocarcinoma of the esophagogastric junction by spraying an enzyme-activatable fluorescent probe targeting Dipeptidyl peptidase-IV
  Keikokw Yamamoto, Shunsuke Ohnishi, Takeshi Mizushima, Junichi Kodaira, Masayoshi Ono, Yutaka Hatanaka, Kanako C. Hatanaka, Yugo Kuriki, Mako Kamiya, Nobuyuki Ehira, Keisuke Shinada, Hiroaki Takahashi, Yuichi Shimizu, Yasuteru Urano, Naoya Sakamoto
  BMC CANCER, 20, 1, Jan. 2020
  English, Scientific journal
• Oleoylethanolamide Ameliorates Dextran Sulfate Sodium-Induced Colitis in Rats.
  Shinsuke Otagiri, Shunsuke Ohnishi, Masatsugu Ohara, Qingjie Fu, Koji Yamamoto, Keiko Yamamoto, Takehiko Katsurada, Naoya Sakamoto
  Frontiers in pharmacology, 11, 1277, 1277, 2020, [International Magazine]
  English, Scientific journal, Oleoylethanolamide (OEA) is an endogenous fatty acid ethanolamide known for its anti-inflammatory effects and its influence on gut microbiota composition; however, the effects of OEA in inflammatory bowel disease (IBD) remain unknown. During in vitro experiments, OEA downregulated the expression of tumor necrosis factor (TNF)-α and reduced phosphorylation of inhibitor of kappa (Iκ) Bα induced by lipopolysaccharide in human embryonic kidney cells. Moreover, OEA downregulated the expression of interleukin (IL)-8 and IL-1β and inhibited the phosphorylation of IκBα and p65 induced by TNF-α in human enterocytes (Caco-2). The effect of OEA in reducing the expression of IL-8 was blocked by the peroxisome proliferator-activated receptor (PPAR)-α antagonist. During in vivo experiments on rats, colitis was induced by the oral administration of 8% dextran sulfate sodium from day 0 through day 5, and OEA (20 mg/kg) was intraperitoneally injected once a day from day 0 for 6 days. OEA administration significantly ameliorated the reduction in body weight, the increase in disease activity index score, and the shortening of colon length. In rectums, OEA administration reduced the infiltration of macrophages and neutrophils and tended to reduce the histological score and the expression of inflammatory cytokines. Administration of OEA produced significant improvement in a colitis model, possibly by inhibiting the nuclear factor kappa B signaling pathway through PPAR-α receptors. OEA could be a potential new treatment for IBD.
• 【遺伝子・免疫異常に伴う消化管病変-最新のトピックスを中心に】免疫チェックポイント阻害薬関連消化管病変
  長島 一哲, 桂田 武彦, 大塚 拓也, 西田 睦, 表原 里実, 桜井 健介, 小田切 信介, 山梨 香菜, 小松 嘉人, 三橋 智子, 坂本 直哉
  胃と腸, 54, 13, 1723, 1732, (株)医学書院, Dec. 2019
  Japanese
• Clinical impact of the perioperative management of oral anticoagulants in bleeding after colonic endoscopic mucosal resection
  Shoko Ono, Marin Ishikawa, Kana Matsuda, Momoko Tsuda, Keiko Yamamoto, Yuichi Shimizu, Naoya Sakamoto
  BMC Gastroenterology, 19, 1, Springer Science and Business Media LLC, Dec. 2019
  Scientific journal,
  
  Heparin bridging therapy (HBT) is indeed related to a high frequency of bleeding after endoscopic mucosal resection (EMR). In this study, our aim was to investigate clinical impact of management of oral anticoagulants without HBT in bleeding after colonic EMR.
  
  
  
  
  From data for patients who underwent consecutive colonic EMR, the relationships of patient factors and procedural factors with the risk of bleeding were analysed. Our management of antithrombotic agents was based on the shortest cessation as follows: the administration of warfarin was generally continued within the therapeutic range, and direct oral anticoagulants (DOACs) were not administered on the day of the procedure. We calculated bleeding risks after EMR in patients who used antithrombotic agents and evaluated whether perioperative management of anticoagulants without HBT was beneficial for bleeding.
  
  
  
  
  A total of 1734 polyps in 825 EMRs were analysed. Bleeding occurred in 4.0% of the patients and 1.9% of the polyps. The odds ratios for bleeding using multivariate logistic regression analysis were 3.67 in patients who used anticoagulants and 4.95 in patients who used both anticoagulants and antiplatelet agents. In patients with one-day skip of DOACs, bleeding occurred in 6.5% of the polyps, and there were no significant differences in bleeding risk between HBT and continuous warfarin or one-day skip DOACs.
  
  
  
  
  The use of oral anticoagulants was related to bleeding after colonic EMR, and perioperative management of oral anticoagulants based on the shortest cessation without HBT would be clinically acceptable.
  
  
  
• Cancer gene profiling explores the possible precision medicine for diffuse-type gastric adenocarcinoma.
  Marin Ishikawa, Hideyuki Hayashi, Naoya Sakamoto, Shinya Tanaka, Hiroshi Nishihara
  Medical oncology (Northwood, London, England), 37, 1, 10, 10, 25 Nov. 2019, [Peer-reviewed], [International Magazine]
  English, Diffuse type gastric cancer (DGC), a pathological subtype, is one of the most common malignant solid tumors, and mortality of this tumor is not negligible, especially in early-onset cancer patients. In fact, affirmative personalized treatments based on gene profile have not been established yet. The aim of this study was to provide the possible genotype-matched treatment for DGC through comprehensive examination of genomic variants and analysis of clinicopathological characteristics. We retrospectively studied 23 formalin-fixed, paraffin-embedded samples of patients diagnosed as DGC between January 2003 and December 2015 at the Department of Cancer Pathology, Hokkaido University Graduate School of Medicine. The cases were divided into two groups: early-onset (< 50 years old) and elderly-onset (≥ 50 years old) DGC groups. We performed targeted genomic sequencing using a 163 cancer-related gene panel. The sequencing data were analyzed using an original bioinformatics pipeline called GenomeJack and were clinicopathologically evaluated. Intestinal metaplasia and atrophy were highly observed in the adjacent non-cancerous mucosa in the elderly-onset DGC group compared with those in the early-onset DGC group. The number of somatic variants was significantly higher in the elderly-onset DGC group than in the early-onset DGC group. Fifteen patients (65.2%) harbored at least one genomic alteration of the potential target for genotype-matched treatment. In addition, one patient with hypermutation phenotype was diagnosed as Lynch syndrome due to MLH1 mutation, suggesting the sensitivity for the treatment with immune checkpoint inhibitors. Not only does our study demonstrated the potential utility of the targeted genomic sequencing approach for making informed therapeutic decisions, but it also sheds light on DGC pathogenesis and progression.
• Gastrointestinal: Endoscopic balloon dilations for an intestinal stricture in a patient with X‐linked inhibitor of apoptosis deficiency
  S Otagiri, R Sugiura, T Katsurada, K Yamanashi, K Nagashima, J Sugita, S Ohnishi, N Sakamoto
  Journal of Gastroenterology and Hepatology, Wiley, 07 Nov. 2019, [Peer-reviewed]
  Scientific journal
• クローン病の腸管病変における体外式超音波検査の有用性の検討　　　　　　　　　　　　　　　
  山梨 香菜, 西田 睦, 表原 里実, 木下 賢治, 大西 礼造, 桂田 武彦, 坂本 直哉
  日本小腸学会学術集会プログラム・抄録集, 57回, 62, 62, 日本小腸学会, Nov. 2019
  Japanese
• 胸部食道扁平上皮癌に対する術前補助化学療法・根治切除術および根治的化学放射線療法についての後方視的検討
  中積 宏之, 村中 徹人, 川本 泰之, 小松 嘉人, 結城 敏志, 中野 真太郎, 澤田 憲太郎, 坂本 直哉, 打浪 雄介, 田口 大志, 白土 博樹, 海老原 裕磨, 七戸 俊明, 平野 聡
  北海道医学雑誌, 94, 2, 120, 121, 北海道医学会, Nov. 2019
  Japanese
• 早期食道癌発癌因子としてのHuman Papilloma Virus感染およびアルコール代謝遺伝子多型に関する検討
  井上 雅貴, 清水 勇一, 田中 一光, 木脇 佐代子, 石川 麻倫, 松田 可奈, 津田 桃子, 山本 桂子, 小野 尚子, 三橋 智子, 坂本 直哉
  日本消化器病学会雑誌, 116, 臨増大会, A810, A810, (一財)日本消化器病学会, Nov. 2019
  Japanese
• Entecavir treatment of hepatitis B virus-infected patients with severe renal impairment and those on hemodialysis.
  Kazuharu Suzuki, Goki Suda, Yoshiya Yamamoto, Ken Furuya, Masaru Baba, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Koji Yamamoto, Taku Shigesawa, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 49, 11, 1294, 1304, Nov. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: Entecavir (ETV), tenofovir disoproxil fumarate (TDF), and tenofovir alafenamide (TAF) are first-line nucleos(t)ide analogues for hepatitis B virus (HBV)-infected patients. However, consecutive TDF treatment causes renal dysfunction, and the safety and efficacy of TAF have not been established in severe renal dysfunction patients, including hemodialysis patients. The efficacy and safety of ETV in these populations has not been clarified. The study aimed to clarify this. METHODS: In this retrospective multicenter study, between 2006 and 2018, a total of 567 HBV-infected patients treated with ETV monotherapy were screened. Patients were included if >20 years old, treated with ETV monotherapy for >1 year, and had proper clinical information. The efficacy of ETV and changes in renal function were evaluated according to renal function. RESULTS: A total of 273 patients were included: 9.2% (25/273), 1.8% (5/273), and 3.7% (10/273) had chronic kidney disease (CKD) stage G3, CKD stage G4/5, and were on hemodialysis, respectively. Overall, 84.2%, 94.0%, and 96.2% of patients experienced serum HBV-DNA disappearance at 1, 2, and 3 years, respectively, after treatment initiation. In patients with CKD stage G3-5, estimated glomerular filtration rate tended to restore with time, which was in contrast to patients without renal dysfunction. The rate of disappearance in serum HBV-DNA, alanine transaminase normalization, and virological breakthrough was similar between patients with or without renal dysfunction. ETV showed high efficacy for all 10 hemodialysis patients without virological breakthrough. CONCLUSIONS: Entecavir for HBV-infected patients with severe renal dysfunction, including hemodialysis patients, is highly effective and does not affect renal function.
• Effects of resistance-associated variants in genotype 2 hepatitis C virus on viral replication and susceptibility to antihepatitis C virus drugs.
  Goki Suda, Megumi Kimura, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Masato Nakai, Takuya Sho, Osamu Maehara, Tomoe Shimazaki, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 49, 11, 1275, 1285, Nov. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIMS: Development of direct-acting antivirals (DAAs) has made antihepatitis C virus (HCV) treatment highly safe and effective. However, the emergence of resistant-associated variants (RAVs) after failure of DAA therapy affects retreatment outcomes. In particular, genotype 1 HCV with P32 deletion has been reported to be highly resistant to all approved non-structural protein (NS)5A inhibitors. However, analysis of RAVs in genotype 2 HCV has been limited. Accordingly, in this study, we evaluated the roles of genotype 2 HCV variants in antiviral drug efficacy. METHODS: We utilized HCV-2b/2a (JFH-1) chimeric virus (genotype 2a), which replicates more robustly than JFH-1. We constructed various genotype 2a JFH-1-based HCV cell culture systems with NS3 (D168E), NS5A (F28S, F28S/M31I, P32 deletion, and Y93H), and NS5B (S282 T) RAVs and analyzed the replication ability and sensitivity to various anti-HCV reagents. RESULTS: Genotype 2a-based HCV with NS5A-P32 deletion could not replicate even in long-term cultures. Genotype 2a-based HCV with NS5A-F28S/M31I showed significantly higher replication ability than the wild-type strain, and replication could not be suppressed, even with high concentrations of NS5A inhibitors, including pibrentasvir and velpatasvir (<1000-10 000 fold-resistance compared with the wild-type strain). However, genotype 2a-based HCV with NA5A-F28S/M31I was sensitive to HCV protease inhibitor, NS5B inhibitor, interferon-α, and ribavirin. Genotype 2a-based HCV with NS5B-S282 T was resistant to sofosbuvir, but was highly sensitive to ribavirin compared with the control. CONCLUSIONS: When undertaking retreatment for genotype 2a HCV-infected patients who fail to respond to DAAs, the optimized retreatment should be chosen according to the sensitivity of the emerging RAVs to anti-HCV drugs.
• 経口フッ化ピリミジン不応の胃がんに対するRPMI療法(HGCSG1502試験)OS・QOL解析結果　　　　　　　　　　　　　　　
  太宰 昌佳, 村中 徹人, 川本 泰之, 中積 宏之, 原田 一顕, 宮城島 拓人, 畑中 一映, 植田 亮, 加藤 総介, 笹木 有佑, 結城 敏志, 坂本 直哉, 西本 尚樹, 坂田 優, 小松 嘉人
  日本癌治療学会学術集会抄録集, 57回, P69, 1, (一社)日本癌治療学会, Oct. 2019
  English
• 転移を有する膵癌に対する化学療法薬剤使用歴と治療成績の関係の検討　　　　　　　　　　　　　　　
  川本 泰之, 斎藤 里佳, 伊藤 憲, 中野 真太郎, 中積 宏之, 結城 敏志, 小松 嘉人, 坂本 直哉
  日本癌治療学会学術集会抄録集, 57回, P86, 7, (一社)日本癌治療学会, Oct. 2019
  English
• 各都道府県における肝疾患対策取り組みの現状 北海道における肝炎対策の現状
  小川 浩司, 辻口 智美, 銭谷 菜子, 山下 真智子, 吉川 昇吾, 坂本 直哉
  肝臓クリニカルアップデート, 5, 2, 221, 225, 医学図書出版(株), Oct. 2019
  Japanese
• 【肝胆膵の救急疾患とその最新の治療現場】肝胆膵における比較的新しい救急疾患概念 膵仮性嚢胞・WONへのアプローチ
  桑谷 将城, 川久保 和道, 加藤 新, 平田 幸司, 平田 甫, 坂本 直哉
  肝胆膵, 79, 4, 705, 711, (株)アークメディア, Oct. 2019
  Japanese
• 悪性肝門部胆管閉塞症例の術前内視鏡的経鼻胆管ドレナージチューブ閉塞の危険因子解析
  杉浦 諒, 桑谷 将城, 平田 甫, 中島 正人, 平田 幸司, 加藤 新, 坂本 直哉
  胆道, 33, 3, 493, 493, 日本胆道学会, Oct. 2019
  Japanese
• 膵頭部癌に対する術前内視鏡的胆管ステント留置術の臨床成績
  平田 甫, 桑谷 将城, 中島 正人, 平田 幸司, 杉浦 諒, 加藤 新, 坂本 直哉, 浅野 賢道, 平野 聡
  胆道, 33, 3, 548, 548, 日本胆道学会, Oct. 2019
  Japanese
• 遠位良性胆道狭窄に対する経乳頭的金属ステント留置の効果
  加藤 新, 桑谷 将城, 平田 甫, 滝新 悠之介, 平田 幸司, 古川 龍太郎, 坂本 直哉
  胆道, 33, 3, 603, 603, 日本胆道学会, Oct. 2019
  Japanese
• さあ、どうする?治療内視鏡におけるトラブルシューティング(胆膵編) 胆管金属ステント留置後reintervention困難例におけるESダイレーターの有用性　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 坂本 直哉
  Gastroenterological Endoscopy, 61, Suppl.2, 2054, 2054, (一社)日本消化器内視鏡学会, Oct. 2019
  Japanese
• 当院における消化管内視鏡検査の鎮静剤使用の現状と課題　　　　　　　　　　　　　　　
  大野 正芳, 霜田 佳彦, 田中 一光, 井上 雅貴, 木脇 佐代子, 石川 麻倫, 山本 桂子, 小野 尚子, 中川 学, 中川 宗一, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 61, Suppl.2, 2260, 2260, (一社)日本消化器内視鏡学会, Oct. 2019
  Japanese
• C型肝炎患者の血清Angiopoietin-2値はDAAs治療後の肝線維化非改善例を予測する　　　　　　　　　　　　　　　
  川岸 直樹, 須田 剛生, 中井 正人, 荘 拓也, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 60, Suppl.2, A653, A653, (一社)日本肝臓学会, Oct. 2019, [Peer-reviewed]
  Japanese
• カルニチンは肝硬変患者における筋肉量減少を抑制する　　　　　　　　　　　　　　　
  大原 正嗣, 須田 剛生, 重沢 拓, 鈴木 和治, 中村 晃久, 川岸 直樹, 中井 正人, 荘 拓也, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 60, Suppl.2, A677, A677, (一社)日本肝臓学会, Oct. 2019, [Peer-reviewed]
  Japanese
• 進行肝細胞癌に対するレンバチニブ投与症例からみた適格使用時期の検討　　　　　　　　　　　　　　　
  荘 拓也, 須田 剛生, 鈴木 和治, 中村 晃久, 大原 正嗣, 川岸 直樹, 中井 正人, 森川 賢一, 小川 浩司, 坂本 直哉
  肝臓, 60, Suppl.2, A705, A705, (一社)日本肝臓学会, Oct. 2019, [Peer-reviewed]
  Japanese
• Comparative Glycomic Analysis of Sialyl Linkage Isomers by Sialic Acid Linkage-Specific Alkylamidation in Combination with Stable Isotope Labeling of α2,3-Linked Sialic Acid Residues.
  Hanamatsu H, Nishikaze T, Tsumoto H, Ogawa K, Kobayashi T, Yokota I, Morikawa K, Suda G, Sho T, Nakai M, Miura N, Higashino K, Sekiya S, Iwamoto S, Miura Y, Furukawa JI, Tanaka K, Sakamoto N
  Analytical chemistry, Oct. 2019, [Peer-reviewed]
• Assessing the risk of hepatocellular carcinoma by combining liver stiffness and the controlled attenuation parameter.
  Takaaki Izumi, Takuya Sho, Kenichi Morikawa, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Tomoe Shimazaki, Megumi Kimura, Masato Nakai, Goki Suda, Mitsuteru Natsuizaka, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Kota Ono, Masaru Baba, Ken Furuya, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 49, 10, 1207, 1217, Oct. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: Ultrasound technology can now be used for liver stiffness measurement (LSM) and for evaluating the amount of hepatic fat quantitatively known as the controlled attenuation parameter (CAP). This study aimed to determine the applicable cut-off values of LSM and the CAP for primary hepatocellular carcinoma (HCC), and to investigate their clinical usefulness for assessing HCC risk in patients with chronic liver disease. METHODS: A total of 1054 patients (88 with primary HCC and 966 without HCC) whose LSM and the CAP were measured by transient elastography with clinically evident hepatitis C virus (419 patients), hepatitis B virus (377 patients), and non-alcoholic fatty liver disease (258 patients) were enrolled in this study. Subsequently, a total of 966 patients who did not have HCC initially were followed, and the usefulness of the cut-off values of LSM and CAP for HCC development were evaluated. RESULTS: In hepatitis C virus patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥8.0 kPa and CAP ≤221 dB/m than among those with other values (log-rank test 0.0239, hazard ratio 2.66, 95%CI 1.07-6.47, P = 0.0362). In non-alcoholic fatty liver disease patients, the incidence of HCC development was significantly higher among those with a combination of LSM ≥5.4 kPa and CAP ≤265 dB/m than among others (log-rank test 0.0040, hazard ratio 8.91, 95% CI 1.47-67.97, P = 0.0192). CONCLUSION: In the hepatitis C virus and non-alcoholic fatty liver disease groups, a combination of LSM and the CAP cut-off values would be useful for screening to identify the high-risk group for primary HCC development.
• Correlation between Liver Elasticity by Ultrasound Elastography and Liver Functional Reserve.
  Ryo Sugiura, Masaki Kuwatani, Mutsumi Nishida, Koji Hirata, Itsuki Sano, Shin Kato, Kazumichi Kawakubo, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Ultrasound in medicine & biology, 45, 10, 2704, 2712, Oct. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, No worldwide consensus on the assessment tool for liver functional reserve is currently available. The aim of this study was to evaluate the correlation between liver elasticity of both hepatic lobes and liver functional reserve tests. This prospective observational study comprised 40 patients scheduled for hepatectomy. Liver elasticity was assessed by Virtual Touch Quantification (VTQ). The mean VTQ value for the right and left lobes was defined as the mVTQ. Liver functional reserve was measured with technetium-99m-diethylenetriaminepentaacetic acid-galactosyl-human serum albumin scintigraphy as LHL15 and HH15 and the indocyanine green (ICG) excretion test as ICG-R15 and ICG-K. All examinations were measured after biliary decompression confirmed serum a total bilirubin level ≤2 mg/dL. Mean VTQ values were moderately correlated with LHL15 (r = -0.42, p < 0.01), HH15 (r = 0.48, p < 0.01), ICG-R15 (r = 0.53, p < 0.01) and ICG-K (r = -0.61, p < 0.01) values. In conclusion, the liver elasticity determined by VTQ would be a useful predictor of liver functional reserve in patients scheduled for hepatectomy.
• 局所進行食道癌に対してspot scanning法による根治的化学陽子線療法を施行した一例　　　　　　　　　　　　　　　
  宮崎 智彦, 打浪 雄介, 田口 大志, 加藤 徳雄, 清水 伸一, 白土 博樹, 中積 宏之, 中野 真太郎, 坂本 直哉, 高尾 聖心, 田村 昌也, 松浦 妙子
  日本医学放射線学会秋季臨床大会抄録集, 55回, S520, S520, (公社)日本医学放射線学会, Sep. 2019
  Japanese
• 局所進行膵癌における化学療法および化学放射線療法の検討　　　　　　　　　　　　　　　
  中野 真太郎, 小松 嘉人, 川本 泰之, 斎藤 里佳, 伊藤 憲, 中積 宏之, 結城 敏志, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 55, 55, 日本消化器病学会-北海道支部, Sep. 2019
  Japanese
• 膵胆管合流異常症における画像所見の検討　　　　　　　　　　　　　　　
  古川 龍太郎, 桑谷 将城, 平田 甫, 滝新 悠之介, 平田 幸司, 加藤 新, 岡村 圭佑, 平野 聡, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 34, 34, 日本消化器病学会-北海道支部, Sep. 2019
  Japanese
• 胆管空腸吻合部狭窄に対するバルーン内視鏡治療の臨床成績　　　　　　　　　　　　　　　
  平田 甫, 桑谷 将城, 瀧新 悠之介, 古川 龍太郎, 平田 幸司, 加藤 新, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 35, 35, 日本消化器病学会-北海道支部, Sep. 2019
  Japanese
• 胆嚢原発神経内分泌腫瘍の4症例　　　　　　　　　　　　　　　
  滝新 悠之介, 桑谷 将城, 古川 龍太郎, 平田 甫, 平田 幸司, 加藤 新, 坂本 直哉, 岡村 圭祐, 平野 聡, 三橋 智子
  日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 37, 37, 日本消化器病学会-北海道支部, Sep. 2019
  Japanese
• Budd-Chiari症候群に対しPercutaneous transluminal angioplastyが奏功した一例　　　　　　　　　　　　　　　
  吉田 苑永, 川岸 直樹, 小田 総一郎, 志藤 茜, 目野 晃光, 吉河 歩, 安孫子 怜史, 原田 一顕, 佐野 逸紀, 小田 寿, 須田 剛生, 小川 浩司, 吉野 裕紀, 阿保 大介, 宮城島 拓人, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 125回, 31, 31, 日本消化器病学会-北海道支部, Sep. 2019
  Japanese
• 肝細胞癌細胞株においてメトホルミンはAMPK-CEBPβ経路を介してCD133の発現を制御する(Metformin regulates the expression of CD133 through the AMPK-CEBPβ pathway in hepatocellular carcinoma cell lines)　　　　　　　　　　　　　　　
  前原 経, 大西 俊介, 夏井坂 光輝, 坂本 直哉
  日本癌学会総会記事, 78回, P, 3258, 日本癌学会, Sep. 2019
  English
• Quantifying Protein-Specific N-Glycome Profiles by Focused Protein and Immunoprecipitation Glycomics.
  Takashi Kobayashi, Koji Ogawa, Jun-Ichi Furukawa, Hisatoshi Hanamatsu, Megumi Hato, Tomoyo Yoshinaga, Kenichi Morikawa, Goki Suda, Takuya Sho, Masato Nakai, Kenichi Higashino, Yoshito Numata, Yasuro Shinohara, Naoya Sakamoto
  Journal of proteome research, 18, 8, 3133, 3141, 02 Aug. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Serum N-glycans have been reported to be potential diagnostic and therapeutic biomarkers for many diseases and conditions, such as inflammation, fibrosis, and cancer progression. We previously described the focused protein glycomic analysis (FPG) from gel-separated serum proteins. With this methodology, we sought novel glycan biomarkers for nonalcoholic steatohepatitis (NASH) and successfully identified some N-glycans that were significantly elevated in NASH patients compared to nonalcoholic fatty liver patients. Among them, trisialylated monofucosylated triantennary glycan (A3F) of alpha-1 antitrypsin showed the most dynamic change. For rapid identification of N-glycans on the focused proteins, we constructed a simplified method called immunoprecipitation glycomics (IPG), where the target proteins were immunoprecipitated with affinity beads and subsequently subjected to glycomic analysis by MALDI-TOF MS. Focusing on alpha-1 antitrypsin and ceruloplasmin as the target proteins, we compared the values of N-glycans determined by FPG and IPG. The quantified values of each N-glycan by these two methods showed a statistically significant correlation, indicating that high throughput and quantitative N-glycomics of targeted proteins can be achieved by the simplified IPG method. Thus, an analytical strategy combining FPG and IPG can be adapted to general biomarker discovery and validation in appropriate disease areas.
• Nutrition is often ignored in management of chronic liver diseases.
  Naoya Sakamoto, Goki Suda, Kennichi Morikawa, Koji Ogawa
  Journal of gastroenterology and hepatology, 34, 7, 1127, 1128, Jul. 2019, [International Magazine]
  English
• Effect of Pancreatic Mass Size on Clinical Outcomes of Endoscopic Ultrasound-Guided Fine-Needle Aspiration.
  Sugiura R, Kuwatani M, Hirata K, Sano I, Kato S, Kawakubo K, Sakamoto N
  Digestive diseases and sciences, 64, 7, 2006, 2013, Jul. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: Endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) has high diagnostic accuracy for pancreatic diseases. However, the effect of mass size on diagnostic accuracy has yet to be determined, especially for small pancreatic lesions. We aimed to determine the effect of pancreatic mass size on the diagnostic yield of EUS-FNA. METHODS: We searched the database in Hokkaido University Hospital between May 2008 and December 2016 and identified solid pancreatic lesions examined by EUS-FNA. All lesions were stratified into five groups based on mass sizes: groups A (< 10 mm), B (10-20 mm), C (20-30 mm), D (30-40 mm) and E (≥ 40 mm). The sensitivity, specificity, diagnostic accuracy and adverse event rate were retrospectively evaluated. RESULTS: We analyzed a total of 788 solid pancreatic lesions in 761 patients. The patients included 440 males (57.8%) with a mean age of 65.7 years. The sensitivities in groups A (n = 36), B (n = 223), C (n = 304), D (n = 147) and E (n = 78) were 89.3%, 95.0%, 97.4%, 98.5% and 98.7%, respectively, and they significantly increased as the mass size increased (P < 0.01, chi-squared test for trend). The diagnostic accuracies were 91.7%, 96.4%, 97.7%, 98.6% and 98.7%, respectively, and they also significantly increased as the mass size increased (P = 0.03). Multivariate analysis showed that pancreatic mass size was associated with diagnostic accuracy. The adverse event rates were not significantly different among the five groups. CONCLUSIONS: The sensitivities and diagnostic accuracies of EUS-FNA for solid pancreatic lesions are higher for lesions ≥ 10 mm in size, and they are strongly correlated with mass size.
• Safety and efficacy of glecaprevir and pibrentasvir in Japanese hemodialysis patients with genotype 2 hepatitis C virus infection.
  Goki Suda, Chitomi Hasebe, Masami Abe, Masayuki Kurosaki, Jun Itakura, Namiki Izumi, Yoshihito Uchida, Satoshi Mochida, Hiroaki Haga, Yoshiyuki Ueno, Kazumichi Abe, Atsushi Takahashi, Hiromasa Ohira, Yoko Tsukuda, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Jun Inoue, Katsumi Terasita, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Journal of gastroenterology, 54, 7, 641, 649, Jul. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: Until recently, interferon-free anti-hepatitis C virus (HCV) therapy for genotype 2 (GT2) HCV-infected hemodialysis patients was an unfulfilled medical need. Recent clinical trials of glecaprevir and pibrentasvir (G/P) for hemodialysis patients showed high efficacy and safety; however, the number of GT2 HCV-infected patients, especially Asian patients, was limited and most of them were treated with a 12-week regimen. In this prospective multicenter study, we aimed to investigate the efficacy and safety of G/P in Japanese hemodialysis patients with GT2 HCV infection. METHODS: Twenty-seven Japanese hemodialysis patients with GT2 HCV infection who were started on with 8- or 12-week G/P regimen between November 2017 and June 2018 were included and followed up for around 12 weeks after treatment completion. RESULTS: Among the 27 included patients, 13 non-liver cirrhosis (LC) and direct-acting antivirals (DAAs)-naïve patients were treated with 8 weeks of G/P and 14 patients with LC (n = 13) or history of failure of DAAs (n = 1) were treated with a 12-week regimen. The overall sustained virological response at 12 weeks after treatment completion (SVR 12) was 96.3% (26/27). All patients with 8 weeks of treatment achieved SVR12. Two patients discontinued the therapy at 2 and 11 weeks after treatment initiation. The patient who discontinued at 2 weeks due to pruritus alone failed to respond to G/P. No patients experienced lethal adverse events during the therapy, and the most common adverse event was pruritus. CONCLUSIONS: An 8- or 12-week G/P regimen is highly effective and safe in GT2 HCV-infected hemodialysis patients.
• Circulating microRNA-1246 as a possible biomarker for early tumor recurrence of hepatocellular carcinoma.
  Makoto Chuma, Hidenori Toyoda, Juntaro Matsuzaki, Yoshimasa Saito, Takashi Kumada, Toshifumi Tada, Yuji Kaneoka, Atsuyuki Maeda, Hideki Yokoo, Koji Ogawa, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Keiichi Yazawa, Kazuhisa Takeda, Chikara Kunisaki, Katsuaki Ogushi, Satoshi Moriya, Koji Hara, Akito Nozaki, Masaaki Kondo, Hiroyuki Fukuda, Kazushi Numata, Katsuaki Tanaka, Shin Maeda, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 49, 7, 810, 822, Jul. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIMS: Early tumor recurrence (ETR) after hepatic resection is a crucial predictor of poor prognosis in patients with hepatocellular carcinoma (HCC). The aim of this study was to identify clinically significant serum microRNAs (miRNAs) involved in the ETR of HCC. METHODS: We compared expression profiles of circulating miRNAs from serum samples between five HCC patients with ETR (recurrence within 12 months after hepatectomy) and five HCC patients without recurrence using microarray analysis of miRNA. The identified miRNA associated with ETR was further verified in 121 HCC patients, 73 liver disease patients, and 15 health controls by real-time quantitative reverse transcription-polymerase chain reaction (PCR). RESULTS: Of the approximately 2000 miRNAs analyzed, we identified 15 miRNAs for which expression levels correlated significantly with ETR. Of these miRNAs, we further investigated expression of miRNA-1246 (miR-1246). Quantitative PCR confirmed that miR-1246 was upregulated in HCC with ETR, compared to the level in HCC without ETR (P < 0.001). Serum miR-1246 showed a receiver operating characteristic curve area of 0.762, with 77.4% specificity and 54.1% sensitivity in discriminating HCC patients with ETR from HCC patients without ETR. Altered expression of miR-1246 was associated with aggressive tumor characteristics, including tumor-node-metastasis classification (P = 0.0413), tumor differentiation (P = 0.0419), and portal vein invasion (P = 0.0394). Moreover, multivariate Cox regression analysis identified serum miR-1246 level as an independent risk factor for overall survival (hazard ratio, 2.784; 95% confidence interval, 1.528-5.071; P = 0.0008). CONCLUSION: Circulating miR-1246 in serum has strong potential as a novel ETR and prognostic biomarker for HCC.
• Short- and long-term outcomes of a novel transpapillary dilation technique using a diathermic dilator for severe benign bile duct stricture.
  Kato S, Kuwatani M, Kawakubo K, Sugiura R, Hirata K, Nakajima M, Hirata H, Kawakami H, Sakamoto N
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31, 4, 448, 452, Jul. 2019, [Peer-reviewed], [International Magazine]
  English, Endoscopic dilation for severe benign biliary stricture using mechanical dilation devices is occasionally ineffective. Hence, diathermic dilation has recently been gaining attention as a salvage procedure. We evaluated the short- and long-term outcomes of diathermic dilation for severe benign biliary stricture that could not be dilated using conventional mechanical dilation. Thirteen consecutive cases with severe benign biliary stricture that underwent diathermic dilation using 6-Fr electrocautery dilator were enrolled. Short- and long-term outcomes were analyzed. Diathermic dilation was successful in 13 cases (100%), whereas stent was successfully placed in 12 cases (92.3%). Adverse events occurred in two cases (15.4%): mild hemobilia and cholangitis. Recurrence of bile duct stricture was observed in five out of 12 cases (41. 7%) in the 1115-day median follow-up period. Finally, eight cases achieved stent-free state (61.5%) and have remained stent-free without any episode of cholangitis and abnormal liver function test. Diathermic dilation using 6-Fr electrocautery dilator is a promising salvage procedure for severe benign biliary stricture when the conventional dilation technique has been ineffective.
• Validity of endoscopic features for the diagnosis of Helicobacter pylori infection status based on the Kyoto classification of gastritis.
  Yoshii S, Mabe K, Watano K, Ohno M, Matsumoto M, Ono S, Kudo T, Nojima M, Kato M, Sakamoto N
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 32, 1, 74, 83, Jul. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVES: Evaluation of Helicobacter pylori infection status (non-infection, past infection, current infection) has become important. This study aimed to determine the usefulness of the Kyoto classification of gastritis for diagnosing H. pylori infection status by endoscopy. METHODS: In this prospective study, 498 subjects were recruited. Seven well-experienced endoscopists blinded to the history of eradication therapy performed the examinations. Endoscopic findings were assessed according to the Kyoto classification of gastritis: diffuse redness, regular arrangement of collecting venules (RAC), fundic gland polyp (FGP), atrophy, xanthoma, hyperplastic polyp, map-like redness, intestinal metaplasia, nodularity, mucosal swelling, white and flat elevated lesion, sticky mucus, depressive erosion, raised erosion, red streak, and enlarged folds. We established prediction models according to a machine learning procedure and compared them with general assessment by endoscopists using the Kyoto classification of gastritis. RESULTS: Significantly higher diagnostic odds were obtained for RAC (32.2), FGP (7.7), and red streak (4.7) in subjects with non-infection, map-like redness (12.9) in subjects with past infection, and diffuse redness (26.8), mucosal swelling (13.3), sticky mucus (10.2) and enlarged fold (8.6) in subjects with current infection. The overall diagnostic accuracy rate was 82.9% with the Kyoto classification of gastritis. The diagnostic accuracy of the prediction model was 88.6% for the model without H. pylori eradication history and 93.4% for the model with eradication history. CONCLUSIONS: The Kyoto classification of gastritis is useful for diagnosing H. pylori infection status based on endoscopic findings. Our prediction model is helpful for novice endoscopists. (UMIN000016674).
• Metformin Regulates the Expression of CD133 Through the AMPK-CEBPβ Pathway in Hepatocellular Carcinoma Cell Lines.
  Maehara O, Ohnishi S, Asano A, Suda G, Natsuizaka M, Nakagawa K, Kobayashi M, Sakamoto N, Takeda H
  Neoplasia (New York, N.Y.), 21, 6, 545, 556, Jun. 2019, [Peer-reviewed]
• Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis.
  Kuwatani M, Kawakami H, Kubota Y, Kawakubo K, Ito YM, Togo S, Ikeda T, Kusama K, Kobayashi Y, Murata T, Sakamoto N
  Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.], 19, 4, 569, 577, Jun. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA. METHODS: PhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA. RESULTS: The sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA. CONCLUSION: PhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.
• miR-27b-mediated suppression of aquaporin-11 expression in hepatocytes reduces HCV genomic RNA levels but not viral titers.
  Fuminori Sakurai, Rina Hashimoto, Chieko Inoue, Keisaku Wakabayashi, Tomohito Tsukamoto, Tsutomu Imaizumi, Taracena Gandara Marcos Andres, Eiko Sakai, Kanae Itsuki, Naoya Sakamoto, Takaji Wakita, Hiroyuki Mizuguchi
  Virology journal, 16, 1, 58, 58, 02 May 2019, [Peer-reviewed], [International Magazine]
  English, BACKGROUND: MicroRNAs (miRNAs) have gained much attention as cellular factors regulating hepatitis C virus (HCV) infection. miR-27b has been shown to regulate HCV infection in the hepatocytes via various mechanisms that have not been fully elucidated. In this study, therefore, we examined the mechanisms of miR-27b-mediated regulation of HCV infection. METHODS: In silico screening analysis, transfection with miR-27b mimic, and a cell-based reporter assay were performed to identify miR-27b target genes. Cell cultured-derived HCV (HCVcc) was added to Huh7.5.1 cells knocked down for aquaporin (AQP) 11 (AQP11) and overexpressing AQP11. HCV replication levels were evaluated by real-time RT-PCR analysis of HCVcc genome. RESULTS: Infection of Huh7.5.1 cells with HCVcc resulted in significant elevation in miR-27b expression levels. In silico analysis revealed that AQP11, which is an AQP family member and is mainly localized in the endoplasmic reticulum (ER), was a candidate for a target gene of miR-27b. Transfection of a miR-27b mimic significantly reduced AQP11 expression, but a cell-based reporter assay demonstrated that miR-27b did not suppress the expression of a reporter gene containing the 3'-untranslated region of the AQP11 gene, suggesting that miR-27b indirectly suppressed AQP11 expression. AQP11 expression levels were significantly reduced by infection with HCVcc in Huh7.5.1 cells. Knockdown and over-expression of AQP11 significantly reduced and increased HCVcc genome levels in the cells following infection, respectively, however, AQP11 knockdown did not show significant effects on the HCVcc titers in the culture supernatants. CONCLUSIONS: These results indicated that HCV infection induced a miR-27b-mediated reduction in AQP11 expression, leading to a modest reduction in HCV genome levels in the cells, not HCV titers in the culture supernatants.
• 主膵管閉塞を伴わない悪性胆管狭窄に対する金属ステント留置時の乳頭括約筋切開の必要性 多施設共同傾向スコア解析研究　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 江藤 和範, 小野 道洋, 大和 弘明, 江平 宣起, 佐野 逸紀, 庵原 秀之, 久保 公利, 坂本 直哉
  Gastroenterological Endoscopy, 61, Suppl.1, 864, 864, (一社)日本消化器内視鏡学会, May 2019
  Japanese
• 内視鏡的乳頭括約筋切開術による出血に対する治療法　　　　　　　　　　　　　　　
  平田 甫, 桑谷 将城, 坂本 直哉, 中島 正人, 平田 幸司, 杉浦 諒, 加藤 新
  Gastroenterological Endoscopy, 61, Suppl.1, 922, 922, (一社)日本消化器内視鏡学会, May 2019
  Japanese
• カプセル内視鏡を施行した経口抗凝固薬服用者のOGIB ワルファリンとDOACの比較　　　　　　　　　　　　　　　
  井上 雅貴, 小野 尚子, 田中 一光, 木脇 佐代子, 石川 麻倫, 松田 可奈, 津田 桃子, 高橋 正和, 山本 桂子, 中川 学, 中川 宗一, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 61, Suppl.1, 885, 885, (一社)日本消化器内視鏡学会, May 2019
  Japanese
• 消化器内視鏡診療におけるトランスレーショナルリサーチ DPP-IV活性により蛍光を発するプローブによる食道胃接合部腺癌の検出　　　　　　　　　　　　　　　
  山本 桂子, 大西 俊介, 坂本 直哉
  Gastroenterological Endoscopy, 61, Suppl.1, 822, 822, (一社)日本消化器内視鏡学会, May 2019
  Japanese
• Spraying l-menthol enhances gastric intestinal metaplasia in linked color imaging.
  Ono S, Ono Y, Sakamoto N
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31, 3, e70, e71, May 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Transcribed ultraconserved region Uc.63+ promotes resistance to cisplatin through regulation of androgen receptor signaling in bladder cancer.
  Yohei Sekino, Naoya Sakamoto, Akira Ishikawa, Ririno Honma, Yoshinori Shigematsu, Tetsutaro Hayashi, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara, Wataru Yasui
  Oncology reports, 41, 5, 3111, 3118, May 2019, [Peer-reviewed], [International Magazine]
  English, Cisplatin (CDDP)‑based combination chemotherapy is the standard for muscle‑invasive bladder cancer (MIBC). However, nearly all patients undergoing CDDP chemotherapy become refractory due to the development of CDDP resistance. Therefore, clarification of the mechanisms of CDDP resistance is urgently needed. The transcribed ultraconserved regions (T‑UCRs) are a novel class of non‑coding RNAs that are highly conserved across species and are associated with carcinogenesis and cancer progression. In addition, emerging evidence has shown the involvement of androgen receptor (AR) signals in urothelial carcinoma (UC) progression. The aim of the present study was to investigate the expression of transcribed ultraconserved region Uc.63+, and to analyze the effects of Uc.63+ on AR expression and CDDP resistance in UC. Quantitative reverse transcription‑polymerase chain reaction (qRT‑PCR) revealed that the expression of Uc.63+ was higher in UC tissues than that in non‑neoplastic bladder tissues and 15 types of normal tissue. An MTT assay revealed that Uc.63+ was involved in cell proliferation. Western blotting demonstrated that the expression of AR was disrupted by the overexpression or knockdown of Uc.63+ in AR‑positive UMUC3 cells. Furthermore, knockdown of Uc.63+ increased sensitivity to CDDP in UMUC3 cells. Conversely, overexpression of Uc.63+ had no effect on CDDP sensitivity in AR‑negative RT112 cells. Additionally, we observed that the expression of Uc.63+ was increased in CDDP‑resistant UMUC3 cells (UMUC3‑CR) in comparison with that in parental UMUC3 cells. Knockdown of Uc.63+ re‑sensitized the UMUC3‑CR cells to CDDP. These results indicated that Uc.63+ may be a promising therapeutic target to overcome CDDP resistance in UC.
• Synchronous multiple pancreatic cancers developed long after severe postendoscopic retrograde cholangiopancreatography pancreatitis.
  Sugiura R, Kuwatani M, Hirata K, Kato S, Kawamoto Y, Kawakubo K, Mitsuhashi T, Asano T, Hirano S, Sakamoto N
  Endoscopic ultrasound, 8, 3, 213, 214, May 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Budesonide foam for prevention of rectal stricture following endoscopic submucosal dissection.
  Miyamoto S, Naruse H, Sakamoto N
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31, 5, 588, 588, May 2019, [Peer-reviewed], [International Magazine]
  English
• Long-term effect of nucleos (t)ide analogs on hepatitis B surface antigen in chronic hepatitis B patients
  Kenichi Morikawa, Machiko Umemura, Koji Ogawa, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Tomoe Shimazaki, Megumi Kimura, Takaaki Izumi, Masato Nakai, Takuya Sho, Goki Suda, Mitsuteru Natsuizaka, Kota Ono, Kazumoto Murata, Masaya Sugiyama, Mizokami Masashi, Naoya Sakamoto
  JOURNAL OF HEPATOLOGY, 70, 1, E477, E477, Apr. 2019, [Peer-reviewed]
  English
• The Successful Retreatment with Glecaprevir and Pibrentasvir of Genotype 1 or 2 HCV-infected Hemodialysis Patients who Failed to Respond to NS5A and Protease Inhibitor Treatment.
  Goki Suda, Masato Nakai, Takuya Sho, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Naoki Kawagishi, Masaru Baba, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Internal medicine (Tokyo, Japan), 58, 7, 943, 947, 01 Apr. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Clinical trials and real-world data have proven that hepatitis C virus (HCV) in most infected patients can be eradicated by direct-acting antivirals (DAAs). However, the proper retreatment regimen for hemodialysis patients with HCV infection who have previously failed to respond to DAAs has not been clarified. We herein report, for the first time, the successful retreatment with glecaprevir and pibrentasvir, of three hemodialysis patients with genotype 1 or 2 HCV infection, who had previously failed to respond to combination therapy with an HCV-NA5A inhibitor (daclatasvir) and an HCV protease inhibitor (asunaprevir).
• Changes of Dyspeptic Symptom after Successful Eradication in Helicobacter pylori-Associated Dyspepsia.
  Tsuda M, Kato M, Ono S, Matsuda K, Miyamoto S, Abiko S, Ono M, Mizushima T, Yamamoto K, Nakagawa M, Mabe K, Nakagawa S, Kudo T, Nishikawa K, Shimizu Y, Asaka M, Sakamoto N
  Digestion, 101, 2, 1, 9, Apr. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: Helicobacter pylori (H. pylori) gastritis could cause dyspepsia, and eradication is recommended as the first-line treatment. Patients who continuously have their symptoms under control > 6 months after eradication are defined as having H. pylori-associated dyspepsia (HPD), whereas patients who do not benefit from successful eradication are defined as having functional dyspepsia. OBJECTIVES: We assessed changes in dyspeptic symptoms after successful eradication of H. pylori by using a questionnaire. METHODS: We studied H. pylori-infected dyspeptic participants with abdominal symptom scores > 4 points on the Global Overall Symptom (GOS) scoring items and received eradication therapy. We evaluated their symptoms using the GOS questionnaire before their eradications, at 1-month and at 1-year check-ups after eradication therapy. RESULTS: Thirty dyspeptic participants (mean age 59.6 ± 15.3 years) answered every questionnaire. Fourteen participants (46.7%) had HPD, whereas 16 participants (53.3%) were non-HPD patients. The questionnaire at 1 month showed sensitivity of 64.3% (9/14) and specificity of 56.3% (9/16) for HPD. Approximately 60% of H. pylori-infected dyspepsia participants were identified as having HPD or non-HPD within 1 month after their eradications. CONCLUSIONS: Approximately 60% of HPD participants improved at 1 month after eradication. The questionnaire at 1 month helped diagnose HPD in advance and guided next treatment choice.
• Detection of gastritis by a deep convolutional neural network from double-contrast upper gastrointestinal barium X-ray radiography
  Ren Togo, Nobutake Yamamichi, Katsuhiro Mabe, Yu Takahashi, Chihiro Takeuchi, Mototsugu Kato, Naoya Sakamoto, Kenta Ishihara, Takahiro Ogawa, Miki Haseyama
  Journal of Gastroenterology, 54, 4, 321, 329, Apr. 2019, [Peer-reviewed]
  Scientific journal
• Glecaprevir and Pibrentasvir for Japanese Patients with Human Immunodeficiency Virus and Genotype 3 Hepatitis C Virus Coinfection: A Report of Three Cases.
  Takuya Sho, Goki Suda, Megumi Kimura, Tomoe Shimazaki, Osamu Maehara, Taku Shigesawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Machiko Umemura, Takaaki Izumi, Naoki Kawagishi, Masaru Baba, Masato Nakai, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Internal medicine (Tokyo, Japan), 58, 6, 797, 802, 15 Mar. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, The efficacy and safety of glecaprevir and pibrentasvir in Japanese patients with human immunodeficiency virus (HIV) and/or genotype 3 hepatitis C virus (HCV) infection is yet to be clarified. This is because no or only a few patients have been included in Japanese phase 3 trials. We herein report for the first time the successful treatment of glecaprevir and pibrentasvir in three Japanese patients with HIV and genotype 3 HCV coinfection as well as hemophilia. Glecaprevir and pibrentasvir treatment is safe and effective for Japanese patients with genotype 3 HCV and HIV coinfection.
• 胆道腫瘍に対する診療の進歩 超音波内視鏡下穿刺生検検体による胆道癌遺伝子解析
  平田 幸司, 桑谷 将城, 坂本 直哉
  日本消化器病学会雑誌, 116, 臨増総会, A74, A74, (一財)日本消化器病学会, Mar. 2019
  Japanese
• 胆道病変に対する超音波内視鏡下穿刺吸引法の臨床成績　　　　　　　　　　　　　　　
  平田 甫, 桑谷 将城, 中島 正人, 平田 幸司, 杉浦 諒, 加藤 新, 坂本 直哉
  日本消化器病学会北海道支部例会プログラム・抄録集, 124回, 66, 66, 日本消化器病学会-北海道支部, Mar. 2019
  Japanese
• 消化器領域における幹細胞研究とその応用 間葉系幹細胞から分泌される生理活性脂質の抗炎症・抗線維化効果
  小田切 信介, 大西 俊介, 坂本 直哉
  日本消化器病学会雑誌, 116, 臨増総会, A87, A87, (一財)日本消化器病学会, Mar. 2019
  Japanese
• Unusual reintervention through a fistula for ampullary penetration of a plastic stent in malignant distal biliary obstruction.
  Sugiura R, Kuwatani M, Sakamoto N
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31, 2, e48, e49, Mar. 2019, [Peer-reviewed]
• Long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography using balloon-assisted enteroscopy for anastomotic stenosis of choledochojejunostomy/pancreaticojejunostomy.
  Sano I, Katanuma A, Kuwatani M, Kawakami H, Kato H, Itoi T, Ono M, Irisawa A, Okabe Y, Iwashita T, Yasuda I, Ryozawa S, Kaino S, Sakamoto N
  Journal of gastroenterology and hepatology, 34, 3, 612, 619, Mar. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Data on long-term outcomes after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) using balloon-assisted enteroscopy (BAE) for choledochojejunal anastomotic stenosis (CJS) or pancreaticojejunal anastomotic stenosis (PJS) remain limited. We retrospectively assessed the long-term results of patients who achieved clinical success using BAE for CJS and PJS. METHODS: Patients who achieved technical and clinical success for CJS or PJS by BAE-ERCP and were followed up for more than 6 months after the initial BAE-ERCP therapy were retrospectively identified at 11 Japanese institutions. The primary end-point was CJS or PJS recurrence rates. The secondary end-points were initial therapy details, initial therapy complications, and CJS or PJS recurrence treatment details. We also evaluated restenosis-associated factors. RESULTS: From September 2008 to December 2015, 67 patients (CJS, 61; PJS, six) were included. The overall CJS and PJS recurrence rates were 34.4% and 33.3%, respectively. The 1-year CJS recurrence rate was 18.5% (95% confidence interval, 10.7-31.0). Of all the patients, 88.1% underwent balloon dilation at the anastomotic stenosis site; stent placement was performed in 15 of 67 patients (22.4%). The complication rate was 8.2% in CJS and 0% in PJS. In patients who underwent balloon dilation, "remaining waist" was significantly associated with CJS recurrence after anastomotic balloon dilation (P = 0.001). CONCLUSIONS: The long-term outcomes of BAE-ERCP were comparable with those of percutaneous transhepatic treatment or surgical re-anastomosis.
• Better too big than too small?
  Kawakubo K, Kuwatani M, Kato S, Sakamoto N
  Gastrointestinal endoscopy, 89, 3, 650, 651, Mar. 2019, [Peer-reviewed], [International Magazine]
  English
• Prospective, multicenter, observational study of tissue acquisition through EUS-guided fine-needle biopsy using a 25G Franseen needle.
  Sugiura R, Kuwatani M, Yane K, Taya Y, Ihara H, Onodera M, Eto K, Sano I, Kudo T, Mitsuhashi T, Katanuma A, Sakamoto N, Hokkaido Interventional EUS, ERCP study, HONEST) group
  Endoscopic ultrasound, Mar. 2019, [Peer-reviewed]
• Comparative sequence analysis of patient-matched primary colorectal cancer, metastatic, and recurrent metastatic tumors after adjuvant FOLFOX chemotherapy.
  Harada K, Okamoto W, Mimaki S, Kawamoto Y, Bando H, Yamashita R, Yuki S, Yoshino T, Komatsu Y, Ohtsu A, Sakamoto N, Tsuchihara K
  BMC cancer, 19, 1, 255, 255, Mar. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: In the era of genome-guided personalized cancer treatment, we must understand chemotherapy-induced genomic changes in tumors. This study evaluated whether adjuvant FOLFOX chemotherapy modifies the mutational profile of recurrent colorectal cancer (CRC). METHODS: Whole exome sequencing was performed on samples from primary CRC tumors, untreated metastatic tumors, and recurrent tumors following adjuvant FOLFOX chemotherapy. The samples were resected from four patients. RESULTS: The number of mutations or the mutation spectrum in individual patients was nearly identical. Copy number variants persisted regardless of FOLFOX therapy administration. The genomic signature of oxaliplatin exposure (G > T/C > A, T > A/A > T) was not enriched after FOLFOX chemotherapy. Overlapping single nucleotide variants (SNVs) and indels remained in 26-65% of the patient-matched tumor samples. One patient harbored an AKT1 E17K mutation in the recurrent tumor, whereas PIK3CA E542K and E88Q mutations were detected in the primary and untreated metastatic tumor samples. Genes related to intracellular Ca2+ homeostasis were enriched among the genes uniquely mutated after FOLFOX chemotherapy. CONCLUSIONS: We found that the mutation rates, mutation spectrum, and copy number variants were nearly identical regardless of the administration of FOLFOX therapy in the four CRC cases. The mutational discordance between the patient-matched tumor samples is likely caused by tumor heterogeneity and chemotherapy-induced clonal selection. These findings might be useful as pilot data for larger studies to clarify the changes in the mutational landscape induced by adjuvant FOLFOX chemotherapy.
• A Novel Approach for the Genetic Analysis of Biliary Tract Cancer Specimens Obtained Through Endoscopic Ultrasound-Guided Fine Needle Aspiration Using Targeted Amplicon Sequencing.
  Hirata K, Kuwatani M, Suda G, Ishikawa M, Sugiura R, Kato S, Kawakubo K, Sakamoto N
  Clinical and translational gastroenterology, 10, 3, e00022, Mar. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVES: Biliary tract cancer (BTC) is an aggressive malignant tumor, and biomarker-based clinical trials for this cancer are currently ongoing. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) is a safe procedure and enables pathological diagnoses; however, it is uncertain whether a tiny tumor sample of BTC obtained through EUS-FNA can be analyzed for diverse genetic alterations in the development and tolerance of BTC. Thus, we aimed to verify the feasibility of genetic analyses with EUS-FNA samples of BTC. METHODS: Targeted amplicon sequencing using a cancer gene panel with 50 genes was performed with tissue samples of 21 BTC patients obtained through EUS-FNA with a novel rapid on-site process compared with paired peripheral blood samples. RESULTS: Pathogenic gene alterations were successfully identified in 20 out of 21 patients (95.2%) with EUS-FNA specimens of BTC, which included 19 adenocarcinomas and 2 adenosquamous carcinomas. Eighty single nucleotide variants and 8 indels in 39 genes were identified in total, and 28 pathogenic alterations in 14 genes were identified (average, 1.4 alterations per patient). The most common alterations were TP53, KRAS, and CDKN2A in gallbladder carcinoma; TP53, KRAS, PIK3CA, and BRAF in intrahepatic cholangiocarcinoma; and TP53 and SMAD4 in extrahepatic cholangiocarcinoma. Actionable gene alterations (BRAF, NRAS, PIK3CA, and IDH1) were identified in 7 out of 21 patients. CONCLUSIONS: A novel approach in genetic analysis using targeted amplicon sequencing with BTC specimens obtained through EUS-FNA was feasible and enabled us to identify genomic alterations.
• Evaluation of gastric acid suppression with vonoprazan using calcium carbonate breath test.
  Miyamoto S, Tsuda M, Kato M, Mabe K, Muto S, Ono S, Shimizu Y, Sakamoto N
  Journal of clinical biochemistry and nutrition, 64, 2, 174, 179, Mar. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Vonoprazan, a potassium-competitive acid blocker, is a new class of acid-suppressing agent. The acid-inhibitory effect of vonoprazan has been well-documented. However, there is no report on the extent to which the amount of gastric acid secretion is suppressed, not pH measurement, by the use of vonoprazan. The aim of this study was to evaluate this suppression effect. This was a single-arm, interventional pilot study involving 7 healthy Japanese men. The subjects were administered 20 mg vonoprazan for 6 days. The amount of gastric acid secretion was determined using the calcium carbonate breath test. The acid outputs were defined as the maximum Δ13C‰ (Δ13C max) and area under the curve (AUC) during the 30 min sampling period. The Δ13C max and AUC values significantly decreased on the administration of 20 mg vonoprazan. The AUC dropped by approximately 78% on day 1 and by 84% on day 6 and subsequently returned to the control level after cessation of vonoprazan therapy (reduction by 68% on day 7 and by 42% on day 8). In conclusion, the amount of gastric acid secretion rapidly decreased by the administration of vonoprazan; this inhibitory effect was found to be potent and long-lasting. (UMIN ID: UMIN000025469).
• DPP-IV活性により蛍光を発するプローブによる頭頸部扁平上皮表在がんの検出
  山本 桂子, 大西 俊介, 水島 健, 清水 勇一, 坂本 直哉
  耳鼻咽喉科展望, 62, 1, 42, 43, 耳鼻咽喉科展望会, Feb. 2019
  Japanese
• Clinicopathological significance of claspin overexpression and its association with spheroid formation in gastric cancer.
  Kobayashi G, Sentani K, Hattori T, Yamamoto Y, Imai T, Sakamoto N, Kuraoka K, Oue N, Sasaki N, Taniyama K, Yasui W
  Human pathology, 84, 8, 17, Feb. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Spheroid colony formation is a useful method to identify cancer stem cells (CSCs). The aim of this study was to identify a novel prognostic marker or therapeutic target for GC using a method to identify CSCs. We analyzed the microarray data in spheroid body-forming and parental cells and focused on the CLSPN gene because it is overexpressed in the spheroid body-forming cells in both the GC cell lines MKN-45 and MKN-74. Quantitative reverse-transcription polymerase chain reaction analysis revealed that CLSPN messenger RNA expression was up-regulated in GC cell lines MKN-45, MKN-74, and TMK-1. Immunohistochemistry of claspin showed that 94 (47%) of 203 GC cases were positive. Claspin-positive GC cases were associated with higher T and N grades, tumor stage, lymphatic invasion, and poor prognosis. In addition, claspin expression was coexpressed with CD44, human epidermal growth factor receptor type 2, and p53. CLSPN small interfering RNA treatment decreased GC cell proliferation and invasion. These results indicate that the expression of claspin might be a key regulator in the progression of GC and might play an important role in CSCs of GC.
• Evaluation of clinical utility of PIVKA-II using a chemiluminescent immunoassay
  Koji Ogawa, Kazuharu Suzuki, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Naoya Sakamoto
  Acta Hepatologica Japonica, 60, 11, 397, 404, Japan Society of Hepatology, 2019
  Japanese, Scientific journal
• Esptein-Barr virus陽性リンパ上皮腫様大腸癌の1例　　　　　　　　　　　　　　　
  木脇 佐代子, 山本 桂子, 井上 雅貴, 田中 一光, 松田 可奈, 石川 麻倫, 津田 桃子, 小野 尚子, 清水 勇一, 岡田 宏美, 三橋 智子, 松野 吉宏, 坂本 直哉
  日本大腸肛門病学会雑誌, 72, 1, 43, 43, (一社)日本大腸肛門病学会, Jan. 2019
  Japanese
• 消化管に多発潰瘍を認めた造血幹細胞移植後EBウイルス関連リンパ増殖性疾患の1例　　　　　　　　　　　　　　　
  松田 可奈, 小野 尚子, 井上 雅貴, 田中 一光, 木脇 佐代子, 石川 麻倫, 津田 桃子, 山本 桂子, 清水 勇一, 坂本 直哉
  日本大腸肛門病学会雑誌, 72, 1, 44, 44, (一社)日本大腸肛門病学会, Jan. 2019
  Japanese
• Analysis of 307 cases with drug-induced liver injury between 2010 and 2018 in Japan.
  Mitsuhiko Aiso, Hajime Takikawa, Keiji Tsuji, Tatehiro Kagawa, Masaaki Watanabe, Atsushi Tanaka, Ken Sato, Shotaro Sakisaka, Yoichi Hiasa, Yoshiyuki Takei, Hiromasa Ohira, Minoru Ayada, Etsuko Hashimoto, Shuichi Kaneko, Yoshiyuki Ueno, Kenji Ohmoto, Akinobu Takaki, Takuji Torimura, Yasushi Matsuzaki, Kazuto Tajiri, Masashi Yoneda, Takayoshi Ito, Naoya Kato, Kenichi Ikejima, Satoshi Mochida, Hiroshi Yasuda, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 49, 1, 105, 110, Jan. 2019, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: In order to know the present status of drug-induced liver injury (DILI) in Japan, we present the data of prospectively collected DILI cases between 2010 and 2018 from 27 hospitals. METHODS: Drug-induced liver injury cases diagnosed by DILI experts from 27 hospitals all over Japan have been prospectively collected since 2010. Alanine aminotransferase level ≥150 U/L and/or alkaline phosphatase ≥2× upper limit of normal were inclusion criteria. RESULTS: In total, data of 307 cases (125 male and 182 female individuals) aged between 17 and 86 years old were collected. The types of liver injury were as follows: 64% hepatocellular type, 20% mixed type, and 16% cholestatic type. A drug-induced lymphocyte stimulation test was carried out in 59% of cases, and was positive in 48% and semipositive in 3% of cases. Eosinophilia ≥6% was observed in 27% of cases. Fifty-three percent of DILI cases occurred within 30 days and 79% of DILI cases occurred within 90 days after starting drug administration. By the diagnostic scale of the Digestive Disease Week (DDW)-Japan 2004 workshop, 93.8% of cases were diagnosed as "highly probable", and 5.9% as "possible". CONCLUSIONS: Japanese DILI patients are somewhat different from those of Europe and North America. The diagnostic scale of the DDW-Japan 2004 workshop has been used in Japan. However, there are many issues to improve the causality assessment of DILI that we must investigate in the future. It is critical to elucidate the mechanisms of drug metabolism and the pathophysiology of liver injury by various drugs to prevent DILI.
• Safety and efficacy of elbasvir and grazoprevir in Japanese hemodialysis patients with genotype 1b hepatitis C virus infection.
  Goki Suda, Masayuki Kurosaki, Jun Itakura, Namiki Izumi, Yoshihito Uchida, Satoshi Mochida, Chitomi Hasebe, Masami Abe, Hiroaki Haga, Yoshiyuki Ueno, Ikuto Masakane, Kazumichi Abe, Atsushi Takahashi, Hiromasa Ohira, Ken Furuya, Masaru Baba, Yoshiya Yamamoto, Tomoe Kobayashi, Atsuhiko Kawakami, Kenichi Kumagai, Katsumi Terasita, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Journal of gastroenterology, 54, 1, 78, 86, Jan. 2019, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: The prevalence of hepatitis C virus (HCV) infection in hemodialysis patients is high and results in a poor prognosis. Thus, safer and more effective treatment regimens are required. In this prospective multicenter study, we investigated the efficacy and safety of the novel HCV-NS5A-inhibitor, elbasvir, and protease inhibitor, grazoprevir in Japanese hemodialysis patients with genotype 1b HCV infection. METHODS: This study is registered at the UMIN Clinical Trials Registry as UMIN00002578. A total of 23 Japanese dialysis patients with genotype 1b HCV infection who were treated with elbasvir and grazoprevir between January 2017 and March 2018 and followed for more than 12 weeks after treatment completion were included. We evaluated the sustained virologic response at 12 weeks after treatment completion (SVR12) and safety during treatment. RESULTS: Of the 23 patients, 7 had advanced liver fibrosis and 2 had a signature resistance-associated variant of NS5A (NS5A RAVs)-L31M/V or Y93H at baseline. All patients completed therapy, and 96.7% (22/23) of the patients achieved SVR12. All patients with advanced liver fibrosis and signature NS5A RAVs at baseline achieved SVR12 with a high safety profile. No patient experienced lethal or severe adverse events during therapy, and the most common adverse event was anemia. One patient, who was a non-responder to this therapy, had a history of failure with daclatasvir and asunaprevir therapies and had NS5A RAVs of A92K at baseline, but not signature NS5A RAVs. CONCLUSIONS: Grazoprevir and elbasvir combination is highly effective and safe for hemodialysis patients with genotype 1b HCV infection.
• Usefulness of transabdominal ultrasonography for assessing ulcerative colitis: a prospective, multicenter study.
  Kinoshita K, Katsurada T, Nishida M, Omotehara S, Onishi R, Mabe K, Onodera A, Sato M, Eto K, Suya M, Maemoto A, Hasegawa T, Yamamoto J, Mitsumori D, Yoshii S, Ono K, Sakamoto N
  Journal of gastroenterology, 54, 6, 521, 529, Dec. 2018, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: Transabdominal ultrasonography (US) has been reported to be a useful tool for evaluating ulcerative colitis (UC) although with less well-established data than for Crohn's disease. This prospective multicenter study aimed to establish the usefulness of US compared with colonoscopy (CS) for assessing disease extent and activity of UC. METHODS: Altogether, 173 patients with UC were prospectively enrolled, among whom 156 were eligible for this study. All patients underwent US and CS within 2 days at five facilities. We divided the colon into six segments and examined each segment and the rectum using US and CS. US severity was graded 1-4 regarding bowel wall thickness, stratification, and ulceration. CS severity was also graded 1-4 according to Matts' endoscopic classification. Concordance between US and CS grades for all colonic segments was analyzed using kappa statistics. US and CS findings were also compared with the clinical disease activity index (CAI) and histological grade using Spearman's correlation coefficient. RESULTS: There was moderate concordance between US and CS grades in all colonic segments (weighted κ = 0.55, p < 0.001). Concordance was rated moderate for each colonic segment but only slight for the rectum. The US grade was significantly correlated with the CAI score (r = 0.40, p < 0.001) and histological grade (r = 0.35, p < 0.001). CONCLUSIONS: This prospective multicenter study showed moderate concordance between US and CS for assessing the disease activity of UC. Hence, US may be used more generally for evaluating UC in daily clinical practice.
• EUS versus transpapillary drainage of malignant biliary obstruction: still a long way to go.
  Kawakubo K, Kuwatani M, Sakamoto N
  Gastrointestinal endoscopy, 88, 5, 884, Nov. 2018, [Peer-reviewed]
• Sialic Acid Linkage Specific Derivatization of Glycosphingolipid Glycans by Ring-Opening Aminolysis of Lactones.
  Hanamatsu H, Nishikaze T, Miura N, Piao J, Okada K, Sekiya S, Iwamoto S, Sakamoto N, Tanaka K, Furukawa JI
  Analytical chemistry, 90, 22, 13193, 13199, Nov. 2018, [Peer-reviewed]
• HBV patients with low HBsAg and high HBcrAg titers have a high risk of HBV-related HCC.
  Suzuki Y, Maekawa S, Komatsu N, Sato M, Tatsumi A, Miura M, Matsuda S, Muraoka M, Nakakuki N, Shindo H, Amemiya F, Takano S, Fukasawa M, Nakayama Y, Yamaguchi T, Inoue T, Sato T, Sakamoto M, Yamashita A, Moriishi K, Enomoto N
  Hepatology research : the official journal of the Japan Society of Hepatology, 49, 1, 51, 63, Wiley, Oct. 2018, [Peer-reviewed]
  Scientific journal
• Interventional EUSのトラブルシューティング 超音波内視鏡下胆管消化管吻合術における瘻孔拡張の実際とトラブルシューティング　　　　　　　　　　　　　　　
  平田 幸司, 桑谷 将城, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.2, 2048, 2048, (一社)日本消化器内視鏡学会, Oct. 2018
  Japanese
• Interventional EUSのトラブルシューティング 超音波内視鏡下胆管消化管吻合術における瘻孔拡張の実際とドラブルシューティング　　　　　　　　　　　　　　　
  平田 幸司, 桑谷 将城, 坂本 直哉
  日本消化器病学会雑誌, 115, 臨増大会, A680, A680, (一財)日本消化器病学会, Oct. 2018
  Japanese
• The Risk of Hepatocellular Carcinoma Development after Sustained Virologic Response Are Similar between Japanese Patients with HCV Genotype 1 Infection Treated with Ledipasvir/Sofosbuvir and Protease Inhibitor with Peg-Interferon Plus Ribavirin.
  Masaaki Korenaga, Namiki Izumi, Nobuharu Tamaki, Osamu Yokosuka, Tetsuo Takehara, Naoya Sakamoto, Goki Suda, Shuhei Nishiguchi, Hirayuki Enomoto, Fusao Ikeda, Mikio Yanase, Hidenori Toyoda, Takuya Genda, Takeji Umemura, Hiroshi Yatsuhashi, Kazumi Yamasaki, Tatsuya Ide, Nobuo Toda, Tatsuo Kanda, Kazushige Nirei, Yoshiyuki Ueno, Hiroaki Haga, Yohichi Nishigaki, Masao Omata, Hitoshi Mochiduki, Tatsuya Kanto, Masashi Mizokami
  HEPATOLOGY, 68, 535A, 536A, Oct. 2018, [Peer-reviewed]
  English
• Innovative therapeutic endoscopy良性胆管・膵管狭窄に対する内視鏡治療 良性胆管・膵管狭窄に対する経乳頭的通電拡張術の効果　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.2, 2013, 2013, (一社)日本消化器内視鏡学会, Oct. 2018
  Japanese
• 良性胆管・膵管狭窄に対する内視鏡治療 良性胆管・膵管狭窄に対する経乳頭的通電拡張術の効果　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 坂本 直哉
  日本消化器病学会雑誌, 115, 臨増大会, A633, A633, (一財)日本消化器病学会, Oct. 2018
  Japanese
• 内視鏡を用いた小腸絨毛萎縮診断の正診率についての検討　　　　　　　　　　　　　　　
  松田 可奈, 小野 尚子, 石川 麻倫, 宮本 秀一, 安孫子 怜史, 津田 桃子, 山本 桂子, 工藤 俊彦, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.2, 2123, 2123, (一社)日本消化器内視鏡学会, Oct. 2018
  Japanese
• 食道癌内視鏡的切除後の異時性多発癌に及ぼす節酒禁煙効果の検討　　　　　　　　　　　　　　　
  安孫子 怜史, 清水 勇一, 石川 麻倫, 松田 可奈, 宮本 秀一, 津田 桃子, 山本 桂子, 小野 尚子, 工藤 俊彦, 坂本 直哉
  日本消化器病学会雑誌, 115, 臨増大会, A756, A756, (一財)日本消化器病学会, Oct. 2018
  Japanese
• 長期予後改善をめざす自己免疫性肝疾患の基礎と臨床 薬剤誘発硬化性胆管炎ラットに対するヒト羊膜由来間葉系幹細胞の治療効果　　　　　　　　　　　　　　　
  杉浦 諒, 大西 俊介, 坂本 直哉
  日本消化器病学会雑誌, 115, 臨増大会, A606, A606, (一財)日本消化器病学会, Oct. 2018
  Japanese
• Higher Wisteria Floribunda Agglutinin-Positive Mac-2 Binding Protein (M2BPGi) Not M2BP and Pre-Sarcopenia Are Prognostic and Recurrence Markers of Primary Hepatocellular Carcinoma Treated By RFA in HCV-Negative and HCV-Eradicated Patients.
  Masato Nakai, Goki Suda, Koji Ogawa, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Naoki Kawagishi, Machiko Umemura, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
  HEPATOLOGY, 68, 843A, 844A, Oct. 2018, [Peer-reviewed]
  English
• Hepatitis B Virus x Protein Attenuate Interferon Signaling Throughup-Regulation of SOCS3 and Protein Phosphatase 2A Via up-Regulation of ER Stress
  Kenichi Morikawa, Ogawa Koji, Goki Suda, Naoya Sakamoto
  HEPATOLOGY, 68, 345A, 345A, Oct. 2018, [Peer-reviewed]
  English
• Clinicopathological significance of RCAN2 production in gastric carcinoma.
  Hattori Y, Sentani K, Shinmei S, Oo HZ, Hattori T, Imai T, Sekino Y, Sakamoto N, Oue N, Niitsu H, Hinoi T, Ohdan H, Yasui W
  Histopathology, 74, 3, 430, 442, Oct. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIMS: Gastric cancer (GC) is one of the leading causes of cancer-related death worldwide. Genes expressed only in cancer tissue may be useful biomarkers for cancer diagnosis and therapeutics. The aims of the present study were to analyse regulator of calcineurin 2 (RCAN2) in a large number of GCs, and to investigate how these expression patterns correlate with clinicopathological parameters and various markers. METHODS AND RESULTS: An immunohistochemical analysis of RCAN2 in 207 GC tissue samples showed that 110 (53%) GCs were positive for RCAN2. RCAN2-positive GCs were more advanced in terms of TNM classification and tumour stage than RCAN2-negative GCs. Furthermore, RCAN2 was an independent prognostic classifier for GC patients. The cell growth and invasiveness of RCAN2 small interfering RNA (siRNA)-transfected GC cell lines were less than those of the negative control siRNA-transfected cell lines, whereas those of RCAN2-transfected cells were significantly increased as compared with those of empty vector-transfected cells. RCAN2 siRNA inhibits the phosphorylation of AKT and p44/p42 (ERK1/2). RCAN2 was colocalised with EGFR, nuclear β-catenin, MMP7, laminin-γ2, VEGF-A, and VEGF-C. CONCLUSION: These results suggest that RCAN2 is involved in tumour progression and is an independent prognostic classifier in patients with GC.
• The Risk of Hepatocellular Carcinoma Development after Sustained Virologic Response Are Similar between Japanese Patients with HCV Genotype 1 Infection Treated with Ledipasvir/Sofosbuvir and Protease Inhibitor with Peg-Interferon Plus Ribavirin.　　　　　　　　　　　　　　　
  Korenaga Masaaki, Izumi Namiki, Tamaki Nobuharu, Yokosuka Osamu, Takehara Tetsuo, Sakamoto Naoya, Suda Goki, Nishiguchi Shuhei, Enomoto Hirayuki, Ikeda Fusao, Yanase Mikio, Toyoda Hidenori, Genda Takuya, Umemura Takeji, Yatsuhashi Hiroshi, Yamasaki Kazumi, Ide Tatsuya, Toda Nobuo, Kanda Tatsuo, Nirei Kazushige, Ueno Yoshiyuki, Haga Hiroaki, Nishigaki Yohichi, Omata Masao, Mochiduki Hitoshi, Kanto Tatsuya, Mizokami Masashi
  HEPATOLOGY, 68, 535A, 536A, Oct. 2018
  Japanese, Scientific journal
• Direct recanalization of pancreaticogastrostomy obstruction with a forward-viewing echoendoscope.
  Kuwatani M, Kato S, Sakamoto N
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31, 1, e18, e19, Oct. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• No difference does not always mean equivalent.
  Kawakubo K, Kuwatani M, Sakamoto N
  Gastrointestinal endoscopy, 88, 3, 573, Sep. 2018, [Peer-reviewed]
• Efficacy and safety of sofosbuvir-velpatasvir with or without ribavirin in HCV-infected Japanese patients with decompensated cirrhosis: an open-label phase 3 trial.
  Takehara T, Sakamoto N, Nishiguchi S, Ikeda F, Tatsumi T, Ueno Y, Yatsuhashi H, Takikawa Y, Kanda T, Sakamoto M, Tamori A, Mita E, Chayama K, Zhang G, De-Oertel S, Dvory-Sobol H, Matsuda T, Stamm LM, Brainard DM, Tanaka Y, Kurosaki M
  Journal of gastroenterology, 54, 1, 87, 95, Sep. 2018, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: In Japan, hepatitis C virus (HCV)-infected patients with decompensated cirrhosis currently have no treatment options. In this Phase 3 study, we evaluated sofosbuvir-velpatasvir with or without ribavirin for 12 weeks in patients with any HCV genotype and decompensated cirrhosis [Child-Pugh-Turcotte (CPT) class B or C] in Japan. METHODS: Patients were randomized 1:1 to receive sofosbuvir-velpatasvir with or without ribavirin for 12 weeks. Randomization was stratified by CPT class and genotype. Sustained virologic response 12 weeks following completion of treatment (SVR12) was the primary efficacy endpoint. RESULTS: Of the 102 patients enrolled, 57% were treatment naive, 78% and 20% had genotype 1 and 2 HCV infection, respectively, and 77% and 20% had CPT class B and C cirrhosis, respectively, at baseline. Overall, 61% of patients were female and the mean age was 66 years (range 41-83). SVR12 rates were 92% (47/51) in each group. Among patients who achieved SVR12, 26% had improved CPT class from baseline to posttreatment week 12. Most adverse events (AEs) were consistent with clinical sequelae of advanced liver disease or known toxicities of ribavirin. Four patients (8%) who received sofosbuvir-velpatasvir and seven (14%) who received sofosbuvir-velpatasvir plus ribavirin experienced a serious AE. The 3 deaths (bacterial sepsis, gastric varices hemorrhage, hepatocellular carcinoma) were attributed to liver disease progression. CONCLUSION: Sofosbuvir-velpatasvir for 12 weeks provides a highly effective and well-tolerated therapy for Japanese patients with HCV and decompensated cirrhosis. Ribavirin did not improve efficacy but increased toxicity.
• Prenatally diagnosed large mediastinal lymphangioma: A case report.
  Tanaka H, Masumoto K, Aoyama T, Sanmoto Y, Ono K, Sakamoto N, Kawakami H
  Clinical case reports, 6, 9, 1880, 1884, Sep. 2018, [Peer-reviewed]
• Regulation of interferon signaling and HCV‑RNA replication by extracellular matrix.
  Kuwashiro T, Iwane S, Jinghe X, Matsuhashi S, Eguchi Y, Anzai K, Fujimoto K, Mizuta T, Sakamoto N, Ikeda M, Kato N, Ozaki I
  International journal of molecular medicine, 42, 2, 957, 965, Aug. 2018, [Peer-reviewed]
• L-Carnitine Suppresses Loss of Skeletal Muscle Mass in Patients With Liver Cirrhosis.
  Masatsugu Ohara, Koji Ogawa, Goki Suda, Megumi Kimura, Osamu Maehara, Tomoe Shimazaki, Kazuharu Suzuki, Akihisa Nakamura, Machiko Umemura, Takaaki Izumi, Naoki Kawagishi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Shunsuke Ohnishi, Naoya Sakamoto
  Hepatology communications, 2, 8, 906, 918, Aug. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Liver cirrhosis (LC) is a major cause of secondary sarcopenia. Sarcopenia makes the prognosis worse; thus, novel therapeutic options for sarcopenia in patients with LC are urgently required as they are currently limited. In this retrospective study, 158 patients with LC were screened, and 35 of those patients who were treated with L-carnitine for more than 6 months and for whom skeletal muscle mass changes could be evaluated by computer tomography were enrolled. Of the 158 patients, 79 patients who did not receive L-carnitine supplementation served as controls. Cases and controls were propensity score matched for age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration, and changes in skeletal muscle mass and clinical data were compared. The 35 patients who received L-carnitine supplementation and 35 propensity score-matched patients who did not receive carnitine supplementation comprised the final enrollment. Compared with control patients, patients who received L-carnitine had significantly worse liver function, which is associated with rapid progress of skeletal muscle depletion. However, loss of skeletal muscle mass was significantly suppressed in patients receiving L-carnitine, and a significant effect was observed in patient subgroups stratified by age, sex, presence of hepatocellular carcinoma, and branched chain amino acid administration. The change ratios of most laboratory data, including vitamin D and insulin-like growth factor 1 levels, were similar in the two groups, but ammonia levels were significantly less in those receiving L-carnitine. However, even in patients receiving L-carnitine but not showing an ammonia decrease, loss of skeletal muscle was significantly suppressed. Conclusion: L-carnitine suppresses loss of skeletal muscle mass and may therefore be a novel therapeutic option for sarcopenia in patients with LC. (Hepatology Communications 2018; 00:000-000).
• Bacterial Meningitis Caused by β-lactamase Non-producing Ampicillin-resistant Haemophilus influenzae Type F in an Immunocompetent Woman.
  Sakamoto S, Sakamoto N
  Internal medicine (Tokyo, Japan), 58, 2, 307, 310, Aug. 2018, [Peer-reviewed]
• Hepatobiliary and Pancreatic: Pancreatic cancer with elevated serum IgG4 level due to multiple myeloma mimicking localized autoimmune pancreatitis
  S. Kato, M. Kuwatani, K. Kawakubo, R. Sugiura, K. Hirata, S. Tanikawa, T. Mitsuhashi, S. Shiratori, N. Sakamoto
  Journal of Gastroenterology and Hepatology (Australia), 33, 7, 1310, Blackwell Publishing, 01 Jul. 2018, [Peer-reviewed]
  English
• Randomized controlled trial: PPI-based triple therapy containing metronidazole versus clarithromycin as first-line treatment for Helicobacter pylori in adolescents and young adults in Japan
  Katushiro Mabe, Masumi Okuda, Shogo Kikuchi, Kenji Amagai, Rie Yoshimura, Mototsugu Kato, Naoya Sakamoto, Masahiro Asaka, Japan Gast Study Group
  Journal of Infection and Chemotherapy, 24, 7, 538, 543, Elsevier B.V., 01 Jul. 2018, [Peer-reviewed]
  English, Scientific journal
• Lavender Color in Linked Color Imaging Enables Noninvasive Detection of Gastric Intestinal Metaplasia.
  Ono S, Kato M, Tsuda M, Miyamoto S, Abiko S, Shimizu Y, Sakamoto N
  Digestion, 98, 4, 222, 230, Jul. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIMS: Recently, there have been some reports that image-enhanced endoscopy may improve detection of gastric intestinal metaplasia (GIM). Our aim was to determine the usefulness of linked color imaging (LCI) for detection of GIM. METHODS: In prospectively recruited patients, the whole antrum was observed by white light imaging (WLI) followed by LCI. When a whitish flat elevation (WFE) in WLI and a lavender color sign (LCS) in LCI were detected, target biopsies were performed after LCI. Random biopsies were performed in patients who had neither WFE nor LCS. The primary endpoint was the diagnostic accuracy of GIM per patient in WLI and LCI and the secondary endpoints were that of GIM per biopsy and interobserver agreement. RESULTS: Data from 128 patients were analyzed and 58 patients (45.3%) had histological GIM in the antrum. The per-patient yields of WLI and LCI to detect GIM were 19.0% (11/58) and 91.4% (53/58) respectively. Diagnostic accuracies of target biopsies for GIM were 23.7% in WLI and 84.2% in LCI. Kappa values among 3 doctors were 0.60 for WFE and 0.78 for LCS respectively. CONCLUSION: LCI could be a new diagnostic tool for detecting GIM during routine endoscopy.
• PREVENTIVE EFFECT OF MESENCHYMAL STEM CELL-CULTURE SUPERNATANT ON LUMINAL STRICTURE AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE RECTUM OF PIGS
  Ohnishi Shunsuke, Tsuda Momoko, Mizushima Takeshi, Ishikawa Marin, Abiko Satoshi, Shimizu Yuichi, Sakamoto Naoya
  GASTROINTESTINAL ENDOSCOPY, 87, 6, AB501, Jun. 2018, [Peer-reviewed]
• Safety and efficacy of sofosbuvir and ribavirin for genotype 2 hepatitis C Japanese patients with renal dysfunction.
  Takuya Sho, Goki Suda, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Kenichi Kumagai, Minoru Uebayashi, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Manabu Onodera, Takashi Meguro, Megumi Kimura, Jun Ito, Machiko Umemura, Takaaki Izumi, Naoki Kawagishi, Masatsugu Ohara, Yuji Ono, Masato Nakai, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 48, 7, 529, 538, Jun. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: The safety and efficacy of sofosbuvir (SOF) and ribavirin (RBV) have not been well clarified in patients with renal dysfunction because clinical trials have not included such patients. We evaluated the safety and efficacy of SOF and RBV for genotype 2 hepatitis C virus (HCV)-infected patients with renal dysfunction. METHODS: The study included genotype 2 HCV-infected patients who received SOF and RBV between July 2014 and May 2017. The sustained virologic response (SVR) after the treatment and safety during the therapy were evaluated according to renal function. RESULTS: A total of 231 patients were included in this study. The median age was 62 years old, and 45.9% (106/231) were men. Of the 231 patients, 191 (82.8%) and 40 (17.2%) were classified as having chronic kidney disease (CKD) stages G1/2 and G3, respectively. The overall SVR rate was 97% (224/231). The SVR rates in patients with CKD stages G1, 2, G3a, and G3b were 98.1%, 98.6%, 87.9%, and 100%, respectively, and this therapy was tolerated. Multivariate analysis indicated that renal dysfunction was significantly associated with a non-SVR (odds ratio, 6.963; 95% confidence interval, 1.494-32.41; P = 0.013). The patients with renal dysfunction were older, had advanced liver fibrosis, lower baseline platelet and hemoglobin levels, and a higher rate of RBV dose reduction. CONCLUSIONS: Sofosbuvir and RBV therapy is highly effective and safe for genotype 2 HCV-infected Japanese patients. However, attention should be paid to baseline renal function when SOF- and RBV-containing regimens are used for patients with renal dysfunction.
• Successful endoscopic sphincterotomy for choledocholithiasis in a patient with severe hemophilia A and inhibitors
  Ryo Sugiura, Masaki Kuwatani, Kazumichi Kawakubo, Itsuki Sano, Shin Kato, Tomoyuki Endo, Naoya Sakamoto
  Clinical Journal of Gastroenterology, 11, 3, 188, 192, Springer Tokyo, 01 Jun. 2018, [Peer-reviewed]
  English, Scientific journal
• Endoscopic papillary large balloon dilation and endoscopic papillary balloon dilation both without sphincterotomy for removal of large bile duct stones: A propensity-matched analysis.
  Hakuta R, Kawahata S, Kogure H, Nakai Y, Saito K, Saito T, Hamada T, Takahara N, Uchino R, Mizuno S, Tsujino T, Tada M, Sakamoto N, Isayama H, Koike K
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 31, 1, 59, 68, Jun. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Endoscopic papillary large balloon dilation (EPLBD) without endoscopic sphincterotomy (EST) may facilitate extraction of large bile duct stones through achieving adequate dilation of the ampulla. However, contrary to favorable long-term outcomes after endoscopic papillary balloon dilation (EPBD), that of EPLBD without EST has been little investigated. Therefore, we conducted the current study to evaluate short- and long-term outcomes of EPLBD without EST and EPBD after removal of large bile duct stones (LBDS; ≥10 mm). METHODS: This retrospective study included patients without a previous history of EST, EPBD or EPLBD who underwent EPLBD without EST or EPBD for removal of LBDS. Each patient in the EPLBD without EST group was matched to a patient in the EPBD group using propensity scores. RESULTS: Forty-four patients in each group were matched for the analysis. Baseline characteristics were balanced after propensity matching. Rate of complete stone removal in a single session was higher (80% vs 16%, P < 0.001), number of ERCP sessions (1.3 ± 0.7 vs 2.4 ± 1.5, P < 0.001) and rate of lithotripsy use (30% vs 80%, P < 0.001) were smaller in the matched EPLBD without EST group. Contrary to null between-group differences in early adverse events (P = 0.99), a cumulative rate of late biliary complications was higher in the EPLBD without EST group (P = 0.02). CONCLUSION: EPLBD without EST showed higher efficacy for removal of LBDS but was associated with worse long-term outcomes when compared to EPBD.
• Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma.
  Hiromi Sawai, Nao Nishida, Seik-Soon Khor, Masao Honda, Masaya Sugiyama, Natsumi Baba, Kayoko Yamada, Norie Sawada, Shoichiro Tsugane, Kazuhiko Koike, Yuji Kondo, Hiroshi Yatsuhashi, Shinya Nagaoka, Akinobu Taketomi, Moto Fukai, Masayuki Kurosaki, Namiki Izumi, Jong-Hon Kang, Kazumoto Murata, Keisuke Hino, Sohji Nishina, Akihiro Matsumoto, Eiji Tanaka, Naoya Sakamoto, Koji Ogawa, Kazuhide Yamamoto, Akihiro Tamori, Osamu Yokosuka, Tatsuo Kanda, Isao Sakaida, Yoshito Itoh, Yuichiro Eguchi, Satoshi Oeda, Satoshi Mochida, Man-Fung Yuen, Wai-Kay Seto, Yong Poovorawan, Nawarat Posuwan, Masashi Mizokami, Katsushi Tokunaga
  Scientific reports, 8, 1, 7958, 7958, 21 May 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10-4 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets. Meta-analysis confirmed the association of the three SNPs (rs2523961: OR = 1.73, P = 7.50 × 10-12; rs1110446: OR = 1.79, P = 1.66 × 10-13; and rs3094137: OR = 1.73, P = 7.09 × 10-9). We then performed two-field HLA genotype imputation for six HLA loci using genotyping data to investigate the association between HLA alleles and HCC. HLA allele association testing revealed that HLA-A * 33:03 (OR = 1.97, P = 4.58 × 10-4) was significantly associated with disease progression to HCC. Conditioning analysis of each of the three SNPs on the HLA class I region abolished the association of HLA-A*33:03 with disease progression to HCC. However, conditioning the HLA allele could not eliminate the association of the three SNPs, suggesting that additional genetic factors may exist in the HLA class I region.
• Treatment of hepatitis C in special populations.
  Goki Suda, Koji Ogawa, Kenichi Morikawa, Naoya Sakamoto
  Journal of gastroenterology, 53, 5, 591, 605, May 2018, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Hepatitis C virus (HCV) infection is one of the primary causes of liver cirrhosis and hepatocellular carcinoma. In hemodialysis patients, the rate of HCV infection is high and is moreover associated with a poor prognosis. In liver transplantation patients with HCV infection, recurrent HCV infection is universal, and re-infected HCV causes rapid progression of liver fibrosis and graft loss. Additionally, in patients with HCV and human immunodeficiency virus (HIV) co-infection, liver fibrosis progresses rapidly. Thus, there is an acute need for prompt treatment of HCV infection in these special populations (i.e., hemodialysis, liver transplantation, HIV co-infection). However, until recently, the standard anti-HCV treatment involved the use of interferon-based therapy. In these special populations, interferon-based therapies could not achieve a high rate of sustained viral response and moreover were associated with a higher rate of adverse events. With the development of novel direct-acting antivirals (DAAs), the landscape of anti-HCV therapy for special populations has changed dramatically. Indeed, in special populations treated with interferon-free DAAs, the sustained viral response rate was above 90%, with a lower incidence and severity of adverse events.
• Cecum ulcer is a reliable endoscopic finding in cytomegalovirus colitis concomitant with graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
  Kana Matsuda, Shoko Ono, Marin Ishikawa, Shuichi Miyamoto, Satoshi Abiko, Momoko Tsuda, Keiko Yamamoto, Takahiko Kudo, Yuichi Shimizu, Eiko Hayase, Daigo Hashimoto, Takanori Teshima, Yoshihiro Matsuno, Naoya Sakamoto
  Annals of Hematology, 97, 5, 877, 883, Springer Verlag, 01 May 2018, [Peer-reviewed]
  English, Scientific journal
• A prospective multicenter study evaluating bleeding risk after endoscopic ultrasound-guided fine needle aspiration in patients prescribed antithrombotic agents
  Kazumichi Kawakubo, Kei Yane, Kazunori Eto, Hirotoshi Ishiwatari, Nobuyuki Ehira, Shin Haba, Ryusuke Matsumoto, Keisuke Shinada, Hiroaki Yamato, Taiki Kudo, Manabu Onodera, Toshinori Okuda, Yoko Taya-Abe, Shuhei Kawahata, Kimitoshi Kubo, Yoshimasa Kubota, Masaki Kuwatani, Hiroshi Kawakami, Akio Katanuma, Michihiro Ono, Tsuyoshi Hayashi, Minoru Uebayashi, Naoya Sakamoto
  Gut and Liver, 12, 3, 353, 359, Editorial Office of Gut and Liver, 01 May 2018, [Peer-reviewed]
  English, Scientific journal
• Preoperative biliary drainage using a fully covered self-expandable metallic stent for pancreatic head cancer: A prospective feasibility study
  Osamu Togawa, Hiroyuki Isayama, Hiroshi Kawakami, Yousuke Nakai, Dai Mohri, Tsuyoshi Hamada, Hirofumi Kogure, Kazumichi Kawakubo, Naoya Sakamoto, Kazuhiko Koike, Hiroto Kita
  Saudi Journal of Gastroenterology, 24, 3, 151, 156, Medknow Publications, 01 May 2018, [Peer-reviewed]
  English, Scientific journal
• Mixed ductal-neuroendocrine carcinoma with unique intraductal growth in the main pancreatic duct.
  Hirata K, Kuwatani M, Mitsuhashi T, Sugiura R, Kato S, Kawakubo K, Yamada T, Asano T, Hirano S, Sakamoto N
  Endoscopic ultrasound, 8, 2, 129, 130, May 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal
• Combined use of a two-channel endoscope and a flexible tip catheter for difficult biliary cannulation
  Masaki Kuwatani, Yoshimasa Kubota, Shuhei Kawahata, Kimitoshi Kubo, Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
  International Journal of Gastrointestinal Intervention, 7, 1, 34, 35, Society of Gastrointestinal Intervention, 30 Apr. 2018, [Peer-reviewed]
  Scientific journal
• 遠位胆管金属ステント閉塞への対処 double stentingとpigtail stentによる工夫　　　　　　　　　　　　　　　
  平田 幸司, 桑谷 将城, 杉浦 諒, 加藤 新, 川久保 和道, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.1, 742, 742, (一社)日本消化器内視鏡学会, Apr. 2018
  Japanese
• 胆管ステントの現況と将来 悪性胆道狭窄に対するメタリックステント留置時の乳頭括約筋切開術付加は、ERCP後膵炎の発症を抑制するか　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.1, 612, 612, (一社)日本消化器内視鏡学会, Apr. 2018
  Japanese
• 咽頭癌CRT後遺残再発に対するサルベージEMR/ESD　　　　　　　　　　　　　　　
  安孫子 怜史, 清水 勇一, 石川 麻倫, 松田 可奈, 宮本 秀一, 津田 桃子, 高橋 正和, 山本 桂子, 森 康明, 中川 学, 小野 尚子, 中川 宗一, 工藤 俊彦, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.1, 684, 684, (一社)日本消化器内視鏡学会, Apr. 2018
  Japanese
• Helicobacter pylori除菌後発見胃癌からみた効率的な内視鏡スクリーニング　　　　　　　　　　　　　　　
  津田 桃子, 小野 尚子, 石川 麻倫, 松田 可奈, 宮本 秀一, 安孫子 怜史, 山下 充孝, 高橋 正和, 山本 桂子, 中川 学, 森 康明, 中川 宗一, 工藤 俊彦, 清水 勇一, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.1, 696, 696, (一社)日本消化器内視鏡学会, Apr. 2018
  Japanese
• DPP-IV活性により蛍光を発するプローブによる食道胃接合部腺癌の検出　　　　　　　　　　　　　　　
  山本 桂子, 大西 俊介, 坂本 直哉
  Gastroenterological Endoscopy, 60, Suppl.1, 715, 715, (一社)日本消化器内視鏡学会, Apr. 2018
  Japanese
• Preventive effect of mesenchymal stem cell culture supernatant on luminal stricture after endoscopic submucosal dissection in the rectum of pigs.
  Tsuda M, Ohnishi S, Mizushima T, Hosono H, Yamahara K, Ishikawa M, Abiko S, Katsurada T, Shimizu Y, Sakamoto N
  Endoscopy, 50, 10, 1001, 1016, Apr. 2018, [Peer-reviewed]
  English, Scientific journal
• 肝門部領域胆管癌の胆管水平方向進展診断における経乳頭的鉗子生検の診断能　　　　　　　　　　　　　　　
  杉浦 諒, 桑谷 将城, 平田 幸司, 加藤 新, 川久保 和道, 坂本 直哉
  日本消化器病学会雑誌, 115, 臨増総会, A301, A301, (一財)日本消化器病学会, Mar. 2018
  Japanese
• Safety of Cold Polypectomy for Colorectal Polyps in Patients on Antithrombotic Medication
  Mio Matsumoto, Shinji Yoshii, Taku Shigesawa, Masayoshi Dazai, Manabu Onodera, Mototsugu Kato, Naoya Sakamoto
  Digestion, 97, 1, 76, 81, S. Karger AG, 01 Mar. 2018, [Peer-reviewed]
  English, Scientific journal
• Rapid detection of superficial head and neck squamous cell carcinoma by topically spraying fluorescent probe targeting dipeptidyl peptidase-IV.
  Mizushima T, Ohnishi S, Shimizu Y, Hatanaka Y, Hatanaka KC, Kuriki Y, Kamiya M, Homma A, Yamamoto K, Ono S, Urano Y, Sakamoto N
  Head & neck, 40, 7, 1466, 1475, Mar. 2018, [Peer-reviewed]
• Direct puncture of the ampulla as a modified Endoscopic ultrasound-guided rendezvous technique
  Kazumichi Kawakubo, Masaki Kuwatani, Shin Kato, Ryo Sugiura, Itsuki Sano, Naoya Sakamoto
  Endoscopic Ultrasound, 7, 2, 133, 134, Spring Media, 01 Mar. 2018, [Peer-reviewed]
  English
• Preliminary study of automatic gastric cancer risk classification from photofluorography
  Ren Togo, Kenta Ishihara, Katsuhiro Mabe, Harufumi Oizumi, Takahiro Ogawa, Mototsugu Kato, Naoya Sakamoto, Shigemi Nakajima, Masahiro Asaka, Miki Haseyama
  World Journal of Gastrointestinal Oncology, 10, 2, 62, 70, Baishideng Publishing Group Co, 15 Feb. 2018, [Peer-reviewed]
  English, Scientific journal
• Risk assessment of metachronous squamous cell carcinoma after endoscopic resection for esophageal carcinoma based on the genetic polymorphisms of alcoholdehydrogense-1B aldehyde dehydrogenase-2: temperance reduces the risk
  Satoshi Abiko, Yuichi Shimizu, Shuichi Miyamoto, Marin Ishikawa, Kana Matsuda, Momoko Tsuda, Takeshi Mizushima, Keiko Yamamoto, Shoko Ono, Takahiko Kudo, Kota Ono, Naoya Sakamoto
  Journal of Gastroenterology, 53, 10, 1, 11, Springer Tokyo, 08 Feb. 2018, [Peer-reviewed]
  English, Scientific journal
• 【肝癌-診断・治療の最新知見-】SVR後の発がん予測因子
  中井 正人, 坂本 直哉
  日本臨床, 76, 2, 330, 336, (株)日本臨床社, Feb. 2018
  Japanese
• Induction of IFN-λ3 as an additional effect of nucleotide, not nucleoside, analogues: a new potential target for HBV infection.
  Kazumoto Murata, Mai Asano, Akihiro Matsumoto, Masaya Sugiyama, Nao Nishida, Eiji Tanaka, Taisuke Inoue, Minoru Sakamoto, Nobuyuki Enomoto, Takayoshi Shirasaki, Masao Honda, Shuichi Kaneko, Hiroyuki Gatanaga, Shinichi Oka, Yuki I Kawamura, Taeko Dohi, Yasutaka Shuno, Hideaki Yano, Masashi Mizokami
  Gut, 67, 2, 362, 371, Feb. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, OBJECTIVE: The clinical significance of polymorphisms in the interleukin-28B gene encoding interferon (IFN)-λ3, which has antiviral effects, is known in chronic HCV but not in HBV infection. Thus, we measured IFN-λ3 levels in patients with HBV and investigated its clinical significance and association with nucleos(t)ide (NUC) analogue administration. DESIGN: Serum IFN-λ3 level was measured in 254 patients with HBV with varying clinical conditions using our own high sensitivity method. The resulting values were compared with various clinical variables. In addition, cell lines originating from various organs were cultured with NUCs, and the production of IFN-λ3 was evaluated. RESULTS: Higher serum IFN-λ3 levels were detected in the patients treated with nucleotide analogues (adefovir or tenofovir) compared with those treated with nucleoside analogues (lamivudine or entecavir). There were no other differences in the clinical background between the two groups. A rise in the serum IFN-λ3 levels was observed during additional administration of the nucleotide analogues. In vitro experiments showed that the nucleotide analogues directly and dose-dependently induced IFN-λ3 production only in colon cancer cells. Furthermore, the supernatant from cultured adefovir-treated colon cancer cells significantly induced IFN-stimulated genes (ISGs) and inhibited hepatitis B surface antigen (HBsAg) production in hepatoma cells, as compared with the supernatant from entecavir-treated cells. CONCLUSIONS: We discovered that the nucleotide analogues show an additional pharmacological effect by inducing IFN-λ3 production, which further induces ISGs and results in a reduction of HBsAg production. These findings provide novel insights for HBV treatment and suggest IFN-λ3 induction as a possible target.
• Conditioned Medium Obtained from Amnion-Derived Mesenchymal Stem Cell Culture Prevents Activation of Keloid Fibroblasts.
  Sato C, Yamamoto Y, Funayama E, Furukawa H, Oyama A, Murao N, Hosono H, Kawakubo K, Sakamoto N, Ohnishi S
  Plastic and reconstructive surgery, 141, 2, 390, 398, Feb. 2018, [Peer-reviewed]
  English, Scientific journal
• Add-on effects of fluvastatin in simeprevir/pegylated-interferon/ribavirin combination therapy for patients with genotype 1 hepatitis C virus infection: A randomized controlled study.
  Goki Suda, Jun Ito, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Munenori Okamoto, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Junichi Yoshida, Takashi Meguro, Masatsugu Ohara, Naoki Kawagishi, Megumi Kimura, Machiko Umemura, Takaaki Izumi, Yoko Tsukuda, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 48, 3, E146-E154, E154, Feb. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: The Japan Society of Hepatology guidelines indicate that hepatitis C virus (HCV) protease inhibitor combination therapy with simeprevir (SMV), pegylated-interferon (Peg-IFN), and ribavirin (RBV) is a therapeutic option for patients who fail to respond to a direct direct-acting antiviral-containing regimen. However, treatment outcomes have room for improvement. Fluvastatin (FLV) add-on treatment in Peg-IFN and RBV combination therapy for HCV-infected patients significantly improved the sustained virologic response (SVR), but the add-on effect of FLV on SMV combination therapy is not well understood. METHODS: This was a prospective, randomized, multicenter study in which a total of 61 HCV genotype 1b-infected patients were recruited and 60 eligible patients were randomly allocated to two groups that received 12 weeks of SMV/Peg-IFN/RBV followed by 12 weeks of Peg-IFN/RBV with or without 24 weeks of FLV. The SVR rate and adverse events were compared between the two groups. RESULTS: Thirty-one patients were allocated to the FLV add-on group and 29 patients were allocated to the control group. Baseline clinical factors, including median age, baseline platelet count, alanine aminotransferase level, HCV RNA titer, Fibrosis-4 index, and rate of IL28B minor genotype, were all similar between the two groups. The rapid virologic response, end-of-treatment response rates, SVR rates at 24 weeks after treatment, and safety profiles were also similar between the two groups. CONCLUSIONS: This prospective, randomized, multicenter study indicated that FLV had no add-on effect when given with SMV/Peg-IFN/RBV combination therapy for genotype 1b HCV-infected patients.
• Increased serum C-reactive protein and decreased urinary aquaporin 2 levels are predictive of the efficacy of tolvaptan in patients with liver cirrhosis.
  Masato Nakai, Koji Ogawa, Rei Takeda, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Machiko Umemura, Jun Ito, Takuya Sho, Goki Suda, Kenichi Morikawa, Naoya Sakamoto
  Hepatology research : the official journal of the Japan Society of Hepatology, 48, 3, E311-E319, E319, Feb. 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: Water retention, hepatic ascites, and peripheral edema are significant problems in patients with liver cirrhosis (LC). Although furosemide and spironolactone are commonly used as treatment, they are often insufficient to treat hyponatremia and renal insufficiency in patients with LC. Tolvaptan (TVP) could provide an effective treatment alternative. However, predictive factors of a therapeutic response to TVP are unclear. Our aim was to examine clinical predictors of the response to TVP in patients with LC and water retention. METHODS: Fifty-two patients were treated with TVP, with therapeutic effects judged by a decrease in body weight (≥2 kg) and increase in urinary volume (≥500 mL) within 7 days. Blood biochemical tests were carried out at baseline and post-treatment, including serum soluble CD14 (sCD14) and urinary aquaporin 2 (AQP2) levels. Clinical and laboratory predictive factors of a TVP response were evaluated by univariate and multivariate analyses. RESULTS: The overall response to TVP was 55.8%. On univariate analyses, serum C-reactive protein (CRP) level, the neutrophil-to-lymphocyte ratio, urinary blood urea nitrogen, and urinary AQP2 were predictors of the TVP response, with only serum CRP retained on multivariate analysis. A higher serum sCD14 level was strongly associated with a non-response to TVP. A decrease in urinary AQP2 to undetectable level was associated with a response. CONCLUSION: Tolvaptan provides a rapid and strong effect to improve water retention in patients with LC. Baseline serum sCD14 and CRP levels are useful predictors of a response to TVP, with a decrease in urinary AQP2 during treatment indicating an early response.
• Multicenter observational study on functional bowel disorders diagnosed using Rome III diagnostic criteria in Japan
  Masayoshi Ono, Mototsugu Kato, Shuichi Miyamoto, Momoko Tsuda, Takeshi Mizushima, Shouko Ono, Manabu Nakagawa, Katsuhiro Mabe, Soichi Nakagawa, Shuichi Muto, Yuichi Shimizu, Mineo Kudo, Shinichi Katsuki, Takashi Meguro, Naoya Sakamoto
  Journal of Gastroenterology, 53, 8, 1, 8, Springer Tokyo, 05 Jan. 2018, [Peer-reviewed]
  English, Scientific journal
• Gastric mucosal cracked and cobblestone-like changes resulting from proton pump inhibitor use
  Shuichi Miyamoto, Mototsugu Kato, Momoko Tsuda, Kana Matsuda, Tetsuhito Muranaka, Satoshi Abiko, Masayoshi Ono, Takeshi Mizushima, Saori Omori, Keiko Yamamoto, Katsuhiro Mabe, Shoko Ono, Takahiko Kudo, Yuichi Shimizu, Naoya Sakamoto
  Gastroenterological Endoscopy, 60, 1, 68, 77, Japan Gastroenterological Endoscopy Society, 01 Jan. 2018, [Peer-reviewed]
  Japanese, Scientific journal
• Detection of Superficial Head and Neck Squamous Cell Carcinoma by Topically Spraying Fluorescent Probe Targeting DPP-IV
  Ohnishi Shunsuke, Mizushima Takeshi, Shimizu Yuichi, Hatanaka Yutaka, Hatanaka Kanako, Yamamoto Keiko, Homma Akihiro, Kuriki Yugo, Kamiya Mako, Urano Yasuteru, Sakamoto Naoya
  CANCER SCIENCE, 109, 730, Jan. 2018, [Peer-reviewed]
• Liver steatosis and dyslipidemia after HCV eradication by direct acting antiviral agents are synergistic risks of atherosclerosis.
  Naoki Kawagishi, Goki Suda, Akinobu Nakamura, Megumi Kimura, Osamu Maehara, Kazuharu Suzuki, Akihisa Nakamura, Masatsugu Ohara, Takaaki Izumi, Machiko Umemura, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Yusuke Kudo, Mutsumi Nishida, Hideaki Miyoshi, Naoya Sakamoto
  PloS one, 13, 12, e0209615, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: We comprehensively analyzed how hepatitis C virus (HCV) eradication by interferon (IFN)-free direct-acting-antiviral-agents (DAAs) affects liver steatosis and atherogenic risk. METHODS: Patients treated with IFN-free-DAAs who underwent transient elastography before and at 24-weeks post-treatment, including controlled attenuation parameter (CAP), and achieved sustained viral response (SVR) were enrolled. The association between changes in liver steatosis, lipid-metabolism, and genetic and clinical factors was analyzed. RESULTS: A total of 117 patients were included. The mean CAP and low-density lipoprotein cholesterol (LDL-C) levels were significantly elevated at SVR24. However, baseline LDL-C and CAP values were significantly negatively correlated with changes in these values after HCV eradication, indicating that in patients with high baseline values, the values generally decreased after HCV eradication. Mean small-dense LDL-C (sdLDL-C), which has greater atherogenic potential, was significantly elevated only in patients with both dyslipidemia (LDL-C >140 mg/dL) and liver steatosis (CAP >248 dB/m) at SVR24. Those patients had significant higher baseline BMI, LDL-C, and total-cholesterol levels. CONCLUSIONS: Generally, successful HCV eradication by IFN-free-DAAs decreases CAP and LDL-C in patients with high baseline values. However, elevated LDL-C was accompanied with elevated sdLDL-C only in patients with liver steatosis and dyslipidemia at SVR24; therefore, those patients may require closer monitoring.
• Extracellular Vesicles from Amnion-Derived Mesenchymal Stem Cells Ameliorate Hepatic Inflammation and Fibrosis in Rats.
  Ohara M, Ohnishi S, Hosono H, Yamamoto K, Yuyama K, Nakamura H, Fu Q, Maehara O, Suda G, Sakamoto N
  Stem cells international, 2018, 3212643, 3212643, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Background: There are no approved drug treatments for liver fibrosis and nonalcoholic steatohepatitis (NASH), an advanced stage of fibrosis which has rapidly become a major cause of cirrhosis. Therefore, development of anti-inflammatory and antifibrotic therapies is desired. Mesenchymal stem cell- (MSC-) based therapy, which has been extensively investigated in regenerative medicine for various organs, can reportedly achieve therapeutic effect in NASH via paracrine action. Extracellular vesicles (EVs) encompass a variety of vesicles released by cells that fulfill functions similar to those of MSCs. We herein investigated the therapeutic effects of EVs from amnion-derived MSCs (AMSCs) in rats with NASH and liver fibrosis. Methods: NASH was induced by a 4-week high-fat diet (HFD), and liver fibrosis was induced by intraperitoneal injection of 2 mL/kg 50% carbon tetrachloride (CCl4) twice a week for six weeks. AMSC-EVs were intravenously injected at weeks 3 and 4 in rats with NASH (15 μg/kg) and at week 3 in rats with liver fibrosis (20 μg/kg). The extent of inflammation and fibrosis was evaluated with quantitative reverse transcription polymerase chain reaction and immunohistochemistry. The effect of AMSC-EVs on inflammatory and fibrogenic response was investigated in vitro. Results: AMSC-EVs significantly decreased the number of Kupffer cells (KCs) in the liver of rats with NASH and the mRNA expression levels of inflammatory cytokines such as tumor necrosis factor- (Tnf-) α, interleukin- (Il-) 1β and Il-6, and transforming growth factor- (Tgf-) β. Furthermore, AMSC-EVs significantly decreased fiber accumulation, KC number, and hepatic stellate cell (HSC) activation in rats with liver fibrosis. In vitro, AMSC-EVs significantly inhibited KC and HSC activation and suppressed the lipopolysaccharide (LPS)/toll-like receptor 4 (TLR4) signaling pathway. Conclusions: AMSC-EVs ameliorated inflammation and fibrogenesis in a rat model of NASH and liver fibrosis, potentially by attenuating HSC and KC activation. AMSC-EV administration should be considered as a new therapeutic strategy for chronic liver disease.
• A Case of Olmesartan-associated Sprue-like Enteropathy
  Kazunori Nagashima, Takehiko Katsurada, Naoya Sakamoto
  Clinical Gastroenterology and Hepatology, 16, 10, A45, A46, W.B. Saunders, 2018, [Peer-reviewed]
  English, Scientific journal
• Daclatasvir and asunaprevir in hemodialysis patients with hepatitis C virus infection: a nationwide retrospective study in Japan.
  Goki Suda, Norihiro Furusyo, Hidenori Toyoda, Yoshiiku Kawakami, Hiroki Ikeda, Michihiro Suzuki, Keiko Arataki, Nami Mori, Keiji Tsuji, Yoshio Katamura, Koichi Takaguchi, Toru Ishikawa, Kunihiko Tsuji, Noritomo Shimada, Atsushi Hiraoka, Sho Yamsaki, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Kanji Kato, Yoshiyuki Ueno, Etsuko Iio, Yasuhito Tanaka, Masayuki Kurosaki, Takashi Kumada, Kazuaki Chayama, Naoya Sakamoto
  Journal of gastroenterology, 53, 1, 119, 128, Jan. 2018, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: Hepatitis C virus (HCV) infection is common in hemodialysis patients and worsens their prognosis, while antiviral therapy options are limited. Recently, clinical trial and real-world, small-scale studies have reported excellent responses to direct-acting antivirals in patients with advanced chronic kidney diseases. However, real-world, large-scale data were lacking. This large multicenter analysis included HCV-infected hemodialysis patients receiving combination therapy with a nonstructural protein 5A (NS5A) inhibitor, daclatasvir (DCV), and a protease inhibitor, asunaprevir (ASV). METHODS: Twenty-three centers in Japan participated in this study of 123 hemodialysis patients with genotype 1 HCV infection, who received DCV/ASV combination therapy between November 2014 and March 2016. We collected and analyzed data relating to treatment outcome, baseline clinical information, laboratory measurements (during and after the treatment), and adverse events. RESULTS: Thirty-nine patients (31.7%) had advanced liver fibrosis, 12 (9.8%) had histories of hepatocellular carcinoma (HCC), and 18 (14.6%) had baseline resistance-associated variants (RAVs) of NS5A. The overall sustained virological response (SVR)12 rate was 95.9% (118/123). Notably, all patients with HCC and 94.4% (17/18) of those with NS5A RAVs achieved SVR12. Significant factors associated with non-SVR were advanced fibrosis and the interleukin-28B non-TT genotype at rs8099917. Four patients (3.3%) discontinued therapy because of adverse events including elevated serum alanine transaminase levels (n = 2), rash (n = 1), and HCC (n = 1); all of these achieved SVR12. CONCLUSIONS: This real-world, nationwide study revealed that DCV/ASV combination therapy was safe and highly effective for hemodialysis patients with genotype 1 HCV infections. This study was registered at the UMIN Clinical Trials Registry (UMIN000024227).
• Mesenchymal stem cell therapy for acute and chronic pancreatitis
  Kazumichi Kawakubo, Shunsuke Ohnishi, Masaki Kuwatani, Naoya Sakamoto
  Journal of Gastroenterology, 53, 1, 1, 5, Springer Tokyo, 01 Jan. 2018, [Peer-reviewed]
  English
• Safety and efficacy of elbasvir/grazoprevir for the treatment of chronic hepatitis C: current evidence.
  Kenichi Morikawa, Akihisa Nakamura, Tomoe Shimazaki, Naoya Sakamoto
  Drug design, development and therapy, 12, 2749, 2756, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Treatments for hepatitis C virus (HCV) have advanced greatly, becoming more efficacious with fewer adverse events, due to the availability of direct-acting antiviral agents, which target specific steps in the HCV life cycle. Recently, a combination regimen consisting of the HCV nonstructural protein 5A inhibitor elbasvir (EBR) and the HCV NS3/4A protease inhibitor grazoprevir (GZR) was approved for the treatment of patients with chronic HCV and genotypes (Gts) 1 and 4 in various countries. In Phase III trials, the combination of EBR/GZR (fixed-dose combination table or single agent) for 12 or 16 weeks of treatment with or without ribavirin resulted in a high sustained virological response at 12 weeks in treatment-naïve and treatment-experienced patients with HCV Gt 1a, 1b, 4, or 6, including special populations, such as individuals with advanced chronic kidney disease, HCV-HIV coinfection, and compensated cirrhosis. In this review, we focus on the mode of action, pharmacokinetics, clinical applications, efficacy, and safety profile of EBR/GZR, including special populations who have been considered refractory from the extensive evidence of clinical trials.
• Conditioned Medium from Human Amnion-Derived Mesenchymal Stem Cells Regulates Activation of Primary Hepatic Stellate Cells.
  Fu Q, Ohnishi S, Sakamoto N
  Stem cells international, 2018, 4898152, 4898152, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Mesenchymal stem cells (MSCs), or multipotent mesenchymal stromal cells, are present in almost all organs and tissues, including the amnion. Human amnion-derived mesenchymal stem cell (hAMSC) transplantation has been reported to ameliorate liver fibrosis in animal models. However, the mechanism for the prevention of liver fibrosis is poorly understood. In this study, we investigated the effects, and underlying mechanisms, of a conditioned medium obtained from hAMSC cultures (hAMSC-CM) on a primary culture of rat hepatic stellate cells (HSCs). We observed that in routine culture, hAMSC-CM in HSCs significantly inhibited the expression of alpha-smooth muscle actin (α-SMA), an activation marker of HSCs, and the production of collagen type 1 (COL1), a dominant component of the extracellular matrix (ECM) in the culture medium. In addition, hAMSC-CM upregulated the expression of ECM degradation-related genes, such as metalloproteinase- (Mmp-) 2, Mmp-9, Mmp-13, and tissue inhibitor of metalloproteinase- (Timp-) 1; however, it did not affect the expression of collagen type 1α1 (Col1a1). These regulatory effects on HSCs were concentration-dependent. A cell proliferation assay indicated that hAMSC-CM significantly suppressed HSC proliferation and downregulated the expression of cyclin B (Ccnb), a proliferation-related gene. Transforming growth factor-beta (TGF-β) treatment further activated HSCs and hAMSC-CM significantly inhibited the upregulation of α-Sma and Col1a1 induced by TGF-β. These findings demonstrated that hAMSC-CM can modulate HSC function via secretory factors and provide a plausible explanation for the protective role of hAMSCs in liver fibrosis.
• Macrophage-Derived Extracellular Vesicles Induce Long-Lasting Immunity Against Hepatitis C Virus Which Is Blunted by Polyunsaturated Fatty Acids.
  Chengcong Cai, Benjamin Koch, Kenichi Morikawa, Goki Suda, Naoya Sakamoto, Sabrina Rueschenbaum, Sami Akhras, Julia Dietz, Eberhard Hildt, Stefan Zeuzem, Christoph Welsch, Christian M Lange
  Frontiers in immunology, 9, 723, 723, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Extracellular vesicles (EVs) are increasingly recognized as important mediators of intercellular communication. In this study, we aimed to further characterize the role of macrophage-derived EVs in immune responses against hepatitis C virus (HCV) and the potential of polyunsaturated fatty acids (PUFAs) to modulate this modality of innate immunity. To this end, EVs were isolated from interferon-stimulated macrophage cultures or from serum of patients with acute or chronic hepatitis C. EVs were characterized by electron microscopy, flow cytometry, RNA-sequencing, and Western blot analysis. The effect of EVs on replication of HCV was assessed in coculture models. Functional analyses were performed to assess the impact of PUFAs on EV-mediated antiviral immunity. We found that macrophages secreted various cytokines shortly after stimulation with type I and II IFN, which orchestrated a fast but short-lasting antiviral state. This rapid innate immune answer was followed by the production of macrophage-derived EVs, which induced a late, but long-lasting inhibitory effect on HCV replication. Of note, exposure of macrophages to PUFAs, which are important regulators of immune responses, dampened EV-mediated antiviral immune responses. Finally, EVs from patients with hepatitis C exhibited long-lasting antiviral activities during IFN therapy as well. The antiviral effect of EVs from Caucasian and Japanese patients differed, which may be explained by different nutritional uptake of PUFAs. In conclusion, our data indicate that macrophage-derived EVs mediate long-lasting inhibitory effects on HCV replication, which may bridge the time until efficient adaptive immune responses are established, and which can be blunted by PUFAs.
• Prognostic and Predictive Value of HER2 Amplification in Patients With Metastatic Colorectal Cancer
  Kentaro Sawada, Yoshiaki Nakamura, Takeharu Yamanaka, Yasutoshi Kuboki, Daisuke Yamaguchi, Satoshi Yuki, Takayuki Yoshino, Yoshito Komatsu, Naoya Sakamoto, Wataru Okamoto, Satoshi Fujii
  Clinical Colorectal Cancer, 17, 3, 198, 205, Elsevier Inc., 2018, [Peer-reviewed]
  English, Scientific journal
• Evaluation of amnion-derived mesenchymal stem cells for treatment-resistant moderate Crohn's disease: study protocol for a phase I/II, dual-centre, open-label, uncontrolled, dose-response trial.
  Shinsuke Otagiri, Shunsuke Ohnishi, Arisa Miura, Hiroshi Hayashi, Izumi Kumagai, Yoichi M Ito, Takehiko Katsurada, Shiro Nakamura, Rika Okamoto, Kenichi Yamahara, Kyu Yong Cho, Toshiyuki Isoe, Norihiro Sato, Naoya Sakamoto
  BMJ open gastroenterology, 5, 1, e000206, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Introduction: The medical treatment options for patients with Crohn's disease (CD) are limited and patients resistant to those therapies are left requiring surgical operations that usually only achieve some symptomatic relief. Mesenchymal stem cells (MSC) have been shown to be effective for the treatment of CD, and we have demonstrated in animal experiments that human amnion-derived MSCs (AMSC) are a potential new therapeutic strategy. Therefore, we designed this study to investigate the safety and efficacy of AMSCs in patients with treatment-resistant CD. Methods and analysis: This is the protocol for an ongoing phase I/II, dual-centre, open-label, uncontrolled, dose-response study. The estimated enrolment is 6-12 patients with treatment-resistant, moderate CD. A dose of 1.0×106 cells/kg will be administered intravenously in the low-dose group at days 0 and 7. After confirming the safety of low-dose administration, a dose of 4.0×106 cells/kg will be administered intravenously in the high-dose group on days 0 and 7. The primary endpoint will measure the occurrence of adverse events related to acute infusion toxicity, and secondary endpoints will include long-term adverse events and efficacy of AMSC administration. Ethics and dissemination: The Institutional Review Board of Hokkaido University Hospital approved this study protocol (approval number H29-6). A report releasing study results will be submitted to an appropriate journal. Discussion: This study is the first to investigate the safety and efficacy of AMSC use for CD treatment. Our results will advance studies on more efficient and convenient methods to overcome the limits of available CD treatments. Trial registration number: UMIN000029841.
• Palmitoylethanolamide Ameliorates Carbon Tetrachloride-Induced Liver Fibrosis in Rats.
  Ohara M, Ohnishi S, Hosono H, Yamamoto K, Fu Q, Maehara O, Suda G, Sakamoto N
  Frontiers in pharmacology, 9, 709, 709, 2018, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Background: Liver fibrosis is a complex inflammatory and fibrogenic process, and the progression of fibrosis leads to cirrhosis. The only therapeutic approaches are the removal of injurious stimuli and liver transplantation. Therefore, the development of anti-fibrotic therapies is desired. Palmitoylethanolamide (PEA) is an endogenous fatty acid amide belonging to the N-acylethanolamines family and contained in foods such as egg yolks and peanuts. PEA has therapeutic anti-inflammatory, analgesic, and neuroprotective effects. However, the effects and roles of PEA in liver fibrosis remain unknown. Here we investigated the therapeutic effects of PEA in rats with liver fibrosis. Methods: We conducted in vitro experiments to investigate the effects of PEA on the activation of hepatic stellate cells (HSCs, LX-2). Liver fibrosis was induced by an intraperitoneal injection of 1.5 mL/kg of 50% carbon tetrachloride twice a week for 4 weeks. Beginning at 3 weeks, PEA (20 mg/kg) was intraperitoneally injected thrice a week for 2 weeks. Then rats were sacrificed and we performed histological and quantitative reverse-transcription polymerase chain reaction analyses. Results: The expression of α-smooth muscle actin (SMA) induced by transforming growth factor (TGF)-β1 in HSCs was significantly downregulated by PEA. PEA treatment inhibited the TGF-β1-induced phosphorylation of SMAD2 in a dose-dependent manner, and upregulated the expression of SMAD7. The reporter gene assay demonstrated that PEA downregulated the transcriptional activity of the SMAD complex upregulated by TGF-β1. Administration of PEA significantly reduced the fibrotic area, deposition of type I collagen, and activation of HSCs and Kupffer cells in rats with liver fibrosis. Conclusion: Activation of HSCs was significantly decreased by PEA through suppression of the TGF-β1/SMAD signaling pathway. Administration of PEA produced significant improvement in a rat model of liver fibrosis, possibly by inhibiting the activation of HSCs and Kupffer cells. PEA may be a potential new treatment for liver fibrosis.
• Effects of human amnion-derived mesenchymal stem cells and conditioned medium in rats with sclerosing cholangitis.
  Sugiura R, Ohnishi S, Ohara M, Ishikawa M, Miyamoto S, Onishi R, Yamamoto K, Kawakubo K, Kuwatani M, Sakamoto N
  American journal of translational research, 10, 7, 2102, 2114, 2018, [Peer-reviewed]
  English, Scientific journal
• Parietal Cell Protrusions and Dilated Oxyntic Glands from Use of Vonoprazan
  Shuichi Miyamoto, Yoshihiro Matsuno, Mototsugu Kato, Takahiko Kudo, Shouko Ono, Yuichi Shimizu, Naoya Sakamoto
  AMERICAN JOURNAL OF GASTROENTEROLOGY, 112, 12, 1899, 1901, Dec. 2017, [Peer-reviewed]
  English
• Study protocol of HGCSG1404 SNOW study: a phase I/II trial of combined chemotherapy of S-1, nab-paclitaxel and oxaliplatin administered biweekly to patients with advanced gastric cancer
  Yasuyuki Kawamoto, Yoshito Komatsu, Satoshi Yuki, Kentaro Sawada, Tetsuhito Muranaka, Kazuaki Harada, Hiroshi Nakatsumi, Hiraku Fukushima, Atsushi Ishiguro, Masayoshi Dazai, Kazuteru Hatanaka, Michio Nakamura, Ichiro Iwanaga, Minoru Uebayashi, Susumu Sogabe, Yoshimitsu Kobayashi, Takuto Miyagishima, Kota Ono, Naoya Sakamoto, Yuh Sakata
  BMC CANCER, 17, 1, 837, Dec. 2017, [Peer-reviewed]
  English, Scientific journal
• Endocytoscopy of Superficial Nonampullary Duodenal Epithelial Tumor: Two Cases of Tubular Adenocarcinoma and Adenoma
  Shuichi Miyamoto, Takahiko Kudo, Satoshi Abiko, Shouko Ono, Yuichi Shimizu, Yoshihiro Matsuno, Naoya Sakamoto
  AMERICAN JOURNAL OF GASTROENTEROLOGY, 112, 11, 1638, 1638, Nov. 2017, [Peer-reviewed]
  English
• Hepatitis B virus reactivation during hepatitis C direct-acting antiviral therapy in patients with previous HBV infection
  Naoki Kawagishi, Goki Suda, Masahiro Onozawa, Megumi Kimura, Osamu Maehara, Jun Ito, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  JOURNAL OF HEPATOLOGY, 67, 5, 1106, 1108, Nov. 2017, [Peer-reviewed]
  English
• Fibroblast growth factor-2-mediated FGFR/Erk signaling supports maintenance of cancer stem-like cells in esophageal squamous cell carcinoma
  Osamu Maehara, Goki Suda, Mitsuteru Natsuizaka, Shunsuke Ohnishi, Yoshito Komatsu, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Tomoe Shimazaki, Megumi Kimura, Ayaka Asano, Yoshiyuki Fujimoto, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Seiji Naganuma, Kelly A. Whelan, Hiroshi Nakagawa, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
  CARCINOGENESIS, 38, 11, 1073, 1083, Nov. 2017, [Peer-reviewed]
  English, Scientific journal
• Safety and efficacy of daclatasvir and asunaprevir in hepatitis C virus-infected patients with renal impairment
  Goki Suda, Atsushi Nagasaka, Yoshiya Yamamoto, Ken Furuya, Kenichi Kumagai, Mineo Kudo, Katsumi Terashita, Tomoe Kobayashi, Izumi Tsunematsu, Junichi Yoshida, Takashi Meguro, Megumi Kimura, Jun Ito, Machiko Umemura, Takaaki Izumi, Seiji Tsunematsu, Fumiyuki Sato, Yoko Tsukuda, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  HEPATOLOGY RESEARCH, 47, 11, 1127, 1136, Oct. 2017, [Peer-reviewed]
  English, Scientific journal
• Retreatment with sofosbuvir, ledipasvir, and add-on ribavirin for patients who failed daclatasvir and asunaprevir combination therapy
  Goki Suda, Koji Ogawa, Yoshiya Yamamoto, Masaki Katagiri, Ken Furuya, Kenichi Kumagai, Jun Konno, Megumi Kimura, Naoki Kawagishi, Masatsugu Ohara, Machiko Umemura, Jun Ito, Takaaki Izumi, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Akihito Tsubota, Noritomo Shimada, Etsuko Iio, Yasuhito Tanaka, Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY, 52, 10, 1122, 1129, Oct. 2017, [Peer-reviewed]
  English, Scientific journal
• Effect on Helicobacter pylori eradication therapy against gastric cancer in Japan
  Momoko Tsuda, Masahiro Asaka, Mototsugu Kato, Rumiko Matsushima, Kenji Fujimori, Kozo Akino, Shogo Kikuchi, Yingsong Lin, Naoya Sakamoto
  HELICOBACTER, 22, 5, Oct. 2017, [Peer-reviewed]
  English, Scientific journal
• Hepatitis C virus-induced innate immune responses in human iPS cell-derived hepatocyte-like cells
  Fuminori Sakurai, Takemaru Kunito, Kazuo Takayama, Rina Hashimoto, Masashi Tachibana, Naoya Sakamoto, Takaji Wakita, Hiroyuki Mizuguchi
  VIRUS RESEARCH, 242, 7, 15, Oct. 2017, [Peer-reviewed]
  English, Scientific journal
• Dipeptidylpeptidase-IVの酵素活性により蛍光を発するプローブによる頭頸部表在癌の検出　　　　　　　　　　　　　　　
  大西 俊介, 水島 健, 清水 勇一, 畑中 豊, 畑中 佳奈子, 山本 桂子, 本間 明宏, 栗木 優五, 神谷 真子, 浦野 泰照, 坂本 直哉
  日本癌学会総会記事, 76回, P, 2320, 日本癌学会, Sep. 2017
  English
• PSM解析による切除不能転移性大腸癌における原発巣切除の意義の検討　　　　　　　　　　　　　　　
  市川 伸樹, 本間 重紀, 吉田 雅, 大野 陽介, 川村 秀樹, 川本 泰之, 中積 宏之, 結城 敏志, 小松 嘉人, 石川 倫啓, 江本 慎, 小笠原 和宏, 曽我部 進, 中西 一彰, 数井 啓蔵, 古家 乾, 上泉 洋, 加藤 寛士, 坂本 直哉, 武冨 紹信
  日本大腸肛門病学会雑誌, 70, 抄録号, A137, A137, (一社)日本大腸肛門病学会, Sep. 2017
  Japanese
• 粘膜下局注併用APCと標準的APCの生体ブタ組織に対する焼灼効果の検討　　　　　　　　　　　　　　　
  安孫子 怜史, 清水 勇一, 大西 俊介, 水島 健, 加藤 麻倫, 松田 可奈, 宮本 秀一, 津田 桃子, 山本 桂子, 小野 尚子, 工藤 俊彦, 坂本 直哉
  Gastroenterological Endoscopy, 59, Suppl.2, 2223, 2223, (一社)日本消化器内視鏡学会, Sep. 2017
  Japanese
• Dipeptidylpeptidase-IVの酵素活性により蛍光を発するプローブによる頭頸部表在癌の検出　　　　　　　　　　　　　　　
  大西 俊介, 水島 健, 清水 勇一, 畑中 豊, 畑中 佳奈子, 山本 桂子, 本間 明宏, 栗木 優五, 神谷 真子, 浦野 泰照, 坂本 直哉
  日本癌学会総会記事, 76回, P, 2320, 日本癌学会, Sep. 2017
  English
• Oral administration of conditioned medium obtained from mesenchymal stem cell culture prevents subsequent stricture formation after esophageal submucosal dissection in pigs
  Takeshi Mizushima, Shunsuke Ohnishi, Hidetaka Hosono, Kenichi Yamahara, Momoko Tsuda, Yuichi Shimizu, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 86, 3, 542, U356, Sep. 2017, [Peer-reviewed]
  English, Scientific journal
• A Phase I Study of Combination Therapy with Sorafenib and 5-Fluorouracil in Patients with Advanced Hepatocellular Carcinoma.
  Takuya Sho, Mitsuru Nakanishi, Kenichi Morikawa, Masatsugu Ohara, Naoki Kawagishi, Takaaki Izumi, Machiko Umemura, Jun Ito, Masato Nakai, Goki Suda, Koji Ogawa, Makoto Chuma, Takashi Meguro, Michio Nakamura, Atsushi Nagasaka, Hiromasa Horimoto, Yoshiya Yamamoto, Naoya Sakamoto
  Drugs in R&D, 17, 3, 381, 388, Sep. 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIMS: Sorafenib is the first molecular targeted drug approved for the treatment of advanced hepatocellular carcinoma (HCC) and is a potent small molecule inhibitor of multiple kinases. Combination therapy with sorafenib and other cytotoxic agents for HCC may result in additive anticancer activity. The purpose of this phase I study was to investigate the safety and tolerability of combination therapy with sorafenib and 5-fluorouracil (5-FU) and to determine the optimum dose of 5-FU for a phase II trial. METHODS: This phase I study used a conventional 3 + 3 dose-escalation design. The primary endpoint was to determine the maximum tolerated dose (MTD) of 5-FU in combination with sorafenib and to determine the recommended dosage (RD) for phase II. The secondary endpoints evaluated were toxicity and the tumor response rate. All patients received 800 mg of sorafenib daily and three different dosages of 5-FU (250, 350, and 450 mg/m2/day) for 20 days by intravenous infusion in 1 month as one cycle. RESULTS: Twelve patients with advanced HCC were evaluated. The MTD of 5-FU in combination with sorafenib was 450 mg/m2/day, and 350 mg/m2/day was selected as the RD for a phase II study. Thrombocytopenia, stomatitis, and hand-foot skin reaction were observed as grade 3 adverse events. Nine patients achieved stable disease (75%), and three patients (25%) were judged to have progressive disease. The disease control rate was 75%. CONCLUSIONS: Combination therapy with sorafenib and 5-FU appears to be well tolerated and may have the potential to be an option for advanced HCC.
• 転移性および原発性病変による肝門部悪性胆管狭窄に対する内視鏡的胆管ドレナージ術の臨床成績
  杉浦 諒, 桑谷 将城, 佐野 逸紀, 加藤 新, 川久保 和道, 坂本 直哉
  胆道, 31, 3, 566, 566, (一社)日本胆道学会, Aug. 2017
  Japanese
• Brain micro-inflammation at specific vessels dysregulates organ-homeostasis via the activation of a new neural circuit
  Yasunobu Arima, Takuto Ohki, Naoki Nishikawa, Kotaro Higuchi, Mitsutoshi Ota, Yuki Tanaka, Junko Nio-Kobayashi, Mohamed Elfeky, Ryota Sakai, Yuki Mori, Tadafumi Kawamoto, Andrea Stofkova, Yukihiro Sakashita, Yuji Morimoto, Masaki Kuwatani, Toshihihiko Iwanaga, Yoshichika Yoshioka, Naoya Sakamoto, Akihiko Yoshimura, Mitsuyoshi Takiguchi, Saburo Sakoda, Marco Prinz, Daisuke Kamimura, Masaaki Murakami
  ELIFE, 6, Aug. 2017, [Peer-reviewed]
  English, Scientific journal
• Utility of Assessing the Number of Mutated KRAS, CDKN2A, TP53, and SMAD4 Genes Using a Targeted Deep Sequencing Assay as a Prognostic Biomarker for Pancreatic Cancer (vol 46, pg 335, 2017)
  H. Hayashi, T. Kohno, H. Ueno, N. Sakamoto
  PANCREAS, 46, 7, E64, E64, Aug. 2017, [Peer-reviewed]
  English
• The first case report of infective endocarditis caused by Gemella taiwanensis
  Mayu Hikone, Naoya Sakamoto, Masayuki Ota, Takuya Washino, Ken-ichiro Kobayashi, Sentaro Iwabuchi, Haruko Kazama, Akiko Kounosu, Kumiko Negishi, Yusuke Ainoda, Shigekazu Iguchi, Atsushi Yoshida, Ken Kikuchi, Kenji Ohnishi
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 23, 8, 567, 571, Aug. 2017, [Peer-reviewed]
  English, Scientific journal
• Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on postendoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial
  Shin Kato, Masaki Kuwatani, Ryo Sugiura, Itsuki Sano, Kazumichi Kawakubo, Kota Ono, Naoya Sakamoto
  BMJ OPEN, 7, 8, e017160, Aug. 2017, [Peer-reviewed]
  English, Scientific journal
• Retinoid derivative Tp80 exhibits anti-hepatitis C virus activity through restoration of GI-GPx expression
  Bao Ngoc Nguyen, Yukiko Okuno, Masahiko Ajiro, Kei Iida, Masatsugu Denawa, Makoto Yamamoto, Naoya Sakamoto, Hiroyuki Kagechika, Masatoshi Hagiwara
  JOURNAL OF MEDICAL VIROLOGY, 89, 7, 1224, 1234, Jul. 2017, [Peer-reviewed]
  English, Scientific journal
• Fluid shear stress combined with shear stress spatial gradients regulates vascular endothelial morphology
  Daisuke Yoshino, Naoya Sakamoto, Masaaki Sato
  INTEGRATIVE BIOLOGY, 9, 7, 584, 594, Jul. 2017, [Peer-reviewed]
  English, Scientific journal
• Vonoprazan improves the efficacy of Helicobacter pylori eradication therapy with a regimen consisting of clarithromycin and metronidazole in patients allergic to penicillin
  Shoko Ono, Mototsugu Kato, Soichi Nakagawa, Katsuhiro Mabe, Naoya Sakamoto
  HELICOBACTER, 22, 3, Jun. 2017, [Peer-reviewed]
  English, Scientific journal
• Endoscopic ultrasonography features of gastric mucosal cobblestone-like changes from a proton-pump inhibitor
  Shuichi Miyamoto, Takahiko Kudo, Mototsugu Kato, Kana Matsuda, Satoshi Abiko, Momoko Tsuda, Takeshi Mizushima, Keiko Yamamoto, Shoko Ono, Yuichi Shimizu, Naoya Sakamoto
  Clinical Journal of Gastroenterology, 10, 3, 220, 223, Springer Tokyo, 01 Jun. 2017, [Peer-reviewed]
  English, Scientific journal
• Interferon-free therapy with sofosbuvir plus ribavirin for successful treatment of genotype 2 hepatitis C virus with lichen planus: a case report.
  Ayumu Yoshikawa, Katsumi Terashita, Kenichi Morikawa, Soichiro Matsuda, Takahiro Yamamura, Koichiro Sarashina, Shintaro Nakano, Yoshimitsu Kobayashi, Susumu Sogabe, Kazuhiro Takahashi, Shin Haba, Hisashi Oda, Tatsuro Takahashi, Takuto Miyagishima, Naoya Sakamoto
  Clinical journal of gastroenterology, 10, 3, 270, 273, Jun. 2017, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, Hepatitis C virus (HCV) infection remains the main cause of liver disease and can lead to chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV may also develop extrahepatic manifestations in the skin, eyes, joints, kidneys, nervous system, and immune system. In fact, several studies reported that up to 70% of HCV patients experienced extrahepatic manifestations. Lichen planus (LP), which is an immune system disorder that is triggered by viral infections, allergens, and stress, can affect the skin, mouth, nails, and scalp. The association of LP with HCV has been reported, but the effect of HCV treatment on LP remission is controversial. We encountered a 53-year-old man with HCV genotype 2a and LP that were successfully treated with sofosbuvir and ribavirin for 12 weeks. After treatment, he achieved sustained virological response against HCV and remission of erosive LP lesions on the lip. In the era of interferon (IFN)-based treatment for HCV, exacerbation of autoimmune diseases is a common adverse event. Therefore, use of an IFN-free regimen of direct-acting antivirals for HCV might prevent the extrahepatic manifestation of an immune disorder.
• Comparison of efficacy and toxicity of FOLFIRINOX and gemcitabine with nab-paclitaxel in unresectable pancreatic cancer
  Tetsuhito Muranaka, Masaki Kuwatani, Yoshito Komatsu, Kentaro Sawada, Hiroshi Nakatsumi, Yasuyuki Kawamoto, Satoshi Yuki, Yoshimasa Kubota, Kimitoshi Kubo, Shuhei Kawahata, Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
  Journal of Gastrointestinal Oncology, 8, 3, 566, 571, AME Publishing Company, 01 Jun. 2017, [Peer-reviewed]
  English, Scientific journal
• ウイルソン病における各診断ガイドラインの有用性の検討
  中井 正人, 森川 賢一, 大原 正嗣, 川岸 直樹, 出水 孝章, 梅村 真知子, 伊藤 淳, 常松 聖司, 佐藤 史幸, 荘 拓也, 須田 剛生, 小川 浩司, 坂本 直哉
  日本消化器病学会雑誌, 114, 5, 839, 845, (一財)日本消化器病学会, May 2017, [Peer-reviewed]
  Japanese
• Rapid Detection of Superficial Head and Neck Squamous Cell Carcinoma by Topically Spraying Fluorescent Probe Targeting Dipeptidylpeptidase-Iv
  Shunsuke Ohnishi, Takeshi Mizushima, Yuichi Shimizu, Yutaka Hatanaka, Kanako Hatanaka, Keiko Yamamoto, Akihiro Homma, Yugo Kuriki, Mako Kamiya, Yasuteru Urano, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 85, 5, AB530, AB530, May 2017, [Peer-reviewed]
  English
• Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection.
  Kentaro Matsuura, Hiromi Sawai, Kazuho Ikeo, Shintaro Ogawa, Etsuko Iio, Masanori Isogawa, Noritomo Shimada, Atsumasa Komori, Hidenori Toyoda, Takashi Kumada, Tadashi Namisaki, Hitoshi Yoshiji, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Asahina, Masayuki Kurosaki, Namiki Izumi, Nobuyuki Enomoto, Atsunori Kusakabe, Eiji Kajiwara, Yoshito Itoh, Tatsuya Ide, Akihiro Tamori, Misako Matsubara, Norifumi Kawada, Ken Shirabe, Eiichi Tomita, Masao Honda, Shuichi Kaneko, Sohji Nishina, Atsushi Suetsugu, Yoichi Hiasa, Hisayoshi Watanabe, Takuya Genda, Isao Sakaida, Shuhei Nishiguchi, Koichi Takaguchi, Eiji Tanaka, Junichi Sugihara, Mitsuo Shimada, Yasuteru Kondo, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Katsushi Tokunaga, Yasuhito Tanaka
  Gastroenterology, 152, 6, 1383, 1394, May 2017, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND & AIMS: There is still a risk for hepatocellular carcinoma (HCC) development after eradication of hepatitis C virus (HCV) infection with antiviral agents. We investigated genetic factors associated with the development of HCC in patients with a sustained virologic response (SVR) to treatment for chronic HCV infection. METHODS: We obtained genomic DNA from 457 patients in Japan with a SVR to interferon-based treatment for chronic HCV infection from 2007 through 2015. We conducted a genome-wide association study (GWAS), followed by a replication analysis of 79 candidate single nucleotide polymorphisms (SNPs) in an independent set of 486 patients in Japan. The study end point was HCC diagnosis or confirmation of lack of HCC (at follow-up examinations until December 2014 in the GWAS cohort, and until January 2016 in the replication cohort). We collected clinical and laboratory data from all patients. We analyzed expression levels of candidate gene variants in human hepatic stellate cells, rats with steatohepatitis caused by a choline-deficient L-amino acid-defined diet, and a mouse model of liver injury caused by administration of carbon tetrachloride. We also analyzed expression levels in liver tissues of patients with chronic HCV infection with different stages of fibrosis or tumors vs patients without HCV infection (controls). RESULTS: We found a strong association between the SNP rs17047200, located within the intron of the tolloid like 1 gene (TLL1) on chromosome 4, and development of HCC; there was a genome-wide level of significance when the results of the GWAS and replication study were combined (odds ratio, 2.37; P = 2.66 × 10-8). Multivariate analysis showed rs17047200 AT/TT to be an independent risk factor for HCC (hazard ratio, 1.78; P = .008), along with male sex, older age, lower level of albumin, advanced stage of hepatic fibrosis, presence of diabetes, and higher post-treatment level of α-fetoprotein. Combining the rs17047200 genotype with other factors, we developed prediction models for HCC development in patients with mild or advanced hepatic fibrosis. Levels of TLL1 messenger RNA (mRNA) in human hepatic stellate cells increased with activation. Levels of Tll1 mRNA increased in liver tissues of rodents with hepatic fibrogenesis compared with controls. Levels of TLL1 mRNA increased in liver tissues of patients with progression of fibrosis. Gene expression levels of TLL1 short variants, including isoform 2, were higher in patients with rs17047200 AT/TT. CONCLUSIONS: In a GWAS, we identified the association between the SNP rs17047200, within the intron of TLL1, and development of HCC in patients who achieved an SVR to treatment for chronic HCV infection. We found levels of Tll1/TLL1 mRNA to be increased in rodent models of liver injury and liver tissues of patients with fibrosis, compared with controls. We propose that this SNP might affect splicing of TLL1 mRNA, yielding short variants with high catalytic activity that accelerates hepatic fibrogenesis and carcinogenesis. Further studies are needed to determine how rs17047200 affects TLL1 mRNA levels, splicing, and translation, as well as the prevalence of this variant among other patients with HCC. Tests for the TLL1 SNP might be used to identify patients at risk for HCC after an SVR to treatment of HCV infection.
• Gastric mucosal cracked and cobblestone-like changes resulting from proton pump inhibitor use
  Shuichi Miyamoto, Mototsugu Kato, Momoko Tsuda, Kana Matsuda, Tetsuhito Muranaka, Satoshi Abiko, Masayoshi Ono, Takeshi Mizushima, Saori Omori, Keiko Yamamoto, Katsuhiro Mabe, Shoko Ono, Takahiko Kudo, Yuichi Shimizu, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 29, 3, 307, 313, May 2017, [Peer-reviewed]
  English, Scientific journal
• Genome-Wide Association Study Identifies TLL1 Variant Associated With Development of Hepatocellular Carcinoma After Eradication of Hepatitis C Virus Infection
  Kentaro Matsuura, Hiromi Sawai, Kazuho Ikeo, Shintaro Ogawa, Etsuko Iio, Masanori Isogawa, Noritomo Shimada, Atsumasa Komori, Hidenori Toyoda, Takashi Kumada, Tadashi Namisaki, Hitoshi Yoshiji, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Asahina, Masayuki Kurosaki, Namiki Izumi, Nobuyuki Enomoto, Atsunori Kusakabe, Eiji Kajiwara, Yoshito Itoh, Tatsuya Ide, Akihiro Tamori, Misako Matsubara, Norifumi Kawada, Ken Shirabe, Eiichi Tomita, Masao Honda, Shuichi Kaneko, Sohji Nishina, Atsushi Suetsugu, Yoichi Hiasa, Hisayoshi Watanabe, Takuya Genda, Isao Sakaida, Shuhei Nishiguchi, Koichi Takaguchi, Eiji Tanaka, Junichi Sugihara, Mitsuo Shimada, Yasuteru Kondo, Yosuke Kawai, Kaname Kojima, Masao Nagasaki, Katsushi Tokunaga, Yasuhito Tanaka
  GASTROENTEROLOGY, 152, 6, 1383, 1394, May 2017, [Peer-reviewed]
  English, Scientific journal
• Combination of neutrophil-to-lymphocyte ratio and early des--carboxyprothrombin change ratio as a useful predictor of treatment response for hepatic arterial infusion chemotherapy against advanced hepatocellular carcinoma
  Seiji Tsunematsu, Goki Suda, Kazushi Yamasaki, Megumi Kimura, Izumi Takaaki, Machiko Umemura, Jun Ito, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Toshiya Kamiyama, Akinobu Taketomi, Naoya Sakamoto
  HEPATOLOGY RESEARCH, 47, 6, 533, 541, May 2017, [Peer-reviewed]
  English, Scientific journal
• Anti-Adipogenic and Antiviral Effects of L-Carnitine on Hepatitis C Virus Infection
  Yoko Tsukuda, Goki Suda, Seiji Tsunematsu, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Takuya Sho, Osamu Maehara, Tomoe Shimazaki, Megumi Kimura, Kenichi Morikawa, Mitsuteru Natsuizaka, Koji Ogawa, Shunsuke Ohnishi, Makoto Chuma, Naoya Sakamoto
  JOURNAL OF MEDICAL VIROLOGY, 89, 5, 857, 866, May 2017, [Peer-reviewed]
  English, Scientific journal
• 高度悪性胆道狭窄に対する経乳頭的通電拡張術の有効性と諸問題　　　　　　　　　　　　　　　
  加藤 新, 桑谷 将城, 杉浦 諒, 佐野 逸紀, 川久保 和道, 坂本 直哉
  Gastroenterological Endoscopy, 59, Suppl.1, 993, 993, (一社)日本消化器内視鏡学会, Apr. 2017
  Japanese
• Utility of Assessing the Number of Mutated KRAS, CDKN2A, TP53, and SMAD4 Genes Using a Targeted Deep Sequencing Assay as a Prognostic Biomarker for Pancreatic Cancer
  Hideyuki Hayashi, Takashi Kohno, Hideki Ueno, Nobuyoshi Hiraoka, Shunsuke Kondo, Motonobu Saito, Yoko Shimada, Hitoshi Ichikawa, Mamoru Kato, Tatsuhiro Shibata, Chigusa Morizane, Yasunari Sakamoto, Kazuaki Shimada, Yoshito Komatsu, Naoya Sakamoto, Takuji Okusaka
  PANCREAS, 46, 3, 335, 340, Mar. 2017, [Peer-reviewed]
  English, Scientific journal
• Too short to choose biliary drainage?
  Kazumichi Kawakubo, Masaki Kuwatani, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 85, 3, 690, 690, Mar. 2017, [Peer-reviewed]
  English
• Decreased RNA-binding motif 5 expression is associated with tumor progression in gastric cancer
  Takahiko Kobayashi, Junich Ishida, Yuichi Shimizu, Hiroshi Kawakami, Goki Suda, Tetsuhito Muranaka, Yoshito Komatsu, Masahiro Asaka, Naoya Sakamoto
  TUMOR BIOLOGY, 39, 3, 1010428317694547, Mar. 2017, [Peer-reviewed]
  English, Scientific journal
• Rescue technique using a diathermic dilator for an unremovable stent in malignant perihilar biliary obstruction
  Ryo Sugiura, Hiroshi Kawakami, Nobuyuki Ehira, Ichiro Iwanaga, Minoru Uebayashi, Masaki Kuwatani, Naoya Sakamoto
  ENDOSCOPY, 49, S 01, E42, E45, Feb. 2017, [Peer-reviewed]
  English
• Hepatitis B virus Xprotein impairs alpha-interferon signaling via up-regulation of suppressor of cytokine signaling 3 and protzin phosphatase 2A
  Seiji Tsunematsu, Goki Suda, Kazushi Yamasaki, Megumi Kimura, Takaaki Izumi, Machiko Umemura, Jun Ito, Fumiyuki Sato, Masato Nakai, Takuya Sho, Kenichi Morikawa, Koji Ogawa, Yasuhito Tanaka, Koichi Watashi, Takaji Wakita, Naoya Sakamoto
  JOURNAL OF MEDICAL VIROLOGY, 89, 2, 267, 275, Feb. 2017, [Peer-reviewed]
  English, Scientific journal
• Hepatobiliary and Pancreatic: A rare case of a well-differentiated neuroendocrine tumor in the bile duct with spontaneous regression diagnosed by EUS-FNA
  I. Sano, M. Kuwatani, R. Sugiura, S. Kato, K. Kawakubo, T. Ueno, Y. Nakanishi, T. Mitsuhashi, H. Hirata, S. Haba, S. Hirano, N. Sakamoto
  Journal of Gastroenterology and Hepatology (Australia), 32, 1, 11, Blackwell Publishing, 01 Jan. 2017, [Peer-reviewed]
  English, Scientific journal
• The paradoxical effects of different Hepatitis C viral loads on host DNA damage and repair abilities
  Shu-Chi Wang, Kuan-Ru Lai, Chia-Yang Li, Chi-Shiun Chiang, Guann-Yi Yu, Naoya Sakamoto, Wen-Yu Tu, Meng-Hsuan Hsieh, Jee-Fu Huang, Wan-Long Chuang, Chia-Yen Dai, Ming-Lung Yu
  PLoS ONE, 12, 1, Public Library of Science, 01 Jan. 2017, [Peer-reviewed]
  English, Scientific journal
• MULTICENTER RANDOMIZED CONTROLLED STUDY to ASSESS the EFFECT of PROPHYLACTIC CLIPPING ON POST-POLYPECTOMY DELAYED BLEEDING
  Matsumoto M, Kato M, Oba K, Abiko S, Tsuda M, Miyamoto S, Mizushima T, Ono M, Omori S, Takahashi M, Ono S, Mabe K, Nakagawa M, Nakagawa S, Kudo T, Shimizu Y, Sakamoto N
  Gastroenterological Endoscopy, 59, 7, 1537, 1545, 2017, [Peer-reviewed]
• Diagnosis and treatment of gastric malignant lymphoma
  Shoko Ono, Yuji Ono, Naoya Sakamoto
  Journal of Japanese Society of Gastroenterology, 114, 11, 1948, 1956, Japanese Society of Gastroenterology, 2017, [Peer-reviewed]
  Japanese, Scientific journal
• Identification of novel serum autoantibodies against EID3 in non-functional pancreatic neuroendocrine tumors
  Koji Hontani, Takahiro Tsuchikawa, Takaki Hiwasa, Toru Nakamura, Takashi Ueno, Toshihiro Kushibiki, Mizuna Takahashi, Kazuho Inoko, Hironobu Takano, Satoshi Takeuchi, Hirotoshi Dosaka-Akita, Masaki Kuwatani, Naoya Sakamoto, Yutaka Hatanaka, Tomoko Mitsuhashi, Hideaki Shimada, Toshiaki Shichinohe, Satoshi Hirano
  Oncotarget, 8, 63, 106206, 106221, Impact Journals LLC, 2017, [Peer-reviewed]
  English, Scientific journal
• Therapeutic effects of human amnion-derived mesenchymal stem cell transplantation and conditioned medium enema in rats with trinitrobenzene sulfonic acid-induced colitis
  Shuichi Miyamoto, Shunsuke Ohnishi, Reizo Onishi, Ikuki Tsuchiya, Hidetaka Hosono, Takehiko Katsurada, Kenichi Yamahara, Hiroshi Takeda, Naoya Sakamoto
  AMERICAN JOURNAL OF TRANSLATIONAL RESEARCH, 9, 3, 940, 952, 2017, [Peer-reviewed]
  English, Scientific journal
• Investigation of the utility of various diagnostic guidelines for Wilson's disease.
  Nakai M, Morikawa K, Ohara M, Kawagishi N, Izumi T, Umemura M, Ito J, Tsunematsu S, Sato F, Sho T, Suda G, Ogawa K, Sakamoto N
  Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology, 114, 5, 839, 845, 2017, [Peer-reviewed]
• Gastric Hyperplastic Polyps Associated with Proton Pump Inhibitor Use in a Case without a History of Helicobacter pylori Infection
  Shuichi Miyamoto, Mototsugu Kato, Kana Matsuda, Satoshi Abiko, Momoko Tsuda, Takeshi Mizushima, Keiko Yamamoto, Shoko Ono, Takahiko Kudo, Yuichi Shimizu, Kanako C. Hatanaka, Izumi Tsunematsu, Naoya Sakamoto
  INTERNAL MEDICINE, 56, 14, 1825, 1829, 2017, [Peer-reviewed]
  English, Scientific journal
• A prospective, multicenter survey on the validity of shorter periendoscopic cessation of antithrombotic agents in Japan.
  Katsuhiro Mabe, Mototsugu Kato, Koji Oba, Soichi Nakagawa, Hideyuki Seki, Shinichi Katsuki, Kentaro Yamashita, Shoko Ono, Yuichi Shimizu, Naoya Sakamoto
  Journal of gastroenterology, 52, 1, 50, 60, Jan. 2017, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: The management of antithrombotic agents for endoscopic procedures has recently focused on preventing periprocedural thrombosis in Western countries. However, this focus on shorter cessation of antithrombotic agents needs to be examined for its implications for post-procedural bleeding, with potential risk factors for such bleeding clarified in real-world clinical settings in Japan. METHODS: A Sapporo consensus group convened and developed a consensus document on the criteria for cessation of antithrombotic agents. In the multicenter, prospective, observational study that followed to validate the criteria in a real-world clinical setting, of all patients ≥20 years of age receiving antithrombotic agents and undergoing endoscopic procedures, all consenting patients were enrolled. All participating facilities were followed up on their adherence to the criteria and clinical outcomes, such as the occurrence of post-procedural bleeding and thrombosis. RESULTS: A total of 5250 patients, who accounted for 6944 endoscopic procedures, were enrolled from 19 study sites. The consensus criteria, which proved to be nearly consistent with the JSGE criteria revised in 2012, had been adhered to in a total of 6531 procedures performed in 4921 patients. Bleeding and thrombosis were reported in 53 (0.76 %) and two (0.03 %) patients, respectively, among those receiving antithrombotic agents. Post-procedural bleeding was significantly associated with high-bleeding-risk procedures, a high thromboembolic risk with heparin bridging, and the presence of renal failure/dialysis. CONCLUSIONS: With the new criteria in place for cessation of antithrombotic agents focused on prevention of periprocedural thrombosis, endoscopic procedures may be safely performed without substantially increasing bleeding in clinical practice in Japan.
• Novel Treatment of Hepatitis C Virus Infection for Patients with Renal Impairment.
  Goki Suda, Koji Ogawa, Megumi Kimura, Masato Nakai, Takuya Sho, Kenichi Morikawa, Naoya Sakamoto
  Journal of clinical and translational hepatology, 4, 4, 320, 327, 28 Dec. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Prevalence of hepatitis C virus (HCV) infection is high in patients with end-stage renal dysfunction, including patients undergoing hemodialysis (HD). The HCV infection itself can cause glomerulonephritis and puts individuals at increased risk of developing end-stage renal disease; fortunately, successful HCV eradication sometimes restore HCV-related renal dysfunction. Moreover, the prognosis of dialysis patients infected with HCV is significantly worse and the renal allograft survival in HCV-infected patients is also worse than in dialysis patients without HCV infection. If life prognosis is favorable, therefore, anti-HCV therapy is strongly recommended for HCV-infected patients with severe renal dysfunction. The standard therapy for HCV-infected patients with severe renal dysfunction has historically been interferon-based therapy. However, this therapy remains ineffective in achieving high, sustained viral response rates and the rate of adverse events and treatment discontinuation due to treatment-induced adverse events continues to be high in patients with severe renal dysfunction. Safe and effective anti-HCV therapies are urgently needed, and crucial, for patients with severe renal dysfunction. Recently, direct-acting antivirals (DAAs) that specifically target viral proteins have been developed, and these targets include the NS3, NS5A, and NS5B of HCV. Clinical trials have revealed high efficacy and safety of the DAA-based therapies, but patients with severe renal dysfunction were not included in the majority of these trials. However, several recent reports have shown high efficacy and safety for some regimens of DAA combination therapy for HCV-infected patients with severe renal dysfunction. In this review, we discuss novel treatments for HCV-infected patients with severe renal dysfunction and the pharmacokinetics of these drugs.
• 【肝硬変を理解する-分子機構から実臨床に至るまで-】 治療 抗ウイルス治療(C型肝硬変)　　　　　　　　　　　　　　　
  中井 正人, 須田 剛生, 坂本 直哉
  肝・胆・膵, 73, 6, 1093, 1099, (株)アークメディア, Dec. 2016
  Japanese
• Prevalence and characteristics of naturally occurring sofosbuvir resistance-associated variants in patients with hepatitis C virus genotype 1b infection
  Jun Ito, Goki Suda, Yoshiya Yamamoto, Atsushi Nagasaka, Ken Furuya, Kenichi Kumagai, Hideaki Kikuchi, Takuto Miyagishima, Tomoe Kobayashi, Megumi Kimura, Kazushi Yamasaki, Machiko Umemura, Takaaki Izumi, Seiji Tsunematsu, Fumiyuki Sato, Yoko Tsukuda, Katsumi Terashita, Masato Nakai, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  HEPATOLOGY RESEARCH, 46, 13, 1294, 1303, Dec. 2016, [Peer-reviewed]
  English, Scientific journal
• Hypergastrinemia and a duodenal ulcer caused by gastric duplication.
  Tanaka H, Masumoto K, Sasaki T, Sakamoto N, Gotoh C, Urita Y, Shinkai T, Takayasu H, Nakano N, Noguchi M, Kudo T
  Surgical case reports, 2, 1, 75, 75, Springer Open, Dec. 2016, [Peer-reviewed]
  English, BackgroundHypergastrinemia and the resultant peptic ulcer related to an enteric duplication has been quite rarely reported in the literature.Case presentationWe herein report the case of a 4-year-old girl who presented with hypergastrinemia and a duodenal ulcer at 2 years of age. She had been followed up with a proton pump inhibitor, which resulted in resolution of the ulcer; however, unexplained hypergastrinemia had continued. A cystic lesion at the antrum was discovered at 4 years of age, which we suspected to be a gastric duplication. After we resected the lesion, the hypergastrinemia resolved without recurrence of the duodenal ulcer. The histology was compatible with a gastric duplication, and the lumen was lined with antral mucosa that strongly stained positive for gastrin. We presumed that the antral mucosa inside the duplication in our case had no hydrogen ion feedback inhibition of gastrin release from gastrin cells and increased release of gastrin from the mucosa inside the duplication led to the duodenal ulcer. Only two cases have been reported in the literature that had hypergastrinemia related to enteric duplication.ConclusionGastric duplication should be included in the differential diagnosis of sustained hypergastrinemia in children.
• No Benefit of Oral Diclofenac on Post-Endoscopic Retrograde Cholangiopancreatography Pancreatitis
  Hirotoshi Ishiwatari, Takahiro Urata, Ichiro Yasuda, Shimpei Matsusaki, Hiroyuki Hisai, Hiroshi Kawakami, Michihiro Ono, Takuji Iwashita, Shinpei Doi, Kazumichi Kawakubo, Tsuyoshi Hayashi, Tomoko Sonoda, Naoya Sakamoto, Junji Kato
  DIGESTIVE DISEASES AND SCIENCES, 61, 11, 3292, 3301, Nov. 2016, [Peer-reviewed]
  English, Scientific journal
• Efficacy and tolerability of IFN-free direct acting antivirals therapy (daclatasvir and asunaprevir) in chronic hemodialysis patients with chronic hepatitis C
  Goki Suda, Koji Ogawa, Kenichi Morikawa, Masato Nakai, Naoya Sakamoto
  HEPATOLOGY, 64, 975A, 975A, Oct. 2016, [Peer-reviewed]
  English
• 頭頸・口腔 頭頸部がんの集学的治療 表在性頭頸部扁平上皮癌のGGT活性化標的薬を用いた蛍光イメージング(Fluorescent imaging of superficial head and neck squamous cell carcinoma using a GGT-Activated targeting agent)　　　　　　　　　　　　　　　
  大西 俊介, 水島 健, 清水 勇一, 畑中 豊, 畑中 佳奈子, 本間 明宏, 浦野 泰照, 坂本 直哉
  日本癌治療学会学術集会抄録集, 54回, WS81, 6, (一社)日本癌治療学会, Oct. 2016
  English
• Resistance Analyses of Japanese Hepatitis C-Infected Patients Receiving Sofosbuvir or Ledipasvir/Sofosbuvir Containing Regimens in Phase 3 Studies
  M. Mizokami, H. Dvory-Sobol, N. Izumi, S. Nishiguchi, B. Doehle, E. S. Svarovskaia, S. De-Oertel, S. Knox, D. M. Brainard, M. D. Miller, H. Mo, N. Sakamoto, T. Takehara, M. Omata
  JOURNAL OF VIRAL HEPATITIS, 23, 10, 780, 788, Oct. 2016, [Peer-reviewed]
  English, Scientific journal
• Significance of fully automated tests for the diagnosis of antiphospholipid syndrome
  Kenji Oku, Olga Amengual, Masaru Kato, Toshiyuki Bohgaki, Tetsuya Horita, Shinsuke Yasuda, Naoya Sakamoto, Masahiro Ieko, Gary L. Norman, Tatsuya Atsumi
  THROMBOSIS RESEARCH, 146, 1, 6, Oct. 2016, [Peer-reviewed]
  English, Scientific journal
• Efficacy and Safety of Bolus 5-Fluorouracil and L-Leucovorin as Salvage Chemotherapy for Oral Fluoropyrimidine-Resistant Unresectable or Recurrent Gastric Cancer: A Single Center Experience
  Tetsuhito Muranaka, Satoshi Yuki, Yoshito Komatsu, Kentaro Sawada, Kazuaki Harada, Yasuyuki Kawamoto, Hiroshi Nakatsumi, Naoya Sakamoto
  JOURNAL OF GASTRIC CANCER, 16, 3, 177, 181, Sep. 2016, [Peer-reviewed]
  English, Scientific journal
• Hepatitis B: progress in understanding chronicity, the innate immune response, and cccDNA protection.
  Kenichi Morikawa, Tomoe Shimazaki, Rei Takeda, Takaaki Izumi, Machiko Umumura, Naoya Sakamoto
  Annals of translational medicine, 4, 18, 337, 337, Sep. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Hepatitis B virus (HBV) infection is a serious health threat around the world. Despite the availability of an effective hepatitis B vaccine, the number of HBV carriers is estimated to be as high as 240 million worldwide. Global mortality due to HBV-related liver diseases such as chronic hepatitis, liver cirrhosis, and hepatocellular carcinoma (HCC) may be as high as 1 million deaths per year. HBV is transmitted via blood and body fluids, and is much more infectious than both human immunodeficiency virus (HIV) and hepatitis C virus. While HBV infection exhibits a variety of clinical presentations, even asymptomatic carriers can develop HCC without liver fibrosis. Current therapeutic options against HBV include pegylated interferon (Peg-IFN) and nucleos(t)ide reverse transcriptase inhibitors (NRTIs), with clinical studies showing a significant association between loss of HBV DNA and a decrease in cancer risk. However, the ultimate goal of HBV therapy is a complete cure of HBV-including the elimination of covalently closed circular DNA (cccDNA)-in order to further decrease the risk of developing HCC. The development of hepatitis B is associated with the host immune response to virus-infected hepatocytes, as HBV is understood to lack direct cytotoxicity. While HBV-specific CD8+ T cells are thus involved in hepatitis development, they also play an important role in eliminating HBV infection. Indeed, the innate immune response during the initial phase of HBV infection is essential to the induction of acquired immunity. However, the innate immune response to HBV infection, including the roles of specific immunocompetent cells and associated molecules, is not well understood. In this review, we focus on the current understanding of the mechanisms underlying hepatitis development by HBV infection. We also address the mechanisms by which HBV protects cccDNA.
• Overexpression of KIF11 in Gastric Cancer with Intestinal Mucin Phenotype
  Takeharu Imai, Naohide Oue, Masahiro Nishioka, Shoichiro Mukai, Takashi Oshima, Naoya Sakamoto, Kazuhiro Sentani, Keisuke Matsusaki, Kazuhiro Yoshida, Wataru Yasui
  PATHOBIOLOGY, 84, 1, 16, 24, Sep. 2016, [Peer-reviewed]
  English, Scientific journal
• Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort study (vol 16, 65, 2016)
  Kimitoshi Kubo, Hiroshi Kawakami, Masaki Kuwatani, Mutsumi Nishida, Kazumichi Kawakubo, Shuhei Kawahata, Yoko Taya, Yoshimasa Kubota, Toraji Amano, Hiroki Shirato, Naoya Sakamoto
  BMC GASTROENTEROLOGY, 16, 1, 116, Sep. 2016, [Peer-reviewed]
  English
• Viral life cycle of hepatitis B virus: Host factors and druggable targets
  Kenichi Morikawa, Goki Suda, Naoya Sakamoto
  HEPATOLOGY RESEARCH, 46, 9, 871, 877, Aug. 2016, [Peer-reviewed]
  English
• Analysis of Helicobacter pylori genotypes in clinical gastric wash samples
  Shuichi Miyamoto, Yoshiyuki Watanabe, Ritsuko Oikawa, Shoko Ono, Katsuhiro Mabe, Takahiko Kudo, Hiroyuki Yamamoto, Fumio Itoh, Mototsugu Kato, Naoya Sakamoto
  TUMOR BIOLOGY, 37, 8, 10123, 10132, Aug. 2016, [Peer-reviewed]
  English, Scientific journal
• ZEB1 expression is associated with prognosis of intrahepatic cholangiocarcinoma
  Katsumi Terashita, Makoto Chuma, Yutaka Hatanaka, Kanako Hatanaka, Tomoko Mitsuhashi, Hideki Yokoo, Takumi Ohmura, Hiroyuki Ishizu, Shunji Muraoka, Atsushi Nagasaka, Takahiro Tsuji, Yoshiya Yamamoto, Nobuaki Kurauchi, Norihiko Shimoyama, Hidenori Toyoda, Takashi Kumada, Yuji Kaneoka, Atsuyuki Maeda, Koji Ogawa, Mitsuteru Natsuizaka, Hirofumi Kamachi, Tatsuhiko Kakisaka, Toshiya Kamiyama, Akinobu Taketomi, Yoshihiro Matsuno, Naoya Sakamoto
  JOURNAL OF CLINICAL PATHOLOGY, 69, 7, 593, 599, Jul. 2016, [Peer-reviewed]
  English, Scientific journal
• Efficacy and safety of daclatasvir and asunaprevir combination therapy in chronic hemodialysis patients with chronic hepatitis C
  Goki Suda, Mineo Kudo, Atsushi Nagasaka, Ken Furuya, Yoshiya Yamamoto, Tomoe Kobayashi, Keisuke Shinada, Miki Tateyama, Jun Konno, Yoko Tsukuda, Kazushi Yamasaki, Megumi Kimura, Machiko Umemura, Takaaki Izumi, Seiji Tsunematsu, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Hiromasa Horimoto, Takuya Sho, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY, 51, 7, 733, 740, Jul. 2016, [Peer-reviewed]
  English, Scientific journal
• Multicenter randomized controlled study to assess the effect of prophylactic clipping on post-polypectomy delayed bleeding.
  Mio Matsumoto, Mototsugu Kato, Koji Oba, Satoshi Abiko, Momoko Tsuda, Shuichi Miyamoto, Takeshi Mizushima, Masayoshi Ono, Saori Omori, Masakazu Takahashi, Shoko Ono, Katsuhiro Mabe, Manabu Nakagawa, Soichi Nakagawa, Takahiko Kudo, Yuichi Shimizu, Naoya Sakamoto
  Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 28, 5, 570, 6, Jul. 2016, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND AND AIM: Prophylactic clipping has been widely used to prevent post-procedural bleeding in colon polypctomy. However, its efficiency has not been confirmed and there is no consensus on the usefulness of prophylactic clipping. The aim of the present study was to evaluate the preventive effect of prophylactic clipping on post-polypectomy bleeding. METHODS: A multicenter randomized controlled study was conducted from January 2012 to July 2013 in Japan. Patients who had polyps <2 cm in diameter were divided into a clipping group and a non-clipping group by cluster randomization. After endoscopic polypectomy, patients allocated to the clipping group underwent prophylactic clipping, whereas the procedure was completed without clipping in patients allocated to the non-clipping group. Occurrence of post-polypectomy bleeding was compared between the two groups. RESULTS: Seven hospitals participated in this study. A total of 3365 polyps in 1499 patients were evaluated. The clipping group consisted of 1636 polyps in 752 patients, and the non-clipping group consisted of 1729 polyps in 747 patients. Post-polypectomy bleeding occurred in 1.10% (18/1636) of the cases in the clipping group, and in 0.87% (15/1729) of those in the non-clipping group. The difference was -0.22% (95% confidence interval [CI]: -0.96, 0.53). Upper limit of the 95% CI was lower than the non-inferiority margin (1.5%), and we could thus prove non-inferiority of non-clipping against clipping. CONCLUSION: Prophylactic clipping is not necessary to prevent post-polypectomy bleeding for polyps <2 cm in diameter.
• Reply to Rimbaş et al
  Hiroshi Kawakami, Kazumichi Kawakubo, Yoshimasa Kubota, Masaki Kuwatani, Naoya Sakamoto
  Endoscopy, 48, 7, 687, Georg Thieme Verlag, 01 Jul. 2016, [Peer-reviewed]
  English
• Reply to Saritas and Ustundag
  Hiroshi Kawakami, Kazumichi Kawakubo, Yoshimasa Kubota, Masaki Kuwatani, Naoya Sakamoto
  Endoscopy, 48, 7, 689, Georg Thieme Verlag, 01 Jul. 2016, [Peer-reviewed]
  English
• Fluorescent imaging of superficial head and neck squamous cell carcinoma using a Upsilon-glutamyltranspeptidase-activated targeting agent: a pilot study
  Takeshi Mizushima, Shunsuke Ohnishi, Yuichi Shimizu, Yutaka Hatanaka, Kanako C. Hatanaka, Hidetaka Hosono, Yoshimasa Kubota, Mitsuteru Natsuizaka, Mako Kamiya, Shouko Ono, Akihiro Homma, Mototsugu Kato, Naoya Sakamoto, Yasuteru Urano
  BMC CANCER, 16, 411, Jul. 2016, [Peer-reviewed]
  English, Scientific journal
• Liver elasticity measurement before and after biliary drainage in patients with obstructive jaundice: a prospective cohort studya prospective cohort study
  Kimitoshi Kubo, Hiroshi Kawakami, Masaki Kuwatani, Mutsumi Nishida, Kazumichi Kawakubo, Shuhei Kawahata, Yoko Taya, Yoshimasa Kubota, Toraji Amano, Hiroki Shirato, Naoya Sakamoto
  BMC GASTROENTEROLOGY, 16, 1, 65, Jul. 2016, [Peer-reviewed]
  English, Scientific journal
• Feasibility of Using an Enzymatically Activatable Fluorescence Probe for the Rapid Evaluation of Pancreatic Tissue Obtained Using Endoscopic Ultrasound-Guided Fine Needle Aspiration: a Pilot Study
  Kazumichi Kawakubo, Shunsuke Ohnishi, Yutaka Hatanaka, Kanako C. Hatanaka, Hidetaka Hosono, Yoshimasa Kubota, Mako Kamiya, Masaki Kuwatani, Hiroshi Kawakami, Yasuteru Urano, Naoya Sakamoto
  MOLECULAR IMAGING AND BIOLOGY, 18, 3, 463, 471, Jun. 2016, [Peer-reviewed]
  English, Scientific journal
• 【肝不全-その常識は正しいか?-】 慢性肝不全 その常識は正しいか? ウイルス性慢性肝不全に対する抗ウイルス治療は有用である
  中井 正人, 須田 剛生, 坂本 直哉
  救急・集中治療, 28, 5-6, 377, 381, (株)総合医学社, May 2016
  Japanese
• Prevention of Subsequent Stricture Formation After Esophageal Endoscopic Submucosal Dissection Using Conditioned Medium Obtained From Amnion-Derived Mesenchymal Stem Cell Culture
  Takeshi Mizushima, Shunsuke Ohnishi, Hidetaka Hosono, Momoko Tsuda, Masayoshi Ono, Reizo Onishi, Mototsugu Kato, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 83, 5, AB583, AB583, May 2016, [Peer-reviewed]
  English
• Effect of Fetal Membrane-Derived Mesenchymal Stem Cell Transplantation in Rats With Acute and Chronic Pancreatitis
  Kazumichi Kawakubo, Shunsuke Ohnishi, Hirotoshi Fujita, Masaki Kuwatani, Reizo Onishi, Atsushi Masamune, Hiroshi Takeda, Naoya Sakamoto
  PANCREAS, 45, 5, 707, 713, May 2016, [Peer-reviewed]
  English, Scientific journal
• Lower incidence of complications in endoscopic nasobiliary drainage for hilar cholangiocarcinoma.
  Kawakubo K, Kawakami H, Kuwatani M, Haba S, Kudo T, Taya YA, Kawahata S, Kubota Y, Kubo K, Eto K, Ehira N, Yamato H, Onodera M, Sakamoto N
  World journal of gastrointestinal endoscopy, 8, 9, 385, 390, May 2016, [Peer-reviewed]
• 切除可能大腸癌の術前精査における、体外式超音波検査による局在診断の有用性　　　　　　　　　　　　　　　
  津田 桃子, 西田 睦, 水島 健, 佐藤 恵美, 工藤 悠輔, 表原 里実, 本間 重紀, 川村 秀樹, 加藤 元嗣, 坂本 直哉
  超音波医学, 43, Suppl., S523, S523, (公社)日本超音波医学会, Apr. 2016
  Japanese
• 肝臓における超音波組織弾性測定の機種間差の検討　　　　　　　　　　　　　　　
  若林 倭, 工藤 悠輔, 西田 睦, 堀江 達則, 岩井 孝仁, 表原 里美, 佐藤 恵美, 高杉 莉佳, 小川 浩司, 坂本 直哉
  超音波医学, 43, Suppl., S618, S618, (公社)日本超音波医学会, Apr. 2016
  Japanese
• Transpapillary selective bile duct cannulation technique: Review of Japanese randomized controlled trials since 2010 and an overview of clinical results in precut sphincterotomy since 2004
  Hiroshi Kawakami, Yoshimasa Kubota, Shuhei Kawahata, Kimitoshi Kubo, Kazumichi Kawakubo, Masaki Kuwatani, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 28, 77, 95, Apr. 2016, [Peer-reviewed]
  English, Scientific journal
• Understanding of HLA-conferred susceptibility to chronic hepatitis B infection requires HLA genotyping-based association analysis
  Nao Nishida, Jun Ohashi, Seik-Soon Khor, Masaya Sugiyama, Takayo Tsuchiura, Hiromi Sawai, Keisuke Hino, Masao Honda, Shuichi Kaneko, Hiroshi Yatsuhashi, Osamu Yokosuka, Kazuhiko Koike, Masayuki Kurosaki, Namiki Izumi, Masaaki Korenaga, Jong-Hon Kang, Eiji Tanaka, Akinobu Taketomi, Yuichiro Eguchi, Naoya Sakamoto, Kazuhide Yamamoto, Akihiro Tamori, Isao Sakaida, Shuhei Hige, Yoshito Itoh, Satoshi Mochida, Eiji Mita, Yasuhiro Takikawa, Tatsuya Ide, Yoichi Hiasa, Hiroto Kojima, Ken Yamamoto, Minoru Nakamura, Hiroh Saji, Takehiko Sasazuki, Tatsuya Kanto, Katsushi Tokunaga, Masashi Mizokami
  SCIENTIFIC REPORTS, 6, 24767, Apr. 2016, [Peer-reviewed]
  English, Scientific journal
• Delayed bleeding and hemorrhage of mucosal defects after gastric endoscopic submucosal dissection on second-look endoscopy
  Shoko Ono, Masayoshi Ono, Manabu Nakagawa, Yuichi Shimizu, Mototsugu Kato, Naoya Sakamoto
  GASTRIC CANCER, 19, 2, 561, 567, Apr. 2016, [Peer-reviewed]
  English, Scientific journal
• Fukutin, identified by the Escherichia coli ampicillin secretion trap (CAST) method, participates in tumor progression in gastric cancer
  Htoo Zarni Oo, Kazuhiro Sentani, Shoichiro Mukai, Takuya Hattori, Shunsuke Shinmei, Keisuke Goto, Naoya Sakamoto, Yutaka Naito, Katsuhiro Anami, Pharm Thi Binh Trang, Kazuyoshi Yanagihara, Naohide Oue, Wataru Yasui
  GASTRIC CANCER, 19, 2, 443, 452, Apr. 2016, [Peer-reviewed]
  English, Scientific journal
• Endoscopic Ultrasound-Guided Fine-Needle Aspiration of Gastrointestinal and Pancreatic Tumors: Is Negative Pressure Helpful or Does It Suck?
  Hiroshi Kawakami, Yoshimasa Kubota, Naoya Sakamoto
  DIGESTIVE DISEASES AND SCIENCES, 61, 3, 660, 662, Mar. 2016, [Peer-reviewed]
  English
• Double Penetrated Duodenal Wall during Endoscopic Ultrasound-Guided Choledochoduodenostomy
  Hiroshi Kawakami, Masaki Kuwatani, Naoya Sakamoto
  GUT AND LIVER, 10, 2, 318, 319, Mar. 2016, [Peer-reviewed]
  English
• [Programs for Continuing Medical Education: A session; 1. New therapeutic strategies for hepatitis C by direct-acting antivirals (DAA)].
  Sakamoto N
  Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 105, 3, 424, 428, The Japanese Society of Internal Medicine, Mar. 2016, [Peer-reviewed]
  Japanese
• Relative contribution of physiological hydrostatic pressure and fluid shear stress to endothelial monolayer integrity
  Toshiro Ohashi, Yoshiaki Sugaya, Naoya Sakamoto, Masaaki Sato
  Biomedical Engineering Letters, 6, 1, 31, 38, Springer Verlag, 01 Feb. 2016, [Peer-reviewed]
  English, Scientific journal
• Observational cohort study of first-line bevacizumab with oxaliplatin or irinotecan and fluoropyrimidines in metastatic colorectal cancer: HGCSG0802-Analysis of early tumor shrinkage (ETS).
  Yuki Satoshi, Nakatsumi Hiroshi, Sawada Kentaro, Kato Takashi, Meguro Takashi, Nakamura Michio, Iwanaga Ichiro, Ehira Nobuyuki, Sonoda Norikazu, Kudo Mineo, Kato Kanji, Sogabe Susumu, Amano Toraji, Ono Kota, Sakamoto Keita, Miyamoto Noriyuki, Kudo Kohsuke, Sakamoto Naoya, Sakata Yuh, Komatsu Yoshito
  JOURNAL OF CLINICAL ONCOLOGY, 34, 4, 01 Feb. 2016, [Peer-reviewed]
• Endoscopic ultrasound-guided choledochoduodenostomy vs. transpapillary stenting for distal biliary obstruction
  Kazumichi Kawakubo, Hiroshi Kawakami, Masaki Kuwatani, Yoshimasa Kubota, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 48, 2, 164, 169, Feb. 2016, [Peer-reviewed]
  English, Scientific journal
• A case with a fibrous polyp of the gallbladder with a formal change that was observed for seven years
  Kubo Kimitoshi, Kawakami Hiroshi, Kubota Yoshimasa, Kawahata Shuhei, Kawakubo Kazumichi, Kuwatani Masaki, Ueno Takashi, Mitsuhashi Tomoko, Sakamoto Naoya
  Tando, 30, 4, 723, 730, Japan Biliary Association, 2016
  Japanese, A 60-year-old male with a tumor of the gallbladder that was detected by screening ultrasonography (US) was referred to our hospital for workup. US revealed a pedunculated polyp at the fundus of gallbladder and diffuse thickened wall of the gallbladder. We followed it on the diagnosis of cholesterol polyp and cholesterosis. During the follow-up period, the polyp tended to enlarge and change morphologically. Since adenoma or gallbladder carcinoma in situ could be considered as a diagnosis of the polyp based on various images, a laparoscopic cholecystectomy was carried out. Resected specimen revealed a light yellowish pedunculated polyp at the fundus of gallbladder and cholesterosis. Histologically, it was covered with a simple epithelium with low-grade atypia and was composed of mucinous edematous stroma with few infiltration of foamy cells in lamina propria, and finally diagnosed as a fibrous polyp. This is a rare case with a fibrous polyp of the gallbladder and has been suspected to change from a cholesterol polyp.
• 切除可能大腸癌の術前精査における、体外式超音波検査による局在診断の有用性　　　　　　　　　　　　　　　
  津田 桃子, 西田 睦, 水島 健, 佐藤 恵美, 工藤 悠輔, 表原 里実, 下國 達志, 本間 重紀, 加藤 元嗣, 坂本 直哉
  超音波医学, 43, 1, 129, 130, (公社)日本超音波医学会, Jan. 2016
  Japanese
• Standard antiviral therapies against HCV infection
  Naoya Sakamoto
  Journal of Japanese Society of Gastroenterology, 113, 1, 20, 24, Japanese Society of Gastroenterology, 01 Jan. 2016, [Peer-reviewed]
  Japanese, Scientific journal
• Peroral transhepatic cholangioscopy-guided electrohydraulic lithotripsy via an endoscopic ultrasonography-guided hepaticogastrostomy route for bile duct stones in a patient with Roux-en-Y anatomy
  Hiroshi Kawakami, Yoshimasa Kubota, Shuhei Kawahata, Kimitoshi Kubo, Shinji Okabayashi, Ryoji Tatsumi, Naoya Sakamoto
  ENDOSCOPY, 48, E146, E147, 2016, [Peer-reviewed]
  English
• Peroral video cholangioscopic findings in a biliary intraductal mucinous cystic neoplasm
  Hiroshi Kawakami, Yoshimasa Kubota, Kimitoshi Kubo, Daisuke Sato, Tomoko Mitsuhashi, Satoshi Hirano, Naoya Sakamoto
  ENDOSCOPY, 48, E152, E153, 2016, [Peer-reviewed]
  English
• Two Cases of Chronic Gastritis with non-Helicobacter pylori Helicobacter Infection
  Satoka Shiratori, Katsuhiro Mabe, Shinji Yoshii, Yasunari Takakuwa, Masaaki Sato, Masahiko Nakamura, Takahiko Kudo, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  INTERNAL MEDICINE, 55, 14, 1865, 1869, 2016, [Peer-reviewed]
  English, Scientific journal
• Effects of HLA-DPB1 genotypes on chronic hepatitis B infection in Japanese individuals
  N. Nishida, J. Ohashi, M. Sugiyama, T. Tsuchiura, K. Yamamoto, K. Hino, M. Honda, S. Kaneko, H. Yatsuhashi, K. Koike, O. Yokosuka, E. Tanaka, A. Taketomi, M. Kurosaki, N. Izumi, N. Sakamoto, Y. Eguchi, T. Sasazuki, K. Tokunaga, M. Mizokami
  TISSUE ANTIGENS, 86, 6, 406, 412, Dec. 2015, [Peer-reviewed]
  English, Scientific journal
• Streptococcal toxic shock syndrome secondary to group A Streptococcus vaginitis
  Mayu Hikone, Ken-ichiro Kobayashi, Takuya Washino, Masayuki Ota, Naoya Sakamoto, Sentaro Iwabuchi, Kenji Ohnishi
  Journal of Infection and Chemotherapy, 21, 12, 873, 876, Elsevier, 01 Dec. 2015, [Peer-reviewed]
  English, Scientific journal
• Single-stage endoscopic treatment for mild to moderate acute cholangitis associated with choledocholithiasis: a multicenter, non-randomized, open-label and exploratory clinical trial
  Kazunori Eto, Hiroshi Kawakami, Shin Haba, Hiroaki Yamato, Toshinori Okuda, Kei Yane, Tsuyoshi Hayashi, Nobuyuki Ehira, Manabu Onodera, Ryusuke Matsumoto, Yu Matsubara, Tomofumi Takagi, Naoya Sakamoto
  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 22, 12, 825, 830, Dec. 2015, [Peer-reviewed]
  English, Scientific journal
• Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression (vol 5, 13994, 2015)
  Megumi Tasaka-Fujita, Nao Sugiyama, Wonseok Kang, Takahiro Masaki, Asako Murayama, Norie Yamada, Ryuichi Sugiyama, Senko Tsukuda, Koichi Watashi, Yasuhiro Asahina, Naoya Sakamoto, Takaji Wakita, Eui-Cheol Shin, Takanobu Kato
  SCIENTIFIC REPORTS, 5, 17208, Dec. 2015, [Peer-reviewed]
  English
• [Inhibitory effect of HCV-NS4B on IFN-λ induction].
  Nitta S, Sakamoto N, Asahina Y
  Nihon rinsho. Japanese journal of clinical medicine, 73 Suppl 9, 124, 127, Dec. 2015, [Peer-reviewed]
• [Predictive factors of response to Direct Acting Antivirals therapy Drug resistance hepatitis C virus].
  Suda G, Yamasaki K, Sakamoto N
  Nihon rinsho. Japanese journal of clinical medicine, 73 Suppl 9, 189, 192, Dec. 2015, [Peer-reviewed]
• Anterior mediastinal abscess diagnosed in a young sumo wrestler after closed blunt chest trauma
  Tatsuro Sassa, Ken-Ichiro Kobayashi, Masayuki Ota, Takuya Washino, Mayu Hikone, Naoya Sakamoto, Sentaro Iwabuchi, Mizuto Otsuji, Kenji Ohnishi
  Chinese Journal of Traumatology - English Edition, 18, 6, 360, 362, Elsevier B.V., 01 Dec. 2015, [Peer-reviewed]
  English, Scientific journal
• Effects of human amnion-derived mesenchymal stromal cell transplantation in rats with radiation proctitis
  Masayoshi Ono, Shunsuke Ohnishi, Minori Honda, Marin Ishikawa, Hidetaka Hosono, Reizo Onishi, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
  CYTOTHERAPY, 17, 11, 1545, 1559, Nov. 2015, [Peer-reviewed]
  English, Scientific journal
• Detection of hypermutated human papillomavirus type 16 genome by Next-Generation Sequencing
  Kousho Wakae, Satoru Aoyama, Zhe Wang, Kouichi Kitamura, Guangyan Liu, Ahasan Md. Monjurul, Miki Koura, Mieko Imayasu, Naoya Sakamoto, Mitsuhiro Nakamura, Satoru Kyo, Satoru Kondo, Hiroshi Fujiwara, Tomokazu Yoshizaki, Iwao Kukimoto, Katsushi Yamaguchi, Shuji Shigenobu, Tomoaki Nishiyama, Masamichi Muramatsu
  VIROLOGY, 485, 460, 466, Nov. 2015, [Peer-reviewed]
  English, Scientific journal
• Tissue-Specific Effects of Reduced β-catenin Expression on Adenomatous Polyposis Coli Mutation-Instigated Tumorigenesis in Mouse Colon and Ovarian Epithelium.
  Feng Y, Sakamoto N, Wu R, Liu JY, Wiese A, Green ME, Green M, Akyol A, Roy BC, Zhai Y, Cho KR, Fearon ER
  PLoS genetics, 11, 11, e1005638, Nov. 2015, [Peer-reviewed]
• Involvement of FKBP6 in hepatitis C virus replication
  Hirotake Kasai, Kunihiro Kawakami, Hiromasa Yokoe, Kentaro Yoshimura, Masanori Matsuda, Jun Yasumoto, Shinya Maekawa, Atsuya Yamashita, Tomohisa Tanaka, Masanori Ikeda, Nobuyuki Kato, Toru Okamoto, Yoshiharu Matsuura, Naoya Sakamoto, Nobuyuki Enomoto, Sen Takeda, Hideki Fujii, Masayoshi Tsubuki, Masami Kusunoki, Kohji Moriishi
  SCIENTIFIC REPORTS, 5, 16699, Nov. 2015, [Peer-reviewed]
  English, Scientific journal
• Effect of a stylet on a histological specimen in EUS-guided fine-needle tissue acquisition by using 22-gauge needles: a multicenter, prospective, randomized, controlled trial.
  Yoko Abe, Hiroshi Kawakami, Koji Oba, Tsuyoshi Hayashi, Ichiro Yasuda, Tsuyoshi Mukai, Hiroyuki Isayama, Hirotoshi Ishiwatari, Shinpei Doi, Masanori Nakashima, Natsuyo Yamamoto, Masaki Kuwatani, Tomoko Mitsuhashi, Tadashi Hasegawa, Yoshinobu Hirose, Tetsuya Yamada, Mariko Tanaka, Naoya Sakamoto
  Gastrointestinal endoscopy, 82, 5, 837, 844, Nov. 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal, BACKGROUND: EUS-guided FNA (EUS-FNA) has become the most efficacious way to obtain specimens from a solid lesion adjacent to the GI tract. Previous reports regarding the use of a stylet during EUS-FNA were all based on cytological diagnosis and have showed no significant superiority in terms of diagnostic yield. OBJECTIVE: To clarify the noninferiority of EUS-FNA without a stylet (S-) compared with EUS-FNA with a stylet (S+) on histological assessment. DESIGN: A prospective, single-blind, randomized, controlled crossover study. SETTING: Five tertiary referral centers in Japan. PATIENTS: Patients referred for EUS-FNA of a solid lesion. INTERVENTION: EUS-FNA S+ and S- in a total of 4 alternate passes with randomization to S+ first or S- first. MAIN OUTCOME MEASUREMENTS: The primary endpoint was the acquisition rate of an appropriate and sufficient specimen for histological assessment. The secondary endpoints were cellularity, contamination, bloodiness, diagnostic ability, and diagnostic accuracy. RESULTS: We enrolled 107 patients (110 lesions) and analyzed 220 specimens each in the S+ and S- groups. The acquisition rate of appropriate and sufficient specimens in the S+ group was 121 of 220 (55.0%) and 122 of 220 (55.5%) in the S- group. The difference in the acquisition rate of the specimen (S- minus S+) based on the generalized estimating equation was 0.42% (95% confidence interval, -6.72% to 7.56%), which was less than 10% of the prespecified noninferiority margin of this study. With regard to cellularity, contamination, bloodiness score, diagnostic ability, and diagnostic accuracy, there were no significant differences between both groups. There were no dropouts in the study. LIMITATIONS: A variety of target lesions, multiple pathologists, lack of an assessment of intraobserver and interobserver variability, and a single-blind study for the pathologists. CONCLUSION: EUS-FNA S- is noninferior to EUS-FNA S+ on histological assessment. ( CLINICAL TRIAL REGISTRATION NUMBER: UMIN000008695.).
• Dynamic Analysis Of Cellular Factors Modulated By Hepatitis B Virus Protein Expression And Replication
  Kenichi Morikawa, Tomoe Shimazaki, Takaaki Izumi, Machiko Umemura, Masato Nakai, Goki Suda, Darius Moradpour, Naoya Sakamoto
  HEPATOLOGY, 62, 1024A, 1024A, Oct. 2015, [Peer-reviewed]
  English
• The decreased urinary aquaporin2 excretion is a predictive factor for the efficacy of Tolvaptan in patients with hepatic cirrhosis
  Masato Nakai, Jun Itoh, Fumiyuki Sato, Seiji Tsunematsu, Takuya Sho, Goki Suda, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  HEPATOLOGY, 62, 358A, 358A, Oct. 2015, [Peer-reviewed]
  English
• Truncated Hepatitis B virus X protein up-regulates CD44+cancer stem like cells through LTBP1
  Goki Suda, Seiji Tsunematsu, Masato Nakai, Jun Itoh, Mitsuteru Natsuizaka, Kenichi Morikawa, Koji Ogawa, Naoya Sakamoto
  HEPATOLOGY, 62, 1157A, 1157A, Oct. 2015, [Peer-reviewed]
  English
• γ-Glutamyltranspeptidaseにより蛍光を発するprobeによる早期頭頸部がんの検出　　　　　　　　　　　　　　　
  大西 俊介, 清水 勇一, 水島 健, 畑中 豊, 畑中 佳奈子, 久保田 良政, 夏井坂 光輝, 神谷 真子, 本間 明宏, 加藤 元嗣, 浦野 泰照, 坂本 直哉
  日本癌学会総会記事, 74回, P, 3308, 日本癌学会, Oct. 2015
  English
• Interferon (IFN) and Cellular Immune Response Evoked in RNA-Pattern Sensing During Infection with Hepatitis C Virus (HCV)
  Masato Nakai, Hiroyuki Oshiumi, Kenji Funami, Masaaki Okamoto, Misako Matsumoto, Tsukasa Seya, Naoya Sakamoto
  SENSORS, 15, 10, 27160, 27173, Oct. 2015, [Peer-reviewed]
  English
• New molecularly targeted therapies against advanced hepatocellular carcinoma: From molecular pathogenesis to clinical trials and future directions
  Makoto Chuma, Katsumi Terashita, Naoya Sakamoto
  HEPATOLOGY RESEARCH, 45, 10, E1, E11, Oct. 2015, [Peer-reviewed]
  English
• A pivotal role of Kruppel-like factor 5 in regulation of cancer stem-like cells in hepatocellular carcinoma
  Osamu Maehara, Fumiyuki Sato, Mitsuteru Natsuizaka, Ayaka Asano, Yoshimasa Kubota, Jun Itoh, Seiji Tsunematsu, Katsumi Terashita, Yoko Tsukuda, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Koji Ogawa, Makoto Chuma, Koji Nakagawa, Shunsuke Ohnishi, Yoshito Komatsu, Kelly A. Whelan, Hiroshi Nakagawa, Hiroshi Takeda, Naoya Sakamoto
  CANCER BIOLOGY & THERAPY, 16, 10, 1453, 1461, Oct. 2015, [Peer-reviewed]
  English, Scientific journal
• 閉塞性黄疸患者における胆道ドレナージ術前後の肝硬度の変化　　　　　　　　　　　　　　　
  久保 公利, 河上 洋, 桑谷 将城, 川久保 和道, 阿部 容子, 川畑 修平, 坂本 直哉, 作原 佑介, 白土 博樹, 工藤 悠輔, 西田 睦
  日本消化器病学会雑誌, 112, 臨増大会, A855, A855, (一財)日本消化器病学会, Sep. 2015
  Japanese
• Amino Acid Polymorphisms in Hepatitis C Virus Core Affect Infectious Virus Production and Major Histocompatibility Complex Class I Molecule Expression
  Megumi Tasaka-Fujita, Nao Sugiyama, Wonseok Kang, Takahiro Masaski, Asako Murayama, Norie Yamada, Ryuichi Sugiyama, Senko Tsukuda, Koichi Watashi, Yasuhiro Asahina, Naoya Sakamoto, Takaji Wakita, Eui-Cheol Shin, Takanobu Kato
  SCIENTIFIC REPORTS, 5, 13994, Sep. 2015, [Peer-reviewed]
  English, Scientific journal
• Recent advances in endoscopic ultrasonography-guided biliary interventions
  Kazumichi Kawakubo, Hiroshi Kawakami, Masaki Kuwatani, Shin Haba, Shuhei Kawahata, Yoko Abe, Yoshimasa Kubota, Kimitoshi Kubo, Hiroyuki Isayama, Naoya Sakamoto
  WORLD JOURNAL OF GASTROENTEROLOGY, 21, 32, 9494, 9502, Aug. 2015, [Peer-reviewed]
  English, Scientific journal
• Serum granulysin levels as a predictor of serious telaprevir-induced dermatological reactions
  Goki Suda, Yoshiya Yamamoto, Astushi Nagasaka, Ken Furuya, Mineo Kudo, Yoshimichi Chuganji, Yoko Tsukuda, Seiji Tsunematsu, Fumiyuki Sato, Katsumi Terasita, Masato Nakai, Hiromasa Horimoto, Takuya Sho, Mitsuteru Natsuizaka, Kouji Ogawa, Shunsuke Ohnishi, Makoto Chuma, Yasuyuki Fujita, Riichiro Abe, Miki Taniguchi, Mina Nakagawa, Yasuhiro Asahina, Naoya Sakamoto
  HEPATOLOGY RESEARCH, 45, 8, 837, 845, Aug. 2015, [Peer-reviewed]
  English, Scientific journal
• Intratumoral artery on contrast-enhanced computed tomography imaging: differentiating intrahepatic cholangiocarcinoma from poorly differentiated hepatocellular carcinoma
  Seiji Tsunematsu, Makoto Chuma, Toshiya Kamiyama, Noriyuki Miyamoto, Satoshi Yabusaki, Kanako Hatanaka, Tomoko Mitsuhashi, Hirofumi Kamachi, Hideki Yokoo, Tatsuhiko Kakisaka, Yousuke Tsuruga, Tatsuya Orimo, Kenji Wakayama, Jun Ito, Fumiyuki Sato, Katsumi Terashita, Masato Nakai, Yoko Tsukuda, Takuya Sho, Goki Suda, Kenichi Morikawa, Mitsuteru Natsuizaka, Mitsuru Nakanishi, Koji Ogawa, Akinobu Taketomi, Yoshihiro Matsuno, Naoya Sakamoto
  ABDOMINAL IMAGING, 40, 6, 1492, 1499, Aug. 2015, [Peer-reviewed]
  English, Scientific journal
• [H. pylori-negative gastric cancer].
  Kato M, Ono S, Shimizu Y, Sakamoto N, Mabe K
  Nihon rinsho. Japanese journal of clinical medicine, 73, 7, 1215, 1220, Jul. 2015, [Peer-reviewed]
• Multicenter study on hemorrhagic risk of heparin bridging therapy for periendoscopic thromboprophylaxis
  Mio Matsumoto, Katsuhiro Mabe, Momoko Tsuda, Masayoshi Ono, Saori Omori, Masakazu Takahashi, Takeshi Yoshida, Shoko Ono, Manabu Nakagawa, Soichi Nakagawa, Yuichi Shimizu, Takahiko Kudo, Naoya Sakamoto, Mototsugu Kato
  BMC GASTROENTEROLOGY, 15, 89, Jul. 2015, [Peer-reviewed]
  English, Scientific journal
• Impaired induction of interleukin 28B and expression of interferon λ 4 associated with nonresponse to interferon-based therapy in chronic hepatitis C
  Miyako Murakawa, Yasuhiro Asahina, Mina Nakagawa, Naoya Sakamoto, Sayuri Nitta, Akiko Kusano-Kitazume, Takako Watanabe, Fukiko Kawai-Kitahata, Satoshi Otani, Miki Taniguchi, Fumio Goto, Yuki Nishimura-Sakurai, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Mamoru Watanabe
  Journal of Gastroenterology and Hepatology (Australia), 30, 6, 1075, 1084, Blackwell Publishing, 01 Jun. 2015, [Peer-reviewed]
  English, Scientific journal
• [Progress in Examination and Treatment of Hepatitis C Virus].
  Suda G, Sakamoto N
  Rinsho byori. The Japanese journal of clinical pathology, 63, 6, 762, 767, 日本臨床検査医学会事務所 ; 1953-, Jun. 2015, [Peer-reviewed]
  Japanese
• Impaired induction of interleukin 28B and expression of interferon lambda 4 associated with nonresponse to interferon-based therapy in chronic hepatitis C
  Miyako Murakawa, Yasuhiro Asahina, Mina Nakagawa, Naoya Sakamoto, Sayuri Nitta, Akiko Kusano-Kitazume, Takako Watanabe, Fukiko Kawai-Kitahata, Satoshi Otani, Miki Taniguchi, Fumio Goto, Yuki Nishimura-Sakurai, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 30, 6, 1075, 1084, Jun. 2015, [Peer-reviewed]
  English, Scientific journal
• Ledipasvir and sofosbuvir fixed-dose combination with and without ribavirin for 12 weeks in treatment-naive and previously treated Japanese patients with genotype 1 hepatitis C: an open-label, randomised, phase 3 trial
  Masashi Mizokami, Osamu Yokosuka, Tetsuo Takehara, Naoya Sakamoto, Masaaki Korenaga, Hitoshi Mochizuki, Kunio Nakane, Hirayuki Enomoto, Fusao Ikeda, Mikio Yanase, Hidenori Toyoda, Takuya Genda, Takeji Umemura, Hiroshi Yatsuhashi, Tatsuya Ide, Nobuo Toda, Kazushige Nirei, Yoshiyuki Ueno, Yoichi Nishigaki, Juan Betular, Bing Gao, Akinobu Ishizaki, Masa Omote, Hongmei Mo, Kim Garrison, Phillip S. Pang, Steven J. Knox, William T. Symonds, John G. McHutchison, Namiki Izumi, Masao Omata
  LANCET INFECTIOUS DISEASES, 15, 6, 645, 653, Jun. 2015, [Peer-reviewed]
  English, Scientific journal
• EGFR inhibitors prevent induction of cancer stem-like cells in esophageal squamous cell carcinoma by suppressing epithelial-mesenchymal transition
  Fumiyuki Sato, Yoshimasa Kubota, Mitsuteru Natsuizaka, Osamu Maehara, Yutaka Hatanaka, Katsuji Marukawa, Katsumi Terashita, Goki Suda, Shunsuke Ohnishi, Yuichi Shimizu, Yoshito Komatsu, Shinya Ohashi, Shingo Kagawa, Hideaki Kinugasa, Kelly A. Whelan, Hiroshi Nakagawa, Naoya Sakamoto
  CANCER BIOLOGY & THERAPY, 16, 6, 933, 940, Jun. 2015, [Peer-reviewed]
  English, Scientific journal
• Pazopanib-induced severe acute pancreatitis
  Kazumichi Kawakubo, Hiroo Hata, Hiroshi Kawakami, Masaki Kuwatani, Shuhei Kawahata, Kimitoshi Kubo, Keisuke Imafuku, Shinya Kitamura, Naoya Sakamoto
  Case Reports in Oncology, 8, 2, 356, 358, S. Karger AG, 06 May 2015, [Peer-reviewed]
  English, Scientific journal
• A Novel Technique for the Detection of Endoscopic Ultrasound-Guided Fine Needle Pancreatic Tissue Acquisition by an Enzymatically Rapid-Activatable Fluorescent Probe
  Kazumichi Kawakubo, Shunsuke Ohnishi, Yasuteru Urano, Yutaka Hatanaka, Kanako C. Hatanaka, Hiroshi Kawakami, Masaki Kuwatani, Shuhei Kawahata, Yoko Abe, Yoshimasa Kubota, Kimitoshi Kubo, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 81, 5, AB536, AB537, May 2015, [Peer-reviewed]
  English
• Early use of double-guidewire technique to facilitate selective bile duct cannulation: the multicenter randomized controlled EDUCATION trial
  Naoki Sasahira, Hiroshi Kawakami, Hiroyuki Isayama, Rie Uchino, Yousuke Nakai, Yukiko Ito, Saburo Matsubara, Hirotoshi Ishiwatari, Minoru Uebayashi, Hiroshi Yagioka, Osamu Togawa, Nobuo Toda, Naoya Sakamoto, Junji Kato, Kazuhiko Koike
  ENDOSCOPY, 47, 5, 421, 429, May 2015, [Peer-reviewed]
  English, Scientific journal
• Rho guanine nucleotide exchange factors involved in cyclic-stretch-induced reorientation of vascular endothelial cells
  Hiyori Abiko, Sachiko Fujiwara, Kazumasa Ohashi, Ryuichi Hiatari, Toshiya Mashiko, Naoya Sakamoto, Masaaki Sato, Kensaku Mizuno
  JOURNAL OF CELL SCIENCE, 128, 9, 1683, 1695, May 2015, [Peer-reviewed]
  English, Scientific journal
• Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Liver Fibrosis in Rats.
  Kubo K, Ohnishi S, Hosono H, Fukai M, Kameya A, Higashi R, Yamada T, Onishi R, Yamahara K, Takeda H, Sakamoto N
  Transplantation direct, 1, 4, e16, May 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal, UNLABELLED: Mesenchymal stem cells (MSCs) are a valuable cell source in regenerative medicine. Recently, several studies have shown that MSCs can be easily isolated from human amnion. In this study, we investigated the therapeutic effect of transplantation of human amnion-derived MSCs (hAMSCs) in rats with liver fibrosis. METHODS: Liver fibrosis was induced by an intraperitoneal injection of 2 mL/kg of 50% carbon tetrachloride twice a week for 6 weeks. At 3 weeks, hAMSCs (1 × 10(6) cells) were transplanted intravenously. Rats were sacrificed at 7 weeks, and histological analyses and quantitative reverse-transcription polymerase chain reaction were performed. In vitro experiments were conducted to investigate the effect of hAMSCs on the activation of Kupffer cells. RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area, deposition of type-I collagen, the number of α-smooth muscle actin-positive hepatic stellate cells, and CD68-positive Kupffer cells in the livers. messenger RNA expression of α-smooth muscle actin and tissue inhibitor of metalloproteinase-1 was significantly decreased and the expression of matrix metalloproteinase-9 and hepatocyte growth factor was significantly increased in the liver of hAMSC-treated rats. Transplantation of hAMSCs at 3 weeks plus 5 weeks did not have an additive effect. In vitro experiments demonstrated that Kupffer cell activation induced by lipopolysaccharide was significantly decreased by culturing with conditioned medium obtained from hAMSCs. CONCLUSIONS: Transplantation of hAMSCs provided significant improvement in a rat model of liver fibrosis, possibly through the inhibition of Kupffer cell and hepatic stellate cell activation. hAMSCs may be a potential new treatment for liver fibrosis.
• スクリーニング経腹的超音波検査による膀胱癌正診率　　　　　　　　　　　　　　　
  津田 桃子, 西田 睦, 佐藤 恵美, 工藤 悠輔, 安部 崇重, 土屋 邦彦, 守屋 仁彦, 篠原 信雄, 加藤 元嗣, 坂本 直哉
  超音波医学, 42, Suppl., S413, S413, (公社)日本超音波医学会, Apr. 2015
  Japanese
• Hepatobiliary and Pancreatic: A splenic artery aneurysm presenting as a calcified pancreatic mass
  K. Kawakubo, H. Kawakami, M. Kuwatani, N. Sakamoto
  Journal of Gastroenterology and Hepatology (Australia), 30, 4, 655, 655, Blackwell Publishing, 01 Apr. 2015, [Peer-reviewed]
  English, Scientific journal
• The Hypophagia After Psychological Stress in Aged Male Mice Is Mediated by an Interaction of Activation of Estrogen Receptor a With Serotonin 2C Receptor
  Ohnishi Shunsuke, Nakagawa Koji, Okubo Naoto, Sadakane Chiharu, Saegusa Yayoi, Nahata Miwa, Yamada Chihiro, Hattori Tomohisa, Sakamoto Naoya, Takeda Hiroshi
  GASTROENTEROLOGY, 148, 4, S25, S26, Apr. 2015, [Peer-reviewed]
• Different Response to Chronic Isolation Stress Between Young and Aged Mice
  Takeda Hiroshi, Ohnishi Shunsuke, Nakagawa Koji, Okubo Naoto, Yamada Chihiro, Saegusa Yayoi, Nahata Miwa, Hattori Tomohisa, Sakamoto Naoya
  GASTROENTEROLOGY, 148, 4, S26, Apr. 2015, [Peer-reviewed]
• KLF5 Promotes Tumorigenicity of Hepatocellular Carcinoma by Upregulation of Cancer Stem-Like Cells
  Fumiyuki Sato, Mitsuteru Natsuizaka, Osamu Maehara, Ayaka Asano, Yoshimasa Kubota, Jun Itoh, Seiji Tsunematsu, Yoko Tsukuda, Katsumi Terashita, Masato Nakai, Takuya Sho, Goki Suda, Kenichi Morikawa, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  GASTROENTEROLOGY, 148, 4, S43, S43, Apr. 2015, [Peer-reviewed]
  English
• Technical tips and troubleshooting of endoscopic biliary drainage for unresectable malignant hilar biliary obstruction
  Hiroshi Kawakami, Takao Itoi, Masaki Kuwatani, Kazumichi Kawakubo, Yoshimasa Kubota, Naoya Sakamoto
  Journal of Hepato-Biliary-Pancreatic Sciences, 22, 4, E12, E21, Apr. 2015, [Peer-reviewed]
  English, Scientific journal
• Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C.
  Etsuko Iio, Kentaro Matsuura, Nao Nishida, Shinya Maekawa, Nobuyuki Enomoto, Mina Nakagawa, Naoya Sakamoto, Hiroshi Yatsuhashi, Masayuki Kurosaki, Namiki Izumi, Yoichi Hiasa, Naohiko Masaki, Tatsuya Ide, Keisuke Hino, Akihiro Tamori, Masao Honda, Shuichi Kaneko, Satoshi Mochida, Hideyuki Nomura, Shuhei Nishiguchi, Chiaki Okuse, Yoshito Itoh, Hitoshi Yoshiji, Isao Sakaida, Kazuhide Yamamoto, Hisayoshi Watanabe, Shuhei Hige, Akihiro Matsumoto, Eiji Tanaka, Katsushi Tokunaga, Yasuhito Tanaka
  Human genetics, 134, 3, 279, 89, Mar. 2015, [Invited], [International Magazine]
  English, Scientific journal, Cytopenia during interferon-based (IFN-based) therapy for chronic hepatitis C (CHC) often necessitates reduction of doses of drugs and premature withdrawal from therapy resulting in poor response to treatment. To identify genetic variants associated with IFN-induced neutropenia, we conducted a genome-wide association study (GWAS) in 416 Japanese CHC patients receiving IFN-based therapy. Based on the results, we selected 192 candidate single nucleotide polymorphisms (SNPs) to carry out a replication analysis in an independent set of 404 subjects. The SNP rs2305482, located in the intron region of the PSMD3 gene on chromosome 17, showed a strong association when the results of GWAS and the replication stage were combined (OR = 2.18, P = 3.05 × 10(-7) in the allele frequency model). Logistic regression analysis showed that rs2305482 CC and neutrophil count at baseline were independent predictive factors for IFN-induced neutropenia (OR = 2.497, P = 0.0072 and OR = 0.998, P < 0.0001, respectively). Furthermore, rs2305482 genotype was associated with the doses of pegylated interferon (PEG-IFN) that could be tolerated in hepatitis C virus genotype 1-infected patients treated with PEG-IFN plus ribavirin, but not with treatment efficacy. Our results suggest that genetic testing for this variant might be useful for establishing personalized drug dosing in order to minimize drug-induced adverse events.
• Genome-wide association study identifies a PSMD3 variant associated with neutropenia in interferon-based therapy for chronic hepatitis C
  Etsuko Iio, Kentaro Matsuura, Nao Nishida, Shinya Maekawa, Nobuyuki Enomoto, Mina Nakagawa, Naoya Sakamoto, Hiroshi Yatsuhashi, Masayuki Kurosaki, Namiki Izumi, Yoichi Hiasa, Naohiko Masaki, Tatsuya Ide, Keisuke Hino, Akihiro Tamori, Masao Honda, Shuichi Kaneko, Satoshi Mochida, Hideyuki Nomura, Shuhei Nishiguchi, Chiaki Okuse, Yoshito Itoh, Hitoshi Yoshiji, Isao Sakaida, Kazuhide Yamamoto, Hisayoshi Watanabe, Shuhei Hige, Akihiro Matsumoto, Eiji Tanaka, Katsushi Tokunaga, Yasuhito Tanaka
  HUMAN GENETICS, 134, 3, 279, 289, Mar. 2015, [Peer-reviewed]
  English, Scientific journal
• The JAK2 inhibitor AZD1480 inhibits hepatitis A virus replication in Huh7 cells
  Xia Jiang, Tatsuo Kanda, Shingo Nakamoto, Kengo Saito, Masato Nakamura, Shuang Wu, Yuki Haga, Reina Sasaki, Naoya Sakamoto, Hiroshi Shirasawa, Hiroaki Okamoto, Osamu Yokosuka
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 458, 4, 908, 912, Mar. 2015, [Peer-reviewed]
  English, Scientific journal
• A Unique Use of a Double-Pigtail Plastic Stent: Correction of Kinking of the Common Bile Duct Due to a Metal Stent
  Masaki Kuwatani, Hiroshi Kawakami, Yoka Abe, Shuhei Kawahata, Kazumichi Kawakubo, Kimitoshi Kubo, Naoya Sakamoto
  GUT AND LIVER, 9, 2, 251, 252, Mar. 2015, [Peer-reviewed]
  English, Scientific journal
• [Multidisciplinary treatment of gallbladder cancer--biliary and duodenal stenting].
  Kawakami H, Kuwatani M, Sakamoto N
  Nihon rinsho. Japanese journal of clinical medicine, 73 Suppl 3, 595, 600, Mar. 2015, [Peer-reviewed]
• Single-step simultaneous side-by-side placement of a self-expandable metallic stent with a 6-Fr delivery system for unresectable malignant hilar biliary obstruction: a feasibility study
  Kazumichi Kawakubo, Hiroshi Kawakami, Masaki Kuwatani, Taiki Kudo, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Yoshimasa Kubota, Naoya Sakamoto
  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 22, 2, 151, 155, Feb. 2015, [Peer-reviewed]
  English, Scientific journal
• [New era of the treatment against hepatitis C virus].
  Natsuizaka M, Sakamoto N
  Nihon rinsho. Japanese journal of clinical medicine, 73, 2, 317, 321, 日本臨床社, Feb. 2015, [Peer-reviewed]
  Japanese
• Association of Peripheral Total and Differential Leukocyte Counts with Obesity-Related Complications in Young Adults
  Aya Yoshimura, Shunsuke Ohnishi, Chieko Orito, Yukako Kawahara, Hiroyo Takasaki, Hiroshi Takeda, Naoya Sakamoto, Satoshi Hashino
  OBESITY FACTS, 8, 1, 1, 16, Feb. 2015, [Peer-reviewed]
  English, Scientific journal
• CTNNB1 mutational analysis of solid-pseudopapillary neoplasms of the pancreas using endoscopic ultrasound-guided fine-needle aspiration and next-generation deep sequencing
  Yoshimasa Kubota, Hiroshi Kawakami, Mitsuteru Natsuizaka, Kazumichi Kawakubo, Katsuji Marukawa, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Masaki Kuwatani, Yutaka Hatanaka, Tomoko Mitsuhashi, Yoshihiro Matsuno, Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY, 50, 2, 203, 210, Feb. 2015, [Peer-reviewed]
  English, Scientific journal
• Preoperative biliary drainage for cholangiocarcinoma;Which approach or stent should be selected?
  河上 洋, 桒谷 将城, 川久保 和道, 阿部 容子, 川畑 修平, 久保 公利, 久保田 良政, 坂本 直哉
  臨床外科, 70, 1, 6, 11, 株式会社医学書院, 20 Jan. 2015
• Association of morphologic response with progression free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.
  Yuki Satoshi, Nakatsumi Hiroshi, Hayashi Hideyuki, Fukushima Hiraku, Kato Takashi, Meguro Takashi, Nakamura Michio, Iwanaga Ichiro, Eto Kazunori, Sato Atsushi, Okuda Hiroyuki, Oba Ayane, Miyagishima Takuto, Muto Osamu, Yabusaki Satoshi, Miyamoto Noriyuki, Kudo Kohsuke, Sakamoto Naoya, Sakata Yuh, Komatsu Yoshito
  JOURNAL OF CLINICAL ONCOLOGY, 33, 3, 20 Jan. 2015, [Peer-reviewed]
• Association of early tumor shrinkage with progression-free survival in patients with metastatic colorectal cancer treated with bevacizumab-based chemotherapy: HGCSG0802.
  Nakatsumi Hiroshi, Yuki Satoshi, Muranaka Tetsuhito, Fukushima Hiraku, Kato Takashi, Meguro Takashi, Nakamura Michio, Iwanaga Ichiro, Ehira Nobuyuki, Sonoda Norikazu, Kudo Mineo, Kato Kanji, Miyashita Kencho, Abe Masakazu, Miyamoto Noriyuki, Sakamoto Keita, Kudo Kohsuke, Sakamoto Naoya, Sakata Yuh, Komatsu Yoshito
  JOURNAL OF CLINICAL ONCOLOGY, 33, 3, 20 Jan. 2015, [Peer-reviewed]
• 閉塞性黄疸患者における胆道ドレナージ後の肝硬度の変化　　　　　　　　　　　　　　　
  久保 公利, 河上 洋, 桑谷 将城, 川久保 和道, 阿部 容子, 川畑 修平, 坂本 直哉, 作原 佑介, 白土 博樹, 西田 睦
  超音波医学, 42, 1, 89, 89, (公社)日本超音波医学会, Jan. 2015
  Japanese
• スクリーニング経腹的超音波検査による膀胱癌正診率　　　　　　　　　　　　　　　
  津田 桃子, 松島 瑠美子, 西田 睦, 佐藤 恵美, 工藤 悠輔, 堀江 達則, 守屋 仁彦, 間部 克裕, 加藤 元嗣, 坂本 直哉
  超音波医学, 42, 1, 89, 89, (公社)日本超音波医学会, Jan. 2015
  Japanese
• 定期超音波検査にて偶然発見されたメトトレキサート関連リンパ増殖性疾患の一症例　　　　　　　　　　　　　　　
  松島 瑠美子, 梅村 真知子, 藤田 與茂, 高野 眞寿, 片桐 雅樹, 工藤 峰生, 津田 桃子, 加藤 元嗣, 坂本 直哉, 西田 睦
  超音波医学, 42, 1, 90, 90, (公社)日本超音波医学会, Jan. 2015
  Japanese
• Pancreatic cancer with infectious pancreatic pseudocyst communicating to the portal vein
  KUBO Kimitoshi, KAWAKAMI Hiroshi, KUWATANI Masaki, MITSUHASHI Tomoko, KAWAKUBO Kazumichi, KAWAHATA Shuhei, KUBOTA Yoshimasa, SAKAMOTO Naoya
  Suizo, 30, 5, 679, 688, Japan Pancreas Society, 2015
  Japanese, A 69-year-old female with fever, a pancreatic mass and portal vein thrombosis was referred to our hospital. Blood culture test was positive for Escherichia coli. Abdominal contrast-enhanced CT revealed a heterogeneously enhanced oval mass in the head of the pancreas with a size of 16×14mm, and a non-enhanced nodule in the portal vein, which was adjacent to a cystic lesion in the body of the pancreas. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of the mass in the head of the pancreas indicated adenocarcinoma. On the diagnosis of pancreatic cancer with infectious pseudocyst and portal vein thrombosis, she underwent subtotal stomach-preserving pancreaticoduodenectomy and partial round resection of the portal vein. Histopathological findings of the resected specimen revealed pancreatic head cancer followed by pancreatitis which caused the pancreatic pseudocyst. Infection of the pancreatic pseudocyst would lead to the communication between the cyst and the portal vein. This is the first case with pancreatic cancer with infectious pancreatic pseudocyst communicating to the portal vein.
• Development of selective bile duct cannulation
  Kawakami Hiroshi, Kuwatani Masaki, Kawakubo Kazumichi, Kawahata Shuhei, Kubota Yoshimasa, Sakamoto Naoya
  J.J.B.A, 29, 4, 752, 761, Japan Biliary Association, 2015
  Japanese, Nearly 50 years have passed since the first report of endoscopic retrograde cholangiography. Ever since, endoscopic retrograde cholangiopancreatography (ERCP) have been a basic procedure for practice in pancreatico-biliary diseases. Of the various procedures of ERCP, selective biliary cannulation is the most basic and important technique. Various cannulation techniques have been reported with the development of endoscopes and devices. However, there still does not exist the perfect technique that enables selective biliary cannulation for whichever cases. Although contrast medium injection cannulation technique is important, wire-guided cannulation technique has been extended and is now widely performed since early 2000s in the US and Europe. We should use various techniques to achieve safe, accurate and effective bile duct cannulation with a shorter procedure time and reduced complications. Nowadays, recent development of bile duct cannulation, especially transpapillary approach, is discussed in this report.
• TGF-beta in tumor microenvironment changes a switch of Notch1-mediated signaling to maintain cancer stem-like cells in esophageal squamous cell carcinoma
  Mitsuteru Natsuizaka, Shingo Kagawa, Kelly Whelan, Shinya Ohashi, Shunsuke Ohnishi, Goki Suda, Naoya Sakamoto, Anil K. Rustgi, Hiroshi Nakagawa
  CANCER RESEARCH, 75, 1, Jan. 2015, [Peer-reviewed]
  English
• Direct peroral ultraslim endoscopy-guided biliary drainage in a patient with cystic duct carcinoma and an occluded self-expandable metallic stent
  Hiroshi Kawakami, Masaki Kuwatani, Yoko Abe, Yoshimasa Kubota, Kazumichi Kawakubo, Kimitoshi Kubo, Shuhei Kawahata, Naoya Sakamoto
  ENDOSCOPY, 47, E43, E44, 2015, [Peer-reviewed]
  English
• Significance of miR-148a in Colorectal Neoplasia: Downregulation of miR-148a Contributes to the Carcinogenesis and Cell Invasion of Colorectal Cancer
  Yumi Hibino, Naoya Sakamoto, Yutaka Naito, Keisuke Goto, Htoo Zarni Oo, Kazuhiro Sentani, Takao Hinoi, Hideki Ohdan, Naohide Oue, Wataru Yasui
  PATHOBIOLOGY, 82, 5, 233, 241, 2015, [Peer-reviewed]
  English, Scientific journal
• Risk factors for technical failure of endoscopic double self-expandable metallic stent placement by partial stent-in-stent method
  Kazumichi Kawakubo, Hiroshi Kawakami, Yoshihide Toyokawa, Koichi Otani, Masaki Kuwatani, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Yoshimasa Kubota, Naoya Sakamoto
  JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES, 22, 1, 79, 85, Jan. 2015, [Peer-reviewed]
  English, Scientific journal
• Serum HER2 levels and HER2 status in tumor cells in advanced gastric cancer patients
  Takahide Sasaki, Nozomu Fuse, Takeshi Kuwata, Shogo Nomura, Kazuhiro Kaneko, Toshihiko Doi, Takayuki Yoshino, Hiromichi Asano, Atsushi Ochiai, Yoshito Komatsu, Naoya Sakamoto, Atsushi Ohtsu
  JAPANESE JOURNAL OF CLINICAL ONCOLOGY, 45, 1, 43, 48, Jan. 2015, [Peer-reviewed]
  English, Scientific journal
• Endoscopic nasogallbladder tube or stent placement in acute cholecystitis: a preliminary prospective randomized trial in Japan (with videos)
  Takao Itoi, Hiroshi Kawakami, Akio Katanuma, Atsushi Irisawa, Atsushi Sofuni, Fumihide Itokawa, Takayoshi Tsuchiya, Reina Tanaka, Junko Umeda, Shomei Ryozawa, Shinpei Doi, Naoya Sakamoto, Ichiro Yasuda
  GASTROINTESTINAL ENDOSCOPY, 81, 1, 111, 118, Jan. 2015, [Peer-reviewed]
  English, Scientific journal
• Chromoendoscopy With Iodine Staining, as Well as Narrow-Band Imaging, Is Still Useful and Reliable for Screening of Early Esophageal Squamous Cell Carcinoma
  Yuichi Shimizu, Masakazu Takahashi, Takeshi Mizushima, Shouko Ono, Katsuhiro Mabe, Shunsuke Ohnishi, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  AMERICAN JOURNAL OF GASTROENTEROLOGY, 110, 1, 193, 194, Jan. 2015, [Peer-reviewed]
  English
• Direct peroral ultraslim endoscopy-guided biliary drainage in a patient with cystic duct carcinoma and an occluded self-expandable metallic stent
  Hiroshi Kawakami, Masaki Kuwatani, Yoko Abe, Yoshimasa Kubota, Kazumichi Kawakubo, Kimitoshi Kubo, Shuhei Kawahata, Naoya Sakamoto
  ENDOSCOPY, 47, E43, E44, 2015, [Peer-reviewed]
  English
• Randomized controlled trial on the skin toxicity of panitumumab in Japanese patients with metastatic colorectal cancer: HGCSG1001 study; J-STEPP.
  Yoshimitsu Kobayashi, Yoshito Komatsu, Satoshi Yuki, Hiraku Fukushima, Takahide Sasaki, Ichiro Iwanaga, Minoru Uebayashi, Hiroyuki Okuda, Takaya Kusumi, Takuto Miyagishima, Susumu Sogabe, Miki Tateyama, Kazuteru Hatanaka, Yasushi Tsuji, Michio Nakamura, Jun Konno, Fumiyasu Yamamoto, Manabu Onodera, Kazuhiro Iwai, Yuh Sakata, Riichiro Abe, Koji Oba, Naoya Sakamoto
  Future oncology (London, England), 11, 4, 617, 27, 2015, [Peer-reviewed], [International Magazine]
  English, Scientific journal, AIM: We planned a randomized, open-label trial to evaluate differences between pre-emptive and reactive skin treatment for panitumumab (Pmab)-associated skin toxicities in Japanese patients with metastatic colorectal cancer. PATIENTS & METHODS: Patients receiving third-line Pmab-containing regimens were randomized to pre-emptive or reactive treatment. The primary end point was the cumulative incidence of ≥grade 2 skin toxicities during 6 weeks. Retrospectively, a dermatologist reviewed skin toxicities, in a blinded manner. RESULTS: A total of 95 patients were enrolled (pre-emptive: 47, reactive: 48). The primary end point was achieved (21.3 and 62.5% [risk ratio: 0.34; p < 0.001], for pre-emptive and reactive treatment, respectively). A similar trend was observed in central review. CONCLUSION: Pre-emptive skin treatment could reduce the severity of Pmab-associated skin toxicities in Japanese metastatic colorectal cancer patients.
• Human Amnion-Derived Mesenchymal Stem Cell Transplantation Ameliorates Dextran Sulfate Sodium-Induced Severe Colitis in Rats
  Reizo Onishi, Shunsuke Ohnishi, Ryosuke Higashi, Michiko Watari, Kenichi Yamahara, Naoto Okubo, Koji Nakagawa, Takehiko Katsurada, Goki Suda, Mitsuteru Natsuizaka, Hiroshi Takeda, Naoya Sakamoto
  CELL TRANSPLANTATION, 24, 12, 2601, 2614, 2015, [Peer-reviewed]
  English, Scientific journal
• Huge hemothorax caused by endoscopic ultrasound-guided fine-needle aspiration of a submucosal tumor of the gastric fornix
  Hiroshi Kawakami, Masaki Kuwatani, Kimitoshi Kubo, Yoshimasa Kubota, Kazumichi Kawakubo, Yoko Abe, Shuhei Kawahata, Naotake Homma, Yasuhiro Hida, Naoya Sakamoto
  ENDOSCOPY, 47, E69, E70, 2015, [Peer-reviewed]
  English
• A guidewire-assisted biopsy technique to assist advancement through a biliary stricture to perform selective mapping biopsy
  Hiroshi Kawakami, Masaki Kuwatani, Yoko Abe, Shuhei Kawahata, Kazumichi Kawakubo, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 47, E217, E218, 2015, [Peer-reviewed]
  English
• Endoscopic ultrasound-guided pelvic abscess drainage using a dedicated, wide, flared-end, fully covered self-expandable metal stent
  Hiroshi Kawakami, Masaki Kuwatani, Shuhei Kawahata, Yoshimasa Kubota, Kimitoshi Kubo, Kazumichi Kawakubo, Naoya Sakamoto
  ENDOSCOPY, 47, E265, E266, 2015, [Peer-reviewed]
  English
• Endoscopic ultrasound-guided antegrade bile duct stone treatment followed by direct peroral transhepatic cholangioscopy in a patient with Roux-en-Y reconstruction
  Hiroshi Kawakami, Masaki Kuwatani, Yoshimasa Kubota, Shuhei Kawahata, Kimitoshi Kubo, Kazumichi Kawakubo, Naoya Sakamoto
  ENDOSCOPY, 47, E340, E341, 2015, [Peer-reviewed]
  English
• Acute pancreatitis-like bile leakage around the portal vein system after endoscopic ultrasound-guided choledochoduodenostomy
  Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Yoshimasa Kubota, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 47, E346, E347, 2015, [Peer-reviewed]
  English
• Technical difficulty according to location, and risk factors for perforation, in endoscopic submucosal dissection of colorectal tumors
  Takeshi Mizushima, Mototsugu Kato, Ichiro Iwanaga, Fumiyuki Sato, Kimitoshi Kubo, Nobuyuki Ehira, Minoru Uebayashi, Shouko Ono, Manabu Nakagawa, Katsuhiro Mabe, Yuichi Shimizu, Naoya Sakamoto
  SURGICAL ENDOSCOPY AND OTHER INTERVENTIONAL TECHNIQUES, 29, 1, 133, 139, Jan. 2015, [Peer-reviewed]
  English, Scientific journal
• Dengue-Associated Hemophagocytic Syndrome in a Japanese Traveler: A Case Report
  Ken-ichiro Kobayashi, Mayu Hikone, Naoya Sakamoto, Sentaro Iwabuchi, Masahiro Kashiura, Tomohiko Takasaki, Hiroshi Fujita, Kenji Ohnishi
  JOURNAL OF TRAVEL MEDICINE, 22, 1, 64, 66, Jan. 2015, [Peer-reviewed]
  English, Scientific journal
• High and low negative pressure suction techniques in EUS- guided fine- needle tissue acquisition by using 25-gauge needles: a multicenter, prospective, randomized, controlled trial
  Taiki Kudo, Hiroshi Kawakami, Tsuyoshi Hayashi, Ichiro Yasuda, Tsuyoshi Mukai, Hiroyuki Inoue, Akio Katanuma, Kazumichi Kawakubo, Hirotoshi Ishiwatari, Shinpei Doi, Reiko Yamada, Hiroyuki Maguchi, Hiroyuki Isayama, Tomoko Mitsuhashi, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 80, 6, 1030, +, Dec. 2014, [Peer-reviewed]
  English, Scientific journal
• [Discussion Meeting on Infectious diseases in the global era--from travel medicine to countermeasures against emerging infectious diseases].
  Kawana A, Genka I, Sakamoto N, Kato Y, Nakashima K
  Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 103, 11, 2770, 2782, Nov. 2014, [Peer-reviewed]
• Hypoxia-mediated CD24 expression is correlated with gastric cancer aggressiveness by promoting cell migration and invasion
  Nobuaki Fujikuni, Hideki Yamamoto, Kazuaki Tanabe, Yutaka Naito, Naoya Sakamoto, Yuka Tanaka, Kazuyoshi Yanagihara, Naohide Oue, Wataru Yasui, Hideki Ohdan
  CANCER SCIENCE, 105, 11, 1411, 1420, Nov. 2014, [Peer-reviewed]
  English, Scientific journal
• Sofosbuvir plus ribavirin in Japanese patients with chronic genotype 2 HCV infection: an open-label, phase 3 trial
  Masao Omata, Shuhei Nishiguchi, Yoshiyuki Ueno, Hitoshi Mochizuki, Namiki Izumi, Fusao Ikeda, Hidenori Toyoda, Osamu Yokosuka, Kazushige Nirei, Takuya Genda, Takeji Umemura, Tetsuo Takehara, Naoya Sakamoto, Yoichi Nishigaki, Kunio Nakane, Nobuo Toda, Tatsuya Ide, Mikio Yanase, Keisuke Hino, Bing Gao, Kimberly L. Garrison, Hadas Dvory-Sobol, Akinobu Ishizaki, Masa Omote, Diana Brainard, Steven Knox, William T. Symonds, John G. McHutchison, Hiroshi Yatsuhashi, Masashi Mizokami
  JOURNAL OF VIRAL HEPATITIS, 21, 11, 762, 768, Nov. 2014, [Peer-reviewed]
  English, Scientific journal
• TRANSPLANTATION OF HUMAN AMNIOTIC MEMBRANE-DERIVED MESENCHYMAL STEM CELLS IMPROVES RADIATION ENTERITIS
  Minori Honda, Shunsuke Ohnishi, Masayoshi Ono, Kenichi Yamahara, Jun Yoshimatsu, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
  PLACENTA, 35, 10, A7, A7, Oct. 2014, [Peer-reviewed]
  English
• THE ANTI-INFLAMMATORY EFFECT OF HUMAN AMNION-DERIVED MESENCHYMAL STEM CELLS
  Reizo Onishi, Shunsuke Ohnishi, Ryosuke Higashi, Kenichi Yamahara, Jun Yoshimatsu, Takehiko Katsurada, Naoto Okubo, Koji Nakagawa, Hiroshi Takeda, Naoya Sakamoto
  PLACENTA, 35, 10, A23, A23, Oct. 2014, [Peer-reviewed]
  English
• Difference from Bile Duct Cancer and Relationship between Bile Duct Wall Thickness And Serum IgG/IgG4 Levels in IgG4-Related Sclerosing Cholangitis
  Masaki Kuwatani, Hiroshi Kawakami, Yoh Zen, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Naoya Sakamoto
  HEPATO-GASTROENTEROLOGY, 61, 135, 1852, 1856, Oct. 2014, [Peer-reviewed]
  English, Scientific journal
• Subjective adverse reactions to metronidazole in patients with amebiasis
  Kenji Ohnishi, Naoya Sakamoto, Ken-ichiro Kobayashi, Sentaro Iwabuchi, Fukumi Nakamura-Uchiyama, Atsushi Ajisawa, Yuko Yamauchi, Nozomi Takeshita, Yasuyuki Yamamoto, Takafumi Tsunoda, Yukihiro Yoshimura, Natsuo Tachikawa, Tomoko Uehira
  PARASITOLOGY INTERNATIONAL, 63, 5, 698, 700, Oct. 2014, [Peer-reviewed]
  English, Scientific journal
• FIP1L1 presence in FIP1L1-RARA or FIP1L1-PDGFRA differentially contributes to the pathogenesis of distinct types of leukemia
  Junko Iwasaki, Takeshi Kondo, Stephanie Darmanin, Makoto Ibata, Masahiro Onozawa, Daigo Hashimoto, Naoya Sakamoto, Takanori Teshima
  ANNALS OF HEMATOLOGY, 93, 9, 1473, 1481, Sep. 2014, [Peer-reviewed]
  English, Scientific journal
• The J6JFH1 Strain of Hepatitis C Virus Infects Human B-Cells with Low Replication Efficacy
  Masato Nakai, Tsukasa Seya, Misako Matsumoto, Kunitada Shimotohno, Naoya Sakamoto, Hussein H. Aly
  VIRAL IMMUNOLOGY, 27, 6, 285, 294, Aug. 2014, [Peer-reviewed]
  English, Scientific journal
• Identification of PRL1 as a novel diagnostic and therapeutic target for castration-resistant prostate cancer by the Escherichia coli ampicillin secretion trap (CAST) method
  Shunsuke Shinmei, Kazuhiro Sentani, Tetsutaro Hayashi, Naoya Sakamoto, Keisuke Goto, Htoo Zarni Oo, Yutaka Naito, Jun Teishima, Akio Matsubara, Naohide Oue, Hiroki Kuniyasu, Wataru Yasui
  UROLOGIC ONCOLOGY-SEMINARS AND ORIGINAL INVESTIGATIONS, 32, 6, 769, 778, Aug. 2014, [Peer-reviewed]
  English, Scientific journal
• ヘリコバクターの現状・今後 病態との関連 ヘリコバクター・ピロリ胃炎に対する飲水超音波検査を用いた病態評価
  工藤 俊彦, 加藤 元嗣, 西田 睦, 坂本 直哉
  胃病態機能研究会誌, 46, 17, 17, (株)勁草書房コミュニケーション事業部, Jul. 2014
  Japanese
• ITPA genetic variants influence efficacy of PEG-IFN/RBV therapy in older patients infected with HCV genotype 1 and favourable IL28B type
  K. Matsuura, Y. Tanaka, T. Watanabe, K. Fujiwara, E. Orito, M. Kurosaki, N. Izumi, N. Sakamoto, N. Enomoto, H. Yatsuhashi, A. Kusakabe, N. Shinkai, S. Nojiri, T. Joh, M. Mizokami
  JOURNAL OF VIRAL HEPATITIS, 21, 7, 466, 474, Jul. 2014, [Peer-reviewed]
  English, Scientific journal
• Pyoderma gangrenosum successfully treated with antiretroviral therapy alone in a human immunodeficiency virus-infected individual
  Naoya Sakamoto, Naoki Yanagisawa, Noritaka Sekiya, Akihiko Suganuma, Akifumi Imamura, Atsushi Ajisawa
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 20, 7-8, 502, 505, Jul. 2014, [Peer-reviewed]
  English, Scientific journal
• Overexpression of ZDHHC14 promotes migration and invasion of scirrhous type gastric cancer
  Htoo Zarni Oo, Kazuhiro Sentani, Naoya Sakamoto, Katsuhiro Anami, Yutaka Naito, Naohiro Uraoka, Takashi Oshima, Kazuyoshi Yanagihara, Naohide Oue, Wataru Yasui
  ONCOLOGY REPORTS, 32, 1, 403, 410, Jul. 2014, [Peer-reviewed]
  English, Scientific journal
• Endoscopic Ultrasound-Guided Transluminal Drainage for Peripancreatic Fluid Collections: Where Are We Now?
  Hiroshi Kawakami, Takao Itoi, Naoya Sakamoto
  GUT AND LIVER, 8, 4, 341, 355, Jul. 2014, [Peer-reviewed]
  English
• Administration of exogenous acylated ghrelin or rikkunshito, an endogenous ghrelin enhancer, improves the decrease in postprandial gastric motility in an acute restraint stress mouse model
  M. Nahata, Y. Saegusa, C. Sadakane, C. Yamada, K. Nakagawa, N. Okubo, S. Ohnishi, T. Hattori, N. Sakamoto, H. Takeda
  NEUROGASTROENTEROLOGY AND MOTILITY, 26, 6, 821, 831, Jun. 2014, [Peer-reviewed]
  English, Scientific journal
• Gender Difference Influences Food Intake Under an Emotional Stress via 5-HT2CR Activation in Aged Mice
  Shunsuke Ohnishi, Shuichi Muto, Koji Nakagawa, Chihiro Yamada, Yayoi Saegusa, Miwa Nahata, Chiharu Sadakane, Tomohisa Hattori, Naoya Sakamoto, Hiroshi Takeda
  GASTROENTEROLOGY, 146, 5, S498, S499, May 2014, [Peer-reviewed]
  English
• Association of Abnormal Ghrelin Dynamics With Delayed Gastric Emptying in Acute Restraint-Stressed Mice
  Hiroshi Takeda, Shunsuke Ohnishi, Shuichi Muto, Koji Nakagawa, Chiharu Sadakane, Yayoi Saegusa, Miwa Nahata, Chihiro Yamada, Tomohisa Hattori, Naoya Sakamoto
  GASTROENTEROLOGY, 146, 5, S658, S658, May 2014, [Peer-reviewed]
  English
• The Possibility of Rikkunshito As a Treatment for Anorexia: a Proposal From a Basic Research Perspective
  Hiroshi Takeda, Shunsuke Ohnishi, Shuichi Muto, Koji Nakagawa, Chiharu Sadakane, Yayoi Saegusa, Miwa Nahata, Chihiro Yamada, Tomohisa Hattori, Naoya Sakamoto
  GASTROENTEROLOGY, 146, 5, S899, S899, May 2014, [Peer-reviewed]
  English
• EGFR Inhibitors Eliminate Esophageal Cancer Stem Cells by Suppressing Epithelial-Mesenchymal Transition
  Mitsuteru Natsuizaka, Bongani Kaimila, Yoshimasa Kubota, Yutaka Hatanaka, Katsuji Marukawa, Katsumi Terashita, Fumiyuki Satou, Shunsuke Ohnishi, Goki Suda, Shinya Ohashi, Shingo Kagawa, Kelly A. Whelan, Anil K. Rustgi, Hiroshi Nakagawa, Naoya Sakamoto
  GASTROENTEROLOGY, 146, 5, S821, S821, May 2014, [Peer-reviewed]
  English
• Rikkunshito, a Traditional Japanese Kampo Medicine, Ameliorates the Decrease in Feeding Behavior in Aged Mice Exposed to Stress via Enhancement of Endogenous Ghrelin Production
  Shuichi Muto, Shunsuke Ohnishi, Koji Nakagawa, Chihiro Yamada, Yayoi Saegusa, Miwa Nahata, Chiharu Sadakane, Tomohisa Hattori, Naoya Sakamoto, Hiroshi Takeda
  GASTROENTEROLOGY, 146, 5, S848, S849, May 2014, [Peer-reviewed]
  English
• Safety and Utility of Single-Session Endoscopic Ultrasonography and Endoscopic Retrograde Cholangiopancreatography for the Evaluation of Pancreatobiliary Diseases
  Kazumichi Kawakubo, Hiroshi Kawakami, Masaki Kuwatani, Shin Haba, Taiki Kudo, Yoko Abe, Shuhei Kawahata, Manabu Onodera, Nobuyuki Ehira, Hiroaki Yamato, Kazunori Eto, Naoya Sakamoto
  GUT AND LIVER, 8, 3, 329, 332, May 2014, [Peer-reviewed]
  English, Scientific journal
• [Future perspectives of hepatitis C therapeutics].
  Sakamoto N
  [Hokkaido igaku zasshi] The Hokkaido journal of medical science, 89, 1, 13, 15, May 2014, [Peer-reviewed]
• Endoscopic diagnosis of early neoplasia of the esophagus with narrow band imaging: Correlations among background coloration and iodine staining findings
  Masakazu Takahashi, Yuichi Shimizu, Masayoshi Ono, Mio Suzuki, Saori Omori, Takeshi Yoshida, Yasuaki Mori, Manabu Nakagawa, Shouko Ono, Soichi Nakagawa, Katsuhiro Mabe, Mototsugu Kato, Kanako Hatanaka, Masahiro Asaka, Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 29, 4, 762, 768, Apr. 2014, [Peer-reviewed]
  English, Scientific journal
• Influence of the safety and diagnostic accuracy of preoperative endoscopic ultrasound-guided fine-needle aspiration for resectable pancreatic cancer on clinical performance
  Taiki Kudo, Hiroshi Kawakami, Masaki Kuwatani, Kazunori Eto, Shuhei Kawahata, Yoko Abe, Manabu Onodera, Nobuyuki Ehira, Hiroaki Yamato, Shin Haba, Kazumichi Kawakubo, Naoya Sakamoto
  WORLD JOURNAL OF GASTROENTEROLOGY, 20, 13, 3620, 3627, Apr. 2014, [Peer-reviewed]
  English, Scientific journal
• 脂肪組織と石灰化成分を内部に含有した胆嚢癌の1例
  桑谷 将城, 河上 洋, 川久保 和道, 工藤 大樹, 阿部 容子, 羽場 真, 田中 栄一, 平野 聡, 三橋 智子, 坂本 直哉
  胆道, 28, 1, 73, 80, 日本胆道学会, Mar. 2014
  Japanese
• Leptospirosis in a Japanese urban area: A case report and literature review
  Yukiko Shimizu, Naoya Sakamoto, Yusuke Ainoda, Mayu Hikone, Kenichiro Kobayashi, Sentaro Iwabuchi, Nobuo Koizumi, Kenji Ohnishi
  JOURNAL OF INFECTION AND CHEMOTHERAPY, 20, 3-4, 278, 281, Mar. 2014, [Peer-reviewed]
  English
• Transpapillary dilation of refractory severe biliary stricture or main pancreatic duct by using a wire-guided diathermic dilator (with video)
  Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Kazunori Eto, Shin Haba, Taiki Kudo, Yoko Abe, Shuhei Kawahata, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 79, 2, 338, 343, Feb. 2014, [Peer-reviewed]
  English, Scientific journal
• Heat shock factor 1 accelerates hepatocellular carcinoma development by activating nuclear factor-B/mitogen-activated protein kinase
  Makoto Chuma, Naoya Sakamoto, Akira Nakai, Shuhei Hige, Mitsuru Nakanishi, Mitsuteru Natsuizaka, Goki Suda, Takuya Sho, Kanako Hatanaka, Yoshihiro Matsuno, Hideki Yokoo, Toshiya Kamiyama, Akinobu Taketomi, Gen Fujii, Kosuke Tashiro, Yoko Hikiba, Mitsuaki Fujimoto, Masahiro Asaka, Shin Maeda
  CARCINOGENESIS, 35, 2, 272, 281, Feb. 2014, [Peer-reviewed]
  English, Scientific journal
• Is wire-guided selective bile duct cannulation effective for prevention of post-ERCP pancreatitis by all endoscopists?
  Hiroshi Kawakami, Hiroyuki Isayama, Hiroyuki Maguchi, Masaki Kuwatani, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Kazuhiko Koike, Naoya Sakamoto
  ENDOSCOPY, 46, 2, 163, 163, Feb. 2014, [Peer-reviewed]
  English
• Randomized controlled trial on the skin toxicity of panitumumab in third-line treatment of KRAS wild-type metastatic colorectal cancer: HGCSG1001 (Japanese Skin Toxicity Evaluation Protocol with Panitumumab; J-STEPP).
  Iwanaga Ichiro, Komatsu Yoshito, Yuki Satoshi, Kobayashi Yoshimitsu, Sakamoto Naoya, Uebayashi Minoru, Okuda Hiroyuki, Kusumi Takaya, Sogabe Susumu, Miyagishima Takuto, Tateyama Miki, Tsuji Yasushi, Hatanaka Kazuteru, Nakamura Michio, Konno Jun, Yamamoto Fumiyasu, Iwai Kazuhiro, Onodera Manabu, Oba Koji, Sakata Yuh
  JOURNAL OF CLINICAL ONCOLOGY, 32, 3, 20 Jan. 2014, [Peer-reviewed]
• Endoscopic ultrasound-guided rendezvous technique for difficult cannulation into the bile duct　　　　　　　　　　　　　　　
  Kazumichi Kawakubo, Hiroshi Kawakami, Hiroyuki Isayama, Naoya Sakamoto
  Gastroenterological Endoscopy, 56, 3, 504, 514, Japan Gastroenterological Endoscopy Society, 2014
  English, Scientific journal
• A pivotal role of KLF5 in regulation of cancer stem-like cells in hepatocellular carcinoma
  Mitsuteru Natsuizaka, Osamu Maehara, Fumiyuki Sato, Yoshimasa Kubota, Goki Suda, Jun Itoh, Seiji Tsunematsu, Yoko Tsukuda, Katsumi Terashita, Masato Nakai, Takuya Sho, Koji Ogawa, Shunsuke Ohnishi, Naoya Sakamoto
  HEPATOLOGY, 60, 825A, 825A, 2014, [Peer-reviewed]
  English
• Characterization of a lymphotropic HCV-J6JFH1 replication in human primary B cells
  Nakai Masato, Seya Tsukasa, Matsumoto Misako, Aly Hussein H, Itoh Jun, Tsunematsu Seiji, Sato Fumiyuki, Tsukuda Yoko, Terashita Katsumi, Sho Takuya, Suda Goki, Natsuizaka Mitsuteru, Ogawa Koji, Sakamoto Naoya
  HEPATOLOGY, 60, 1083A, 1084A, 2014, [Peer-reviewed]
• Hepatosplenic Gamma-delta T-cell Lymphoma Associated with Epstein-Barr Virus
  Seiji Tsunematsu, Mitsuteru Natsuizaka, Hiromi Fujita, Noriyuki Otsuka, Katsumi Terashita, Fumiyuki Sato, Tomoe Kobayashi, Masato Nakai, Yoko Tsukuda, Hiromasa Horimoto, Takuya Sho, Goki Suda, Mitsuru Nakanishi, Satoshi Hashino, Makoto Chuma, Naoya Sakamoto
  INTERNAL MEDICINE, 53, 18, 2079, 2082, 2014, [Peer-reviewed]
  English, Scientific journal
• Candy-like sign during endoscopic ultrasound-guided choledochoduodenostomy as an indication of the long distance between the bile duct and duodenal wall
  Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Yoshimasa Kubota, Naoya Sakamoto
  ENDOSCOPY, 46, E406, E407, 2014, [Peer-reviewed]
  English
• Rendezvous biliary recanalization combining percutaneous and endoscopic techniques using a diathermic dilator for bile duct obstruction
  Hiroshi Kawakami, Daisuke Abo, Kazumichi Kawakubo, Masaki Kuwatani, Yuki Yoshino, Yoshimasa Kubota, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Yusuke Sakuhara, Hiroki Shirato, Naoya Sakamoto
  ENDOSCOPY, 46, E460, E461, 2014, [Peer-reviewed]
  English
• Endoscopic ultrasonography-guided antegrade diathermic dilation for the treatment of complete obstruction of a pancreaticogastrostomy
  Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Yoshimasa Kubota, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 46, E517, E518, 2014, [Peer-reviewed]
  English
• Endoscopic placement of a fully covered self-expandable metallic stent to treat an arteriobiliary fistula
  Hiroshi Kawakami, Munenori Okamoto, Masaki Kuwatani, Yoshimasa Kubota, Kazumichi Kawakubo, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 46, E566, E567, 2014, [Peer-reviewed]
  English
• Endoscopic ultrasonography-guided liver abscess drainage using a dedicated, wide, fully covered self-expandable metallic stent with flared-ends
  Hiroshi Kawakami, Kazumichi Kawakubo, Masaki Kuwatani, Yoshimasa Kubota, Yoko Abe, Shuhei Kawahata, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 46, E982, E983, 2014, [Peer-reviewed]
  English
• Endoscopic ultrasound-guided antegrade diathermic dilation followed by self-expandable metallic stent placement for anastomotic stricture after hepaticojejunostomy (with video)
  Hiroshi Kawakami, Masaki Kuwatani, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 26, 1, 121, 122, Jan. 2014, [Peer-reviewed]
  English
• Roadmap to eliminate gastric cancer with Helicobacter pylori eradication and consecutive surveillance in Japan
  Masahiro Asaka, Mototsugu Kato, Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY, 49, 1, 1, 8, Jan. 2014, [Peer-reviewed]
  English
• A "resect and watch" strategy with endoscopic resection for pharyngeal cancer with massive subepithelial invasion would not be rational
  Yuichi Shimizu, Masakazu Takahashi, Takeshi Yoshida, Shouko Ono, Katsuhiro Mabe, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 79, 1, 178, 179, Jan. 2014, [Peer-reviewed]
  English
• Bilateral Facial Nerve Palsy and Appendicitis Occurring during Acute Retroviral Syndrome
  Hiroshi Morioka, Naoya Sakamoto, Sentaro Iwabuchi, Kenji Ohnishi
  INTERNAL MEDICINE, 53, 2, 155, 158, 2014, [Peer-reviewed]
  English, Scientific journal
• Acute pancreatitis caused by Anisakis
  Hiroaki Yamato, Hiroshi Kawakami, Kikuko Takagi, Koji Ogawa, Kazuteru Hatanaka, Yoshiya Yamamoto, Hirohito Naruse, Kazumichi Kawakubo, Naoya Sakamoto
  Gastrointestinal Endoscopy, 79, 4, 676, 678, Mosby Inc., 2014, [Peer-reviewed]
  English
• Endoscopic salvage technique for spontaneous dislocation and tumor ingrowth of a partially covered, self-expandable metallic stent after endoscopic ultrasound-guided choledochoduodenostomy
  Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Naoya Sakamoto
  ENDOSCOPY, 46, E58, E59, Jan. 2014, [Peer-reviewed]
  English
• Multiple Ring-enhancing Lesions in the Brain of a Patient with AIDS
  Kenichiro Kobayashi, Naoya Sakamoto, Sentaro Iwabuchi, Kenji Ohnishi
  INTERNAL MEDICINE, 53, 6, 641, 641, 2014, [Peer-reviewed]
  English
• Human intestinal spirochetosis is significantly associated with sessile serrated adenomas/polyps
  Saori Omori, Katsuhiro Mabe, Kanako Hatanaka, Masayoshi Ono, Mio Matsumoto, Masakazu Takahashi, Takeshi Yoshida, Shoko Ono, Yuichi Shimizu, Nozomi Sugai, Akira Suzuki, Shinichi Katsuki, Takahiro Fujii, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  PATHOLOGY RESEARCH AND PRACTICE, 210, 7, 440, 443, 2014, [Peer-reviewed]
  English, Scientific journal
• Endoscopic ultrasound-guided antegrade diathermic dilation followed by self-expandable metal stent placement for malignant distal biliary stricture
  Hiroshi Kawakami, Masaki Kuwatani, Kazumichi Kawakubo, Taiki Kudo, Yoko Abe, Kimitoshi Kubo, Yoshimasa Kubota, Naoya Sakamoto
  ENDOSCOPY, 46, E328, 9, 2014, [Peer-reviewed]
  English
• Inhibitory Effects of Caffeic Acid Phenethyl Ester Derivatives on Replication of Hepatitis C Virus
  Hui Shen, Atsuya Yamashita, Masamichi Nakakoshi, Hiromasa Yokoe, Masashi Sudo, Hirotake Kasai, Tomohisa Tanaka, Yuusuke Fujimoto, Masanori Ikeda, Nobuyuki Kato, Naoya Sakamoto, Hiroko Shindo, Shinya Maekawa, Nobuyuki Enomoto, Masayoshi Tsubuki, Kohji Moriishi
  PLOS ONE, 8, 12, e82299, Dec. 2013, [Peer-reviewed]
  English, Scientific journal
• Substitution of amino acid 70/91 in the hepatitis C virus core region affects infectious virus production and cell surface expression of MHC class I
  Tasaka-Fujita Megumi, Sugiyama Nao, Kang Wonseok, Murayama Asako, Asahina Yasuhiro, Sakamoto Naoya, Wakita Takaji, Shin Eui-Cheol, Kato Takanobu
  HEPATOLOGY, 58, 932A, Oct. 2013, [Peer-reviewed]
• Pathophysiologic basis of anorexia: Focus on the interaction between ghrelin dynamics and the serotonergic system
  Hiroshi Takeda, Koji Nakagawa, Naoto Okubo, Mie Nishimura, Shuichi Muto, Shunsuke Ohnishi, Naoya Sakamoto, Hidetaka Hosono, Masahiro Asaka
  Biological and Pharmaceutical Bulletin, 36, 9, 1401, 1405, Sep. 2013, [Peer-reviewed]
  English, Scientific journal
• [Case report: focal adenocarcinoma arising from sessile serrated adenoma/polyp with intestinal spirochetosis, report of a case].
  Omori S, Mabe K, Ono M, Suzuki M, Takahashi M, Ono S, Simizu Y, Kato M, Hatanaka K, Sakamoto N
  Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine, 102, 8, 2046, 2049, Aug. 2013, [Peer-reviewed]
• Diagnostic ability and factors affecting accuracy of endoscopic ultrasound-guided fine needle aspiration for pancreatic solid lesions: Japanese large single center experience
  Shin Haba, Kenji Yamao, Vikram Bhatia, Nobumasa Mizuno, Kazuo Hara, Susumu Hijioka, Hiroshi Imaoka, Yasumasa Niwa, Masahiro Tajika, Shinya Kondo, Tsutomu Tanaka, Yasuhiro Shimizu, Yasushi Yatabe, Waki Hosoda, Hiroshi Kawakami, Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY, 48, 8, 973, 981, Aug. 2013, [Peer-reviewed]
  English, Scientific journal
• Therapeutic effect of praziquantel against taeniasis asiatica
  Kenji Ohnishi, Naoya Sakamoto, Ken-ichiro Kobayashi, Sentaro Iwabuchi, Fukumi Nakamura-Uchiyama
  INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES, 17, 8, E656, E657, Aug. 2013, [Peer-reviewed]
  English, Scientific journal
• Endoscopic in vivo cellular imaging of superficial squamous cell carcinoma of the head and neck by using an integrated endocytoscopy system (with video)
  Yuichi Shimizu, Masakazu Takahashi, Takeshi Yoshida, Shouko Ono, Katsuhiro Mabe, Mototsugu Kato, Masahiro Asaka, Kanako Hatanaka, Naoya Sakamoto
  Gastrointestinal Endoscopy, 78, 2, 351, 358, Aug. 2013, [Peer-reviewed]
  English, Scientific journal
• [After endoscopic treatment of early stage gastric cancer].
  Kato M, Ono S, Mabe K, Sakamoto N, Asaka M
  Nihon rinsho. Japanese journal of clinical medicine, 71, 8, 1429, 1435, Aug. 2013, [Peer-reviewed]
• Endoscopic ultrasound-guided rendezvous procedure for unidentifiable papilla and non-dilated pancreatic duct (with video)
  Hiroshi Kawakami, Masaki Kuwatani, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 25, 4, 466, 466, Jul. 2013, [Peer-reviewed]
  English
• Synthesis of ¹⁸O-labeled RNA for application to kinetic studies and imaging.
  Tomohiro Hamasaki, Takahiro Matsumoto, Naoya Sakamoto, Akiko Shimahara, Shiori Kato, Ayumi Yoshitake, Ayumi Utsunomiya, Hisayoshi Yurimoto, Esteban C Gabazza, Tadaaki Ohgi
  Nucleic acids research, 41, 12, e126, Jul. 2013, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Radioisotopes and fluorescent compounds are frequently used for RNA labeling but are unsuitable for clinical studies of RNA drugs because of the risk from radiation exposure or the nonequivalence arising from covalently attached fluorophores. Here, we report a practical phosphoramidite solid-phase synthesis of (18)O-labeled RNA that avoids these disadvantages, and we demonstrate its application to quantification and imaging. The synthesis involves the introduction of a nonbridging (18)O atom into the phosphate group during the oxidation step of the synthetic cycle by using (18)O water as the oxygen donor. The (18)O label in the RNA was stable at pH 3-8.5, while the physicochemical and biological properties of labeled and unlabeled short interfering RNA were indistinguishable by circular dichroism, melting temperature and RNA-interference activity. The (18)O/(16)O ratio as measured by isotope ratio mass spectrometry increased linearly with the concentration of (18)O-labeled RNA, and this technique was used to determine the blood concentration of (18)O-labeled RNA after administration to mice. (18)O-labeled RNA transfected into human A549 cells was visualized by isotope microscopy. The RNA was observed in foci in the cytoplasm around the nucleus, presumably corresponding to endosomes. These methodologies may be useful for kinetic and cellular-localization studies of RNA in basic and pharmaceutical studies.
• Hypoxia-Inducible Factors Activate CD133 Promoter through ETS Family Transcription Factors
  Shunsuke Ohnishi, Osamu Maehara, Koji Nakagawa, Ayano Kameya, Kanako Otaki, Hirotoshi Fujita, Ryosuke Higashi, Kikuko Takagi, Masahiro Asaka, Naoya Sakamoto, Masanobu Kobayashi, Hiroshi Takeda
  PLoS ONE, 8, 6, e66255, 20 Jun. 2013, [Peer-reviewed]
  English, Scientific journal
• Wnt5a signaling mediates biliary differentiation of fetal hepatic stem/progenitor cells in mice
  Kei Kiyohashi, Sei Kakinuma, Akihide Kamiya, Naoya Sakamoto, Sayuri Nitta, Hideto Yamanaka, Kouhei Yoshino, Junko Fujiki, Miyako Murakawa, Akiko Kusano-Kitazume, Hiromichi Shimizu, Ryuichi Okamoto, Seishin Azuma, Mina Nakagawa, Yasuhiro Asahina, Naoki Tanimizu, Akira Kikuchi, Hiromitsu Nakauchi, Mamoru Watanabe
  Hepatology, 57, 6, 2502, 2513, Jun. 2013, [Peer-reviewed]
  English, Scientific journal
• Expression of olfactomedin 4 and claudin-18 in serrated neoplasia of the colorectum: A characteristic pattern is associated with sessile serrated lesion
  Kazuhiro Sentani, Naoya Sakamoto, Fumio Shimamoto, Katsuhiro Anami, Naohide Oue, Wataru Yasui
  Histopathology, 62, 7, 1018, 1027, 7, Jun. 2013, [Peer-reviewed]
  English, Scientific journal
• Wnt5a signaling mediates biliary differentiation of fetal hepatic stem/progenitor cells in mice
  Kei Kiyohashi, Sei Kakinuma, Akihide Kamiya, Naoya Sakamoto, Sayuri Nitta, Hideto Yamanaka, Kouhei Yoshino, Junko Fujiki, Miyako Murakawa, Akiko Kusano-Kitazume, Hiromichi Shimizu, Ryuichi Okamoto, Seishin Azuma, Mina Nakagawa, Yasuhiro Asahina, Naoki Tanimizu, Akira Kikuchi, Hiromitsu Nakauchi, Mamoru Watanabe
  HEPATOLOGY, 57, 6, 2502, 2513, Jun. 2013, [Peer-reviewed]
  English, Scientific journal
• What is an adequate management strategy for pharyngeal low-grade dysplasia?
  Yuichi Shimizu, Masakazu Takahashi, Takeshi Yoshida, Shouko Ono, Katsuhiro Mabe, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 77, 6, 972, 973, Jun. 2013, [Peer-reviewed]
  English
• Involvement of Ghrelin Signaling Dysfunction in Acute Restraint Stress-Induced Delayed Gastric Emptying
  Shunsuke Ohnishi, Shuichi Muto, Koji Nakagawa, Chiharu Sadakane, Yayoi Saegusa, Miwa Nahata, Chihiro Yamada, Tomohisa Hattori, Masahiro Asaka, Naoya Sakamoto, Hiroshi Takeda
  GASTROENTEROLOGY, 144, 5, S542, S542, May 2013, [Peer-reviewed]
  English
• Transplantaion of Human Fetal Membrane-Derived Mesenchymal Stem Cells Improves Severe Colitis Induced by Dextran Sulfate Sodium in Rats
  Reizo Onishi, Shunsuke Ohnishi, Ryosuke Higashi, Michiko Watari, Waka Kobayashi, Takehiko Katsurada, Hiroshi Takeda, Naoya Sakamoto
  GASTROENTEROLOGY, 144, 5, S811, S812, May 2013, [Peer-reviewed]
  English
• MicroRNA-155 is a predictive marker for survival in patients with clear cell renal cell carcinoma
  Shunsuke Shinmei, Naoya Sakamoto, Keisuke Goto, Kazuhiro Sentani, Katsuhiro Anami, Tetsutaro Hayashi, Jun Teishima, Akio Matsubara, Naohide Oue, Yasuhiko Kitadai, Wataru Yasui
  International Journal of Urology, 20, 5, 468, 477, May 2013, [Peer-reviewed]
  English, Scientific journal
• Hepatobiliary alveolar echinococcosis infiltration of the hepatic hilum diagnosed by endoscopic ultrasonography-guided fine-needle aspiration
  Hiroshi Kawakami, Masaki Kuwatani, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 25, 3, 339, 340, May 2013, [Peer-reviewed]
  English
• Hepatitis C Virus Replication Is Modulated by the Interaction of Nonstructural Protein NS5B and Fatty Acid Synthase
  Jing-Tang Huang, Ching-Ping Tseng, Mei-Huei Liao, Shao-Chun Lu, Wei-Zhou Yeh, Naoya Sakamoto, Chuan-Mu Chen, Ju-Chien Cheng
  JOURNAL OF VIROLOGY, 87, 9, 4994, 5004, May 2013, [Peer-reviewed]
  English, Scientific journal
• New stent exchange technique following endoscopic ultrasound-guided nasobiliary drainage (with video)
  Hiroshi Kawakami, Masaki Kuwatani, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 25, 3, 343, 344, May 2013, [Peer-reviewed]
  English
• NX-PVKA assay, a conventional but refined prognostic biomarker for hepatocellular carcinoma
  Naoya Sakamoto
  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 28, 5, 755, 756, May 2013, [Peer-reviewed]
  English
• Human equilibrative nucleoside transporter 1 and Notch3 can predict gemcitabine effects in patients with unresectable pancreatic cancer
  K. Eto, H. Kawakami, M. Kuwatani, T. Kudo, Y. Abe, S. Kawahata, A. Takasawa, M. Fukuoka, Y. Matsuno, M. Asaka, N. Sakamoto
  British Journal of Cancer, 108, 7, 1488, 1494, 16 Apr. 2013, [Peer-reviewed]
  English, Scientific journal
• IL-28B (IFN-λ3) and IFN-α synergistically inhibit HCV replication
  H. Shindo, S. Maekawa, K. Komase, M. Miura, M. Kadokura, R. Sueki, N. Komatsu, K. Shindo, F. Amemiya, Y. Nakayama, T. Inoue, M. Sakamoto, A. Yamashita, K. Moriishi, N. Enomoto
  Journal of Viral Hepatitis, 20, 4, 281, 289, Apr. 2013, [Peer-reviewed]
  English, Scientific journal
• Model incorporating the ITPA genotype identifies patients at high risk of anemia and treatment failure with pegylated-interferon plus ribavirin therapy for chronic hepatitis C
  Masayuki Kurosaki, Yasuhito Tanaka, Nao Nishida, Naoya Sakamoto, Nobuyuki Enomoto, Kentaro Matsuura, Yasuhiro Asahina, Mina Nakagawa, Mamoru Watanabe, Minoru Sakamoto, Shinya Maekawa, Katsushi Tokunaga, Masashi Mizokami, Namiki Izumi
  JOURNAL OF MEDICAL VIROLOGY, 85, 3, 449, 458, Mar. 2013, [Peer-reviewed]
  English, Scientific journal
• Association of ITPA gene variation and serum ribavirin concentration with a decline in blood cell concentrations during pegylated interferon-alpha plus ribavirin therapy for chronic hepatitis C
  Mina Nakagawa, Naoya Sakamoto, Takako Watanabe, Yuki Nishimura-Sakurai, Izumi Onozuka, Seishin Azuma, Sei Kakinuma, Sayuri Nitta, Kei Kiyohashi, Akiko Kusano-Kitazume, Miyako Murakawa, Kohei Yoshino, Yasuhiro Itsui, Yasuhito Tanaka, Masashi Mizokami, Mamoru Watanabe
  HEPATOLOGY INTERNATIONAL, 7, 1, 153, 161, Mar. 2013, [Peer-reviewed]
  English, Scientific journal
• Carbon dioxide insufflation for endoscopic retrograde cholangiopancreatography: Is this beneficial for all patients?
  Masaki Kuwatani, Hiroshi Kawakami, Naoya Sakamoto
  DIGESTIVE ENDOSCOPY, 25, 2, 205, 205, Mar. 2013, [Peer-reviewed]
  English
• Endoscopic resection (endoscopic mucosal resection/endoscopic submucosal dissection) for superficial esophageal squamous cell carcinoma: Current status of various techniques
  Yuichi Shimizu, Masakazu Takahashi, Takeshi Yoshida, Shouko Ono, Katsuhiro Mabe, Mototsugu Kato, Masahiro Asaka, Naoya Sakamoto
  Digestive Endoscopy, 25, 1, 13, 19, Mar. 2013, [Peer-reviewed]
  English
• Add-on therapy of pitavastatin and eicosapentaenoic acid improves outcome of peginterferon plus ribavirin treatment for chronic hepatitis C
  Motoyuki Kohjima, Munechika Enjoji, Tsuyoshi Yoshimoto, Ryoko Yada, Tatsuya Fujino, Yoko Aoyagi, Nobuyoshi Fukushima, Kunitaka Fukuizumi, Naohiko Harada, Masayoshi Yada, Masaki Kato, Kazuhiro Kotoh, Manabu Nakashima, Naoya Sakamoto, Yasuhito Tanaka, Makoto Nakamuta
  JOURNAL OF MEDICAL VIROLOGY, 85, 2, 250, 260, Feb. 2013, [Peer-reviewed]
  English, Scientific journal
• Serum pepsinogen and gastric cancer risk
  Katsuhiro Mabe, Mototsugu Kato, Naoya Sakamoto, Masahiro Asaka
  Journal of Japanese Society of Gastroenterology, 110, 2, 218, 224, Feb. 2013, [Peer-reviewed]
  Japanese, Scientific journal
• C型肝炎ウイルス蛋白によるシグナル伝達制御
  須田 剛生, 坂本 直哉
  分子消化器病, 10, 68, 72, 2013
  Scientific journal
• Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type I interferon-dependent innate immunity
  Sayuri Nitta, Naoya Sakamoto, Mina Nakagawa, Sei Kakinuma, Kako Mishima, Akiko Kusano-Kitazume, Kei Kiyohashi, Miyako Murakawa, Yuki Nishimura-Sakurai, Seishin Azuma, Megumi Tasaka-Fujita, Yasuhiro Asahina, Mitsutoshi Yoneyama, Takashi Fujita, Mamoru Watanabe
  Hepatology, 57, 1, 46, 58, Jan. 2013
  English, Scientific journal
• Rikkunshito, a Japanese Kampo Medicine, Ameliorates Decreased Feeding Behavior via Ghrelin and Serotonin 2B Receptor Signaling in a Novelty Stress Murine Model
  Chihiro Yamada, Yayoi Saegusa, Koji Nakagawa, Shunsuke Ohnishi, Shuichi Muto, Miwa Nahata, Chiharu Sadakane, Tomohisa Hattori, Naoya Sakamoto, Hiroshi Takeda
  BIOMED RESEARCH INTERNATIONAL, 2013, 792940, 2013, [Peer-reviewed]
  English, Scientific journal
• Large Solid-pseudopapillary Neoplasm of the Pancreas with Aberrant Protein Expression and Mutation of beta-Catenin: A Case Report and Literature Review of the Distribution of beta-Catenin Mutation
  Takahiko Kobayashi, Mariko Ozasa, Kencho Miyashita, Akiyoshi Saga, Kimiaki Miwa, Makoto Saito, Masanobu Morioka, Motoya Takeuchi, Nobuo Takenouchi, Takashi Yabiku, Hiromi Kanno, Sayaka Yuzawa, Mishie Tanino, Shinya Tanaka, Hiroshi Kawakami, Masahiro Asaka, Naoya Sakamoto
  INTERNAL MEDICINE, 52, 18, 2051, 2056, 2013, [Peer-reviewed]
  English, Scientific journal
• Hypoxia suppresses stretch-induced elongation and orientation of macrophages
  Koki Oya, Naoya Sakamoto, Masaaki Sato
  BIO-MEDICAL MATERIALS AND ENGINEERING, 23, 6, 463, 471, 2013, [Peer-reviewed]
  English, Scientific journal
• Hepatitis C virus NS4B protein targets STING and abrogates RIG-I-mediated type I interferon-dependent innate immunity
  Sayuri Nitta, Naoya Sakamoto, Mina Nakagawa, Sei Kakinuma, Kako Mishima, Akiko Kusano-Kitazume, Kei Kiyohashi, Miyako Murakawa, Yuki Nishimura-Sakurai, Seishin Azuma, Megumi Tasaka-Fujita, Yasuhiro Asahina, Mitsutoshi Yoneyama, Takashi Fujita, Mamoru Watanabe
  HEPATOLOGY, 57, 1, 46, 58, Jan. 2013, [Peer-reviewed]
  English, Scientific journal
• Severe Murine Typhus With Shock and Acute Respiratory Failure in a Japanese Traveler After Returning From Thailand
  Naoya Sakamoto, Fukumi Nakamura-Uchiyama, Ken-ichiro Kobayashi, Tomohiko Takasaki, Yumiko Ogasawara, Shuji Ando, Sentaro Iwabuchi, Kenji Ohnishi
  JOURNAL OF TRAVEL MEDICINE, 20, 1, 50, 53, Jan. 2013, [Peer-reviewed]
  English, Scientific journal
• A multicenter survey of re-treatment with pegylated interferon plus ribavirin combination therapy for patients with chronic hepatitis C in Japan
  Tsugiko Oze, Naoki Hiramatsu, Eiji Mita, Norio Akuta, Naoya Sakamoto, Hiroaki Nagano, Yoshito Itoh, Shuichi Kaneko, Namiki Izumi, Hideyuki Nomura, Norio Hayashi, Tetsuo Takehara
  HEPATOLOGY RESEARCH, 43, 1, 35, 43, Jan. 2013, [Peer-reviewed]
  English, Scientific journal
• Duplicated Wirsung duct
  Kazumichi Kawakubo, Hiroshi Kawakami, Naoya Sakamoto
  PANCREATOLOGY, 13, 1, 98, 98, Jan. 2013, [Peer-reviewed]
  English
• Anemia and thrombocytosis induced by ribavirin monotherapy in patients with chronic hepatitis C
  Tomoe Kobayashi, Shuhei Hige, Katsumi Terashita, Masato Nakai, Hiromasa Horimoto, Takuya Sho, Mitsuru Nakanishi, Koji Ogawa, Makoto Chuma, Naoya Sakamoto, Masahiro Asaka
  JOURNAL OF GASTROENTEROLOGY, 47, 11, 1228, 1237, Nov. 2012, [Peer-reviewed]
  English, Scientific journal
• Reg IV Is a Direct Target of Intestinal Transcriptional Factor CDX2 in Gastric Cancer
  Yutaka Naito, Naohide Oue, Takao Hinoi, Naoya Sakamoto, Kazuhiro Sentani, Hideki Ohdan, Kazuyoshi Yanagihara, Hiroki Sasaki, Wataru Yasui
  PLOS ONE, 7, 11, e47545, Nov. 2012, [Peer-reviewed]
  English, Scientific journal
• Inhibition of Both Protease and Helicase Activities of Hepatitis C Virus NS3 by an Ethyl Acetate Extract of Marine Sponge Amphimedon sp.
  Yuusuke Fujimoto, Kazi Abdus Salam, Atsushi Furuta, Yasuyoshi Matsuda, Osamu Fujita, Hidenori Tani, Masanori Ikeda, Nobuyuki Kato, Naoya Sakamoto, Shinya Maekawa, Nobuyuki Enomoto, Nicole J. de Voogd, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Satoshi Tsuneda, Nobuyoshi Akimitsu, Naohiro Noda, Atsuya Yamashita, Junichi Tanaka, Kohji Moriishi
  PLOS ONE, 7, 11, e48685, Nov. 2012, [Peer-reviewed]
  English, Scientific journal
• Guidewire cannulation: friend or foe Response
  Hiroshi Kawakami, Hiroyuki Isayama, Hiroyuki Maguchi, Masaki Kuwatani, Yousuke Nakai, Kazumichi Kawakubo, Shin Haba, Taiki Kudo, Yoko Abe, Kazuhiko Koike, Naoya Sakamoto
  GASTROINTESTINAL ENDOSCOPY, 76, 4, 920, 921, Oct. 2012, [Peer-reviewed]
  English
• Factors responsible for the discrepancy between IL28B polymorphism prediction and the viral response to peginterferon plus ribavirin therapy in Japanese chronic hepatitis C patients
  Hiroaki Saito, Kiyoaki Ito, Masaya Sugiyama, Teppei Matsui, Yoshihiko Aoki, Masatoshi Imamura, Kazumoto Murata, Naohiko Masaki, Hideyuki Nomura, Hiroshi Adachi, Shuhei Hige, Nobuyuki Enomoto, Naoya Sakamoto, Masayuki Kurosaki, Masashi Mizokami, Sumio Watanabe
  HEPATOLOGY RESEARCH, 42, 10, 958, 965, Oct. 2012, [Peer-reviewed]
  English, Scientific journal
• [The effect of H. pylori eradication against prevention of gastric cancer].
  Mabe K, Kato M, Ono S, Asaka M, Sakamoto N
  Nihon rinsho. Japanese journal of clinical medicine, 70, 10, 1726, 1730, 日本臨床社, Oct. 2012, [Peer-reviewed]
  Japanese
• Liver-intestine cadherin induction by epidermal growth factor receptor is associated with intestinal differentiation of gastric cancer
  Naoya Sakamoto, Naohide Oue, Kazuhiro Sentani, Katsuhiro Anami, Naohiro Uraoka, Yutaka Naito, Htoo Zarni Oo, Takao Hinoi, Hideki Ohdan, Kazuyoshi Yanagihara, Kazuhiko Aoyagi, Hiroki Sasaki, Wataru Yasui
  CANCER SCIENCE, 103, 9, 1744, 1750, Sep. 2012, [Peer-reviewed]
  English, Scientific journal
• Decrease of Peripheral and Intestinal NKG2A-Positive T Cells in Patients with Ulcerative Colitis
  Takehiko Katsurada, Waka Kobayashi, Utano Tomaru, Tomohisa Baba, Shigeru Furukawa, Akihiro Ishizu, Kazuyoshi Takeda, Naoya Sakamoto, Masahiro Asaka, Hiroshi Takeda, Masanori Kasahara
  PLOS ONE, 7, 9, e44113, Sep. 2012, [Peer-reviewed]
  English, Scientific journal
• Medial Regeneration Using a Biodegradable Felt as a Scaffold Preserves Integrity and Compliance of a Canine Dissected Aorta
  Mitsuru Sato, Shunsuke Kawamoto, Mika Watanabe, Naoya Sakamoto, Masaaki Sato, Yasuhiko Tabata, Yoshikatsu Saiki
  CIRCULATION, 126, 11, S102, +, Sep. 2012, [Peer-reviewed]
  English, Scientific journal
• Let-7b is a novel regulator of hepatitis C virus replication
  Ju-Chien Cheng, Yung-Ju Yeh, Ching-Ping Tseng, Sheng-Da Hsu, Yu-Ling Chang, Naoya Sakamoto, Hsien-Da Huang
  CELLULAR AND MOLECULAR LIFE SCIENCES, 69, 15, 2621, 2633, Aug. 2012, [Peer-reviewed]
  English, Scientific journal
• Preoperative Biliary Drainage for Hilar Cholangiocarcinoma
  KAWAKAMI Hiroshi, KATO Mototsugu, HIRANO Satoshi, SAKAMOTO Naoya
  Gastroenterological Endoscopy, 54, 7, 1975, 1990, Japan Gastroenterological Endoscopy Society, 20 Jul. 2012
  Japanese, The controversy over whether and how to perform preoperative biliary drainage (PBD) in patients with hilar cholangiocarcinoma (HCA) remains unsettled. Arguments against PBD before pancreatoduodenectomy have recently been gaining momentum. However, the complication-related mortality rate is as high as 5% for patients with HCA who have undergone major liver resection, and liver failure is a major cause of postoperative death. This suggests the need for PBD to treat jaundice in HCA patients scheduled for major surgical resection of the liver and to perform major surgery only after recovery of the hepatic function. However, no definite criteria or guidelines outlining indications for PBD are currently available. In patients with HCA, PBD may be performed by either percutaneous transhepatic biliary drainage (PTBD) or endoscopic biliary drainage (EBD). No consensus has been reached regarding which PBD method is more appropriate. No reported study has compared the effectiveness of PTBD, endoscopic biliary stenting and endoscopic nasobiliary drainage in patients with HCA. Recently, a few Japanese high-volume centers have recommended EBD of the future remnant lobe for PBD in patients expected to undergo definitive surgery for HCA. This review summarizes the purpose, transition, current situation, and future of PBD in HCA patients undergoing PBD.
• Role of nesprin-1 in nuclear deformation in endothelial cells under static and uniaxial stretching conditions
  Toshiro Anno, Naoya Sakamoto, Masaaki Sato
  Biochemical and Biophysical Research Communications, 424, 1, 94, 99, 20 Jul. 2012, [Peer-reviewed]
  English, Scientific journal
• Suppression of hepatitis C virus replicon by adenovirus vector-mediated expression of tough decoy RNA against miR-122a
  Fuminori Sakurai, Norihisa Furukawa, Maiko Higuchi, Sayuri Okamoto, Kaori Ono, Takeshi Yoshida, Masuo Kondoh, Kiyohito Yagi, Naoya Sakamoto, Kazufumi Katayama, Hiroyuki Mizuguchi
  VIRUS RESEARCH, 165, 2, 214, 218, May 2012, [Peer-reviewed]
  English, Scientific journal
• Inhibition of Hepatitis C Virus Replication and Viral Helicase by Ethyl Acetate Extract of the Marine Feather Star Alloeocomatella polycladia
  Atsuya Yamashita, Kazi Abdus Salam, Atsushi Furuta, Yasuyoshi Matsuda, Osamu Fujita, Hidenori Tani, Yoshihisa Fujita, Yuusuke Fujimoto, Masanori Ikeda, Nobuyuki Kato, Naoya Sakamoto, Shinya Maekawa, Nobuyuki Enomoto, Masamichi Nakakoshi, Masayoshi Tsubuki, Yuji Sekiguchi, Satoshi Tsuneda, Nobuyoshi Akimitsu, Naohiro Noda, Junichi Tanaka, Kohji Moriishi
  MARINE DRUGS, 10, 4, 744, 761, Apr. 2012, [Peer-reviewed]
  English, Scientific journal
• Identification of novel N-(morpholine-4-carbonyloxy) amidine compounds as potent inhibitors against hepatitis C virus replication
  Akiko Kusano-Kitazume, Naoya Sakamoto, Yukiko Okuno, Yuko Sekine-Osajima, Mina Nakagawa, Sei Kakinuma, Kei Kiyohashi, Sayuri Nitta, Miyako Murakawa, Seishin Azuma, Yuki Nishimura-Sakurai, Masatoshi Hagiwara, Mamoru Watanabe
  Antimicrobial Agents and Chemotherapy, 56, 3, 1315, 1323, Mar. 2012
  English, Scientific journal
• Inhibition of hepatitis C virus NS5B polymerase by S-trityl-L-cysteine derivatives
  Daniel B. Nichols, Guy Fournet, K. R. Gurukumar, Amartya Basu, Jin-Ching Lee, Naoya Sakamoto, Frank Kozielski, Ira Musmuca, Benoit Joseph, Rino Ragno, Neerja Kaushik-Basu
  EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 49, 191, 199, Mar. 2012, [Peer-reviewed]
  English, Scientific journal
• Data mining model using simple and readily available factors could identify patients at high risk for hepatocellular carcinoma in chronic hepatitis C
  Masayuki Kurosaki, Naoki Hiramatsu, Minoru Sakamoto, Yoshiyuki Suzuki, Manabu Iwasaki, Akihiro Tamori, Kentaro Matsuura, Sei Kakinuma, Fuminaka Sugauchi, Naoya Sakamoto, Mina Nakagawa, Namiki Izumi
  JOURNAL OF HEPATOLOGY, 56, 3, 602, 608, Mar. 2012, [Peer-reviewed]
  English, Scientific journal
• Identification of Novel N-(Morpholine-4-Carbonyloxy) Amidine Compounds as Potent Inhibitors against Hepatitis C Virus Replication
  Akiko Kusano-Kitazume, Naoya Sakamoto, Yukiko Okuno, Yuko Sekine-Osajima, Mina Nakagawa, Sei Kakinuma, Kei Kiyohashi, Sayuri Nitta, Miyako Murakawa, Seishin Azuma, Yuki Nishimura-Sakurai, Masatoshi Hagiwara, Mamoru Watanabe
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 56, 3, 1315, 1323, Mar. 2012, [Peer-reviewed]
  English, Scientific journal
• Expression of cancer stem cell markers ALDH1, CD44 and CD133 in primary tumor and lymph node metastasis of gastric cancer
  Yuta Wakamatsu, Naoya Sakamoto, Htoo Zarni Oo, Yutaka Naito, Naohiro Uraoka, Katsuhiro Anami, Kazuhiro Sentani, Naohide Oue, Wataru Yasui
  PATHOLOGY INTERNATIONAL, 62, 2, 112, 119, Feb. 2012, [Peer-reviewed]
  English, Scientific journal
• Cytokeratin Expression Profiling in Gastric Carcinoma: Clinicopathologic Significance and Comparison with Tumor-Associated Molecules
  Hokuto Takami, Kazuhiro Sentani, Miho Matsuda, Naohide Oue, Naoya Sakamoto, Wataru Yasui
  PATHOBIOLOGY, 79, 3, 154, 161, 2012, [Peer-reviewed]
  English, Scientific journal
• alpha-Bridged BODIPY oligomers with switchable near-IR photoproperties by external-stimuli-induced foldamer formation and disruption
  Naoya Sakamoto, Chusaku Ikeda, Masaki Yamamura, Tatsuya Nabeshima
  CHEMICAL COMMUNICATIONS, 48, 40, 4818, 4820, 2012, [Peer-reviewed]
  English, Scientific journal
• Association of gene expression involving innate immunity and genetic variation in interleukin 28B with antiviral response
  Yasuhiro Asahina, Kaoru Tsuchiya, Masaru Muraoka, Keisuke Tanaka, Yuichiro Suzuki, Nobuharu Tamaki, Yoshihide Hoshioka, Yutaka Yasui, Tomoji Katoh, Takanori Hosokawa, Ken Ueda, Hiroyuki Nakanishi, Jun Itakura, Yuka Takahashi, Masayuki Kurosaki, Nobuyuki Enomoto, Sayuri Nitta, Naoya Sakamoto, Namiki Izumi
  HEPATOLOGY, 55, 1, 20, 29, Jan. 2012, [Peer-reviewed]
  English, Scientific journal
• Age and total ribavirin dose are independent predictors of relapse after interferon therapy in chronic hepatitis C revealed by data mining analysis
  Masayuki Kurosaki, Naoki Hiramatsu, Minoru Sakamoto, Yoshiyuki Suzuki, Manabu Iwasaki, Akihiro Tamori, Kentaro Matsuura, Sei Kakinuma, Fuminaka Sugauchi, Naoya Sakamoto, Mina Nakagawa, Hiroshi Yatsuhashi, Namiki Izumi
  ANTIVIRAL THERAPY, 17, 1, 35, 43, 2012, [Peer-reviewed]
  English, Scientific journal
• Use of human hepatocyte-like cells derived from induced pluripotent stem cells as a model for hepatocytes in hepatitis C virus infection
  Takeshi Yoshida, Kazuo Takayama, Masuo Kondoh, Fuminori Sakurai, Hideki Tani, Naoya Sakamoto, Yoshiharu Matsuura, Hiroyuki Mizuguchi, Kiyohito Yagi
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 416, 1-2, 119, 124, Dec. 2011, [Peer-reviewed]
  English, Scientific journal
• Suppression of Hath1 Gene Expression Directly Regulated by Hes1 Via Notch Signaling Is Associated with Goblet Cell Depletion in Ulcerative Colitis
  Xiu Zheng, Kiichiro Tsuchiya, Ryuichi Okamoto, Michiko Iwasaki, Yoshihito Kano, Naoya Sakamoto, Tetsuya Nakamura, Mamoru Watanabe
  INFLAMMATORY BOWEL DISEASES, 17, 11, 2251, 2260, Nov. 2011, [Peer-reviewed]
  English, Scientific journal
• A new method for induced fit docking (GENIUS) and its application to virtual screening of novel HCV NS3-4A protease inhibitors
  Daisuke Takaya, Atsuya Yamashita, Kazue Kamijo, Junko Gomi, Masahiko Ito, Shinya Maekawa, Nobuyuki Enomoto, Naoya Sakamoto, Yoshiaki Watanabe, Ryoichi Arai, Hideaki Umeyama, Teruki Honma, Takehisa Matsumoto, Shigeyuki Yokoyama
  BIOORGANIC & MEDICINAL CHEMISTRY, 19, 22, 6892, 6905, Nov. 2011, [Peer-reviewed]
  English, Scientific journal
• NIK-333(非環式レチノイド)は自然免疫系やISG15システムを介してC型肝炎ウイルスの増殖を抑制する　　　　　　　　　　　　　　　
  中牟田 誠, 国府島 庸之, 矢田 雅佳, 坂本 直哉, 後藤 和人, 吉本 剛志, 福嶋 伸良, 福泉 公仁隆, 河邉 顕, 水谷 孝弘, 原田 直彦, 武冨 紹信, 前原 喜彦, 遠城寺 宗近
  肝臓, 52, Suppl.2, A587, A587, (一社)日本肝臓学会, Sep. 2011, [Peer-reviewed]
  Japanese
• Pretreatment prediction of anemia progression by pegylated interferon alpha-2b plus ribavirin combination therapy in chronic hepatitis C infection: decision-tree analysis.
  Naoki Hiramatsu, Masayuki Kurosaki, Naoya Sakamoto, Manabu Iwasaki, Minoru Sakamoto, Yoshiyuki Suzuki, Fuminaka Sugauchi, Akihiro Tamori, Sei Kakinnuma, Kentaro Matsuura, Namiki Izumi
  Journal of gastroenterology, 46, 9, 1111, 9, Sep. 2011, [Peer-reviewed], [Domestic magazines]
  English, Scientific journal, BACKGROUND: This study aimed to develop a model to predict the development of severe anemia during pegylated interferon alpha-2b plus ribavirin combination therapy. METHODS: Data were collected from 1081 genotype 1b chronic hepatitis C patients who were treated at 6 hospitals in Japan. These patients were randomly assigned to a model-building group (n = 691) or an internal validation group (n = 390). Factors predictive of severe anemia (hemoglobin, Hb < 8.5 g/dl) were explored using data-mining analysis. RESULTS: Hb values at baseline, creatinine clearance (Ccr), and an Hb concentration decline by 2 g/dl at week 2 were used to build a decision-tree model, in which the patients were divided into 5 subgroups based on variable rates of severe anemia ranging from 0.4 to 11.8%. The reproducibility of the model was confirmed by the internal validation group (r² = 0.96). The probability of severe anemia was high in patients whose Hb value was <14 g/dl before treatment (6.5%), especially (a) in those whose Ccr was <80 ml/min (11.8%) and (b) those whose Ccr was ≥ 80 ml/min but whose Hb concentration decline at week 2 was ≥ 2 g/dl (11.5%). The probability of severe anemia was low in the other patients (0.4-2.5%). CONCLUSIONS: The decision-tree model that included Hb values at baseline, Ccr, and an Hb concentration decline by 2 g/dl at week 2 was useful for predicting the probability of severe anemia, and has the potential to support clinical decisions regarding early dose reduction of ribavirin.
• Combined stimulation with cyclic stretching and hypoxia increases production of matrix metalloproteinase-9 and cytokines by macrophages
  Koki Oya, Naoya Sakamoto, Toshiro Ohashi, Masaaki Sato
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 412, 4, 678, 682, Sep. 2011, [Peer-reviewed]
  English, Scientific journal
• Analysis of the complete open reading frame of hepatitis C virus in genotype 2a infection reveals critical sites influencing the response to peginterferon and ribavirin therapy
  Makoto Kadokura, Shinya Maekawa, Ryota Sueki, Mika Miura, Kazuki Komase, Hiroko Shindo, Fumitake Amemiya, Tomoyoshi Uetake, Taisuke Inoue, Minoru Sakamoto, Mina Nakagawa, Naoya Sakamoto, Mamoru Watanabe, Nobuyuki Enomoto
  HEPATOLOGY INTERNATIONAL, 5, 3, 789, 799, Sep. 2011, [Peer-reviewed]
  English, Scientific journal
• Genome-wide association study identified ITPA/DDRGK1 variants reflecting thrombocytopenia in pegylated interferon and ribavirin therapy for chronic hepatitis C
  Yasuhito Tanaka, Masayuki Kurosaki, Nao Nishida, Masaya Sugiyama, Kentaro Matsuura, Naoya Sakamoto, Nobuyuki Enomoto, Hiroshi Yatsuhashi, Shuhei Nishiguchi, Keisuke Hino, Shuhei Hige, Yoshito Itoh, Eiji Tanaka, Satoshi Mochida, Masao Honda, Yoichi Hiasa, Asako Koike, Fuminaka Sugauchi, Shuichi Kaneko, Namiki Izumi, Katsushi Tokunaga, Masashi Mizokami
  HUMAN MOLECULAR GENETICS, 20, 17, 3507, 3516, Sep. 2011, [Peer-reviewed]
  English, Scientific journal
• Pretreatment prediction of anemia progression by pegylated interferon alpha-2b plus ribavirin combination therapy in chronic hepatitis C infection: decision-tree analysis
  Naoki Hiramatsu, Masayuki Kurosaki, Naoya Sakamoto, Manabu Iwasaki, Minoru Sakamoto, Yoshiyuki Suzuki, Fuminaka Sugauchi, Akihiro Tamori, Sei Kakinnuma, Kentaro Matsuura, Namiki Izumi
  JOURNAL OF GASTROENTEROLOGY, 46, 9, 1111, 1119, Sep. 2011, [Peer-reviewed]
  English, Scientific journal
• Analysis of the Complete Open Reading Frame of Genotype 2b Hepatitis C Virus in Association with the Response to Peginterferon and Ribavirin Therapy
  Makoto Kadokura, Shinya Maekawa, Ryota Sueki, Mika Miura, Kazuki Komase, Hiroko Shindo, Fumitake Amemiya, Tomoyoshi Uetake, Taisuke Inoue, Minoru Sakamoto, Mina Nakagawa, Naoya Sakamoto, Mamoru Watanabe, Nobuyuki Enomoto
  PLOS ONE, 6, 9, e24514, Sep. 2011, [Peer-reviewed]
  English, Scientific journal
• Oxygen isotopic compositions of asteroidal materials returned from Itokawa by the Hayabusa mission.
  Hisayoshi Yurimoto, Ken-ichi Abe, Masanao Abe, Mitsuru Ebihara, Akio Fujimura, Minako Hashiguchi, Ko Hashizume, Trevor R Ireland, Shoichi Itoh, Juri Katayama, Chizu Kato, Junichiro Kawaguchi, Noriyuki Kawasaki, Fumio Kitajima, Sachio Kobayashi, Tatsuji Meike, Toshifumi Mukai, Keisuke Nagao, Tomoki Nakamura, Hiroshi Naraoka, Takaaki Noguchi, Ryuji Okazaki, Changkun Park, Naoya Sakamoto, Yusuke Seto, Masashi Takei, Akira Tsuchiyama, Masayuki Uesugi, Shigeyuki Wakaki, Toru Yada, Kosuke Yamamoto, Makoto Yoshikawa, Michael E Zolensky
  Science (New York, N.Y.), 333, 6046, 1116, 9, 26 Aug. 2011, [Peer-reviewed], [International Magazine]
  English, Scientific journal, Meteorite studies suggest that each solar system object has a unique oxygen isotopic composition. Chondrites, the most primitive of meteorites, have been believed to be derived from asteroids, but oxygen isotopic compositions of asteroids themselves have not been established. We measured, using secondary ion mass spectrometry, oxygen isotopic compositions of rock particles from asteroid 25143 Itokawa returned by the Hayabusa spacecraft. Compositions of the particles are depleted in (16)O relative to terrestrial materials and indicate that Itokawa, an S-type asteroid, is one of the sources of the LL or L group of equilibrated ordinary chondrites. This is a direct oxygen-isotope link between chondrites and their parent asteroid.
• Inhibitory Effect of a Triterpenoid Compound, with or without Alpha Interferon, on Hepatitis C Virus Infection
  Takako Watanabe, Naoya Sakamoto, Mina Nakagawa, Sei Kakinuma, Yasuhiro Itsui, Yuki Nishimura-Sakurai, Mayumi Ueyama, Yusuke Funaoka, Akiko Kitazume, Sayuri Nitta, Kei Kiyohashi, Miyako Murakawa, Seishin Azuma, Kiichiro Tsuchiya, Shinya Oooka, Mamoru Watanabe
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 55, 6, 2537, 2545, Jun. 2011, [Peer-reviewed]
  English, Scientific journal
• Analysis of Interferon Signaling by Infectious Hepatitis C Virus Clones with Substitutions of Core Amino Acids 70 and 91
  Yusuke Funaoka, Naoya Sakamoto, Goki Suda, Yasuhiro Itsui, Mina Nakagawa, Sei Kakinuma, Takako Watanabe, Kako Mishima, Mayumi Ueyama, Izumi Onozuka, Sayuri Nitta, Akiko Kitazume, Kei Kiyohashi, Miyako Murakawa, Seishin Azuma, Kiichiro Tsuchiya, Mamoru Watanabe
  JOURNAL OF VIROLOGY, 85, 12, 5986, 5994, Jun. 2011, [Peer-reviewed]
  English, Scientific journal
• Adenovirus vector-mediated assay system for hepatitis C virus replication
  Takeshi Yoshida, Masuo Kondoh, Manabu Ojima, Hiroyuki Mizuguchi, Yoshiaki Yamagishi, Naoya Sakamoto, Kiyohito Yagi
  NUCLEIC ACIDS RESEARCH, 39, 10, e64, May 2011, [Peer-reviewed]
  English, Scientific journal
• Association between lipid accumulation and the cannabinoid system in Huh7 cells expressing HCV genes
  Mako Toyoda, Akira Kitaoka, Kazuyuki Machida, Takuya Nishinakagawa, Ryoko Yada, Motoyuki Kohjima, Masaki Kato, Kazuhiro Kotoh, Naoya Sakamoto, Goshi Shiota, Makoto Nakamuta, Manabu Nakashima, Munechika Enjoji
  INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 27, 5, 619, 624, May 2011, [Peer-reviewed]
  English, Scientific journal
• Association of IL28B Variants With Response to Pegylated-Interferon Alpha Plus Ribavirin Combination Therapy Reveals Intersubgenotypic Differences Between Genotypes 2a and 2b
  Naoya Sakamoto, Mina Nakagawa, Yasuhito Tanaka, Yuko Sekine-Osajima, Mayumi Ueyama, Masayuki Kurosaki, Nao Nishida, Akihiro Tamori, Nishimura-Sakurai Yuki, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Shuhei Hige, Yoshito Itoh, Eiji Tanaka, Yoichi Hiasa, Namiki Izumi, Katsushi Tokunaga, Masashi Mizokami, Mamoru Watanabe
  JOURNAL OF MEDICAL VIROLOGY, 83, 5, 871, 878, May 2011, [Peer-reviewed]
  English, Scientific journal
• [Mechanism of hepatitis C virus (HCV) RNA replication and HCV genetic variability].
  Sekine-Osajima Y, Nakagawa M, Sakamoto N
  Nihon rinsho. Japanese journal of clinical medicine, 69 Suppl 4, 52, 58, 日本臨床社, May 2011, [Peer-reviewed]
  Japanese
• Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice
  Izumi Onozuka, Sei Kakinuma, Akihide Kamiya, Masato Miyoshi, Naoya Sakamoto, Kei Kiyohashi, Takako Watanabe, Yusuke Funaoka, Mayumi Ueyama, Mina Nakagawa, Naohiko Koshikawa, Motoharu Seiki, Hiromitsu Nakauchi, Mamoru Watanabe
  Biochemical and Biophysical Research Communications, 406, 1, 134, 140, 04 Mar. 2011
  English, Scientific journal
• Clinicopathological significance of nuclear factor-kappa B activation in hepatocellular carcinoma
  Hideki Yokoo, Jun Yasuda, Kazuaki Nakanishi, Makoto Chuma, Toshiya Kamiyama, Satoru Todo, Setsuo Hirohashi, Michiie Sakamoto
  HEPATOLOGY RESEARCH, 41, 3, 240, 249, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Pretreatment prediction of response to peginterferon plus ribavirin therapy in genotype 1 chronic hepatitis C using data mining analysis
  Masayuki Kurosaki, Naoya Sakamoto, Manabu Iwasaki, Minoru Sakamoto, Yoshiyuki Suzuki, Naoki Hiramatsu, Fuminaka Sugauchi, Hiroshi Yatsuhashi, Namiki Izumi
  JOURNAL OF GASTROENTEROLOGY, 46, 3, 401, 409, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Pre-treatment prediction of response to pegylated-interferon plus ribavirin for chronic hepatitis C using genetic polymorphism in IL28B and viral factors
  Masayuki Kurosaki, Yasuhito Tanaka, Nao Nishida, Naoya Sakamoto, Nobuyuki Enomoto, Masao Honda, Masaya Sugiyama, Kentaro Matsuura, Fuminaka Sugauchi, Yasuhiro Asahina, Mina Nakagawa, Mamoru Watanabe, Minoru Sakamoto, Shinya Maekawa, Akito Sakai, Shuichi Kaneko, Kiyoaki Ito, Naohiko Masaki, Katsushi Tokunaga, Namiki Izumi, Masashi Mizokami
  JOURNAL OF HEPATOLOGY, 54, 3, 439, 448, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Sequences in the Interferon Sensitivity-Determining Region and Core Region of Hepatitis C Virus Impact Pretreatment Prediction of Response to PEG-Interferon Plus Ribavirin: Data Mining Analysis
  Masayuki Kurosaki, Naoya Sakamoto, Manabu Iwasaki, Minoru Sakamoto, Yoshiyuki Suzuki, Naoki Hiramatsu, Fuminaka Sugauchi, Akihiro Tamori, Mina Nakagawa, Namiki Izumi
  JOURNAL OF MEDICAL VIROLOGY, 83, 3, 445, 452, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Studies on virus kinetics using infectious fluorescence-tagged hepatitis C virus cell culture
  Machi Yamamoto, Naoya Sakamoto, Tetsuya Nakamura, Yasuhiro Itsui, Mina Nakagawa, Yuki Nishimura-Sakurai, Sei Kakinuma, Seishin Azuma, Kiichiro Tsuchiya, Takanobu Kato, Takaji Wakita, Mamoru Watanabe
  HEPATOLOGY RESEARCH, 41, 3, 258, 269, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Cholestatic liver fibrosis and toxin-induced fibrosis are exacerbated in matrix metalloproteinase-2 deficient mice
  Izumi Onozuka, Sei Kakinuma, Akihide Kamiya, Masato Miyoshi, Naoya Sakamoto, Kei Kiyohashi, Takako Watanabe, Yusuke Funaoka, Mayumi Ueyama, Mina Nakagawa, Naohiko Koshikawa, Motoharu Seiki, Hiromitsu Nakauchi, Mamoru Watanabe
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 406, 1, 134, 140, Mar. 2011, [Peer-reviewed]
  English, Scientific journal
• Longitudinal cell formation in the entire human small intestine is correlated with the localization of Hath1 and Klf4
  Michiko Iwasaki, Kiichiro Tsuchiya, Ryuichi Okamoto, Xiu Zheng, Yoshihito Kano, Eiko Okamoto, Eriko Okada, Akihiro Araki, Shinji Suzuki, Naoya Sakamoto, Keisuke Kitagaki, Takumi Akashi, Yoshinobu Eishi, Tetsuya Nakamura, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY, 46, 2, 191, 202, Feb. 2011, [Peer-reviewed]
  English, Scientific journal
• カプセル内視鏡では診断できず、ダブルバルーン小腸内視鏡で診断しえた空腸GISTの1例　　　　　　　　　　　　　　　
  福田将義, 鈴木伸治, 東正新, 長沼誠, 長堀正和, 土屋輝一郎, 坂本直哉, 渡辺守, 岡田英理子, 荒木昭博, 大岡真也, 小林宏敏, 杉原健一, 伊藤栄作, 江石義信
  Progress of Digestive Endoscopy, 78, 2, 124, 125,10, 2011
  Japanese, Scientific journal
• Serum interleukin-6 levels correlate with resistance to treatment of chronic hepatitis C infection with pegylated-interferon-alpha 2b plus ribavirin
  Mayumi Ueyama, Mina Nakagawa, Naoya Sakamoto, Izumi Onozuka, Yusuke Funaoka, Takako Watanabe, Sayuri Nitta, Kei Kiyohashi, Akiko Kitazume, Miyako Murakawa, Yuki Nishimura-Sakurai, Yuko Sekine-Osajima, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Mamoru Watanabe
  ANTIVIRAL THERAPY, 16, 7, 1081, 1091, 2011, [Peer-reviewed]
  English, Scientific journal
• IL-6-mediated intersubgenotypic variation of interferon sensitivity in hepatitis C virus genotype 2a/2b chimeric clones
  Goki Suda, Naoya Sakamoto, Yasuhiro Itsui, Mina Nakagawa, Megumi Tasaka-Fujita, Yusuke Funaoka, Takako Watanabe, Sayuri Nitta, Kei Kiyohashi, Seishin Azuma, Sei Kakinuma, Kiichiro Tsuchiya, Michio Imamura, Nobuhiko Hiraga, Kazuaki Chayama, Mamoru Watanabe
  VIROLOGY, 407, 1, 80, 90, Nov. 2010, [Peer-reviewed]
  English, Scientific journal
• ITPA gene variant protects against anemia induced by pegylated interferon-alpha and ribavirin therapy for Japanese patients with chronic hepatitis C
  Naoya Sakamoto, Yasuhito Tanaka, Mina Nakagawa, Hiroshi Yatsuhashi, Shuhei Nishiguchi, Nobuyuki Enomoto, Seishin Azuma, Yuki Nishimura-Sakurai, Sei Kakinuma, Nao Nishida, Katsushi Tokunaga, Masao Honda, Kiyoaki Ito, Masashi Mizokami, Mamoru Watanabe
  HEPATOLOGY RESEARCH, 40, 11, 1063, 1071, Nov. 2010, [Peer-reviewed]
  English, Scientific journal
• Cell culture and in vivo analyses of cytopathic hepatitis C virus mutants
  Kako Mishima, Naoya Sakamoto, Yuko Sekine-Osajima, Mina Nakagawa, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Kei Kiyohashi, Akiko Kitazume, Kiichiro Tsuchiya, Michio Imamura, Nobuhiko Hiraga, Kazuaki Chayama, Takaji Wakita, Mamoru Watanabe
  VIROLOGY, 405, 2, 361, 369, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• IL-2 is positively involved in the development of colitogenic CD4(+) IL-7R alpha(high) memory T cells in chronic colitis
  Kaori Kameyama, Yasuhiro Nemoto, Takanori Kanai, Tamako Shinohara, Ryuichi Okamoto, Kuechiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Teruji Totsuka, Toshifumi Hibi, Mamoru Watanabe
  EUROPEAN JOURNAL OF IMMUNOLOGY, 40, 9, 2423, 2436, Sep. 2010, [Peer-reviewed]
  English, Scientific journal
• Inhibition of Hepatitis C Virus Replication by a Specific Inhibitor of Serine-Arginine-Rich Protein Kinase
  Yuko Karakama, Naoya Sakamoto, Yasuhiro Itsui, Mina Nakagawa, Megumi Tasaka-Fujita, Yuki Nishimura-Sakurai, Sei Kakinuma, Masaya Oooka, Seishin Azuma, Kiichiro Tsuchiya, Hiroshi Onogi, Masatoshi Hagiwara, Mamoru Watanabe
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 54, 8, 3179, 3186, Aug. 2010, [Peer-reviewed]
  English, Scientific journal
• Role of p120-catenin in the morphological changes of endothelial cells exposed to fluid shear stress
  Naoya Sakamoto, Kei Segawa, Makoto Kanzaki, Toshiro Ohashi, Masaaki Sato
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 398, 3, 426, 432, Jul. 2010, [Peer-reviewed]
  English, Scientific journal
• Mutations in the interferon sensitivity determining region and virological response to combination therapy with pegylated-interferon alpha 2b plus ribavirin in patients with chronic hepatitis C-1b infection
  Mina Nakagawa, Naoya Sakamoto, Mayumi Ueyama, Kaoru Mogushi, Satoshi Nagaie, Yasuhiro Itsui, Seishin Azuma, Sei Kakinuma, Hiroshi Tanaka, Nobuyuki Enomoto, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY, 45, 6, 656, 665, Jun. 2010, [Peer-reviewed]
  English, Scientific journal
• Comparison of HCV-associated gene expression and cell signaling pathways in cells with or without HCV replicon and in replicon-cured cells
  Yuki Nishimura-Sakurai, Naoya Sakamoto, Kaoru Mogushi, Satoshi Nagaie, Mina Nakagawa, Yasuhiro Itsui, Megumi Tasaka-Fujita, Yuko Onuki-Karakama, Goki Suda, Kako Mishima, Machi Yamamoto, Mayumi Ueyama, Yusuke Funaoka, Takako Watanabe, Seishin Azuma, Yuko Sekine-Osajima, Sei Kakinuma, Kiichiro Tsuchiya, Nobuyuki Enomoto, Hiroshi Tanaka, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY, 45, 5, 523, 536, May 2010, [Peer-reviewed]
  English, Scientific journal
• Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy
  Tomokazu Mizui, Shunhei Yamashina, Isei Tanida, Yoshiyuki Takei, Takashi Ueno, Naoya Sakamoto, Kenichi Ikejima, Tsuneo Kitamura, Nobuyuki Enomoto, Tatsuo Sakai, Eiki Kominami, Sumio Watanabe
  JOURNAL OF GASTROENTEROLOGY, 45, 2, 195, 203, Feb. 2010, [Peer-reviewed]
  English, Scientific journal
• Curcumin inhibits hepatitis C virus replication via suppressing the Akt-SREBP-1 pathway
  KyeongJin Kim, Kook Hwan Kim, Hye Young Kim, Hyun Kook Cho, Naoya Sakamoto, JaeHun Cheong
  FEBS LETTERS, 584, 4, 707, 712, Feb. 2010, [Peer-reviewed]
  English, Scientific journal
• カプセル内視鏡では診断できず、ダブルバルーン小腸内視鏡で診断しえた空腸GISTの1症例　　　　　　　　　　　　　　　
  福田将義, 藤井俊光, 竹中健人, 吉野耕平, 秋山純子, 櫻井幸, 岡田英理子, 東正新, 大岡真也, 鈴木伸治, 長沼誠, 長堀正和, 土屋輝一郎, 荒木昭博, 坂本直哉, 渡辺守, 小林宏寿, 杉原健一, 伊藤栄作, 江石義信
  Progress of Digestive Endoscopy, 78, 1, 92, 2010
  Japanese, Scientific journal
• IBD 内視鏡的粘膜治癒の意義 当科における難治性潰瘍性大腸炎におけるタクロリムスの臨床成績と粘膜治癒効果　　　　　　　　　　　　　　　
  秋山純子, 藤井俊光, 長沼誠, 長堀正和, 玄世鋒, 鈴木伸治, 櫻井幸, 吉野耕平, 福田将義, 竹中健人, 東正新, 土屋輝一郎, 岡本隆一, 中村哲也, 坂本直哉, 渡辺守, 岡田英理子, 荒木昭博
  Progress of Digestive Endoscopy, 78, 1, 70, 2010
  Japanese, Scientific journal
• 診断に難渋した小腸腫瘍の1例
  平尾龍彦, 荒木昭博, 鈴木伸治, 岡田英理子, 藤井俊光, 櫻井幸, 松本浩之, 小田柿智之, 岡本英子, 岩嵜美智子, 長堀正和, 長沼誠, 東正新, 大岡真也, 土屋輝一郎, 岡本隆一, 中村哲也, 秋山純子, 坂本直哉, 渡辺守
  Progress of Digestive Endoscopy, 77, 1, 106, 106, (一社)日本消化器内視鏡学会-関東支部, 2010
  Japanese, Scientific journal
• 【C型肝炎ウイルスの感染・増殖メカニズムと臨床応用】 SR蛋白リン酸化酵素阻害剤によるHCV増殖抑制効果の解析　　　　　　　　　　　　　　　
  唐鎌優子, 坂本直哉, 井津井康浩, 中川美奈, 藤田めぐみ, 櫻井幸, 柿沼晴, 大岡真也, 東正新, 土屋輝一郎, 小野木博, 萩原正敏, 渡辺守
  消化器内科, 51, 6, 632, 635, 2010
  Japanese, Scientific journal
• IL-2 is positively involved in the development of colitogenic CD4 + IL-7Rαhigh memory T cells in chronic colitis
  Kaori Kameyama, Yasuhiro Nemoto, Takanori Kanai, Tamako Shinohara, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Teruji Totsuka, Toshifumi Hibi, Mamoru Watanabe
  European Journal of Immunology, 40, 9, 2423, 2436, Wiley-VCH Verlag, 2010, [Peer-reviewed]
  English, Scientific journal
• Cation recognition and pseudorotaxane formation of tris-dipyrrin BF2 macrocycles
  Naoya Sakamoto, Chusaku Ikeda, Tatsuya Nabeshima
  CHEMICAL COMMUNICATIONS, 46, 36, 6732, 6734, 2010, [Peer-reviewed]
  English, Scientific journal
• Upregulation of Connexin 30 in Intestinal Phenotype Gastric Cancer and Its Reduction during Tumor Progression
  Kazuhiro Sentani, Naohide Oue, Naoya Sakamoto, Katsuhiro Anami, Yutaka Naito, Kazuhiko Aoyagi, Hiroki Sasaki, Wataru Yasui
  PATHOBIOLOGY, 77, 5, 241, 248, 2010, [Peer-reviewed]
  English, Scientific journal
• Antiviral Effects of the Interferon-Induced Protein Guanylate Binding Protein 1 and Its Interaction with the Hepatitis C Virus NS5B Protein
  Yasuhiro Itsui, Naoya Sakamoto, Sei Kakinuma, Mina Nakagawa, Yuko Sekine-Osajima, Megumi Tasaka-Fujita, Yuki Nishimura-Sakurai, Gokui Suda, Yuko Karakama, Kako Mishima, Machi Yamamoto, Takako Watanabe, Mayumi Ueyama, Yusuke Funaoka, Seishin Azuma, Mamoru Watanabe
  HEPATOLOGY, 50, 6, 1727, 1737, Dec. 2009, [Peer-reviewed]
  English, Scientific journal
• Serum olfactomedin 4 (GWI 12, hGC4) in combination with Reg IV is a highly sensitive biomarker for gastric cancer patients
  Naohide Oue, Kazuhiro Sentani, Tsuyoshi Noguchi, Shinya Ohara, Naoya Sakamoto, Tetsutaro Hayashi, Katsuhirio Anami, Junichi Motoshita, Masanori Ito, Shinji Tanaka, Kazuhiro Yoshida, Wataru Yasui
  INTERNATIONAL JOURNAL OF CANCER, 125, 10, 2383, 2392, Nov. 2009, [Peer-reviewed]
  English, Scientific journal
• Adoptive immunotherapy with liver allograft-derived lymphocytes induces anti-HCV activity after liver transplantation in humans and humanized mice
  Masahiro Ohira, Kohei Ishiyama, Yuka Tanaka, Marlen Doskali, Yuka Igarashi, Hirotaka Tashiro, Nobuhiko Hiraga, Michio Imamura, Naoya Sakamoto, Toshimasa Asahara, Kazuaki Chayama, Hideki Ohdan
  JOURNAL OF CLINICAL INVESTIGATION, 119, 11, 3226, 3235, Nov. 2009, [Peer-reviewed]
  English, Scientific journal
• IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4+ memory T cells in chronic colitis
  Takayuki Tomita, Takanori Kanai, Teruji Totsuka, Yasuhiro Nemoto, Ryuichi Okamoto, Kiichiro Tsuchiya, Naoya Sakamoto, Toshiaki Ohteki, Toshifumi Hibi, Mamoru Watanabe
  European Journal of Immunology, 39, 10, 2737, 2747, Oct. 2009, [Peer-reviewed]
  English, Scientific journal
• IL-7 is essential for lymphopenia-driven turnover of colitogenic CD4(+) memory T cells in chronic colitis
  Takayuki Tomita, Takanori Kanai, Teruji Totsuka, Yasuhiro Nemoto, Ryuichi Okamoto, Kiichiro Tsuchiya, Naoya Sakamoto, Toshiaki Ohteki, Toshifumi Hibi, Mamoru Watanabe
  EUROPEAN JOURNAL OF IMMUNOLOGY, 39, 10, 2737, 2747, Oct. 2009, [Peer-reviewed]
  English, Scientific journal
• Genome-wide association of IL28B with response to pegylated interferon-alpha and ribavirin therapy for chronic hepatitis C
  Yasuhito Tanaka, Nao Nishida, Masaya Sugiyama, Masayuki Kurosaki, Kentaro Matsuura, Naoya Sakamoto, Mina Nakagawa, Masaaki Korenaga, Keisuke Hino, Shuhei Hige, Yoshito Ito, Eiji Mita, Eiji Tanaka, Satoshi Mochida, Yoshikazu Murawaki, Masao Honda, Akito Sakai, Yoichi Hiasa, Shuhei Nishiguchi, Asako Koike, Isao Sakaida, Masatoshi Imamura, Kiyoaki Ito, Koji Yano, Naohiko Masaki, Fuminaka Sugauchi, Namiki Izumi, Katsushi Tokunaga, Masashi Mizokami
  NATURE GENETICS, 41, 10, 1105, U81, Oct. 2009, [Peer-reviewed]
  English, Scientific journal
• Long-Lived Colitogenic CD4(+) Memory T Cells Residing Outside the Intestine Participate in the Perpetuation of Chronic Colitis
  Yasuhiro Nemoto, Takanori Kanai, Kaori Kameyama, Tamako Shinohara, Naoya Sakamoto, Teruji Totsuka, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Tetsuo Sudo, Satoshi Matsumoto, Mamoru Watanabe
  JOURNAL OF IMMUNOLOGY, 183, 8, 5059, 5068, Oct. 2009, [Peer-reviewed]
  English, Scientific journal
• Hepatitis C virus NS5A protein increases hepatic lipid accumulation via induction of activation and expression of PPARgamma
  KyeongJin Kim, Kook Hwan Kim, Eunsin Ha, Jin Young Park, Naoya Sakamoto, JaeHun Cheong
  FEBS LETTERS, 583, 17, 2720, 2726, Sep. 2009, [Peer-reviewed]
  English, Scientific journal
• Inhibition of intracellular hepatitis C virus replication by nelfinavir and synergistic effect with interferon-α
  S. Toma, T. Yamashiro, S. Arakaki, J. Shiroma, T. Maeshiro, K. Hibiya, N. Sakamoto, F. Kinjo, M. Tateyama, J. Fujita
  Journal of Viral Hepatitis, 16, 7, 506, 512, Jul. 2009, [Peer-reviewed]
  English, Scientific journal
• Bioactivity-guided screening identifies pheophytin a as a potent anti-hepatitis C virus compound from Lonicera hypoglauca Miq.
  Sheng-Yang Wang, Ching-Ping Tseng, Keng-Chang Tsai, Chia-Fan Lin, Ching-Ya Wen, Hsin-Sheng Tsaye, Naoya Sakamoto, Chin-Hsiao Tseng, Ju-Chien Cheng
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 385, 2, 230, 235, Jul. 2009, [Peer-reviewed]
  English, Scientific journal
• New therapeutic approaches to hepatitis C virus
  Naoya Sakamoto, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY, 44, 7, 643, 649, Jul. 2009, [Peer-reviewed]
  English
• Rank-rankl signaling pathway is critically involved in the function of CD4+CD25+ regulatory T cells in chronic colitis
  Teruji Totsuka, Takanori Kanai, Yasuhiro Nemoto, Takayuki Tomita, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Hisaya Akiba, Ko Okumura, Hideo Yagita, Mamoru Watanabe
  Journal of Immunology, 182, 10, 6079, 6087, 15 May 2009, [Peer-reviewed]
  English, Scientific journal
• RANK-RANKL Signaling Pathway Is Critically Involved in the Function of CD4(+)CD25(+) Regulatory T Cells in Chronic Colitis
  Teruji Totsuka, Takanori Kanai, Yasuhiro Nemoto, Takayuki Tomita, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Hisaya Akiba, Ko Okumura, Hideo Yagita, Mamoru Watanabe
  JOURNAL OF IMMUNOLOGY, 182, 10, 6079, 6087, May 2009, [Peer-reviewed]
  English, Scientific journal
• Signaling pathway via TNF-alpha/NF-kappa B in intestinal epithelial cells may be directly involved in colitis-associated carcinogenesis
  Michio Onizawa, Takashi Nagaishi, Takanori Kanai, Ken-ichi Nagano, Shigeru Oshima, Yasuhiro Nemoto, Atsushi Yoshioka, Teruji Totsuka, Ryuichi Okamoto, Tetsuya Nakamura, Naoya Sakamoto, Kiichiro Tsuchiya, Kazuhiro Aoki, Keiichi Ohya, Hideo Yagita, Mamoru Watanabe
  AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 296, 4, G850, G859, Apr. 2009, [Peer-reviewed]
  English, Scientific journal
• Musashi-1 suppresses expression of Paneth cell-specific genes in human intestinal epithelial cells
  Minekazu Murayama, Ryuichi Okamoto, Kiichiro Tsuchiya, Junko Akiyama, Tetsuya Nakamura, Naoya Sakamoto, Takanori Kanai, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY, 44, 3, 173, 182, Mar. 2009, [Peer-reviewed]
  English, Scientific journal
• A Functional Genomic Screen Identifies Cellular Cofactors of Hepatitis C Virus Replication
  Andrew W. Tai, Yair Benita, Lee F. Peng, Sun-Suk Kim, Naoya Sakamoto, Ramnik J. Xavier, Raymond T. Chung
  CELL HOST & MICROBE, 5, 3, 298, 307, Mar. 2009, [Peer-reviewed]
  English, Scientific journal
• Two flavonoids extracts from Glycyrrhizae radix inhibit in vitro hepatitis C virus replication
  Yuko Sekine-Osajima, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Itsui, Megumi Tasaka, Yuki Nishimura-Sakurai, Cheng-Hsin Chen, Goki Suda, Kako Mishima, Yuko Onuki, Machi Yamamoto, Shinya Maekawa, Nobuyuki Enomoto, Takanori Kanai, Kiichiro Tsuchiya, Mamoru Watanabe
  HEPATOLOGY RESEARCH, 39, 1, 60, 69, Jan. 2009, [Peer-reviewed]
  English, Scientific journal
• Colitogenic CD4(+) Effector-memory T Cells Actively Recirculate in Chronic Colitic Mice
  Takayuki Tomita, Takanori Kanai, Yasuhiro Nemoto, Toshimitsu Fujii, Kengo Nozaki, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Teruji Totsuka, Mamoru Watanabe
  INFLAMMATORY BOWEL DISEASES, 14, 12, 1630, 1640, Dec. 2008, [Peer-reviewed]
  English, Scientific journal
• FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4(+) T cells in bone marrow
  Toshimitsu Fujii, Takayuki Tomita, Takanori Kanai, Yasuhiro Nemoto, Teruji Totsuka, Naoya Sakamoto, Tetsuya Nakamura, Kiichiro Tsuchiya, Ryuichi Okamoto, Mamoru Watanabe
  EUROPEAN JOURNAL OF IMMUNOLOGY, 38, 12, 3290, 3303, Dec. 2008, [Peer-reviewed]
  English, Scientific journal
• Negative Feedback Regulation of Colitogenic CD4(+) T Cells by Increased Granulopoiesis
  Yosuhiro Nemoto, Takanori Kanai, Shuji Tohda, Teruji Totsuka, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Tetsuya Fukuda, Osamu Miura, Hideo Yagita, Mamoru Watanabe
  INFLAMMATORY BOWEL DISEASES, 14, 11, 1491, 1503, Nov. 2008, [Peer-reviewed]
  English, Scientific journal
• Griseofulvin, an oral antifungal agent, suppresses hepatitis C virus replication in vitro.
  Jin H, Yamashita A, Maekawa S, Yang P, He L, Takayanagi S, Wakita T, Sakamoto N, Enomoto N, Ito M
  Hepatology Research, 38, 9, 909, 918, 01 Sep. 2008, [Peer-reviewed]
  English, Scientific journal
• Griseofulvin, an oral antifungal agent, suppresses hepatitis C virus replication in vitro
  Haofan Jin, Atsuya Yamashita, Shinya Maekawa, Pinting Yang, Limin He, Satoru Takayanagi, Takaji Wakita, Naoya Sakamoto, Nobuyuki Enomoto, Masahiko Ito
  HEPATOLOGY RESEARCH, 38, 9, 909, 918, Sep. 2008, [Peer-reviewed]
  English, Scientific journal
• Inhibition of hepatitis C virus infection and expression in vitro and in vivo by recombinant adenovirus expressing short hairpin RNA
  Naoya Sakamoto, Yoko Tanabe, Takanori Yokota, Kenichi Satoh, Yuko Sekine-Osajima, Mina Nakagawa, Yasuhiro Itsui, Megumi Tasaka, Yuki Sakurai, Chen Cheng-Hsin, Masahiko Yano, Shogo Ohkoshi, Yutaka Aoyagi, Shinya Maekawa, Nobuyuki Enomoto, Michinori Kohara, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 23, 9, 1437, 1447, Sep. 2008, [Peer-reviewed]
  English, Scientific journal
• Immunohistochemical staining of Reg IV and claudin-18 is useful in the diagnosis of gastrointestinal signet ring cell carcinoma
  Kazuhiro Sentani, Naohide Oue, Takashi Tashiro, Naoya Sakamoto, Takashi Nishisaka, Toshiyuki Fukuhara, Kiyorni Taniyama, Hiroo Matsuura, Koji Arihiro, Atsushi Ochiai, Wataru Yasui
  AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 32, 8, 1182, 1189, Aug. 2008, [Peer-reviewed]
  English, Scientific journal
• Continuous generation of colitogenic CD4(+) T cells in persistent colitis
  Takayuki Tomita, Takanori Kanai, Toshimitsu Fujii, Yasuhiro Nemoto, Ryuichi Okamoto, Kiichiro Tsuchiya, Teruji Totsuka, Naoya Sakamoto, Mamoru Watanabe
  EUROPEAN JOURNAL OF IMMUNOLOGY, 38, 5, 1264, 1274, May 2008, [Peer-reviewed]
  English, Scientific journal
• Immunosenescent colitogenic CD4(+) T cells convert to regulatory cells and suppress colitis
  Teruji Totsuka, Takanori Kanai, Yasuhiro Nemoto, Takayuki Tomita, Kiichiro Tsuchiya, Naoya Sakamoto, Ryuichi Okamoto, Mamoru Watanabe
  EUROPEAN JOURNAL OF IMMUNOLOGY, 38, 5, 1275, 1286, May 2008, [Peer-reviewed]
  English, Scientific journal
• Potential relevance of cytoplasmic viral sensors and related regulators involving innate immunity in antiviral response
  Yasuhiro Asahina, Namiki Izumi, Itsuko Hirayama, Tomohiro Tanaka, Mitsuaki Sato, Yutaka Yasui, Nobutoshi Komatsu, Naoki Umeda, Takanori Hosokawa, Ken Ueda, Kaoru Tsuchiya, Hiroyuki Nakanishi, Jun Itakura, Masayuki Kurosaki, Nobuyuki Enomoto, Megumi Tasaka, Naoya Sakamoto, Shozo Miyake
  GASTROENTEROLOGY, 134, 5, 1396, 1405, May 2008, [Peer-reviewed]
  English, Scientific journal
• Proteasomal degradation of Atoh1 by aberrant Wnt signaling maintains the undifferentiated state of colon cancer
  Mikayo Aragaki, Kiichiro Tsuchiya, Ryuichi Okamoto, Sanae Yoshioka, Tetsuya Nakamura, Naoya Sakamoto, Takanori Kanai, Mamoru Watanabe
  Biochemical and Biophysical Research Communications, 368, 4, 923, 929, 18 Apr. 2008, [Peer-reviewed]
  English, Scientific journal
• Gene expression profiling with microarray and SAGE identifies PLUNC as a marker for hepatoid adenocarcinoma of the stomach
  Kazuhiro Sentani, Naohide Oue, Naoya Sakamoto, Koji Arihiro, Kazuhiko Aoyagi, Hiroki Sasaki, Wataru Yasui
  MODERN PATHOLOGY, 21, 4, 464, 475, Apr. 2008, [Peer-reviewed]
  English, Scientific journal
• Proteasomal degradation of Atoh1 by aberrant Wnt signaling maintains the undifferentiated state of colon cancer
  Mikayo Aragaki, Kiichiro Tsuchiya, Ryuichi Okamoto, Sanae Yoshioka, Tetsuya Nakamura, Naoya Sakamoto, Takanorl Kanai, Mamoru Watanabe
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 368, 4, 923, 929, Apr. 2008, [Peer-reviewed]
  English, Scientific journal
• MyD88-dependent pathway in T cells directly modulates the expansion of colitogenic CD4(+) T cells in chronic colitis
  Takayuki Tomita, Takanori Kanai, Toshimitsu Fujii, Yasuhiro Nemoto, Ryuichi Okamoto, Kiichiro Tsuchiya, Teruji Totsuka, Naoya Sakamoto, Shizuo Akira, Mamoru Watanabe
  JOURNAL OF IMMUNOLOGY, 180, 8, 5291, 5299, Apr. 2008, [Peer-reviewed]
  English, Scientific journal
• Development of plaque assays for hepatitis C virus-JFH1 strain and isolation of mutants with enhanced cytopathogenicity and replication capacity
  Yuko Sekine-Osajima, Naoya Sakamoto, Kako Mishima, Mina Nakagawa, Yasuhiro Itsui, Megumi Tasaka, Yuki Nishimura-Sakurai, Cheng-Hsin Chen, Takanori Kanai, Kiiehiro Tsuchiya, Takaji Wakita, Nobuyuki Enomoto, Mamoru Watanabe
  VIROLOGY, 371, 1, 71, 85, Feb. 2008, [Peer-reviewed]
  English, Scientific journal
• Targeting lipid metabolism in the treatment of hepatitis C virus infection
  Fumitake Amemiya, Shinya Maekawa, Yoshie Itakura, Asuka Kanayama, Akira Matsui, Shinichi Takano, Tatsuya Yamaguchi, Jun Itakura, Takatoshi Kitamura, Taisuke Inoue, Minoru Sakamoto, Kozue Yamauchi, Shunichi Okada, Atsuya Yamashita, Naoya Sakamoto, Masahiko Itoh, Nobuyuki Enomoto
  JOURNAL OF INFECTIOUS DISEASES, 197, 3, 361, 370, Feb. 2008, [Peer-reviewed]
  English, Scientific journal
• 2. Progression of Type C Chronic Hepatitis and Resistance to Treatment 1) From a Viewpoint of Viral Mutation
  Sakamoto Naoya
  Nihon Naika Gakkai Kaishi, 97, 1, 64, 68, The Japanese Society of Internal Medicine, 10 Jan. 2008
  Japanese, C型肝炎ウイルス（HCV）は変位速度が速く，慢性持続感染の機構のひとつと考えられる．日本に多いゲノタイプ1型は2型に比べインターフェロン治療抵抗性である．ウイルスゲノムのコア領域·NS5A領域にインターフェロン治療の感受性を規定する部位が存在する．今後ウイルス蛋白を標的とした治療薬が登場するがウイルス耐性変異の克服が課題となる．
  
• Blockade of NKG2D signaling prevents the development of murine CD4(+) T cell-mediated colitis
  Y. Ito, T. Kanai, T. Totsuka, R. Okamoto, K. Tsuchiya, Y. Nemoto, A. Yoshioka, T. Tomita, T. Nagaishi, N. Sakamoto, T. Sakanishi, K. Okumura, H. Yagita, M. Watanabe
  AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 294, 1, G199, G207, Jan. 2008, [Peer-reviewed]
  English, Scientific journal
• Negative feedback regulation of colitogenic CD4+ T cells by increased granulopoiesis
  Yasuhiro Nemoto, Takanori Kanai, Shuji Tohda, Teruji Totsuka, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Tetsuya Fukuda, Osamu Miura, Hideo Yagita, Mamoru Watanabe
  Inflammatory Bowel Diseases, 14, 11, 1491, 1503, 2008, [Peer-reviewed]
  English, Scientific journal
• Colitogenic CD4+ effector-memory T cells actively recirculate in chronic colitic mice
  Takayuki Tomita, Takanori Kanai, Yasuhiro Nemoto, Toshimitsu Fujii, Kengo Nozaki, Ryuichi Okamoto, Kiichiro Tsuchiya, Tetsuya Nakamura, Naoya Sakamoto, Teruji Totsuka, Mamoru Watanabe
  Inflammatory Bowel Diseases, 14, 12, 1630, 1640, 2008, [Peer-reviewed]
  English, Scientific journal
• FTY720 suppresses the development of colitis in lymphoid-null mice by modulating the trafficking of colitogenic CD4+ T cells in bone marrow
  Toshimitsu Fujii, Takayuki Tomita, Takanori Kanai, Yasuhiro Nemoto, Teruji Totsuka, Naoya Sakamoto, Tetsuya Nakamura, Kiichiro Tsuchiya, Ryuichi Okamoto, Mamoru Watanabe
  European Journal of Immunology, 38, 12, 3290, 3303, 2008, [Peer-reviewed]
  English, Scientific journal
• Systemic, but not intestinal, IL-7 is essential for the persistence of chronic colitis.
  Tomita T, Kanai T, Nemoto Y, Totsuka T, Okamoto R, Tsuchiya K, Sakamoto N, Watanabe M
  Journal of immunology (Baltimore, Md. : 1950), 180, 1, 383, 390, Jan. 2008, [Peer-reviewed]
• Hepatitis C virus non-structural proteins responsible for suppression of the RIG-I/Cardif-induced interferon response
  Megumi Tasaka, Naoya Sakamoto, Mina Nakagawa, Yasuhiro Itsui, Yuko Sekine-Osajima, Yuki Nishimura-Sakurai, Cheng-Hsin Chen, Mitsutoshi Yoneyama, Takashi Fujita, Takaji Wakita, Shinya Maekawa, Nobuyuki Enomoto, Mamoru Watanabe
  JOURNAL OF GENERAL VIROLOGY, 88, Pt 12, 3323, 3333, Dec. 2007, [Peer-reviewed]
  English, Scientific journal
• Identification of novel epoxide inhibitors of hepatitis C virus replication using a high-throughput screen
  Lee F. Peng, Sun Suk Kim, Sirinya Matchacheep, Xiaoguang Lei, Shun Su, Wenyu Lin, Weerawat Runguphan, Won-Hyeok Choe, Naoya Sakamoto, Masanori Ikeda, Nobuyuki Kato, Aaron B. Beeler, John A. Porco, Stuart L. Schreiber, Raymond T. Chung
  ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 51, 10, 3756, 3759, Oct. 2007, [Peer-reviewed]
  English, Scientific journal
• Bone morphogenetic protein-7 and interferon-alpha synergistically suppress hepatitis C virus replicon
  Naoya Sakamoto, Mika Yoshimura, Tomomi Kimura, Keisuke Toyama, Yuko Sekine-Osajima, Mamoru Watanabe, Masaaki Muramatsu
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 357, 2, 467, 473, Jun. 2007, [Peer-reviewed]
  English, Scientific journal
• Human Cord Blood Cells Transplanted Into Chronically Damaged Liver Exhibit Similar Characteristics to Functional Hepatocytes
  S. Kakinuma, K. Asahina, K. Okamura, K. Teramoto, C. Tateno, K. Yoshizato, Y. Tanaka, T. Yasumizu, N. Sakamoto, M. Watanabe, H. Teraoka
  Transplantation Proceedings, 39, 1, 240, 243, Jan. 2007, [Peer-reviewed]
  English, Scientific journal
• 高用量ステロイド投与を行わず、シクロスポリンにて緩解導入した潰瘍性大腸炎の1例　　　　　　　　　　　　　　　
  久保田大輔, 金井隆典, 油井史郎, 松本智子, 河村貴広, 井津井康浩, 岡田英理子, 陳正新, 大岡真也, 長堀正和, 土屋輝一郎, 荒木昭博, 坂本直哉, 宮田達也, 渡辺守
  日本消化器病学会雑誌, 104, 1, 42, 46, 2007
  Japanese, Scientific journal
• ダブルバルーン小腸内視鏡(DBE)を用いて小腸ポリープを切除したPeutz-Jeghers syndromeの1例　　　　　　　　　　　　　　　
  渡辺貴子, 玄世鋒, 植山真由美, 小野塚泉, 久保田大輔, 岡田英理子, 鈴木伸治, 陳正新, 長堀正和, 岡本隆一, 中川美奈, 戸塚輝治, 土屋輝一郎, 永石宇司, 中村哲也, 荒木昭博, 坂本直哉, 金井隆典, 渡辺守
  Progress of Digestive Endoscopy, 72, 1, 107, 2007
  Japanese, Scientific journal
• ダブルバルーン内視鏡で診断し治療後経過観察し得た、空腸follicular lymphomaの一例　　　　　　　　　　　　　　　
  岡本英子, 岡田英理子, 荒木昭博, 土屋輝一郎, 小貫優子, 三島果子, 山本満千, 須田剛生, 松本智子, 久保田大輔, 陳正新, 大岡真也, 長堀正和, 吉岡早苗, 鈴木伸治, 坂本直哉, 金井隆典, 渡辺守
  Progress of Digestive Endoscopy, 71, 1, 103, 2007
  Japanese, Scientific journal
• A case of severe ulcerative colitis successfully with intravenous cyclosporine without high dose corticosteroid
  Daisuke Kubota, Takanori Kanai, Fumiro Yui, Tomoko Matsumoto, Takahiro Kawamura, Yasuhiro Itsui, Eriko Okada, Seishin Chin, Shinya Ooka, Masakazu Nagahori, Kiichiro Tsuchiya, Akihiro Araki, Naoya Sakamoto, Tatsuya Miyata, Mamoru Watanabe
  Japanese Journal of Gastroenterology, 104, 1, 42, 46, Jan. 2007
  Japanese, Scientific journal
• A cell-based, high-throughput screen for small molecule regulators of hepatitis C virus replication
  Sun Suk Kim, Lee F. Peng, Wenyu Lin, Won-Hyeok Choe, Naoya Sakamoto, Stuart L. Schreiber, Raymond T. Chung
  GASTROENTEROLOGY, 132, 1, 311, 320, Jan. 2007, [Peer-reviewed]
  English, Scientific journal
• Expressional screening of interferon-stimulated genes for antiviral activity against hepatitis C virus replication
  Y. Itsui, N. Sakamoto, M. Kurosaki, N. Kanazawa, Y. Tanabe, T. Koyama, Y. Takeda, M. Nakagawa, S. Kakinuma, Y. Sekine, S. Maekawa, N. Enomoto, M. Watanabe
  JOURNAL OF VIRAL HEPATITIS, 13, 10, 690, 700, Oct. 2006, [Peer-reviewed]
  English, Scientific journal
• Site-specific mutation of the interferon sensitivity-determining region (ISDR) modulates hepatitis C virus replication
  T. Kohashi, S. Maekawa, N. Sakamoto, M. Kurosaki, H. Watanabe, Y. Tanabe, C. -H. Chen, N. Kanazawa, M. Nakagawa, S. Kakinuma, T. Yamashiro, Y. Itsui, T. Koyama, N. Enomoto, M. Watanabe
  JOURNAL OF VIRAL HEPATITIS, 13, 9, 582, 590, Sep. 2006, [Peer-reviewed]
  English, Scientific journal
• A case report: Severe bone marrow suppression caused by 6-mercaptopurin in Crohn's disease patient
  Daisuke Kubota, Chizuru Takishima, Ken-Ichi Ishii, Takahiro Kawamura, Tomoko Matsumoto, Yasuhiro Itsui, Eriko Okada, Seishin Chin, Shinya Oooka, Kiichiro Tsuchiya, Akihiro Araki, Naoya Sakamoto, Tatsuya Miyata, Takanori Kanai, Mamoru Watanabe
  Japanese Journal of Gastroenterology, 103, 9, 1044, 1049, Sep. 2006
  Japanese, Scientific journal
• Negative regulation of intracellular hepatitis C virus replication by interferon regulatory factor 3
  Tsuyoshi Yamashiro, Naoya Sakamoto, Masayuki Kurosaki, Nobuhiko Kanazawa, Yoko Tanabe, Mina Nakagawa, Cheng-Hsin Chen, Yasuhiro Itsui, Tomoyuki Koyama, Yoshie Takeda, Shinya Maekawa, Nobuyuki Enomoto, Hiroshi Sakugawa, Mamoru Watanabe
  JOURNAL OF GASTROENTEROLOGY, 41, 8, 750, 757, Sep. 2006, [Peer-reviewed]
  English, Scientific journal
• The wrapping method using biodegradable felt strips has a preventive effect on the thinning of the aortic wall: Experimental study in the canine aorta
  Hidenori Fujiwara, Katsuhiko Oda, Yoshikatsu Saiki, Naoya Sakamoto, Toshiro Ohashi, Masaaki Sato, Yasuhiko Tabata, Koichi Tabayashi
  Journal of Vascular Surgery, 43, 2, 349, 356, Feb. 2006, [Peer-reviewed]
  English, Scientific journal
• ダブルバルーン内視鏡が診断、治療効果判定に有用であったT-cell lymphomaの一例　　　　　　　　　　　　　　　
  松本智子, 荒木昭博, 土屋輝一郎, 大島茂, 岡田英理子, 久保田大輔, 陳正新, 長堀正和, 大岡真也, 坂本直哉, 金井隆典, 渡辺守
  Gastroenterological Endoscopy, 48, Suppl.2, 2156, 2006
  Japanese, Scientific journal
• 消化管出血とその対策 動脈瘤の小腸穿通が疑われた消化管出血に対する緊急術中ダブルバルーン内視鏡2例の報告　　　　　　　　　　　　　　　
  荒木昭博, 土屋輝一郎, 大島茂, 柴田早苗, 岡田英理子, 松本智子, 久保田大輔, 長堀正和, 河村貴弘, 井津井康浩, 陳正新, 大岡真也, 宮田達也, 坂本直哉, 金井隆典, 渡辺守
  Progress of Digestive Endoscopy, 69, 1, 53, 2006
  Japanese, Scientific journal
• 6-mercaptopurineにより重症骨髄抑制をきたしたクローン病の1例　　　　　　　　　　　　　　　
  久保田大輔, 滝島千尋, 石井賢一, 河村貴広, 松本智子, 井津井康浩, 岡田英理子, 陳正新, 大岡真也, 土屋輝一郎, 荒木昭博, 坂本直哉, 宮田達也, 金井隆典, 渡辺守
  日本消化器病学会雑誌, 103, 9, 1044, 1049, 2006
  Japanese, Scientific journal
• 潰瘍性大腸炎に合併した仙腸関節炎に対しステロイドが奏効した1例　　　　　　　　　　　　　　　
  久保田大輔, 金井隆典, 松本智子, 河村貴広, 井津井康浩, 岡田英理子, 陳正新, 大岡信也, 土屋輝一郎, 荒木昭博, 坂本直哉, 宮田達也, 渡辺守
  日本消化器病学会雑誌, 103, 8, 936, 942, 2006
  Japanese, Scientific journal
• A case of sacroiliitis complicated by ulcerative colitis that was successfully treated with steroid
  Daisuke Kubota, Takanori Kanai, Tomoko Matsumoto, Takahiro Kawamura, Yasuhiro Itsui, Eriko Okada, Seishin Chin, Shinya Ohoka, Kiichiro Tsuchiya, Akihiro Araki, Naoya Sakamoto, Tatsuya Miyata, Mamoru Watanabe
  Japanese Journal of Gastroenterology, 103, 8, 936, 942, 2006
  Japanese, Scientific journal
• Divergent activities of interferon-alpha subtypes against intracellular hepatitis C virus replication
  T Koyama, N Sakamoto, Y Tanabe, M Nakagawa, Y Itsui, Y Takeda, S Kakinuma, Y Sekine, S Maekawa, Y Yanai, M Kurimoto, M Watanabe
  HEPATOLOGY RESEARCH, 34, 1, 41, 49, Jan. 2006, [Peer-reviewed]
  English, Scientific journal
• Viral load change and sequential evolution of entire hepatitis C virus genome in Irish recipients of single source-contaminated anti-D immunoglobulin
  J Itakura, K Nagayama, N Enomoto, K Hamano, N Sakamoto, LJ Fanning, E Kenny-Walsh, F Shanahan, M Watanabe
  JOURNAL OF VIRAL HEPATITIS, 12, 6, 594, 603, Nov. 2005, [Peer-reviewed]
  English, Scientific journal
• Mutations in the NS5B region of the hepatitis C virus genome correlate with clinical outcomes of interferon-alpha plus ribavirin combination therapy
  K Hamano, N Sakamoto, N Enomoto, N Izumi, Y Asahina, M Kurosaki, E Ueda, Y Tanabe, S Maekawa, J Itakura, H Watanabe, S Kakinuma, M Watanabe
  JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 20, 9, 1401, 1409, Sep. 2005, [Peer-reviewed]
  English, Scientific journal
• Suppression of hepatitis C virus replication by cyclosporin A is mediated by blockade of cyclophilins
  M Nakagawa, N Sakamoto, Y Tanabe, T Koyama, Y Itsui, Y Takeda, CH Chen, S Kakinuma, S Oooka, S Maekawa, N Enomoto, M Watanabe
  GASTROENTEROLOGY, 129, 3, 1031, 1041, Sep. 2005, [Peer-reviewed]
  English, Scientific journal
• Characteristic sequence changes of hepatitis C virus genotype 2b associated with sustained biochemical response to IFN therapy
  Y Tanabe, K Nagayama, N Enomoto, N Izumi, J Tazawa, M Kurosaki, N Sakamoto, C Sato, M Watanabe
  JOURNAL OF VIRAL HEPATITIS, 12, 3, 251, 261, May 2005, [Peer-reviewed]
  English, Scientific journal
• Enhancement of mitochondrial gene expression in the liver of primary biliary cirrhosis
  CH Chen, K Nagayama, N Enomoto, Y Miyasaka, M Kurosaki, N Sakamoto, S Maekawa, S Kakinuma, T Ikeda, N Izumi, C Sato, M Watanabe
  HEPATOLOGY RESEARCH, 31, 1, 24, 30, Jan. 2005, [Peer-reviewed]
  English, Scientific journal
• 新しい工夫・ダブルオーバーチューブ法によるダブルバルーン内視鏡の報告,および当院でのダブルバルーン内視鏡の現状　　　　　　　　　　　　　　　
  荒木昭博, 土屋輝一郎, 大島茂, 岡田英理子, 久保田大輔, 井津井康浩, 河村貴広, 松本智子, 飯山稜一, 吉岡篤史, 柴田早苗, 陳正新, 大岡真也, 坂本直哉, 宮田達也, 金井隆典, 渡辺守
  Progress of Digestive Endoscopy, 68, 1, 61, 2005
  Japanese, Scientific journal
• ダブルバルーン内視鏡のみにて発見,および術前に確定診断し得た小腸がんの二例　　　　　　　　　　　　　　　
  荒木昭博, 土屋輝一郎, 岡田英理子, 久保田大輔, 陳正新, 石井賢一, 柿沼晴, 大岡真也, 中村哲也, 坂本直哉, 宮田達也, 金井隆典, 渡辺守, 大貫和美, 金澤信彦
  Progress of Digestive Endoscopy, 67, 1, 57, 2005
  Japanese, Scientific journal
• ダブルバルーン小腸内視鏡を用いて全消化管を検索し得た好酸球性胃腸炎の一例　　　　　　　　　　　　　　　
  高山啓, 土屋輝一郎, 荒木昭博, 岡田英理子, 久保田大輔, 陳正新, 石井賢一, 柿沼晴, 大岡真也, 中村哲也, 坂本直哉, 宮田達也, 金井隆典, 渡辺守
  Progress of Digestive Endoscopy, 67, 1, 91, 2005
  Japanese, Scientific journal
• Down-regulation of p27(Kip1) promotes cell proliferation of rat neonatal cardiomyocytes induced by nuclear expression of cyclin d1 and CDK4-Evidence for impaired Skp2-dependent degradation of p27 in terminal differentiation
  M Tamamori-Adachi, K Hayashida, K Nobori, C Omizu, K Yamada, N Sakamoto, T Kamura, K Fukuda, S Ogawa, KI Nakayama, S Kitajima
  JOURNAL OF BIOLOGICAL CHEMISTRY, 279, 48, 50429, 50436, Nov. 2004, [Peer-reviewed]
  English, Scientific journal
• Introduction of NS5A mutations enables subgenomic HCV replicon derived from chimpanzee-infectious HC-J4 isolate to replicate efficiently in Huh-7 cells
  S Maekawa, N Enomoto, N Sakamoto, M Kurosaki, E Ueda, T Kohashi, H Watanabe, CH Chen, T Yamashiro, Y Tanabe, N Kanazawa, M Nakagawa, C Sato, M Watanabe
  JOURNAL OF VIRAL HEPATITIS, 11, 5, 394, 403, Sep. 2004, [Peer-reviewed]
  English, Scientific journal
• Regulation of hepatitis C virus replication by interferon regulatory factor 1
  N Kanazawa, M Kurosaki, N Sakamoto, N Enomoto, Y Itsui, T Yamashiro, Y Tanabe, S Maekawa, M Nakagawa, CH Chen, S Kakinuma, S Oshima, T Nakamura, T Kato, T Wakita, M Watanabe
  JOURNAL OF VIROLOGY, 78, 18, 9713, 9720, Sep. 2004, [Peer-reviewed]
  English, Scientific journal
• Changes of HCV quasispecies during combination therapy with interferon and ribavirin
  E Ueda, N Enomoto, N Sakamoto, K Hamano, C Sato, N Izumi, M Watanabe
  HEPATOLOGY RESEARCH, 29, 2, 89, 96, Jun. 2004, [Peer-reviewed]
  English, Scientific journal
• Synergistic inhibition of intracellular hepatitis C virus replication by combination of ribavirin and interferon-alpha
  Y Tanabe, N Sakamoto, N Enomoto, M Kurosaki, E Ueda, S Maekawa, T Yamashiro, M Nakagawa, CH Chen, N Kanazawa, S Kakinuma, M Watanabe
  JOURNAL OF INFECTIOUS DISEASES, 189, 7, 1129, 1139, Apr. 2004, [Peer-reviewed]
  English, Scientific journal
• Establishment of a new hepatitis C virus-1b replicon
  N Enomoto, N Sakamoto, M Kurosaki, S Maekawa, Y Tanabe, T Yamashiro, CH Chen, M Nakagawa, N Kanazawa, H Watanabe, C Sato, M Watanabe
  THERAPY FOR VIRAL HEPATITIS AND PREVENTION OF HEPATOCELLULAR CARCINOMA, 97, 107, 2004, [Peer-reviewed]
  English, International conference proceedings
• Differential gene-expression profiles associated with gastric adenoma
  H Takenawa, M Kurosaki, N Enomoto, Y Miyasaka, N Kanazawa, N Sakamoto, T Ikeda, N Izumi, C Sato, M Watanabe
  BRITISH JOURNAL OF CANCER, 90, 1, 216, 223, Jan. 2004, [Peer-reviewed]
  English, Scientific journal
• 放射線性腸炎による出血に対しアルゴンプラズマ凝固療法が有効であった特発性血小板減少性紫斑病の1例　　　　　　　　　　　　　　　
  深山雄大, 土屋輝一郎, 荒木昭博, 岡田英理子, 久保田大輔, 陳正新, 石井賢一, 長堀正和, 柿沼晴, 大岡真也, 中村哲也, 坂本直哉, 宮田達也, 金井隆典, 渡辺守
  Progress of Digestive Endoscopy, 66, 1, 68, 2004
  Japanese, Scientific journal
• Specific inhibition of hepatitis C virus replication by cyclosporin A
  M Nakagawa, N Sakamoto, N Enomoto, Y Tanabe, N Kanazawa, T Koyama, M Kurosaki, S Maekawa, T Yamashiro, CH Chen, Y Itsui, S Kakinuma, M Watanabe
  BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 313, 1, 42, 47, Jan. 2004, [Peer-reviewed]
  English, Scientific journal
• Hepatitis C virus nonstructural protein 5A inhibits tumor necrosis factor-alpha-mediated apoptosis in Huh7 cells
  Y Miyasaka, N Enomoto, M Kurosaki, N Sakamoto, N Kanazawa, T Kohashi, E Ueda, S Maekawa, H Watanabe, N Izumi, C Sato, M Watanabe
  JOURNAL OF INFECTIOUS DISEASES, 188, 10, 1537, 1544, Nov. 2003, [Peer-reviewed]
  English, Scientific journal
• Inhibition of intracellular hepatitis C virus replication by synthetic and vector-derived small interfering RNAs
  T Yokota, N Sakamoto, N Enomoto, Y Tanabe, M Miyagishi, S Maekawa, L Yi, M Kurosaki, K Taira, M Watanabe, H Mizusawa
  EMBO REPORTS, 4, 6, 602, 608, Jun. 2003, [Peer-reviewed]
  English, Scientific journal
• [Hepatitis C virus infection].
  Nakagawa M, Enomoto N, Sakamoto N
  Nihon rinsho. Japanese journal of clinical medicine, 61 Suppl 3, 627, 633, Mar. 2003, [Peer-reviewed]
• Oxygen tension modulates Ca2+ response to flow stimulus in endothelial cells exposed to hydrostatic pressure
  Toshiro Ohashi, Naoya Sakamoto, Akiyo Iwao, Masaaki Sato
  Technology and Health Care, 11, 4, 263, 274, 2003, [Peer-reviewed]
  English, Scientific journal
• Role of sarcolemmal K-ATP channels in cardioprotection against ischemia/reperfusion injury in mice
  M Suzuki, N Sasaki, T Miki, N Sakamoto, Y Ohmoto-Sekine, M Tamagawa, S Seino, E Marban, H Nakaya
  JOURNAL OF CLINICAL INVESTIGATION, 109, 4, 509, 516, Feb. 2002, [Peer-reviewed]
  English, Scientific journal
• Overexpression of interferon gamma-inducible protein 10 in the liver of patients with type I autoimmune hepatitis identified by suppression subtractive hybridization
  K Nagayama, N Enomoto, Y Miyasaka, M Kurosaki, CH Chen, N Sakamoto, M Nakagawa, C Sato, J Tazawa, T Ikeda, N Izumi, M Watanabe
  AMERICAN JOURNAL OF GASTROENTEROLOGY, 96, 7, 2211, 2217, Jul. 2001, [Peer-reviewed]
  English, Scientific journal
• CD81 nucleotide mutation in hepatocellular carcinoma and lack of CD81 polymorphism in patients at stages of hepatitis C virus infection
  J Itakura, K Nagayama, N Enomoto, N Sakamoto, J Tazawa, N Izumi, F Marumo, C Sato
  JOURNAL OF MEDICAL VIROLOGY, 63, 1, 22, 28, Jan. 2001, [Peer-reviewed]
  English, Scientific journal
• DETECTION AND ANALYSIS OF REPLICATING HEPATITIS-C VIRUS-RNA IN HEPATOCELLULAR-CARCINOMA TISSUES
  M KUROSAKI, N ENOMOTO, N SAKAMOTO, Y TANAKA, L TANG, Y HOSHINO, N IZUMI, F MARUMO, C SATO
  JOURNAL OF HEPATOLOGY, 22, 5, 527, 535, May 1995, [Peer-reviewed]
  English, Scientific journal
• Detection and analysis of replicating hepatitis C virus RNA in hepatocellular carcinoma tissues
  Masayuki Kurosaki, Nobuyuki Enomoto, Naoya Sakamoto, Yujiro Tanaka, Liang Tang, Yuji Hoshino, Namiki Izumi, Fumiaki Marumo, Chifumi Sato
  Journal of Hepatology, 22, 5, 527, 535, 1995, [Peer-reviewed]
  English, Scientific journal
• Comparison of the hypervariable region of hepatitis C virus genomes in plasma and liver
  Naoya Sakamoto, Nobuyuki Enomoto, Masayuki Kurosaki, Yasuhiro Asahina, Shinya Maekawa, Kazuhiko Koizumi, Ikuo Sakuma, Takeshi Murakami, Fumiaki Marumo, Chifumi Sato
  Journal of Medical Virology, 46, 1, 7, 11, 1995, [Peer-reviewed]
  English, Scientific journal
• DETECTION AND QUANTIFICATION OF HEPATITIS-C VIRUS-RNA REPLICATION IN THE LIVER
  N SAKAMOTO, N ENOMOTO, M KUROSAKI, F MARUMO, C SATO
  JOURNAL OF HEPATOLOGY, 20, 5, 593, 597, May 1994, [Peer-reviewed]
  English, Scientific journal
• SEQUENTIAL CHANGE OF THE HYPERVARIABLE REGION OF THE HEPATITIS-C VIRUS GENOME IN ACUTE INFECTION
  N SAKAMOTO, N ENOMOTO, M KUROSAKI, F MARUMO, C SATO
  JOURNAL OF MEDICAL VIROLOGY, 42, 1, 103, 108, Jan. 1994, [Peer-reviewed]
  English, Scientific journal
• CORRELATION OF PLASMA HEPATITIS-C VIRUS-RNA LEVELS WITH SERUM ALANINE AMINOTRANSFERASE IN NON-A CHRONIC LIVER-DISEASE, NON-B CHRONIC LIVER-DISEASE
  M KUROSAKI, N ENOMOTO, C SATO, N SAKAMOTO, Y HOSHINO, H HARITANI, F MARUMO
  JOURNAL OF MEDICAL VIROLOGY, 39, 3, 246, 250, Mar. 1993, [Peer-reviewed]
  English, Scientific journal
• PREVALENCE OF HEPATITIS-C VIRUS-INFECTION AMONG LONG-TERM HEMODIALYSIS-PATIENTS - DETECTION OF HEPATITIS-C VIRUS-RNA IN PLASMA
  N SAKAMOTO, N ENOMOTO, F MARUMO, C SATO
  JOURNAL OF MEDICAL VIROLOGY, 39, 1, 11, 15, Jan. 1993, [Peer-reviewed]
  English, Scientific journal