研究者詳細 - 寺井　崇二

Mesenchymal stromal cell administration promotes macrophage-mediated bile duct regeneration. 国際誌

Takanori Igarashi, Naruhiro Kimura, Hiroyuki Abe, Tomoaki Yoshida, Yusuke Watanabe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Regenerative therapy 31 101065 - 101065 2026年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Mesenchymal stromal cell (MSC) therapy is used in cirrhosis models of chronic hepatocellular damage and represents a novel therapeutic approach for liver regeneration. However, no studies have examined MSC therapy for bile duct injury and its effects on bile duct regeneration. This study aimed to elucidate the mechanism underlying bile duct regeneration by establishing a regeneration model and administering MSCs. METHODS: A model of bile duct regeneration was developed by feeding mice a 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-containing diet to induce bile duct injury, followed by a normal diet to promote bile duct regeneration. MSCs were administered concurrently with the normal diet, and the livers were analyzed after 2 days. An experimental system was also developed in which clodronate liposomes were administered alongside MSCs to eliminate the influence of macrophages. RESULTS: MSC administration significantly increased the rate of body weight gain and the liver-to-body weight ratio on day 2 after the change to a normal diet. Immunostaining revealed an increase in the number of CK19+ cholangiocytes. The numbers of Hnf4α+ and Sox9+ cells were significantly elevated in the MSC-treated group. Flow cytometric analysis of liver lymphocytes showed a significant increase in the number of Ly6C- macrophages in the MSC-treated group. Furthermore, analysis of liver lymphocyte populations and cap analysis of gene expression revealed alterations in the immune response and macrophage-related genes, whereas macrophage removal during MSC treatment abolished the bile duct regenerative effects observed with MSC treatment. CONCLUSIONS: Macrophages play a crucial role in bile duct regeneration, and MSC administration has regenerative effects. This approach has potential as a novel treatment modality for bile duct injuries.

DOI： 10.1016/j.reth.2026.101065

Azathioprine Inhibits Hepatitis A Virus Replication In Vitro

Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Kazunao Hayashi, Hiroteru Kamimura, Kenya Kamimura, Ryota Masuzaki, Hirofumi Kogure, Hiroaki Okamoto, Shuji Terai

Pathogens 2026年2月

STRIDE sustained an overall survival benefit with safety profiles in unresectable hepatocellular carcinoma at 5-year follow-up

Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroteru Kamimura, Kazunao Hayashi, Kenya Kamimura, Shuji Terai

Hepatobiliary Surgery and Nutrition 15 ( 1 ) 17 - 17 2026年2月

Liver Volumetry Enhances Prediction of Acute Pancreatitis in Acute Liver Failure: A Nationwide Registry Study. 国際誌

Keisuke Kakisaka, Nobuaki Nakayama, Tokio Sasaki, Kotaro Kumagai, Hidekatsu Kuroda, Ryuzo Abe, Taro Takami, Kazuaki Chayama, Masahito Shimizu, Takuya Genda, Shuji Terai, Kazuaki Inoue, Atsushi Tanaka, Takayuki Matsumoto, Satoshi Mochida

Hepatology research : the official journal of the Japan Society of Hepatology 56 ( 2 ) 233 - 245 2026年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Acute pancreatitis is a recognized complication of acute liver failure (ALF), but its incidence and predictive factors remain poorly defined. Current risk stratification relies primarily on conventional laboratory markers with limited discriminatory ability for pancreatic complications. This study aimed to determine the incidence and prognostic impact of acute pancreatitis in ALF patients and evaluate whether liver volumetry improves prediction beyond conventional markers. METHODS: This cross-sectional retrospective study utilized data from a nationwide survey-based registry conducted by the Intractable Hepato-Biliary Disease Study Group of Japan (2011-2021). We analyzed 142 ALF patients with available liver volumetry data and 90-day outcome information. Patients with pre-existing acute pancreatitis were excluded. Predictive models were developed comparing conventional markers (MELD score) versus an enhanced model incorporating computed tomography liver volume to standard liver volume ratio (CTLV/SLV). Model performance was evaluated using ROC analysis, net reclassification index, and clinical validation. RESULTS: Acute pancreatitis developed in 19 patients (13.4%), typically within the first 8 weeks (84.3% of cases). Logistic regression identified acute pancreatitis as an independent risk factor for poor prognosis (β = 0.2556, p = 0.031). The CTLV/SLV ratio was significantly lower in patients developing pancreatitis (0.80 vs. 1.07, p < 0.001). The enhanced model (MELD + CTLV/SLV) achieved superior discrimination (AUC 0.810) compared to MELD alone (AUC 0.704), with 81% relative risk reduction in the low-risk category. CONCLUSION: Incorporating liver volumetry significantly improves acute pancreatitis prediction in ALF patients, enabling more precise risk stratification and potentially optimizing clinical management strategies.

DOI： 10.1111/hepr.70054

Artificial Intelligence Model for Automated Identification of Bowel Preparation for Colonoscopy (AI-PREPOO): A Multicenter Study. 国際誌

Kosuke Kojima, Kazuya Takahashi, Hiroki Maruyama, Nao Nakajima, Hiroki Sato, Ken-Ichi Mizuno, Shuji Terai

Journal of gastroenterology and hepatology 2026年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Adequate bowel preparation is crucial for high-quality colonoscopy; however, assessing preparation adequacy can be burdensome for both healthcare providers and patients. In this study, we aimed to develop artificial intelligence (AI) models for the automated identification of bowel PREParation for cOlonoscOpy (AI-PREPOO). METHODS: On the day of colonoscopy, participants were instructed to use smartphones to photograph their stool in the toilet after each bowel movement following initiation of polyethylene glycol solution and upload the images to a secure web server. All images were labeled as "ready" or "not ready" for colonoscopy based on clarity and the absence of solid content. Using these labeled images, four image-recognition models based on different deep learning architectures (AI-PREPOO 1-4) were developed using transfer learning to classify stool status as "ready" or "not ready." RESULTS: A total of 282 stool images were collected from 37 patients, with 141 images labeled as "ready" and 141 as "not ready." These images were divided into training (224 images) and test (58 images) sets, and the training set was augmented to 2240 images. All models trained on the augmented dataset achieved high performance, with area under the curve (AUC) values exceeding 0.90. AI-PREPOO 1, based on MobileNetV3-Small, demonstrated the most balanced sensitivity-specificity profile (AUC, 0.95; sensitivity, 0.93; specificity, 0.86). CONCLUSIONS: We developed AI-based models capable of accurately assessing bowel preparation adequacy. AI-PREPOO 1 showed a well-balanced diagnostic performance, suggesting its potential to facilitate bowel preparation assessment and reduce the burden on healthcare providers and patients.

DOI： 10.1111/jgh.70235

Small Bowel Gastrointestinal Stromal Tumors: A 15-Year Cohort Study Focusing on Jejuno-Ileal Site-Specific Outcomes and Prognostic Factors

Yuichi Kojima, Kentaro Tominaga, Yuzo Kawata, Chizuru Kaneko, Shuhei Kondo, Yoshifumi Shimada, Junji Yokoyama, Toshifumi Wakai, Shuji Terai

Cancers 2026年1月

Regulatory T cell stability determines the efficiency of bile duct regeneration during cholangitis. 国際誌

Naruhiro Kimura, Man Chun Wong, Ben Higgins, Gareth Hardisty, Pei-Chi Huang, Matamoana Muller, Maxym Besh, Daniel A Patten, Timothy Kendall, Prakash Ramachandran, Adriano G Rossi, Graham Anderson, Shishir Shetty, David Withers, Atsunori Tsuchiya, Shuji Terai, Wei-Yu Lu

Cell reports 44 ( 11 ) 116557 - 116557 2025年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cholangiopathies such as primary sclerosing cholangitis (PSC) cause damage to the bile ducts with no effective cure. Reduction and impairment in the function of regulatory T cells (Tregs) occur in PSC. We investigate whether Tregs regulate bile duct regeneration and the dynamics of Treg turnover during bile duct injury. We use the transgenic Foxp3GFPDTR model to mimic reduced Treg infiltration in PSC and show that Tregs mediate cholangiocyte response to biliary injury. Fate mapping of Tregs reveals that intrahepatic Tregs acquire a pro-inflammatory phenotype, even after interleukin-2 (IL-2)-mediated Treg expansion. Ox40L expression correlates with fibrosis in PSC patients. Enhancing Treg numbers through IL-2 complex administration and blocking Ox40 signaling simultaneously suppresses the inflammatory phenotype of Tregs and reduces bile duct damage and fibrosis. We demonstrate that bile duct regeneration can be enhanced by combining Treg-based therapy and targeting co-stimulatory molecules, such as Ox40L.

DOI： 10.1016/j.celrep.2025.116557

Is higher body mass index correlated with worse clinical outcomes in acute liver failure?

Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroteru Kamimura, Shuji Terai

World Journal of Clinical Cases 13 ( 32 ) 2025年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：Baishideng Publishing Group Inc.

Krishnan et al ’s article is a comprehensive and vigorous retrospective cohort study regarding the association between obesity and clinical outcomes in acute liver failure (ALF). Among patients with ALF in the United States, mean body mass index (BMI) was significantly greater in those who underwent liver transplantation or who died than among survivors, although acetaminophen induced ALF was the most common etiology. A high BMI was associated with renal failure and high grades of hepatic encephalopathy. The prevalence of obesity and its related fatty liver diseases, such as metabolic dysfunction-associated fatty liver disease/ metabolic dysfunction-associated steatotic liver disease and metabolic dysfunction-associated steatohepatitis, has increased worldwide. Obesity is related to increased serum cytokines and immune abnormalities. These findings may explain why ALF in patients with high BMI is associated with worse clinical outcomes. Further studies are needed to determine the associations among BMI, ALF and acute-on-chronic liver failure.

DOI： 10.12998/wjcc.v13.i32.113514

A rare case of ulcerative colitis relapse in a diverted colon after rectal cancer surgery: efficacy of carotegrast methyl.

Takanori Igarashi, Kentaro Tominaga, Yuichi Kojima, Mai Nakamura, Takafumi Tonouchi, Nobutaka Takeda, Tomoaki Yoshida, Yuzo Kawata, Akira Sakamaki, Shuji Terai

Clinical journal of gastroenterology 2025年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

This case presents a rare instance of ulcerative colitis (UC) relapse in the functionally isolated left colon following surgery for rectal cancer associated with UC. A 62-year-old man, suspected of having cancer based on positron emission tomography (PET)-computed tomography (CT) findings and elevated carcinoembryonic antigen levels, underwent robot-assisted low anterior resection and temporary transverse colostomy. Postoperatively, leakage and infection made it difficult to administer conventional local treatments or corticosteroids; however, remission was achieved with the oral α4-integrin inhibitor, carotegrast methyl, allowing for stoma closure. To our knowledge, this report is the first to describe the use of carotegrast methyl for recurrent UC in a diverted colon. This case demonstrates that carotegrast methyl may serve as an effective steroid-sparing option for UC relapse in complex postoperative anatomical contexts. It also highlights the potential utility of PET-CT as an adjunctive diagnostic tool for UC-associated cancer.

DOI： 10.1007/s12328-025-02243-7

An exploratory machine learning study on paediatric abdominal pain phenotyping and prediction

Kazuya Takahashi, Michalina Lubiatowska, Huma Shehwana, James K. Ruffle, John A. Williams, Animesh Acharjee, Shuji Terai, Georgios V. Gkoutos, Humayoon Satti, Qasim Aziz

PLOS One 20 ( 11 ) e0336215 - e0336215 2025年11月

掲載種別：研究論文（学術雑誌）出版者・発行元：Public Library of Science (PLoS)

Background

The exact mechanisms underlying paediatric abdominal pain (AP) remain unclear due to patient heterogeneity. This preliminary study aimed to identify AP phenotypes and develop predictive models to explore associated factors, with the goal of guiding future research.

Methods

In 13,790 children from a large birth cohort, data on paediatric and maternal demographics and comorbidities were extracted from general practitioner records. Machine learning (ML) clustering was used to identify distinct AP phenotypes, and an ML-based predictive model was developed using demographics and clinical features.

Results

1,274 children experienced AP (9.2%) (average age: 8.4 ± 1.1 years, male/female: 615/659), who clustered into three distinct phenotypes: Phenotype 1 with an allergic predisposition (n = 137), Phenotype 2 with maternal comorbidities (n = 676), and Phenotype 3 with minimal other comorbidities (n = 340). As the number of allergic diseases or maternal comorbidities increased, so did the frequency of AP, with 17.6% of children with ≥ 3 allergic diseases and 25.6% of children with ≥ 3 maternal comorbidities. The predictive model demonstrated moderate performance in predicting paediatric AP (AUC 0.67), showing that a child’s ethnicity, paediatric allergic diseases, and maternal comorbidities were key predictive factors. When stratified by ML-predicted probability, observed AP rates were 18.9% in the < 40% group, 44.8% in the 40–50% group, 60.6% in the 50–60% group, and 100.0% in the > 60% group.

Conclusions

This study identified distinct AP phenotypes and key risk factors using ML. Furthermore, the predictive ML model enabled risk stratification for paediatric AP. These analyses provide valuable insights to guide future investigations into the mechanisms of AP and may facilitate research aimed at identifying targeted interventions to improve patient outcomes.

DOI： 10.1371/journal.pone.0336215

Tongue shear wave elastography for bulbar dysfunction in amyotrophic lateral sclerosis

Kaori Yanagawa, Makiko Ike, Azusa Aoyama, Takeshi Yokoo, Shuji Terai, Takafumi Hayashi, Osamu Onodera

Clinical Neurophysiology 2025年11月

Efficacy of budesonide and vedolizumab for IBD-U associated with Muckle-Wells syndrome.

Yuzo Kawata, Kentaro Tominaga, Daisuke Kobayashi, Annenkov Alexey, Kosuke Kojima, Osamu Shibata, Yuichi Kojima, Kazuya Takahashi, Hiroteru Kamimura, Shuji Terai

Clinical journal of gastroenterology 2025年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cryopyrin-associated periodic syndrome (CAPS) is a rare, autosomal dominant inflammatory disorder linked to interleukin (IL)-1β dysregulation. Muckle-Wells syndrome (MWS) is a clinical subtype of CAPS that is often managed with canakinumab, an anti-IL-1β monoclonal antibody. Canakinumab has been approved for all phenotypes of CAPS, with no age restrictions, since 2011. Despite its efficacy in controlling systemic inflammation, its gastrointestinal side effects remain unclear. This report presents the case of a 28 year-old man who developed abdominal pain and diarrhea during treatment with canakinumab for MWS. Colonoscopy revealed findings suggestive of inflammatory bowel disease, and a diagnosis of IBD-unclassified (IBD-U) was made after exclusion of other conditions. Treatment with oral budesonide and vedolizumab led to marked clinical and endoscopic improvements, maintaining remission after budesonide discontinuation. Although the usefulness of systemic prednisolone and anti-TNFα antibody preparations for treating IBD-U in patients with MWS has been previously reported, to the best of our knowledge, this is the first report to highlight the therapeutic effects of budesonide and vedolizumab. Therefore, IBD-U should be considered in the differential diagnosis of patients with CAPS who develop gastrointestinal symptoms. Considering their favorable side-effect profiles, budesonide and vedolizumab may serve as promising treatment alternatives in the future.

DOI： 10.1007/s12328-025-02234-8

Hydrogen-Positive Small Intestinal Bacterial Overgrowth (SIBO) in Japanese Patients With Chronic Intestinal Pseudo-Obstruction (CIPO): A Cross-Sectional Study. 国際誌

Takanori Igarashi, Kentaro Tominaga, Kunihiko Yokoyama, Takuya Wakabayashi, Yuichi Kojima, Yuzo Kawata, Naruhiro Kimura, Kazuya Takahashi, Akira Sakamaki, Shuji Terai

Cureus 17 ( 10 ) e94054 2025年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Evidence for small intestinal bacterial overgrowth (SIBO) in chronic intestinal pseudo‑obstruction (CIPO) remains limited in Asian populations and by gas phenotype. This study aimed to determine the prevalence and gas phenotype distribution (hydrogen-positive SIBO vs. intestinal methanogen overgrowth) in Japanese patients with CIPO using glucose breath testing and to describe associated clinical features. METHODS: This single‑center cross‑sectional study was conducted at Niigata University, Niigata, Japan (April 2019-March 2022), and included 10 CIPO outpatients and 10 healthy controls. Participants fasted for 12 hours and avoided high-fiber foods for 24 hours before testing. Glucose breath testing (50 g, institutional SOP) measured hydrogen (H₂) and methane (CH₄); positivity followed North American Consensus criteria (ΔH₂ ≥20 ppm by 90 min; CH₄ ≥10 ppm). The primary outcome was hydrogen‑positive SIBO (H₂‑SIBO); intestinal methanogen overgrowth (IMO) was analyzed separately. Exact tests accounted for the small sample size. RESULTS: H₂‑SIBO was more frequent in CIPO than in controls (5/10 vs. 0/10; Fisher two‑sided p = 0.0325; continuity‑corrected OR = 21). Overall SIBO (H₂ or CH₄) was 5/10 vs. 1/10 (p = 0.141, two‑sided). No CIPO patient met IMO criteria; one control was methane‑positive. Among CIPO patients, H₂‑SIBO was associated with lower BMI and a higher frequency of diarrhea. CONCLUSIONS: In this small Japanese cohort, CIPO was associated with H₂‑SIBO, whereas IMO was uncommon. These findings should be interpreted with caution due to limited statistical power and potential under-detection of distal overgrowth with glucose substrate. These findings may inform on diagnostic strategies and nutritional management in severe motility disorders.

DOI： 10.7759/cureus.94054

Image analysis of cardiac hepatopathy secondary to heart failure: Machine learning vs gastroenterologists and radiologists. 国際誌

Suguru Miida, Hiroteru Kamimura, Shinya Fujiki, Taichi Kobayashi, Saori Endo, Hiroki Maruyama, Tomoaki Yoshida, Yusuke Watanabe, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Takeshi Yokoo, Masanori Tsukada, Fujito Numano, Takeshi Kashimura, Takayuki Inomata, Yuma Fuzawa, Tetsuhiro Hirata, Yosuke Horii, Hiroyuki Ishikawa, Hirofumi Nonaka, Kenya Kamimura, Shuji Terai

World journal of gastroenterology 31 ( 34 ) 108807 - 108807 2025年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Congestive hepatopathy, also known as nutmeg liver, is liver damage secondary to chronic heart failure (HF). Its morphological characteristics in terms of medical imaging are not defined and remain unclear. AIM: To leverage machine learning to capture imaging features of congestive hepatopathy using incidentally acquired computed tomography (CT) scans. METHODS: We retrospectively analyzed 179 chronic HF patients who underwent echocardiography and CT within one year. Right HF severity was classified into three grades. Liver CT images at the paraumbilical vein level were used to develop a ResNet-based machine learning model to predict tricuspid regurgitation (TR) severity. Model accuracy was compared with that of six gastroenterology and four radiology experts. RESULTS: In the included patients, 120 were male (mean age: 73.1 ± 14.4 years). The accuracy of the results predicting TR severity from a single CT image for the machine learning model was significantly higher than the average accuracy of the experts. The model was found to be exceptionally reliable for predicting severe TR. CONCLUSION: Deep learning models, particularly those using ResNet architectures, can help identify morphological changes associated with TR severity, aiding in early liver dysfunction detection in patients with HF, thereby improving outcomes.

DOI： 10.3748/wjg.v31.i34.108807

Zinc Acetate Inhibits Hepatitis A Virus Replication: Possible Treatment for Patients with Type A Acute-on-Chronic Liver Failure

Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Kazunao Hayashi, Hiroteru Kamimura, Atsunori Tsuchiya, Ryota Masuzaki, Hirofumi Kogure, Hiroaki Okamoto, Shuji Terai

Pathogens 2025年9月

Pretreatment serum angiopoietin-2 predicts prognosis and liver functional reserve after successful HCV eradication with sofosbuvir and velpatasvir in patients with HCV-related decompensated cirrhosis.

Naoki Kawagishi, Goki Suda, Yuki Tahata, Hayato Hikita, Takahiro Kodama, Satoshi Mochida, Nobuyuki Enomoto, Seiichi Mawatari, Hidekatsu Kuroda, Daiki Miki, Masayuki Kurosaki, Yoichi Hiasa, Norifumi Kawada, Taro Yamashita, Hiroshi Yatsuhashi, Hitoshi Yoshiji, Naoya Kato, Taro Takami, Hisamitsu Miyaaki, Kentaro Matsuura, Yasuhiro Asahina, Yoshito Itoh, Ryosuke Tateishi, Yasunari Nakamoto, Eiji Kakazu, Shuji Terai, Masahito Shimizu, Yoshiyuki Ueno, Norio Akuta, Masatsugu Ohara, Naoya Sakamoto, Tetsuo Takehara

Journal of gastroenterology 60 ( 9 ) 1145 - 1156 2025年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Direct-acting-antivirals (DAAs) achieve high sustained-virologic response (SVR) rates, even in patients with hepatitis C virus (HCV)-related decompensated liver cirrhosis (LC). However, predictors of post-treatment liver function improvement and survival remain unclear. This study evaluated pretreatment angiopoietin-2 (Ang2) levels as a predictor of prognosis and liver functional reserve after DAA treatment. METHODS: This multicenter retrospective study included 123 patients with HCV-related decompensated LC treated with sofosbuvir/velpatasvir. Serum Ang2 levels were quantified, and liver function was assessed using the Child-Pugh grading at baseline and 12 weeks after the end of treatment (SVR12). Factors associated with prognosis and post-SVR liver functional reserve (Child-Pugh grade C) were investigated. RESULTS: Multivariate Cox regression analysis revealed that, in addition to age and creatinine levels at SVR12, baseline Ang2 levels (hazard ratio [HR] = 1.151 per 1000 pg/mL, P = 0.033) and Child-Pugh grade C at SVR12 (HR = 11.765, P < 0.001), but not baseline Child-Pugh grade C, were significantly associated with the overall survival. Multivariate analysis revealed that baseline Ang2 levels and baseline Child-Pugh grade C were significantly and independently associated with Child-Pugh grade C at SVR12. The combination of elevated baseline Ang2 levels (≥ 8684 pg/mL; 1 point) and baseline Child-Pugh grade C (1 point) effectively stratified patients with a high likelihood of having Child-Pugh Grade C at SVR12. The incidence rates were as follows: 0 points, 2.1% (2/96); 1 point, 37.5% (9/24); and 2 points, 100% (2/2) (P < 0.001). CONCLUSIONS: Pretreatment Ang2 levels predict survival and liver functional reserve after SVR in HCV-related decompensated LC.

DOI： 10.1007/s00535-025-02275-3

Restoration of the gut-microbiota-liver axis after hepatitis C virus eradication. 国際誌

Takako Inoue, Jiro Nakayama, Hiroshi Mori, Masaru Tanaka, Daisuke Nakagawa, Masaya Ohnishi, Yui Funatsu, Kei Moriya, Hideto Kawaratani, Hisayoshi Watanabe, Goki Suda, Yasuteru Kondo, Tatsuya Ide, Satoru Kakizaki, Satoshi Miuma, Atsushi Suetsugu, Kazuhito Kawata, Takao Watanabe, Etsuko Iio, Rie Momoda, Yutaka Suzuki, Akira Sakamaki, Tsunamasa Watanabe, Takehisa Watanabe, Katsuya Nagaoka, Yoichi Hiasa, Shuji Terai, Hitoshi Yoshiji, Atsushi Toyoda, Ken Kurokawa, Yasuhito Tanaka

JHEP reports : innovation in hepatology 7 ( 9 ) 101494 - 101494 2025年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND & AIMS: We previously reported altered intestinal environmental features during HCV infection. Here, we aimed to characterize the gut-microbiota-liver axis in patients with chronic hepatitis C after a sustained virological response (SVR). METHODS: A total of 174 patients with HCV infection were enrolled in a cross-sectional study: 95 with chronic hepatitis (CH-HCV group) and 79 with cirrhosis or hepatocellular carcinoma (LC/HCC-HCV group). In addition, 75 post-SVR patients were included (CH-SVR group, n = 29; LC/HCC-SVR group, n = 46), along with 23 healthy individuals. A longitudinal study was subsequently conducted on 49 patients (CH, n = 29; LC/HCC, n = 20) with SVR at 24 and 48 weeks after the end of treatment. RNA sequencing was performed on 65 patients with HCV infection, 28 post-SVR patients, and 12 healthy controls. RESULTS: In the cross-sectional analysis, HCV eradication was associated with partial restoration of the dysbiotic gut microbiota, including reduced streptococcal overgrowth and an increase in the potentially beneficial genus Blautia, approaching levels seen in healthy individuals. Additionally, the aberrant fecal bile acid profile showed rebalancing, accompanied by restored expression of genes involved in the classical pathway of cholic and chenodeoxycholic acid biosynthesis. In the longitudinal study, improvements in liver fibrosis and function - evidenced by decreased Fibrosis-4 index and alanine aminotransferase levels - were significantly correlated with increased abundance of Blautia (p <0.0001 and p = 0.0344, respectively), suggesting a beneficial role in liver recovery. CONCLUSION: The gut-microbiota-liver axis is partially restored following HCV eradication, with recovery from liver damage associated with the resurgence of commensal Lachnospiraceae species. IMPACT AND IMPLICATIONS: This study offers significant insights into the gut-microbiota-liver axis in patients with chronic hepatitis C following a sustained virological response. The findings demonstrate that HCV eradication promotes partial restoration of the dysbiotic gut microbiota, particularly an increase in the beneficial genus Blautia, as well as a rebalancing of the fecal bile acid profile. These changes are closely associated with significant improvements in liver fibrosis and function, highlighting a potential role of the gut microbiota in liver recovery and regeneration.

DOI： 10.1016/j.jhepr.2025.101494

Myelodysplastic Syndrome With Trisomy 8 and Behçet Disease-Like Intestinal and Upper Gastrointestinal Involvement. 国際誌

Yuzo Kawata, Kentaro Tominaga, Yusuke Kaneko, Saori Takashima, Yusuke Tani, Yuichi Kojima, Kazuya Takahashi, Shuji Terai

Clinical case reports 13 ( 9 ) e70575 2025年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

We found an extremely rare case of upper gastrointestinal involvement in trisomy 8-positive myelodysplastic syndrome. This is the first reported case of trisomy 8-positive myelodysplastic syndrome with both upper and lower gastrointestinal involvement, which was successfully treated with bone marrow transplantation.

DOI： 10.1002/ccr3.70575

Carbon-Ion Radiotherapy for Hepatocellular Carcinoma: Current Status and Future Prospects: A Narrative Review

Reina Sasaki-Tanaka, Hiroyuki Abe, Tomoaki Yoshida, Yusuke Watanabe, Naruhiro Kimura, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Kenya Kamimura, Tatsuo Kanda, Shuji Terai

Journal of Clinical Medicine 14 ( 17 ) 6107 - 6107 2025年8月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

Because hepatocellular carcinoma (HCC) is a radiosensitive cancer, radiation therapy has been used for the treatment of HCC; however, external beam therapies are currently not described in most of the guidelines for the treatment of HCC. External beam therapies include photon beam therapies and particle beam therapies, which are composed of X-rays or gamma rays and beams of carbon ions or protons, respectively. The focus of this narrative review is carbon-ion radiotherapy (C-ion RT). C-ion RT is well tolerated by elderly patients with HCC and/or sarcopenic patients. In general, a single HCC greater than 30 mm is a good indication for C-ion RT in patients with Child Grade A/B or ALBI Grade 1/2. The local control rates and overall survival rates at 5 years after C-ion RT for HCCs larger than 30 mm are excellent, with fewer adverse events, such as radiation-induced liver damage. Advanced HCC with portal vein tumor thrombus is also an indication for C-ion RT in certain selected patients. C-ion RT is a promising therapeutic option for patients with HCC.

DOI： 10.3390/jcm14176107

Revisiting Hepatic Fibrosis Risk in Congenital Heart Disease: Insights from Non-Invasive Markers and Echocardiography

Fusako Yamazaki, Hiroteru Kamimura, Saori Endo, Suguru Miida, Hiroki Maruyama, Tomoaki Yoshida, Masaru Kumagai, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Takeshi Yokoo, Masanori Tsukada, Fujito Numano, Akihiko Saitoh, Maya Watanabe, Shuichi Shiraishi, Masanori Tsuchida, Shinya Fujiki, Takeshi Kashimura, Takayuki Inomata, Hirofumi Nonaka, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Children 2025年8月

門脈圧亢進関連疾患における病態と診断の未来予想図先天性心疾患術後における肝線維化有病率と心エコー所見との関連非侵襲的マーカーを用いた予測因子の検討

上村博輝, 山崎文紗子, 堀端祐介, 福島直弥, 小島雄一, 川田雄三, 冨永顕太郎, 弥久保俊太, 熊谷優, 吉田智彰, 渡邊雄介, 木村成宏, 阿部寛幸, 横尾健, 坂牧僚, 寺井崇二

日本門脈圧亢進症学会雑誌 31 ( 3 ) 114 - 114 2025年8月

Simultaneous Evaluation of Shear Wave Elastography and C-Peptide Index for Predicting Need of Insulin Therapy in Type 2 Diabetes: A Pilot Study

Moeno Sugita-Hamada, Takeshi Yokoo, Nao Nakajima, Yoshifumi Takahashi, Akihiko Osaki, Masaki Maruyama, Masaaki Takamura, Nobuo Waguri, Osamu Isokawa, Shuji Terai

Journal of Personalized Medicine 2025年7月

医療機関連携急性肝不全ネットワークを円滑に行い生体肝移植にて救命できた急性肝不全昏睡型の1例

武田信峻, 土屋淳紀, 石井結唯, 夏井一輝, 荒生祥尚, 林和直, 寺井崇二

肝臓 66 ( 7 ) 319 - 319 2025年7月

Validation of PBC-10 in Japanese patients with primary biliary cholangitis. 国際誌

Akihito Takeuchi, Masanori Abe, Sachiko Furukawa, Tadashi Namisaki, Atsushi Takahashi, Kazumichi Abe, Kentaro Kikuchi, Ryo Miura, Naoko Tachizawa, Yoshinari Asaoka, Akinobu Takaki, Yoshiyuki Ueno, Akira Honda, Shuji Terai, Atsumasa Komori, Hiromasa Ohira, Hitoshi Yoshiji, Atsuko Yonezawa, Atsushi Tanaka

Hepatology research : the official journal of the Japan Society of Hepatology 55 ( 7 ) 986 - 993 2025年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Primary biliary cholangitis (PBC) is a chronic cholestatic liver disease that significantly impairs health-related quality of life (HRQOL). The PBC-10, a short-form HRQOL assessment tool, was developed for rapid screening in clinical settings. This study aimed to verify the reliability and validity of the Japanese version of the PBC-10 in Japanese patients with PBC. METHODS: We retrospectively analyzed HRQOL data from 496 Japanese outpatients with PBC, collected between 2015 and 2016. Reliability was assessed using Cronbach's alpha, item-total score correlations, and ceiling and floor effects. Validity was evaluated by examining correlations between PBC-10 scores and the total and subdomain scores of the Japanese version of the PBC-40, a validated PBC-specific HRQOL questionnaire. RESULTS: Cronbach's alpha for the PBC-10 was 0.872, demonstrating high internal consistency. Strong item-total score correlations were observed for all items. No ceiling effects were noted, but floor effects were present across all items. The PBC-10 total score showed a very strong positive correlation with the PBC-40 total score (ρ = 0.964, p < 0.001). Strong correlations were also found between most PBC-10 items and the PBC-40 subdomains, supporting validity. CONCLUSION: The Japanese version of the PBC-10 is a reliable and valid tool for rapidly assessing HRQOL in Japanese PBC outpatients. It has potential utility for identifying patients who may benefit from emerging treatments targeting symptom relief.

DOI： 10.1111/hepr.14199

Machine‐Learning Prediction of Bleeding After Endoscopic Submucosal Dissection for Early Gastric Cancer: A Multicenter Study

Hiroki Maruyama, Kazuya Takahashi, Kosuke Kojima, Nao Nakajima, Hiroki Sato, Ken‐ichi Mizuno, Soichi Sugitani, Shuji Terai

JGH Open 9 ( 7 ) 2025年6月

掲載種別：研究論文（学術雑誌）出版者・発行元：Wiley

ABSTRACT

Background

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for early gastric cancer (GC); however, post‐ESD bleeding remains a serious and unpredictable complication. This study aimed to develop machine‐learning (ML) models to predict post‐ESD bleeding and identify associated risk factors, ensuring accurate and interpretable predictions.

Methods

A retrospective, multicenter clinical database was constructed for patients who underwent ESD for early GC. An ML model was developed using patient characteristics and perioperative findings to predict bleeding within 28 days post‐ESD. Its performance was compared with that of a logistic regression–based non‐ML model. Feature importance analysis was performed to aid interpretation.

Results

Among 1084 patients (median age: 75 years), post‐ESD bleeding occurred in 63 (5.8%). The area under the curve of the ML model was better than that of the non‐ML model (0.80 vs. 0.71, p = 0.03). Furthermore, the ML model demonstrated a trend toward higher sensitivity compared with the non‐ML model (0.74 vs. 0.58, p = 0.58). When stratified by ML‐estimated bleeding probability, observed bleeding rates were 2.3%, 8.8%, and 28.6% in the low‐ (< 50%), intermediate‐ (50%–80%), and high‐probability (≥ 80%) groups, respectively. The odds of bleeding were significantly higher in the intermediate‐ (OR 4.03, p = 0.03) and high‐probability (OR 16.7, p < 0.01) groups compared to the low‐probability group. Anticoagulant use with atrial fibrillation emerged as a key predictor.

Conclusions

The ML model effectively rules out post‐ESD bleeding and identifies clinically meaningful risk factors, supporting its use in personalized prophylactic strategies.

DOI： 10.1002/jgh3.70203

Guidance on the clinical application of extracellular vesicles. 国際誌

Shuji Terai, Motohiro Asonuma, Ayuko Hoshino, Masahiro Kino-Oka, Takahiro Ochiya, Kiyoshi Okada, Yoji Sato, Yuki Takahashi, Morikuni Tobita, Atsunori Tsuchiya

Regenerative therapy 29 43 - 50 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Therapies using extracellular vesicles (EVs), exosomes, or cell culture supernatants containing EVs or exosomes (referred to as "EV therapies" in this Guidance) have garnered an increasing amount of interest. However, pharmaceutical products containing EVs as their main active ingredient are yet to receive regulatory approval. The "Basic points to consider regarding the preparation of extracellular vesicles and their clinical applications in Japan," was announced by the Japanese Society for Regenerative Medicine (JSRM) on March 10, 2021, with a specific focus on exosomes among EVs to promote high safety standards in this evolving field and facilitate the application of EV clinically. The Scientific Committee of the Pharmaceuticals and Medical Devices Agency and the Japanese Society for Extracellular Vesicles have issued reports and statements regarding treatment, resulting in a growing momentum toward treatment in Japan. This article summarized the basic items that should be recognized comprehensively for clinical practice in three categories: (1) risk profiling, (2) preparation (manufacturing) process and quality, and (3) verification of EVs checking items and effectiveness. This guideline will be revised in the future with technological innovations and new findings; nevertheless, it will serve as a guide for the development of treatments.

DOI： 10.1016/j.reth.2025.02.008

Multidirectional therapeutic effects of synthesized HMGB1 peptide on liver cirrhosis in mice. 国際誌

Masaki Mito, Atsunori Tsuchiya, Soichi Ishii, Takafumi Tonouchi, Kaito Furuyama, Ryo Jinbo, Nobutaka Takeda, Hiroyuki Abe, Katsuto Tamai, Shuji Terai

Biochemistry and biophysics reports 42 102061 - 102061 2025年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Liver cirrhosis is a serious disease characterized by liver dysfunction and severe fibrosis; however, no breakthrough drugs have effectively improved fibrosis, making it an unmet medical need. We have previously reported that the HMGB1 peptide, synthesized from box A of the HMGB1 protein, ameliorates liver fibrosis and is a promising candidate for fibrosis-improving drugs against liver cirrhosis. In this study, we used spatial analysis to observe treatment-induced changes over time. METHODS: Liver cirrhosis was induced in C57BL/6J mice using carbon tetrachloride (CCl4) injections, followed by HMGB1 peptide treatment. To assess the temporal effects of HMGB1 on the liver in a CCl4-induced cirrhosis mouse model, we used GeoMx spatial analysis. We focused on αSMA-positive active hepatic stellate cells (HSCs), F4/80-positive macrophages, and CK8/18-positive hepatocytes to determine how each cell type was affected over time. Statistical analyses were conducted using GraphPad Prism9, with significance set at p < 0.05. RESULTS: In cirrhotic mice, we first observed a decrease in the number of activated HSCs over time, two weeks after treatment initiation. Macrophage-associated genes ceased to induce fibrosis-related pathways early in the treatment. This suggests that the effect of macrophages on fibrosis was weakened by the treatment. We also confirmed that lipid metabolism of hepatocytes may be improved during treatment. Furthermore, Cxcl12 and Ccl25 expression were induced in the peptide-treated group, indicating possible cell migration to the liver. CONCLUSION: Over time, macrophages followed by HSCs, showed the most notable changes with treatment, resulting in improved fibrosis. The HMGB1 peptide drug also affected lipid metabolism in hepatocytes, suggesting a positive therapeutic effect on steatohepatitis. Elevated factors that promote cell migration may have also enhanced the healing effect.

DOI： 10.1016/j.bbrep.2025.102061

Polygenic Risk Score for Metabolic Dysfunction-Associated Steatotic Liver Disease and Steatohepatitis: A Narrative Review. 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Hiroyuki Abe, Naruhiro Kimura, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai

International journal of molecular sciences 26 ( 11 ) 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are spreading worldwide as the most critical causes of cirrhosis and hepatocellular carcinoma (HCC). Thus, improving the screening and managing strategies for patients with MASLD or MASH is necessary. A traditional non-systemic review provided this narrative. Genetic variations associated with the development of MASLD and MASH, such as PNPLA3, TM6SF2, GCKR, MBOAT7, MERTK, and HSD17B13, were initially reviewed. PNPLA3 genetic variants appeared to be strongly associated with the increased pathogenesis of MASLD, MASH, cirrhosis, and HCC. We also reviewed the useful polygenic risk score (PRS) for the development of MASLD, MASH, their related cirrhosis, and the occurrence of HCC. PRSs appeared to be better predictors of MASLD, MASH, the development of cirrhosis, and the occurrence of HCC in patients with MASLD or MASH than any single-nucleotide polymorphisms. RNA interference and antisense nucleotides against the genetic variations of PNPLA3 and HSD17B13 are also being developed. Multidisciplinary collaboration and cooperation involving hepatologists, geneticists, pharmacologists, and pathologists should resolve complicated problems in MASLD and MASH. This narrative review highlights the importance of the genetic susceptibility and PRS as predictive markers and personalized medicine for patients with MASLD or MASH in the future.

DOI： 10.3390/ijms26115164

Importance of understanding a diagnostic-treatment algorithm for primary hyperparathyroidism-induced acute pancreatitis during pregnancy. 国際誌

Kenya Kamimura, Shuji Terai

World journal of gastroenterology 31 ( 18 ) 105866 - 105866 2025年5月

記述言語：英語

In this article, we have commented on the article by Augustin et al. The authors presented a systematic review of the diagnosis, treatment, and outcomes of primary hyperparathyroidism-induced acute pancreatitis in pregnant women. Since acute pancreatitis during pregnancy could cause maternal as well as fetal adverse outcomes, understanding this pathology is essential. Although there are various etiologies of acute pancreatitis during pregnancy, primary hyperparathyroidism is one of the causes that complicate hypercalcemia. Along with conventional treatment for acute pancreatitis, parathyroidectomy can effectively normalize calcium levels and improve acute pancreatitis. Augustin et al have provided vital information that can enable physicians to understand and treat hyperparathyroidism-induced acute pancreatitis in pregnant women, which could contribute to better maternal and fetal outcomes. In addition, since primary hyperparathyroidism is associated with multiple endocrine neoplasia, further consideration regarding screening for multiple endocrine neoplasia might lead to better prognoses.

DOI： 10.3748/wjg.v31.i18.105866

Hepatitis A and E Viruses Are Important Agents of Acute Severe Hepatitis in Asia: A Narrative Review. 国際誌

Reina Sasaki-Tanaka, Tatsuo Kanda, Takeshi Yokoo, Hiroyuki Abe, Kazunao Hayashi, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

Pathogens (Basel, Switzerland) 14 ( 5 ) 2025年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Acute-on-chronic liver failure (ACLF) and acute liver failure (ALF) are severe hepatitis that occur in patients with and without chronic liver diseases and/or cirrhosis, respectively, and both often result in death. Hepatitis A virus (HAV) and hepatitis E virus (HEV) infection can cause these severe conditions. We reviewed the role of HAV and HEV, which infect humans through the fecal-oral route, in ALF and ACLF in Asian countries. This narrative review was the derived from a traditional non-systematic review. Hepatitis A should be recognized as one of the sexually transmitted infections, especially among men who have sex with men. HAV genotype IIIA infection seems to present a more severe clinical manifestation. Acute HEV-1 infection is associated with ALF in pregnant women in India. HEV-4, rather than HEV-3, was found in severe hepatitis in Japan. HEV also plays a role as a cause of acute insult and/or chronic liver disease in immunocompromised patients with ACLF. Further studies are needed for the development of vaccines and antivirals against HAV and HEV infections. Despite the limitations of the recording of cases and the extent of specific vaccinations, multidisciplinary cooperation, involving hepatologists, virologists, experts in public health, etc., may improve the treatment of HAV and HEV infection.

DOI： 10.3390/pathogens14050454

UC関連腫瘍術後の空置腸管にUCを再燃し、カロテグラストメチルが奏功した一例

五十嵐崇徳, 小島雄一, 登内孝文, 吉田智彰, 高橋一也, 林和直, 坂牧僚, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 76回 31 - 31 2025年5月

Cholestasis in hepatitis E virus infection. 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Takeshi Yokoo, Kazunao Hayashi, Hiroteru Kamimura, Atsunori Tsuchiya, Shuji Terai

World journal of hepatology 17 ( 4 ) 99899 - 99899 2025年4月

記述言語：英語

Hepatitis E virus (HEV) infection causes acute hepatitis, chronic hepatitis, particularly in compromised hosts, and various extrahepatic manifestations. HEV infection is reportedly associated with biliary-pancreatic diseases, such as gallstones, cholangitis, choledocholithiasis, and acute pancreatitis. Severe jaundice and prolonged cholestasis are also atypical manifestations of HEV infection. The mechanism and genes involved in cholestasis, namely sinusoidal uptake of blood, bile salt synthesis and secretion from hepatocytes to the canaliculus, have been elucidated. HEV infection triggers severe jaundice and prolonged cholestasis in patients with genetic variants in adenosine triphosphatase phospholipid transporting 8B1, adenosine triphosphate-binding cassette (ABC) protein B4, ABCB11, Myosin VB, and/or farnesoid X receptor (FXR/NR1H4). Although prolonged cholestasis associated with these gene mutations does not seem to be specific to HEV infection, these mutations may be risk factors related to the severity of HEV infection. The use of the pregnane X receptor agonist rifampicin and the peroxisome proliferator-activated receptor activator bezafibrate may be useful for the treatment of cholestasis. These studies provide new insights into understanding the mechanisms of severe jaundice and prolonged cholestasis caused by HEV infection.

DOI： 10.4254/wjh.v17.i4.99899

Mapping of rehabilitation interventions and assessment methods for patients with liver cirrhosis: a scoping review. 国際誌

Yuichiro Hosoi, Michiyuki Kawakami, Daisuke Ito, Takayuki Kamimoto, Hiroteru Kamimura, Takumi Kawaguchi, Shuji Terai, Tetsuya Tsuji

BMC gastroenterology 25 ( 1 ) 291 - 291 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: This scoping review aimed to delineate the detailed components of exercise therapy and the evaluation methods used for patients with liver cirrhosis. METHODS: The methodology involved searching the original PubMed, Web of Science, and Scopus for studies published between January 1975 and March 2025. The search was completed on 13 March 2025. Studies describing exercise therapy for liver cirrhosis patients were selected. Relevant information matching the study objectives, such as intervention duration, content, intensity setting, evaluation criteria, and outcomes, was extracted and documented. RESULTS: Of the 2314 articles identified, 18 fit the inclusion and exclusion criteria, with a total of 950 participants. The most prevalent form of exercise therapy was a combined aerobic exercise and strength training program (55.6%). Commonly used assessment criteria included the 6-minute walking distance for endurance evaluation (44.4%) and the Chronic Liver Disease Questionnaire for quality of life assessment (33.3%). Intervention durations ranged from 30 to 60 min per day, 2 to 7 days per week, and 8 to 12 weeks. Concerning intensity setting, subjective fatigue levels and heart rate were frequently used (38.9%), though detailed descriptions were limited. CONCLUSIONS: For the establishment of effective exercise therapy for patients with liver cirrhosis, future research should concentrate on tailoring intensity settings according to individual patient needs. Additionally, standardized reporting of intervention details and assessment methods is crucial for improving the quality and comparability of studies in this field.

DOI： 10.1186/s12876-025-03881-4

Safety of edoxaban for delayed bleeding in gastrointestinal endoscopic procedures with a high risk of bleeding. 国際誌

Ken-Ichi Mizuno, Junji Yokoyama, Osamu Shibata, Yuichi Kojima, Yuzo Kawata, Kazuya Takahashi, Kentaro Tominaga, Igarashi Satoshi, Hayashi Kazunao, Shuji Terai

DEN open 5 ( 1 ) e70018 2025年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: There are limited reports on the safety of gastrointestinal endoscopic procedures in individuals taking edoxaban, one of the direct oral anticoagulants. We clarified the incidence of delayed bleeding in patients who were on edoxaban in the perioperative period of gastrointestinal endoscopic procedures with a high risk of bleeding. METHODS: This was an investigator-initiated, single-center, open-label, prospective, single-arm study. Patients on warfarin or edoxaban undergoing endoscopy with a high risk of bleeding were enrolled from June 2018 to September 2021. Warfarin was replaced with edoxaban in patients on warfarin. Patients taking other direct oral anticoagulants, and antiplatelet drugs, were excluded. The primary endpoint was severe delayed bleeding (Common Terminology Criteria for Adverse Events [CTCAE] grades III-V) and the secondary endpoints included thromboembolism, all adverse events, any delayed bleeding (CTCAE grades I or II), and hospital stay durations. RESULTS: Twenty-one patients on edoxaban underwent high-risk endoscopy. Three cases (14%) experienced CTCAE grade III delayed bleeding, requiring endoscopic hemostasis. No CTCAE grade I-II delayed bleeding or thromboembolic events occurred. Cholangitis and aspiration pneumonia (conservatively treated) occurred during the hospital stay. The median length of hospital stay was 8 days (range 3-24 days). Patients with delayed bleeding had higher systolic blood pressure at admission and longer hospital stays. CONCLUSIONS: The delayed bleeding incidence in high-risk endoscopic procedures for patients on edoxaban was acceptable. Higher blood pressure may be associated with increased risk, but further research is needed.

DOI： 10.1002/deo2.70018

MASHモデルマウスに対する自走式回転かごによる運動負荷が肝組織や筋肉に及ぼす影響とそのメカニズム

三井田秀, 上村博輝, 丸山紘貴, 渡邉雄介, 木村成宏, 阿部寛幸, 佐々木玲奈, 横尾健, 坂牧僚, 上村顕也, 寺井崇二

肝臓 66 ( Suppl.1 ) A382 - A382 2025年4月

A型肝炎の薬剤開発現状と将来

神田達郎, 佐々木玲奈, 上村博輝, 阿部寛幸, 水戸將貴, 杉田萌乃, 荒生祥尚, 阿部聡司, 坂牧僚, 林和直, 横尾健, 上村顕也, 須田剛士, 寺井崇二

肝臓 66 ( Suppl.1 ) A362 - A362 2025年4月

Coexistence of Relapsing Polychondritis, Crohn's Disease, and Pyoderma Gangrenosum Treated Successfully with Adalimumab: A Case Report and Literature Review.

Shun Yamazaki, Kentaro Tominaga, Kotaro Watanabe, Makoto Watanabe, Shuhei Kondo, Norihiro Sakai, Tomoaki Yoshida, Yuichi Kojima, Yusuke Watanabe, Yuzo Kawata, Naruhiro Kimura, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Hiroteru Kamimura, Kazunao Hayashi, Shuji Terai

Internal medicine (Tokyo, Japan) 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Relapsing polychondritis (RP) is a rare, progressive, immune-mediated systemic inflammatory disease of unknown etiology characterized by recurrent inflammation of cartilaginous structures. Approximately 30% of RP cases are associated with autoimmune disease. However, co-occurrence of RP and Crohn's disease (CD) has rarely been reported. We herein report a case of coexisting RP, CD, and pyoderma gangrenosum that was successfully treated with adalimumab in combination with methotrexate. We believe that this case and literature review will facilitate the accurate and prompt diagnosis and treatment of RP combined with CD and various other complications.

DOI： 10.2169/internalmedicine.5024-24

Current management and future perspectives of covert hepatic encephalopathy in Japan: a nationwide survey.

Takao Miwa, Mio Tsuruoka, Hajime Ueda, Tamami Abe, Hiroki Inada, Yoshimi Yukawa-Muto, Masatsugu Ohara, Taeang Arai, Yasuyuki Tamai, Hiroshi Isoda, Tomoko Tadokoro, Tatsunori Hanai, Takanori Ito, Nobuharu Tamaki, Akira Sakamaki, Yoshihiko Aoki, Fujimasa Tada, Sachiyo Yoshio, Hirokazu Takahashi, Asahiro Morishita, Tsuyoshi Ishikawa, Jun Inoue, Goki Suda, Chikara Ogawa, Masanori Atsukawa, Atsushi Hiraoka, Hidekatsu Kuroda, Tadashi Namisaki, Takashi Honda, Takumi Kawaguchi, Yasuhito Tanaka, Shuji Terai, Tadashi Ikegami, Hitoshi Yoshiji, Motoh Iwasa, Masahito Shimizu

Journal of gastroenterology 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Covert hepatic encephalopathy (CHE) leads to devastating outcomes in patients with cirrhosis. This study aims to elucidate the current management and future perspectives of CHE in Japan. METHODS: A questionnaire-based cross-sectional study was conducted among physicians involved in managing cirrhosis in Japan. The primary aim was to elucidate the real-world management of CHE, including testing and treatment. Factors influencing the implementation of CHE testing were analyzed using a logistic regression model. Limitations and future perspectives for improving the management of CHE were also evaluated. RESULTS: Of 511 physicians surveyed, 93.9% recognized CHE as a significant problem, and 86.9% agreed that it should be tested. Overall, 62.8% of physicians tested for CHE, whereas 37.2% did not. Multivariable analysis identified institutional factors and certifying board as significant determinants of CHE test implementation. The Stroop (68.2%) and neuropsychiatric tests (57.5%) were the most commonly used methods of identifying CHE. Among those who tested for CHE, 87.7% treated CHE; the most common treatments were lactulose (81.5%), rifaximin (76.3%), and branched-chain amino acids (70.4%). Among non-testers, the primary barrier was the time requirement for testing. Proposals to encourage CHE testing included the development of simple tests and integration of multidisciplinary teams. CONCLUSIONS: Most physicians involved in cirrhosis care in Japan recognize CHE as a significant problem that warrants testing. However, testing for CHE remains limited by institutional factors and physician specialties. Time requirements for CHE testing are the primary barrier, and simple tests and multidisciplinary teams are recommended to enhance CHE management.

DOI： 10.1007/s00535-025-02232-0

Targeted animal models for preclinical assessment of cellular and gene therapies in pancreatic and liver diseases: regulatory and practical insights. 国際誌

Hongjun Wang, Rachele Ciccocioppo, Shuji Terai, Sara Shoeibi, Gianluca Carnevale, Giulia De Marchi, Atsunori Tsuchiya, Soichi Ishii, Takafumi Tonouchi, Kaito Furuyama, Yuan Yang, Masaki Mito, Hiroyuki Abe, Rosanna Di Tinco, Vincenzo Cardinale

Cytotherapy 27 ( 3 ) 259 - 278 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cellular and gene therapy (CGT) products have emerged as a popular approach in regenerative medicine, showing promise in treating various pancreatic and liver diseases in numerous clinical trials. Before these therapies can be tested in human clinical trials, it is essential to evaluate their safety and efficacy in relevant animal models. Such preclinical testing is often required to obtain regulatory approval for investigational new drugs. However, there is a lack of detailed guidance on selecting appropriate animal models for CGT therapies targeting specific pancreatic and liver conditions, such as pancreatitis and chronic liver diseases. In this review, the gastrointestinal committee for the International Society for Cell and Gene Therapy provides a summary of current recommendations for animal species and disease model selection, as outlined by the US Food and Drug Administration, with references to EU EMA and Japan PMDA. We discuss a range of small and large animal models, as well as humanized models, that are suitable for preclinical testing of CGT products aimed at treating pancreatic and liver diseases. For each model, we cover the associated pathophysiology, commonly used metrics for assessing disease status, the pros and limitations of the models, and the relevance of these models to human conditions. We also summarize the use and application of humanized mouse and other animal models in evaluating the safety and efficacy of CGT products. This review aims to provide comprehensive guidance for selecting appropriate animal species and models to help bridge the gap between the preclinical research and clinical trials using CGT therapies for specific pancreatic and liver diseases.

DOI： 10.1016/j.jcyt.2024.11.008

Human placental extract improves liver cirrhosis in mice with regulation of macrophages and senescent cells. 国際誌

Natsuki Ishikawa, Yusuke Watanabe, Yuichirou Maeda, Tomoaki Yoshida, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Regenerative therapy 28 509 - 516 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Cirrhosis is a disease with poor prognosis that requires the development of a novel therapeutic approach alternative to liver transplantation. In this study, we focused on the placenta and aimed to clarify the effects of human placental extract (HPE) on cirrhosis. METHODS: A mouse model of carbon tetrachloride-induced cirrhosis was used to evaluate the effect of HPE administration subcutaneously and compared with the control group (n = 8 for each group). In vitro and in vivo, real time-PCR and immunostaining were performed for HPE mechanistic analysis. Spatial transcriptomics was also performed for detailed analysis of the effect of HPE on cirrhosis. RESULTS: HPE administration improved serum ALT levels compared to control mice. Furthermore, there was a decrease in the number of senescent cells in the liver and the mRNA levels of secrete senescence-associated secretory phenotype factors and Cdkn2a (p16). In vitro, HPE induced macrophage polarization to the anti-inflammatory M2 phenotype. Spatial transcriptomics was also performed to analyze the underlying anti-inflammatory mechanism. The results showed that HPE strongly polarized macrophages to the M2 phenotype, especially in macrophage-rich regions in the liver. Gene expression pathway analysis using spatial transcriptomics also revealed the possibility of improving senescent cell-derived inflammation via mitochondrial function. CONCLUSIONS: HPE improves serum ALT levels via anti-inflammatory mechanisms in macrophages and senescent cells. HPE serves as a novel agent for cirrhosis treatment.

DOI： 10.1016/j.reth.2025.01.017

Extremely Rare Isolated Small-Intestinal Polyp Diagnosed by Double-Balloon Endoscopy in an Asymptomatic Adult Patient. 国際誌

Kentaro Tominaga, Annenkov Alexey, Yuto Tanaka, Osamu Shibata, Yuichi Kojima, Yuzo Kawata, Nao Nakajima, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Ken-Ichi Mizuno, Shuji Terai

Clinical case reports 13 ( 3 ) e70255 2025年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

We present the first reported case of an isolated small-bowel intestinal juvenile polyp in an adult. This case is particularly noteworthy as it was asymptomatic, detected via computed tomography, localized by capsule endoscopy, and successfully resected via double-balloon endoscopy before the development of acute symptoms.

DOI： 10.1002/ccr3.70255

小腸内細菌異常増殖症(SIBO)のcontroversy 小腸狭窄を伴うクローン病と慢性偽性腸閉塞(CIPO)における,既報との相違点

五十嵐崇徳, 冨永顕太郎, 若林拓哉, 横山邦彦, 小島雄一, 川田雄三, 木村成宏, 坂牧僚, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 122 ( 臨増総会 ) A365 - A365 2025年3月

小腸疾患の内視鏡診断・治療法の工夫当院における小腸GIST27例の臨床的特徴

小島雄一, 川田雄三, 冨永顕太郎, 寺井崇二

日本消化器病学会雑誌 122 ( 臨増総会 ) A81 - A81 2025年3月

Small Intestinal Bacterial Overgrowth Is a Predictor of Overt Hepatic Encephalopathy in Patients with Liver Cirrhosis. 国際誌

Akira Sakamaki, Kunihiko Yokoyama, Hanako Yamazaki, Takuya Wakabayashi, Yuichi Kojima, Kentaro Tominaga, Atsunori Tsuchiya, Kenya Kamimura, Junji Yokoyama, Shuji Terai

Journal of clinical medicine 14 ( 5 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective: Liver cirrhosis (LC) progression induces intestinal microbiota abnormalities, such as small intestinal bacterial overgrowth (SIBO), and these changes lead to the inflow of gut pathogens and their degradation products into the vessels, causing cirrhotic complications such as hepatic encephalopathy (HE). Methods: To clarify the relationship between the development of overt HE and SIBO, we conducted a three-year observation after assessment of SIBO in patients with LC. Results: In the analysis of 107 patients, with a mean follow-up duration of 29.4 months, 31 were diagnosed with SIBO and 30 with covert HE. In the Cox multivariate regression analysis for prognosis, the Child-Pugh score, blood urea nitrogen level, and the Union for International Cancer Control (UICC) stage of hepatocellular carcinoma were derived using the following five factors: white blood cell count, blood urea nitrogen level, Child-Pugh score, UICC stage, and serum aspartate aminotransferase and alkaline phosphatase levels (p = 0.002, hazard ratio [HR] 3.733, 95% confidence interval [CI] 1.592-8.754, p = 0.001, HR 1.076, 95% CI 1.030-1.123, and p < 0.001, HR 2.767, 95% CI 1.780-4.302, respectively). Furthermore, in the Cox multivariate regression analysis for overt HE development, covert HE and methane-producing SIBO were derived using the following four factors: methane-producing SIBO, UICC stage, covert HE, and serum ammonia levels (p = 0.038, HR 5.008, 95% CI 1.096-22.892 and p = 0.006, HR 8.597, 95% CI 1.881-39.291, respectively). Conclusions: M-SIBO positivity was a significant predictor of overt HE.

DOI： 10.3390/jcm14051491

Pruritus in Chronic Cholestatic Liver Diseases, Especially in Primary Biliary Cholangitis: A Narrative Review. 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Naruhiro Kimura, Hiroyuki Abe, Tomoaki Yoshida, Kazunao Hayashi, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai

International journal of molecular sciences 26 ( 5 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with chronic cholestatic liver diseases often experience itch and struggle with this symptom. We discuss the mechanism of itch in patients with chronic cholestatic liver diseases, such as primary biliary cholangitis (PBC) and others, and their therapies, including ileal bile acid transporter (IBAT) inhibitors. In patients with PBC, there are high serum/plasma concentrations of multiple factors, including bile salts, bilirubin, endogenous opioids, lysophosphatidic acid (LPA), autotaxin, and histamine. Bile salts, bilirubin, LPA, and autotaxin affect itch mediators in the skin and sensory nerves, while the endogenous opioid balance affects mediators in the spinal cord. Itch is sensitized by both the peripheral and central nervous systems. Both mechanisms are involved in itch in patients with chronic cholestatic liver disease. Although IBAT inhibitors have been approved for use in pediatric cholestatic conditions, such as progressive familial intrahepatic cholestasis and Alagille syndrome, IBAT inhibition seems to be a promising treatment for chronic refractory itch in patients with PBC. A traditional non-systematic review results in this narrative review. Multidisciplinary cooperation, involving hepatologists, dermatologists, and pharmacists, could provide better treatment for PBC patients suffering from refractory itch. In conclusion, we summarized the existing knowledge on itch caused by chronic cholestatic liver diseases, especially in PBC with a focus on the mechanisms and therapies. This narrative review provides the mechanisms and therapeutic options for itch in patients with chronic cholestatic liver diseases.

DOI： 10.3390/ijms26051883

Real-World Setting of Efficacy and Safety of 3 Years of Rifaximin Administration in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study. 国際誌

Hideto Kawaratani, Tadashi Namisaki, Yasuteru Kondo, Ryoji Tatsumi, Naoto Kawabe, Norikazu Tanabe, Akira Sakamaki, Kyoko Hoshikawa, Yoshihito Uchida, Kei Endo, Takumi Kawaguchi, Tsunekazu Oikawa, Yoji Ishizu, Shuhei Hige, Taro Takami, Shuji Terai, Yoshiyuki Ueno, Satoshi Mochida, Kazuhiko Koike, Hitoshi Yoshiji

Journal of clinical medicine 14 ( 4 ) 2025年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Objectives: Rifaximin is a therapeutic agent for patients with hepatic encephalopathy (HE); however, there is little data on the effects of its long-term (>1 year) administration in Japanese patients with cirrhosis. The effects and safety of 3-year rifaximin treatment on HE was investigated in Japan. Methods: A total of 190 Japanese patients with cirrhosis who were continuously administered rifaximin for more than 1 year suffered overt or covert HE, which was diagnosed by a physician. Laboratory data were collected at baseline, 3, 6, 12, 18, 24, 30, and 36 months following rifaximin administration. We examined the cumulative overt HE incidences, overall survival rates, and hepatic functional reserves following rifaximin treatment. The occurrence of adverse events was also assessed. Results: The levels of ammonia improved significantly after 3 months of rifaximin administration, which continued for 3 years. Serum albumin and prothrombin activity also significantly improved 3 years after initiation of rifaximin treatment. Cumulative overt HE incidences were 12.1%, 19.7%, and 24.9% at 1, 2, and 3 years, respectively. The survival rates following rifaximin treatment were 100%, 88.9%, and 77.8% at 1, 2, and 3 years, respectively. In contrast, renal function and electrolytes did not change following rifaximin administration. Only three (1.6%) patients discontinued rifaximin therapy because of severe diarrhea after 1 year of rifaximin administration. No other serious adverse events were observed. Conclusions: Three years of continuous rifaximin (RFX) treatment was both effective and safe for patients with hepatic encephalopathy. Liver function improved and did not worsen during treatment.

DOI： 10.3390/jcm14041358

Correction: Watanabe et al. Pemafibrate Improves Alanine Aminotransferase Levels Independently of Its Lipid-Lowering Effect. Livers 2023, 3, 562–568

Combination therapies with immune checkpoint inhibitor-based combination therapies for hepatocellular carcinoma with major vascular invasion. 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Shuji Terai

Hepatology international 2025年2月

Azuma Watanabe, Ryoko Horigome, Yumiko Nakatsuka, Shuji Terai

Livers 2025年2月

Hepatitis B virus infection and its treatment in Eastern Ethiopia 国際誌

Tatsuo Kanda, Reina Sasaki-Tanaka, Atsunori Tsuchiya, Shuji Terai

World Journal of Hepatology 17 ( 1 ) 99209 - 99209 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Baishideng Publishing Group Inc.

Hepatitis B virus (HBV) infection causes acute and chronic hepatitis, compensated and decompensated cirrhosis, and hepatocellular carcinoma worldwide. The actual status of HBV infection and its treatment in certain regions of Asian and African countries, including Ethiopia, has not been well-documented thus far. Antiviral therapy for HBV infection can prevent the progression of HBV-related liver diseases and decrease the HBV-related symptoms, such as abdominal symptoms, fatigue, systemic symptoms and others. In Eastern Ethiopia, HBV-infected patients with cirrhosis were found to be positive for the HBV e antigen and to have a higher viral load than those without cirrhosis. Notably, 54.4% of patients practiced khat chewing and 18.1% consumed excessive amounts of alcohol. Tenofovir disoproxil fumarate effectively suppressed HBV DNA in those infected with HBV. It is important to elucidate the actual status of HBV infection in Eastern Ethiopia to eliminate HBV infection worldwide by 2030. HBV vaccination and the educational programs for Health Science students that provide practical strategies could help to reduce HBV infection in Eastern Ethiopia.

DOI： 10.4254/wjh.v17.i1.99209

消化管とフレイル・サルコペニアクローン病患者におけるサルコペニアおよびサルコペニア肥満の臨床的特徴

冨永顕太郎, 中島尚, 佐藤裕樹, 林和直, 寺井崇二

日本消化管学会雑誌 9 ( Suppl. ) 216 - 216 2025年1月

Aligning cellular and molecular components in age-dependent tertiary lymphoid tissues of kidney and liver. 国際誌

Naoya Toriu, Yuki Sato, Hiroteru Kamimura, Takahisa Yoshikawa, Masaou Tanaka, Shinya Yamamoto, Shingo Fukuma, Masakazu Hattori, Shuji Terai, Motoko Yanagita

PloS one 20 ( 2 ) e0311193 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）

Tertiary lymphoid tissues (TLTs) are ectopic lymphoid structures induced by multiple stimuli, including infection and tissue injuries; however, their clinical relevance in disease progression has remained unclear. We demonstrated previously that TLTs develop in mouse and human kidneys with aging and can be a potential marker of kidney injury and prognosis, and therapeutic targets. In addition, we found that two types of unique lymphocytes that emerge with aging, senescence-associated T cells and age-associated B cells, are essential for TLT formation in the kidney. Although TLTs develop with aging in other organs as well, their cellular and molecular components, and clinical significance remain unclear. In the present study, we found that TLTs developed in the liver with aging, and that their cellular and molecular components were similar to those in the kidneys. Notably, senescence-associated T cells and age-associated B cells were also present in hepatic TLTs. Furthermore, analysis of publicly available data on human liver biopsy transcriptomes revealed that the expression of TLT-related genes was elevated in the liver biopsy samples from hepatitis C virus (HCV)-infected patients compared with those without HCV infection and was associated with liver injury and fibrosis. Therefore, we analyzed liver biopsy samples from 47 HCV patients and found that TLTs were present in 87.2% of cases and that the numbers and stages of TLTs were higher in aged patients and cellular and molecular components of TLTs in humans were similar to those in mice. Our findings suggesting that age-dependent TLT formation is a systemic phenomenon across the tissues and aging is also a predisposing factor for TLT formation across organs.

DOI： 10.1371/journal.pone.0311193

Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies. 国際誌

Shunya Motosugi, Naoki Takahashi, Shuhei Mineo, Keisuke Sato, Takahiro Tsuzuno, Yukari Aoki-Nonaka, Nao Nakajima, Kazuya Takahashi, Hiroki Sato, Haruna Miyazawa, Koji Taniguchi, Shuji Terai, Koichi Tabeta

PloS one 20 ( 3 ) e0320383 2025年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: The oral-gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to CRC progression. Fusobacterium nucleatum is a putative periodontal pathogen recognized as a specific bacterium that promotes CRC development. However, the possible involvement of other periodontal pathogens in CRC is poorly understood. This study aimed to explore the effects of ingested periodontal pathogens on experimental CRC in mice and elucidate the underlying mechanisms. METHODS: In this study, experimental colitis-induced CRC mouse models were used. The mice were orally administered periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) three times a week during the experimental period. The CRC severity between the P. gingivalis-treated and P. intermedia-treated groups was compared. Lumen-associated microbiota (LAM) and mucosa-associated microbiota (MAM) were analyzed in both mouse and human samples. In vitro studies were conducted using intestinal epithelial cells to explore the possible mechanisms by which the periodontal pathogens affect the CRC development. RESULTS: The P. gingivalis-treated group exhibited significantly increased CRC severity compared to the other groups among azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse models. The LAM and MAM exhibited distinct bacterial compositions, and P. gingivalis was enriched more in MAM than in LAM. In vitro adhesion assays revealed that P. gingivalis had higher adhesive capacity to intestinal epithelial cells than P. intermedia and indicated the possible involvement of gingipains in such a capacity. CONCLUSION: P. gingivalis is enriched in MAM, and its subsequent adhesion to intestinal epithelial cells is potentially involved in the progression of CRC.

DOI： 10.1371/journal.pone.0320383

Persistent body-weight change on achalasia and peroral endoscopic myotomy: a multicenter cohort study.

Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Takuya Satomi, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue

Journal of gastroenterology 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The distribution of body weight in patients with achalasia and after peroral endoscopic myotomy (POEM) has not been investigated. The role of body weight assessment after treatment remains unclear. METHODS: Using the multicenter achalasia cohort, the frequency of underweight (body mass index [BMI] < 18.5 kg/m2) and overweight (BMI ≥ 25.0 kg/m2) and their associated clinical characteristics were analyzed. After POEM, risk factors for insufficient- (underweight persistently) and excessive- (responded to overweight) weight gainers were investigated. The correlation between BMI-increase rate and severity of esophageal symptoms post-POEM was evaluated. RESULTS: Among 3,410 patients, 23.0% and 15.7% were underweight and overweight, respectively. Factors associated with underweight were higher age, female sex, severe symptoms, high lower esophageal sphincter (LES) pressure, and non-dilated esophagus (all p < 0.01). Longitudinal analyses revealed that weight gain post-POEM was achieved after a long duration (≥ 12 months; p < 0.01). In 528 patients post-POEM, the frequency of underweight reduced to 8.3% (p < 0.01). Risk factors for insufficient-weight gain (36.1% of underweight patients) included low BMI (p < 0.01) and high LES pressure (p = 0.03) and conversely for excessive-weight gain. Machine learning models based on patient characteristics successfully predicted insufficient- and excessive-weight gainers with an area under the curve value of 0.74 and 0.75, respectively. Esophageal symptoms post-POEM did not correlate with BMI increase. CONCLUSION: Underweight is not solely a condition of advanced achalasia. After POEM, insufficient- or excessive-weight gainers are not rare and can be predicted preoperatively. Body weight change is an independent nutrition parameter rather than a part of the assessment of residual esophageal symptoms.

DOI： 10.1007/s00535-024-02205-9

Dasatinib and Quercetin as Senolytic Drugs Improve Fat Deposition and Exhibit Antifibrotic Effects in the Medaka Metabolic Dysfunction-Associated Steatotic Liver Disease Model. 国際誌

Shunta Yakubo, Hiroyuki Abe, Yawen Li, Marina Kudo, Atsushi Kimura, Takuya Wakabayashi, Yusuke Watanabe, Naruhiro Kimura, Toru Setsu, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai

Diseases (Basel, Switzerland) 12 ( 12 ) 2024年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metabolic dysfunction-associated steatotic liver disease (MASLD) causes cellular senescence due to oxidative stress, endoplasmic reticulum stress, and ectopic fat deposition in the liver. Recently, dasatinib, an antitumor agent, and quercetin, a dietary supplement, were combined as a senolytic drug to eliminate senescent cells. Thus, this study aimed to examine the effects of dasatinib and quercetin administration on removing senescent cells and their therapeutic effects on MASLD in a medaka MASLD model. Dasatinib and quercetin were administered to a medaka MASLD model, which was fed a high-fat diet by dissolving them in aquarium water. The results revealed that senescent cells in the liver were increased in the HFD group but improved in the treatment group. Hematoxylin and eosin staining also showed that treatment improved fat deposition in hepatocytes. In addition, TGFβ1, a driver factor of fibrosis, was reduced in the treatment group. Dasatinib and quercetin eliminated senescent cells in MASLD, attenuated fat deposition, and suppressed fibrosis gene expression. The results indicate that dasatinib and quercetin as senolytic drugs are novel therapeutic agents that reduce MASLD.

DOI： 10.3390/diseases12120317

ROI Selection to Improve Prediction Performance of CNN for Cirrhosis Detection Using Ultrasound Images 査読

一般消化器内科外来における危険飲酒者のスクリーニングについて

若林拓哉, 坂牧僚, 林和直, 柴田理, 酒井規裕, 小島雄一, 中島尚, 阿部寛幸, 寺井崇二

アルコールと医学生物学 43 71 - 73 2024年12月

高脂肪食は雌マウスにおけるアルコール性肝炎の発症に抑制的に作用する

坂牧僚, 若林拓哉, 林和直, 酒井規裕, 木村成宏, 阿部寛幸, 上村顕也, 寺井崇二

アルコールと医学生物学 43 76 - 77 2024年12月

Kazuma Nakata, Yusuke Fujita, Yoshihiro Mitani, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai

2024 IEEE 13th Global Conference on Consumer Electronics (GCCE) 636 - 640 2024年11月

Factors involved in gastroesophageal varix-related events in patients with hepatitis C virus-related compensated and decompensated cirrhosis after direct-acting antiviral therapy. 国際誌

Yuki Tahata, Hayato Hikita, Satoshi Mochida, Nobuyuki Enomoto, Norifumi Kawada, Akio Ido, Daiki Miki, Masayuki Kurosaki, Hitoshi Yoshiji, Ryotaro Sakamori, Hidekatsu Kuroda, Hiroshi Yatsuhashi, Taro Yamashita, Yoichi Hiasa, Naoya Kato, Hisamitsu Miyaaki, Yoshiyuki Ueno, Yoshito Itoh, Kentaro Matsuura, Taro Takami, Yasuhiro Asahina, Goki Suda, Norio Akuta, Ryosuke Tateishi, Yasunari Nakamoto, Eiji Kakazu, Shuji Terai, Masahito Shimizu, Masanori Miyazaki, Yasutoshi Nozaki, Satoshi Sobue, Hiroki Yano, Tomokatsu Miyaki, Akihiro Moriuchi, Takeshi Hori, Kumiko Shirai, Kazuhiro Murai, Yoshinobu Saito, Takahiro Kodama, Tomohide Tatsumi, Tomomi Yamada, Tetsuo Takehara

Hepatology research : the official journal of the Japan Society of Hepatology 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: The incidence of and factors involved in gastroesophageal varix-related events in hepatitis C virus-related cirrhosis patients, including decompensated cirrhosis, after direct-acting antiviral therapy are unclear. METHODS: We conducted a multicenter study using prospective data from 478 hepatitis C virus-related cirrhosis patients treated with direct-acting antiviral therapy from February 2019 to December 2021 at 33 Japanese hospitals. Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), or F3 (markedly enlarged) according to the Japanese criteria. Patients without varix or with F1 without red color signs were defined as low-risk varix, and patients with ≥F2 or red color signs or a history of rupture were defined as high-risk varix. Varix-related events were defined as prophylactic treatment or rupture of gastroesophageal varix. RESULTS: The median age was 70 years, 43% of patients had decompensated cirrhosis, and 16% had high-risk varices (13% in compensated and 33% in decompensated, p < 0.001). Sustained virologic response rates were 94.9% for compensated cirrhosis and 91.3% for decompensated cirrhosis (p = 0.120). Across 35.7 months, 25 patients received prophylactic treatment, and four experienced varix rupture. The 3-year incidence rate of varix-related events was 6.2% (3.5% in compensated and 9.9% in decompensated, p = 0.001). In the multivariate analysis, high-risk varix (p < 0.001), high baseline gamma-glutamyl transpeptidase levels (p < 0.001), and virologic failure (p = 0.004) were significantly involved in varix-related events. CONCLUSIONS: The cumulative incidence rate of varix-related events was significantly higher in decompensated cirrhosis than in compensated cirrhosis. Baseline varix status, baseline gamma-glutamyl transpeptidase levels, and virologic response were related to varix-related events after direct-acting antiviral therapy.

DOI： 10.1111/hepr.14131

Association between Clinical Characteristics and Sarcopenia or Sarcopenic Obesity in Crohn's Disease.

Takumi Naruse, Hiroki Sato, Kazuya Takahashi, Chihiro Sato, Yuichi Kojima, Yuzo Kawata, Kentaro Tominaga, Ken-Ichi Mizuno, Shuji Terai

Internal medicine (Tokyo, Japan) 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective Crohn's disease (CD) is a chronic inflammatory bowel disease that is associated with malnutrition. Sarcopenia is a malnutrition condition characterized by skeletal muscle loss that impairs the physical function. We investigated the clinical characteristics of patients with CD with sarcopenia and sarcopenic obesity (sarcopenic-o). Methods The body composition of patients with CD was evaluated using a bioelectrical impedance analysis. The clinical characteristics of patients with sarcopenia and sarcopenic-o were analyzed, and a predictive model for sarcopenia was developed. Patients: Patients with CD recruited from 2019 to 2021 were included. Results Among the 104 patients, 35 (33.7%) and 10 (9.6%) had sarcopenia and sarcopenic-o, respectively. In the sarcopenia group, the skeletal muscle index (SMI) and body mass index (BMI) were lower than those in the control group (SMI, 6.3 kg/m2 vs. 7.7 kg/m2, p<0.01; BMI, 18.8 kg/m2 vs. 22.6 kg/m2, p<0.01), whereas the Crohn's disease activity index (CDAI) was higher than in the control group (114.2 vs. 42.0, p<0.01). The predictive models of sarcopenia using the BMI and CDAI revealed high performance with areas under the receiver operating characteristic curve (AUC) of 0.87 and 0.72, respectively, and high specificity (0.94) and sensitivity (0.71), respectively. Sarcopenic-o patients could not be screened using the BMI (25 kg/m2), and the SMI and body fat percentage were negatively correlated in patients with sarcopenia (p<0.01). Conclusion Sarcopenia and sarcopenic-o are relatively common conditions among patients with CD. Sarcopenia can be predicted using the clinical parameters of BMI and CDAI. Sarcopenic-o can be a severe form of sarcopenia.

DOI： 10.2169/internalmedicine.4420-24

Diffuse Large B-cell Lymphoma with Severe Lactic Acidosis and Liver Failure: A Case Report and Literature Review.

Shun Yamazaki, Yusuke Watanabe, Kazuya Takahashi, Kentaro Tominaga, Satoshi Ikarashi, Takeshi Yokoo, Hiroteru Kamimura, Atsunori Tsuchiya, Shuji Terai

Internal medicine (Tokyo, Japan) 2024年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Among causes of liver failure, liver failure due to lymphocytic infiltration is rare. Unlike typical liver failure, some cases present with severe lactic acidosis and a poor prognosis. We herein report a case of diffuse large B-cell lymphoma with severe lactic acidosis and liver failure. We further discuss the characteristics of similar cases in the literature, suggesting that intrahepatic infiltration by hematological malignant cells should be considered as a differential diagnosis in the presence of severe lactic acidosis and liver failure. This study underscores the importance of early recognition and serves as a reference for future cases.

DOI： 10.2169/internalmedicine.4450-24

自験例から考察したHBV de novo再活性化診療のピットフォール

木村究, 横尾健, 吉田智彰, 渡邉雄介, 木村成宏, 阿部寛幸, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 75回・97回 70 - 70 2024年10月

非切除肝門部領域胆管癌に対する内視鏡的胆管ステント留置術の検討

林和直, 柴田理, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 66 ( Suppl.2 ) 2292 - 2292 2024年10月

治療困難胆管結石に対する経口胆道鏡下治療の有用性

五十嵐聡, 林和直, 柴田理, 寺井崇二

Gastroenterological Endoscopy 66 ( Suppl.2 ) 2301 - 2301 2024年10月

「長期臨床経過を見据えた消化器疾患の治療・管理における工夫と課題」自己免疫性膵炎のステロイド治療導入後再燃例における臨床経過の検証

田中裕登, 柴田理, 五十嵐聡, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 75回・97回 51 - 51 2024年10月

治療困難胆管結石に対する経口胆道鏡下治療の有用性

五十嵐聡, 林和直, 柴田理, 寺井崇二

Gastroenterological Endoscopy 66 ( Suppl.2 ) 2301 - 2301 2024年10月

非切除肝門部領域胆管癌に対する内視鏡的胆管ステント留置術の検討

林和直, 柴田理, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 66 ( Suppl.2 ) 2292 - 2292 2024年10月

Esophageal Varices as an Independent Predictor of Fatal Outcomes after Balloon-Occluded Retrograde Transvenous Obliteration in Patients with Hepatic Encephalopathy. 国際誌

Shuichiro Iwasaki, Haruki Uojima, Shinya Sakita, Sakue Masuda, Kousuke Kubota, Tomoaki Fujikawa, Tomomi Okubo, Toru Setsu, Norio Itokawa, Yoshihiro Furuichi, Yoshitaka Arase, Toshiki Tukiyama, Kaoru Fujii, Hisashi Hidaka, Masanori Atsukawa, Tatehiro Kagawa, Makoto Kako, Shuji Terai, Chika Kusano

Digestive diseases (Basel, Switzerland) 42 ( 6 ) 80 - 89 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: The objective of this study was to evaluate esophageal varices (EVs) as predictors of poor prognosis with low tolerability after balloon-occluded retrograde transvenous obliteration (BRTO) in patients with overt hepatic encephalopathy (HE). METHODS: This study retrospectively enrolled 107 patients who underwent BRTO for uncontrollable overt HE. The enrolled patients were divided into two groups based on the presence of EVs using propensity matching. The present study assessed the technical success rate and safety of BRTO in both the groups. Further, the event-free survival, HE-free survival, and the overall survival (OS) were compared between the two groups. Event-free survival was defined as the time period during which the patients did not developed complications related to portal hypertension, including EVs, hepatic ascites, and portal vein thrombosis. RESULTS: After propensity matching, the EV and non-EV groups had 37 and 36 patients, respectively. Only 1 patient experienced an unsuccessful procedure in the EV group. Procedure-related adverse events in the EV group and non-EV group occurred in 11 and 7 patients, respectively (p = 0.417). The event-free survival after BRTO in the EV and non-EV group were 1,283 (95% CI: 798-1,767) days and 2,257 (1,722-2,792) days, respectively. Event-free survival was significantly worse in the EV group than in the non-EV group (p = 0.014). Furthermore, the EV group experienced worse OS than the non-EV group (p = 0.001 and p < 0.001, respectively). CONCLUSIONS: The presence of EVs could potentially be associated with a higher risk of adverse outcomes or mortality after BRTO treatment in individuals with HE.

DOI： 10.1159/000541660

Maid gene dysfunction promotes hyperobesity via the reduction of adipose tissue inflammation in Mc4r gene-deficient mice. 国際誌

Kyutaro Koyama, Akira Sakamaki, Shinichi Morita, Itsuo Nagayama, Marina Kudo, Yuto Tanaka, Naruhiro Kimura, Yoshihisa Arao, Hiroyuki Abe, Kenya Kamimura, Shuji Terai

Scientific reports 14 ( 1 ) 21126 - 21126 2024年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The onset and progression mechanisms of metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) are being studied. We developed and analyzed a new mouse model of obesity by combining maternal Id-like molecule (Maid) and melanocortin-4 receptor (Mc4r) gene deletions. Four mice, each at 12 and 28 weeks of age, were analyzed for each genotype: Maid gene knockout, Mc4r gene knockout, combined Mc4r and Maid gene knockout, and Mc4r gene knockout with a high-fat diet. Mice with a combined deficiency of Mc4r and Maid gene showed significantly more severe obesity compared to all other genotypes, but no liver fibrosis or a decline in metabolic status were observed. In visceral white adipose tissue, Maid and Mc4r gene knockout mice had fewer CD11c-positive cells and lower mRNA expression of both inflammatory and anti-inflammatory cytokines. Furthermore, Maid and Mc4r gene knockout mice showed lower expression of adipocytokines in visceral white adipose tissue and uncoupling protein-1 in scapular brown adipose tissue. The expression of adipocytokines and uncoupling protein-1 is regulated by sympathetic nerve signaling that contribute severe obesity in Maid and Mc4r gene knockout mice. These mechanisms contribute hyperobesity in Maid and Mc4r gene knockout mice.

DOI： 10.1038/s41598-024-72217-1

症候性巨大肝嚢胞に対する嚢胞内洗浄併用の塩酸ミノサイクリン硬化療法が長期的効果を呈した1例

小川和也, 上村顕也, 石井壮一, 遠藤沙織, 石川夏生, 阿部寛幸, 坂牧僚, 寺井崇二

日本消化器病学会雑誌 121 ( 9 ) 769 - 776 2024年9月

PCPE-1, a brown adipose tissue-derived cytokine, promotes obesity-induced liver fibrosis. 国際誌

Yung Ting Hsiao, Yohko Yoshida, Shujiro Okuda, Manabu Abe, Seiya Mizuno, Satoru Takahashi, Hironori Nakagami, Ryuichi Morishita, Kenya Kamimura, Shuji Terai, Tin May Aung, Ji Li, Takaaki Furihata, Jing Yuan Tang, Kenneth Walsh, Akihito Ishigami, Tohru Minamino, Ippei Shimizu

The EMBO journal 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metabolic dysfunction-associated steatohepatitis (MASH, previously termed non-alcoholic steatohepatitis (NASH)), is a major complication of obesity that promotes fatty liver disease. MASH is characterized by progressive tissue fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH and its systemic control remain poorly understood. Here, we identified the secreted-type pro-fibrotic protein, procollagen C-endopeptidase enhancer-1 (PCPE-1), as a brown adipose tissue (BAT)-derived adipokine that promotes liver fibrosis in a murine obesity-induced MASH model. BAT-specific or systemic PCPE-1 depletion in mice ameliorated liver fibrosis, whereas, PCPE-1 gain of function in BAT enhanced hepatic fibrosis. High-calorie diet-induced ER stress increased PCPE-1 production in BAT through the activation of IRE-1/JNK/c-Fos/c-Jun signaling. Circulating PCPE-1 levels are increased in the plasma of MASH patients, suggesting a therapeutic possibility. In sum, our results uncover PCPE-1 as a novel systemic control factor of liver fibrosis.

DOI： 10.1038/s44318-024-00196-0

Urinary NGAL in gastrointestinal diseases can be used as an indicator of early infection in addition to acute kidney injury marker. 国際誌

Yuichi Kojima, Atsunori Tsuchiya, Masaki Mito, Yusuke Watanabe, Yuzo Kawata, Kentaro Tominaga, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 8 ( 8 ) e70009 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Neutrophil gelatinase-associated lipocalin (NGAL) is characterized by increased expression before the rise in serum creatinine and has been used as a biomarker for the early prediction of acute kidney injury (AKI). However, there have been no comprehensive analyses of its significance in gastrointestinal diseases. This study aimed to analyze the usefulness of measuring urinary NGAL levels in patients with gastrointestinal diseases. METHODS: This study included 171 patients with a wide range of gastrointestinal diseases. Urinary NGAL levels were measured in all patients within 24 h of admission and 72 h later. RESULTS: Urinary NGAL levels were higher in patients with acute pancreatitis and acute cholangitis/cholecystitis than in those with other diseases. Although lower than in these diseases, urinary NGAL tends to be higher in inflammatory bowel diseases, such as ulcerative colitis and Crohn's disease, as well as in acute and chronic liver diseases, and is higher in liver cirrhosis as the Child-Pugh grade increases. Furthermore, we found that the group with higher urinary NGAL levels, which continued to increase over time, had worse hospital stays and prognosis. CONCLUSION: Urinary NGAL could be used as an indicator of infectious diseases rather than an indicator of AKI in inflammatory bowel diseases and cirrhosis, and could predict the prognosis of patients with gastrointestinal diseases.

DOI： 10.1002/jgh3.70009

【肝臓リハビリテーションの現状と問題点】

寺井崇二, 吉治仁志, 川口巧, 清水雅仁, 辻哲也

肝臓 65 ( 8 ) 351 - 367 2024年8月

Diagnosis and resolution of olmesartan-associated sprue-like enteropathy confirmed by capsule endoscopy: a case report and literature review.

Erina Kodama, Yuzo Kawata, Shun Yamazaki, Takanori Igarashi, Yuichi Kojima, Kentaro Tominaga, Junji Yokoyama, Terasu Honma, Shuji Terai

Clinical journal of gastroenterology 2024年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Herein, we describe a case of olmesartan-associated sprue-like enteropathy, in which improvement in villous atrophy was confirmed using small bowel capsule endoscopy. The patient was a 69-year-old woman who had persistent watery diarrhea (20 bowel movements/day) for 1 year and experienced a weight loss of 10 kg in the same period. Abdominal computed tomography revealed no abnormalities, and blood test results revealed no inflammatory reactions. Upper endoscopy and colonoscopy revealed villous atrophy in the duodenum and terminal ileum. As the patient was administered olmesartan for a long time and capsule endoscopy showed villous atrophy throughout the small bowel, she was diagnosed with olmesartan-associated sprue-like disease. Following the discontinuation of the medication, symptoms of diarrhea soon improved, and repeat capsule endoscopy indicated improvement in small intestinal villous atrophy. Olmesartan-associated sprue-like enteropathy should be considered a differential diagnosis in patients with severe chronic watery diarrhea. Our report is the first in which capsule endoscopy was performed multiple times over a long period for follow-up observation of improvements in the small intestine. In addition, our literature review regarding capsule endoscopy for olmesartan-associated enteritis might aid clinicians in the early diagnosis of the condition and the assessment of treatment efficacy.

DOI： 10.1007/s12328-024-02023-9

Automatic ROI Selection with Reliability Evaluation Method for Cirrhosis Detection using Ultrasound Images 査読

Kazuma Nakata, Yusuke Fujita, Yoshihiro Mitani, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

IEEJ Transactions on Electrical and Electronic Engineering 19 ( 7 ) 2024年7月

Inflammation of the liver, HCC development and HCC establishment 招待査読

Tatsuo Kanda, Reina Sasaki-Tanaka, Shuji Terai

Hepatology International 2024年6月

Fibulin-4 as a potential extracellular vesicle marker of fibrosis in patients with cirrhosis. 国際誌

Masaru Kumagai, Atsunori Tsuchiya, Yuan Yang, Nobutaka Takeda, Kazuki Natsui, Yui Natusi, Kei Tomiyoshi, Fusako Yamazaki, Yohei Koseki, Hiroki Shinchi, Naoko Imawaka, Ryo Ukekawa, Takahiro Nishibu, Hiroyuki Abe, Takako Sasaki, Koji Ueda, Shuji Terai

FEBS open bio 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Chronic liver injury leads to decreased liver function and increased fibrosis. Fibrosis is not only associated with the development of portal hypertension and carcinogenesis, but with the occurrence of events and a poor prognosis, highlighting the importance of non-invasive fibrosis assessment in patients. In the present study, we searched for markers related to liver fibrosis via proteomic analysis of small extracellular vesicles (sEVs). In the discovery cohort, proteomic analysis was carried out in the sEVs extracted from the sera of 5 patients with decompensated cirrhosis, 5 patients with compensated cirrhosis, and 5 controls without liver disease. Interestingly, in this cohort, fibulin-4 was significantly associated with cirrhosis while in the validation cohort [formed by 191 patients: 7 patients without disease, 16 patients without liver disease (other diseases), 38 patients with chronic liver disease (CLD), 75 patients with cirrhosis of Child-Pugh class A (36 without hepatocellular carcinoma [HCC], 29 with HCC), and 65 patients with cirrhosis of Child-Pugh class B-C (39 without HCC, 26 with HCC)], fibulin-4/CD9 levels increased with cirrhosis progression. Furthermore, the fibulin-4/CD9 ratio was significantly higher in patients with varices. Immunostaining also revealed strong fibulin-4 expression in cholangiocytes within the fibrous areas and mesothelial cells in liver tissue blood vessels. Taken together, our results suggest that fibulin-4, essential for lysyl oxidase activation, might be a new liver fibrosis marker found in the sEVs of patients with cirrhosis.

DOI： 10.1002/2211-5463.13842

胆膵内視鏡検査・治療における工夫とトラブルシューティング当院における副乳頭アプローチカニュレーション

名古屋拓郎, 小川光平, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 154 - 154 2024年6月

小川光平, 名古屋拓郎, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 148 - 148 2024年6月

Platelet-rich plasma-derived extracellular vesicles improve liver cirrhosis in mice. 国際誌

Yuichirou Maeda, Yusuke Watanabe, Natsuki Ishikawa, Tomoaki Yoshida, Naruhiro Kimura, Hiroyuki Abe, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Regenerative therapy 26 1048 - 1057 2024年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Cirrhosis remains a significant clinical challenge due to its poor prognosis and limited treatment options, creating a high unmet medical need for the development of novel therapies. In this study, we analyzed the effects of a novel approach to treat cirrhosis using platelet-rich plasma-derived extracellular vesicles (PRPEV) in mice. METHODS: PRPEV were collected from platelet-rich plasma using ultrafiltration, and their proteomes were analyzed. The carbon tetrachloride (CCl4)-induced cirrhosis model of mice was used to evaluate the effect of PRPEV administration and compared with the control group (n = 8). In vitro and in vivo mechanistic analyses of PRPEV administration were confirmed using real time-PCR and immunostaining. RESULTS: Gene ontology analysis based on the proteome revealed that PRPEV contain many factors associated with EV and immune responses. In vitro, PRPEV polarize macrophages into an anti-inflammatory phenotype. Following PRPEV administration, there was a decrease in serum alanine aminotransferase levels and reduction in liver fibrosis, while mRNA levels of regenerative factors were upregulated and transforming growth factor β-1 was downregulated. Furthermore, the number of anti-inflammatory macrophages in the liver increased. CONCLUSIONS: PRPEV may contribute to hepatocyte proliferation, anti-inflammation, and anti-fibrogenesis in the liver. This novel concept paves the way for cirrhosis treatment.

DOI： 10.1016/j.reth.2024.10.010

胆膵内視鏡検査・治療における工夫とトラブルシューティング当院における副乳頭アプローチカニュレーション

名古屋拓郎, 小川光平, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 154 - 154 2024年6月

小川光平, 名古屋拓郎, 五十嵐聡, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 2 ) 148 - 148 2024年6月

Acute pancreatitis as a rare complication of leptospirosis: A case report and literature review. 国際誌

Suguru Miida, Masaki Maruyama, Takeki Sato, Takuro Nagoya, Ryo Goto, Osamu Isokawa, Nobuo Koizumi, Shuji Terai

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 30 ( 6 ) 552 - 556 2024年6月

記述言語：英語

Leptospirosis is a zoonotic disease. We present a case of acute pancreatitis associated with leptospirosis. An 88-year-old woman was admitted to the hospital with high fever and severe myalgia of the lower extremities. Based on the clinical presentation, hepatic dysfunction with a mild increase in bilirubin, renal dysfunction, and life history, the possibility of leptospirosis was considered. Plain computed tomography of the trunk on admission revealed no special findings. Appropriate antimicrobial therapy was administered at an early stage. After treatment initiation, the clinical symptoms and blood test abnormalities began to improve, and the patient appeared to be doing well. Although no abdominal or back pain was consistently noted during hospitalization, the serum amylase level increased over time; therefore, the patient underwent another computed tomography scan on the ninth day. Acute pancreatitis, which was absent upon admission, was noted. Appropriate treatment for pancreatitis was administered, and the patient was discharged. A subsequent serum antibody test confirmed the diagnosis of leptospirosis. Herein, we also summarized previous cases of acute pancreatitis associated with leptospirosis. The time of onset for pancreatitis was inconsistent, and there were a few cases of pancreatitis without abdominal or back pain. In contrast, serum amylase or lipase levels were elevated in all patients, which could be an important trigger for suspected complications of pancreatitis. When leptospirosis is suspected, complications of pancreatitis should always be considered, even in the absence of apparent abdominal pain. Regular monitoring of pancreatic enzymes such as amylase and lipase is recommended.

DOI： 10.1016/j.jiac.2023.11.027

Correction to: Complementary role of peripheral and central autonomic nervous system on insulin-like growth factor-1 activation to prevent fatty liver disease. 国際誌

Itsuo Nagayama, Kenya Kamimura, Takashi Owaki, Masayoshi Ko, Takuro Nagoya, Yuto Tanaka, Marina Ohkoshi, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Shuji Terai

Hepatology international 18 ( 3 ) 1067 - 1069 2024年6月

Novel scale for evaluating the therapeutic efficacy of per-oral endoscopic myotomy in achalasia.

Kazuya Takahashi, Hiroki Sato, Yuto Shimamura, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Kenta Hamada, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Shuji Terai, Haruhiro Inoue

Journal of gastroenterology 2024年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients' quality of life (QOL) post-POEM. METHODS: Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with "occasional" symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom. RESULTS: Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9%) had persistent symptoms post-POEM, and 23 of them had m-ES-specific symptom frequency ≥ once a month, which was determined as the optimal frequency threshold for screening persistent symptoms. The total m-ES predicted persistent symptoms more accurately than the total c-ES (area under the curve: 0.95 vs. 0.79, p < 0.01). Furthermore, dysphagia and chest pain were the major residual symptoms post-POEM covering 91.4% of regurgitation. CONCLUSIONS: The new post-POEM scale successfully evaluated the QOL-based patient symptom severities. Our study implied the possibility of a simpler scale using residual dysphagia and chest pain.

DOI： 10.1007/s00535-024-02119-6

Bioinformatic evaluation of the potential oral-gut translocation of periodontal pathogens in patients with colorectal polyps

Liver Diseases: From Bench to Bedside 招待査読

Tatsuo Kanda, Reina Sasaki-Tanaka, Shuji Terai

International Journal of Molecular Sciences 25 ( 10 ) 5454 2024年5月

Naoki Takahashi, Marin Yamaguchi, Keisuke Sato, Takahiro Tsuzuno, Shuhei Mineo, Nao Nakajima, Kazuya Takahashi, Hiroki Sato, Haruna Miyazawa, Yukari Aoki-Nonaka, Yutaro Ito, Koji Taniguchi, Shuji Terai, Kohei Ito, Koichi Tabeta

2024年5月

出版者・発行元：Cold Spring Harbor Laboratory

Objective: This study aimed to characterize the profiles of the oral and gut microbiota of patients with colorectal polyps using 16S rRNA gene sequencing and bioinformatic approaches. Background: Previous studies have shown microbial translocation from the oral cavity to the gut, implying pathogenic impacts on gastroesophageal disease, including colorectal cancer (CRC). However, its details remain unclear. Methods: Twenty patients scheduled for endoscopic colorectal polypectomy were enrolled in this study. Oral samples (saliva and subgingival dental plaque) and intestinal samples (feces and swab of intestinal mucosa) were collected during preoperative and 6–month–postoperative reassessment periods. After sequencing the V3–V4 region of the bacterial 16S rRNA gene, several bioinformatic analyses (bacterial composition, diversity, core microbiome, and shared ASV) were performed on pre– and postoperative samples for each subject. Results: The bacterial composition was dominated by Bacteroides, Streptococcus, Fusobacterium, Veillonella, and Prevotella_7 in all four samples. Beta diversity analysis using weighted UniFrac distance distinctly segregated the samples between oral and intestinal environments in the principal coordinate analysis plot. Core microbiome analysis revealed that Streptococcus and Porphyromonas were dominantly shared in intra–oral environments. Additionally, alongside Streptococcus, periodontitis–related bacteria, such as Veillonella, Fusobacterium, Porphyromonas, Prevotella_7, Haemophilus, and Prevotella, were identified as shared genera between oral and intestinal environments. Finally, shared ASV analysis demonstrated that Streptococcus was shared in the oral and intestinal environments of most patients, while periodontal pathogens were shared in some patients. Conclusions: The core microbiome and shared ASV analyses revealed that several genes are shared between oral and intestinal environments in patients with colorectal polyps, indicating the oral–gut translocation of periodontitis–related bacteria. Further large–scale studies are needed to elucidate their involvement in CRC.

DOI： 10.1101/2024.04.29.591540

Acute on chronic liver failureモデルに対する肝細胞老化除去治療の基礎的検討

渡邉雄介, 土屋淳紀, 寺井崇二

肝臓 65 ( 5 ) 252 - 252 2024年5月

消化器救急疾患における診断・治療と課題当院における重症急性膵炎の予後・感染性被包化膵壊死合併の検討

柴田理, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 74回・96回 35 - 35 2024年5月

A rare cause of esophageal stenosis: Compression due to a thoracic osteophyte. 国際誌

Suguru Miida, Yoshihisa Arao, Nobutaka Takeda, Shu Goto, Yuichi Kojima, Naruhiro Kimura, Kazunao Hayashi, Atsunori Tsuchiya, Shuji Terai

DEN open 4 ( 1 ) e260 2024年4月

記述言語：英語

Several cases of esophageal stenosis caused by cervical vertebral osteophytes have been reported; however, few reports of esophageal stenosis caused by thoracic osteophytes are available. We describe the case of an 86-year-old man with esophageal stenosis caused by a thoracic osteophyte near the tracheal bifurcation. An endoscopic ultrasonography examination was scheduled to determine the cause of acute pancreatitis; however, lacerations observed at the bifurcation following endoscope removal during prior esophagogastroduodenoscopy led us to cancel the ultrasonography to avoid potential esophageal perforation. A review of the present case and six similar previous cases of thoracic osteophyte-associated esophageal stenosis (identified via a systematic search of the PubMed database) demonstrated the clinical importance of a thoracic osteophyte near physiological esophageal stenosis. Esophagogastroduodenoscopy and computed tomography should be performed to screen for vertebral osteophytes before endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, and transesophageal echocardiography to avoid iatrogenic accidents.

DOI： 10.1002/deo2.260

オルガノイドが切り拓く消化器病研究新時代組織常在型マクロファージを有する新規小腸オルガノイドの開発

ダサチニブ及びケルセチンは老化細胞除去剤としてMASHメダカモデルにおいて老化細胞を減少させ病態改善に寄与する

阿部寛幸, 弥久保俊太, 渡邉雄介, 木村成宏, 横尾健, 坂牧僚, 上村博輝, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 65 ( Suppl.1 ) A514 - A514 2024年4月

Portal biliopathyにより胆管消失症候群を来したと考えられる一例

木村究, 上村博輝, 渡邉雄介, 五十嵐聡, 土屋淳紀, 寺井崇二, 佐久間康成, 大西康晴, 眞田幸弘, 脇屋太一, 平田雄大, 大豆生田尚彦

肝臓 65 ( Suppl.1 ) A301 - A301 2024年4月

顕性肝性脳症の発症予測における,呼気中水素・メタン分析によるSIBO診断の有用性の検討

坂牧僚, 横山邦彦, 若林拓哉, 阿部寛幸, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 65 ( Suppl.1 ) A410 - A410 2024年4月

再生と老化研究のCutting edge-臨床への展開を踏まえて- S-005151の慢性肝疾患患者を対象にした第2相医師主導治験での線維化改善と肝機能改善効果の検証

土屋淳紀, 阿部寛幸, 寺井崇二

肝臓 65 ( Suppl.1 ) A78 - A78 2024年4月

ダサチニブ及びケルセチンは老化細胞除去剤としてMASHメダカモデルにおいて老化細胞を減少させ病態改善に寄与する

阿部寛幸, 弥久保俊太, 渡邉雄介, 木村成宏, 横尾健, 坂牧僚, 上村博輝, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 65 ( Suppl.1 ) A514 - A514 2024年4月

顕性肝性脳症の発症予測における,呼気中水素・メタン分析によるSIBO診断の有用性の検討

坂牧僚, 横山邦彦, 若林拓哉, 阿部寛幸, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 65 ( Suppl.1 ) A410 - A410 2024年4月

メダカを用いた脂肪性肝疾患の多臓器合併症の検討

上村顕也, 大越麻理奈, 木村淳史, 寺井崇二

肝臓 65 ( Suppl.1 ) A332 - A332 2024年4月

冨永顕太郎, Wells James, 寺井崇二

日本消化器病学会雑誌 121 ( 臨増総会 ) A186 - A186 2024年3月

小腸腫瘍の内視鏡診断・治療の最前線当院における原発性小腸癌13例の臨床的特徴

小島雄一, 川田雄三, 冨永顕太郎, 寺井崇二

日本消化器病学会雑誌 121 ( 臨増総会 ) A77 - A77 2024年3月

当院における慢性膵炎に伴う膵仮性嚢胞の合併症治療

林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 121 ( 臨増総会 ) A334 - A334 2024年3月

【膵癌基礎研究の最前線RELOADED】臓器選択的ハイドロダイナミック遺伝子導入法によるラット膵癌モデルの作製

柴田理, 上村顕也, 寺井崇二

胆と膵 45 ( 2 ) 123 - 126 2024年2月

【慢性肝臓病の克服を目指して】肝臓リハビリテーションと再生医療の開発状況

上村博輝, 土屋淳紀, 寺井崇二

日本内科学会雑誌 113 ( 1 ) 69 - 75 2024年1月

An updated review on the treatment for diversion colitis and pouchitis, with a focus on the utility of autologous fecal microbiota transplantation and its relationship with the intestinal microbiota.

Kentaro Tominaga, Yuichi Kojima, Yuzo Kawata, Kazuya Takahashi, Hiroki Sato, Atsunori Tsuchiya, Kenya Kamimura, Shuji Terai

Bioscience of microbiota, food and health 43 ( 3 ) 162 - 169 2024年

記述言語：英語掲載種別：研究論文（学術雑誌）

Diversion colitis (DC) is characterized by mucosal inﬂammation in the defunctioned segment of the colon following a colostomy or ileostomy. The major causes of DC are an increase in the number of aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon. However, its exact pathogenesis remains unknown. Various treatment strategies for DC have been explored, although none have been definitively established. Treatment approaches such as SCFAs, 5-aminosalicylic acid enemas, steroid enemas, and irrigation with fibers have been attempted, yielding various degrees of efficacies in mitigating mucosal inflammation. However, only individual case reports demonstrating the limited effect of the following therapies have been published: leukocytapheresis, dextrose (hypertonic glucose) spray, infliximab, an elemental diet, and coconut oil. The usefulness of probiotics for treating DC has recently been reported. Furthermore, fecal microbiota transplantation (FMT) has emerged as a promising treatment for DC. This review provides an update on the treatment strategies of DC, with a particular focus on FMT and its relationship with the intestinal microbiota. FMT may become the first choice of treatment for some patients in the future because of its low medical costs, ease of use, and minimal side effects. Furthermore, FMT can also be used for postoperative DC prophylaxis.

DOI： 10.12938/bmfh.2024-014

[A case of long-term efficacy of minocycline hydrochloride sclerotherapy combined with intra-cystic lavage for a symptomatic giant liver cyst].

Kazuya Ogawa, Kenya Kamimura, Soichi Ishii, Saori Endo, Natsuki Ishikawa, Hiroyuki Abe, Akira Sakamaki, Shuji Terai

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 121 ( 9 ) 769 - 776 2024年

記述言語：日本語掲載種別：研究論文（学術雑誌）

Herein, we report a case of a man with a large symptomatic hepatic cyst that gradually enlarged over a follow-up period of 15 years, which eventually caused epigastric fullness and obstructive jaundice. The patient underwent percutaneous cystic drainage followed by sclerotherapy using minocycline hydrochloride combined with intracystic lavage. The treatment resulted in a significant reduction in the hepatic cyst size, symptom improvement, and absence of recurrence for 670 days.

DOI： 10.11405/nisshoshi.121.769

Pyogenic Granuloma Accompanied by Esophageal Squamous Cell Carcinoma

Kazuya Takahashi, Chihiro Sato, Ken-ichi Mizuno, Shuji Terai

Internal Medicine 62 ( 24 ) 3715 - 3716 2023年12月

Correction: Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver. 国際誌

Masayoshi Ko, Kenya Kamimura, Takashi Owaki, Takuro Nagoya, Norihiro Sakai, Itsuo Nagayama, Yusuke Niwa, Osamu Shibata, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Ryosuke Inoue, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Shuji Terai

Disease models & mechanisms 16 ( 12 ) 2023年12月

Solid pseudopapillary neoplasm in a woman presenting with acute pancreatitis: a case report and review of literature.

Soichi Ishii, Hiroyuki Abe, Saori Endo, Shuhei Kondo, Nao Nakajima, Kazunao Hayashi, Akira Sakamaki, Takashi Kobayashi, Hajime Umezu, Shuji Terai

Clinical journal of gastroenterology 16 ( 6 ) 937 - 941 2023年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Solid pseudopapillary neoplasm (SPN) is a rare pancreatic tumor that typically affects young women in the body and tail of the pancreas. SPN is often asymptomatic in the early stages, so it is initially discovered as a large tumor. In this report, we experienced a case of a relatively small SPN discovered in the setting of acute pancreatitis. Because there have been few reports of SPN being discovered in the situation like our case, we report this case based on a review of the literature.

DOI： 10.1007/s12328-023-01850-6

【消化器領域における再生医療の現状と展望】間葉系幹細胞,細胞外小胞,ペプチドを用いた肝線維化改善・再生療法を目指して

土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 12 ) 973 - 979 2023年12月

MC4R、Maid両遺伝子欠損マウスを用いた慢性アルコール性肝障害モデルマウスの開発

坂牧僚, 酒井規裕, 小川和也, 木村成宏, 荒生祥尚, 阿部寛幸, 上村顕也, 寺井崇二

アルコールと医学生物学 42 44 - 46 2023年12月

MC4R、Maid両遺伝子欠損マウスを用いた慢性アルコール性肝障害モデルマウスの開発

坂牧僚, 酒井規裕, 小川和也, 木村成宏, 荒生祥尚, 阿部寛幸, 上村顕也, 寺井崇二

アルコールと医学生物学 42 44 - 46 2023年12月

EUS-FNAが診断に有用であった原発性舌下腺癌に合併した多発膵腫瘍の1例

渡邊誠, 五十嵐聡, 渡邊浩太朗, 山崎駿, 酒井規裕, 渡邉雄介, 冨永顕太郎, 高橋一也, 上村博輝, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 73回・95回 68 - 68 2023年11月

炎症性腸疾患に対する新規治療とバイオ治療再考多剤使用歴のある潰瘍性大腸炎難治例の臨床的特徴

小島雄一, 川田雄三, 冨永顕太郎, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 73回・95回 41 - 41 2023年11月

小腸内細菌異常増殖症(SIBO)の病態と臨床顕性肝性脳症の発症予測における、呼気中水素・メタン分析によるSIBO診断の有用性の検討

坂巻僚, 横山邦彦, 若林拓哉, 小島雄一, 川田雄三, 冨永顕太郎, 水野研一, 上村顕也, 寺井崇二

日本小腸学会学術集会プログラム・抄録集 61回 26 - 26 2023年11月

小腸内細菌異常増殖症(SIBO)の病態と臨床顕性肝性脳症の発症予測における、呼気中水素・メタン分析によるSIBO診断の有用性の検討

坂巻僚, 横山邦彦, 若林拓哉, 小島雄一, 川田雄三, 冨永顕太郎, 水野研一, 上村顕也, 寺井崇二

日本小腸学会学術集会プログラム・抄録集 61回 26 - 26 2023年11月

Achalasia phenotypes and prediction of per-oral endoscopic myotomy outcomes using machine learning. 国際誌

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: High-resolution manometry (HRM) and esophagography are used for achalasia diagnosis; however, achalasia phenotypes combining esophageal motility and morphology are unknown. Moreover, predicting treatment outcomes of per-oral endoscopic myotomy (POEM) in treatment-naïve patients remains an unmet need. METHODS: In this multicenter cohort study, we included 1,824 treatment-naïve patients diagnosed with achalasia. In total, 1,778 patients underwent POEM. Clustering by machine learning (ML) was conducted to identify achalasia phenotypes using patients' demographic data, including age, sex, disease duration, body mass index, and HRM/esophagography findings. ML models were developed to predict persistent symptoms (Eckardt score ≥3) and reflux esophagitis (RE) (Los Angeles grades A to D) after POEM. RESULTS: ML identified three achalasia phenotypes: phenotype 1, type I achalasia with a dilated esophagus (n=676; 37.0%); phenotype 2, type II achalasia with a dilated esophagus (n=203; 11.1%); phenotype 3, late-onset type I-III achalasia with a non-dilated esophagus (n=619, 33.9%). Types I and II achalasia in phenotypes 1 and 2 exhibited different clinical characteristics from those in phenotype 3, implying different pathophysiologies within the same HRM diagnosis. A predictive model for persistent symptoms exhibited an area under the curve (AUC) of 0.70. Pre-POEM Eckardt score ≥6 was the greatest contributing factor for persistent symptoms. The AUC for post-POEM RE was 0.61. CONCLUSION: Achalasia phenotypes combining esophageal motility and morphology indicated multiple disease pathophysiologies. ML helped develop an optimal risk stratification model for persistent symptoms with novel insights into treatment resistance factors.

DOI： 10.1111/den.14714

Improving diagnostic performance of coronavirus disease 2019 rapid antigen testing through computer-based feedback training using open-source experimental psychology software. 国際誌

Masato Matsuda, Kosuke Itoh, Takahiro Sugai, Yoshiki Hoshiyama, Toshiaki Kikuchi, Shuji Terai

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Rapid antigen testing (RAT) results are visually read as whether colored line is present or absent. The subjective interpretation potentially misses detecting weak lines due to lower analyte concentration in samples tested, requiring training. Although routine test experience has improved the result readout skills, it consumes time and resources. Therefore, we created a computer-based feedback training method using open-source experimental psychology software, wherein participants accumulate RAT result readout experience by repeatedly responding positive/negative to randomly presented pictures showing RAT results; then, they receive feedback on their answers as correct or incorrect and are asked to stare at the pictures again with the knowledge of correct answer. This study aimed to examine the training effects in improving the skills, using coronavirus disease 2019 (COVID-19) RAT. METHODS: Twenty-two medical technologists were randomly divided into two groups: the feedback-training and test-experience groups. Using several pictures showing positive and negative results of COVID-19 RAT, after examination of their initial result readout skills, feedback-training group received the feedback training, whereas test-experience group performed an equal number of tests without feedback to accumulate test experience, and their skills were examined again. The ratio of "positive" answers to the pictures showing positive results (i.e., hit rate) was statistically analyzed. RESULTS: The feedback-training group showed a significantly higher hit rate after their training, whereas the test-experience group did not. The feedback training effects were manifested in weak line detection. CONCLUSIONS: This computer-based feedback training method can be an effective tool for improving RAT result readout skills.

DOI： 10.1016/j.jiac.2023.10.019

Complementary role of peripheral and central autonomic nervous system on insulin-like growth factor-1 activation to prevent fatty liver disease. 国際誌

Itsuo Nagayama, Kenya Kamimura, Takashi Owaki, Masayoshi Ko, Takuro Nagoya, Yuto Tanaka, Marina Ohkoshi, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Shuji Terai

Hepatology international 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Insulin-like growth factor-1 (IGF-1) is involved in the pathology of non-alcoholic fatty liver disease (NAFLD) and ameliorates fatty infiltration in the liver. It is activated by growth hormone (GH); however, the role of GH-IGF-1 axis in NAFLD developmental phase has not been well identified. Therefore, in this study, we focused on the effect of IGF-1 in NAFLD pathology and GH excretion activation from the pituitary gland by peripheral autonomic neural pathways relaying liver-brain-gut pathway and by central neuropeptides. METHODS: GH and IGF-1 levels were assessed in wild-type and melanocortin-4 receptor knockout mice upon the development of diet-induced NAFLD. The contribution of the peripheral autonomic nervous system connecting the liver-brain-gut axis was assessed by its blockade using capsaicin and that of the central nervous system was assessed by the expression of hypothalamic brain-derived neurotrophic factor (BDNF) and corticotropin-releasing factor (CRH), which activates GH release from the pituitary gland. RESULTS: In the NAFLD mouse models, the levels of GH and IGF-1 increased (p < .05). Further, hepatic fatty infiltration was suppressed even under peripheral autonomic nervous system blockade (p < .001), which inhibited gastric ghrelin expression. In mice with peripheral autonomic nervous blockade, hypothalamic BDNF and CRH were inhibited (p < .05), resulting in GH and IGF-1 excretion, whereas other neuropeptides of somatostatin and cortistatin showed no changes. These complementary effects were canceled in melanocortin-4 receptor knockout mice, which diminished BDNF and CRH release control. CONCLUSIONS: Our study demonstrates that the release of IGF-1 by the nervous system is a key factor in maintaining the pathological homeostasis of NAFLD, suggesting its therapeutic potential.

DOI： 10.1007/s12072-023-10601-1

Analysis of distribution, collection, and confirmation of capacity dependency of small extracellular vesicles toward a therapy for liver cirrhosis. 国際誌

Nobutaka Takeda, Atsunori Tsuchiya, Masaki Mito, Kazuki Natsui, Yui Natusi, Yohei Koseki, Kei Tomiyoshi, Fusako Yamazaki, Yuki Yoshida, Hiroyuki Abe, Masayuki Sano, Taketomo Kido, Yusuke Yoshioka, Junichi Kikuta, Tohru Itoh, Ken Nishimura, Masaru Ishii, Takahiro Ochiya, Atsushi Miyajima, Shuji Terai

Inflammation and regeneration 43 ( 1 ) 48 - 48 2023年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The progression of liver fibrosis leads to portal hypertension and liver dysfunction. However, no antifibrotic agents have been approved for cirrhosis to date, making them an unmet medical need. Small extracellular vesicles (sEVs) of mesenchymal stem cells (MSCs) are among these candidate agents. In this study, we investigated the effects of sEVs of MSCs, analyzed their distribution in the liver post-administration, whether their effect was dose-dependent, and whether it was possible to collect a large number of sEVs. METHODS: sEVs expressing tdTomato were generated, and their uptake into constituent liver cells was observed in vitro, as well as their sites of uptake and cells in the liver using a mouse model of liver cirrhosis. The efficiency of sEV collection using tangential flow filtration (TFF) and changes in the therapeutic effects of sEVs in a volume-dependent manner were examined. RESULTS: The sEVs of MSCs accumulated mostly in macrophages in damaged areas of the liver. In addition, the therapeutic effect of sEVs was not necessarily dose-dependent, and it reached a plateau when the dosage exceeded a certain level. Furthermore, although ultracentrifugation was commonly used to collect sEVs for research purposes, we verified that TFF could be used for efficient sEV collection and that their effectiveness is not reduced. CONCLUSION: In this study, we identified some unknown aspects regarding the dynamics, collection, and capacity dependence of sEVs. Our results provide important fundamentals for the development of therapies using sEVs and hold potential implications for the therapeutic applications of sEV-based therapies for liver cirrhosis.

DOI： 10.1186/s41232-023-00299-x

自律神経経路を基軸とする脂肪性肝疾患の脂質代謝制御機構の解明と治療薬探索

機能性消化管疾患の病態解明と臨床応用腸管運動機能に関わる組織常在型マクロファージを有する腸管オルガノイドの開発

冨永顕太郎, Wells James, 寺井崇二

Gastroenterological Endoscopy 65 ( Suppl.2 ) 1809 - 1809 2023年10月

重症急性膵炎後Walled-off necrosisの内視鏡治療における最適なステントの選択

五十嵐聡, 林和直, 寺井崇二

Gastroenterological Endoscopy 65 ( Suppl.2 ) 2046 - 2046 2023年10月

高齢者の術後再建腸管結石例に対するダブルバルーン内視鏡下ERCPの検討

林和直, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 65 ( Suppl.2 ) 2022 - 2022 2023年10月

上村顕也, 大脇崇史, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増大会 ) A452 - A452 2023年10月

脂肪性肝疾患の個別化医療に向けた提案 NAFLDの病態進展に関わるエフェクターを標的とした治療法の開発

上村顕也, 薛徹, 寺井崇二

肝臓 64 ( Suppl.3 ) A743 - A743 2023年10月

Similarity of oncogenic protein expression in KRASG12D gene delivery-based rat pancreatic cancer model to that of human pancreatic cancer. 国際誌

Yuto Tanaka, Kenya Kamimura, Osamu Shibata, Kohei Ogawa, Chiyumi Oda, Hiroyuki Abe, Satoshi Ikarashi, Kazunao Hayashi, Takeshi Yokoo, Toshifumi Wakai, Shuji Terai

Biochemical and biophysical research communications 673 29 - 35 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The development of effective therapies and biomarkers for pancreatic cancer is an unmet clinical need. To address this, we have developed an easy-to-use pancreatic cancer rat animal model via pancreas-targeted hydrodynamic gene delivery of human pancreatic cancer-related genes. Our study aimed to determine the molecular similarity between the pancreatic tumor in the rat model and human pancreatic cancer. METHODS: KRASG12D gene-expressing plasmid was delivered to the pancreas of wild type rats via pancreas-targeted hydrodynamic gene delivery as previously reported. Tissue samples were collected at 5 weeks after the first gene delivery. The tumors developed in the rats were assessed for the expression of oncogenic proteins that are involved in human pancreatic cancer development. RESULTS: The development of a tumor mimicking pancreatic ductal adenocarcinoma was confirmed. The expression levels of Cyclin D1, c-Jun, IL-33, and Zip4 proteins in the tumor were immunohistochemically assessed and the correlation of the proteins was confirmed. The expression pattern showed similarity to that of surgically resected human pancreatic cancer tissues. CONCLUSIONS: Our study findings showing a similar pattern of oncogenic protein expression in novel KRASG12D gene-induced rat pancreatic cancer model and human pancreatic cancer will be useful for establishing novel tumor markers and therapeutic options for pancreatic cancer.

DOI： 10.1016/j.bbrc.2023.06.057

Development and validation of machine learning model for predicting treatment responders in patients with primary biliary cholangitis. 国際誌

Naruhiro Kimura, Kazuya Takahashi, Toru Setsu, Yusuke Horibata, Yusuke Kaneko, Haruka Miyazaki, Kohei Ogawa, Yuzo Kawata, Norihiro Sakai, Yusuke Watanabe, Hiroyuki Abe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 2023年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Ursodeoxycholic acid is the first-line treatment for primary biliary cholangitis, and treatment response is one of the factors predicting the outcome. To prescribe alternative therapies, clinicians might need additional information before deciphering the treatment response to ursodeoxycholic acid, contributing to a better patient prognosis. In this study, we developed and validated machine learning (ML) algorithms to predict treatment responses using pretreatment data. METHODS: This multicenter cohort study included collecting datasets from two data samples. Data 1 included 245 patients from 18 hospitals for ML development, and was divided into (i) training and (ii) development sets. Data 2 (iii: test set) included 51 patients from our hospital for validation. An extreme gradient boosted tree predicted the treatment response in the ML model. The area under the curve was used to evaluate the efficacy of the algorithm. RESULTS: Data 1 showed that patients complying with the Paris II treatment response had significantly lower serum alkaline phosphatase and total bilirubin levels than those who did not respond. Three factors, total bilirubin, total protein, and alanine aminotransferase levels were selected as essential variables for prediction. Data 2 showed that patients complying with the Paris II criteria had significantly high prothrombin time and low total bilirubin levels. The area under the curve of extreme gradient boosted tree was good for (ii) (0.811) and (iii) (0.856). CONCLUSIONS: We demonstrated the efficacy of ML in predicting the treatment response for patients with primary biliary cholangitis. Early identification of cases requiring additional treatment with our novel ML model may improve prognosis.

DOI： 10.1111/hepr.13966

【肝疾患とサルコペニア】総論肝疾患とサルコペニア未来のリハビリテーション医療楽しくないと続かない

肝疾患に対する再生医療のNew normal New Normalへの提案肝硬変に対する線維化改善を目指したトランスレーショナルリサーチ

土屋淳紀, 渡邉雄介, 寺井崇二

肝臓 64 ( Suppl.2 ) A570 - A570 2023年9月

多職種の肝炎医療コーディネーターとの連携による,院内におけるC型肝炎患者の拾い上げと紹介率向上の効果

荒生祥尚, 酒井規裕, 薛徹, 渡邉雄介, 木村成宏, 阿部寛幸, 坂牧僚, 上村博輝, 横尾健, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 64 ( Suppl.2 ) A634 - A634 2023年9月

寺井崇二, 上村博輝

日本消化器病学会雑誌 120 ( 9 ) 701 - 708 2023年9月

消化器病に対する低侵襲治療切除不能肝内胆管癌に対して肝動脈化学塞栓療法(TACE)および重粒子線治療を行った1例

内山敦司, 上村博輝, 木村莉菓, 佐藤千紘, 木村究, 渡邉雄介, 高橋一也, 五十嵐聡, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 39 ( 1 ) 37 - 37 2023年9月

Repurposable Drugs for Immunotherapy and Strategies to Find Candidate Drugs. 国際誌

Norihiro Sakai, Kenya Kamimura, Shuji Terai

Pharmaceutics 15 ( 9 ) 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Conventional drug discovery involves significant steps, time, and expenses; therefore, novel methods for drug discovery remain unmet, particularly for patients with intractable diseases. For this purpose, the drug repurposing method has been recently used to search for new therapeutic agents. Repurposed drugs are mostly previously approved drugs, which were carefully tested for their efficacy for other diseases and had their safety for the human body confirmed following careful pre-clinical trials, clinical trials, and post-marketing surveillance. Therefore, using these approved drugs for other diseases that cannot be treated using conventional therapeutic methods could save time and economic costs for testing their clinical applicability. In this review, we have summarized the methods for identifying repurposable drugs focusing on immunotherapy.

DOI： 10.3390/pharmaceutics15092190

【ここまで進んだ肝硬変診療】肝硬変症の次世代治療の開発抗線維化治療と肝再生療法

寺井崇二, 土屋淳紀, 渡邊雄介, 阿部寛幸

臨床消化器内科 38 ( 10 ) 1329 - 1333 2023年8月

【ここまで進んだ肝硬変診療】肝硬変症の次世代治療の開発抗線維化治療と肝再生療法

寺井崇二, 土屋淳紀, 渡邊雄介, 阿部寛幸

臨床消化器内科 38 ( 10 ) 1329 - 1333 2023年8月

Correction: Medaka as a model for human nonalcoholic steatohepatitis. 国際誌

Toshihiko Matsumoto, Shuji Terai, Toshiyuki Oishi, Shinya Kuwashiro, Koichi Fujisawa, Naoki Yamamoto, Yusuke Fujita, Yoshihiko Hamamoto, Makoto Furutani-Seiki, Hiroshi Nishina, Isao Sakaida

Disease models & mechanisms 16 ( 7 ) 2023年7月

細胞および細胞外小胞で拓く創薬モダリティ細胞外小胞を用いた肝硬変に対する線維化改善、修復療法の開発

土屋淳紀, 寺井崇二

日本DDS学会学術集会プログラム予稿集 39回 101 - 101 2023年7月

BCL11B expression in hepatocellular carcinoma relates to chemosensitivity and clinical prognosis. 国際誌

Hiroyuki Abe, Kenya Kamimura, Shujiro Okuda, Yu Watanabe, Jun Inoue, Yutaka Aoyagi, Toshifumi Wakai, Ryo Kominami, Shuji Terai

Cancer medicine 12 ( 14 ) 15650 - 15663 2023年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: B-cell lymphoma/leukemia 11B (BCL11B) is a subunit of SWI/SNF chromatin remodeling complexes and functions in cell cycle regulation and apoptosis upon DNA replication stress and damages via transcription. Many malignancies were reported to exhibit changes in BCL11B gene expression; however, no study has focused on the relationship between BCL11B and hepatocellular carcinoma, which potentially exhibits DNA replication stress and damages upon its oncogenesis. Thus, in this study, we examined the molecular characterization of BCL11B expression in hepatocellular carcinoma. METHODS AND RESULTS: The cumulative progression-free survival and overall survival were significantly longer in the clinical cases of BCL11B-negative hepatocellular carcinoma than BCL11B-positve cases. Microarray and real-time PCR analyses in hepatocellular carcinoma cell lines indicated a correlation between BCL11B and GATA6, a gene reported to be correlated with oncogenic activities and resistance to anthracycline, which is often used for hepatocellular carcinoma chemotherapy. Consequently, BCL11B-overexpressing cell lines exhibited resistance to anthracycline in cell growth assays and the resistance has been evidenced by the increased expression of BCL-xL in cell lines. The results were supported by the analyses of human HCC samples showing the correlation between BCL11B and GATA6 expressions. DISCUSSIONS AND CONCLUSION: Our results indicated that overexpression of BCL11B amplifies GATA6 expression in hepatocellular carcinoma in vitro and in vivo that leads to anti-apoptotic signal activation, and induces resistance to chemotherapy, which influenced the postoperative prognosis.

DOI： 10.1002/cam4.6167

Portal venous gas caused by barium swallow examination: An extremely rare clinical finding. 国際誌

Takuya Wakabayashi, Kentaro Tominaga, Akira Sakamaki, Shuji Terai

Clinical case reports 11 ( 7 ) e7480 2023年7月

記述言語：英語

We found an extremely rare case of PVG after a barium swallow examination. This may be related to vulnerable intestinal mucosa in the patient undergoing prednisolone treatment. Conservative therapy should be considered for patients with PVG without bowel ischemia or perforation. Caution should be exercised during barium examination undergoing prednisolone treatment.

DOI： 10.1002/ccr3.7480

エンドトキシン吸着療法を行い救命し得た重症胆道感染症の2例

細胞および細胞外小胞で拓く創薬モダリティ細胞外小胞を用いた肝硬変に対する線維化改善、修復療法の開発

土屋淳紀, 寺井崇二

日本DDS学会学術集会プログラム予稿集 39回 101 - 101 2023年7月

エンドトキシン吸着療法を行い救命し得た重症胆道感染症の2例

齋藤征爾, 坂田純, 滝沢一泰, 三浦宏平, 石川博補, 廣瀬雄己, 安藤拓也, 安部舜, 宗岡悠介, 田島陽介, 市川寛, 島田能史, 阿部寛幸, 小川光平, 寺井崇二, 若井俊文

新潟医学会雑誌 137 ( 7 ) 243 - 248 2023年7月

新潟医学会雑誌 137 ( 7 ) 243 - 248 2023年7月

Machine learning prediction model for treatment responders in patients with primary biliary cholangitis. 国際誌

Naruhiro Kimura, Kazuya Takahashi, Toru Setsu, Shu Goto, Suguru Miida, Nobutaka Takeda, Yuichi Kojima, Yoshihisa Arao, Kazunao Hayashi, Norihiro Sakai, Yusuke Watanabe, Hiroyuki Abe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 7 ( 6 ) 431 - 438 2023年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Treatment response to ursodeoxycholic acid may predict the prognosis of patients with primary biliary cholangitis (PBC). Recent studies have suggested the benefits of using machine learning (ML) to forecast complex medical predictions. We aimed to predict treatment response in patients with PBC using ML and pretreatment data. METHODS: We conducted a single-center retrospective study and collected data from 194 patients with PBC who were followed up for at least 12 months after treatment initiation. Patient data were analyzed with five ML models, namely random forest, extreme gradient boosting (XGB), decision tree, naïve Bayes, or logistic regression, to predict treatment response using the Paris II criteria. The established models were assessed using an out-of-sample validation. The area under the curve (AUC) was used to evaluate the efficacy of each algorithm. Overall survival and liver-related deaths were analyzed using Kaplan-Meier analysis. RESULTS: Compared to logistic regression (AUC = 0.595, P = 0.0219, 0.031 models), ML analyses showed significantly high AUC in the random forest (AUC = 0.84) and XGB (AUC = 0.83) models; however, the AUC was not significantly high for decision tree (AUC = 0.633) or naïve Bayes (AUC = 0.584) models. Kaplan-Meier analysis showed significantly improved prognoses in patients predicted to achieve the Paris II criteria by XGB (log-rank = 0.005 and 0.007). CONCLUSION: ML algorithms could improve treatment response prediction using pretreatment data, which could lead to better prognoses. In addition, the ML model using XGB could predict the prognosis of patients before treatment initiation.

DOI： 10.1002/jgh3.12915

急性腎障害を合併した消化器疾患における尿中NGAL測定による予後予測

エクソソーム研究の最前線間葉系幹細胞由来エクソソームによる肝硬変線維化改善を目指した研究開発

阿部寛幸, 武田信峻, 水戸將貴, 土屋淳紀, 寺井崇二

The Journal of Toxicological Sciences 48 ( Suppl. ) S54 - S55 2023年6月

IgG4関連疾患における診断・治療困難例に対する取り組み自己免疫性膵炎のステロイド治療導入後再燃例における臨床経過の検証

小川光平, 名古屋拓郎, 五十嵐聡, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 72回 40 - 40 2023年6月

胆膵内視鏡検査・治療における工夫とトラブルシューティング当院における副乳頭アプローチカニュレーション

名古屋拓郎, 小川光平, 五十嵐聡, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 72回 48 - 48 2023年6月

ヘパプラスチンテストを取り入れた出血原因鑑別の検査戦略後天性第V因子欠乏症における経験

松田将門, 山田隆, 古山悠里, 柴崎康彦, 関義信, 星山良樹, 寺井崇二, 瀧澤淳, 曽根博仁, 増子正義

日本血栓止血学会誌 34 ( 2 ) 262 - 262 2023年5月

ヘパプラスチンテストを取り入れた出血原因鑑別の検査戦略後天性第V因子欠乏症における経験

松田将門, 山田隆, 古山悠里, 柴崎康彦, 関義信, 星山良樹, 寺井崇二, 瀧澤淳, 曽根博仁, 増子正義

日本血栓止血学会誌 34 ( 2 ) 262 - 262 2023年5月

各種クロスミキシングテストで因子欠乏パターンを示した後天性第V因子欠乏症

山田隆, 松田将門, 関義信, 古山悠里, 柴崎康彦, 星山良樹, 寺井崇二, 増子正義, 瀧澤淳, 曽根博仁

日本血栓止血学会誌 34 ( 2 ) 263 - 263 2023年5月

急性肝不全・ACLF診療の未来予想図(現状と課題) 肝線維化と老化細胞の出現から考えたAcute on chronic liver failureの病態解明

渡邉雄介, 土屋淳紀, 寺井崇二

肝臓 64 ( Suppl.1 ) A78 - A78 2023年4月

FDA,PMDAデータベース20年の副作用報告から報告形態による国際比較の解析

上村博輝, 酒井規裕, 木村成宏, 薛徹, 土屋淳紀, 寺井崇二

肝臓 64 ( Suppl.1 ) A412 - A412 2023年4月

NASHメダカモデルにおける老化細胞除去剤としてのダサチニブ及びケルセチンの有用性に関する検証

阿部寛幸, 弥久保俊太, 酒井規裕, 木村成宏, 坂牧僚, 土屋淳紀, 上村顕也, 寺井崇二

肝臓 64 ( Suppl.1 ) A364 - A364 2023年4月

小島雄一, 渡邉雄介, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A393 - A393 2023年3月

消化器疾患とビッグデータインターネット普及による薬物関連有害事象報告の変遷 FDAの20年の副作用報告からの解析

上村博輝, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A40 - A40 2023年3月

十全大補湯と間葉系幹細胞の併用療法は肝硬変・急性肝障害モデルマウスにおいて効果的な抗炎症・抗線維化効果を及ぼす

野尻俊介, 土屋淳紀, 佐藤毅昂, 熊谷優, 茂木聡子, 岩澤貴宏, 小川雅裕, 竹内卓, 寺井崇二

肝臓 64 ( 3 ) 172 - 172 2023年3月

臨床応用を目指した消化器領域の再生医療研究肝硬変のエクソソーム治療を目指した基礎的検討

武田信峻, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A166 - A166 2023年3月

消化器診療とliquid biopsy 肝硬変の線維化の新たなエクソソームマーカー開発

土屋淳紀, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A159 - A159 2023年3月

肝線維化研究の最前線と治療への展開 HMGB1部分ペプチドを用いた肝線維化改善検証と医師主導治験

土屋淳紀, 渡邉雄介, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A77 - A77 2023年3月

膵癌早期診断の最前線 cStage 0/I膵癌の臨床像膵癌病態解析に関する多施設後方視的観察研究の結果より

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A135 - A135 2023年3月

当院における膵小病変に対するEUS-FNA/Bの成績

林和直, 小川光平, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 120 ( 臨増総会 ) A375 - A375 2023年3月

肥満モデルマウスを用いた、脂肪細胞の機能に着目した肥満制御メカニズムの解明

坂牧僚, 阿部寛幸, 上村顕也, 寺井崇二

新潟県医師会報 ( 876 ) 12 - 13 2023年3月

肝疾患における血中セロトニン値のバイオマーカーとしての有用性の検討

薛徹, 上村顕也, 寺井崇二

肝臓 64 ( 3 ) 171 - 171 2023年3月

Escherichia coli-derived outer-membrane vesicles induce immune activation and progression of cirrhosis in mice and humans. 国際誌

Kazuki Natsui, Atsunori Tsuchiya, Risa Imamiya, Mayuko Osada-Oka, Yui Ishii, Yohei Koseki, Nobutaka Takeda, Kei Tomiyoshi, Fusako Yamazaki, Yuki Yoshida, Riuko Ohashi, Yiwei Ling, Koji Ueda, Nobuko Moritoki, Kazuhiro Sato, Takahiro Nakajima, Yoshinori Hasegawa, Shujiro Okuda, Shinsuke Shibata, Shuji Terai

Liver international : official journal of the International Association for the Study of the Liver 43 ( 5 ) 1126 - 1140 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND & AIMS: Decompensated cirrhosis with fibrosis progression causes portal hypertension followed by an oedematous intestinal tract. These conditions weaken the barrier function against bacteria in the intestinal tract, a condition called leaky gut, resulting in invasion by bacteria and bacterial components. Here, we investigated the role of outer membrane vesicles (OMVs) of Escherichia coli which is the representative pathogenic gut-derived bacteria in patients with cirrhosis in the pathogenesis of cirrhosis. METHODS: We investigated the involvement of OMVs in humans using human serum and ascites samples and also investigated the involvement of OMVs from Escherichia coli in mice using mouse liver-derived cells and a mouse cirrhosis model. RESULTS: In vitro, OMVs induced inflammatory responses to macrophages and neutrophils, including the upregulation of C-type lectin domain family 4 member E (Clec4e), and induced the suppression of albumin production in hepatocytes but had a relatively little direct effect on hepatic stellate cells. In a mouse cirrhosis model, administration of OMVs led to increased liver inflammation, especially affecting the activation of macrophages, worsening fibrosis, and decreasing albumin production. Albumin administration weakened these inflammatory changes. In addition, multiple antibodies against bacterial components were increased with a progressing Child-Pugh grade, and OMVs were detected in ascites of patients with decompensated cirrhosis. CONCLUSIONS: In conclusion, OMVs induce inflammation, fibrosis and suppression of albumin production, affecting the pathogenesis of cirrhosis. We believe that our study paves the way for the future prevention and treatment of cirrhosis.

DOI： 10.1111/liv.15539

Performance characteristics of 5 numerical indexes in mixing test interpretation under coexistence of lupus anticoagulant and coagulation factor deficiency. 国際誌

Masato Matsuda, Yoshiki Hoshiyama, Kazuei Ogawa, Mari Emmi, Shuji Terai, Masato Moriyama

Research and practice in thrombosis and haemostasis 7 ( 2 ) 100065 - 100065 2023年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The mixing test is useful to investigate the cause of unexpectedly prolonged activated partial thromboplastin time (APTT). Several indexes are available for distinguishing correction from non-correction (ie, factor deficiency from inhibitors), but their performance characteristics may differ because of their different formulas. Furthermore, it is unclear how each index performs under the coexistence of factor deficiency and inhibitors. OBJECTIVES: The objective of this study was to examine the differences in indexes, depending on factor VIII activity (FVIII:C) levels and lupus anticoagulant (LA) titers in test samples. METHODS: APTT was measured in spiked samples with various FVIII:C levels and LA titers, normal pooled plasma (NPP), and their 4:1, 1:1, and 1:4 mixtures. The following 5 indexes were calculated: index of circulating anticoagulant, mixing test normalized ratio, 4:1 and 1:1 percent corrections, and an APTT difference between the 1:1 mixture and NPP. The samples with LA, showing correction, were measured for FVIII:C in a one-stage assay to check parallelism. RESULTS: All indexes showed correction under FVIII deficiency and non-correction under higher LA titers. However, under lower LA titers, some indexes showed non-correction but others showed correction because of dilution effects and variations in formulas and/or sample mix ratios. The differences among the indexes were more pronounced under coexistent FVIII deficiency and LA, even though LA titers were equal in the tested samples; samples with lower FVIII:C showed correction, whereas those with normal FVIII:C showed non-correction. The samples tested for FVIII:C showed non-parallelism. CONCLUSION: Each index had different performance characteristics to LA samples, which were pronounced under low FVIII:C levels in test samples.

DOI： 10.1016/j.rpth.2023.100065

【高齢者の消化器疾患-最新の診断と治療-】肝硬変・肝細胞癌

急性肝不全に対する治療内科,外科の立場から新潟県での急性肝不全診療ネットワークの構築とOn line HD導入への取り組み

薛徹, 上村博輝, 坂牧僚, 横尾健, 上村顕也, 土屋淳紀, 高村昌明, 寺井崇二

肝臓 64 ( 2 ) 92 - 93 2023年2月

坂牧僚, 寺井崇二

日本臨床 81 ( 2 ) 256 - 260 2023年2月

Analysis of Genetic Relatedness between Gastric and Oral Helicobacter pylori in Patients with Early Gastric Cancer Using Multilocus Sequence Typing

Ryoko Nagata, Hiroki Sato, Shoji Takenaka, Junji Yokoyama, Shuji Terai, Hitomi Mimuro, Yuichiro Noiri

International Journal of Molecular Sciences 24 ( 3 ) 2211 - 2211 2023年1月

掲載種別：研究論文（学術雑誌）出版者・発行元：MDPI AG

The oral cavity is the second most colonized site of Helicobacter pylori after the stomach. This study aimed to compare the genetic relatedness between gastric and oral H. pylori in Japanese patients with early gastric cancer through multilocus sequence typing (MLST) analysis using eight housekeeping genes. Gastric biopsy specimens and oral samples were collected from 21 patients with a fecal antigen test positive for H. pylori. The number of H. pylori allelic profiles ranged from zero to eight since the yield of DNA was small even when the nested PCR was performed. MLST analysis revealed that only one patient had a matching oral and gastric H. pylori genotype, suggesting that different genotypes of H. pylori inhabit the oral cavity and gastric mucosa. The phylogenetic analysis showed that oral H. pylori in six patients was similar to gastric H. pylori, implying that the two strains are related but not of the same origin, and those strains may be infected on separate occasions. It is necessary to establish a culture method for oral H. pylori to elucidate whether the oral cavity acts as the source of gastric infection, as our analysis was based on a limited number of allele sequences.

DOI： 10.3390/ijms24032211

Analysis of drug-induced liver-related adverse event trend reporting between 1997 and 2019. 国際誌

Hiroteru Kamimura, Toru Setsu, Naruhiro Kimura, Makoto Miyazawa, Shota Kaneko, Kenya Kamimura, Atsunori Tsuchiya, Yoshihiro Uesawa, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 53 ( 6 ) 556 - 568 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: This study aimed to analyze the current trends of drug-induced liver-related adverse events in the Food and Drug Administration Adverse Event Reporting System (FAERS) and Japanese Adverse Drug Event Report (JADER) databases. METHODS: The characteristics of implicated drugs were investigated by analyzing big data on drug-induced liver-related adverse events over the past 20 years in FAERS, comparing drug rankings between the JADER and FAERS databases, and calculating rankings of drugs inducing liver-related adverse events using the Medical Dictionary for Regulatory Activities Terminology. RESULTS: In the 452,272 cases registered in FAERS from 1997 to 2019, warfarin, paracetamol, and adalimumab were the drugs most related to DILI. In the 38,919 cases registered in the JADER from 2004 to 2019, sorafenib, nivolumab, and herbal extracts were the drugs most related to DILI. No associations were found between the top 30 drugs in either of the two databases. Notably, the number of drug-induced liver-related adverse event reports and total adverse events has sharply increased in recent years. CONCLUSIONS: Although liver-related adverse events are largely caused by host immunity and other constitutional factors, differences in primary diseases, countries, and historical backgrounds lead to differences in the number of reports. Securing an appropriate database and a mechanism to collect real-time information on the frequency of adverse drug reactions is warranted. This article is protected by copyright. All rights reserved.

DOI： 10.1111/hepr.13883

Navitoclax improves acute-on-chronic liver failure by eliminating senescent cells in mice. 国際誌

Yusuke Watanabe, Hiroyuki Abe, Naruhiro Kimura, Yoshihisa Arao, Natsuki Ishikawa, Maeda Yuichiro, Toru Setsu, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 53 ( 5 ) 460 - 472 2023年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Acute-on-chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263/navitoclax (Navi) that selectively eliminates senescent cells. METHODS: Irradiation-induced senescent hepatocytes were used for in vitro evaluation of the effects of Navi on ACLF (n = 6 for each group). Lipopolysaccharide- and carbon tetrachloride-induced ACLF mouse model was used for in vivo evaluation of the effects of Navi administration compared with the control using one-way or two-way analysis of variance, followed by Student's t-test or Kruskal-Wallis test. The effects on the senescence-associated secretory phenotype (n = 8 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (n = 8 for each group), were investigated using real-time polymerase chain reaction, immunohistochemistry, and enzyme analysis. RESULTS: Navi eliminated irradiation-induced senescent hepatocytes in vitro, leading to non-senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver in vivo, resulting in downregulation of mRNA expression of senescence-associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non-senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration in vitro and in vivo. CONCLUSIONS: Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence-associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.

DOI： 10.1111/hepr.13879

Reducing relapse through maintenance steroid treatment can decrease the cancer risk in patients with IgG4-sclerosing cholangitis: Based on a Japanese nationwide study

Kubota, K., Kamisawa, T., Nakazawa, T., Tanaka, A., Naitoh, I., Kurita, Y., Takikawa, H., Unno, M., Kawa, S., Masamune, A., Nakamura, S., Okazaki, K., Furumatsu, K., Sawai, S., Goto, T., Okumura, T., Suzuki, D., Otsuka, M., Kobori, I., Tamano, M., Koizumi, M., Hiasa, Y., Kawabe, N., Hirooka, Y., Yamamoto, S., Asano, Y., Inui, K., Horiguchi, A., Watanabe, H., Toya, D., Hatayama, K., Ueki, T., Kinoshita, N., Sugimoto, M., Ohira, H., Mukai, T., Tomita, E., Iwata, K., Shimizu, S., Suetsugu, J., Shimizu, M., Tsuji, K., Ishida, R., Ito, M., Furukawa, R., Sakamoto, N., Araki, M., Tanno, S., Sakamoto, Y., Ito, T., Takai, S., Ikeya, S., Yamada, T., Kudara, N., Shimizu, A., Hanada, K., Ichiki, Y., Kitada, H., Hifumi, M., Kimura, H., Kurosaki, M., Izumi, N., Sumi, H., Haruta, J.-I., Hayashi, K., Harada, R., Inoue, M., Nakamura, S., Ito, T., Tomishima, K., Isayama, H., Oura, K., Masaki, T., Shimokawahara, N., Tanoue, S., Maemura, K., Ido, A., Mizushima, I., Kawano, M., Yoshida, K., Naganuma, M., Murata, M., Nishio, A., Fujita, Y., Teratani, T., Matsubara, S., Tamai, H., Yoshida, Y., Azemoto, R., Kamata, K., Watanabe, T., Kurosu, T., Koizumi, W., Fujita, J., Seki, H., Ueda, Y., Fukumoto, T., Kousaki, T., Uchida, K., Ochiai, T., Kawasaki, T., Tanaka, M., Ishida, E., Notohara, K., Mori, H., Mori, T., Kawabata, H., Miyata, M., Sakagami, J., Itoh, Y., Shiokawa, M., Seno, H., Watanabe, N., Kataoka, H., Aoki, T., Fujishiro, M., Niihara, T., Nishimata, H., Mitoro, A., Yoshiji, H., Yoshida, M., Ikeda, M., Tomita, K., Hokari, R., Hayasaka, K., Amano, Y., Shioji, K., Hayashi, K., Terai, S., Nakajima, M., Yamahana, J., Matsumoto, R., Kikuchi, H., Kanamori, A., Kiriyama, S., Iwatsu, S., Kato, Y., Horiguchi, S., Yagi, T., Okada, H., Ohkawa, K., Hirao, M., Hiramatsu, N., Oza, N., Imamura, H., Baba, T., Nakano, S., Shinobi, T., Ryozawa, S., Motoya, M., Nakase, H., Kinoshita, N., Ito, K., Miyake, T., Kohge, N., Tobita, H., Joshita, S., Umemura, T., Kawaguchi, S., Ohno, K., Sonobe, K., Satoh, A., Shimosegawa, T., Miura, F., Yagi, M., Sano, K., Kin, T., Katanuma, A., Koike, K., Miura, S., Kawashima, Y., Kagawa, T., Azuma, S., Watanabe, M., Honjyo, M., Itoi, T., Honda, A., Kobayashi, K., Asano, T., Mizuno, S., Koike, K., Nishino, T., Taniguchi, H., Tajiri, K., Yasuda, I., Tanaka, Y., Oe, S., Harada, M., Kurata, M., Fukasawa, M., Enomoto, N., Kawaji, Y., Kitano, M., Nishise, Y., Hirakawa, H., Ishizawa, T., Ueno, Y., Kaino, M., Fujimoto, Y., Sakaida, I.

Journal of Gastroenterology and Hepatology (Australia) 38 ( 4 ) 2023年

[Toward liver fibrosis amelioration and regenerative therapy using mesenchymal stem cells, extracellular vesicles, and peptides].

Atsunori Tsuchiya, Shuji Terai

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 120 ( 12 ) 973 - 979 2023年

Curative Management After Endoscopic Resection for Esophageal Squamous Cell Carcinoma Invading Muscularis Mucosa or Shallow Submucosal Layer–Multicenter Real-World Survey in Japan

Chikatoshi Katada, Tetsuji Yokoyama, Dai Hirasawa, Toshiro Iizuka, Daisuke Kikuchi, Tomonori Yano, Takuya Hombu, Toshiyuki Yoshio, Shoichi Yoshimizu, Hiroyuki Ono, Yohei Yabuuchi, Shuji Terai, Satoru Hashimoto, Kazuya Takahashi, Shinji Tanaka, Yuji Urabe, Miwako Arima, Satoshi Tanabe, Takuya Wada, Yasuaki Furue, Tsuneo Oyama, Akiko Takahashi, Yasutoshi Sakamoto, Manabu Muto

American Journal of Gastroenterology 118 ( 7 ) 1175 - 1183 2022年12月

掲載種別：研究論文（学術雑誌）出版者・発行元：Ovid Technologies (Wolters Kluwer Health)

INTRODUCTION:

Curative management after endoscopic resection (ER) for esophageal squamous cell carcinoma (ESCC), which invades the muscularis mucosa (pMM-ESCC) or shallow submucosal layer (pSM1-ESCC), has been controversial.

METHODS:

We identified patients with pMM-ESCC and pSM1-ESCC treated by ER. Outcomes were the predictive factors for regional lymph node and distant recurrence, and survival data were based on the depth of invasion, lymphovascular invasion (LVI), and additional treatment immediately after ER.

RESULTS:

A total of 992 patients with pMM-ESCC (n = 749) and pSM1-ESCC (n = 243) were registered. According to the multivariate Cox proportional hazards analysis, pSM1-ESCC (hazard ratio = 1.88, 95% confidence interval 1.15–3.07, P = 0.012) and LVI (hazard ratio = 6.92, 95% confidence interval 4.09–11.7, P < 0.0001) were associated with a risk of regional lymph node and distant recurrence. In the median follow-up period of 58.6 months (range 1–233), among patients with risk factors (pMM-ESCC with LVI or pSM1-ESCC), the 5-year overall survival rates, relapse-free survival rates, and cause-specific survival rates of patients with additional treatment were significantly better than those of patients without additional treatment; 85.4% vs 61.5% (P < 0.0001), 80.5% vs 53.3% (P < 0.0001), and 98.5% vs 93.1% (P = 0.004), respectively. There was no difference in survival rate between the chemoradiotherapy and surgery groups.

DISCUSSION:

pSM1 and LVI were risk factors for metastasis after ER for ESCC. To improve the survival, additional treatment immediately after ER, such as chemoradiotherapy or surgery, is effective in patients with these risk factors.

DOI： 10.14309/ajg.0000000000002106

Basic points to consider regarding the preparation of extracellular vesicles and their clinical applications in Japan

Tsuchiya, A., Terai, S., Horiguchi, I., Homma, Y., Saito, A., Nakamura, N., Sato, Y., Ochiya, T., Kino-oka, M.

Regenerative Therapy 21 19 - 24 2022年12月

Edwardsiella tardaによる大量膿瘍をきたした肝硬変患者の1例症例報告(Massive empyema with Edwardsiella tarda in a patient with liver cirrhosis: a case report)

水戸將貴, 木村成宏, 山崎華子, 神保遼, 小島雄一, 荒生祥尚, 林和直, 土屋淳紀, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 71回・93回 47 - 47 2022年12月

HBx and YAP expression could promote tumor development and progression in HBV-related hepatocellular carcinoma. 国際誌

Chiyumi Oda, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Yuto Tanaka, Toru Setsu, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Satoshi Kofuji, Toshifumi Wakai, Hiroshi Nishina, Shuji Terai

Biochemistry and biophysics reports 32 101352 - 101352 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) accounts for 10%-20% of the total HCC numbers. Its clinical features include the occurrence in the younger generation, large tumors, and poor prognosis. The contribution of hepatitis B virus X (HBx) protein in hepatocytes during activation of various oncogenic pathways has been reported. We aimed to assess the possible association between HBx and Yes-associated protein (YAP) expression in the liver tissue and the clinical features of HBV-related HCC. Methods: The relationship between HBx and YAP expression was examined in vivo using HCC tumor and peritumor tissues (n = 55). The clinical information including tumor size, marker, and the prognosis was assessed with protein expressions. The in vitro gene expression analyses were conducted using HBx- and YAP-overexpressing HCC cell lines. Results: Among 19 cases of HBV-related, 17 cases of hepatitis C virus (HCV)-related, and 19 cases of nonviral-related HCC, the HBV-related tumor showed the largest size. The HBx-stained area in the tumor and peritumor tissue showed a significant correlation with tumor size and serum α-fetoprotein level. YAP expression was higher in HBV-related tumor tissue than in the peritumor tissue and HCV-related tumor. Additionally, HBx and YAP protein expressions are correlated and both expressions in the tumor contributed to the poor prognosis. An in vitro study demonstrated that HBx and YAP overexpression in the hepatocytes activate the various oncogenic signaling pathways. Conclusions: Our study demonstrated that YAP expression in the liver of HBV-infected patients might be the key factor in HBV-related HCC development and control of tumor-related features.

DOI： 10.1016/j.bbrep.2022.101352

Gene panel testing detects important genetic alterations in ulcerative colitis-associated colorectal neoplasia. 国際誌

Yoshifumi Shimada, Mae Nakano, Ken-Ichi Mizuno, Junji Yokoyama, Akio Matsumoto, Kana Tanaka, Hidehito Oyanagi, Masato Nakano, Yuki Hirose, Hiroshi Ichikawa, Jun Sakata, Hitoshi Kameyama, Yasumasa Takii, Mika Sugai, Yiwei Ling, Shiho Takeuchi, Shujiro Okuda, Shuji Terai, Yoichi Ajioka, Toshifumi Wakai

Oncology letters 24 ( 6 ) 442 - 442 2022年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Ulcerative colitis-associated neoplasia (UCAN) harbors unique genetic alterations and mutational tendencies. The clinical application of gene panel testing enables precision medicine by tailoring treatment to individual gene alterations. We hypothesized that gene panel testing may detect clinically important genetic alterations in UCAN, with potential usefulness for the diagnosis and treatment of UCAN. In the present study, gene panel testing was used to identify genetic alterations in UCAN, and the possibility of clinical utility of gene panel testing in UCAN was investigated. The present study included 15 patients with UCAN, and gene panel testing was performed to identify genetic alterations associated with diagnosis and treatment. Genetic alterations of UCAN were compared with those of 203 patients with sporadic colorectal cancer (CRC). APC and PTEN mutations were less frequent, while RNF43 frameshift or nonsense mutations were more frequent in UCAN compared with sporadic CRC. TP53 mutations were identified in 13/15 patients (87%) with UCAN. Notably, 4/15 patients (27%) with UCAN had no genetic alterations other than TP53 mutation, while this occurred in 1/203 patients (0.5%) with sporadic CRC (P<0.001). Microsatellite instability-high was identified in 2/15 patients (13%) with UCAN. Mutational signature 3, which is associated with homologous recombination deficiency, was detected in 14/15 patients (93%) with UCAN, and enriched in UCAN compared with sporadic CRC (P=0.030). In conclusion, gene panel testing can detect important genetic alterations that can be useful for diagnosis and treatment in UCAN, and may provide clinicians with important information for tailored treatment strategies.

DOI： 10.3892/ol.2022.13562

術後再建腸管例の悪性胆道狭窄に対するバルーン内視鏡下胆道ドレナージの有用性

名古屋拓郎, 寺井崇二, 林和直, 五十嵐聡, 小川光平

ENDOSCOPIC FORUM for digestive disease 38 ( 2 ) 153 - 153 2022年12月

糖鎖欠損トランスフェリン値はγ-GTP値と相補的にアルコール性肝硬変の予後不良に関連する

坂牧僚, 小山究太郎, 酒井規裕, 阿部寛幸, 上村顕也, 寺井崇二

アルコールと医学生物学 41 71 - 73 2022年12月

記述言語：日本語出版者・発行元：梵天書房

アルコール性肝硬変症例67例(男性86.6%:年齢中央値65歳)を対象に、糖鎖欠損トランスフェリン(CDT)値とγ-GTP値と予後の関連について後方視的に検討した。経過観察期間は3年とした。Cox回帰分析の結果、%CDT値は単変量で有意な予後不良因子であったが多変量では抽出されず、γ-GTP高値が独立した予後不良因子であることが分かった。対象を%CDT値およびγ-GTP値ともに正常値であった12例(1群)、一方が高値であった34例(2群)、両方とも高値であった21例(3群)に分けて予後比較した。その結果、3年生存率は1群が100.0%で有意に予後良好であった。以上より、%CDTかγ-GTPの一方が高値であると予後不良に関連することが示された。

Two rare pancreatic parenchymal hemorrhagic lesions associated with acute pancreatitis in acute liver failure: a case report and literature review.

Ryo Jimbo, Yoshihisa Arao, Atsunori Tsuchiya, Hanako Yamazaki, Masaki Mito, Yuichi Kojima, Yuji Kobayashi, Naruhiro Kimura, Kazunao Hayashi, Shuji Terai

Clinical journal of gastroenterology 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Acute pancreatitis is an uncommon occurrence in acute liver failure. Furthermore, such cases are rarely complicated by parenchymal hemorrhages. Herein, we report the case of a 69-year-old male patient with multiple pancreatic parenchymal hemorrhages concomitant with acute liver failure. The patient underwent conservative treatment for acute liver failure caused by hepatitis B virus infection. Plain computed tomography on the 30th day revealed two high-density mass lesions in the pancreatic body and tail, which were suspected to be multiple pancreatic parenchymal hemorrhages. Despite restarting gabexate mesylate, the patient died of multiple organ failure on the 49th day. The clinical information of the present case and our literature review of 61 similar cases in 43 case reports identified via a systematic keyword search of the PubMed database, which described acute pancreatitis concomitant with acute hepatitis and acute liver failure, will aid physicians in the diagnosis and treatment of this rare condition.

DOI： 10.1007/s12328-022-01738-x

Cell-free and concentrated ascites reinfusion therapy versus large-volume paracentesis for the treatment of cirrhotic patients with refractory ascites: A multicenter prospective observational study. 国際誌

Tatsunori Hanai, Hideto Kawaratani, Junji Nagano, Hirokazu Suii, Akira Sakamaki, Yoshitaka Arase, Hiroyuki Nakanishi, Tomomi Kogiso, Tomomi Okubo, Takao Miwa, Shogo Shimizu, Shuhei Hige, Masanori Atsukawa, Masahito Shimizu, Masayuki Kurosaki, Shuji Terai, Tatehiro Kagawa, Katsutoshi Tokushige, Hitoshi Yoshiji

Hepatology research : the official journal of the Japan Society of Hepatology 53 ( 3 ) 238 - 246 2022年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Cell-free and concentrated ascites reinfusion therapy (CART) and large-volume paracentesis (LVP) with albumin infusion are useful for managing refractory ascites (RA). However, it remains unclear which therapy is more effective in patients with cirrhosis with RA. METHODS: From June 2018 to March 2022, 25 patients with RA treated with CART or LVP with albumin infusion were enrolled in this multicenter prospective observational study to investigate the number of abdominal paracenteses, albumin preparations used, and drainage volume during an 8-week observation period. RESULTS: Among all patients at entry (median age, 63 years; 52% men; 60% Child-Pugh B and 40% Child-Pugh C), 92% were treated with furosemide (median, 20 mg/day), 92% with spironolactone (25 mg/day), and all with tolvaptan (7.5 mg/day). Patients with RA had a poor health-related quality of life (HRQOL) and prominent ascites-related symptoms. Four of the 20 eligible patients were treated with CART, 11 with LVP with albumin infusion, and five with their combination. The median number of paracenteses, total drainage volume, and albumin infusions were 1.5, 7.4 L, and 0, respectively, in the CART group; 5.0, 22.0 L, and 5.0, respectively, in the LVP group; and 5.0, 30.0 L, and 5.0, respectively in their combination group. The treatment effects did not differ significantly among the three groups regarding weight loss, liver function, renal function, electrolytes, and HRQOL. However, patients treated with CART had fewer paracenteses and albumin infusions than those treated with LVP. CONCLUSIONS: CART and LVP have comparable therapeutic efficacy for RA in patients with cirrhosis.

DOI： 10.1111/hepr.13860

Weakly Supervised Multiple Instance Learning for Liver Cirrhosis Classification using Ultrasound Images

Yusuke Fujita, Kaito Ishihara, Kazuma Nakata, Yoshihiko Hamamoto, Makoto Segawa, Isao Sakaida, Yoshihiro Mitani, Shuji Terai

2022 7th International Conference on Intelligent Informatics and Biomedical Science (ICIIBMS) 2022年11月

Early‐phase prothrombin time‐international normalized ratio in acute liver injury indicates the timing of therapeutic intervention and predicts prognostic improvement

Kotaro Kumagai, Seiichi Mawatari, Akihiro Moriuchi, Kohei Oda, Yasuhiro Takikawa, Naoya Kato, Shigeto Oda, Kazuaki Inoue, Shuji Terai, Takuya Genda, Masahito Shimizu, Isao Sakaida, Satoshi Mochida, Akio Ido

Hepatology Research 53 ( 2 ) 160 - 171 2022年11月

【再生医療の現状と展望】間葉系幹細胞を用いた肝疾患の再生医療

土屋淳紀, 寺井崇二

BIO Clinica 37 ( 12 ) 1089 - 1093 2022年11月

小児NAFLD患者の背景疾患と移行医療への課題

上村博輝, 佐藤毅昂, 山崎文紗子, 坂牧僚, 土屋淳紀, 寺井崇二, 長崎啓祐, 齋藤昭彦

肥満研究 28 ( Suppl. ) 290 - 290 2022年11月

小児NAFLD患者の背景疾患と移行医療への課題

上村博輝, 佐藤毅昂, 山崎文紗子, 坂牧僚, 土屋淳紀, 寺井崇二, 長崎啓祐, 齋藤昭彦

肥満研究 28 ( Suppl. ) 290 - 290 2022年11月

Letrozole ameliorates liver fibrosis through the inhibition of the CTGF pathway and 17β-hydroxysteroid dehydrogenase 13 expression.

Norihiro Sakai, Kenya Kamimura, Hirotaka Miyamoto, Masayoshi Ko, Takuro Nagoya, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Hiroyuki Soki, Ayako Tokunaga, Tatsuo Inamine, Mikiro Nakashima, Hatsune Enomoto, Kazuki Kousaka, Hidehisa Tachiki, Kaname Ohyama, Shuji Terai

Journal of gastroenterology 58 ( 1 ) 53 - 68 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: To establish a treatment option for liver fibrosis, the possibility of the drug repurposing theory was investigated, with a focus on the off-target effects of active pharmaceutical ingredients. METHODS: First, several active pharmaceutical ingredients were screened for their effects on the gene expression in the hepatocytes using chimeric mice with humanized hepatocytes. As per the gene expression-based screening assay for 36 medications, we assessed the mechanism of the antifibrotic effect of letrozole, a third-generation aromatase inhibitor, in mouse models of liver fibrosis induced by carbon tetrachloride (CCl4) and a methionine choline-deficient (MCD) diet. We assessed liver histology, serum biochemical markers, and fibrosis-related gene and protein expressions in the hepatocytes. RESULTS: A gene expression-based screening assay revealed that letrozole had a modifying effect on fibrosis-related gene expression in the hepatocytes, including YAP, CTGF, TGF-β, and CYP26A1. Letrozole was administered to mouse models of CCl4- and MCD-induced liver fibrosis and it ameliorated the liver fibrosis. The mechanisms involved the inhibition of the Yap-Ctgf profibrotic pathway following a decrease in retinoic acid levels in the hepatocytes caused by suppression of the hepatic retinol dehydrogenase, Hsd17b13 and activation of the retinoic acid hydrogenase, Cyp26a1. CONCLUSIONS: Letrozole slowed the progression of liver fibrosis by inhibiting the Yap-Ctgf pathway. The mechanisms involved the modification of the Hsd17b13 and Cyp26a1 expressions led to the suppression of retinoic acid in the hepatocytes, which contributed to the activation of Yap-Ctgf pathway. Because of its off-target effect, letrozole could be repurposed for the treatment of liver fibrosis. The third-generation aromatase inhibitor letrozole ameliorated liver fibrosis by suppressing the Yap-Ctgf pathway by partially modifying the Hsd17b13 and Cyp26a1 expressions, which reduced the retinoic acid level in the hepatocytes. The gene expression analysis using chimeric mice with humanized liver revealed that the mechanisms are letrozole specific and, therefore, may be repurposed for the treatment of liver fibrosis.

DOI： 10.1007/s00535-022-01929-w

門脈圧亢進症に対する診断・治療における新たな挑戦機械学習を用いた慢性心不全に続発した肝臓への障害(Cardiac Hepatopathy)の画像解析

肝再生・移植医療への新規トランスレーショナルリサーチ肝硬変に対するHMGB1部分ペプチドを用いた基礎研究から医師主導治験実施へ

土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.3 ) A710 - A710 2022年10月

肝硬変,肝癌治療薬の薬物関連有害事象報告の国際比較把握とその解釈による今後のマネージメント

上村博輝, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.3 ) A792 - A792 2022年10月

機械学習を用いた上部内視鏡施行時の咽頭老化の予測

上村博輝, 小島雄一, 高橋一也, 高綱将史, 平野正明, 政二文明, 水野研一, 横山純二, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増大会 ) A812 - A812 2022年10月

三井田秀, 上村博輝, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増大会 ) A640 - A640 2022年10月

重症急性膵炎後Walled-off necrosisの内視鏡治療におけるLumen apposing metal stentの有効性

林和直, 五十嵐聡, 小川光平, 寺井崇二

Gastroenterological Endoscopy 64 ( Suppl.2 ) 2126 - 2126 2022年10月

ガイドライン改訂後の膵炎診療の現状と課題重症急性膵炎後Walled-off necrosisの経過における抗菌薬投与の影響

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増大会 ) A534 - A534 2022年10月

Acute-on-chronic liver failure(ACLF):わが国の現状と今後の課題 ACLFの新規治療開発に向けた基盤研究

渡邉雄介, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.2 ) A508 - A508 2022年9月

慢性肝疾患におけるTGFβ3の発現と肝予備能との関連性についての検討

阿部寛幸, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 上村博輝, 坂牧僚, 横尾健, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.2 ) A597 - A597 2022年9月

大腸菌の外膜小胞は肝硬変での更なる炎症・線維化増悪に寄与する

夏井一輝, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.2 ) A593 - A593 2022年9月

アテゾリズマブ+ベバシズマブ併用療法の非奏効例におけるLate line移行時期についての検討

横尾健, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.2 ) A582 - A582 2022年9月

慢性肝疾患におけるTGFβ3の発現と肝予備能との関連性についての検討

阿部寛幸, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 上村博輝, 坂牧僚, 横尾健, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.2 ) A597 - A597 2022年9月

ウイルス駆除時代における,院内非専門医での効果的なC型肝炎患者の拾い上げ

荒生祥尚, 酒井規裕, 寺井崇二

肝臓 63 ( Suppl.2 ) A557 - A557 2022年9月

アテゾリズマブ+ベバシズマブ併用療法の非奏効例におけるLate line移行時期についての検討

横尾健, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.2 ) A582 - A582 2022年9月

Synthesized HMGB1 peptide prevents the progression of inflammation, steatosis, fibrosis, and tumor occurrence in a non-alcoholic steatohepatitis mouse model. 国際誌

Yui Ishii, Atsunori Tsuchiya, Kazuki Natsui, Youhei Koseki, Nobutaka Takeda, Kei Tomiyoshi, Fusako Yamazaki, Yuki Yoshida, Takashi Shimbo, Katsuto Tamai, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Non-alcoholic steatohepatitis (NASH) with fibrosis eventually leads to cirrhosis and hepatocellular carcinoma. Thus, the development of therapies other than dietary restriction and exercise, particularly those that suppress steatosis and fibrosis of the liver and have a long-term beneficial effect, is necessary. We aimed to evaluate the therapeutic effects of the HMGB1 peptide synthesized from box A using the melanocortin-4 receptor-deficient (Mc4r-KO) NASH model mouse. METHODS: We performed short- and long-term administration of this peptide and evaluated the effects on steatosis, fibrosis, and carcinogenesis using Mc4r-KO mice. We also analyzed the direct effect of this peptide on macrophages and hepatic stellate cells in vitro and performed lipidomics and metabolomics techniques to evaluate the effect. RESULTS: Although this peptide did not show direct effects on macrophages and hepatic stellate cells in vitro, in the short-term administration model, we could confirm the reduction of liver damage, steatosis, and fibrosis progression. The results of lipidomics and metabolomics suggested that the peptide might ameliorate NASH by promoting lipolysis via the activation of fatty acid β-oxidation and improving insulin resistance. In the long-term administration model, this peptide prevented progression to cirrhosis but retained the steatosis state, that is, the peptide prevents the progression to "burnt-out NASH." This peptide inhibited carcinogenesis by about one-third. CONCLUSION: This HMGB1 peptide can reduce liver damage, improve fibrosis and steatosis, and inhibit carcinogenesis, suggesting that the peptide would be a new treatment candidate for NASH and can contribute to the long-term prognosis for patients with NASH.

DOI： 10.1111/hepr.13825

Effects of a selective PPARα modulator, sodium-glucose cotransporter 2 inhibitor, and statin on the myocardial morphology of medaka nonalcoholic fatty liver disease model. 国際誌

Marina Ohkoshi-Yamada, Kenya Kamimura, Atsushi Kimura, Yuto Tanaka, Itsuo Nagayama, Shunta Yakubo, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

Biochemical and biophysical research communications 625 116 - 121 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Nonalcoholic fatty liver disease (NAFLD) is associated with metabolic dysregulation and is linked with various cardiovascular complications, which often lead to poor prognostic outcomes. To develop a standard therapy for NAFLD and to urgently address its complications, the current study aimed to investigate the mechanisms of NAFLD-related heart disease and the therapeutic effects of drugs targeting various metabolic pathways. METHODS: To explore the mechanism of NAFLD-related heart disease, a medaka model of high-fat diet-induced NAFLD was utilized. The gross structural, histological, and inflammatory changes in the myocardium were evaluated in a time-dependent manner. In addition, the therapeutic effects of medicines used for NAFLD treatment including, selective peroxisome proliferator-activated receptor α modulator (SPPARMα, pemafibrate), sodium-glucose cotransporter 2 (SGLT2) inhibitor (tofogliflozin), and statin (pitavastatin), and their combinations on heart pathology were evaluated. To determine the mechanisms underlying the therapeutic effects, the expression of genes related to liver inflammation was assessed via whole transcriptome sequencing analysis. RESULTS: The fish with NAFLD-related heart injury presented with cardiomyocyte hypertrophy, which led to cardiac hypertrophy. This morphological change was caused by the infiltration of inflammatory cells, including macrophages and CD4- and CD8-positive lymphocytes, in the cardiac wall and the expression of transforming growth factor beta 1 in the cardiomyocytes. Further, the livers of the fish had upregulated expressions of senescence-associated secretory phenotype-related genes. Treatment with pemafibrate, tofogliflozin, and pitavastatin reduced these changes and, consequently, cardiomyopathy. CONCLUSION: Our results demonstrated that NAFLD-related heart disease was attributed to the senescence-associated secretory phenotype-induced inflammatory activity in the cardiac wall, which resulted in myocardial hypertrophy. Moreover, the effects of SPPARMα, SGLT2 inhibitor, and statin on NAFLD-related heart disease were evident in the medaka NAFLD model.

DOI： 10.1016/j.bbrc.2022.07.117

機械学習を用いた慢性心不全に続発した肝臓への障害(Cardiac Hepatopathy)の画像解析

三井田秀, 上村博輝, 山崎文紗子, 渡邉雄介, 荒生祥尚, 木村成宏, 薛徹, 横尾健, 坂牧僚, 土屋淳紀, 藤木伸也, 猪又孝元, 寺井崇二

日本門脈圧亢進症学会雑誌 28 ( 3 ) 152 - 152 2022年8月

Cumulative risk of developing a new symptom in patients with primary biliary cholangitis and its impact on prognosis. 国際誌

Naruhiro Kimura, Toru Setsu, Yoshihisa Arao, Norihiro Sakai, Yusuke Watanabe, Hiroyuki Abe, Hiroteru Kamimura, Akira Sakamaki, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Akihiko Osaki, Kentarou Igarashi, Nobuo Waguri, Masahiko Yanagi, Toru Takahashi, Soichi Sugitani, Yuka Kobayashi, Masaaki Takamura, Akira Yoshikawa, Toru Ishikawa, Toshiaki Yoshida, Toshiaki Watanabe, Hitoshi Bannai, Tomoyuki Kubota, Kazuhiro Funakoshi, Hiroto Wakabayashi, So Kurita, Norio Ogata, Masashi Watanabe, Yuhsaku Mita, Shigeki Mori, Motoya Sugiyama, Toru Miyajima, Sumio Takahashi, Shuichi Sato, Kisei Ishizuka, Hironobu Ohta, Yutaka Aoyagi, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 6 ( 8 ) 577 - 586 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Aim: Symptoms of primary biliary cholangitis (PBC) frequently impair one's quality of life (QOL). Nonetheless, with improved treatment, the prognosis of PBC also improves. QOL plays an important role in patients with PBC. In this study, we aimed to reevaluate the transition of new symptom development in PBC and its predictive factors. Methods: This retrospective multicenter study enrolled 382 patients with PBC for symptom analysis. The impact of a newly developed symptom on PBC prognosis was investigated by Kaplan-Meier analysis with propensity score matching and logistic progression analysis. Results: The cumulative risk of developing a new symptom after 10 and 20 years of follow-up was 7.6 and 28.2%, and specifically that of pruritus, which was the most common symptom, was 6.7 and 23.3%, respectively. In Cox hazard risk analysis, serum Alb level (hazard ratio [HR], 1.097; 95% confidence interval [CI], 1.033-1.165; P = 0.002), the serum D-Bil level (HR, 6.262; 95% CI, 2.522-15.553, P < 0.001), and Paris II criteria (HR, 0.435; 95% CI, 0.183-1.036; P = 0.037) were significant independent predictors of a new symptom. Kaplan-Meier analysis showed that the overall survival and liver-related death were not significant between patients with and without a new symptom. Conclusion: The cumulative risk of new symptom development is roughly 30% 20 years after diagnosis and could be predicted by factors including serum albumin levels, serum D-Bil level, and Paris II criteria.

DOI： 10.1002/jgh3.12789

機械学習を用いた慢性心不全に続発した肝臓への障害(Cardiac Hepatopathy)の画像解析

三井田秀, 上村博輝, 山崎文紗子, 渡邉雄介, 荒生祥尚, 木村成宏, 薛徹, 横尾健, 坂牧僚, 土屋淳紀, 藤木伸也, 猪又孝元, 寺井崇二

日本門脈圧亢進症学会雑誌 28 ( 3 ) 152 - 152 2022年8月

上村顕也, 永山逸夫, 大脇崇史, 高昌良, 名古屋拓郎, 井上良介, 坂牧僚, 寺井崇二

日本アルコール・薬物医学会雑誌 57 ( 4 ) 121 - 121 2022年8月

Allograft liver failure awaiting liver transplantation in Japan.

Takuya Genda, Takafumi Ichida, Eiji Tanaka, Satoshi Mochida, Yoshiyuki Ueno, Shuji Terai, Ayano Inui, Yoshihide Ueda, Hideki Ohdan, Hiroto Egawa, Koji Umeshita, Hiroyuki Furukawa, Yukihiro Inomata

Journal of gastroenterology 57 ( 7 ) 495 - 504 2022年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Following liver transplantation (LT), allograft liver failure can be developed by various causes and requires re-LT. Hence, this study aimed to clarify the characteristics and prognostic factors of patients with allograft liver failure awaiting deceased donor LT (DDLT) in Japan. METHODS: Of the 2686 DDLT candidates in Japan between 2007 and 2016, 192 adult patients listed for re-LT were retrospectively enrolled in this study. Factors associated with waitlist mortality were assessed using the Cox proportional hazards model. The transplant-free survival probabilities were evaluated using the Kaplan-Meier analysis and log-rank test. RESULTS: The median period from the previous LT to listing for re-LT was 1548 days (range, 4-8449 days). Primary sclerosing cholangitis (PSC), which was a primary indication, showed a higher listing probability for re-LT as compared with other primary etiologies. Recurrent liver disease was a leading cause of allograft failure and was more frequently observed in the primary indication of hepatitis C virus (HCV) infection and PSC in contrast with other etiologies. Multivariate analysis identified the following independent risk factors associated with waitlist mortality: age, Child-Turcotte-Pugh (CTP) score, mode for end-stage liver disease (MELD) score, alanine aminotransferase (ALT), and causes of allograft failure. CONCLUSIONS: Recurrent HCV and PSC were major causes of allograft liver failure in Japan. In addition to CTP and MELD scores, either serum ALT levels or causes of allograft failure should be considered as graft liver allocation measures.

DOI： 10.1007/s00535-022-01880-w

肝性腹水が腹部コンパートメント症候群を介して腎機能へ与える影響の検討

(II章)肝肝硬変に対する再生医療

寺井崇二, 土屋淳紀

消化器内科学レビュー 2022-'23 213 - 216 2022年7月

上村博輝, 酒井規裕, 小島雄一, 川田雄三, 渡邊雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 横尾健, 坂牧僚, 土屋淳紀, 上村顕也, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 28 ( 2 ) 199 - 203 2022年7月

『高齢者(75歳以上)の非アルコール性脂肪性肝疾患の現状と課題』非アルコール性脂肪性肝炎を背景とした高齢者肝硬変に対する非侵襲的スコアリングシステムの有用性の検討

坂牧僚, 酒井規裕, 阿部寛幸, 横尾健, 上村顕也, 寺井崇二

日本高齢消化器病学会誌 25 ( 1 ) 74 - 74 2022年7月

【肝性脳症の病態と治療】肝性脳症と腸内細菌病態と治療

坂牧僚, 上村顕也, 横山邦彦, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 薛徹, 阿部寛幸, 上村博輝, 横尾健, 土屋淳紀, 寺井崇二

消化器・肝臓内科 12 ( 1 ) 68 - 72 2022年7月

各都道府県における肝疾患対策取り組みの現状新潟県の肝炎対策について

荒生祥尚, 薛徹, 酒井規裕, 寺井崇二

肝臓クリニカルアップデート 8 ( 1 ) 82 - 85 2022年7月

肝性腹水が腹部コンパートメント症候群を介して腎機能へ与える影響の検討

上村博輝, 酒井規裕, 小島雄一, 川田雄三, 渡邊雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 横尾健, 坂牧僚, 土屋淳紀, 上村顕也, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 28 ( 2 ) 199 - 203 2022年7月

The liver-gut peripheral neural axis and nonalcoholic fatty liver disease pathologies via hepatic serotonin receptor 2A. 国際誌

Takashi Owaki, Kenya Kamimura, Masayoshi Ko, Itsuo Nagayama, Takuro Nagoya, Osamu Shibata, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Takeki Sato, Toru Setsu, Akira Sakamaki, Hiroteru Kamimura, Takeshi Yokoo, Shuji Terai

Disease models & mechanisms 15 ( 7 ) 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Serotonin (5-HT) is one of the key bioamines of nonalcoholic fatty liver disease (NAFLD). Its mechanism via autonomic neural signal pathways remains unexplained; hence, we evaluated the involvement of 5-HT and related-signaling pathways via autonomic nerves in NAFLD. Diet-induced NAFLD animal models were developed using wild-type and melanocortin 4 receptor knockout (MC4RKO) mice, and the effects of autonomic neural axis on NAFLD physiology, 5-HT and its receptors (Htrs), and lipid metabolism-related genes were assessed applying hepatic nerve blockade. Hepatic neural blockade retarded the progression of NAFLD by reducing 5-HT in the small intestine, hepatic Htr2a, and hepatic lipogenic genes expression, and HTR2A antagonist reproduced these effects. The effects were milder in MC4RKO, and brain 5-HT and Htr2c expression did not correlate with peripheral neural blockade. Our study demonstrates that the autonomic liver-gut neural axis is involved in the etiology of diet-induced NAFLD and that 5-HT and HTR2A are key factors, implying that the modulation of the axis and use of HTR2A antagonists are potentially novel therapeutic strategies for NAFLD treatment.

DOI： 10.1242/dmm.049612

Involvement of DNA Damage Response via the Ccndbp1-Atm-Chk2 Pathway in Mice with Dextran-Sodium-Sulfate-Induced Colitis. 国際誌

Ryoko Horigome, Kenya Kamimura, Yusuke Niwa, Kohei Ogawa, Ken-Ichi Mizuno, Koichi Fujisawa, Naoki Yamamoto, Taro Takami, Tomoyuki Sugano, Akira Sakamaki, Hiroteru Kamimura, Masaaki Takamura, Shuji Terai

Journal of clinical medicine 11 ( 13 ) 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The dextran sodium sulfate (DSS)-induced colitis mouse model has been widely utilized for human colitis research. While its mechanism involves a response to double-strand deoxyribonucleic acid (DNA) damage, ataxia telangiectasia mutated (Atm)-checkpoint kinase 2 (Chk2) pathway activation related to such response remains unreported. Recently, we reported that cyclin D1-binding protein 1 (Ccndbp1) activates the pathway reflecting DNA damage in its knockout mice. Thus, this study aimed to examine the contribution of Ccndbp1 and the Atm-Chk2 pathway in DSS-induced colitis. We assessed the effect of DSS-induced colitis on colon length, disease activity index, and histological score and on the Atm-Chk2 pathway and the subsequent apoptosis in Ccndbp1-knockout mice. DSS-induced colitis showed distal colon-dominant Atm and Chk2 phosphorylation, increase in TdT-mediated dUTP-biotin nick end labeling and cleaved caspase 3-positive cells, and histological score increase, causing disease activity index elevation and colon length shortening. These changes were significantly ameliorated in Ccndbp1-knockout mice. In conclusion, Ccndbp1 contributed to Atm-Chk2 pathway activation in the DSS-induced colitis mouse model, causing inflammation and apoptosis of mucosal cells in the colon.

DOI： 10.3390/jcm11133674

Daisaikoto improves fatty liver and obesity in melanocortin-4 receptor gene-deficient mice via the activation of brown adipose tissue. 国際誌

Shinichi Morita, Akira Sakamaki, Kyutaro Koyama, Osamu Shibata, Takashi Owaki, Chiyumi Oda, Atsushi Kimura, Taiki Nakaya, Katsuya Ohbuchi, Miwa Nahata, Naoki Fujitsuka, Norihiro Sakai, Hiroyuki Abe, Kenya Kamimura, Shuji Terai

Scientific reports 12 ( 1 ) 10105 - 10105 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Melanocortin 4 receptor gene-knockout (MC4R-KO) mice are known to develop obesity with a high-fat diet. Meanwhile, daisaikoto, one of Kampo medicines, is a drug that is expected to have therapeutic effects on obesity. Here, we report the efficacy of daisaikoto in MC4R-KO mice. Eight-week-old MC4R-KO male mice (n = 12) were divided into three groups as follows: the SD group, which is fed with a standard diet; the HFD group, fed a high-fat diet; and the DSK group, fed with a high-fat diet containing 10% of daisaikoto. After the four-week observation period, mice in each group were sacrificed and samples were collected. The body weights at 12 weeks were significantly higher in the HFD group than in the other groups, indicating that daisaikoto significantly reduced body weight gain and fat deposition of the liver. The metabolome analysis indicated that degradation of triglycerides and fatty acid oxidation in the liver were enhanced by daisaikoto administration. In MC4R-KO mice, the cytoplasm and uncoupling protein 1 expression of brown adipose tissue was decreased; however, it was reversed in the DSK group. In conclusion, daisaikoto has potentially improved fatty liver and obesity, making it a useful therapeutic agent for obesity and fatty liver.

DOI： 10.1038/s41598-022-14371-y

Establishment of a pancreatic cancer animal model using the pancreas-targeted hydrodynamic gene delivery method. 国際誌

Osamu Shibata, Kenya Kamimura, Yuto Tanaka, Kohei Ogawa, Takashi Owaki, Chiyumi Oda, Shinichi Morita, Atsushi Kimura, Hiroyuki Abe, Satoshi Ikarashi, Kazunao Hayashi, Takeshi Yokoo, Shuji Terai

Molecular therapy. Nucleic acids 28 342 - 352 2022年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

This research developed an easy-to-use, reproducible pancreatic cancer animal model utilizing pancreas-targeted hydrodynamic gene delivery to deliver human pancreatic cancer-related genes to the pancreas of wild-type rats. KRAS G12D -induced pancreatic intraepithelial neoplasia lesions showed malignant transformation in the main pancreatic duct at 4 weeks and developed acinar-to-ductal metaplasia, which led to pancreatic ductal adenocarcinoma within 5 weeks, and the gene combination of KRAS G12D and YAP enhanced these effects. The repeat hydrodynamic gene delivery of KRAS G12D + YAP combination at 4 weeks showed acinar-to-ductal metaplasia in all rats and pancreatic ductal adenocarcinoma in 80% of rats 1 week later. Metastatic tumors in the liver, lymph nodes, and subcutaneous lesions and nervous invasion were confirmed. KRAS G12D and YAP combined transfer contributes to the E- to N-cadherin switch in pancreatic ductal adenocarcinoma cells and to tumor metastases. This pancreatic cancer model will speed up pancreatic cancer research for novel treatments and biomarkers for early diagnosis.

DOI： 10.1016/j.omtn.2022.03.019

多発性出血性膵炎を伴う重度の急性肝不全の一例(A case of severe acute liver failure with multiple hemorrhagic pancreatitis)

神保遼, 荒生祥尚, 山崎華子, 水戸將貴, 小島雄一, 木村成宏, 小林雄司, 林和直, 土屋淳紀, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 70回 np41 - np41 2022年6月

【肝臓と他臓器相関】脂肪性肝疾患における自律神経系を介した消化管ホルモンの関与

大脇崇史, 上村顕也, 永山逸夫, 高昌良, 名古屋拓郎, 井上良介, 薛徹, 寺井崇二

消化器・肝臓内科 11 ( 6 ) 709 - 713 2022年6月

多発性出血性膵炎を伴う重度の急性肝不全の一例(A case of severe acute liver failure with multiple hemorrhagic pancreatitis)

神保遼, 荒生祥尚, 山崎華子, 水戸將貴, 小島雄一, 木村成宏, 小林雄司, 林和直, 土屋淳紀, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 70回 np41 - np41 2022年6月

悪性胆道狭窄に対する治療戦略術後再建腸管例の悪性胆道狭窄に対するバルーン内視鏡下胆道ドレナージの有用性

名古屋拓郎, 寺井崇二, 林和直, 五十嵐聡, 小川光平

日本消化器病学会甲信越支部例会抄録集 70回 np46 - np46 2022年6月

NAFLDにおける肝-脳-腸関連と自律神経の関係

永山逸夫, 上村顕也, 高昌良, 大脇崇史, 名古屋拓郎, 寺井崇二

自律神経 59 ( 2 ) 208 - 211 2022年6月

Diagnostic criteria for acute-on-chronic liver failure and related disease conditions in Japan. 国際誌

Satoshi Mochida, Nobuaki Nakayama, Shuji Terai, Hitoshi Yoshiji, Masahito Shimizu, Akio Ido, Kazuaki Inoue, Takuya Genda, Yasuhiro Takikawa, Taro Takami, Naoya Kato, Masanori Abe, Ryuzo Abe, Ayano Inui, Hiromasa Ohira, Mureo Kasahara, Kazuaki Chayama, Kiyoshi Hasegawa, Atsushi Tanaka

Hepatology research : the official journal of the Japan Society of Hepatology 52 ( 5 ) 417 - 421 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

The Intractable Hepato-Biliary Disease Study Group of Japan, sponsored by the Ministry of Health, Labor and Wealth, proposed in 2018 that patients with cirrhosis and a Child-Pugh score of 5-9 should be diagnosed as having acute-on-chronic liver failure (ACLF) when a deterioration of liver function ("serum bilirubin level of 5.0 mg/dl or more" and "prothrombin time value of 40% or less of the standardized values and/or international normalization rates of 1.5 or more") caused by severe liver damage develops within 28 days after an acute insult, including alcohol abuse, bacterial infection, gastrointestinal bleeding, and the exacerbation of underlying liver diseases. Disease severity can be classified into 4 grades depending on the extent of the deterioration in organ functions, including liver, kidney, cerebral, blood coagulation, circulatory and respiratory functions. The Study Group has since performed an annual nationwide survey of patients with ACLF diagnosed according to the proposed diagnostic criteria as well as those with disease conditions related to ACLF. A total of 501 patients, including 183 patients diagnosed as having ACLF, seen between 2017 and 2019 were enrolled, and univariate and multivariate analyses revealed that the proposed diagnostic criteria were useful for identifying cirrhotic patients with an unfavorable outcome following an acute insult. Consequently, the Study Group determined that the proposed diagnostic criteria should be used in both clinical practice and clinical research as formal diagnostic criteria.

DOI： 10.1111/hepr.13763

Development of Dilated Esophagus, Sigmoid Esophagus, and Esophageal Diverticulum in Patients With Achalasia: Japan Achalasia Multicenter Study. 国際誌

Hiroki Sato, Yusuke Fujiyoshi, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Hiroyuki Sakae, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Hiroshi Yokomichi, Shuji Terai, Haruhiro Inoue

Journal of neurogastroenterology and motility 28 ( 2 ) 222 - 230 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background/Aims: Patients with achalasia-related esophageal motility disorders (AEMDs) frequently present with dilated and sigmoid esophagus, and develop esophageal diverticulum (ED), although the prevalence and patients characteristics require further elucidation. Methods: We conducted a multicenter cohort study of 3707 patients with AEMDs from 14 facilities in Japan. Esophagography on 3682 patients were analyzed. Results: Straight (n = 2798), sigmoid (n = 684), and advanced sigmoid esophagus (n = 200) were diagnosed. Multivariate analysis revealed that long disease duration, advanced age, obesity, and type I achalasia correlate positively, whereas severe symptoms and integrated relaxation pressure correlate negatively with development of sigmoid esophagus. In contrast, Grade II dilation (3.5-6.0 cm) was the most common (52.9%), while grade III dilation (≥ 6 cm) was rare (5.0%). We found early onset, male, obesity, and type I achalasia correlated positively, while advanced age correlated negatively with esophageal dilation. Dilated and sigmoid esophagus were found mostly in types I and II achalasia, but typically not found in spastic disorders. The prevalence of ED was low (n = 63, 1.7%), and non-dilated esophagus and advanced age correlated with ED development. Patients with right-sided ED (n = 35) had a long disease duration (P = 0.005) with low integrated relaxation pressure values (P = 0.008) compared with patients with left-sided ED (n = 22). Patients with multiple EDs (n = 6) had lower symptom severity than patients with a single ED (P = 0.022). Conclusions: The etiologies of dilated esophagus, sigmoid esophagus, and ED are considered multifactorial and different. Early diagnosis and optimal treatment of AEMDs are necessary to prevent these conditions.

DOI： 10.5056/jnm21188

Effects of Atezolizumab and Bevacizumab on Adrenal Gland Metastasis of Hepatocellular Carcinoma: A Case Report and Review of Literature.

Natsuki Ishikawa, Kenya Kamimura, Saori Endo, Soichi Ishii, Kazuya Ogawa, Norihiro Sakai, Hiroyuki Abe, Masayoshi Ko, Osamu Shibata, Youhei Koseki, Junji Yokoyama, Akira Sakamaki, Shuji Terai

Internal medicine (Tokyo, Japan) 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Regarding the prognosis of cases with advanced-stage hepatocellular carcinoma (HCC), a recent clinical study showed that the immune checkpoint inhibitors atezolizumab plus bevacizumab have superior efficacy to sorafenib. However, only a few reports have focused on their effects on extrahepatic metastases. We herein report a case of HCC in a 59-year-old man with intrahepatic lesions treated successfully by hepatic arterial chemoembolization, radiotherapy, and sorafenib; the extrahepatic lesion in the adrenal gland was treated by atezolizumab plus bevacizumab. The patient showed a tumor-free condition for one year. We have summarized the clinical course and reviewed the literature to underscore the efficacy of atezolizumab plus bevacizumab for treating extrahepatic lesions of HCC.

DOI： 10.2169/internalmedicine.9341-22

老化細胞除去治療のAcute on chronic liverfailureに対する効果の検証

渡邉雄介, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.1 ) A371 - A371 2022年4月

肝硬変-合併症の管理(含む門脈圧亢進症) 水素型の小腸内細菌異常増殖は肝疾患の不顕性肝性脳症と筋肉量低下に関連する

坂牧僚, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.1 ) A64 - A64 2022年4月

【革新的技術が変える肝疾患診療】間葉系幹細胞・エクソソームを用いた肝硬変治療

土屋淳紀, 寺井崇二

消化器・肝臓内科 11 ( 4 ) 494 - 499 2022年4月

Relative Dose Intensityに基づく高齢者レンバチニブ投与における全生存期間の検討

横尾健, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.1 ) A302 - A302 2022年4月

Utility of autologous fecal microbiota transplantation and elucidation of microbiota in diversion colitis. 国際誌

Kentaro Tominaga, Atsunori Tsuchiya, Takeshi Mizusawa, Asami Matsumoto, Ayaka Minemura, Kentaro Oka, Motomichi Takahashi, Tomoaki Yoshida, Yuichi Kojima, Kohei Ogawa, Yuzo Kawata, Nao Nakajima, Naruhiro Kimura, Hiroyuki Abe, Toru Setsu, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Ken-Ichi Mizuno, Junji Yokoyama, Yosuke Tajima, Masato Nakano, Yoshifumi Shimada, Hitoshi Kameyama, Toshifumi Wakai, Shuji Terai

DEN open 2 ( 1 ) e63 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Objectives: Diversion colitis (DC) is an inflammatory disorder caused by interruption of the fecal stream and subsequent nutrient deficiency from luminal bacteria. The utility of fecal microbiota transplantation (FMT) for DC was recently investigated; however, the precise pathogenesis of this condition remains unclear. This study aimed to evaluate the utility of autologous FMT in DC and to determine the related changes in the intestinal microbiota. Methods: Autologous FMT was performed to reestablish the intestinal microbiota in five patients (average age, 64.6 ± 8.3 years) with DC. They underwent double-ended colostomy. We assessed the diverted colon by endoscopy and evaluated the microbiota before and after FMT using the 16S rRNA gene sequencing method. Results: All five patients had mild inflammation (ulcerative colitis endoscopic index of severity [UCEIS] 2-3) in the diverted colon based on the colonoscopic findings. Three patients presented with symptoms, such as tenesmus, mucoid stool, and bloody stool. With FMT treatment, all patients achieved endoscopic remission (UCEIS score of 0 or 1) and symptomatic improvement. We observed a significantly decreased α-diversity in DC patients compared to healthy controls. The frequency of aerobic bacteria, such as Enterobacteriaceae, in the diverted colon decreased after autologous FMT. Conclusions: This study was the first to show that the microbiota in the diverted colon was significantly affected by autologous FMT. Since interruption of the fecal stream is central to the development of DC, FMT can be considered a promising treatment.

DOI： 10.1002/deo2.63

Intestinal duplication diagnosed preoperatively with double-balloon enteroscopy: an extremely rare case report and literature review.

Yusuke Niwa, Kentaro Tominaga, Yuzo Kawata, Takamasa Kobayashi, Takeshi Mizuwasa, Kazuya Takahashi, Hiroki Sato, Junji Kohisa, Satoshi Abe, Kenya Kamimura, Junji Yokoyama, Hirokazu Kawai, Hideaki Sugino, Hajime Umezu, Yumiko Hirai, Masato Nakano, Yoshifumi Shimada, Hitoshi Kameyama, Toshifumi Wakai, Shuji Terai

Clinical journal of gastroenterology 15 ( 2 ) 381 - 387 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Gastrointestinal duplications are congenital malformations that are usually observed in pediatric patients. Diagnosis in adulthood is quite rare, and preoperative diagnosis of gastrointestinal duplication is difficult, particularly in the small intestine. We encountered an extremely rare adult case of duplication of the jejunum, which showed a stomach-like form diagnosed using double-balloon enteroscopy (DBE). The patient was an 18-year-old male who had been experiencing upper abdominal pain and vomiting repeatedly without any triggers for 3 years. Various examinations were performed, but no cause of symptoms was found. DBE revealed a narrow opening of the lumen at the upper jejunum, and the lumen was covered with mucosal folds similar to those of the stomach. Enteroclysis via DBE showed a tubular structure on the mesenteric side of the jejunum. We diagnosed a jejunal tubular duplication with ectopic gastric mucosa and underwent partial small bowel resection. The patient's abdominal symptoms resolved. From this, DBE can be a useful tool for diagnosing intestinal duplication in adults. We believe that this case and literature review will facilitate the accurate and prompt diagnosis of small intestinal duplication.

DOI： 10.1007/s12328-022-01596-7

Methotrexate-associated proliferative disorder in the lower esophagus extending to the gastroesophageal junction: A case report. 国際誌

Yuki Hojo, Masafumi Takatsuna, Satoshi Ikarashi, Hiroteru Kamimura, Rika Kimura, Masaki Mito, Yusuke Watanabe, Yusuke Tani, Junji Yokoyama, Shuji Terai

DEN open 2 ( 1 ) e14 2022年4月

記述言語：英語

A 64-year-old woman was receiving oral methotrexate (MTX) for rheumatoid arthritis (RA) for 15 years. She underwent esophagogastroduodenoscopy because of discomfort in the chest. Endoscopic findings revealed an ulcer in the lower esophagus extending to the gastroesophageal junction (EGJ). The ulcer occupied half of the esophageal lumen and had a sharp and clear margin. Magnifying narrow-band imaging endoscopy revealed the deposition of white plaque, and there were few microvessels in the edge and bottom of the ulcer. Histologic examination of the biopsy specimens from the oral edge of the lesion revealed proliferation of atypical lymphoid cells (immunophenotype results: CD20 [+], CD3 [partially +], CD5 [-], and BCL-2 [-]]. The patient was diagnosed with methotrexate-associated lymphoproliferative disorder (MTX-LPD) and was advised to stop MTX intake. After 2 months of stopping MTX, the ulcer was found to be almost regressed and showed signs of healing. MTX-LPD in the lower esophagus extending to the EGJ is extremely rare. This case can help in expanding the understanding of esophageal MTX-LPD.

DOI： 10.1002/deo2.14

【1ページでわかる内科疾患の診療ノート-"あたりまえ"のなかにある大事な視点】(第7章)肝・胆・膵非代償性肝硬変

脂肪性肝疾患における自律神経系経路を介した脂質代謝制御の解明と治療薬スクリーニング

上村顕也, 大脇崇史, 寺井崇二

肝臓 63 ( Suppl.1 ) A254 - A254 2022年4月

Relative Dose Intensityに基づく高齢者レンバチニブ投与における全生存期間の検討

横尾健, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 63 ( Suppl.1 ) A302 - A302 2022年4月

肝疾患の小児・成人移行期医療の課題-全人的ケアの確立を目指して成人外来へ受診する可能性をもつ小児脂肪肝の特徴

上村博輝, 上村顕也, 寺井崇二

肝臓 63 ( Suppl.1 ) A169 - A169 2022年4月

肝線維化研究Revisited-肝臓学のBiologyからTranslationalへヒト肝細胞キメラマウスを用いた薬剤のスクリーニングドラッグリポジショニングによる肝線維化治療薬の探索・メカニズムの検証

酒井規裕, 上村顕也, 寺井崇二

肝臓 63 ( Suppl.1 ) A174 - A174 2022年4月

医療機関連携急性肝不全ネットワークを円滑に行い生体肝移植にて救命できた急性肝不全昏睡型の1例

武田信峻, 土屋淳紀, 石井結唯, 夏井一輝, 荒生祥尚, 冨永顕太郎, 林和直, 寺井崇二

肝臓 63 ( Suppl.1 ) A265 - A265 2022年4月

本県での肝炎医療コーディネーター養成の現状と活動事例紹介

酒井規裕, 薛徹, 荒生祥尚, 澤栗裕美, 廣川光, 星田和哉, 是永匡紹, 寺井崇二, 新たな手法を用いた肝炎ウイルス検査受検率・陽性者受診率の向上に資する研究班

肝臓 63 ( Suppl.1 ) A243 - A243 2022年4月

FALD(フォンタン術後肝障害)の疫学・病態・臨床-診療ガイドラインの確立を目指して先天性心疾患術後の肝線維化進展に影響を及ぼす因子の解析

山崎文紗子, 上村博輝, 寺井崇二

肝臓 63 ( Suppl.1 ) A192 - A192 2022年4月

上村博輝, 寺井崇二

内科 129 ( 4 ) 867 - 871 2022年4月

肝疾患の小児・成人移行期医療の課題-全人的ケアの確立を目指して成人外来へ受診する可能性をもつ小児脂肪肝の特徴

上村博輝, 上村顕也, 寺井崇二

肝臓 63 ( Suppl.1 ) A169 - A169 2022年4月

Effects of a novel selective PPARα modulator, statin, sodium-glucose cotransporter 2 inhibitor, and combinatorial therapy on the liver and vasculature of medaka nonalcoholic steatohepatitis model. 国際誌

Atsushi Kimura, Kenya Kamimura, Marina Ohkoshi-Yamada, Yoko Shinagawa-Kobayashi, Ryo Goto, Takashi Owaki, Chiyumi Oda, Osamu Shibata, Shinichi Morita, Norihiro Sakai, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

Biochemical and biophysical research communications 596 76 - 82 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Nonalcoholic steatohepatitis (NASH) is a disease entity with an increasing incidence, with involvement of several metabolic pathways. Various organs, including the liver, kidneys, and the vasculature, are damaged in NASH, indicating the urgent need to develop a standard therapy. Therefore, this study was conducted to investigate the effects of drugs targeting various metabolic pathways and their combinations on a high-fat diet (HFD)-induced NASH medaka model. METHODS: To investigate the effects of drugs on vascular structures, the NASH animal model was developed using the fli::GFP transgenic medaka fed with HFD at 20 mg/fish daily. The physiological changes, histological changes in the liver, vascular structures in the fin, and serum biochemical markers were evaluated in a time-dependent manner after treatment with selective peroxisome proliferator-activated receptor α modulator (pemafibrate), statin (pitavastatin), sodium-glucose cotransporter 2 inhibitor (tofogliflozin), and their combinations. Furthermore, to determine the mechanisms underlying the effects, whole transcriptome sequencing was conducted using medaka liver samples. RESULTS: Histological analyses revealed significant suppression of fat accumulation and fibrotic changes in the liver after treatment with drugs and their combinations. The expression levels of steatosis- and fibrosis-related genes were modified by the treatments. Moreover, the HFD-induced vascular damages in the fin exhibited milder changes after treatment with the drugs. CONCLUSION: The effects of treating various metabolic pathways on the medaka body, liver, and vascular structures of the NASH medaka model were evidenced. Moreover, to our knowledge, this study is the first to report whole genome sequence and gene expression evaluation of medaka livers, which could be helpful in clarifying the molecular mechanisms of drugs.

DOI： 10.1016/j.bbrc.2022.01.086

Long-Term Efficacy and Safety of Rifaximin in Japanese Patients with Hepatic Encephalopathy: A Multicenter Retrospective Study. 国際誌

Hideto Kawaratani, Yasuteru Kondo, Ryoji Tatsumi, Naoto Kawabe, Norikazu Tanabe, Akira Sakamaki, Kazuo Okumoto, Yoshihito Uchida, Kei Endo, Takumi Kawaguchi, Tsunekazu Oikawa, Yoji Ishizu, Shuhei Hige, Taro Takami, Shuji Terai, Yoshiyuki Ueno, Satoshi Mochida, Yasuhiro Takikawa, Takuji Torimura, Tomokazu Matsuura, Masatoshi Ishigami, Kazuhiko Koike, Hitoshi Yoshiji

Journal of clinical medicine 11 ( 6 ) 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Rifaximin is commonly used for hepatic encephalopathy (HE). However, the effects of long-term treatment for Japanese people are limited. Therefore, this study aimed to investigate the effects and safety of long-term treatment with rifaximin on HE. METHODS: A total of 215 patients with cirrhosis administered with rifaximin developed overt or covert HE, which was diagnosed by an attending physician for >12 months. Laboratory data were extracted at pretreatment and 3, 6, and 12 months after rifaximin administration. The long-term effect of rifaximin was evaluated, and the incidence of overt HE during 12 months and adverse events was extracted. RESULTS: Ammonia levels were significantly improved after 3 months of rifaximin administration and were continued until 12 months. There were no serious adverse events after rifaximin administration. The number of overt HE incidents was 9, 14, and 27 patients within 3, 6, and 12 months, respectively. Liver enzymes, renal function, and electrolytes did not change after rifaximin administration. Prothrombin activity is a significant risk factor for the occurrence of overt HE. The serum albumin, prothrombin activity, and albumin-bilirubin (ALBI) scores were statistically improved after 3 and 6 months of rifaximin administration. Moreover, the same results were obtained in patients with Child-Pugh C. CONCLUSIONS: The long-term rifaximin treatment was effective and safe for patients with HE, including Child-Pugh C.

DOI： 10.3390/jcm11061571

消化器疾患に対する分化・老化・再生研究の展開 Acute on chronic liver failureに対する老化細胞除去治療の新規開発のための基盤研究

渡邉雄介, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A32 - A32 2022年3月

肝疾患の画像情報による病態解明と診療応用心不全患者が肝形態に及ぼす影響(Cardiac Hepatopathy)の画像による解析

上村博輝, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A223 - A223 2022年3月

消化器疾患診療に必要なバイオマーカー開発のための研究エクソソームタンパクEps8の膵癌バイオマーカーとしての検討

林和直, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A172 - A172 2022年3月

脂肪肝炎:今後の展開自律神経経路が制御する多臓器連関の解析と脂肪肝炎制御への展開

上村顕也, 大脇崇史, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A60 - A60 2022年3月

酒井規裕, 上村顕也, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A138 - A138 2022年3月

老化と消化器がんの病態・診療 Relative Dose Intensityに注目した高齢者レンバチニブ治療の安全性と有効性

横尾健, 上村顕也, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A186 - A186 2022年3月

肝移植適応疾患の病態解明と診療展開肝障害に伴う臓器連関による血中セロトニン濃度変化と病態の検討肝不全の病態変化を推測するマーカーの樹立へ

薛徹, 上村顕也, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A219 - A219 2022年3月

脂肪肝炎:今後の展開自律神経経路が制御する多臓器連関の解析と脂肪肝炎制御への展開

上村顕也, 大脇崇史, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A60 - A60 2022年3月

薛徹, 上村顕也, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A219 - A219 2022年3月

老化と消化器がんの病態・診療 Relative Dose Intensityに注目した高齢者レンバチニブ治療の安全性と有効性

横尾健, 上村顕也, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A186 - A186 2022年3月

酒井規裕, 上村顕也, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A138 - A138 2022年3月

病態に基づく肝疾患医療連携の今後肝炎医療コーディネーターと連携した院内における肝炎ウイルス陽性者の拾い上げ

荒生祥尚, 薛徹, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A229 - A229 2022年3月

重症急性膵炎後Walled-off necrosisの経過に対する抗菌薬投与の影響

五十嵐聡, 林和直, 寺井崇二, 小川光平

日本消化器病学会雑誌 119 ( 臨増総会 ) A344 - A344 2022年3月

栄養・代謝機能と消化器疾患の病態解明と治療膵臓癌における脂肪酸分画の臨床的意義についての検証

小川光平, 林和直, 寺井崇二

日本消化器病学会雑誌 119 ( 臨増総会 ) A174 - A174 2022年3月

Cyclin D1 Binding Protein 1 Responds to DNA Damage through the ATM-CHK2 Pathway. 国際誌

Yusuke Niwa, Kenya Kamimura, Kohei Ogawa, Chiyumi Oda, Yuto Tanaka, Ryoko Horigome, Masato Ohtsuka, Hiromi Miura, Koichi Fujisawa, Naoki Yamamoto, Taro Takami, Shujiro Okuda, Masayoshi Ko, Takashi Owaki, Atsushi Kimura, Osamu Shibata, Shinichi Morita, Norihiro Sakai, Hiroyuki Abe, Takeshi Yokoo, Akira Sakamaki, Hiroteru Kamimura, Shuji Terai

Journal of clinical medicine 11 ( 3 ) 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cyclin D1 binding protein 1 (CCNDBP1) is considered a tumor suppressor, and when expressed in tumor cells, CCNDBP1 can contribute to the viability of cancer cells by rescuing these cells from chemotherapy-induced DNA damage. Therefore, this study focused on investigating the function of CCNDBP1, which is directly related to the survival of cancer cells by escaping DNA damage and chemoresistance. Hepatocellular carcinoma (HCC) cells and tissues obtained from Ccndbp1 knockout mice were used for the in vitro and in vivo examination of the molecular mechanisms of CCNDBP1 associated with the recovery of cells from DNA damage. Subsequently, gene and protein expression changes associated with the upregulation, downregulation, and irradiation of CCNDBP1 were assessed. The overexpression of CCNDBP1 in HCC cells stimulated cell growth and showed resistance to X-ray-induced DNA damage. Gene expression analysis of CCNDBP1-overexpressed cells and Ccndbp1 knockout mice revealed that Ccndbp1 activated the Atm-Chk2 pathway through the inhibition of Ezh2 expression, accounting for resistance to DNA damage. Our study demonstrated that by inhibiting EZH2, CCNDBP1 contributed to the activation of the ATM-CHK2 pathway to alleviate DNA damage, leading to chemoresistance.

DOI： 10.3390/jcm11030851

A novel prostaglandin I2 agonist, ONO-1301, attenuates liver inflammation and suppresses fibrosis in non-alcoholic steatohepatitis model mice. 国際誌

Satoko Motegi, Atsunori Tsuchiya, Takahiro Iwasawa, Takeki Sato, Masaru Kumagai, Kazuki Natsui, Shunsuke Nojiri, Masahiro Ogawa, Suguru Takeuchi, Yosiki Sakai, Shigeru Miyagawa, Yoshiki Sawa, Shuji Terai

Inflammation and regeneration 42 ( 1 ) 3 - 3 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: ONO-1301 is a novel long-lasting prostaglandin (PG) I2 mimetic with inhibitory activity on thromboxane (TX) A2 synthase. This drug can also induce endogenous prostaglandin (PG)I2 and PGE2 levels. Furthermore, ONO-1301 acts as a cytokine inducer and can initiate tissue repair in a variety of diseases, such as pulmonary hypertension, pulmonary fibrosis, cardiac infarction, and obstructive nephropathy. In this study, our aim was to evaluate the effect of ONO-1301 on liver inflammation and fibrosis in a mouse model of non-alcoholic steatohepatitis (NASH). METHODS: The therapeutic effects of ONO-1301 against liver damage, fibrosis, and occurrence of liver tumors were evaluated using melanocortin 4 receptor-deficient (Mc4r-KO) NASH model mice. The effects of ONO-1301 against macrophages, hepatic stellate cells, and endothelial cells were also evaluated in vitro. RESULTS: ONO-1301 ameliorated liver damage and fibrosis progression, was effective regardless of NASH status, and suppressed the occurrence of liver tumors in Mc4r-KO NASH model mice. In the in vitro study, ONO-1301 suppressed LPS-induced inflammatory responses in cultured macrophages, suppressed hepatic stellate cell (HSC) activation, upregulated vascular endothelial growth factor (VEGF) expression in HSCs, and upregulated hepatocyte growth factor (HGF) and VEGF expression in endothelial cells. CONCLUSIONS: The results of our study highlight the potential of ONO-1301 to reverse the progression and prevent the occurrence of liver tumors in NASH using in vivo and in vitro models. ONO-1301 is a multidirectional drug that can play a key role in various pathways and can be further analyzed for use as a new drug candidate against NASH.

DOI： 10.1186/s41232-021-00191-6

Simultaneous muscular hemorrhages in two regions three years after successfully controlling refractory ascites using transjugular intrahepatic portosystemic shunt treatment: a case report.

Hiroteru Kamimura, Michitaka Imai, Hiroyuki Abe, Aiko Yoshioka, Kanae Hirose, Noriko Ishihara, Toru Ishikawa, Shuji Terai

Clinical journal of gastroenterology 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Various therapies and drugs have been developed to extend the life expectancy of patients with liver cirrhosis. The prolonged prognosis of cirrhotic patients may change the final cause of death in the future. Deep bleeding into the muscle is an uncommon but potentially life-threatening complication of liver cirrhosis. CASE REPORT: A 53-year-old man had undergone transjugular intrahepatic portosystemic shunt treatment for refractory ascites, which successfully controlled it for three years. However, he had started drinking again and experienced acute-on-chronic liver failure. He also had severe back pain. Abdominal computed tomography showed hyperdensities in the retroperitoneum and right pleural cavity. Despite blood infusion, he died from acute-on-chronic liver failure. A pathological autopsy revealed bleeding from the iliopsoas and right diaphragmatic muscle simultaneously, evident from the presence of red blood cells located between the muscle sheaths. Disruption of the small vessels in the skeletal muscle fibers was inferred. CONCLUSION: This is a critical case that underscores the significance of improving available knowledge based on the cause of final death of the patients with cirrhosis, who now have a good long-term prognosis owing to the latest medical developments.

DOI： 10.1007/s12328-022-01591-y

Use of a Deep Learning Approach for the Sensitive Prediction of Hepatitis B Surface Antigen Levels in Inactive Carrier Patients. 国際誌

Hiroteru Kamimura, Hirofumi Nonaka, Masaya Mori, Taichi Kobayashi, Toru Setsu, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Journal of clinical medicine 11 ( 2 ) 2022年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Deep learning is a subset of machine learning that can be employed to accurately predict biological transitions. Eliminating hepatitis B surface antigens (HBsAgs) is the final therapeutic endpoint for chronic hepatitis B. Reliable predictors of the disappearance or reduction in HBsAg levels have not been established. Accurate predictions are vital to successful treatment, and corresponding efforts are ongoing worldwide. Therefore, this study aimed to identify an optimal deep learning model to predict the changes in HBsAg levels in daily clinical practice for inactive carrier patients. We identified patients whose HBsAg levels were evaluated over 10 years. The results of routine liver biochemical function tests, including serum HBsAg levels for 1, 2, 5, and 10 years, and biometric information were obtained. Data of 90 patients were included for adaptive training. The predictive models were built based on algorithms set up by SONY Neural Network Console, and their accuracy was compared using statistical analysis. Multiple regression analysis revealed a mean absolute percentage error of 58%, and deep learning revealed a mean absolute percentage error of 15%; thus, deep learning is an accurate predictive discriminant tool. This study demonstrated the potential of deep learning algorithms to predict clinical outcomes.

DOI： 10.3390/jcm11020387

患者まで届いている再生医療より効果のある肝硬変症に対する再生医療の実現を目指して

寺井崇二, 土屋淳紀, 渡邊雄介, 竹内卓, 野尻俊介, 酒井規裕, 木村成宏, 阿部寛幸

再生医療 21 ( 1 ) 20 - 23 2022年1月

Diet-related changes of basal lamina fenestrations in the villous epithelium of the rat small intestine: Statistical analysis on scanning electron microscopy.

Masatoshi Sato, Keisuke Morita, Rie Azumi, Yusuke Mizutani, Manabu Hayatsu, Tatsuo Ushiki, Shuji Terai

Biomedical research (Tokyo, Japan) 43 ( 1 ) 11 - 22 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

The epithelial basal lamina of the small intestine has numerous fenestrations for intraepithelial migration of leukocytes. We have reported dynamic changes of fenestrations in dietary conditions. To investigate this phenomenon, we performed statistical analyses using scanning electron microscopy images of the epithelial basal lamina of rat intestinal villi after removal of the villous epithelium by osmium maceration. We examined structural changes in the number and size of fenestrations in the rat jejunum and ileum under fasted and fed states for 24 h. Our findings revealed that, in the jejunum, the number of free cells migrating into the epithelium through fenestrations increased from 2 h after feeding, resulting in an increase in the fenestration size of intestinal villi; the number of free cells then tended to decrease at 6 h after feeding, and the fenestration size also gradually decreased. By contrast, the increase in the fenestration size by feeding was not statistically significant in the ileum. These findings indicate that the number of migrating cells increases in the upper part of the small intestine under dietary conditions, which may influence the absorption efficiency of nutrients including lipids, as well as the induction of nutrient-induced inflammation.

DOI： 10.2220/biomedres.43.11

Longitudinal increase in albumin-bilirubin score is associated with non-malignancy-related mortality and quality of life in patients with liver cirrhosis. 国際誌

Akira Sakamaki, Masaaki Takamura, Norihiro Sakai, Yusuke Watanabe, Yoshihisa Arao, Naruhiro Kimura, Toru Setsu, Hiroyuki Abe, Takeshi Yokoo, Hiroteru Kamimura, Shunsuke Tsubata, Nobuo Waguri, Toru Ishikawa, Hirokazu Kawai, Soichi Sugitani, Tomomi Sato, Kazuhiro Funakoshi, Masashi Watanabe, Kentarou Igarashi, Kenya Kamimura, Atsunori Tsuchiya, Yutaka Aoyagi, Shuji Terai

PloS one 17 ( 2 ) e0263464 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

Due to the developments in the treatment for hepatitis, it is possible to prevent the progression of liver fibrosis and improve patients' prognosis even if it has already led to liver cirrhosis (LC). Consequently, a two-step study was conducted. To begin with, a retrospective study was conducted to identify the potential predictors of non-malignancy-related mortality from LC. Then, we prospectively analyzed the validity of these parameters as well as their association with patients' quality of life. In the retrospective study, 89 cases were included, and the multivariate Cox regression analysis indicated that age (P = 0.012), model for end-stage liver disease (MELD) score (P = 0.012), and annual rate of change of the albumin-bilirubin (ALBI) score (P < 0.001) were significantly associated with LC prognosis. In the prospective study, 70 patients were included, and the patients were divided into cirrhosis progression and non-progression groups. The univariate logistic regression analysis indicated the serum procollagen type III N-terminal peptide level (P = 0.040) and MELD score (P = 0.010) were significantly associated with the annual rate of change of the ALBI score. Furthermore, the mean Chronic Liver Disease Questionnaire score worsened from 5.3 to 4.9 in the cirrhosis progression group (P = 0.034). In conclusion, a longitudinal increase in the ALBI score is closely associated with non-malignancy-related mortality and quality of life.

DOI： 10.1371/journal.pone.0263464

Esophageal Diverticulum - Indications and Efficacy of Therapeutic Endoscopy.

Hiroki Sato, Manabu Takeuchi, Kazuya Takahashi, Ken-Ichi Mizuno, Koichi Furukawa, Akito Sato, Nao Nakajima, Junji Yokoyama, Shuji Terai

Internal medicine (Tokyo, Japan) 61 ( 7 ) 943 - 949 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

Objective Esophageal diverticulum is rare, and the concomitance of esophageal motility disorders (EMDs) and the efficacy of novel endoscopic treatment have not been investigated in Japan. Methods An examination including high-resolution manometry (HRM) was performed for patients with both EMDs and epiphrenic diverticulum. EMD-related epiphrenic diverticulum and Zenker's diverticulum were treated using salvage peroral endoscopic myotomy (s-POEM) and endoscopic diverticulotomy, respectively. Results Six cases of epiphrenic diverticulum were diagnosed in this study. Among 125 patients with achalasia and spastic disorders, concomitant epiphrenic diverticulum was observed in 4 (3.2%). Of these, three showed a normal lower esophageal sphincter pressure on HRM, although gastroscopy and esophagography revealed typical findings of an impaired lower esophageal sphincter relaxation. These four patients were successfully treated with s-POEM, and the Eckardt score improved from 6.3 to 0.25 at 32.5 (range: 13-56) months of follow-up, with equivalent treatment efficacy to that observed for achalasia and spastic disorders without epiphrenic diverticulum. In contrast, the two remaining cases of epiphrenic diverticulum had normal esophageal motility. Six cases of Zenker's diverticulum were diagnosed, and endoscopic diverticulotomy was successfully performed in all. The dysphagia score decreased from 2.8 to 0.17 at 14.8 (range: 2-36) months of follow-up. Overall, 12 endoscopic treatments were performed for esophageal diverticulum; no adverse events were observed. Conclusion In epiphrenic diverticulum patients, concomitant EMDs are not rare and should be carefully diagnosed. A normal lower esophageal sphincter pressure on HRM does not always mean a normal lower esophageal sphincter relaxation. S-POEM and endoscopic diverticulotomy are effective minimally invasive treatment options for EMD-related epiphrenic diverticulum and Zenker's diverticulum.

DOI： 10.2169/internalmedicine.8196-21

Endoscopic Submucosal Dissection for Gastric Tube Carcinoma after Esophagectomy Contributes to Long-Term Outcomes. 国際誌

Satoru Hashimoto, Hiroki Sato, Ken-Ichi Mizuno, Kazuya Takahashi, Masafumi Takatsuna, Junji Yokoyama, Hiroshi Ichikawa, Manabu Takeuchi, Masaaki Kobayashi, Shuji Terai

Canadian journal of gastroenterology & hepatology 2022 1631415 - 1631415 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

The incidence of gastric tube carcinoma (GTC) after esophagectomy for esophageal carcinoma has increased in recent years. Surgical removal of the reconstructed gastric tube is associated with high mortality, and endoscopic submucosal dissection (ESD) is a promising alternative. There are limited reports of ESD for GTC. This study investigated the efficacy and safety of ESD in GTC. This single-center retrospective study examined patients who underwent ESD for GTC after esophagectomy at our institution between 2003 and 2018. The curability of GTC with ESD was evaluated histologically according to the Japanese Gastric Cancer Treatment Guidelines. Patient characteristics and procedural and long-term outcomes were analyzed. Overall, 31 patients (29 men and 2 women; median age, 73 years) with 45 GTC lesions underwent ESD. The mean period between primary esophagectomy and the diagnosis of GTC was 10.6 years. Bleeding during ESD was noted in two patients (6.5%). No other adverse or fatal events such as perforation were noted. Complete resection and curative resection were documented in 80.6% and 48.4% of cases, respectively. The 3-year and 5-year overall survival rates were 67.6% and 47.7%, respectively. The 3-year and 5-year disease-specific survival rates were 100% and 92.9%, respectively. One patient died of GTC, and fourteen patients died of other diseases, including primary carcinoma in five cases. ESD was safe and provided good long-term outcomes in patients with GTC. Regular long-term gastroscopy is required for the early detection of GTC. Patients with GTC after esophagectomy for esophageal carcinoma have a high risk of other primary carcinomas or comorbidities after ESD.

DOI： 10.1155/2022/1631415

Hydrogen-producing small intestinal bacterial overgrowth is associated with hepatic encephalopathy and liver function. 国際誌

Kunihiko Yokoyama, Akira Sakamaki, Kazuya Takahashi, Takumi Naruse, Chihiro Sato, Yuzo Kawata, Kentaro Tominaga, Hiroyuki Abe, Hiroki Sato, Atsunori Tsuchiya, Kenya Kamimura, Masaaki Takamura, Junji Yokoyama, Shuji Terai

PloS one 17 ( 2 ) e0264459 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

Overt hepatic encephalopathy (HE) is one of the complications of liver cirrhosis (LC), which negatively affects the prognosis and quality of life of patients. Small intestinal bacterial overgrowth (SIBO) is significantly associated with LC and its complications, including HE. We investigated the relationship between SIBO and LC, and the difference between hydrogen-producing and methane-producing SIBO (H-SIBO and M-SIBO, respectively). This is a prospective cohort study of 107 cases. Breath measurements of hydrogen and methane concentrations were performed for the diagnosis of SIBO. The study cohort included 81 males with a median age of 70 (40-86) years, and SIBO was detected in 31 cases (29.0%). There were no significant differences between the SIBO positive and SIBO negative groups. Reclassification into H-SIBO (16 cases) and others (91 cases) was performed, and the Child-Pugh score was only derived in the multivariate logistic analysis (P = 0.028, odds ratio 1.39, 95% confidence interval 1.04-1.85). Furthermore, H-SIBO was significantly associated with covert HE in chi-square test (50.0% vs. 24.2%, P = 0.034). In addition, we evaluated the therapeutic response on SIBO of rifaximin in eight covert HE patients. 20% patients with M-SIBO and 67% patients with H-SIBO showed an improvement of the breath test. In conclusion, H-SIBO, but not M-SIBO, is significantly associated with liver function, and rifaximin might be more effective for covert HE with H-SIBO. Therefore, the diagnosis of SIBO, including the classification as H-SIBO and M-SIBO, might help to determine the choice of treatment for HE.

DOI： 10.1371/journal.pone.0264459

Tumor-to-tumor metastasis of colon cancer metastasizing to a pancreatic neuroendocrine tumor associated with von Hippel-Lindau disease: a case report

Tahata, Y., Hikita, H., Mochida, S., Enomoto, N., Kawada, N., Kurosaki, M., Ido, A., Miki, D., Yoshiji, H., Takikawa, Y., Sakamori, R., Hiasa, Y., Nakao, K., Kato, N., Ueno, Y., Yatsuhashi, H., Itoh, Y., Tateishi, R., Suda, G., Takami, T., Nakamoto, Y., Asahina, Y., Matsuura, K., Yamashita, T., Kanto, T., Akuta, N., Terai, S., Shimizu, M., Sobue, S., Miyaki, T., Moriuchi, A., Yamada, R., Kodama, T., Tatsumi, T., Yamada, T., Takehara, T.

Journal of Gastroenterology 57 ( 2 ) 2022年

Natsui, H., Kohisa, J., Yoshikawa, S., Takeuchi, M., Yagi, R., Minagawa, M., Tani, T., Usuda, H., Terai, S.

Clinical Journal of Gastroenterology 15 ( 6 ) 2022年

Small extracellular vesicles and liver diseases: From diagnosis to therapy

Tsuchiya, A., Natsui, K., Ishii, Y., Koseki, Y., Takeda, N., Tomiyoshi, K., Yamazaki, F., Yoshida, Y., Terai, S.

World Journal of Hepatology 14 ( 7 ) 2022年

Prognostic study of acute-on-chronic liver failure patients Usefulness of the fibrosis-4 index

Watanabe, Y., Osaki, A., Waguri, N., Tsuchiya, A., Terai, S.

Medicine (United States) 101 ( 44 ) 2022年

Small G1 type III gastric neuroendocrine cell tumor showing scirrhous invasion and lymph node metastasis

Sato, A., Sato, Y., Oka, H., Honda, Y., Terai, S.

Gastrointestinal Endoscopy 95 ( 1 ) 2022年

Two cases of portal-systemic encephalopathy caused by multiple portosystemic shunts successfully treated with percutaneous transhepatic obliteration

Watanabe, Y., Osaki, A., Yamazaki, S., Yamazaki, H., Kimura, K., Takaku, K., Sato, M., Waguri, N., Terai, S.

Clinical Journal of Gastroenterology 15 ( 5 ) 2022年

Needle tract seeding after endoscopic ultrasound-guided tissue acquisition of pancreatic tumors: Nationwide survey in Japan

Kitano, M., Yoshida, M., Ashida, R., Kita, E., Katanuma, A., Itoi, T., Mikata, R., Nishikawa, K., Matsubayashi, H., Takayama, Y., Kato, H., Takenaka, M., Ueki, T., Kawashima, Y., Nakai, Y., Hashimoto, S., Shigekawa, M., Nebiki, H., Tsumura, H., Okabe, Y., Ryozawa, S., Harada, Y., Mitoro, A., Sasaki, T., Yasuda, H., Miura, N., Ikemoto, T., Ozawa, E., Shioji, K., Yamaguchi, A., Okuzono, T., Moriyama, I., Hisai, H., Fujita, K., Goto, T., Shirahata, N., Iwata, Y., Okabe, Y., Hara, K., Hashimoto, Y., Kuwatani, M., Isayama, H., Fujimori, N., Masamune, A., Hatamaru, K., Shimokawa, T., Okazaki, K., Takeyama, Y., Yamaue, H., Abue, M., Aiura, K., Akashi, T., Akiyama, T., Aoyagi, H., Araki, M., Arizumi, T., Aruga, Y., Asada, M., Asai, S., Baba, T., Ban, S., Chinen, K., Doi, S., Eguchi, T., Endo, M., Endo, S., Ezaki, T., Fujii, K., Fujii, M., Fujimori, M., Fujimoto, Y., Fujita, Y., Fujita, Y., Fukasawa, M., Fukuba, N., Fukuchi, S., Fukuda, K., Furukawa, M., Furumatsu, K., Hakamada, K., Hanada, K., Harada, K., Harano, M., Hashigo, S., Hashiguchi, K., Hayashi, K., Hayashi, N., Hayatsu, S., Hijioka, S., Hirano, A., Hirao, M., Hirooka, Y., Hirota, M., Horino, K., Hotta, Y., Ijima, M., Ikuta, Y., Imakiire, K., Imamura, T., Inatomi, O., Inoue, T., Irisawa, A., Ishida, E., Ishihara, K., Ishii, S., Ishii, T., Ito, H., Ito, J., Ito, T., Iwahashi, K., Iwano, H., Iwasaki, E., Iwashita, T., Iwata, K., Kakimoto, T., Kaku, T., Kamochi, J., Kanamori, A., Kaneto, H., Karasaki, H., Kato, Y., Kawaguchi, Y., Kawakami, H., Kawase, T., Kawashima, H., Kikuyama, M., Kimura, K., Kimura, T., Kitamura, K., Kobashigawa, K., Kobayashi, A., Kobayashi, K., Kobayashi, M., Kodama, R., Kodama, Y., Koike, Y., Komaki, T., Komura, T., Kondo, H., Kondo, H., Koshita, S., Koya, T., Ku, Y., Kuriyama, K., Kuroda, T., Kuroki, M., Kuroki, T., Kushiyama, Y., Maekawa, H., Makino, N., M, ai, K., Maruyama, H., Maruyama, M., Matsubara, S., Matsumoto, R., Matsunaga, K., Matsusaki, S., Matsushita, A., Mihara, M., Miyaike, J., Miyata, H., Miyoshi, H., Mizuno, S., Morita, T., Mouri, T., Mukai, T., Murakami, K., Nagano, H., Nakahara, K., Nakahara, O., Nakai, Y., Nakaji, S., Nakajima, J., Nakanishi, F., Nakano, Y., Nakashima, S., Naota, H., Nishida, N., Nishide, T., Nishikiori, H., Nomura, Y., Ochi, Y., Ochiai, T., Oe, S., Ogura, T., Ohata, A., Ohshima, T., Ohtsubo, K., Oka, H., Okazaki, A., Okochi, O., Onishi, Y., Otsuka, Y., Sagami, R., Sakakihara, I., Sakata, T., Sasahira, N., Sasaki, A., Sato, H., Sato, S., Sato, T., Satoh, A., Sekine, M., Sen-yo, M., Serikawa, M., Shibuya, H., Shimizu, S., Shinzato, M., Shitani, M., Suda, T., Sugimori, K., Sumi, H., Suzuki, N., Suzuki, R., Suzuki, Y., Tadauchi, A., Takahashi, K., Takahashi, K., Takaya, H., Takeda, Y., Takeda, O., Takihara, H., Tanaka, Y., Tanno, S., Tawada, K., Taya, Y., Terai, S., Terauchi, T., Togashi, J., Toki, M., Toyama, T., Tsuda, H., Tsugeno, H., Tsutsui, S., Uchida, K., Ueki, T., Usuba, T., Uza, N., Wakiyama, S., Watanabe, M., Yagi, Y., Yamada, R., Yamamoto, R., Yamazaki, M., Yasuda, I., Yawata, A., Yokota, T., Yokoyama, K., Yoshida, K., Yoshikawa, S., Yoshikawa, T.

Digestive Endoscopy 34 ( 7 ) 2022年

Characteristics of colorectal neuroendocrine tumors in patients prospectively enrolled in a Japanese multicenter study: a first report from the C-NET STUDY

Sekiguchi, M., Hotta, K., Takeuchi, Y., Tanaka, S., Yamamoto, H., Shinmura, K., Harada, K., Uraoka, T., Hisabe, T., Sano, Y., Kondo, H., Horimatsu, T., Kikuchi, H., Kawamura, T., Nagata, S., Yamamoto, K., Tajika, M., Tsuji, S., Kusaka, T., Okuyama, Y., Yoshida, N., Moriyama, T., Hasebe, A., So, S., Kobara, H., Kashida, H., Miyanaga, R., Kato, S., Hayashi, Y., Sada, M., Fukuzawa, M., Kato, H., Takayama, T., Konishi, J., Matsushita, H.-O., Narasaka, T., Ohata, K., Togashi, K., Nakamura, H., Moriichi, K., Oda, Y., K, a, N., Kuwai, T., Terai, S., Sanomura, M., Kitamura, S., Miyamoto, H., Kiriyama, S., Mizuno, C., Saito, Y., Sekine, S., Ito, S., Nakahira, H., Oka, S., Hayashi, Y., Yoshimura, K., Ishikawa, H., Matsuda, T.

Journal of Gastroenterology 57 ( 8 ) 2022年

Gastric alarmin release: A warning signal in the development of gastric mucosal diseases

Wu, E., Zhu, J., Ma, Z., Tuo, B., Terai, S., Mizuno, K., Li, T., Liu, X.

Frontiers in Immunology 13 2022年

Steroid therapy still plays a crucial role and could serve as a bridge to the next promising treatments in patients with IgG4-related sclerosing cholangitis: Results of a Japanese nationwide study

Kubota, K., Kamisawa, T., Nakazawa, T., Tanaka, A., Naitoh, I., Takikawa, H., Unno, M., Kawa, S., Masamune, A., Nakamura, S., Okazaki, K., Furumatsu, K., Sawai, S., Goto, T., Okumura, T., Suzuki, D., Otsuka, M., Kobori, I., Tamano, M., Koizumi, M., Hiasa, Y., Kawabe, N., Hirooka, Y., Yamamoto, S., Asano, Y., Inui, K., Horiguchi, A., Watanabe, H., Toya, D., Hatayama, K., Ueki, T., Kinoshita, N., Sugimoto, M., Ohira, H., Mukai, T., Tomita, E., Iwata, K., Shimizu, S., Suetsugu, J., Shimizu, M., Tsuji, K., Ishida, R., Ito, M., Furukawa, R., Sakamoto, N., Araki, M., Tanno, S., Sakamoto, Y., Ito, T., Takai, S., Ikeya, S., Yamada, T., Kudara, N., Shimizu, A., Hanada, K., Ichiki, Y., Kitada, H., Hifumi, M., Kimura, H., Kurosaki, M., Izumi, N., Sumi, H., Haruta, Hayashi, K., Harada, R., Inoue, M., Nakamura, S., Ito, T., Tomishima, K., Isayama, H., Oura, K., Masaki, T., Shimokawahara, N., Tanoue, S., Maemura, K., Ido, A., Mizushima, I., Kawano, M., Yoshida, K., Naganuma, M., Murata, M., Nishio, A., Fujita, Y., Teratani, T., Matsubara, S., Tamai, H., Yoshida, Y., Azemoto, R., Kamata, K., Watanabe, T., Kurosu, T., Koizumi, W., Fujita, J., Seki, H., Ueda, Y., Fukumoto, T., Kousaki, T., Uchida, K., Ochiai, T., Kawasaki, T., Tanaka, M., Ishida, E., Notohara, K., Mori, H., Mori, T., Kawabata, H., Miyata, M., Sakagami, J., Itoh, Y., Shiokawa, M., Seno, H., Watanabe, N., Naitoh, I., Kataoka, H., Aoki, T., Fujishiro, M., Niihara, T., Nishimata, H., Mitoro, A., Yoshiji, H., Yoshida, M., Ikeda, M., Tomita, K., Hokari, R., Hayasaka, K., Amano, Y., Shioji, K., Hayashi, K., Terai, S., Nakajima, M., Yamahana, J., Matsumoto, R., Kikuchi, H., Kanamori, A., Kiriyama, S., Iwatsu, S., Kato, Y., Horiguchi, S., Yagi, T., Okada, H., Ohkawa, K., Hirao, M., Hiramatsu, N., Oza, N., Imamura, H., Baba, T., Nakano, S., Shinobi, T., Ryozawa, S., Motoya, M., Nakase, H., Kinoshita, N., Ito, K., Miyake, T., Kohge, N., Tobita, H., Joshita, S., Umemura, T., Kawaguchi, S., Ohno, K., Sonobe, K., Satoh, A., Shimosegawa, T., Miura, F., Yagi, M., Sano, K., Kin, T., Katanuma, A., Koike, K., Miura, S., Kawashima, Y., Kagawa, T., Azuma, S., Watanabe, M., Honjyo, M., Itoi, T., Honda, A., Kobayashi, K., Asano, T., Mizuno, S., Koike, K., Nishino, T., Taniguchi, H., Tajiri, K., Yasuda, I., Tanaka, Y., Oe, S., Harada, M., Kurata, M., Fukasawa, M., Enomoto, N., Kawaji, Y., Kitano, M., Nishise, Y., Hirakawa, H., Ishizawa, T., Ueno, Y., Kaino, M., Fujimoto, Y., Sakaida, I.

Journal of Hepato-Biliary-Pancreatic Sciences 29 ( 8 ) 2022年

A rare case of duodenal variceal bleeding due to extrahepatic portal vein obstruction successfully treated with endoscopic injection sclerotherapy

Hori, A., Watanabe, Y., Takahashi, K., Tonouchi, T., Kimura, N., Setsu, T., Ikarashi, S., Kamimura, H., Yokoyama, J., Terai, S.

Clinical Journal of Gastroenterology 15 ( 3 ) 2022年

A difficult-to-diagnose case of Borrmann type IV gastric cancer with marked transverse colon stenosis

Natsui, K., Maruyama, M., Terai, S.

JGH Open 6 ( 11 ) 2022年

The Visceral-to-subcutaneous Adipose Tissue Area Ratio Is Associated with Retreatment in Chronic Pancreatitis Patients with Pancreatolithiasis after Extracorporeal Shock Wave Lithotripsy

Yokoyama, K., Takamura, M., Watanabe, J., Nakamura, A., Sato, Y., Sekine, A., Terai, S.

Internal Medicine 61 ( 24 ) 2022年

Environmental factors, medical and family history, and comorbidities associated with primary biliary cholangitis in Japan: a multicenter case–control study

Matsumoto, K., Ohfuji, S., Abe, M., Komori, A., Takahashi, A., Fujii, H., Kawata, K., Noritake, H., Tadokoro, T., Honda, A., Asami, M., Namisaki, T., Ueno, M., Sato, K., Kakisaka, K., Arakawa, M., Ito, T., Tanaka, K., Matsui, T., Setsu, T., Takamura, M., Yasuda, S., Katsumi, T., Itakura, J., Sano, T., Tamura, Y., Miura, R., Arizumi, T., Asaoka, Y., Uno, K., Nishitani, A., Ueno, Y., Terai, S., Takikawa, Y., Morimoto, Y., Yoshiji, H., Mochida, S., Ikegami, T., Masaki, T., Kawada, N., Ohira, H., Tanaka, A.

Journal of Gastroenterology 57 ( 1 ) 2022年

Delayed and Synchronous Recurrence of Breast Cancer Metastases in Multiple Organs

Owaki, T., Hashimoto, S., Umezu, H., Terai, S.

Internal Medicine 61 ( 22 ) 2022年

Intrahepatic Bile Duct Foreign Body With Cholangitis After Pylorus-preserving Pancreatoduodenectomy: Is It a Fish Bone?

Natsui, K., Maruyama, M., Terai, S.

Gastroenterology 163 ( 4 ) 2022年

Endoscopic Findings and Treatment of Gastric Neoplasms in Familial Adenomatous Polyposis

Sato, C., Takahashi, K., Sato, H., Naruse, T., Nakajima, N., Takatsuna, M., Mizuno, K.-I., Hashimoto, S., Takeuchi, M., Yokoyama, J., Kobayashi, M., Terai, S.

Journal of Gastric Cancer 22 ( 4 ) 2022年

Case report: New subtype of gastric adenocarcinoma arising from an H. pylori infection-negative stomach: Foveolar epithelium and mucous neck cell-mixed type adenocarcinoma

Liu, X., Wu, X., Zhu, J., Yagi, K., Ajioka, Y., Terai, S., Mizuno, K., Li, H., Tuo, B., Di, L.

Frontiers in Oncology 12 2022年

Benign Duodenal Stenosis Caused by Huge Mesenteric Hematoma Conservatively Improved with Long-term Use of Double Elementary Diet Tube

Setsu, T., Yokoo, T., Sato, T., Kumagai, M., Motegi, S., Kawata, Y., Ogawa, K., Mizuno, K.-I., Terai, S.

Internal Medicine 61 ( 13 ) 2022年

Gravity assistance enables liver stiffness measurements to detect liver fibrosis under congestive circumstances

Suda, T., Sugimoto, A., Kanefuji, T., Abe, A., Yokoo, T., Hoshi, T., Abe, S., Morita, S., Yagi, K., Takahashi, M., Terai, S.

World Journal of Hepatology 14 ( 4 ) 2022年

Combination therapy of Juzentaihoto and mesenchymal stem cells attenuates liver damage and regresses fibrosis in mice. 国際誌

Takahiro Iwasawa, Shunsuke Nojiri, Atsunori Tsuchiya, Suguru Takeuchi, Takayuki Watanabe, Masahiro Ogawa, Satoko Motegi, Takeki Sato, Masaru Kumagai, Taiki Nakaya, Katsuya Ohbuchi, Miwa Nahata, Naoki Fujitsuka, Masaaki Takamura, Shuji Terai

Regenerative therapy 18 231 - 241 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Liver cirrhosis is an end-stage multiple liver disease. Mesenchymal stem cells (MSCs) are an attractive cell source for reducing liver damage and regressing fibrosis; additional therapies accompanying MSCs can potentially enhance their therapeutic effects. Kampo medicines exhibit anti-inflammatory and anti-oxidative effects. Here, we investigated the therapeutic effect of MSCs combined with the Kampo medicine Juzentaihoto (JTT) as a combination therapy in a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. Methods: C57BL/6 mice were administered JTT (orally) and/or MSCs (one time, intravenously). The levels of liver proteins were measured in the sera. Sirius Red staining and hydroxyproline quantitation of hepatic tissues and immune cells were conducted, and their associated properties were evaluated. Liver metabolomics of liver tissues was performed. Results: JTT monotherapy attenuated liver damage and increased serum albumin level, but it did not effectively induce fibrolysis. JTT rapidly reduced liver damage, in a dose-dependent manner, after a single-dose CCl4 administration. Furthermore, JTT-MSC combination therapy attenuated liver damage, improved liver function, and regressed liver fibrosis. The combination increased the CD4+/CD8+ ratio. JTT had stronger effects on NK and regulatory T cell induction, whereas MSCs more strongly induced anti-inflammatory macrophages. The combination therapy further induced anti-inflammatory macrophages. JTT normalized lipid mediators, and tricarboxylic acid cycle- and urea cycle-related mediators effectively. Conclusions: The addition of JTT enhanced the therapeutic effects of MSCs; this combination could be a potential treatment option for cirrhosis.

DOI： 10.1016/j.reth.2021.07.002

Nationwide survey for patients with acute-on-chronic liver failure occurring between 2017 and 2019 and diagnosed according to proposed Japanese criteria

Nobuaki Nakayama, Hayato Uemura, Yoshihito Uchida, Yukinori Imai, Tomoaki Tomiya, Shuji Terai, Hitoshi Yoshiji, Takuya Genda, Akio Ido, Kazuaki Inoue, Naoya Kato, Isao Sakaida, Masahito Shimizu, Yasuhiro Takikawa, Masanori Abe, Ryuzo Abe, Kazuaki Chayama, Kiyoshi Hasegawa, Ayano Inui, Mureo Kasahara, Hiromasa Ohira, Atsushi Tanaka, Hajime Takikawa, Satoshi Mochida

Journal of Gastroenterology 56 ( 12 ) 1092 - 1106 2021年12月

【再生医療への期待〜各疾患領域における現況と展望〜】肝臓領域における細胞を用いた再生医療の将来展望

寺井崇二, 渡邊雄介, 土屋淳紀

Pharma Medica 39 ( 12 ) 37 - 40 2021年12月

アルコール性肝硬変におけるB型肝炎ウイルス感染の発癌と予後に対する関与についての検討

坂牧僚, 小山究太郎, 森田真一, 阿部寛幸, 上村顕也, 高村昌昭, 寺井崇二

アルコールと医学生物学 40 47 - 49 2021年12月

New cine magnetic resonance imaging parameters for the differential diagnosis of chronic intestinal pseudo-obstruction. 国際誌

Hiroki Sato, Hiroyuki Ogihara, Kazuya Takahashi, Yuzo Kawata, Yuichi Kojima, Kentaro Tominaga, Junji Yokoyama, Yoshihiko Hamamoto, Shuji Terai

Scientific reports 11 ( 1 ) 22974 - 22974 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder whose diagnosis currently relies on subjective imaging assessments. Cine magnetic resonance imaging (MRI) may potentially improve the quantitative analysis of gastrointestinal motility; however, suitable CIPO detection parameters should be determined. Cine MRI was performed in seven patients with CIPO and 11 healthy controls. The logarithm of the Mahalanobis distance (x1) and distance variation per time (x2) were used as the original parameters to determine CIPO diagnostic thresholds. Furthermore, the correlation between cine MRI findings and CIPO severity was investigated. Threshold values of α = 1.10 and β = 0.15 for x1 and x2, respectively, produced a CIPO diagnosis sensitivity of 1.00 (7/7) and specificity of 0.82 (9/11). The resulting error was 0.11 (2/18). The two parameters were correlated (Pearson's correlation coefficient: - 0.52). Any of the intestinal tracts of patients with severe CIPO requiring home parenteral nutrition belonged to the region defined by x1 ≥ 1.10 and x2 ≤ 0.15. Cine MRI is effective for the quantitative evaluation of small intestinal motility and CIPO diagnosis when using the abovementioned parameters and can be useful for treatment decision-making. However, these parameters have a wide distribution in healthy volunteers; this may complicate the detection of other disorders.

DOI： 10.1038/s41598-021-02268-1

The risk of cirrhosis and its complications based on PNPLA3 rs738409 G allele frequency. 国際誌

Xue Shao, Haruki Uojima, Taeang Arai, Yuji Ogawa, Toru Setsu, Masanori Atsukawa, Yoshihiro Furuichi, Yoshitaka Arase, Kazue Horio, Hisashi Hidaka, Takahide Nakazawa, Makoto Kako, Tatehiro Kagawa, Katsuhiko Iwakiri, Atsushi Nakajima, Shuji Terai, Yasuhito Tanaka, Wasaburo Koizumi

Digestive diseases (Basel, Switzerland) 40 ( 5 ) 625 - 634 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Data regarding the influence of patatin-like phospholipase domain-containing 3 (PNPLA3) polymorphism for patients with liver cirrhosis (LC) are scarce. OBJECTIVE: This study assesses the role of the PNPLA3 polymorphism for the development of LC and its complications by the findings of genetic examinations. METHODS: Patients with LC caused by virus (n = 157), alcohol (n = 104), nonalcoholic fatty liver disease (NAFLD) (n = 106), or autoimmune disease (n = 33) and without LC (n = 128) were enrolled. LC were composed of the present and absent of complications, such as variceal bleeding, hepatic ascites, and/or hepatic encephalopathy. To assess the role of the PNPLA3 polymorphism, odds ratio (OR) for the rs738409 variant was calculated for the patients between (i) with LC and without LC in the entire cohort, and (ii) the present and absent of complications in the patients with LC. RESULTS: There was a significant difference among the patients without LC and those with alcohol, NAFLD related LC in the frequency of G alleles (p < 0.001, both). According to complications of LC, the OR for NAFLD related cirrhosis significantly increased in the presence of the two mutated alleles (OR = 3.165; p = 0.046) when the wild type was used as the reference. However, there were no significant risks for the complications in the virus and alcohol related cirrhosis unless there was a presence of G alleles. CONCLUSION: The PNPLA3 polymorphism was associated with the risk of NAFLD related LC and its complications.

DOI： 10.1159/000521062

Esophageal carcinoma in achalasia patients managed with endoscopic submucosal dissection and peroral endoscopic myotomy: Japan Achalasia Multicenter Study. 国際誌

Hiroki Sato, Yohei Nishikawa, Hirofumi Abe, Hironari Shiwaku, Junya Shiota, Chiaki Sato, Hiroyuki Sakae, Masaki Ominami, Yoshitaka Hata, Hisashi Fukuda, Ryo Ogawa, Jun Nakamura, Tetsuya Tatsuta, Yuichiro Ikebuchi, Hiroshi Yokomichi, Shuji Terai, Haruhiro Inoue

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 34 ( 5 ) 965 - 973 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Indications for peroral endoscopic myotomy (POEM) and endoscopic submucosal dissection (ESD) in patients with achalasia concomitant with esophageal carcinoma (EC) are unclear. This study aimed to clarify the role of POEM in cases of achalasia concomitant with EC and to elucidate the indications for ESD and efficient surveillance for EC. METHODS: We conducted a multicenter cohort study at 14 hospitals in Japan, including 3707 cases of achalasia-related esophageal motility disorders (EMDs). Factors contributing to EC risk, the characteristics of EC, and clinical outcomes of POEM/ESD were analyzed. RESULTS: In patients undergoing POEM, screening and surveillance endoscopy throughout a 1-year period resulted in diagnosis of 72.1% new EC cases. Of 62 patients with 123 ECs, 40.3% had multiple or metachronous lesions within 37.5 months. EC was predominantly observed in the middle thoracic esophagus (58.5%) and posteriorly (73.2%). POEM had comparable safety and efficacy in cases of concomitant EC even after ESD. Endoscopic en bloc resection was performed in 95.8% and 89.3% of ECs diagnosed before and after POEM, respectively (P = 0.351); however, ESD on the POEM-line was impaired by fibrosis. Multivariate analysis revealed risk factors for EC, including regular alcohol consumption, a history of smoking, advanced age, and extended disease duration. Alcohol intake and smoking had a synergistic effect on EC development. CONCLUSIONS: Screening and surveillance of POEM help in detecting EC. ESD is feasible in achalasia, although on the POEM-line is challenging. Surveillance endoscopy for EC is recommended for cases with specific risks and a history of ECs.

DOI： 10.1111/den.14197

脾動脈瘤破裂を契機にC型肝炎治療に至った肝硬変の1例

北條雄暉, 上村博輝, 大脇崇史, 木村莉菓, 岩澤貴宏, 渡邊雄介, 高綱将史, 五十嵐聡, 高村昌昭, 薛徹, 荒生祥尚, 堀井陽祐, 佐藤辰彦, 寺井崇二

肝臓 62 ( 11 ) 749 - 755 2021年11月

脾動脈瘤破裂を契機にC型肝炎治療に至った肝硬変の1例

北條雄暉, 上村博輝, 大脇崇史, 木村莉菓, 岩澤貴宏, 渡邊雄介, 高綱将史, 五十嵐聡, 高村昌昭, 薛徹, 荒生祥尚, 堀井陽祐, 佐藤辰彦, 寺井崇二

肝臓 62 ( 11 ) 749 - 755 2021年11月

【肝不全・肝硬変に対する再生療法-最先端の今】基礎的知見の進歩自律神経経路を介した臓器連関と肝再生

上村顕也, 井上良介, 名古屋拓郎, 高昌良, 大脇崇史, 寺井崇二

臨床消化器内科 36 ( 13 ) 1623 - 1628 2021年11月

【肝硬変は治るか?組織改築改善・研究の最前線】トランスレーショナルリサーチ間葉系幹細胞、エクソソームを用いた肝硬変治療

土屋淳紀, 寺井崇二

医学のあゆみ 279 ( 8 ) 790 - 794 2021年11月

【肝不全・肝硬変に対する再生療法-最先端の今】開発中の肝再生医療間葉系幹細胞,マクロファージ,エクソソームを用いた再生療法

土屋淳紀, 寺井崇二

臨床消化器内科 36 ( 13 ) 1647 - 1652 2021年11月

Rapid progression of colonic mucinous adenocarcinoma with immunosuppressive condition: A case report and review of literature. 国際誌

Youhei Koseki, Kenya Kamimura, Yuto Tanaka, Marina Ohkoshi-Yamada, Qiliang Zhou, Yoshifumi Matsumoto, Takeshi Mizusawa, Hiroki Sato, Akira Sakamaki, Hajime Umezu, Junji Yokoyama, Shuji Terai

World journal of clinical cases 9 ( 30 ) 9182 - 9191 2021年10月

記述言語：英語

BACKGROUND: Colorectal mucinous adenocarcinoma is a rare subtype of colorectal cancer and is characterized by an abundance of mucin in the tumor. In addition, the colorectal mucinous adenocarcinoma often demonstrates poor differentiation in the histology of tumor cells and poor prognosis compared with those with adenocarcinoma. Here, we present the case of a young woman with colonic mucinous adenocarcinoma showing significantly rapid progression within four months of immunosuppressant therapy for Henoch-Schönlein purpura. CASE SUMMARY: Here we report a rare case of ascending colon mucinous adenocarcinoma with lymph node and liver metastases which developed and progressed rapidly within four months during the treatment of Henoch-Schönlein purpura using corticosteroids. The systemic screening examinations showed no tumors before the immunosuppressant therapy. Fortunately, the patient was successfully treated with chemotherapy. CONCLUSION: While no direct evidence that the immunosuppressants accelerated the tumor development, the case presenta tion and review of the literature demonstrated that surveillance for malignancies before and during treatment with immunosuppressive agents is essential.

DOI： 10.12998/wjcc.v9.i30.9182

胆管への浸潤を伴う胆管内乳頭状粘液性腺癌 1症例報告(Intraductal papillary mucinous adenocarcinoma with bile duct invasion: A case report)

水戸將貴, 戸田遼, 木村究, 小島雄一, 小川光平, 木村成宏, 荒生祥尚, 五十嵐聡, 林和直, 土屋淳紀, 寺井崇二, 加藤卓, 味岡洋一, 石川博補, 滝沢一泰, 若井俊文

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 69回・91回 53 - 53 2021年10月

Rare complication of hepatocellular carcinoma in Wilson's disease. 国際誌

Marina Ohkoshi-Yamada, Kenya Kamimura, Hiroteru Kamimura, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 5 ( 10 ) 1220 - 1222 2021年10月

記述言語：英語

The complication of hepatocellular carcinoma (HCC) in Wilson's disease is rare. Wilson's disease treatment using D-penicillamine (DPA) is useful to prevent HCC occurrence; however, it also causes iron accumulation and synergistic radical formation in the liver, which may enhance carcinogenesis. Reported herein is a case of HCC in Wilson's disease treated with DPA for 36 years. The tumor was surgically resected and histologically diagnosed with moderately differentiated HCC surrounded by cirrhotic tissue with fatty infiltration. Rhodanine staining revealed a slight positively stained area in both tumor and surrounding tissues. Information obtained from this case and literature review highlight the feature of HCC in Wilson's disease.

DOI： 10.1002/jgh3.12648

消化器診療におけるサルコペニアの意義 1-kestoseが高齢サルコペニアの腸内細菌と筋肉量に与える影響

有症化した症候性巨大肝嚢胞に対して、ミノサイクリン硬化療法が著効した一例

木南佳也, 小川和也, 石井壮一, 遠藤沙織, 石川夏生, 阿部寛幸, 佐藤裕樹, 坂牧僚, 上村顕也, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 69回・91回 93 - 93 2021年10月

冨永顕太郎, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増大会 ) A461 - A461 2021年10月

自律神経経路を介した臓器連関と肝疾患

上村顕也, 大脇崇史, 高昌良, 永山逸夫, 名古屋拓郎, 井上良介, 上野将紀, 寺井崇二

日本自律神経学会総会プログラム・抄録集 74回 87 - 87 2021年10月

胆管への浸潤を伴う胆管内乳頭状粘液性腺癌 1症例報告(Intraductal papillary mucinous adenocarcinoma with bile duct invasion: A case report)

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 69回・91回 53 - 53 2021年10月

原発性胆汁性胆管炎患者の予後を最もよく予想する治療反応性判定Criteriaについて

木村成宏, 高村昌昭, 武田信峻, 荒生祥尚, 高綱将史, 渡邉雄介, 竹内卓, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増大会 ) A698 - A698 2021年10月

消化器診療におけるサルコペニアの意義 1-kestoseが高齢サルコペニアの腸内細菌と筋肉量に与える影響

冨永顕太郎, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増大会 ) A461 - A461 2021年10月

原発性胆汁性胆管炎患者の予後を最もよく予想する治療反応性判定Criteriaについて

木村成宏, 高村昌昭, 武田信峻, 荒生祥尚, 高綱将史, 渡邉雄介, 竹内卓, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増大会 ) A698 - A698 2021年10月

有症化した症候性巨大肝嚢胞に対して、ミノサイクリン硬化療法が著効した一例

木南佳也, 小川和也, 石井壮一, 遠藤沙織, 石川夏生, 阿部寛幸, 佐藤裕樹, 坂牧僚, 上村顕也, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 69回・91回 93 - 93 2021年10月

Interventional EUS超音波内視鏡下瘻孔形成術の現状と問題点(膵) 重症急性膵炎後Walled-off necrosisの自然軽快に関連する因子

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増大会 ) A550 - A550 2021年10月

大腸がん検診を受診しない理由に関するアンケート調査

水野研一, 川田雄三, 林和直, 寺井崇二, 中島尚

日本消化器病学会雑誌 118 ( 臨増大会 ) A706 - A706 2021年10月

超音波内視鏡システムにおける音速補正モードの膵癌診断における有用性の検討

林和直, 小川光平, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 63 ( Suppl.2 ) 2046 - 2046 2021年10月

当院における自己免疫性膵炎およびIgG4関連硬化性胆管炎の内視鏡診断と治療

小川光平, 五十嵐聡, 林和直, 寺井崇二

Gastroenterological Endoscopy 63 ( Suppl.2 ) 2073 - 2073 2021年10月

Synthesized HMGB1 peptide attenuates liver inflammation and suppresses fibrosis in mice. 国際誌

Shunsuke Nojiri, Atsunori Tsuchiya, Kazuki Natsui, Suguru Takeuchi, Takayuki Watanabe, Yuichi Kojima, Yusuke Watanabe, Hiroteru Kamimura, Masahiro Ogawa, Satoko Motegi, Takahiro Iwasawa, Takeki Sato, Masaru Kumagai, Yui Ishii, Tomomi Kitayama, Yu-Tung Li, Yuya Ouchi, Takashi Shimbo, Masaaki Takamura, Katsuto Tamai, Shuji Terai

Inflammation and regeneration 41 ( 1 ) 28 - 28 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The liver has a high regenerative ability and can induce spontaneous regression of fibrosis when early liver damage occurs; however, these abilities are lost when chronic liver damage results in decompensated cirrhosis. Cell therapies, such as mesenchymal stem cell (MSC) and macrophage therapies, have attracted attention as potential strategies for mitigating liver fibrosis. Here, we evaluated the therapeutic effects of HMGB1 peptide synthesized from box A of high mobility group box 1 protein. Liver damage and fibrosis were evaluated using a carbon tetrachloride (CCl4)-induced cirrhosis mouse model. The effects of HMGB1 peptide against immune cells were evaluated by single-cell RNA-seq using liver tissues, and those against monocytes/macrophages were further evaluated by in vitro analyses. Administration of HMGB1 peptide did not elicit a rapid response within 36 h, but attenuated liver damage after 1 week and suppressed fibrosis after 2 weeks. Fibrosis regression developed over time, despite continuous liver damage, suggesting that administration of this peptide could induce fibrolysis. In vitro analyses could not confirm a direct effect of HMGB1 peptide against monocyte/macrophages. However, macrophages were the most affected immune cells in the liver, and the number of scar-associated macrophages (Trem2+Cd9+ cells) with anti-inflammatory markers increased in the liver following HMGB1 treatment, suggesting that indirect effects of monocytes/macrophages were important for therapeutic efficacy. Overall, we established a new concept for cell-free therapy using HMGB1 peptide for cirrhosis through the induction of anti-inflammatory macrophages.

DOI： 10.1186/s41232-021-00177-4

Transition of clinical and basic studies on liver cirrhosis treatment using cells to seek the best treatment. 国際誌

Shuji Terai, Atsunori Tsuchiya, Yusuke Watanabe, Suguru Takeuchi

Inflammation and regeneration 41 ( 1 ) 27 - 27 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

The liver is a highly regenerative organ; however, its regeneration potential is reduced by chronic inflammation with fibrosis accumulation, leading to cirrhosis. With an aim to tackle liver cirrhosis, a life-threatening disease, trials of autologous bone marrow cell infusion (ABMi) therapy started in 2003. Clinical studies revealed that ABMi attenuated liver fibrosis and improved liver function in some patients; however, this therapy has some limitations such as the need of general anesthesia. Following ABMi therapy, studies have focused on specific cells such as mesenchymal stromal cells (MSCs) from a variety of tissues such as bone marrow, adipose tissue, and umbilical cord tissues. Particularly, studies have focused on gaining mechanistic insights into MSC distribution and effects on immune cells, especially macrophages. Several basic studies have reported the use of MSCs for liver cirrhosis models, while a number of clinical studies have used autologous and allogeneic MSCs; however, there are only a few reports on the obvious substantial effect of MSCs in clinical studies. Since then, studies have analyzed and identified the important signals or components in MSCs that regulate immune cells, such as macrophages, under cirrhotic conditions and have revealed that MSC-derived exosomes are key regulators. Researchers are still seeking the best approach and filling the gap between basic and clinical studies to treat liver cirrhosis. This paper highlights the timeline of basic and clinical studies analyzing ABMi and MSC therapies for cirrhosis and the scope for future studies and therapy.

DOI： 10.1186/s41232-021-00178-3

Advances in the Treatment of Gastrointestinal Bleeding: Safety and Efficiency of Transnasal Endoscopy. 国際誌

Hiroyuki Abe, Kenya Kamimura, Yoshihisa Arao, Junji Kohisa, Shuji Terai

Medicines (Basel, Switzerland) 8 ( 9 ) 2021年9月

記述言語：英語

Acute upper gastrointestinal bleeding (UGIB) is a common disorder and a gastroenterological emergency. With the development of new techniques and devices, the survivability after gastrointestinal bleeding is improving. However, at the same time, we are facing the difficulty of severely complicated cases with various diseases. For example, while endoscopic examination with a normal diameter endoscope is essential for the diagnosis and treatment of UGIB, there are several cases in which it cannot be used. In these cases, transnasal endoscopy (TNE) may be a viable treatment option. This report reviews current hemostatic devices for endoscopic treatment and the safety and efficiency of using TNE in complicated cases. The latter will be demonstrated in a case report where TNE was employed in a patient with severe esophageal stenosis. This review summarizes the advances made in the devices used and will provide further ideas for the physician in terms of combining these devices and TNE.

DOI： 10.3390/medicines8090053

【肝疾患エキスパートブック栄養管理に活かすための最新情報】(Part 1)肝硬変肝硬変に対する運動療法について

上村博輝, 寺井崇二, 眞田菜緒, 小師優子

臨床栄養 139 ( 4 ) 445 - 451 2021年9月

【膵癌研究最前線】膵臓選択的ハイドロダイナミック遺伝子導入法

柴田理, 上村顕也, 田中裕登, 小川光平, 阿部寛幸, 五十嵐聡, 横尾健, 寺井崇二

消化器・肝臓内科 10 ( 3 ) 342 - 346 2021年9月

急性肝障害からの回復の予測バイオマーカーとしての血中セロトニン測定の意義

薛徹, 上村顕也, 大脇崇史, 荒生祥尚, 横尾健, 坂牧僚, 上村博輝, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.2 ) A536 - A536 2021年9月

消化器領域における再生医療の研究と新たな臨床応用肝硬変に対する間葉系幹細胞やそのエクソソームを用いた治療法開発を目指して

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.2 ) A533 - A533 2021年9月

肝硬変の近未来診療肝硬変の線維化改善を目指したHMGB1部分ペプチド療法の基礎検討と医師主導治験への展開

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.2 ) A511 - A511 2021年9月

The prognosis and incidence of hepatic encephalopathy of patients with liver cirrhosis treated with proton pump inhibitors: A multicenter retrospective study in Japan. 国際誌

Akira Sakamaki, Kenya Kamimura, Takeshi Yokoo, Akihiko Osaki, Seiichi Yoshikawa, Yoshihisa Arao, Toru Setsu, Hiroteru Kamimura, Nobuo Waguri, Manabu Takeuchi, Kazuhiro Funakoshi, Shuji Terai

Medicine 100 ( 32 ) e26902 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

ABSTRACT: Gastrointestinal bleeding, hepatic encephalopathy (HE), and hepatocarcinogenesis are associated with the prognosis of patients with liver cirrhosis (LC). Proton pump inhibitors (PPIs) have been used to prevent bleeding, however the effects of PPIs on overall survival have not yet been elucidated. Therefore, this multicenter retrospective study aimed to assess the effect of PPI on the prognosis and HE occurrence of the patients with liver cirrhosis in Japan.A total of 456 patients diagnosed with LC at the 4 institutes during the study period (2010-2014) were assessed. PPI-treated and non-treated patients were compared using propensity score matching analysis. Primary and secondary endpoints of the study were set as the occurrence of HE and overall survival, respectively.A comparison of all cases showed a significantly poorer hepatic reserve function in the PPI-treated patients. The propensity-score matching analysis was performed and 120 PPI-treated patients were 1:1 matched with non-treated patients. The analysis revealed a higher incidence of HE in the PPI-treated than in the non-treated patients (P = .032; hazard ratio [HR], 2.162; 95% confidence interval [CI], 1.066-4.176), but the prognosis of PPI-treated patients was no worse than that of non-treated patients (P = .676; HR, 1.101; 95% CI, 0.702-1.726).This retrospective study showed that PPI administration for the patients with liver cirrhosis may partly be related to the increased incidence of HE but not worsen the patient prognosis.

DOI： 10.1097/MD.0000000000026902

A Rare Case of Ulcerative Colitis with Severe Pneumocystis jirovecii Pneumonia and Cytomegalovirus Colitis: A Case Report and Literature Review.

Yusuke Watanabe, Kazunao Hayashi, Shuji Terai

Internal medicine (Tokyo, Japan) 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pneumocystis jirovecii pneumonia (PJP) and cytomegalovirus (CMV) colitis are opportunistic infections that occur during immunosuppressive treatments for ulcerative colitis (UC). The prognosis of PJP and CMV colitis is very poor. We herein report a rare case of a 74-year-old UC patient with PJP and CMV colitis that was successfully treated with intensive therapy. PJP progresses rapidly, so the timing and choice of treatment are critical. Furthermore, a literature review of similar cases suggested that prophylactic therapy for opportunistic infections might be important, especially in the elderly. This case will serve as a reference for successful treatment in future cases.

DOI： 10.2169/internalmedicine.7953-21

Risk of delayed bleeding after hot snare polypectomy and endoscopic mucosal resection in the colorectum with continuation of anticoagulants. 国際誌

Takamasa Kobayashi, Manabu Takeuchi, Yuki Hojo, Yui Ishii, Youhei Koseki, Yoko Kobayashi, Motoi Azumi, Yuji Kobayashi, Junji Kohisa, Seiichi Yoshikawa, Shuji Terai

Journal of gastrointestinal oncology 12 ( 4 ) 1518 - 1530 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Current guidelines recommend the temporary discontinuation of anticoagulants before colonoscopic polypectomy, but the effect of this practice on reducing the risk of delayed bleeding after hot snare polypectomy (HSP) and endoscopic mucosal resection (EMR) remains unclear. Our aim was to assess the impact of anticoagulants on the risk of colorectal delayed bleeding after HSP and EMR, and evaluate the necessity of drug withdrawal. Methods: We reviewed the clinical data of patients with colorectal polyps using antithrombotic drugs who underwent HSP and/or EMR between January 2016 and September 2020 at Nagaoka Red Cross Hospital. After excluding antiplatelet users, patients were classified into those who continued anticoagulants [continuation group: 50 patients (93 lesions)] and those who discontinued anticoagulants [discontinuation group: 87 patients (190 lesions)]. Results: Delayed bleeding occurred in 12 lesions, and there was no significant difference in the incidence rates between the continuation and the discontinuation groups (3.2% vs. 4.7%; P=0.756). Logistic regression analysis showed that continued use of anticoagulants was not a significant risk factor for delayed bleeding compared to anticoagulant discontinuation (odds ratio, 0.670; 95% CI, 0.177-2.537; P=0.556). There was no significant difference in the incidence rate and risk of delayed bleeding, regardless of the length of the anticoagulant withdrawal period. Conclusions: Continued use of anticoagulants, compared to their discontinuation, did not increase the risk of colorectal delayed bleeding after HSP and EMR. Our results suggest that current guideline recommendations for anticoagulant withdrawal before colonoscopic polypectomy may be reconsidered. Trial Registration: UMIN000040449.

DOI： 10.21037/jgo-21-3

The promise of radiotherapy for hepatocellular carcinoma. 国際誌

Kenya Kamimura, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 51 ( 8 ) 837 - 838 2021年8月

Pyloric-gland metaplasia may be an origin of cancer and intestinal metaplasia with possible CDX2 expression. 国際誌

Kazuyoshi Yagi, Atsunori Tsuchiya, Satoru Hashimoto, Taisuke Kato, Osamu Onodera, Shuji Terai

Gastroenterology report 9 ( 4 ) 370 - 373 2021年8月

門脈圧亢進症と臓器相関心、肝、肺、腎、脾当院における心不全に伴う肝臓への影響(Cardiac Hepatopathy)の解析

上村博輝, 寺井崇二, 猪又孝文, 三井田秀, 山崎文紗子, 柏村健, 藤木信也, 渡邊雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 坂牧僚, 横尾健

日本門脈圧亢進症学会雑誌 27 ( 3 ) 109 - 109 2021年8月

急性膵炎後の膵仮性嚢胞門脈瘻による広範な門脈血栓症を発症した2例

木村成宏, 林和直, 土屋淳紀, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 147 - 147 2021年8月

門脈圧亢進症を伴う肝硬変に対する薬物療法の進歩〜QOL、予後の改善を目指して〜肝硬変に伴うサルコペニアに対する難吸収性抗菌薬の有用性についての検討

坂牧僚, 土屋淳紀, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 106 - 106 2021年8月

潜在性肝性脳症は水素型SIBOに関連し、その治療にはリファキシミンが有効である

坂牧僚, 横山邦彦, 高橋一也, 成瀬匠, 冨永顕太郎, 佐藤裕樹, 上村顕也, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 176 - 176 2021年8月

BRTO中に出血を来し、NBCAによるEISを併用し治療を完遂した十二指腸静脈瘤の1例

前田悠一郎, 荒生祥尚, 小島雄一, 川田雄三, 渡邉雄介, 薛徹, 阿部寛幸, 坂牧僚, 上村博輝, 横尾健, 土屋淳紀, 上村顕也, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 27 ( 3 ) 134 - 134 2021年8月

Suppression of Noncoding RNAs as Shared Early Genetic Events in Multistep Hepatocarcinogenesis. 国際誌

Takeshi Suda, Seiichi Yoshikawa, Tsutomu Kanefuji, Satoshi Abe, Takahiro Hoshi, Shinichi Morita, Kazuyoshi Yagi, Shuji Terai

Hepatology (Baltimore, Md.) 2021年7月

A genome-wide association study identifying SVEP1 variant as a predictor of response to tolvaptan for cirrhotic ascites. 国際誌

Hideto Kawaratani, Hiromi Sawai, Masaya Onishi, Tomomi Kogiso, Noritomo Shimada, Haruki Uojima, Tomoaki Nakajima, Naoki Matsumoto, Kenichi Ikejima, Toru Ishikawa, Shuji Terai, Hiroyuki Motoyama, Atsumasa Komori, Noboru Hirashima, Satoru Saito, Yuichiro Eguchi, Masanori Nojima, Yosuke Kawai, Masakuni Tateyama, Hitoshi Yoshiji, Yasuhito Tanaka

Liver international : official journal of the International Association for the Study of the Liver 41 ( 12 ) 2944 - 2953 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND & AIMS: Tolvaptan, vasopressin V2-receptor antagonist, has been used for patients with difficult-to-treat ascites in Japan. In this study, we conducted a genome-wide association study (GWAS) in the Japanese population to identify genetic variants associated with tolvaptan's efficacy for patients with hepatic ascites. METHODS: From 2014 through 2018, genomic DNA samples were obtained from 550 patients who were treated with tolvaptan. Of those, 80 cases (non-responder; increase of body weight [BW]) and 333 controls (responder; >1.5 kg decrease of BW) were included in the GWAS and replication study. RESULTS: Genome-wide association study showed 5 candidate SNPs around the miR818, KIAA1109, and SVEP1 genes. After validation and performing a replication study, an SNP (rs2991364) located in the SVEP1 gene was found to have a significant genome-wide association (OR = 3.55, P = 2.01 × 10-8 ). Multivariate analyses showed that serum sodium (Na), blood urea nitrogen (BUN) and SVEP1 SNP were significantly associated with the response (OR = 0.92, P = .003; OR = 1.02, P = .02 and OR = 3.98, P = .000008, respectively). Based on a prediction model of logistic regression analysis in a population with the rs2991364 risk allele, the failure probability (=exp (score: 22.234 + BUN*0.077 + Na*-0.179) (1 + exp (score)) was determined for the detection of non-responders. Assuming a cutoff of failure probability at 38.6%, sensitivity was 84.4%, specificity was 70% and AUC was 0.774. CONCLUSION: SVEP1 rs2991364 was identified as the specific SNP for the tolvaptan response. The prediction score (>38.6%) can identify tolvaptan non-responders and help to avoid a lengthy period of futile treatment.

DOI： 10.1111/liv.15022

Evidence-based clinical practice guidelines for Liver Cirrhosis 2020.

Hitoshi Yoshiji, Sumiko Nagoshi, Takemi Akahane, Yoshinari Asaoka, Yoshiyuki Ueno, Koji Ogawa, Takumi Kawaguchi, Masayuki Kurosaki, Isao Sakaida, Masahito Shimizu, Makiko Taniai, Shuji Terai, Hiroki Nishikawa, Yoichi Hiasa, Hisashi Hidaka, Hiroto Miwa, Kazuaki Chayama, Nobuyuki Enomoto, Tooru Shimosegawa, Tetsuo Takehara, Kazuhiko Koike

Journal of gastroenterology 56 ( 7 ) 593 - 619 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japan Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

DOI： 10.1007/s00535-021-01788-x

Evidence-based clinical practice guidelines for liver cirrhosis 2020. 国際誌

Hepatology research : the official journal of the Japan Society of Hepatology 51 ( 7 ) 725 - 749 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

The first edition of the clinical practice guidelines for liver cirrhosis was published in 2010, and the second edition was published in 2015 by the Japanese Society of Gastroenterology (JSGE). The revised third edition was recently published in 2020. This version has become a joint guideline by the JSGE and the Japanese Society of Hepatology (JSH). In addition to the clinical questions (CQs), background questions (BQs) are new items for basic clinical knowledge, and future research questions (FRQs) are newly added clinically important items. Concerning the clinical treatment of liver cirrhosis, new findings have been reported over the past 5 years since the second edition. In this revision, we decided to match the international standards as much as possible by referring to the latest international guidelines. Newly developed agents for various complications have also made great progress. In comparison with the latest global guidelines, such as the European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases (AASLD), we are introducing data based on the evidence for clinical practice in Japan. The flowchart for nutrition therapy was reviewed to be useful for daily medical care by referring to overseas guidelines. We also explain several clinically important items that have recently received focus and were not mentioned in the last editions. This digest version describes the issues related to the management of liver cirrhosis and several complications in clinical practice. The content begins with a diagnostic algorithm, the revised flowchart for nutritional therapy, and refracted ascites, which are of great importance to patients with cirrhosis. In addition to the updated antiviral therapy for hepatitis B and C liver cirrhosis, the latest treatments for non-viral cirrhosis, such as alcoholic steatohepatitis/non-alcoholic steatohepatitis (ASH/NASH) and autoimmune-related cirrhosis, are also described. It also covers the latest evidence regarding the diagnosis and treatment of liver cirrhosis complications, namely gastrointestinal bleeding, ascites, hepatorenal syndrome and acute kidney injury, hepatic encephalopathy, portal thrombus, sarcopenia, muscle cramp, thrombocytopenia, pruritus, hepatopulmonary syndrome, portopulmonary hypertension, and vitamin D deficiency, including BQ, CQ and FRQ. Finally, this guideline covers prognosis prediction and liver transplantation, especially focusing on several new findings since the last version. Since this revision is a joint guideline by both societies, the same content is published simultaneously in the official English journal of JSGE and JSH.

DOI： 10.1111/hepr.13678

Impact of continuous positive airway pressure therapy for nonalcoholic fatty liver disease in patients with obstructive sleep apnea. 国際誌

Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa, Masaki Kohno, Shuji Terai, Shogo Ohkoshi

World journal of clinical cases 9 ( 19 ) 5112 - 5125 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Obstructive sleep apnea (OSA) has been suggested as an independent risk factor for nonalcoholic fatty liver disease (NAFLD), and continuous positive airway pressure (CPAP) is the first-line therapy for OSA. AIM: To clarify the efficacy of effective CPAP therapy on NAFLD of OSA patients by serum markers and transient elastography (TE) using FibroScan® (Echosens, Paris, France). METHODS: We prospectively enrolled 123 consecutive patients with OSA who met the indications for CPAP. Liver fibrosis and steatosis were assessed using TE. Before and after 6 mo of CPAP therapy, serum markers and TE were assessed for all patients. The mean usage rate of CPAP therapy for 6 mo was arbitrarily calculated in each patient and expressed as "mean compliance index" (m-CI). RESULTS: In 50 OSA patients with NAFLD, both aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly decreased after 6 mo of CPAP therapy. Univariate analysis showed that decreased body weight (BW), decreased body mass index (BMI), decreased AST level, decreased hemoglobin A1c, and high m-CI were significantly related with improved ALT level. In multivariate regression model adjusted for quantities of BW change during 6 mo of CPAP therapy, high m-CI tended to improve ALT level (P = 0.051). All 17 OSA patients with NAFLD, high m-CI and no BMI changes showed significant improvements in AST and ALT levels. Meanwhile, no significant changes in TE data or serum fibrosis markers were seen. CONCLUSION: Some NAFLD could be associated with chronic intermittent hypoxia due to OSA independent of BW changes. In those cases, adequate reoxygenation from effective CPAP therapy may improve NAFLD.

DOI： 10.12998/wjcc.v9.i19.5112

Biliary Obstruction Caused by B-Cell Lymphoma Associated With IgG4-Related Disease. 国際誌

Kazuya Ogawa, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Shuji Terai

The American journal of gastroenterology 2021年7月

Tuberculous Spondylitis in a Woman without Pulmonary Lesions.

Shinichi Morita, Toshinori Takada, Kazumasa Ohashi, Shuji Terai

Internal medicine (Tokyo, Japan) 60 ( 13 ) 2157 - 2158 2021年7月

当院における腹腔鏡・内視鏡合同手術(LECS)の現状と課題

加納陽介, 羽入隆晃, 佐藤裕樹, 水野研一, 市川寛, 石川卓, 宗岡悠介, 茂木大輔, 須藤翔, 小柳英人, 三浦宏平, 滝沢一泰, 中野雅人, 島田能史, 永橋昌幸, 坂田純, 寺井崇二, 若井俊文

ENDOSCOPIC FORUM for digestive disease 37 ( 1 ) 36 - 36 2021年7月

Rapid decline in visceral adipose tissue over 1 month is associated with poor prognosis in patients with unresectable pancreatic cancer. 国際誌

Oki Nakano, Hirokazu Kawai, Takamasa Kobayashi, Junji Kohisa, Satoshi Ikarashi, Kazunao Hayashi, Junji Yokoyama, Shuji Terai

Cancer medicine 10 ( 13 ) 4291 - 4301 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Involuntary weight loss related to cachexia is common in patients with advanced cancer, but the association between body composition changes and survival is still unclear in pancreatic cancer. METHODS: We retrospectively reviewed the clinical outcomes of 55 patients with advanced pancreatic cancer undergoing palliative therapy or best supportive care (BSC). The skeletal muscle index (SMI), visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue area ratio (VSR) were calculated based on the cross-sectional area on two sets of computed tomography images obtained at cancer diagnosis and 1 month later before treatment. The prognostic value of body composition indexes at diagnosis and the changes in those indexes over 1 month was then evaluated. RESULTS: In total, 45 patients (81.8%) received chemotherapy, chemoradiation, or radiation therapy, whereas the remaining patients underwent BSC. There were 27 patients (49.1%) who had low SMI at cancer diagnosis. Univariate analysis showed no significant associations between the baseline body composition indexes including SMI, VATI, SATI, and VSR and survival. Meanwhile, male sex (HR, 2.79; 95% CI, 1.16-6.71, p = 0.022) and higher decrease in VATI over 1 month (HR, 2.41; 95% CI, 1.13-5.13, p = 0.023) were identified as independent risk factors for mortality in multivariate analysis. CONCLUSION: Rapid decline in VAT over 1 month is closely associated with poorer survival in unresectable advanced pancreatic cancer. A short-term assessment of body composition changes may be a rational approach to predict prognosis in these patients.

DOI： 10.1002/cam4.3964

Rapid Onset of Weight Gain and Liver Dysfunction Successfully Treated With Nutrition and Exercise. 国際誌

Hiroteru Kamimura, Masakazu Sano, Takanori Tsujimura, Yasunaga Takeda, Yuko Komoro, Junji Yokoyama, Shuji Terai

Cureus 13 ( 7 ) e16530 2021年7月

記述言語：英語

Physical inactivity is one of the causes of most metabolic syndromes. The incidence of metabolic syndrome is expected to increase in the near future because of the reduced opportunities for exercise caused by COVID-19. Non-alcoholic fatty liver disease (NAFLD) is currently the most common cause of chronic liver disease. Changes in diet and lifestyle have led to a dramatic increase in the prevalence of NAFLD in the world. NAFLD is characterized by excessive triglyceride (TG) accumulation in the hepatocytes due to both increased inflow of free fatty acids and de novo hepatic lipogenesis. Thus far, no study quantitatively assessed the liver fat deposition after a rapid decline in physical activity. Herein, we describe a case of a 17-year-old Japanese boy with severe fat infiltration of the liver, due to a rapid decline in physical activity, treated at our facility. Our rehabilitation and nutritional support teams administered appropriate exercise and nutrition support to reduce weight and improve liver dysfunction. Our findings support dietary changes and exercise therapy to manage such cases.

DOI： 10.7759/cureus.16530

高齢者消化器がん化学療法〜高齢者のがん治療を安全・効果的に遂行するための取り組み高齢肝細胞癌症例における分子標的治療薬の生存期間延長効果と予測因子の検討

横尾健, 酒井規裕, 渡邉雄介, 荒生祥尚, 木村成宏, 阿部寛幸, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

日本高齢消化器病学会誌 24 ( 1 ) 115 - 115 2021年7月

被包化膵壊死への真菌感染による敗血症性ショックをきたした一例

山田麻理奈[大越], 上村顕也, 石川夏生, 小関洋平, 田中裕登, 水澤健, 佐藤裕樹, 五十嵐聡, 林和直, 坂牧僚, 横山純二, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 37 ( 1 ) 30 - 30 2021年7月

自己免疫性膵炎と膵癌との鑑別の現状と課題

小川光平, 林和直, 五十嵐聡, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 37 ( 1 ) 32 - 32 2021年7月

Shrinkage of a Submucosal Tumor in the Rectum. 国際誌

Takamasa Kobayashi, Manabu Takeuchi, Shuji Terai

Journal of gastrointestinal and liver diseases : JGLD 30 ( 2 ) 183 - 184 2021年6月

Severe steatosis and mild colitis are important for the early occurrence of hepatocellular carcinoma. 国際誌

Takeki Sato, Atsunori Tsuchiya, Takashi Owaki, Masaru Kumagai, Satoko Motegi, Takahiro Iwasawa, Shunsuke Nojiri, Masahiro Ogawa, Suguru Takeuchi, Yusuke Watanabe, Yuzo Kawata, Hiroteru Kamimura, Shuji Terai

Biochemical and biophysical research communications 566 36 - 44 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The number of patients with non-alcoholic steatohepatitis (NASH) and inflammatory bowel disease (IBD) is increasing. This study elucidates the effect of both NASH and IBD on hepatocellular carcinoma (HCC) using a mouse model combining NASH and IBD. The melanocortin 4 receptor-deficient (Mc4r-KO) mice were divided into four groups with or without a high-fat diet (HFD) and with or without dextran sulfate sodium (DSS) to induce colitis, and the differences in liver damage and occurrence of HCC were analyzed. In the HFD + DSS group, the body weight, liver weight/body weight ratio, and serum levels of albumin and alanine aminotransferase were significantly lower than those in the HFD group. We further found that steatosis was significantly lower and lobular inflammation was significantly higher in the HFD + DSS group than those in the HFD group, and that individual steatosis and lobular inflammation state in the HFD + DSS mice varied. We detected HCC only in the HFD + DSS group, and mice with severe steatosis and mild colitis were found to be at high risk of HCC. Presently, the prediction of HCC is very difficult. In some cases, severe colitis reverses the fat accumulation due to appetite loss. Our findings clearly showed that severe steatohepatitis and mild colitis are simultaneously essential for the occurrence of HCC in patients with NASH and IBD.

DOI： 10.1016/j.bbrc.2021.05.097

Effect of Lenvatinib on a Hepatocellular Carcinoma with Fibroblast Growth Factor Receptor 4 Expression: A Case Report and Review of the Literature.

Osamu Shibata, Kenya Kamimura, Masayoshi Ko, Norihiro Sakai, Hiroyuki Abe, Shinichi Morita, Takeshi Mizusawa, Hiroki Sato, Akira Sakamaki, Shuji Terai

Internal medicine (Tokyo, Japan) 60 ( 11 ) 1709 - 1715 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Basic and clinical research have shown that the expression of molecules involved in the hepatocellular carcinoma (HCC) cell signaling pathway is related to the sensitivity to molecular-targeted agents. We herein report a case of HCC that was effectively treated with lenvatinib after a poor response to sorafenib. The tumor showed a high expression of fibroblast growth factor receptor 4, which is reportedly related to the sensitivity to lenvatinib in vitro. The information obtained from this case and from our literature review highlights the importance of assessing the expression of the molecules involved in tumors for effective precision medicine.

DOI： 10.2169/internalmedicine.6580-20

A case of Helicobacter pylori -negative early gastric adenocarcinoma with gastrointestinal phenotype. 国際誌

Masafumi Takatsuna, Rie Azumi, Takeshi Mizusawa, Hiroki Sato, Ken-Ichi Mizuno, Takashi Kato, Junji Yokoyama, Yoichi Ajioka, Shuji Terai

Endoscopy international open 9 ( 6 ) E863-E866 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 40-year-old man with slightly depressed (0-IIc) type gastric cancer of the pyloric anterior gastric area underwent pre-operative screening for tetralogy of Fallot and endoscopic submucosal dissection (ESD) and was tested for Helicobacter pylori antigens and antibodies. Both tests were negative. He did not have a history of eradication. Pathological diagnosis of ESD showed a well-differentiated adenocarcinoma. The tumor was CD10-positive, MUC5AC-negative, and MUC6-confocal positive; it showed differentiation with gastrointestinal phenotype. Moreover, the tumor cells were lysozyme-positive, resembling Paneth cells. Mucosal glands exhibited intestinal metaplasia on the anal side of the tumor lesion. On the oral side of the tumor, metaplasia was non-existent, with normal pyloric glands present in the mucosal layer. The patient was not infected with H. pylori ; however, intestinal metaplasia existed around the early gastric cancer. This suggested that the intestinal metaplasia occurred due to bile reflux, and the gastric neoplasia arose with the metaplasia without an H. pylori infection. This case may potentially help explain gastric cancer development in the absence of H. pylori infection.

DOI： 10.1055/a-1396-3854

Transoral surgery for superficial head and neck cancer: National Multi-Center Survey in Japan. 国際誌

Chikatoshi Katada, Manabu Muto, Satoshi Fujii, Tetsuji Yokoyama, Tomonori Yano, Akihito Watanabe, Toshiro Iizuka, Shigetaka Yoshinaga, Ichiro Tateya, Hiroki Mitani, Yuichi Shimizu, Akiko Takahashi, Tomoyuki Kamijo, Noboru Hanaoka, Makoto Abe, Akihiro Shiotani, Koichi Kano, Yukinori Asada, Tamotsu Matsuhashi, Hirohito Umeno, Kenji Okami, Kenichi Goda, Shinichiro Hori, Yoichiro Ono, Shuji Terai, Yasuaki Nagami, Kenichi Takemura, Kenro Kawada, Mizuo Ando, Naoto Shimeno, Akihito Arai, Yasutoshi Sakamoto, Masaaki Ichinoe, Tetsuo Nemoto, Masahiro Fujita, Hidenobu Watanabe, Tadakazu Shimoda, Atsushi Ochiai, Takakuni Kato, Ryuichi Hayashi

Cancer medicine 10 ( 12 ) 3848 - 3861 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Head and neck cancers, especially in hypopharynx and oropharynx, are often detected at advanced stage with poor prognosis. Narrow band imaging enables detection of superficial cancers and transoral surgery is performed with curative intent. However, pathological evaluation and real-world safety and clinical outcomes have not been clearly understood. The aim of this nationwide multicenter study was to investigate the safety and efficacy of transoral surgery for superficial head and neck cancer. We collected the patients with superficial head and neck squamous cell carcinoma who were treated by transoral surgery from 27 hospitals in Japan. Central pathology review was undertaken on all of the resected specimens. The primary objective was effectiveness of transoral surgery, and the secondary objective was safety including incidence and severity of adverse events. Among the 568 patients, a total of 662 lesions were primarily treated by 575 sessions of transoral surgery. The median tumor diameter was 12 mm (range 1-75) endoscopically. Among the lesions, 57.4% were diagnosed as squamous cell carcinoma in situ. The median procedure time was 48 minutes (range 2-357). Adverse events occurred in 12.7%. Life-threatening complications occurred in 0.5%, but there were no treatment-related deaths. During a median follow-up period of 46.1 months (range 1-113), the 3-year overall survival rate, relapse-free survival rate, cause-specific survival rate, and larynx-preservation survival rate were 88.1%, 84.4%, 99.6%, and 87.5%, respectively. Transoral surgery for superficial head and neck cancer offers effective minimally invasive treatment. Clinical trials registry number: UMIN000008276.

DOI： 10.1002/cam4.3927

併存する疾患のあることが多い高齢者における上部消化管疾患のマネージメント地域病院における消化器サルコペニア疾患診療の有用性

上村博輝, 小島雄一, 高橋一也, 高綱将史, 平野正明, 政二文明, 藤田一, 辻村恭憲, 小林太一, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 68回 52 - 52 2021年6月

感染性被包化と壊死門脈瘻を伴う膵仮性嚢胞の一例(A case of pancreatic pseudocyst-portal vein fistula with infected walled off necrosis)

前田悠一郎, 林和直, 戸田遼, 若林拓哉, 木村究, 水戸將貴, 小島雄一, 小川光平, 荒生祥尚, 木村成宏, 五十嵐聡, 土屋淳紀, 徳永麻美, 佐藤知巳, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 68回 35 - 35 2021年6月

Effectiveness of EUS-Guided Fine-Needle Biopsy versus EUS-Guided Fine-Needle Aspiration: A Retrospective Analysis. 国際誌

Naosuke Kuraoka, Satoru Hashimoto, Shigeru Matsui, Shuji Terai

Diagnostics (Basel, Switzerland) 11 ( 6 ) 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic tumors and subepithelial lesions (SEL) of the gastrointestinal tract are effective for histological diagnosis. There are also reports that tissue sampling is possible with a smaller number of punctures by EUS-guided fine-needle biopsy (EUS-FNB). In this study, we retrospectively compared the diagnostic abilities of EUS-FNA and EUS-FNB. We examined 130 patients who underwent EUS-FNA/EUS-FNB for pancreatic tumors and SEL from July 2018 to January 2021. None of the cases underwent rapid on-site evaluation. There were 94 and 36 cases in the EUS-FNA and EUS-FNB groups, respectively. The median tumor size in the EUS-FNB group was 30 mm, which was significantly larger than the EUS-FNA group (p = 0.02). In addition, transgastric puncture was significantly more common in the EUS-FNB group (p = 0.01). The EUS-FNA and EUS-FNB groups had a sensitivity of 82.9% and 91.7% and an accuracy rate of 85.1% and 91.7%, respectively. However, both procedures had a comparable diagnostic ability.

DOI： 10.3390/diagnostics11060965

Long-term survival of 11 years with multidisciplinary therapy for hepatocellular carcinoma metastasis to the ovary and peritoneum: a case report.

Satoko Motegi, Takeshi Yokoo, Ryosuke Nozawa, Rie Azumi, Yuzo Kawata, Kohei Ogawa, Toru Setsu, Ken-Ichi Mizuno, Koji Nishino, Hajime Umezu, Hirokazu Kawai, Takeshi Suda, Shuji Terai

Clinical journal of gastroenterology 14 ( 4 ) 1211 - 1220 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

We herein report a rare case of HCC metastases to the ovary and peritoneum in a 61-year-old female patient who has achieved 11-year survival with multidisciplinary therapy. The patient was diagnosed with HCC during balloon angioplasty performed for Budd-Chiari syndrome in 1994 and underwent partial hepatectomy twice. Five years after the second hepatectomy, allochronic recurrence of a single nodule detected in S8 was treated by radiofrequency ablation, followed by percutaneous ethanol injection therapy and stereotactic body radiotherapy. However, her α-fetoprotein level rose to 1862 ng/mL within one year and computed tomography revealed a large pelvic tumor suggesting HCC metastasis to the ovary. The subsequent laparotomy revealed one 11-cm left ovarian tumor, one small right ovarian nodule, and numerous peritoneal nodules. Bilateral salpingo-oophorectomy and peritoneal resection of as many nodules as possible were performed. Combination therapy with intravenous 5-fluorouracil plus cisplatin and ramucirumab monotherapy effectively suppressed tumor progression with maintenance of hepatic functional reserve, and she has achieved long-term survival of 11 years, illustrating that multidisciplinary therapy with favorable hepatic functional reserve maintenance can contribute to long-term survival in HCC with extrahepatic spread.

DOI： 10.1007/s12328-021-01434-2

Endoscopic retrieval of multiple sewing needles by using the tip of a magnetic tube. 国際誌

Shinichi Morita, Kazuyoshi Yagi, Takahiro Hoshi, Satoshi Abe, Shuji Terai

VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy 6 ( 5 ) 228 - 230 2021年5月

Paris II and Rotterdam criteria are the best predictors of outcomes in patients with primary biliary cholangitis in Japan. 国際誌

Naruhiro Kimura, Masaaki Takamura, Nobutaka Takeda, Yusuke Watanabe, Yoshihisa Arao, Masahumi Takatsuna, Suguru Takeuchi, Hiroyuki Abe, Toru Setsu, Hiroteru Kamimura, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

Hepatology international 15 ( 2 ) 437 - 443 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Biochemical response to treatment in patients with primary biliary cholangitis (PBC) reflects prognosis. However, the best predictive criteria to detect biochemical response remain undetermined. In addition, because these criteria need > 6 months until definition, parameters that can estimate its results before initiating treatment are needed. METHODS: We conducted a single-center retrospective study on 196 patients with PBC, followed up for at least 12 months after initiating treatment. RESULTS: Kaplan-Meier analysis showed that Paris II (p = 0.002) and Rotterdam criteria (p = 0.001) could estimate the overall survival of PBC patients, whereas Paris II (p = 0.001), Rotterdam (p = 0.001), and Rochester criteria (p= 0.025) could estimate liver-related deaths. Cox hazard analysis revealed Paris II and Rotterdam criteria as significantly independent predictors of overall survival (hazard ratio (HR) 3.948, 95% CI 1.293-12.054, p = 0.016 and HR 6.040, 95% CI 1.969-18.527, p = 0.002, respectively) and liver-related deaths (HR 10.461, 95% CI 1.231-88.936, p = 0.032 and HR 10.824, 95% CI 1.252-93.572, p = 0.032, respectively). The results of Paris II criteria could be estimated by serum prothrombin time (Odds ratio (OR) 1.052, 95% CI 1.008-1.098, p = 0.021) and alanine transaminase level (OR 0.954, 95% CI 0.919-0.991, p = 0.014) whereas, those of Rotterdam criteria could be estimated by serum albumin level (OR 3.649, 95% CI 1.098-12.128, p = 0.035) at the time of diagnosis. CONCLUSIONS: This study highlights the best prediction criteria and pre-treatment parameters that facilitate the prognosis of PBC patients.

DOI： 10.1007/s12072-021-10163-0

Analysis of the safety of pretransplant corticosteroid therapy in patients with acute liver failure and late-onset hepatic failure in Japan. 国際誌

Takuro Hisanaga, Isao Hidaka, Isao Sakaida, Nobuaki Nakayama, Akio Ido, Naoya Kato, Yasuhiro Takikawa, Kazuaki Inoue, Masahito Shimizu, Takuya Genda, Shuji Terai, Hirohito Tsubouchi, Hajime Takikawa, Satoshi Mochida, Intractable Hepato-Biliary Disease Study Group Of Japan

JGH open : an open access journal of gastroenterology and hepatology 5 ( 4 ) 428 - 433 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Aim: In Japan, corticosteroids have been commonly used as a part of multidisciplinary therapy for patients with acute liver failure and late-onset hepatic failure. However, there is controversy regarding the development of infections and other complications. In this study, the influence of corticosteroids on patient outcomes after liver transplantation was investigated. Methods: This study included 167 patients with acute liver failure and late-onset hepatic failure who underwent liver transplantation between 2010 and 2015. The effects of pretransplant corticosteroid therapy on patient outcomes were evaluated using a database constructed by the subcommittee for fulminant hepatitis in the Intractable Hepato-Biliary Diseases Study Group of Japan. Results: The subacute type and the median total bilirubin levels were higher in those receiving corticosteroids than in those not receiving corticosteroids. Although infections tended to be higher in patients receiving corticosteroids, pretransplant corticosteroid administration did not affect the survival rates. The duration from corticosteroid initiation to liver transplantation was longer in patients who developed infections. The survival rates, however, did not differ between patients with and without infections. Conclusions: Corticosteroids were administered to patients with poor prognoses. Otherwise, the overall outcome in those administered corticosteroids was not significantly different from that in those administered without corticosteroids. Although infectious complications tended to occur, they were generally controllable and nonfatal. Pretransplant corticosteroid therapy may be permissible, with regarding for infections and performed within the minimum duration.

DOI： 10.1002/jgh3.12508

Achalasia and esophageal cancer: a large database analysis in Japan.

Hiroki Sato, Shuji Terai, Yuto Shimamura, Shinwa Tanaka, Hironari Shiwaku, Hitomi Minami, Chiaki Sato, Ryo Ogawa, Hiroshi Yokomichi, Haruhiro Inoue

Journal of gastroenterology 56 ( 4 ) 360 - 370 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Achalasia has been reported to be associated with esophageal cancers (ECs). However, owing to the rarity of achalasia, details of achalasia-related ECs are not well investigated. METHOD: The incidence of ECs in Japanese patients with achalasia and achalasia-related esophageal motility disorders (EMDs) was estimated, and risk factors for achalasia-related ECs were determined. Characteristics of ECs and treatment courses were also analyzed. RESULTS: Between 2010 and 2019, 2714 Japanese patients with achalasia and achalasia-related EMDs were recorded in 7 high-volume centers; 24 patients (21 men, 3 women) developed ECs. The incidence of ECs was estimated at 0.078 and 0.28 per 100 person-years from the onset and the diagnosis of disease, respectively. Kaplan-Meier estimate suggested that, in addition to a long history of achalasia, advanced age, male sex, and regular alcohol consumption were statistically significant risk factors for EC development. A prevalence of 40 ECs (12.5% multiple lesions, and 22.7% metachronal lesions) was also noted, predominantly distributed over the thoracic esophagus. All were histologically diagnosed as squamous cell carcinoma. Superficial ECs were successfully treated with endoscopic treatment in all cases, except one. Achalasia-related Barret esophagus was extremely rare, and Barret adenocarcinoma was not detected in our cohort. CONCLUSION: The high relative risk of ECs was clarified in Japanese achalasia patients, although the absolute risk remained low. Therefore, surveillance endoscopy may be recommended in limited patients with several aforementioned risk factors determined. Superficial cancer can be treated with endoscopic treatment. Multiple and metachronal ECs should be screened.

DOI： 10.1007/s00535-021-01763-6

The first case of balloon-occluded retrograde transvenous obliteration and partial splenic embolization for gastric varices in situs inversus abdominus.

Yusuke Watanabe, Akihiko Osaki, Nobuo Waguri, Shuji Terai

Clinical journal of gastroenterology 14 ( 2 ) 656 - 661 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Situs inversus abdominus is a congenital abnormality characterized by the mirror image positioning of the abdominal organs, making it difficult to diagnosis and treatment of many diseases. Here, we report a rare case of gastric varices in situs inversus abdominus patient. A 55-year-old man was diagnosed with F2-shaped gastric varices associated with alcoholic cirrhosis. Abdominal dynamic computed tomography showed situs inversus abdominus, and gastric varices with a gastrorenal shunt. Due to the complex anatomy, emergency interventional radiology during bleeding was extremely difficult. Therefore, after thorough consultation, we decided to treat gastric varices prophylactically by balloon-occluded retrograde transvenous obliteration. After treatment, the patient's clinical course was generally good, with no adverse events, and the gastric varices disappeared. It is important to assess anatomical positioning using three-dimensional reconstruction computed tomography images before treatment, to adequately prepare, including selecting appropriate devices (i.e., catheters and sheath). Although preventive treatment of gastric varices is controversial, in cases with anatomical complexity, preventive treatment with sufficient preparation would be recommended. To the best of our knowledge, there are no reports of treatment for gastric varices in situs inversus abdominus patient. This case will serve as a reference for successful treatment in future cases.

DOI： 10.1007/s12328-020-01332-z

当センターでの肝炎医療コーディネーター養成の現状と院内非専門医対策について

薛徹, 荒生祥尚, 廣川光, 寺井崇二

肝臓 62 ( Suppl.1 ) A242 - A242 2021年4月

新潟県における自治体肝炎ウイルス検診の現状

薛徹, 菊田玲, 中島徹, 荒生祥尚, 中山均, 寺井崇二

肝臓 62 ( Suppl.1 ) A230 - A230 2021年4月

当センターでの肝炎医療コーディネーター養成の現状と院内非専門医対策について

薛徹, 荒生祥尚, 廣川光, 寺井崇二

肝臓 62 ( Suppl.1 ) A242 - A242 2021年4月

新潟県における自治体肝炎ウイルス検診の現状

薛徹, 菊田玲, 中島徹, 荒生祥尚, 中山均, 寺井崇二

肝臓 62 ( Suppl.1 ) A230 - A230 2021年4月

臨床応用を目指したバイオマーカー研究の最前線急性肝障害条件下での血中セロトニン量の病態・予後予測バイオマーカーとしての有用性の検討

薛徹, 上村顕也, 寺井崇二

肝臓 62 ( Suppl.1 ) A170 - A170 2021年4月

肝移植の現状と課題当県での肝障害症例を対象としたネットワークの運用と、アンケート調査からみた県内の肝障害診療の現状と今後の啓発の必要性

薛徹, 寺井崇二

肝臓 62 ( Suppl.1 ) A113 - A113 2021年4月

肝疾患におけるビックデータとAI(人工知能)の臨床応用ディープラーニングを活用したPBC多施設データから予測する高齢者PBCの介入の必要性の検討

上村博輝, 高村昌昭, 寺井崇二

肝臓 62 ( Suppl.1 ) A208 - A208 2021年4月

肝疾患移行期医療の現状と問題点先天性心疾患術後に肝線維化悪化に影響を及ぼす因子の解析

山崎文紗子, 上村博輝, 寺井崇二

肝臓 62 ( Suppl.1 ) A167 - A167 2021年4月

【肝類洞壁細胞研究における新知見】肝の炎症、線維化と類洞壁細胞間葉系幹細胞を用いた新規治療法の開発

渡邉雄介, 土屋淳紀, 寺井崇二

肝胆膵 82 ( 4 ) 525 - 529 2021年4月

肝癌に対する局所療法としての放射線療法の安全性と有効性の検証

山田麻理奈, 上村顕也, 柴田理, 森田真一, 寺井崇二

肝臓 62 ( Suppl.1 ) A338 - A338 2021年4月

多発肝転移、リンパ節転移を伴う直腸原発神経内分泌腫瘍に対して集学的治療が有効であった一例当院での症例群の検討と共に

小川和也, 阿部寛幸, 上村顕也, 寺井崇二

肝臓 62 ( Suppl.1 ) A266 - A266 2021年4月

肝再生の可能性と障壁 HMGB1の部分ペプチドを用いた慢性肝疾患に対するセルフリー治療の開発

土屋淳紀, 野尻俊介, 寺井崇二

肝臓 62 ( Suppl.1 ) A69 - A69 2021年4月

point shear wave elastographyを利用した肝線維化のheterogeneityの検証

横尾健, 杉田萌乃, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

超音波医学 48 ( Suppl. ) S713 - S713 2021年4月

Small extracellular vesicles derived from interferon-γ pre-conditioned mesenchymal stromal cells effectively treat liver fibrosis. 国際誌

Suguru Takeuchi, Atsunori Tsuchiya, Takahiro Iwasawa, Shunsuke Nojiri, Takayuki Watanabe, Masahiro Ogawa, Tomoaki Yoshida, Katsunori Fujiki, Yuta Koui, Taketomo Kido, Yusuke Yoshioka, Mayu Fujita, Junichi Kikuta, Tohru Itoh, Masaaki Takamura, Katsuhiko Shirahige, Masaru Ishii, Takahiro Ochiya, Atsushi Miyajima, Shuji Terai

NPJ Regenerative medicine 6 ( 1 ) 19 - 19 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Mesenchymal stromal cells (MSCs) are used for ameliorating liver fibrosis and aiding liver regeneration after cirrhosis; Here, we analyzed the therapeutic potential of small extracellular vesicles (sEVs) derived from interferon-γ (IFN-γ) pre-conditioned MSCs (γ-sEVs). γ-sEVs effectively induced anti-inflammatory macrophages with high motility and phagocytic abilities in vitro, while not preventing hepatic stellate cell (HSC; the major source of collagen fiber) activation in vitro. The proteome analysis of MSC-derived sEVs revealed anti-inflammatory macrophage inducible proteins (e.g., annexin-A1, lactotransferrin, and aminopeptidase N) upon IFN-γ stimulation. Furthermore, by enabling CX3CR1+ macrophage accumulation in the damaged area, γ-sEVs ameliorated inflammation and fibrosis in the cirrhosis mouse model more effectively than sEVs. Single cell RNA-Seq analysis revealed diverse effects, such as induction of anti-inflammatory macrophages and regulatory T cells, in the cirrhotic liver after γ-sEV administration. Overall, IFN-γ pre-conditioning altered sEVs resulted in efficient tissue repair indicating a new therapeutic strategy.

DOI： 10.1038/s41536-021-00132-4

Modulation of serotonin in the gut-liver neural axis ameliorates the fatty and fibrotic changes in non-alcoholic fatty liver. 国際誌

Disease models & mechanisms 14 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

The etiology of non-alcoholic fatty liver disease (NAFLD) consists of various factors, including neural signal pathways. However, the molecular mechanisms of the autonomic neural signals influencing NAFLD progression have not been elucidated. Therefore, we examined the involvement of the gut-liver neural axis in NAFLD development and tested the therapeutic effect of modulation of this axis in this study. To test the contribution of the gut-liver neural axis, we examined NAFLD progression with respect to body weight, hepatic steatosis, fibrosis, intestinal tight junction, microbiota and short-chain fatty acids in NAFLD models of choline-deficient defined L-amino-acid and high-fat diet-fed mice with or without blockades of autonomic nerves from the liver. Blockade of the neural signal from the liver to the gut in these NAFLD mice models ameliorated the progression of liver weight, hepatic steatosis and fibrosis by modulating serotonin expression in the small intestine. It was related to the severity of the liver pathology, the tight junction protein expression, microbiota diversity and short-chain fatty acids. These effects were reproduced by administrating serotonin antagonist, which ameliorated the NAFLD progression in the NAFLD mice models. Our study demonstrated that the gut-liver neural axis is involved in the etiologies of NAFLD progression and that serotonin expression through this signaling network is the key factor of this axis. Therefore, modulation of the gut-liver neural axis and serotonin antagonist ameliorates fatty and fibrotic changes in non-alcoholic fatty liver, and can be a potential therapeutic target of NAFLD.This article has an associated First Person interview with the first author of the paper.

DOI： 10.1242/dmm.048922

Successful treatment of positive-sense RNA virus coinfection with autoimmune hepatitis using double filtration plasmapheresis. 国際誌

Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

BMJ case reports 14 ( 3 ) 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Double filtration plasmapheresis (DFPP) is an apheretic technique that selectively removes high molecular weight substances using a plasma component filter. DFPP has been used to treat positive-sense RNA virus infections, mainly chronic hepatitis C virus (HCV) infection, because of its ability to directly eliminate viral particles from blood plasma from 2008 to about 2015, before direct-acting antiviral agents was marketed. This effect has been termed virus removal and eradication by DFPP. HCV is a positive-sense RNA virus similar to West Nile virus, dengue virus and the SARS and Middle East respiratory syndrome coronaviruses. SARS-CoV-2 is classified same viral species. These viruses are all classified in Family Flaviviridae which are family of single-stranded plus-stranded RNA viruses. Viral particles are 40-60 nm in diameter, enveloped and spherical in shape. We present a rare case of HCV removal where an RNA virus infection that copresented with virus-associated autoimmune hepatitis was eliminated using DFPP. Our results indicate that DFPP may facilitate prompt viraemia reduction and may have novel treatment applications for SARS-CoV-2, that is, use of therapeutic plasma exchange for fulminant COVID-19.

DOI： 10.1136/bcr-2020-236984

Adipose most abundant 2 protein is a predictive marker for cisplatin sensitivity in cancers. 国際誌

Kenya Kamimura, Takeshi Suda, Yasuo Fukuhara, Shujiro Okuda, Yu Watanabe, Takeshi Yokoo, Akihiko Osaki, Nobuo Waguri, Toru Ishikawa, Toshihiro Sato, Yutaka Aoyagi, Masaaki Takamura, Toshifumi Wakai, Shuji Terai

Scientific reports 11 ( 1 ) 6255 - 6255 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cisplatin (CDDP) is one of the chemotherapeutic drugs being used to treat various cancers. Although effective in many cases, as high doses of CDDP cause cytotoxic effects that may worsen patients' condition, therefore, a marker of sensitivity to CDDP is necessary to enhance the safety and efficiency of CDDP administration. This study focused on adipose most abundant 2 (APM2) to examine its potential as a marker of CDDP sensitivity. The relationship of APM2 expression with the mechanisms of CDDP resistance was examined in vitro and in vivo using hepatocellular carcinoma (HCC) cells, tissues and serum of HCC patients (n = 71) treated initially with intrahepatic arterial infusion of CDDP followed by surgical resection. The predictability of serum APM2 for CDDP sensitivity was assessed in additional 54 HCC patients and 14 gastric cancer (GC) patients. APM2 expression in CDDP-resistant HCC was significantly higher both in serum and the tissue. Bioinformatic analyses and histological analyses demonstrated upregulation of ERCC6L (DNA excision repair protein ERCC6-like) by APM2, which accounts for the degree of APM2 expression. The serum APM2 level and chemosensitivity for CDDP were assessed and cut-off value of serum APM2 for predicting the sensitivity to CDDP was determined to be 18.7 µg/mL. The value was assessed in HCC (n = 54) and GC (n = 14) patients for its predictability of CDDP sensitivity, resulted in predictive value of 77.3% and 100%, respectively. Our study demonstrated that APM2 expression is related to CDDP sensitivity and serum APM2 can be an effective biomarker of HCC and GC for determining the sensitivity to CDDP.Trial registration: This study was registered with the University Hospital Medical Information Network Clinical Trials Registry (UMIN000028487).

DOI： 10.1038/s41598-021-85498-7

Evaluation of intestinal microbiota, short-chain fatty acids, and immunoglobulin a in diversion colitis. 国際誌

Kentaro Tominaga, Atsunori Tsuchiya, Takeshi Mizusawa, Asami Matsumoto, Ayaka Minemura, Kentaro Oka, Motomichi Takahashi, Tomoaki Yosida, Yuzo Kawata, Kazuya Takahashi, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Ken-Ichi Mizuno, Yosuke Tajima, Masato Nakano, Yoshifumi Shimada, Hitoshi Kameyama, Junji Yokoyama, Toshifumi Wakai, Shuji Terai

Biochemistry and biophysics reports 25 100892 - 100892 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

It is reported that an increase in aerobic bacteria, a lack of short-chain fatty acids (SCFAs), and immune disorders in the diverted colon are major causes of diversion colitis. However, the precise pathogenesis of this condition remains unclear. The aim of the present study was to examine the microbiota, intestinal SCFAs, and immunoglobulin A (IgA) in the diverted colon. Eight patients underwent operative procedures for colostomies. We assessed the diverted colon using endoscopy and obtained intestinal samples from the diverted colon and oral colon in these patients. We analyzed the microbiota and SCFAs of the intestinal samples. The bacterial communities were investigated using a 16S rRNA gene sequencing method. The microbiota demonstrated a change in the proportion of some species, especially Lactobacillus, which significantly decreased in the diverted colon at the genus level. We also showed that intestinal SCFA values were significantly decreased in the diverted colon. Furthermore, intestinal IgA levels were significantly increased in the diverted colon. This study was the first to show that intestinal SCFAs were significantly decreased and intestinal IgA was significantly increased in the diverted colon. Our data suggest that SCFAs affect the microbiota and may play an immunological role in diversion colitis.

DOI： 10.1016/j.bbrep.2020.100892

Comorbidities and healthcare costs and resource use of patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) in the Japan medical data vision database.

Shuji Terai, Amy Buchanan-Hughes, Alvin Ng, I-Heng Lee, Ken Hasegawa

Journal of gastroenterology 56 ( 3 ) 274 - 284 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: This study examined demographics, comorbidities and healthcare resource use (HCRU) and costs among Japanese patients with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). METHODS: We conducted a repeated cross-sectional analysis of the Medical Data Vision (MDV) claims database, from January 2011 to March 2018. Demographics were described at index date and by calendar year; a "NASH" subpopulation included patients with ≥ 1 claim for NASH at any time. Prevalence of pre-specified comorbidities of interest and data-emergent top comorbidities were estimated. All-cause HCRU and costs were quantified by calendar year. Outcomes were compared between 2011 and 2017 using partially overlapping t tests. RESULTS: 58,958 patients (mean age 61.6 years; 55.5% male) were included. 1139 patients (2%) were in the NASH subpopulation. At baseline, comorbid cardiovascular disease (69.4%), diabetes (62.1%) and hyperlipidaemia (54.4%) were most prevalent; comorbidity prevalence increased with age. Mean outpatient visits decreased from 9.36 per patient in 2011 to 7.80 in 2017; mean inpatient admissions increased (both p < 0.001 for 2011 vs 2017). Mean total all-cause healthcare costs ranged from \322,206 to \340,399 per patient per year between 2011 and 2017. Although total all-cause healthcare costs did not change significantly (p = 0.552), cost burden shifted from the outpatient to inpatient setting between 2011 and 2017. All-cause healthcare resource use/costs were generally higher for the NASH subgroup compared with the overall population. CONCLUSIONS: There is a high burden of disease among Japanese NAFLD/NASH patients, including a high prevalence of comorbidities which generally increase with age. Accordingly, substantial all-cause HCRU and costs were incurred.

DOI： 10.1007/s00535-021-01759-2

Relationship between detection of hepatitis B virus in saliva and periodontal disease in hepatitis B virus carriers in Japan. 国際誌

Hiroteru Kamimura, Jun Watanabe, Tomoyuki Sugano, Junji Kohisa, Hiroyuki Abe, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shogo Okoshi, Yoshinari Tanabe, Ritsuo Takagi, Hirofumi Nonaka, Shuji Terai

Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy 27 ( 3 ) 492 - 496 2021年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Although hepatitis B virus infection is well-described, the additional risk posed by oral bleeding in individuals with chronic hepatitis B virus infection has not been determined. This study aimed to determine the quantity of hepatitis B virus in the saliva of carriers in Japan, as a means of understanding the potential risk for horizontal transmission. METHODS: Saliva samples from 48 confirmed hepatitis B virus carriers were included in the analysis. Hepatitis B virus concentrations and the presence of occult blood as periodontal disease were evaluated in each sample. RESULTS: Hepatitis B surface antigen was identified in 46 of the 48 samples (98%), with hepatitis B virus DNA identified in 19 of the 48 saliva samples (40%). Occult blood was detected in 32 (67%) samples with the prevalence increasing as a function of age (r = 0.413; P = 0.003). There was a significantly positive correlation between hepatitis B virus DNA levels in the serum and saliva specimens (r = 0.895; P < 0.001). CONCLUSIONS: Occult blood in saliva was detected in most participants. The detection of hepatitis B virus DNA correlated positively with hepatitis B virus in the serum and occult blood in the saliva. Therefore, improved care of periodontal disease among older people is important for preventing horizontal transmission of hepatitis B virus.

DOI： 10.1016/j.jiac.2020.10.028

当院における肝炎医療コーディネーターの取り組み・課題と今後の展望

廣川光, 荒生祥尚, 薛徹, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A266 - A266 2021年3月

Hepatocellular carcinoma development in diabetic patients: a nationwide survey in Japan

Ryosuke Tateishi, Takeshi Matsumura, Takeshi Okanoue, Toshihide Shima, Koji Uchino, Naoto Fujiwara, Takafumi Senokuchi, Kazuyoshi Kon, Takayoshi Sasako, Makiko Taniai, Takumi Kawaguchi, Hiroshi Inoue, Hirotaka Watada, Naoto Kubota, Hitoshi Shimano, Shuichi Kaneko, Etsuko Hashimoto, Sumio Watanabe, Goshi Shiota, Kohjiro Ueki, Kosuke Kashiwabara, Yutaka Matsuyama, Hideo Tanaka, Masato Kasuga, Eiichi Araki, Kazuhiko Koike, Yoshiyasu Karino, Shuhei Hige, Masatomo Sekiguchi, Koji Ogawa, Hideaki Miyoshi, Kyu Yong Cho, Masaru Baba, Atsushi Inoue, Kazuobu Aso, Mitsuyoshi Okada, Yasuhiro Takikawa, Kei Endo, Yasushi Ishigaki, Hirobumi Togashi, Michiaki Unno, Takanori Morikawa, Hideki Katagiri, Shojiro Sawada, Hiromasa Ohira, Atsushi Takahashi, Michio Shimabukuro, Akihiro Kudo, Naomi Tanaka, Junko Mitsuhashi, Toshifumi Tokai, Yasushi Matsuzaki, Tadashi Ikegami, Masato Imai, Kou Nishikawa, Sadao Takahashi, Sumiko Nagoshi, Kosuke Maezawa, Masafumi Matsuda, Tetsuhiro Chiba, Masayuki Yokoyama, Koutaro Yokote, Yoko Hidetaka, Mitsuhiko Moriyama, Hitomi Nakamura, Midori Fujishiro, Tadakazu Hisamatsu, Kaori Nishikawa, Toshihiko Nouchi, Yuki Sakurai, Harumi Daikoku, Michinori Murayama, Yoshinori Saigusa, Takashi Matsui, Ryosuke Tateishi, Hidenari Nagai, Takanori Mukozu, Takahisa Hirose, Masahiko Miyagi, Hiroaki Sato, Akira Mizuki, Masanori Miura, Yuzuru Sato, Rena Kaneko, Kumiko Hamano, Hiroko Kato, Kentaro Kikuchi, Yusuke Kajiyama, Makoto Chuma, Hiroko Ito, Hiroshi Yasuda, Nobuyuki Matsumoto, Yasushi Tanaka, Yoshio Nagai, Kento Imajo, Yasuo Terauchi, Yuzuru Ito, Shuji Terai, Hirohito Sone, Satoshi Matsunaga

Journal of Gastroenterology 56 ( 3 ) 261 - 273 2021年3月

門脈圧亢進症:診断と治療の最前線傍食道静脈の発達の有無を指標としたEVL/EISの選択による治療成績

薛徹, 横山純二, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A201 - A201 2021年3月

地域病院健診時の消化器サルコペニア疾患診療の有用性

上村博輝, 小島雄一, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A345 - A345 2021年3月

【小児期発症慢性肝疾患における移行期医療の現状と課題-小児と成人のダイアログ-】NAFLD Pediatric fatty liver disease(PeFLD)における概説と成人との比較(肝組織学的検討を含めて) 小児と成人の相違

上村博輝, 山崎文紗子, 佐藤毅昂, 薛徹, 土屋淳紀, 上村顕也, 高村昌昭, 寺井崇二, 長崎啓祐, 斎藤昭彦, 梅津哉

肝胆膵 82 ( 3 ) 425 - 440 2021年3月

消化器疾患診療におけるディープラーニングの有用性の検証

上村博輝, 野中尋史, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A354 - A354 2021年3月

脂肪性肝疾患:新規治療法を目指した基礎研究とトランスレーショナルリサーチ ONO-1301を用いた肝硬変に対するセルフリー治療の開発

茂木聡子, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A223 - A223 2021年3月

消化器疾患と神経系の臓器相関脂肪性肝疾患における自律神経系ネットワークを介したセロトニンの関与

大脇崇史, 上村顕也, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A144 - A144 2021年3月

肝発癌抑制を目指したB型肝炎の最新治療肝細胞癌におけるYAPとHBx蛋白の臨床的有用性の検討

小田知友美, 上村顕也, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A73 - A73 2021年3月

消化器領域におけるバイオマーカーの新展開エクソソームタンパクEps8の膵癌バイオマーカーとしての検討

林和直, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A151 - A151 2021年3月

消化器領域における再生医療:基礎的研究の最前線 HMGB1の部分ペプチドを用いた新たな肝硬変治療開発

土屋淳紀, 野尻俊介, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A132 - A132 2021年3月

ACLF:欧米、アジアと我が国での差異 Acute on chronic liver failureに対する肝細胞老化改善の検証

渡邉雄介, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A110 - A110 2021年3月

胆膵疾患研究の最前線〜from bench to bedside, from bedside to bench〜膵臓選択的ハイドロダイナミック遺伝子導入法による新規膵癌モデル動物の確立

柴田理, 上村顕也, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A232 - A232 2021年3月

消化器領域の救急医療、集中治療:急性膵炎予後因子・CT gradeを用いた重症急性膵炎の予後・感染性被包化膵壊死合併の予測

林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A251 - A251 2021年3月

高齢者膵癌に対する治療の適応と限界県全域における高齢者膵癌診療の現状多施設後方視的研究の結果より

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 118 ( 臨増総会 ) A237 - A237 2021年3月

Potential Effect of a Selective Peroxisome Proliferator-activated Receptor Alpha Modulator on Metabolic Dysfunction-associated Fatty Liver Disease.

Hiroteru Kamimura, Atsushi Kimura, Shuji Terai

Internal medicine (Tokyo, Japan) 60 ( 14 ) 2165 - 2166 2021年2月

Rare paraneoplastic syndromes in digestive systems caused by lung cancer. 国際誌

Hiroteru Kamimura, Tomohiro Iwasaki, Kazunao Hayashi, Shuji Terai

BMJ case reports 14 ( 2 ) 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

We observed a rare case of two different digestive paraneoplastic syndromes that improved with the treatment of the neoplasms. The first syndrome was chronic intestinal pseudo-obstruction (CIPO), which is a subtype of paraneoplastic syndromes called a paraneoplastic neurological syndrome (PNS). The second was Stauffer's syndrome, which is a unique paraneoplastic syndrome characterised by non-metastatic intrahepatic cholestasis associated with neoplasms. Here, we report the case of a 55-year-old man who presented with two concurrent paraneoplastic syndromes in the digestive system. The intestinal pseudo-obstruction and elevated biliary enzyme levels improved as the lung cancer responded to chemotherapy. In this case, CIPO as a PNS led to the detection of lung cancer. To our knowledge, this is the first report of Stauffer's syndrome caused by lung adenocarcinoma.

DOI： 10.1136/bcr-2020-240161

Immunoglobulin therapy for successful management of prolonged, recurrent jaundice in a young adult male with combined immunodeficiency.

Chiyumi Oda, Atsunori Tsuchiya, Atsushi Kimura, Kentaro Tominaga, Kazunao Hayashi, Takashi Ushiki, Hajime Umezu, Shuji Terai

Clinical journal of gastroenterology 14 ( 4 ) 1197 - 1201 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Jaundice may be persistent in drug-induced liver injury associated with vanishing bile duct syndrome. However, recurrent jaundice is atypical, following bile flow restoration. Here, we report a 28-year-old man with prolonged, recurrent jaundice (more than 300 days) and combined immunodeficiency (CID) of B-cells, T-cells, and natural killer (NK) cells. Hypogammaglobulinemia was observed throughout his hospitalization, and peripheral blood flow cytometry detected a few B-cells (2% of CD19 + cells and 2% of CD20 + cells). We further detected the dysfunction of T-cells and NK cells. Based on these findings, CID was diagnosed. We presumed that hypogammaglobulinemia was related to the jaundice. After regular injections of intravenous immunoglobulin (IVIG), the stool color gradually turned brown. However, the color returned to white as IgG levels decreased. The brown-to-white stool pattern was repeated with another IVIG administration, suggesting that the patient's serum immunoglobulin levels were related to the jaundice. On follow-up, IVIG was performed every two to three weeks, and his total bilirubin improved gradually. Immunoglobulin replacement therapy could be one of the treatment choices for jaundice with CID.

DOI： 10.1007/s12328-021-01347-0

Multiple Tumor-Like Fatty Changes in the Liver Disappeared After Hepatitis C Virus Eradication With Direct-Acting Antiviral Treatment. 査読国際誌

Norihiro Sakai, Kenya Kamimura, Shuji Terai

The American journal of gastroenterology 116 ( 2 ) 237 - 237 2021年2月

Changes in disease characteristics of primary biliary cholangitis: An observational retrospective study from 1982 to 2016. 国際誌

Masaaki Takamura, Yasunobu Matsuda, Naruhiro Kimura, Masafumi Takatsuna, Toru Setsu, Atsunori Tsuchiya, Akihiko Osaki, Nobuo Waguri, Masahiko Yanagi, Toru Takahashi, Soichi Sugitani, Yuka Kobayashi, Akira Yoshikawa, Toru Ishikawa, Toshiaki Yoshida, Toshiaki Watanabe, Hitoshi Bannai, Tomoyuki Kubota, Kazuhiro Funakoshi, Hiroto Wakabayashi, So Kurita, Norio Ogata, Masashi Watanabe, Yuhsaku Mita, Shigeki Mori, Motoya Sugiyama, Toru Miyajima, Sumio Takahashi, Shuichi Sato, Kisei Ishizuka, Hironobu Ohta, Yutaka Aoyagi, Shuji Terai

Hepatology research : the official journal of the Japan Society of Hepatology 51 ( 2 ) 166 - 175 2021年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIM: Disease characteristics of primary biliary cholangitis have changed recently. However, detailed studies on the subject have been limited. Therefore, we aimed to clarify disease characteristics of patients with recent primary biliary cholangitis using the cohort from Niigata University and 21 affiliated hospitals. METHODS: Overall, 508 patients were enrolled in this study from 1982 to 2016, divided into three cohorts according to their year of diagnosis: ≤1999, 2000-2009 and ≥2010. We compared differences in clinical characteristics, response to ursodeoxycholic acid and prognosis. RESULTS: The male-to-female ratio increased incrementally from 1:16.4 (≤1999) to 1:3.8 (≥2010) (P < 0.001). In women, the median age at diagnosis increased incrementally from 54.0 years (≤1999) to 60.5 years (≥2010) (P < 0.001) and serum albumin decreased gradually (P = 0.001), which might have affected the increase in the Fibrosis-4 Index and albumin-bilirubin score. The ursodeoxycholic acid response rate according to the Barcelona criteria increased incrementally from 26.7% (≤1999) to 78.4% (≥2010) (P < 0.010), and those according to other criteria (Paris-I, Rotterdam and Toronto) were approximately ≥80% in all cohorts. Ten-year survival rate in the ≤1999 and 2000-2009 cohorts were 98.6% and 95.6%, respectively. These earlier cohorts were also characterized by a higher rate of asymptomatic state and mild histology (83.5% [≤1999] and 84.7% [2000-2009], and 93.6% [≤1999] and 91.1% [2000-2009]). CONCLUSIONS: Patients with primary biliary cholangitis were characterized by older age at diagnosis and an increase in male to female ratio as well as higher response rates of ursodeoxycholic acid and longer survival, resulting from the early recognition of primary biliary cholangitis.

DOI： 10.1111/hepr.13586

【肝硬変診療ガイドラインの改正をめぐって】肝腎症候群

坂牧僚, 薛徹, 阿部寛幸, 上村顕也, 高村昌昭, 寺井崇二

消化器・肝臓内科 9 ( 2 ) 155 - 159 2021年2月

Acute on chronicの新展開当科における我が国の新診断基準でのAcute On Chronic Liver Failure症例の検討

野尻俊介, 土屋淳紀, 阿部聡司, 坂牧僚, 上村博輝, 上村顕也, 高村昌昭, 寺井崇二

肝臓 62 ( 2 ) 107 - 107 2021年2月

Molecular Mechanisms and Treatment of Sarcopenia in Liver Disease: A Review of Current Knowledge. 国際誌

Hiroteru Kamimura, Takeki Sato, Kazuki Natsui, Takamasa Kobayashi, Tomoaki Yoshida, Kenya Kamimura, Atsunori Tsuchiya, Toshiko Murayama, Junji Yokoyama, Hirokazu Kawai, Masaaki Takamura, Shuji Terai

International journal of molecular sciences 22 ( 3 ) 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcopenia is characterized by progressive and generalized loss of skeletal muscle mass and strength that occurs with aging or in association with various diseases. The condition is prevalent worldwide and occurs more frequently in patients with chronic diseases owing to the intrinsic relationship of muscles with glucose, lipid, and protein metabolism. Liver cirrhosis is characterized by the progression of necro-inflammatory liver diseases, which leads to fibrosis, portal hypertension, and a catabolic state, which causes loss of muscle tissue. Sarcopenia is of significant concern in the state of liver cirrhosis because sarcopenia has been associated with higher mortality, increased hospital admissions, worse post-liver transplant outcomes, decreased quality of life, and increased risk for other complications associated with cirrhosis. Therefore, sarcopenia is also an important feature of liver cirrhosis, representing a negative prognostic factor and influencing mortality. An increased understanding of sarcopenia could lead to the development of novel therapeutic approaches that could help improve the cognitive impairment of cirrhotic patients; therefore, we present a review of the mechanisms and diagnosis of sarcopenia in liver disease and existing therapeutic approaches.

DOI： 10.3390/ijms22031425

Usefulness of an artificial intelligence system for the detection of esophageal squamous cell carcinoma evaluated with videos simulating overlooking situation. 国際誌

Kotaro Waki, Ryu Ishihara, Yusuke Kato, Ayaka Shoji, Takahiro Inoue, Katsunori Matsueda, Muneaki Miyake, Yusaku Shimamoto, Hiromu Fukuda, Noriko Matsuura, Yoichiro Ono, Kenshi Yao, Satoru Hashimoto, Shuji Terai, Masayasu Ohmori, Kyosuke Tanaka, Motohiko Kato, Takashi Shono, Hideaki Miyamoto, Yasuhito Tanaka, Tomohiro Tada

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 33 ( 7 ) 1101 - 1109 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: Artificial intelligence (AI) systems have shown favorable performance in the detection of esophageal squamous cell carcinoma (ESCC). However, previous studies were limited by the quality of their validation methods. In this study, we evaluated the performance of an AI system with videos simulating situations in which ESCC has been overlooked. METHODS: We used 17,336 images from 1376 superficial ESCCs and 1461 images from 196 noncancerous and normal esophagi to construct the AI system. To record validation videos, the endoscope was passed through the esophagus at a constant speed without focusing on the lesion to simulate situations in which ESCC has been missed. Validation videos were evaluated by the AI system and 21 endoscopists. RESULTS: We prepared 100 video datasets, including 50 superficial ESCCs, 22 noncancerous lesions, and 28 normal esophagi. The AI system had sensitivity of 85.7% (54 of 63 ESCCs) and specificity of 40%. Initial evaluation by endoscopists conducted with plain video (without AI support) had average sensitivity of 75.0% (47.3 of 63 ESCC) and specificity of 91.4%. Subsequent evaluation by endoscopists was conducted with AI assistance, which improved their sensitivity to 77.7% (P = 0.00696) without changing their specificity (91.6%, P = 0.756). CONCLUSIONS: Our AI system had high sensitivity for the detection of ESCC. As a support tool, the system has the potential to enhance detection of ESCC without reducing specificity. (UMIN000039645).

DOI： 10.1111/den.13934

Transcatheter Arterial Embolization Using Microspheres for Palliating Pain from Bone Metastasis in a Patient with Cholangiocellular Carcinoma.

Shinichi Morita, Shunsuke Sugawara, Takeshi Suda, Didik Prasetyo, Takahiro Hoshi, Satoshi Abe, Kazuyoshi Yagi, Shuji Terai

Internal medicine (Tokyo, Japan) 60 ( 2 ) 241 - 246 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 72-year-old man with intractable left shoulder pain due to bone metastasis from cholangiocellular carcinoma was admitted to our hospital. Computed tomography showed an osteoblastic metastatic lesion of the left scapula. Since the pain persisted even after the administration of opioids and external irradiation, microspheres were injected through a catheter; the catheter tip was placed at the arteries feeding the metastatic lesion. After the intervention, the shoulder pain was alleviated without any procedure-related complications, leading to a reduction in the opioid dose. This case suggests the efficacy of transcatheter arterial embolization using microspheres for palliating pain from bone metastasis.

DOI： 10.2169/internalmedicine.5351-20

Comparison of Oral and Esophageal Microbiota in Patients with Achalasia Before and After Peroral Endoscopic Myotomy. 国際誌

Kazuya Takahashi, Hiroki Sato, Takeshi Mizusawa, Kentaro Tominaga, Satoshi Ikarashi, Kazunao Hayashi, Ken-Ichi Mizuno, Satoru Hashimoto, Junji Yokoyama, Shuji Terai

The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology 32 ( 1 ) 42 - 52 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: Patients with achalasia have a high incidence of esophageal squamous cell carcinoma (ESCC), which may be associated with alterations in oral and esophageal microbiota caused by food stasis. This study compared the oral and esophageal microbiota of patients with achalasia before and after peroral endoscopic myotomy (POEM). It also compared patients with achalasia to those with ESCC. MATERIALS AND METHODS: The study prospectively examined 6 patients with achalasia and 14 with superficial ESCC. Oral samples obtained from the buccal mucosa using a swab and esophageal samples obtained from the mid-esophagus using a brush via endoscopy were analyzed by 16S rRNA metagenome sequencing. Additionally, endoscopic and histological findings of patients with achalasia before and after POEM were prospectively compared. RESULTS: In patients with achalasia, Streptococcus was most abundant in both the oral and the esophageal microbiota, and these microbiota were significantly different. Although the overall structure of the oral and esophageal microbiota did not change after POEM, the relative abundance rate of Haemophilus and Neisseria increased in the esophagus, and endoscopic findings of inflammation improved after POEM (P = .04). The relative abundance of microbiota was not different among patients with achalasia from those with ESCC. CONCLUSIONS: The oral and esophageal microbiota were significantly different in patients with achalasia, and some of the composition of the esophageal microbiota changed after POEM. However, these findings and disease-specific microbiota should be further evaluated in large-scale studies.

DOI： 10.5152/tjg.2020.19995

Sofosbuvir plus velpatasvir treatment for hepatitis C virus in patients with decompensated cirrhosis: a Japanese real-world multicenter study.

Yuki Tahata, Hayato Hikita, Satoshi Mochida, Norifumi Kawada, Nobuyuki Enomoto, Akio Ido, Hitoshi Yoshiji, Daiki Miki, Yoichi Hiasa, Yasuhiro Takikawa, Ryotaro Sakamori, Masayuki Kurosaki, Hiroshi Yatsuhashi, Ryosuke Tateishi, Yoshiyuki Ueno, Yoshito Itoh, Taro Yamashita, Tatsuya Kanto, Goki Suda, Yasunari Nakamoto, Naoya Kato, Yasuhiro Asahina, Kentaro Matsuura, Shuji Terai, Kazuhiko Nakao, Masahito Shimizu, Taro Takami, Norio Akuta, Ryoko Yamada, Takahiro Kodama, Tomohide Tatsumi, Tomomi Yamada, Tetsuo Takehara

Journal of gastroenterology 56 ( 1 ) 67 - 77 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Real-world data on the efficacy and safety of sofosbuvir plus velpatasvir (SOF/VEL) treatment for patients with hepatitis C virus (HCV)-related decompensated cirrhosis are limited in Japan. METHODS: A total of 190 patients with compensated (108) or decompensated (82) cirrhosis who initiated direct-acting antiviral (DAA) treatment between February 2019 and August 2019 were enrolled. Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 weeks after the end of treatment (EOT). RESULTS: The SVR12 rates were 92.6% in patients with compensated cirrhosis and 90.2% in patients with decompensated cirrhosis (p = 0.564), and the treatment completion rates were 98.1% and 96.3%, respectively (p = 0.372). In patients with decompensated cirrhosis, 3 patients discontinued treatment and 2 patients died because of liver-related events. In patients with decompensated cirrhosis with SVR12, 50% of patients with Child-Pugh class B at baseline showed improvement to class A at SVR12, and 27% and 9% of patients with Child-Pugh class C at baseline showed improvement to class B and class A at SVR12, respectively. Patients who achieved SVR12 showed elevated serum albumin levels at the EOT, which were further elevated at SVR12, but no elevated serum albumin levels after the EOT were observed in patients with baseline serum albumin levels less than 2.8 g/dl. CONCLUSIONS: Real-world efficacy of SOF/VEL treatment for patients with decompensated cirrhosis was similar to Japanese phase 3 study, although treatment discontinuation and death related to liver disease occurred. In patients with poor hepatic reserve, whether it improves continuously after viral clearance requires further evaluation.

DOI： 10.1007/s00535-020-01733-4

The development of mesenchymal stem cell therapy in the present, and the perspective of cell-free therapy in the future. 国際誌

Yusuke Watanabe, Atsunori Tsuchiya, Shuji Terai

Clinical and molecular hepatology 27 ( 1 ) 70 - 80 2021年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cirrhosis is a chronic condition that can lead to liver failure. Currently, the viable option for decreasing mortality is liver transplantation. However, transplant surgery is highly invasive. Therefore, cell-based therapy has been developed as an alternative. Based on promising findings from preclinical research, some new trials have been registered. One of them was autologous bone marrow cell infusion therapy and found that ameliorating liver fibrosis activated liver regeneration. Now, majority of trials focus on low-immunogenicity mesenchymal stem cells (MSCs) appropriate for allogeneic administration. However, despite about 20 years of research, only a limited number of cell-based therapies have entered routine practice. Furthermore, potential shortcomings of cell-based therapy include a limit on the number of cells, which may be administered, as well as their failure to infiltrate target organs. On the other hand, these research show that MSCs act as "conducting cells" and regulate host cells including macrophages via extracellular vesicles (EVs) or exosome signals, leading to ameliorate liver fibrosis and promote regeneration. Therefore, the concept of cell-free therapy, which makes use of cell-derived EVs or exosomes, is attracting attention. Cell-free therapies may be safely administered in large doses and are able to infiltrate target organs. However, development of cell-free therapy exhibits its own set of challenges and such therapy may not be completely curative in the context of liver disease. This review describes the history of cell-based therapy research and recent advances in cell-free therapy, as well as discussing the need for more effective therapies.

DOI： 10.3350/cmh.2020.0194

【新しい肝硬変診療〜ガイドライン2020を紐解く〜】肝硬変診療の課題と今後の展望

寺井崇二, 坂牧僚

日本消化器病学会雑誌 118 ( 1 ) 41 - 45 2021年1月

Visceral Adipose Tissue Index and Hepatocellular Carcinoma Are Independent Predictors of Outcome in Patients with Cirrhosis Having Endoscopic Treatment for Esophageal Varices. 査読国際誌

Naruhiro Kimura, Atsunori Tsuchiya, Chiyumi Oda, Atsushi Kimura, Kazunori Hosaka, Kentaro Tominaga, Kazunao Hayashi, Junji Yokoyama, Shuji Terai

Digestive diseases (Basel, Switzerland) 39 ( 1 ) 58 - 65 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The relationship between the amount of adipose tissue and advanced-stage liver cirrhosis with esophageal varices (EV) is unknown. We aimed to reveal the prognostic significance of adipose tissues in patients with liver cirrhosis. METHODS: We enrolled 87 patients with EV who received initial endoscopic treatment and underwent scheduled treatments in our hospital. Computed tomography (CT) images were obtained of a 5-mm slice at the umbilical level. We evaluated the effect of mortality based on the visceral adipose tissue index (VATI), subcutaneous adipose tissue index (SATI), and visceral to subcutaneous adipose tissue ratio (VSR). RESULTS: Cox hazard multivariate analysis showed that the presence of hepatocellular carcinoma (HCC; hazard ratio [HR]: 4.650, 95% confidence interval [CI]: 1.750-12.353, p = 0.002), γ-GTP (HR: 1.003, 95% CI: 1.001-1.006, p = 0.026), and VATI (HR: 1.057, 95% CI: 1.030-1.085, p < 0.001) significantly affected mortality. Cox hazard multivariate analysis for liver-related death was also significantly affected by HCC (HR: 1.057, 95% CI: 1.030-1.085, p < 0.001) and VATI (HR: 1.052, 95% CI: 1.019-1.086, p = 0.002). The difference between the Child-Pugh scores 12 months after treatment and that during initial treatment were significantly positively correlated with VATI (r = 0.326, p = 0.027). Patients with high VATI had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis (p = 0.044). CONCLUSION: Our findings suggest that VATI measured by CT could significantly predict mortality in cirrhosis patients through decreasing liver function and increasing HCC frequency, and appropriately controlling VATI could improve their prognosis.

DOI： 10.1159/000508867

[Problems and future questions in the clinical practice of liver cirrhosis].

Shuji Terai, Akira Sakamaki

Nihon Shokakibyo Gakkai zasshi = The Japanese journal of gastro-enterology 118 ( 1 ) 41 - 45 2021年

Increase in muscle mass associated with the prebiotic effects of 1-kestose in super-elderly patients with sarcopenia.

Kentaro Tominaga, Atsunori Tsuchiya, Oki Nakano, Yasutoshi Kuroki, Kentaro Oka, Ayaka Minemura, Asami Matsumoto, Motomichi Takahashi, Yoshihiro Kadota, Takumi Tochio, Yusuke Niwa, Tomoaki Yoshida, Masatoshi Sato, Takeshi Yokoo, Satoru Hashimoto, Junji Yokoyama, Jun Matsuzawa, Katsuya Fujimori, Shuji Terai

Bioscience of microbiota, food and health 40 ( 3 ) 150 - 155 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcopenia causes functional disorders and decreases the quality of life. Thus, it has attracted substantial attention in the aging modern world. Dysbiosis of the intestinal microbiota is associated with sarcopenia; however, it remains unclear whether prebiotics change the microbiota composition and result in the subsequent recovery of muscle atrophy in elderly patients with sarcopenia. This study aimed to assess the effects of prebiotics in super-elderly patients with sarcopenia. We analyzed the effects of 1-kestose on the changes in the intestinal microbiota and body composition using a next-generation sequencer and a multi-frequency bioimpedance analysis device. The Bifidobacterium longum population was significantly increased in the intestine after 1-kestose administration. In addition, in all six patients after 12 weeks of 1-kestose administration, the skeletal muscle mass index was greater, and the body fat percentage was lower. This is the first study to show that administration of a prebiotic increased the population of B. longum in the intestinal microbiota and caused recovery of muscle atrophy in super-elderly patients with sarcopenia.

DOI： 10.12938/bmfh.2020-063

Clinical characteristics of immunoglobulin IgG4-related sclerosing cholangitis: Comparison of cases with and without autoimmune pancreatitis in a large cohort

Novel Strategy for Diagnosis of Focal Nodular Hyperplasia Using Gadolinium Ethoxybenzyl Diethylenetriaminepentaacetic Acid: Enhanced Magnetic Resonance Imaging and Magnetic Resonance Elastography

Nobutaka Takeda, Atsunori Tsuchiya, Kazuki Natsui, Yui Ishii, Yoshihisa Arao, Naruhiro Kimura, Kentaro Tominaga, Suguru Takeuchi, Kazunao Hayashi, Masaaki Takamura, Shuji Terai

CASE REPORTS IN GASTROENTEROLOGY 15 ( 2 ) 507 - 512 2021年

Naitoh, I., Kamisawa, T., Tanaka, A., Nakazawa, T., Kubota, K., Takikawa, H., Unno, M., Masamune, A., Kawa, S., Nakamura, S., Okazaki, K., Furumatsu, K., Sawai, S., Goto, T., Okumura, T., Suzuki, D., Otsuka, M., Kobori, I., Tamano, M., Koizumi, M., Hiasa, Y., Kawabe, N., Hirooka, Y., Yamamoto, S., Asano, Y., Inui, K., Horiguchi, A., Watanabe, H., Toya, D., Hatayama, K., Ueki, T., Kinoshita, N., Sugimoto, M., Ohira, H., Mukai, T., Tomita, E., Iwata, K., Shimizu, S., Suetsugu, J., Shimizu, M., Tsuji, K., Ishida, R., Ito, M., Furukawa, R., Sakamoto, N., Araki, M., Tanno, S., Sakamoto, Y., Ito, T., Takai, S., Ikeya, S., Yamada, T., Kudara, N., Shimizu, A., Hanada, K., Ichiki, Y., Kitada, H., Hifumi, M., Kimura, H., Kurosaki, M., Izumi, N., Sumi, H., Haruta, J.-I., Hayashi, K., Harada, R., Inoue, M., Nakamura, S., Ito, T., Tomishima, K., Isayama, H., Oura, K., Masaki, T., Shimokawahara, N., Tanoue, S., Maemura, K., Ido, A., Mizushima, I., Kawano, M., Yoshida, K., Naganuma, M., Murata, M., Nishio, A., Fujita, Y., Teratani, T., Matsubara, S., Tamai, H., Yoshida, Y., Azemoto, R., Kamata, K., Watanabe, T., Kurosu, T., Koizumi, W., Fujita, J., Seki, H., Ueda, Y., Fukumoto, T., Kousaki, T., Uchida, K., Ochiai, T., Kawasaki, T., Tanaka, M., Ishida, E., Notohara, K., Mori, H., Mori, T., Kawabata, H., Miyata, M., Sakagami, J., Itoh, Y., Shiokawa, M., Seno, H., Watanabe, N., Kataoka, H., Aoki, T., Fujishiro, M., Niihara, T., Nishimata, H., Mitoro, A., Yoshiji, H., Yoshida, M., Ikeda, M., Tomita, K., Hokari, R., Hayasaka, K., Amano, Y., Shioji, K., Hayashi, K., Terai, S., Nakajima, M., Yamahana, J., Matsumoto, R., Kikuchi, H., Kanamori, A., Kiriyama, S., Iwatsu, S., Kato, Y., Horiguchi, S., Yagi, T., Okada, H., Ohkawa, K., Hirao, M., Hiramatsu, N., Oza, N., Imamura, H., Baba, T., Nakano, S., Shinobi, T., Ryozawa, S., Motoya, M., Nakase, H., Kinoshita, N., Ito, K., Miyake, T., Kohge, N., Tobita, H., Joshita, S., Umemura, T., Kawaguchi, S., Ohno, K., Sonobe, K., Satoh, A., Shimosegawa, T., Miura, F., Yagi, M., Sano, K., Kin, T., Katanuma, A., Koike, K., Miura, S., Kawashima, Y., Kagawa, T., Azuma, S., Watanabe, M., Honjyo, M., Itoi, T., Honda, A., Kobayashi, K., Asano, T., Mizuno, S., Nishino, T., Taniguchi, H., Tajiri, K., Yasuda, I., Tanaka, Y., Oe, S., Harada, M., Kurata, M., Fukasawa, M., Enomoto, N., Kawaji, Y., Kitano, M., Nishise, Y., Hirakawa, H., Ishizawa, T., Ueno, Y., Kaino, M., Fujimoto, Y., Sakaida, I.

Digestive and Liver Disease 53 ( 10 ) 2021年

Liver cirrhosis with ruptured splenic artery aneurysm leading to hepatitis c treatment: A case report

Hojo, Y., Kamimura, H., Owaki, T., Kimura, R., Iwasawa, T., Watanabe, Y., Takatsuna, M., Ikarashi, S., Takamura, M., Setsu, T., Arao, Y., Horii, Y., Sato, T., Terai, S.

Kanzo/Acta Hepatologica Japonica 62 ( 11 ) 2021年

Predicting Cervical Lymph Node Metastasis Following Endoscopic Surgery in Superficial Head and Neck Carcinoma. 国際誌

Ryuichi Okabe, Yushi Ueki, Riuko Ohashi, Manabu Takeuchi, Satoru Hashimoto, Takeshi Takahashi, Ryusuke Shodo, Keisuke Yamazaki, Hiroshi Matsuyama, Hajime Umezu, Shuji Terai, Yoichi Ajioka, Arata Horii

Frontiers in surgery 8 813260 - 813260 2021年

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Early detection of head and neck carcinoma (HNC) as superficial HNC (SHNC) identified using recently developed optical techniques, such as magnifying endoscopy and narrow-band imaging (NBI), in combination with endoscopic surgeries enables minimally invasive treatment with favorable outcomes for HNC. This study aimed to identify the predictive factors for the rare but important clinical issue of SHNC, namely cervical lymph node metastasis (CLNM), following endoscopic resection. METHODS: Sixty-nine patients with SHNC who underwent endoscopic resection were enrolled in the study. Clinical data, preoperative endoscopic findings, pathological findings, and treatment outcomes were retrospectively reviewed. Because the pharyngeal mucosa lacks the muscularis mucosa, we measured tumor thickness in permanent pathology as an alternative to the depth of invasion. Correlations with the occurrence of CLNM were statistically examined. RESULTS: The 5-year disease-specific survival rate was 100%. Of 69 patients, 3 (4.3%) developed CLNM. All had subepithelial but not epithelial tumors. The 0-IIa type in the macroscopic findings, type B2/B3 vessels in narrow-band imaging, tumors ≥ pathological stage T2, lymphatic invasion, positive surgical margins, and tumor thickness >1,000 μm showed significant correlations with CLNM following endoscopic resection. Furthermore, the classification of type B vessels was significantly associated with tumor thickness. CONCLUSION: The treatment outcomes following endoscopic resection for SHNC were favorable. The risk of CLNM following endoscopic resection in SHNC can be predicted by several preoperative endoscopic and postoperative pathological findings. Among them, the classification of type B vessels, which correlated with both tumor thickness and CLNM, might be a useful predictive factor.

DOI： 10.3389/fsurg.2021.813260

Outcomes of endoscopic ultrasound-guided biliary drainage in a general hospital for patients with endoscopic retrograde cholangiopancreatography-difficult transpapillary biliary drainage

Kuraoka, N., Hashimoto, S., Matsui, S., Terai, S.

Journal of Clinical Medicine 10 ( 18 ) 2021年

Unresectable primary hepatic adenosquamous carcinoma successfully treated with systemic and transcatheter hepatic arterial injection chemotherapies followed by conversion surgery: a case report and literature review

Watanabe, Y., Osaki, A., Kimura, K., Yakubo, S., Takaku, K., Sato, M., Hashidate, H., Waguri, N., Terai, S.

BMC Gastroenterology 21 ( 1 ) 2021年

Choledochocele observed on direct peroral cholangioscopy using an ultra-slim endoscope.

Satoshi Ikarashi, Kazunao Hayashi, Shuji Terai

Journal of hepato-biliary-pancreatic sciences 2020年12月

Monitoring chronological change by liver-to-spleen attenuation ratio for secondary hepatic steatosis for a short term. 査読

Hiroteru Kamimura, Kunihiko Yokoyama, Shunsuke Nojiri, Yuko Komoro, Toshiko Murayama, Yu Koyama, Kenya Kamimura, Masaaki Takamura, Junji Yokoyama, Shuji Terai

Clinical journal of gastroenterology 13 ( 6 ) 1219 - 1224 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Parenteral nutrition-associated liver disease (PNALD) causes hepatic steatosis and moderate liver enzyme elevation due to lack of enteral nutrition and deficiency of some nutrients. However, the period for recovery from PNALD after a nutritional intervention is unknown with no report. Herein, we report a case of a 44-year-old Japanese woman with severe fatty infiltration of the liver due to malnutrition. Our nutritional support team administered appropriate total parenteral, especially fat and carnitine, nutrition to improve her malnutrition. Chronological changes in liver-to-spleen attenuation ratio were also considered because of her disease state. Computed tomography demonstrated improved attenuation of the liver, and the liver enzymes level normalized after 5 weeks from appropriate nutrition. Understanding the nutritional condition of a patient may help in elucidating an appropriate treatment strategy.

DOI： 10.1007/s12328-020-01165-w

Rare case of gastric perforation due to ischemic gastropathy. 国際誌

Yui Ishii, Hiroki Sato, Shuji Terai

Gastrointestinal endoscopy 92 ( 6 ) 1266 - 1268 2020年12月

Daily Monitoring of Serum Wisteria floribunda Agglutinin-Positive Mac-2 Binding Protein Is Useful for Predicting Therapeutic Effect of Tolvaptan in Cirrhotic Ascites.

Masaaki Takamura, Akira Sakamaki, Yoshihisa Arao, Toru Setsu, Hiroteru Kamimura, Takeshi Yokoo, Kenya Kamimura, Atsunori Tsuchiya, Shuji Terai

The Tohoku journal of experimental medicine 252 ( 4 ) 287 - 296 2020年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Wisteria floribunda agglutinin (WFA) is a lectin that binds to the sugar chain of Mac-2 binding protein (M2BP), and WFA-positive M2BP (WFA+-M2BP) has been reported as a useful marker for assessing liver fibrosis in chronic liver disease. Tolvaptan (TLV), a selective vasopressin V2 receptor antagonist, is used for cirrhotic ascites in Japan, but good predictors of treatment efficacy remain to be established. Our aim was to investigate whether WFA+-M2BP monitoring before and after TLV administration can predict treatment efficacy in patients with cirrhotic ascites. Twenty patients (10 men), with a median age of 72 years, were enrolled. Cirrhosis was caused by hepatitis B virus (n = 3), hepatitis C virus (n = 4), alcohol (n = 8), and others (n = 5). Responders were defined as having a body weight loss of ≥ 1.5 kg/week after TLV administration. Serum WFA+-M2BP levels were measured at baseline and days 1, 3, and 7 after TLV treatment. Twelve patients (60%) were responders. Baseline WFA+-M2BP levels were correlated with serum albumin levels (r = -0.544, P = 0.013). The baseline furosemide dose was lower and platelet count was higher in responders than in non-responders (P < 0.05). The ratio of WFA+-M2BP levels on day 1 after TLV administration to baseline was lower in responders than in non-responders (P < 0.05). The decrease in the ratio discriminated responders from non-responders (AUC = 0.844, P < 0.05). In conclusion, monitoring serum WFA+-M2BP is helpful for predicting the efficacy of TLV treatment in patients with cirrhotic ascites.

DOI： 10.1620/tjem.252.287

キーワード(No.39) Leaky GUT

夏井一輝, 土屋淳紀, 寺井崇二

消化器病学サイエンス 4 ( 4 ) 227 - 227 2020年12月

アルコール性肝硬変におけるALD/NAFLD Index低値例の臨床的特徴

坂牧僚, 横山邦彦, 森田真一, 上村顕也, 高村昌昭, 寺井崇二

アルコールと医学生物学 39 96 - 97 2020年12月

急性肝炎後再生不良性貧血の1例

阿部聡司, 名古屋拓郎, 土屋淳紀, 川合弘一, 山際訓, 寺井崇二

肝臓 61 ( 12 ) 753 - 753 2020年12月

Usefulness of ultrasonography to assess the response to steroidal therapy for the rare case of type 2b immunoglobulin G4-related sclerosing cholangitis without pancreatitis: A case report. 国際誌

Yuto Tanaka, Kenya Kamimura, Ryota Nakamura, Marina Ohkoshi-Yamada, Yohei Koseki, Takeshi Mizusawa, Satoshi Ikarashi, Kazunao Hayashi, Hiroki Sato, Akira Sakamaki, Junji Yokoyama, Shuji Terai

World journal of clinical cases 8 ( 22 ) 5821 - 5830 2020年11月

記述言語：英語

BACKGROUND: A type 2b immunoglobulin G4 (IgG4)-related sclerosing cholangitis (SC) without autoimmune pancreatitis is a rare condition with IgG4-SC. While the variety of the imaging modalities have tested its usefulness in diagnosing the IgG4-SC, however, the usage of ultrasonography for the assessment of the response to steroidal therapy on the changes of bile duct wall thickness have not been reported in the condition. Therefore, the information of our recent case and reported cases have been summarized. CASE SUMMARY: We report the case of an 82-year-old Japanese man diagnosed with isolated IgG4-related SC based on the increase of serum IgG4, narrowing of the bile duct, its wall thickness, no complication of autoimmune pancreatitis, and IgG4 positive inflammatory cell infiltration to the wall with the fibrotic changes. The cholangiogram revealed type 2b according to the classification. Corticosteroid treatment showed a favorable effect, with the smooth decrease in serum IgG4 and the improvement of the bile duct wall thickness. CONCLUSION: As isolated type 2b, IgG4-SC is rare, the images, histological findings, and clinical course of our case will be helpful for physicians to diagnose and treat the new cases appropriately.

DOI： 10.12998/wjcc.v8.i22.5821

Stent Placement for Malignant Inferior Vena Cava Syndrome in a Patient with Recurrent Colon Cancer.

Shinichi Morita, Shunsuke Sugawara, Takeshi Suda, Didik Prasetyo, Yuka Kobayashi, Takahiro Hoshi, Satoshi Abe, Kazuyoshi Yagi, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 22 ) 2885 - 2890 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 70-year-old man was admitted to our hospital with gait disturbance due to marked edema of the lower limbs for more than 6 months. He had been receiving systemic chemotherapy over two years for multiple recurrence after sigmoid colon cancer resection. Contrast-enhanced computed tomography demonstrated severe inferior vena cava (IVC) stenosis due to compression by lymph node metastases, i.e. IVC syndrome. As increased doses of diuretic agents failed to improve the edema, IVC stent placement was performed. This led to significant improvement of the edema and complete gait normalization. This case demonstrates the efficacy of IVC stent placement for IVC syndrome.

DOI： 10.2169/internalmedicine.5033-20

Pancreas Gas Gangrene Caused by Klebsiella pneumoniae.

Yui Ishii, Atsunori Tsuchiya, Kazunao Hayashi, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 22 ) 2963 - 2964 2020年11月

Esophageal High-Resolution Manometry for Diagnosing the Severity of the Chronic Intestinal Pseudo-Obstruction: A Case Series. 国際誌

Hiroki Sato, Kenya Kamimura, Hideaki Matsui, Takashi Owaki, Shinichi Morita, Yuto Tanaka, Natsuki Ishikawa, Yoshifumi Shimada, Junji Yokoyama, Toshifumi Wakai, Shuji Terai

Digestive diseases and sciences 66 ( 11 ) 3960 - 3967 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Chronic intestinal pseudo-obstruction (CIPO) is a severe and refractory intestinal motility disorder. However, due to its rarity and difficult histological investigation, its pathophysiology has not been characterized. AIM: Therefore, in this study, we aimed to determine the role of esophageal high-resolution manometry (HRM) in CIPO and the histological and clinical characteristics of the disease. METHODS: Patients with CIPO were analyzed for clinical characteristics; histological findings; and clinical courses after therapeutic intervention. In addition, HRM was performed to determine the esophageal involvement. RESULTS: Eleven patients were diagnosed with CIPO, and five required the long period of parenteral nutrition showing impaired esophageal motility including achalasia and absent contractility diagnosed with HRM. The four of these five cases showed acute onset of the CIPO following the triggering events of pregnancy, appendicitis, and surgery. In contrast, other six patients with normal or Jackhammer esophagus on HRM had moderate severity of CIPO with gradual onset. The histological analyses revealed that the loss of the intestinal neural ganglion cells and layers by inflammation, destruction, and atrophy are related to the severity of the clinical course of the disease and esophageal HRM findings of achalasia and absent contractility. CONCLUSIONS: HRM may be useful to diagnose the severity of the clinical course and to determine the therapeutic options for CIPO.

DOI： 10.1007/s10620-020-06701-9

消化管疾患に対する低侵襲治療の現状と今後の展開-内科、外科の立場から- 当院における腹腔鏡・内視鏡合同手術(LECS)の現状と課題

日本消化器病学会甲信越支部例会抄録集 67回 69 - 69 2020年11月

Risk factors for walled-off necrosis associated with severe acute pancreatitis: A multicenter retrospective observational study.

Satoshi Ikarashi, Hirokazu Kawai, Kazunao Hayashi, Junji Kohisa, Toshifumi Sato, Yujiro Nozawa, Shinichi Morita, Hiromitsu Oka, Munehiro Sato, Yukio Aruga, Seiichi Yoshikawa, Shuji Terai

Journal of hepato-biliary-pancreatic sciences 27 ( 11 ) 887 - 895 2020年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: This study aimed to identify the risk factors for walled-off necrosis (WON) associated with severe acute pancreatitis (SAP). METHODS: This retrospective study was conducted in eight institutions in Japan between 2014 and 2017. We analyzed WON incidence, patient characteristics, and risk factors for WON in patients with SAP who were observed for >28 days. RESULTS: Of 134 patients with SAP, WON occurred in 40 (29.9%). Male sex (P = .045), body mass index (BMI) ≥25 (P < .001), post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (P = .020), and disseminated intravascular coagulation (DIC) (P = .001) were more frequent in the WON group than in the non-WON group. On admission, the frequency of white blood cell counts ≥ 12 000/µL (P = .037) and hypoenhanced pancreatic lesion on computed tomography (P = .047) were significantly higher in the WON group. In multivariate analysis, BMI ≥ 25 (odds ratio [OR] 5.73, 95% confidence interval [CI] 1.95-16.8; P = .002), post-ERCP (OR 8.08, 95% CI 1.57-41.7; P = .013), and DIC (OR 3.52, 95% CI 1.20-10.4; P = .022) were independent risk factors for WON. CONCLUSIONS: High BMI, post-ERCP pancreatitis, and DIC are risk factors for the development of WON associated with SAP.

DOI： 10.1002/jhbp.787

急性腹症を契機にC型慢性肝炎が発見された1例

北條雄暉, 上村博輝, 木村莉菓, 大脇崇史, 岩澤貴宏, 渡邉雄介, 高綱将史, 荒生祥尚, 薛徹, 五十嵐聡, 高村昌昭, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 67回 96 - 96 2020年11月

良悪性鑑別困難な胆膵疾患の診断と治療の最前線-内科、外科の立場から- 自己免疫性膵炎と膵癌との鑑別の現状と課題

小川光平, 林和直, 五十嵐聡, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 67回 32 - 32 2020年11月

ウイルス肝炎診療:新旧の課題と解決への戦略当院・関連施設におけるソホスブビル/ベルパタスビル11症例での治療効果と安全性の検討

荒生祥尚, 薛徹, 寺井崇二

肝臓 61 ( Suppl.3 ) A775 - A775 2020年11月

ステロイド治療前後で肝硬度と病理像を評価し得た肝サルコイドーシスの一例

水戸將貴, 荒生祥尚, 夏井一輝, 前田悠一郎, 小島雄一, 林和直, 土屋敦紀, 梅津哉, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 67回 95 - 95 2020年11月

被包化膵壊死への真菌感染による敗血症性ショックをきたした一例

山田麻理奈[大越], 上村顕也, 石川夏生, 小関洋平, 田中裕登, 水澤健, 佐藤裕樹, 五十嵐聡, 林和直, 坂牧僚, 横山純二, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 67回 26 - 26 2020年11月

肝疾患に対するPrecision Medicineの実現可能性を探る:新規バイオマーカーを含めて肝障害の程度、機能回復の指標としての血中セロトニンの検証

薛徹, 上村顕也, 寺井崇二

肝臓 61 ( Suppl.3 ) A832 - A832 2020年11月

よりよい肝移植医療のあり方を探る当県での移植へのゲートウェイとしてのネットワークシステムの取り組み

薛徹, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.3 ) A800 - A800 2020年11月

短期間に急速な肝脂肪沈着と栄養・運動介入による肝機能の改善を確認できたアスリートの一例

上村博輝, 木村莉菓, 北條雄暉, 渡邊雄介, 高綱将史, 五十嵐聡, 佐野正和, 真田奈緒, 武田安永, 小師優子, 高村昌昭, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 67回 97 - 97 2020年11月

Shear wave elastographyを用いたNAFLDにおける肝線維化の左右差の検討

横尾健, 杉田萌乃, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

超音波医学 47 ( Suppl. ) S349 - S349 2020年11月

令和の時代に求められる肝硬変の多角的治療戦略十全大補湯と間葉系幹細胞の併用療法はCC14投与肝硬変モデルマウスにおいて効果的な抗炎症・抗線維化効果を及ぼす

野尻俊介, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.3 ) A853 - A853 2020年11月

臨床応用を見据えた肝の臓器再生研究の展望肝硬変に対する間葉系細胞治療とそのエクソソーム治療の可能性

土屋淳紀, 竹内卓, 寺井崇二

肝臓 61 ( Suppl.3 ) A827 - A827 2020年11月

【肝硬変診療の新時代】肝再生治療開発の現況

竹内卓, 渡邉雄介, 土屋淳紀, 寺井崇二

臨床消化器内科 35 ( 13 ) 1601 - 1605 2020年11月

脂肪性肝疾患:治療のターゲットとゴール脂肪性疾患の病態進行と自律神経ネットワークを介する臓器連関の関与

上村顕也, 大脇崇史, 寺井崇二

肝臓 61 ( Suppl.3 ) A758 - A758 2020年11月

進行肝細胞癌に対する集学的治療:エビデンスとコンセンサス肝癌に対する放射線治療の安全性と有用性の検討

上村顕也, 大越麻理奈, 寺井崇二

肝臓 61 ( Suppl.3 ) A811 - A811 2020年11月

MC4R遺伝子及びMaid遺伝子両欠損マウスを用いた新規脂肪肝モデルマウスの検討

森田真一, 坂牧僚, 永山逸夫, 大越麻理奈, 小山究太郎, 田中裕登, 大脇崇史, 小田知友美, 柴田理, 木村淳史, 阿部寛幸, 上村顕也, 寺井崇二

肝臓 61 ( Suppl.3 ) A876 - A876 2020年11月

Efficacy and Safety of the Radiotherapy for Liver Cancer: Assessment of Local Controllability and its Role in Multidisciplinary Therapy. 国際誌

Marina Ohkoshi-Yamada, Kenya Kamimura, Osamu Shibata, Shinichi Morita, Motoki Kaidu, Toshimichi Nakano, Katsuya Maruyama, Atsushi Ota, Hirotake Saito, Nobuko Yamana, Tomoya Oshikane, Yukiyo Goto, Natsumi Yoshimura, Satoshi Tanabe, Hisashi Nakano, Madoka Sakai, Yuto Tanaka, Yohei Koseki, Yoshihisa Arao, Hiroyuki Abe, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Hidefumi Aoyama, Shuji Terai

Cancers 12 ( 10 ) 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

This study investigated the efficacy and safety of radiotherapy as part of multidisciplinary therapy for advanced hepatocellular carcinoma (HCC). Clinical data of 49 HCC patients treated with radiotherapy were assessed retrospectively. The efficacy of radiotherapy was assessed by progression-free survival, disease control rate, and overall survival. Safety was assessed by symptoms and hematological assay, and changes in hepatic reserve function were determined by Child-Pugh score and albumin-bilirubin (ALBI) score. Forty patients underwent curative radiotherapy, and nine patients with portal vein tumor thrombus (PVTT) underwent palliative radiotherapy as part of multidisciplinary therapy. Local disease control for curative therapy was 80.0% and stereotactic body radiotherapy was 86.7% which was greater than that of conventional radiotherapy (60.0%). Patients with PVTT had a median observation period of 651 days and 75% three-year survival when treated with multitherapy, including radiotherapy for palliative intent, transcatheter arterial chemoembolization, and administration of molecular targeted agents. No adverse events higher than grade 3 and no changes in the Child-Pugh score and ALBI score were seen. Radiotherapy is safe and effective for HCC treatment and can be a part of multidisciplinary therapy.

DOI： 10.3390/cancers12102955

Blocking sphingosine 1-phosphate receptor 2 accelerates hepatocellular carcinoma progression in a mouse model of NASH. 査読国際誌

Tomoaki Yoshida, Atsunori Tsuchiya, Masaru Kumagai, Suguru Takeuchi, Shunsuke Nojiri, Takayuki Watanabe, Masahiro Ogawa, Michiko Itoh, Masaaki Takamura, Takayoshi Suganami, Yoshihiro Ogawa, Shuji Terai

Biochemical and biophysical research communications 530 ( 4 ) 665 - 672 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

The role of sphingosine 1-phosphate (S1P) and its sphingosine-1-phosphate receptors (S1PRs) in non-alcoholic steatohepatitis (NASH) is unclear. We aimed to analyze the role of S1P/S1PRs in a Melanocortin-4 receptor (Mc4r)-deficient NASH murine model using FTY720, the functional antagonist of S1PR1, S1PR3, S1PR4, and S1PR5, and JTE-013, the antagonist of S1PR2. We observed that, compared to that in the control, the mRNA of S1pr1 tended to decrease, whereas those of S1pr2 and S1pr3 significantly increased in Mc4r-knockout (KO) mice subjected to a Western diet (WD). While the fat area did not differ, fibrosis progression differed significantly between control mice and mice in which liver S1PRs were blocked. Lipidomic and metabolomic analysis of liver tissues showed that JTE-013-administered mice showed elevation of S-adenosyl-l-methionine level, which can induce aberrant methylation due to reduction in glycine N-methyltransferase (GNMT) and elevation in diacylglycerol (DG) and triacylglycerol (TG) levels, leading to increased susceptibility to hepatocellular carcinoma (HCC). These phenotypes are similar to those of Gnmt-KO mice, suggesting that blocking the S1P/S1PR2 axis triggers aberrant methylation, which may increase DG and TG, and hepatocarcinogenesis. Our observations that the S1P/S1PR2 axis averts HCC occurrence may assist in HCC prevention in NASH.

DOI： 10.1016/j.bbrc.2020.07.099

Screening and follow-up of chronic liver diseases with understanding their etiology in clinics and hospitals. 国際誌

Masahiro Ogawa, Atsunori Tsuchiya, Takayuki Watanabe, Toru Setsu, Naruhiro Kimura, Masato Matsuda, Yoshiki Hoshiyama, Hiroaki Saito, Tsutomu Kanazawa, Motoi Shiotani, Tatsuhiko Sato, Takuya Yagi, Koji Igarashi, Norihiko Yoshimura, Masaaki Takamura, Hidefumi Aoyama, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 4 ( 5 ) 827 - 837 2020年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and Aim: Considering the increasing prevalence of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis (NASH), the development of an effective screening and follow-up system that enables the recognition of etiological changes by primary physicians in clinics and specialists in hospitals is required. Methods: Chronic hepatitis B (HBV) and C (HCV), NASH, and alcoholic steatohepatitis (ASH) patients who were assayed for Mac-2-binding protein glycosylation isomer (M2BPGi) (n = 272) and underwent magnetic resonance elastography (MRE) (n = 119) were enrolled. Patients who underwent MRE were also tested by ultrasound elastography (USE) (n = 80) and for M2BPGi (n = 97), autotaxin (ATX) (n = 62), and platelet count (n = 119), and their fibrosis-4 (FIB-4) index was calculated (n = 119). Results: FIB-4 index >2, excluding HBV-infected patients, M2BPGi >0.5, ATX >0.5, and platelet count <20 × 104/μL were the benchmark indices, and we took into consideration other risk factors, such as diabetes mellitus and age, to recommend further examinations, such as USE, based on the local situation to avoid overlooking hepatocellular carcinoma (HCC) in the clinic. During specialty care in the hospital, MRE exhibited high diagnostic ability for fibrosis stages >F3 or F4; it could efficiently predict collateral circulation with high sensitivity, which can replace USE. We also identified etiological features and found that collateral circulation in NASH/ASH patients tended to exceed high-risk levels; moreover, these patients exhibited more variation in HCC-associated liver stiffness than the HBV and HCV patients. Conclusions: Using appropriate markers and tools, we can establish a stepwise, practical, noninvasive, and etiology-based screening and follow-up system in primary and specialty care.

DOI： 10.1002/jgh3.12406

Refractory hemorrhagic esophageal ulcers by Candida esophagitis with advanced systemic sclerosis. 国際誌

Kazuki Natsui, Atsunori Tsuchiya, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 4 ( 5 ) 1007 - 1008 2020年10月

記述言語：英語

A 64-year-old woman diagnosed with rheumatoid arthritis (RA) and systemic sclerosis (SSc) was admitted to our hospital with chief complaints of uncontrolled bleeding from esophageal ulcers and an inability to consume meals. For RA and SSc, she was treated with prednisolone and abatacept and was taking vonoprazan as prophylaxis for steroid-induced gastric ulcers. She was diagnosed with severe Candida esophagitis, with multiple large and small ulcers with bleeding, based on esophagogastroduodenoscopy and pathological findings. We performed comprehensive treatment; abatacept was discontinued, and total parenteral nutrition was initiated along with antifungal therapy. Improvement in the esophageal ulcers was observed. Although severe Candida esophagitis is a rare condition, we should keep in mind that severe Candida esophagitis can occur in patients with an immunosuppressive compromised host and esophageal movement disorders such as SSc. Regular follow up by endoscopy and prophylactic treatment to prevent severe esophagitis may be necessary.

DOI： 10.1002/jgh3.12353

急性膵炎およびその合併症治療の最前線新潟県における重症急性膵炎の予後改善を目指して Niigata SAP network

重症急性膵炎後Walled-off necrosisの内視鏡治療におけるLumen apposing metal stentの有効性

五十嵐聡, 林和直, 寺井崇二

Gastroenterological Endoscopy 62 ( Suppl.2 ) 2162 - 2162 2020年10月

林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増大会 ) A624 - A624 2020年10月

食道・胃静脈瘤治療の現状と今後の展望門亢症の病態から考えたEIS/EVLの長期予後

薛徹, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 26 ( 3 ) 68 - 68 2020年10月

【肝硬変のトータルマネジメント】肝腎症候群に対する治療海外での動向

坂牧僚, 薛徹, 阿部寛幸, 上村顕也, 高村昌昭, 寺井崇二

肝臓クリニカルアップデート 6 ( 2 ) 205 - 211 2020年10月

再生医療はどこまで進んだか(vol.17) 間葉系幹細胞投与による肝線維化改善、再生誘導効果基礎研究成果の臨床応用

寺井崇二, 土屋淳紀

医学のあゆみ 275 ( 4 ) 367 - 370 2020年10月

Translational researchを目指した下部消化管研究炎症性腸疾患に対する間葉系幹細胞(MSC)、エクソソーム療法の可能性の検討

川田雄三, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増大会 ) A602 - A602 2020年10月

肝性脳症〜わが国における現状と課題〜潜在性肝性脳症患者における呼気中水素・メタン分析の有用性の検討

坂牧僚, 横山邦彦, 小山究太郎, 森田真一, 阿部寛幸, 上村顕也, 高村昌昭, 横山純二, 寺井崇二

日本門脈圧亢進症学会雑誌 26 ( 3 ) 76 - 76 2020年10月

急性膵炎およびその合併症治療の最前線新潟県における重症急性膵炎の予後改善を目指して Niigata SAP network

林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増大会 ) A624 - A624 2020年10月

Synchronous Double Bile Duct Cancers with Distinct Genetic Features.

Shinichi Morita, Takeshi Suda, Yoji Kishi, Toshimitsu Iwasaki, Nobuyoshi Hiraoka, Itsuo Nagayama, Takahiro Hoshi, Satoshi Abe, Kazuyoshi Yagi, Go Hasegawa, Toshihiko Ikarashi, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 17 ) 2129 - 2134 2020年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 69-year-old man was referred to our hospital because of appetite loss. Imaging showed a nodular tumor in the perihilar bile duct and a second flat lesion in the distal bile duct. Right hepatopancreaticoduodenectomy was performed, and the histopathological findings demonstrated that the perihilar and distal lesions were moderately and poorly differentiated adenocarcinoma, respectively, and anatomically separated. Furthermore, the resected specimens showed no pancreaticobiliary maljunction. Histological and TP53 gene analyses in a rare case of synchronous double bile duct cancers suggest that there are various genetic pathways through which bile duct cancer develops, highlighting the complexity of its pathogenesis.

DOI： 10.2169/internalmedicine.4613-20

Transcriptomic Dissection of Hepatocyte Heterogeneity: Linking Ploidy, Zonation, and Stem/Progenitor Cell Characteristics 査読

Takeshi Katsuda, Kazunori Hosaka, Juntaro Matsuzaki, Wataru Usuba, Marta Prieto-Vila, Tomoko Yamaguchi, Atsunori Tsuchiya, Shuji Terai, Takahiro Ochiya

Cellular and Molecular Gastroenterology and Hepatology 9 ( 1 ) 161 - 183 2020年9月

2D-Shear Wave ElastographyとTransient Elastographyの乖離症例の特徴

杉田萌乃, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A695 - A695 2020年9月

健診受検者における年齢層別NAFLDの解析と高齢者の意識変化

横尾健, 佐藤公俊, 丹羽佑輔, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A671 - A671 2020年9月

mALBI score/gradeからみたNASH薬物治療に対する肝予備能への影響

高村昌昭, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.2 ) A691 - A691 2020年9月

2D-Shear Wave ElastographyとTransient Elastographyの乖離症例の特徴

杉田萌乃, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A695 - A695 2020年9月

mALBI score/gradeからみたNASH薬物治療に対する肝予備能への影響

高村昌昭, 横尾健, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.2 ) A691 - A691 2020年9月

健診受検者における年齢層別NAFLDの解析と高齢者の意識変化

横尾健, 佐藤公俊, 丹羽佑輔, 荒生祥尚, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A671 - A671 2020年9月

消化器疾患に対する再生医療の応用間葉系幹細胞の治療効果メカニズム検証に基づく肝硬変に対するより効果的な治療法開発

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.2 ) A583 - A583 2020年9月

Effectiveness of Endoscopic Pancreatic Stenting for Pancreatic Pseudocyst-Portal Vein Fistula

Atsushi Kimura, Kazunao Hayashi, Chiyumi Oda, Kazunori Hosaka, Naruhiro Kimura, Kentaro Tominaga, Satoshi Ikarashi, Atsunori Tsuchiya, Shuji Terai

CASE REPORTS IN GASTROENTEROLOGY 14 ( 3 ) 570 - 576 2020年9月

脂肪性肝疾患における自律神経系ネットワークを介したセロトニンの関与

大脇崇史, 上村顕也, 高昌良, 名古屋拓郎, 永山逸夫, 大越麻理奈, 薛徹, 寺井崇二

肝臓 61 ( Suppl.2 ) A670 - A670 2020年9月

肝臓を基軸とした臓器連関肝臓を基軸とし自律神経系経路を介する多臓器連関の肝病態への関与の解明

上村顕也, 大脇崇史, 寺井崇二

肝臓 61 ( Suppl.2 ) A613 - A613 2020年9月

Portal Vein Thrombosis Associated with Trousseau Syndrome due to Urinary Bladder Squamous Cell Carcinoma in a Liver Cirrhosis Patient. 査読

Naruhiro Kimura, Atsunori Tsuchiya, Chiyumi Oda, Atsushi Kimura, Kazunori Hosaka, Kentaro Tominaga, Kazunao Hayashi, Tatsuya Abé, Hajime Umezu, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 16 ) 1971 - 1975 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 75-year-old woman with liver cirrhosis was admitted for treatment of portal vein thrombosis (PVT). Computed tomography (CT) showed PVT, massive ascites, and multiple abdominal organ embolism. Blood tests revealed a decreased liver function (Child-Pugh grade C). Language impairment followed by progressive left hemi-paralysis was subsequently detected. Magnetic resonance imaging revealed multiple small acute cerebral infarctions and, on CT, a 30-mm bladder tumour; a biopsy specimen examination showed squamous cell carcinoma. Her general condition worsened rapidly, and the best supportive care was chosen. Our findings suggest that, in patients with PVT, Trousseau syndrome should be considered, even in cases of liver cirrhosis.

DOI： 10.2169/internalmedicine.4112-19

Esophageal Ulcers Associated with Ulcerative Colitis: A Case Series and Literature Review. 査読

Kentaro Tominaga, Atsunori Tsuchiya, Hiroki Sato, Takeshi Mizusawa, Shinichi Morita, Yui Ishii, Nobutaka Takeda, Kazuki Natsui, Yuzo Kawata, Naruhiro Kimura, Yoshihisa Arao, Kazuya Takahashi, Kazunao Hayashi, Junji Yokoyama, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 16 ) 1983 - 1989 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Ulcerative colitis, a chronic and recurrent inflammatory disease, is localized to the colonic mucosa but can affect other organs and lead to various complications. Gastroduodenitis associated with ulcerative colitis has been reported. However, little is known about esophageal ulcers. We herein report two rare cases of esophageal ulcers associated with ulcerative colitis. Furthermore, the clinical and histological characteristics of 18 previously reported cases are summarized. This case series and literature review will encourage the accurate diagnosis and treatment of esophageal ulcers associated with ulcerative colitis.

DOI： 10.2169/internalmedicine.4437-20

Advanced squamous cell carcinoma in an asymptomatic, large, epiphrenic esophageal diverticulum.

Tomoaki Yoshida, Satoru Hashimoto, Ken-Ichi Mizuno, Hiroshi Ichikawa, Junji Yokoyama, Hajime Umezu, Shuji Terai

Clinical journal of gastroenterology 13 ( 4 ) 477 - 482 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

An asymptomatic epiphrenic diverticulum (ED) was diagnosed in a man undergoing annual esophagogastroduodenoscopy (EGD) at another hospital 40 years before he presented to our hospital at age 63 years for his annual EGD. However, because substantial food retention was found in the ED, we could not confirm a lesion. After the retained food was removed endoscopically, a second EGD showed a reddish, flat lesion with an elevated mass within the ED. Endoscopic ultrasonography indicated that the elevated mass was deep in the submucosal layer. An esophagram showed that the ED was approximately 80 mm in diameter, which is considered large. An endoscopic biopsy of the lesion confirmed squamous cell carcinoma. Total esophagectomy was performed. Microscopic examination revealed well-differentiated to moderately differentiated squamous cell carcinoma invading the adventitia at the elevated lesion. The final pathological stage was pT3N0M0. There was no evidence of recurrence for 3 years during the quarterly follow-up examinations. To our knowledge, this case involved the longest asymptomatic term (40 years) since the ED was detected. A review of 18 reported cases of carcinoma in an ED indicated that advanced cancer has a poor prognosis. Periodic follow-up of ED patients is essential for early diagnosis.

DOI： 10.1007/s12328-020-01098-4

Real-world effectiveness and safety of tolvaptan in liver cirrhosis patients with hepatic edema: results from a post-marketing surveillance study (START study).

Isao Sakaida, Shuji Terai, Masayuki Kurosaki, Mitsuru Okada, Takahiro Hirano, Yasuhiko Fukuta

Journal of gastroenterology 55 ( 8 ) 800 - 810 2020年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: This large-scale post-marketing surveillance study (START study) evaluated the effectiveness and safety of tolvaptan in Japanese liver cirrhosis patients with hepatic edema in real-world clinical settings. Here, we present the final analysis outcomes. METHODS: A prospective, multicenter, non-interventional study involving patients who received tolvaptan for the treatment of liver cirrhosis with hepatic edema with an insufficient response to conventional diuretics. The observation period was up to 6 months. Effectiveness evaluation included changes in body weight and clinical symptoms. Safety analysis included evaluation of adverse drug reactions (ADRs). RESULTS: Case reports of 1111 patients were collected. Of these, 1109 were included in the safety analysis and 1098 in the effectiveness analysis. The mean age was 69.4 ± 11.5 years and 695 (62.7%) patients were male. After tolvaptan treatment, a decrease in body weight from baseline was - 2.6 ± 2.7 kg on day 7 and - 3.8 ± 4.1 kg on day 14. Moreover, clinical symptoms significantly improved over the 14-day treatment. Frequently reported ADRs were thirst (6.6%), hepatic encephalopathy (2.3%), dehydration (1.5%), and hypernatremia (1.2%). A serum sodium level of ≥ 150 mEq/L was reported in five patients (0.5%). Multivariate analyses showed that the baseline blood urea nitrogen (BUN) level (cut-off value: 22.4 mg/dL) was the predictive factor for tolvaptan treatment response. CONCLUSIONS: The results suggest that tolvaptan was effective and well-tolerated in liver cirrhosis patients with hepatic edema. In the real-world clinical setting, tolvaptan provides a useful option for the treatment of hepatic edema.

DOI： 10.1007/s00535-020-01691-x

【線維化慢性疾患のキープロセス多彩な間質細胞が織りなす組織リモデリング"fibrosis"の理解】(第3章)各臓器疾患における線維化間葉系幹細胞投与による肝線維化改善、再生誘導効果

側方発育型大腸腫瘍と肥満ならびに代謝指数に関する検討

高綱将史, 水野研一, 川田雄三, 冨永顕太郎, 水澤健, 佐藤裕樹, 五十嵐聡, 林和直, 横山純二, 橋本哲, 寺井崇二

Gastroenterological Endoscopy 62 ( Suppl.1 ) 1332 - 1332 2020年8月

寺井崇二, 土屋淳紀

実験医学 38 ( 12 ) 2059 - 2062 2020年8月

当院におけるクローン病の患者に対する内視鏡的小腸結腸拡張術の臨床的検討

富吉圭, 川田雄三, 冨永顕太郎, 橋本哲, 横山純二, 寺井崇二

Gastroenterological Endoscopy 62 ( Suppl.1 ) 1332 - 1332 2020年8月

Changes in Magnetic Resonance Imaging Findings in a Malignant Melanoma Patient.

Toru Setsu, Atsunori Tsuchiya, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 13 ) 1671 - 1672 2020年7月

三次リンパ組織の臓器普遍性の解明

鳥生直哉, 佐藤有紀, 上村博輝, 田中真生, 寺井崇二, 柳田素子

日本腎臓学会誌 62 ( 4 ) 262 - 262 2020年7月

Rare case of circumferential esophageal peeling. 査読国際誌

Kentaro Tominaga, Atsunori Tsuchiya, Hiroki Sato, Yui Ishii, Nobutaka Takeda, Kazuki Natsui, Yuzo Kawata, Naruhiro Kimura, Yoshihisa Arao, Suguru Takeuchi, Kazunao Hayashi, Junji Yokoyama, Shuji Terai

Clinical case reports 8 ( 7 ) 1306 - 1308 2020年7月

Outcomes of EUS-guided choledochoduodenostomy as primary drainage for distal biliary obstruction with covered self-expandable metallic stents. 国際誌

Naosuke Kuraoka, Kazuo Hara, Nozomi Okuno, Takamichi Kuwahara, Nobumasa Mizuno, Yasuhiro Shimizu, Yasumasa Niwa, Shuji Terai

Endoscopy international open 8 ( 7 ) E861-E868 2020年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and study aims Endoscopic ultrasonography-guided choledochoduodenostomy (EUS-CDS) is an alternative therapy for percutaneous transhepatic biliary drainage. Outcomes of EUS-CDS for distal biliary tract obstruction with a covered self-expandable metallic stent (SEMS) as a primary drainage technique are unclear because there are few relevant reports. This study aimed to determine outcomes in patients undergoing EUS-CDS using SEMS as the primary drainage technique for malignant distal biliary duct obstruction. Patients and methods This retrospective study was conducted at Aichi Cancer Center Hospital, from January 2010 to July 2018, using data from our database. Results EUS-CDS was performed as a primary drainage technique for 92 patients. The technical success rate was 92.8 %, and the clinical success rate was 91.6 %. The overall incidence of adverse events was 15.7 %. The median stent patency time for the EUS-CDS was 396 days. Nineteen patients required re-intervention because of cholangitis or jaundice. Conclusion EUS-CDS as a primary drainage technique using SEMS has high technical and clinical success rates. It should be considered an effective drainage method with respect to long-term stent patency, low re-intervention rates, and absence of severe complications.

DOI： 10.1055/a-1161-8488

当院における心疾患に合併する遠隔期肝合併症における右心負荷系因子の重要性

三次リンパ組織の臓器普遍性の解明

鳥生直哉, 佐藤有紀, 上村博輝, 田中真生, 寺井崇二, 柳田素子

日本腎臓学会誌 62 ( 4 ) 262 - 262 2020年7月

上村博輝, 高村昌昭, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A252 - A252 2020年7月

EUS-FNAが術前診断に有用であった十二指腸Brunner腺過誤腫出血の1切除例

荒生祥尚, 小林正明, 池見雅俊, 塩路和彦, 清野智, 阿部寛幸, 岩城孝和, 田口貴博, 谷優佑, 寺井崇二

Gastroenterological Endoscopy 62 ( 7 ) 778 - 784 2020年7月

オステオポンチン・脂肪酸・高トリグリセライド血症による膵癌高リスク患者の同定

五十嵐聡, 林和直, 寺井崇二

膵臓 35 ( 3 ) A305 - A305 2020年7月

膵癌早期発見を目指した新潟県膵癌ネットワーク(Phoenix Study)の構築と膵癌病態解析に関する多施設後方視的観察研究

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A258 - A258 2020年7月

当院におけるIgG4関連硬化性胆管炎の診断の現状と課題

田中裕登, 林和直, 五十嵐聡, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A298 - A298 2020年7月

EUS-FNAが術前診断に有用であった十二指腸Brunner腺過誤腫出血の1切除例

荒生祥尚, 小林正明, 池見雅俊, 塩路和彦, 清野智, 阿部寛幸, 岩城孝和, 田口貴博, 谷優佑, 寺井崇二

Gastroenterological Endoscopy 62 ( 7 ) 778 - 784 2020年7月

肝胆膵疾患における血清DPPIV解析

林和直, 五十嵐聡, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A387 - A387 2020年7月

消化器疾患における移植医療の現状と問題点本県の急性肝不全診療におけるネットワーク構築の取り組み

薛徹, 土屋淳紀, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A73 - A73 2020年7月

肝硬変に対する間葉系幹細胞由来エクソソーム治療のライブイメージング技術、Single cell RNA-seqを用いたメカニズム解析

土屋淳紀, 竹内卓, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A238 - A238 2020年7月

肝硬変患者のQOL・予後の改善と基盤研究の最前線 IFN-γ刺激下間葉系幹細胞由来エクソソームの肝線維化改善における効果・メカニズムの検証

土屋淳紀, 竹内卓, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A97 - A97 2020年7月

胃瘻造設によりS状結腸間膜穿孔をきたした一例

吉田悠紀, 川田雄三, 永山逸夫, 野澤良祐, 冨永顕太郎, 薛徹, 横尾健, 水野研一, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 36 ( 1 ) 46 - 46 2020年7月

肝癌治療に対する内科外科のすみわけと連携における放射線治療の役割

上村顕也, 柴田理, 大越麻理奈, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A292 - A292 2020年7月

非アルコール性脂肪性肝疾患(NAFLD)の病態進行における自律神経を介した臓器間ネットワークの関与

高昌良, 上村顕也, 名古屋拓郎, 酒井規裕, 坂牧僚, 横尾健, 寺井崇二

日本門脈圧亢進症学会雑誌 26 ( 2 ) 143 - 146 2020年7月

消化器疾患における共生微生物叢研究の新たな知見 NAFLDの病態における自律神経ネットワークを介した腸内細菌叢の関与

高昌良, 上村顕也, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A78 - A78 2020年7月

肝癌分子標的薬治療時の鰹だし併用による肝予備能維持効果

小関洋平, 上村顕也, 坂牧僚, 大越麻理奈, 田中裕登, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A296 - A296 2020年7月

臨床応用に向けた肝癌の病態解明放射線照射によるDNA損傷時のHHMの役割

丹羽佑輔, 上村顕也, 寺井崇二

日本消化器病学会雑誌 117 ( 臨増総会 ) A161 - A161 2020年7月

Cytapheresis for pyoderma gangrenosum associated with inflammatory bowel disease: A review of current status. 査読国際誌

Kentaro Tominaga, Kenya Kamimura, Hiroki Sato, Masayoshi Ko, Yuzo Kawata, Takeshi Mizusawa, Junji Yokoyama, Shuji Terai

World journal of clinical cases 8 ( 11 ) 2092 - 2101 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pyoderma gangrenosum (PG) is a neutrophilic dermatosis clinically characterized by the presence of painful skin ulcerations with erythematous. As it is frequently associated with inflammatory bowel diseases, including ulcerative colitis, gastroenterologists should be familiar with the disease including therapeutic options. Therefore, we have conducted a review focusing on the cytapheresis for PG in cases of inflammatory bowel diseases. A literature search was conducted to extract studies published in the last 20 years, with information on demographics, clinical symptoms, treatment, and the clinical course from a total of 22 cases reported and our recent case. In most patients, cytapheresis was associated with improvement or resolution of PG after failure of conventional therapeutic options such as corticosteroids, antibiotics, immunosuppressive agents and immunoglobulin. Based on the information summarized, cytapheresis is helpful in the majority of patients with PG refractory to medical treatment associated with inflammatory bowel diseases and could be further studied in a multicenter, randomized trial.

DOI： 10.12998/wjcc.v8.i11.2092

Development of a non-alcoholic steatohepatitis model with rapid accumulation of fibrosis, and its treatment using mesenchymal stem cells and their small extracellular vesicles. 査読国際誌

Takayuki Watanabe, Atsunori Tsuchiya, Suguru Takeuchi, Shunsuke Nojiri, Tomoaki Yoshida, Masahiro Ogawa, Michiko Itoh, Masaaki Takamura, Takayoshi Suganami, Yoshihiro Ogawa, Shuji Terai

Regenerative therapy 14 252 - 261 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Introduction: Currently, there are no approved drugs for treating non-alcoholic steatohepatitis (NASH); however, mesenchymal stem cells (MSCs) and their small extracellular vesicles (sEVs), which possess immunomodulatory activities, are potential candidates. This study aimed to develop a mouse model of NASH with rapid accumulation of fibrosis using the pre-established melanocortin type-4 receptor knockout (Mc4r-KO) NASH mouse model and lipopolysaccharide (LPS), and to evaluate the therapeutic effect of MSCs and their sEVs. Methods: Mc4r-KO mice (8 weeks old, male) were fed a western diet (WD) for 8 weeks. Next, the mice were intraperitoneally injected with lipopolysaccharide (LPS) twice a week for 4 weeks while continuing the WD. To confirm the therapeutic effect of MSCs and sEVs, human adipose tissue-derived MSCs or their sEVs were administered 12 weeks after initiation of the WD, and serum testing, quantitative analysis of fibrosis, and quantitative reverse transcription-polymerase chain reaction qRT-PCR were performed. Results: By providing a WD combined with LPS treatment, we successfully developed a NASH model with rapid accumulation of fibrosis. Both human MSCs and their sEVs decreased serum alanine transaminase levels and inflammatory markers based on qRT-PCR. Histological analysis showed that MSC or sEV treatment did not affect fat accumulation. However, an improvement in fibrosis in the groups treated with MSCs and their sEVs was observed. Furthermore, after administering MSCs and sEVs, there was a significant increase in anti-inflammatory macrophages in the liver. Conclusion: We successfully developed a NASH model with rapid accumulation of fibrosis and confirmed the anti-inflammatory and anti-fibrotic effects of MSCs and their sEVs, which may be options for future therapy.

DOI： 10.1016/j.reth.2020.03.012

A rare case of peliosis hepatis in a patient with chronic renal failure and renal cell carcinoma.

Hiroki Maruyama, Kazuya Takahashi, Natsuki Ishikawa, Kazunori Hosaka, Daisuke Kumaki, Yukio Aruga, Masashi Yamakawa, Masaaki Hirano, Kazuhiro Funakoshi, Shuji Terai

Clinical journal of gastroenterology 13 ( 3 ) 403 - 407 2020年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Peliosis hepatis (PH) is a rare disease characterized by the presence of sinusoidal dilation and blood-filled cysts throughout the hepatic parenchyma. We report a case of PH in a 49-year-old woman with chronic renal failure (CRF) on hemodialysis and with renal cell carcinoma (RCC). Dynamic contrast-enhanced computed tomography (CT) showed a 35-mm-diameter, hypervascular tumor in the liver and RCC in the right renal cyst. Ultrasound and superparamagnetic iron oxide-enhanced magnetic resonance imaging were also performed; however, the liver tumor could not be distinguished from the metastasis of RCC. Therefore, echo-guided biopsy of the liver tumor using an 18-G Majima needle was performed. Histological evaluation of the specimen showed irregular sinusoidal dilatation and blood-filled cavities without malignant cells. She was ultimately diagnosed with PH. Subsequently, she underwent total right nephrectomy for RCC and was diagnosed with RCC stage 1 (pT1N0M0). A follow-up CT performed 4 months after nephrectomy showed no growth of PH. Although the development of PH in patients with CRF or RCC who do not undergo renal transplantation is extremely rare, it should be considered in the differential diagnosis to distinguish PH from the metastasis of RCC.

DOI： 10.1007/s12328-019-01068-5

【幹細胞治療と疾患】間葉系幹細胞は"指揮細胞"としてマクロファージに作用し肝硬変の肝線維化改善、再生を誘導する自己骨髄細胞投与療法から他家脂肪組織由来間葉系幹細胞投与へ

寺井崇二, 土屋淳紀

BIO Clinica 35 ( 5 ) 406 - 410 2020年5月

Small Intestinal Bacterial Overgrowth Diagnosed by a Breath Test and Improved by Rifaximin in a Patient with Hepatic Encephalopathy and Alcoholic Liver Cirrhosis: A Case Report. 査読

Akira Sakamaki, Kunihiko Yokoyama, Fusako Yamazaki, Hiroteru Kamimura, Kenya Kamimura, Masaaki Takamura, Junji Yokoyama, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 15 ) 1849 - 1853 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

A 66-year-old Japanese man was admitted to our hospital with grade 2 hepatic encephalopathy (HE). Abdominal computed tomography and laboratory examinations revealed decompensated liver cirrhosis. Intravenous administration of branched-chain amino acids immediately ameliorated the HE, and lactulose was initiated. However, a breath test revealed small intestinal bacterial overgrowth (SIBO); therefore, rifaximin was additionally initiated. The breath test was repeated after discharge, when no evidence of SIBO or overt HE was identified. This case suggested that a breath test is effective for the identification of SIBO and that the administration of a poorly absorbed antibiotic should be considered in SIBO-positive HE patients taking lactulose.

DOI： 10.2169/internalmedicine.4593-20

Effect of methionine/choline-deficient diet and high-fat diet-induced steatohepatitis on mitochondrial homeostasis in mice. 査読国際誌

Yoshihisa Arao, Hirokazu Kawai, Kenya Kamimura, Takamasa Kobayashi, Oki Nakano, Manabu Hayatsu, Tatsuo Ushiki, Shuji Terai

Biochemical and biophysical research communications 527 ( 2 ) 365 - 371 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Considering the increase in cases of non-alcoholic steatohepatitis (NASH), the use of appropriate animal model of NASH is essential to understand the underlying pathogenesis mechanism. To date, several mice models have been used; however, significant differences in the etiologies and food administered affected the results, with inconsistent conclusions. Therefore, it is necessary to understand these models and their differences to be able to choose appropriate models. Inspired by the fact that mitochondrial (mt)DNA content is changed in non-alcoholic fatty liver disease in humans, we investigated the mtDNA copy number in the NASH mice models induced by high-fat diet (HFD) and methionine/choline-deficient diet (MCD) to understand the differences between these models. Megamitochondria were observed in both MCD and HFD groups. However, the MCD group showed significant decrease in liver mtDNA content compared with that in the HFD group. These changes were associated with significant upregulation of mitochondrial biogenesis- and degradation-related genes in MCD model than in HFD model. Thus, stability of mtDNA is associated with the differences between MCD and HFD-induced NASH models often used in studies; these findings could help in choosing appropriate models for studies on NASH.

DOI： 10.1016/j.bbrc.2020.03.180

Rare Genotype of His/His in NUDT15 Codon 139 and Thiopurine-associated Adverse Events in a Case of Ulcerative Colitis. 査読

Kei Tomiyoshi, Hiroki Sato, Kentaro Tominaga, Yuzo Kawata, Daisuke Okamoto, Yoichi Kakuta, Junji Yokoyama, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 13 ) 1611 - 1613 2020年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Thiopurine drugs are commonly used to treat immunologic diseases. However, the narrow therapeutic safety margin demands evidence-based precision medicine approaches. NUDT15 variants are associated with thiopurine-induced adverse events, particularly in Asians. We herein report a rare genotype of His/His in NUDT15 codon 139 in a case of ulcerative colitis and review the relevant literature. The patient experienced severe thiopurine-associated adverse events, including leukopenia and alopecia. There is no literature on the His/His genotype in NUDT15 codon 139, and our case suggests cautious use or the contraindication of thiopurines for patients with this genotype.

DOI： 10.2169/internalmedicine.4261-19

新潟県における肝炎対策査読

荒生祥尚, 菊田玲, 渡辺和仁, 中山均, 田村務, 薛徹, 寺井崇二

肝臓 61 ( Suppl.1 ) A263 - A263 2020年4月

当院における肝炎医療コーディネーターの取り組みと今後の課題査読

廣川光, 薛徹, 荒生祥尚, 澤栗裕美, 寺井崇二

肝臓 61 ( Suppl.1 ) A246 - A246 2020年4月

Huge liver tumor in young man. 査読国際誌

Osamu Shibata, Kenya Kamimura, Rie Azumi, Kei Shibuya, Shintaro Shiba, Tatsuya Ohno, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 4 ( 2 ) 301 - 302 2020年4月

記述言語：英語

Intrahepatic cholangiocarcinoma is the second leading primary hepatic tumors, accounting for 5% of all hepatic tumors. The curability depends on the operability; however, the difficulty of early diagnosis and late clinical presentation account for the poor prognosis. Therefore, development of a novel therapeutic option and a method to determine the viability of the primary tumor, which hinder the assessment of the impact of other therapies, including chemotherapy and radiotherapy are needed. Although FDG-PET has been used to detect distant metastases of ICC, which are present in 20% of patients at the initial diagnosis, little is known about the efficacy of FDG-PET of the primary lesion of ICC. Here, we present the case of a 31-year-old male diagnosed with unresectable ICC and successfully treated with carbon-ion radiation, and present the usefulness of fluorodeoxyglucose-positron emission tomography in the determination of the viability of the tumor.

DOI： 10.1002/jgh3.12234

Hypereosinophilia-related liver pseudotumor with elevated interleukin-5 levels preceding T-cell lymphoma. 国際誌

Atsunori Tsuchiya, Tomoyuki Tanaka, Yasuhiko Shibasaki, Shuji Terai

JGH open : an open access journal of gastroenterology and hepatology 4 ( 2 ) 312 - 314 2020年4月

記述言語：英語

A 61-year-old woman with hypereosinophilia and elevated interleukin (IL)-5 level was admitted to our hospital after detection of multiple liver tumors. Liver biopsy demonstrated that the tumor consisted of scar tissue with remnants of eosinophilic infiltration, suggesting that it had formed by massive eosinophilic infiltration. The hypereosinophilia was treated mainly by prednisolone, and thereafter, the liver tumors disappeared. However, 10 months postadmission, CD4+ T-cell lymphoma, which can produce IL-5, was detected in the nasopharynx and oropharynx. Therefore, we believe that this is a rare case of hypereosinophilia-related liver pseudotumor induced by presumed by IL-5 elevation.

DOI： 10.1002/jgh3.12253

自己免疫性肝炎における赤血球容量粒度分布幅変動係数の臨床的意義

高村昌昭, 高綱将史, 薛徹, 上村博輝, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.1 ) A433 - A433 2020年4月

肝疾患における移行期医療小児NAFLD患者の背景疾患と移行医療への課題

上村博輝, 上村顕也, 寺井崇二

肝臓 61 ( Suppl.1 ) A142 - A142 2020年4月

肝移植医療における内科・外科連携の現状と問題点本県における急性肝不全に対する肝移植再開に向けた診療ネットワーク運用の検討

薛徹, 寺井崇二

肝臓 61 ( Suppl.1 ) A125 - A125 2020年4月

門脈圧亢進症の診断と治療原発性胆汁性胆管炎における食道静脈瘤発生の検討

薛徹, 横山純二, 寺井崇二

肝臓 61 ( Suppl.1 ) A151 - A151 2020年4月

NAFLDの病態解明及び新規治療法の探索非アルコール性脂肪性肝炎(NASH)モデルマウスを用いたスフィンゴシン1リン酸受容体ブロックによる脂質構成の変化と発癌機構の解明

吉田智彰, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.1 ) A215 - A215 2020年4月

肝硬変の予後改善を目指した治療戦略肝硬変に対する間葉系幹細胞由来のエクソソーム療法の開発に向けて

土屋淳紀, 竹内卓, 寺井崇二

肝臓 61 ( Suppl.1 ) A92 - A92 2020年4月

生体試料を用いた研究の最前線間葉系幹細胞のエクソソームによる肝線維化改善抗炎症性マクロファージ誘導法の開発

竹内卓, 土屋淳紀, 寺井崇二

肝臓 61 ( Suppl.1 ) A33 - A33 2020年4月

健診での生活歴から考察したNAFLD症例に対する新しい生活指導法の提案

横尾健, 中野応央樹, 佐藤公俊, 冨永顕太郎, 橋本哲, 高村昌昭, 寺井崇二

肝臓 61 ( Suppl.1 ) A454 - A454 2020年4月

肝発癌進展研究の最前線肝発癌,治療抵抗性にかかわるHHM遺伝子のDNA損傷応答メカニズムの解析

上村顕也, 丹羽佑輔, 寺井崇二

肝臓 61 ( Suppl.1 ) A44 - A44 2020年4月

臓器間ネットワークと肝疾患自律神経経路を介する肝-脳-消化管軸の非アルコール性脂肪肝炎の病態への関与

上村顕也, 大脇崇史, 寺井崇二

肝臓 61 ( Suppl.1 ) A182 - A182 2020年4月

An unusual case of esophageal motility disorder. 査読国際誌

Youhei Koseki, Hiroki Sato, Shuji Terai

Gastroenterology 159 ( 3 ) 838 - 841 2020年3月

Secondary Achalasia in Myotonic Dystrophy May Have a Different Pathology and Management. 査読

Hiroki Sato, Ken-Ichi Mizuno, Satoru Hashimoto, Masafumi Takatsuna, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 6 ) 875 - 875 2020年3月

Variations of small bowel transit time on capsule endoscopy 査読国際誌

Tominaga K, Sato H, Yokomichi H, Tsuchiya A, Yoshida T, Kawata Y, Yokoyama J, Terai S

Annals of Translational Medicine in Press ( 6 ) 348 - 348 2020年3月

Rare gastric outlet obstruction owing to ectopic pancreas: a case report and literature review. 国際誌

Kunihiko Yokoyama, Hiroki Sato, Yuichi Sato, Jun Watanabe, Atsuo Nakamura, Shuji Terai

Annals of translational medicine 8 ( 5 ) 252 - 252 2020年3月

記述言語：英語

The ectopic pancreas is often observed in the gastrointestinal tract, and is typically asymptomatic. A 28-year-old woman was referred to our hospital following repeated vomiting after every meal. Following gastroscopy, contrast-enhanced computed tomography (CE-CT), and endoscopic ultrasonography (EUS), she was diagnosed with gastric outlet obstruction, also known as pyloric obstruction, caused by a giant submucosal cystic tumor. The condition was successfully treated with EUS-guided cystic drainage, and she was diagnosed with a cystic tumor originating from the ectopic pancreas. The tumor shrank following EUS-guided cystic drainage, and her obstructive symptoms resolved. In cases with overgrowth of the ectopic pancreas, the differential diagnosis of malignancy is important but challenging. Herein, we report a unique final pathology of this rare case and discuss the findings with a literature review.

DOI： 10.21037/atm.2020.01.64

Percutaneous Gastrojejunostomy Catheter Placement Using a Slow-Leak Balloon through the Reconstructed Gastric Tube after Esophagectomy. 国際誌

Shinichi Morita, Yasuaki Arai, Shunsuke Sugawara, Miyuki Sone, Koji Tomita, Hiroaki Ishii, Shuji Terai

Journal of vascular and interventional radiology : JVIR 31 ( 3 ) 478 - 481 2020年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Twelve patients who had undergone esophageal reconstruction because of cancer and in whom conventional percutaneous radiologic or endoscopic gastrostomy was considered difficult are reported. These patients underwent placement of a percutaneous gastrojejunostomy catheter through the reconstructed gastric tube using a slow-leak balloon that had been developed for percutaneous transesophageal gastrotubing. Retrospective evaluation showed successful outcomes without severe complications in all patients. Eight (66.6%) were able to resume oral intake, which allowed gastrojejunostomy catheter withdrawal in 3 (25%). This technique is feasible with acceptable clinical outcomes for patients who have undergone gastric tube reconstruction after esophagectomy.

DOI： 10.1016/j.jvir.2019.09.009

肝悪性腫瘍との鑑別に苦慮した原発性肝放線菌症の1例

本田博樹, 野澤優次郎, 高村昌昭, 上村博輝, 土屋淳紀, 寺井崇二

肝臓 61 ( 3 ) 109 - 115 2020年3月

【間葉系幹細胞の基礎と臨床応用】疾患治療他家脂肪組織由来間葉系幹細胞投与療法の開発

寺井崇二, 土屋淳紀

医学のあゆみ 272 ( 10 ) 1032 - 1039 2020年3月

Effect of Diphtheria Toxin-Based Gene Therapy for Hepatocellular Carcinoma. 査読国際誌

Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Norihiro Sakai, Takuro Nagoya, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Akira Sakamaki, Hiroteru Kamimura, Norio Miyamura, Hiroshi Nishina, Shuji Terai

Cancers 12 ( 2 ) 2020年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Hepatocellular carcinoma (HCC) is a major global malignancy, responsible for >90% of primary liver cancers. Currently available therapeutic options have poor performances due to the highly heterogeneous nature of the tumor cells; recurrence is highly probable, and some patients develop resistances to the therapies. Accordingly, the development of a novel therapy is essential. We assessed gene therapy for HCC using a diphtheria toxin fragment A (DTA) gene-expressing plasmid, utilizing a non-viral hydrodynamics-based procedure. The antitumor effect of DTA expression in HCC cell lines (and alpha-fetoprotein (AFP) promoter selectivity) is assessed in vitro by examining HCC cell growth. Moreover, the effect and safety of the AFP promoter-selective DTA expression was examined in vivo using an HCC mice model established by the hydrodynamic gene delivery of the yes-associated protein (YAP)-expressing plasmid. The protein synthesis in DTA transfected cells is inhibited by the disappearance of tdTomato and GFP expression co-transfected upon the delivery of the DTA plasmid; the HCC cell growth is inhibited by the expression of DTA in HCC cells in an AFP promoter-selective manner. A significant inhibition of HCC occurrence and the suppression of the tumor marker of AFP and des-gamma-carboxy prothrombin can be seen in mice groups treated with hydrodynamic gene delivery of DTA, both 0 and 2 months after the YAP gene delivery. These results suggest that DTA gene therapy is effective for HCC.

DOI： 10.3390/cancers12020472

On-line HDFを急性肝不全の患者に施行する際の診療ガイド

井上和明, 織田成人, 安部隆三, 滝川康裕, 中山伸朗, 加藤直也, 藤原慶一, 安井伸, 寺井崇二, 井戸章雄, 坂井田功, 玄田拓哉, 清水雅仁, 持田智, 滝川一

肝臓 61 ( 2 ) 47 - 60 2020年2月

Septicemic listeriosis during adalimumab- and golimumab-based treatment for ulcerative colitis: case presentation and literature review. 査読

Ryoko Horigome, Hiroki Sato, Terasu Honma, Shuji Terai

Clinical journal of gastroenterology 13 ( 1 ) 22 - 25 2020年2月

記述言語：英語

Listeria monocytogenes is a common bacterium that can trigger an episode of amphixenosis from the consumption of contaminated food. It survives in the host as an intracellular parasite and can get reactivated when the host's immune system is compromised. The use of anti-tumor necrosis factor-α (TNF-α) blockers is reported to increase the risk of L. monocytogenes infections. In the field of gastroenterology, the use of TNF-α blockers is on the rise due to remarkable efficacy in select patients with inflammatory bowel diseases (IBDs) such as ulcerative colitis and Crohn's disease and the rise in the incidence and prevalence of IBDs. There are few case reports on this topic, despite the rapid development of novel TNF-α blockers. Here, we report two cases of septicemic listeriosis encountered during treatment with the more recent TNF-α blockers, namely, adalimumab and golimumab, in ulcerative colitis and review the published literature on the topic.

DOI： 10.1007/s12328-019-01005-6

Rare paradoxical adverse event in Crohn's disease: a case report. 査読国際誌

Marina Okoshi, Hiroki Sato, Terasu Honma, Shuji Terai

Annals of translational medicine 8 ( 4 ) 133 - 133 2020年2月

記述言語：英語

An 18-year-old male adolescent diagnosed with ileocolitis-type Crohn's disease received therapy involving an anti-tumor necrosis factor-α (TNF-α) blocker, which resulted in remission for 2 years. The patient presented with fever, stomatitis, and cough with respiratory distress. Chest radiography revealed bilateral hilar lymphadenopathy; bronchoalveolar lavage showed high lymphocyte level: 40.8% and CD4/8 value: 3.9. Transbronchial lung biopsy identified multiple non-caseating granulomas fused to each other with connective tissue septa, leading to the diagnosis of sarcoidosis. The sarcoidosis was defined as a paradoxical adverse event (PAE) due to the use of TNF-α blocker; therefore, cessation of TNF-α blocker administration was sufficient to induce remission. We report a rare case of PAE on Crohn's disease. The characteristics and distinguishing histologies of PAE and Crohn's disease are described. Biological agent therapy has been reported to cause several PAEs during the treatment of immune-mediated inflammatory disorders. PAEs are defined as pathological conditions that occur during biological agent therapy usually effective in treatment. The laboratory, radiography, and histological findings shown in this case are useful for differential diagnosis and management of PAE.

DOI： 10.21037/atm.2019.12.122

肝癌に対する局所療法としての放射線療法の安全性と有効性の検証

大越麻理奈, 上村顕也, 柴田修, 森田慎一, 坂牧僚, 田中裕登, 小関洋平, 寺井崇二

日本内科学会雑誌 109 ( Suppl. ) 155 - 155 2020年2月

Ghrelin-insulin-like growth factor-1 axis is activated via autonomic neural circuits in the non-alcoholic fatty liver disease. 査読国際誌

Takuro Nagoya, Kenya Kamimura, Ryosuke Inoue, Masayoshi Ko, Takashi Owaki, Yusuke Niwa, Norihiro Sakai, Toru Setsu, Akira Sakamaki, Takeshi Yokoo, Hiroteru Kamimura, Yuka Nakamura, Masaki Ueno, Shuji Terai

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society 32 ( 5 ) e13799 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The correlation of the growth hormone (GH) and insulin-like growth factor-1 (IGF-1) with non-alcoholic fatty liver disease (NAFLD) has been reported in epidemiological studies. However, the mechanisms of molecular and inter-organ systems that render these factors to influence on NAFLD have not been elucidated. In this study, we examined the induction of ghrelin which is the GH-releasing hormone and IGF-1, and involvement of autonomic neural circuits, in the pathogenesis of NAFLD. METHODS: The expression of gastric and hypothalamic ghrelin, neural activation in the brain, and serum IGF-1 were examined in NAFLD models of choline-deficient defined l-amino-acid diet-fed, melanocortin 4 receptor knockout mice, and partial hepatectomy mice with or without the blockades of autonomic nerves to test the contribution of neural circuits connecting the brain, liver, and stomach. KEY RESULTS: The fatty changes in the liver increased the expression of gastric ghrelin through the autonomic pathways which sends the neural signals to the arcuate nucleus in the hypothalamus through the afferent vagal nerve which reached the pituitary gland to release GH and then stimulate the IGF-1 release from the liver. In addition, high levels of ghrelin expression in the arcuate nucleus were correlated with NAFLD progression regardless of the circuits. CONCLUSIONS: Our study demonstrated that the fatty liver stimulates the autonomic nervous signal circuits which suppress the progression of the disease by activating the gastric ghrelin expression, the neural signal transduction in the brain, and the release of IGF-1 from the liver.

DOI： 10.1111/nmo.13799

Prostaglandin E2 and its receptor EP2 trigger signaling that contributes to YAP-mediated cell competition. 査読国際誌

Erika Ishihara, Yuya Nagaoka, Toshiaki Okuno, Satoshi Kofuji, Mari Ishigami-Yuasa, Hiroyuki Kagechika, Kenya Kamimura, Shuji Terai, Takehiko Yokomizo, Yukihiko Sugimoto, Yasuyuki Fujita, Akira Suzuki, Hiroshi Nishina

Genes to cells : devoted to molecular & cellular mechanisms 25 ( 3 ) 197 - 214 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Cell competition is a biological process by which unfit cells are eliminated from "cell society." We previously showed that cultured mammalian epithelial Madin-Darby canine kidney (MDCK) cells expressing constitutively active YAP were eliminated by apical extrusion when surrounded by "normal" MDCK cells. However, the molecular mechanism underlying the elimination of active YAP-expressing cells was unknown. Here, we used high-throughput chemical compound screening to identify cyclooxygenase-2 (COX-2) as a key molecule triggering cell competition. Our work shows that COX-2-mediated PGE2 secretion engages its receptor EP2 on abnormal and nearby normal cells. This engagement of EP2 triggers downstream signaling via an adenylyl cyclase-cyclic AMP-PKA pathway that, in the presence of active YAP, induces E-cadherin internalization leading to apical extrusion. Thus, COX-2-induced PGE2 appears a warning signal to both abnormal and surrounding normal cells to drive cell competition.

DOI： 10.1111/gtc.12750

Usefulness of autotaxin for the complications of liver cirrhosis. 国際誌

Xue Shao, Haruki Uojima, Toru Setsu, Tomomi Okubo, Masanori Atsukawa, Yoshihiro Furuichi, Yoshitaka Arase, Hisashi Hidaka, Yoshiaki Tanaka, Takahide Nakazawa, Makoto Kako, Tatehiro Kagawa, Katsuhiko Iwakiri, Shuji Terai, Wasaburo Koizumi

World journal of gastroenterology 26 ( 1 ) 97 - 108 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Autotaxin (ATX) has been reported as a direct biomarker for estimating the evaluation of liver fibrosis. But available data on ATX as a useful biomarker for the complications of liver cirrhosis (LC) are scant. AIM: To assess the clinical usefulness of ATX for assessing the complications of LC. METHODS: This multicenter, retrospective study was conducted at six locations in Japan. We include patients with LC, n = 400. The ATX level was evaluated separately in men and women because of its high level in female patients. To assess the clinical usefulness of ATX for the complications of LC, the area under the curve (AUC) of ATX assessing for the severe complications was analyzed in comparison with the model for end-stage liver disease score, albumin-bilirubin (ALBI) score, fibrosis-4 index, and aspartate aminotransferase-to-platelet ratio index. RESULTS: The mean age was 68.4 ± 11.4 years, 240 patients (60.0%) were male. A total of 213 (53.3%) and 187 (46.8%) patients were compensated and decompensated, respectively. The numbers of patients with varix rupture, hepatic ascites, and hepatic encephalopathy were 35 (8.8%), 131 (32.8%), and 103 (25.8%), respectively. The AUCs of ATX in men for hepatic encephalopathy, hepatic ascites, and varix ruptures were 0.853, 0.816, and 0.706, respectively. The AUCs of ATX in women for hepatic encephalopathy, hepatic ascites, and varix rupture were 0.759, 0.717, and 0.697, respectively. The AUCs of ATX in men were higher than those in women, as were all the other biomarkers used to detect encephalopathy and varix ruptures. However, for detecting ascites, the AUC of ALBI in men was more effective than using ATX. CONCLUSION: ATX in men was more effective than any other biomarkers for detecting hepatic encephalopathy and varix ruptures.

DOI： 10.3748/wjg.v26.i1.97

Achalasia in a Patient with Myotonic Dystrophy. 査読

Hiroki Sato, Ken-Ichi Mizuno, Satoru Hashimoto, Masafumi Takatsuna, Shuji Terai

Internal medicine (Tokyo, Japan) 59 ( 1 ) 67 - 68 2020年1月

記述言語：英語

Myotonic dystrophy is a progressive disorder mainly affecting the voluntary muscles. We herein report a rare case of myotonic dystrophy complicated with high-resolution manometry-defined achalasia, the pathology of which is absent relaxation of the smooth muscles of lower esophageal sphincter (LES). In the present case, achalasia was considered a complication of myotonic dystrophy instead of sporadic achalasia, as on performing high-resolution manometry, the finding of an impaired LES relaxation (myotonic phase) changed to a totally emaciated LES function (muscle weakness phase) as myotonic dystrophy progressed.

DOI： 10.2169/internalmedicine.3360-19

Rare Brain Metastasis From a Pancreatobiliary Subtype of Intraductal Papillary Mucinous Neoplasm. 査読国際誌

Arao Y, Kamimura K, Ikemi M, Hayashi K, Takaki M, Takahashi S, Seino S, Abe H, Tsuboguchi S, Otsu Y, Sanpei K, Kohisa J, Kondo S, Tani Y, Ito J, Toyoshima Y, Kakita A, Ajioka Y, Terai S

Pancreas 49 ( 1 ) e8 - e11 2020年1月

Endoscopic diverticulectomy for Zenker's diverticulum with heterotopic gastric mucosa. 査読国際誌

Hiroki Sato, Manabu Takeuchi, Shuji Terai

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 32 ( 1 ) 145 - 145 2020年1月

Loss of autophagy impairs physiological steatosis by accumulation of NCoR1. 国際誌

Shun-Saku Takahashi, Yu-Shin Sou, Tetsuya Saito, Akiko Kuma, Takayuki Yabe, Yuki Sugiura, Hyeon-Cheol Lee, Makoto Suematsu, Takehiko Yokomizo, Masato Koike, Shuji Terai, Noboru Mizushima, Satoshi Waguri, Masaaki Komatsu

Life science alliance 3 ( 1 ) 2020年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Lipid droplets (LDs) are dynamic organelles that store neutral lipids during times of energy excess, such as after a meal. LDs serve as an energy reservoir during fasting and have a buffering capacity that prevents lipotoxicity. Autophagy and the autophagic machinery have been proposed to play a role in LD biogenesis, but the underlying molecular mechanism remains unclear. Here, we show that when nuclear receptor co-repressor 1 (NCoR1), which inhibits the transactivation of nuclear receptors, accumulates because of autophagy suppression, LDs decrease in size and number. Ablation of ATG7, a gene essential for autophagy, suppressed the expression of gene targets of liver X receptor α, a nuclear receptor responsible for fatty acid and triglyceride synthesis in an NCoR1-dependent manner. LD accumulation in response to fasting and after hepatectomy was hampered by the suppression of autophagy. These results suggest that autophagy controls physiological hepatosteatosis by fine-tuning NCoR1 protein levels.

DOI： 10.26508/lsa.201900513

Therapeutic potential of mesenchymal stem cells and their exosomes in severe novel coronavirus disease 2019 (COVID-19) cases. 査読国際誌

Atsunori Tsuchiya, Suguru Takeuchi, Takahiro Iwasawa, Masaru Kumagai, Takeki Sato, Satoko Motegi, Yui Ishii, Youhei Koseki, Kei Tomiyoshi, Kazuki Natsui, Nobutaka Takeda, Yuki Yoshida, Fusako Yamazaki, Yuichi Kojima, Yusuke Watanabe, Naruhiro Kimura, Kentaro Tominaga, Hiroteru Kamimura, Masaaki Takamura, Shuji Terai

Inflammation and regeneration 40 14 - 14 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and the ensuing worldwide pandemic. The spread of the virus has had global effects such as activity restriction, economic stagnation, and collapse of healthcare infrastructure. Severe SARS-CoV-2 infection induces a cytokine storm, leading to acute respiratory distress syndrome (ARDS) and multiple organ failure, which are very serious health conditions and must be mitigated or resolved as soon as possible. Mesenchymal stem cells (MSCs) and their exosomes can affect immune cells by inducing anti-inflammatory macrophages, regulatory T and B cells, and regulatory dendritic cells, and can inactivate T cells. Hence, they are potential candidate agents for treatment of severe cases of COVID-19. In this review, we report the background of severe cases of COVID-19, basic aspects and mechanisms of action of MSCs and their exosomes, and discuss basic and clinical studies based on MSCs and exosomes for influenza-induced ARDS. Finally, we report the potential of MSC and exosome therapy in severe cases of COVID-19 in recently initiated or planned clinical trials of MSCs (33 trials) and exosomes (1 trial) registered in 13 countries on ClinicalTrials.gov.

DOI： 10.1186/s41232-020-00121-y

10年目を迎えた新潟県肝疾患相談センターの現況査読

上村博輝, 高村昌昭, 五十嵐正人, 青栁豊, 菊田玲, 渡辺和仁, 中山均, 田村務, 寺井崇二, 薛徹, 荒生祥尚, 廣川光, 澤栗裕美, 渡邊文子, 小師優子, 坂牧僚, 土屋淳紀

肝臓 61 ( 5 ) 245 - 254 2020年

記述言語：日本語出版者・発行元：一般社団法人日本肝臓学会

平成21年に設立された新潟大学医歯学総合病院肝疾患相談センターは令和元年に10年目を迎え，236万人の新潟県民や医療従事者に対するウイルス性肝炎の情報の提供，啓発活動，助成制度のサポート等を新潟県健康対策課，厚生労働省健康局がん・疾病対策課肝炎対策室，国立国際医療センター肝炎情報センターとともに行ってきた．新潟県内の各種肝炎ウイルスの発生動向の報告，助成対象人数の把握や非受検者に対する啓発活動を各年度で行ってきた．C型肝炎については他県と同じく新規治療者数については減少段階にある．しかし，肝炎ウイルスは世界最大級の感染症であることにかわりなく，A型肝炎のエンデミック，B型肝炎ウイルスに対する耐性ウイルス発生や核酸アナログ製剤の長期利用による諸問題，E型肝炎の報告例の増加などについては今後も監視が必要である．また肝炎検査未受検者も多く，啓発活動を行う肝疾患相談センターの存在意義は今後も重要である．

DOI： 10.2957/kanzo.61.245

Obesity and accumulation of subcutaneous adipose tissue are poor prognostic factors in patients with alcoholic liver cirrhosis. 国際誌

Akira Sakamaki, Kunihiko Yokoyama, Kyutaro Koyama, Shinichi Morita, Hiroyuki Abe, Kenya Kamimura, Masaaki Takamura, Shuji Terai

PloS one 15 ( 11 ) e0242582 2020年

記述言語：英語掲載種別：研究論文（学術雑誌）

In alcoholic liver cirrhosis (LC) patients, obesity has become a problem that progresses into liver dysfunction. Herein, we investigated the relationship between the prognosis of steatohepatitis and body weight, along with fat accumulation in patients with alcoholic LC. We conducted a single-center retrospective study, enrolled 104 alcoholic LC patients without hepatocellular carcinoma (HCC) based on histological and clinical evidence, and investigated factors related to poor prognosis using multivariate Cox regression and cluster analyses. Cox regression analysis revealed three independent relevant factors: subcutaneous adipose tissue (SAT) index (median 34.8 cm2/m2, P = 0.009, hazard ratio [HR] 1.017, 95% confidence interval [CI] 1.004-1.030), total bilirubin level (median 1.7 mg/dL, P = 0.003, HR 1.129, 95% CI 1.042-1.223), and prothrombin time value (median 64%, P = 0.007, HR 0.967, 95% CI 0.943-0.991). In the cluster analysis, we categorized the patients into three groups: no adipose tissue accumulation (NAT group), SAT prior accumulation (SAT group), and visceral adipose tissue prior accumulation (VAT group). The results of the three groups revealed that the SAT group displayed a significantly poor prognosis of the Kaplan-Meier curve (67.1 vs 21.2 vs 65.3, P<0.001) of a 5-year survival rate. Propensity score matching analysis of the SAT and VAT groups was performed to adjust the patient's background, but no significant differences were found between them; however, the prognosis was poorer (21.2 vs 66.3, P<0.001), and hemostatic factors were still at a lower level in the SAT group. These findings suggest that SAT accumulation type of obesity is a poor prognostic factor in alcoholic LC patients without HCC, and the hemorrhagic tendency might worsen the poor prognosis in such cases.

DOI： 10.1371/journal.pone.0242582

Nationwide epidemiological survey of autoimmune pancreatitis in Japan in 2016

Masamune, A., Kikuta, K., Hamada, S., Tsuji, I., Takeyama, Y., Shimosegawa, T., Okazaki, K., Kanno, A., Sano, T., Uchida, K., Ikeura, T., Fujimori, N., Nakai, Y., Kamisawa, T., Kubota, K., Motoya, M., Shimizu, K., Ushijima, T., Fukasawa, M., Naitoh, I., Ueno, M., Okuwaki, K., Uza, N., Asada, M., Mukai, T., Kudo, Y., Uetsuki, K., Mitoro, A., Watanabe, H., Terai, S., Hayashi, K., Imamura, Y., Haba, S., Hara, K., Fujisawa, T., Iwasaki, E., Okumura, F., Kawaji, Y., Kitano, M., Nishino, T., Nagahama, M., Hirano, A., Aruga, Y., Yamamoto, S., Inui, K., Kubota, Y., Takahashi, K., Sakagami, J., Kobayashi, T., Miraki, T., Watanabe, T., Sato, H., Takeda, Y., Satoh, M., Kobashigawa, K., Chiba, M., Tamura, T., Sawada, N., Mizukami, K., Sekine, M., Unno, J., Ishizawa, T., Funayama, H., Hatayama, K., Miyakawa, H., Sakai, T., Kuwatani, M., Toki, M., Toyokawa, T., Hashimoto, S., Itoi, T., Iwashita, Y., Sato, A., Kato, H., Takatori, H., Iizawa, Y., Iwashita, T., Kondo, H., Sato, Y., Tanabe, M., Ogura, T., Yamamoto, K., Masaka, T., Setsuda, M., Sano, T., Matsubara, S., Kitamura, K., Iwata, K., Shirahata, N., Hagiwara, H., Yoshida, M., Yokota, T., Shigoka, H., Kaneko, N., Abue, M., Tsuruoka, N.

Journal of Gastroenterology 55 ( 4 ) 2020年

Nationwide epidemiological survey of chronic pancreatitis in Japan: introduction and validation of the new Japanese diagnostic criteria 2019

Masamune, A., Kikuta, K., Kume, K., Hamada, S., Tsuji, I., Takeyama, Y., Shimosegawa, T., Okazaki, K., Miura, S., Takikawa, T., Hongo, S., Nakano, E., Nabeshima, T., Matsumoto, R., Tanaka, Y., Ueno, M., Mukai, T., Matsumoto, M., Kudo, Y., Azuma, S., Okuwaki, K., Yamamoto, S., Inui, K., Kobashigawa, K., Unno, J., Fujimori, N., Kitamura, K., Miyakawa, H., Takahashi, K., Ikeura, T., Takenaka, M., Fukasawa, M., Funayama, H., Mitoro, A., Takagi, T., Sekine, M., Suwa, K., Sakagami, J., Ishida, M., Ohtsuka, M., Kagawa, S., Muraki, T., Watanabe, T., Watanabe, T., Yamamoto, K., Masaka, T., Nagahama, M., Sato, A., Aruga, Y., Nakai, Y., Iwasaki, E., Itoi, T., Kawaji, Y., Kitano, M., Mizukami, K., Iwasaki, S., Mori, M., Kaneko, N., Kodama, Y., Sato, H., Yoshida, N., Hatayama, K., Kobayashi, T., Hirano, A., Kaino, M., Fujisawa, T., Ushijima, T., Chiba, M., Shimizu, K., Ota, H., Toki, M., Nishikawa, T., Yoshida, Y., Tanaka, K., Uetsuki, K., Motoya, D., Muro, S., Watanabe, H., Imamura, Y., Ishizawa, T., Kamisawa, T., Tsuruoka, M., Hayashi, K., Terai, S., Iwatsuka, K., Iwata, K., Yoshida, M., Takagi, T., Goto, M., Oza, N., Takeda, Y., Hagiwara, H., Tadano, T., Sakai, T., Sumimoto, K., Nishimura, N., Irisawa, A., Kuwatani, M., Shirahata, N., Satoh, M., Fujikawa, T., Iizawa, Y., Watanabe, N., Ishiguro, H., Sawada, N., Katada, K., Kondo, H., Sakakihara, I., Nishida, J., Tamura, T., Dairaku, N., Kamezaki, H., Okano, H., Suzuki, S., Okamoto, T., Matsugu, Y., Imamura, M., Honjo, M., Sugiyama, G., Ohta, H., Higashide, S., Ishii, S., Hoshi, T., Takagi, Y., Satoh, A., Yamaji, N., Nishimura, N., Shibasaki, M., Tamura, H., Iwashita, T., Motoya, M., Tanisaka, Y., Ryozawa, S., Takatori, H., Tsuruoka, N., Hashimoto, S., Suzuki, N., Sato, Y., Tamai, H., Hara, K., Ashida, K., Yokota, T., Tsuji, T., Abue, M., Tomaki, H., Fukunishi, M., Koga, H., Takehara, Y., Kawamura, H., Shimokawahara, N., Otsu, N., Kimura, Y., Ishido, K., Kofunato, Y., Shiihara, M., Sakaguchi, T., Masui, T., Eguchi, H., Suzumura, K., Ide, T., Inomata, M., Maemura, K., Iizawa, H., Nakajima, A., Uyama, S., Shiozaki, S., Yokoyama, S., Wakabayashi, T., Furuuchi, T., Gushima, T., Satoh, S., Shioya, T., Nakazawa, K., Takahashi, Y., Fukuba, N., Matsubara, S.

Journal of Gastroenterology 55 ( 11 ) 2020年

Usefulness of endoscopic ultrasound (EUS)-fine needle aspiration (FNA) for local excision of brunner's gland hamartoma with hemorrhage: A case report and literature review,EUS-FNA が術前診断に有用であった十二指腸 Brunner 腺過誤腫出血の 1 切除例

Arao, Y., Kobayashi, M., Ikemi, M., Shioji, K., Seino, S., Abe, H., Iwaki, T., Taguchi, T., Tani, Y., Terai, S.

Gastroenterological Endoscopy 62 ( 7 ) 2020年

Practical guide on on-line hemodiafiltration for acute liver failure

Inoue, K., Oda, S., Abe, R., Takikawa, Y., Nakayama, N., Kato, N., Fujiwara, K., Yasui, S., Terai, S., Ido, A., Sakaida, I., Genda, T., Shimizu, M., Mochida, S., Takikawa, H.

Kanzo/Acta Hepatologica Japonica 61 ( 2 ) 2020年

Clinical practice of acute pancreatitis in Japan: An analysis of nationwide epidemiological survey in 2016

Masamune, A., Kikuta, K., Hamada, S., Tsuji, I., Takeyama, Y., Shimosegawa, T., Okazaki, K., Matsumoto, R., Kume, K., Miura, S., Takikawa, T., Hongo, S., Tanaka, Y., Sakai, T., Ueno, M., Unno, J., Toki, M., Nishimura, M., Kitamura, K., Kobashigawa, K., Ashida, K., Takahashi, K., Watanabe, T., Sato, Y., Satoh, A., Yoshida, N., Tanaka, K., Kondo, H., Suzuki, N., Sato, H., Mitoro, A., Minami, K., Iwasaki, E., Okuwaki, K., Mukai, T., Kudo, Y., Azuma, S., Takeda, Y., Setsuda, M., Tsuchida, K., Irisawa, A., Motoya, D., Shirahata, N., Iwata, K., Oza, N., Kawaguchi, Y., Hoshino, A., Hirano, A., Sakakihara, I., Watanabe, N., Funayama, H., Nakamura, Y., Yamamoto, T., Uchida, H.H., Iizawa, Y., Imamura, M., Sekine, M., Inui, K., Yamamoto, S., Sato, S., Ishii, S., Yakushijin, T., Yamamoto, K., Masaka, T., Yoshida, M., Arizumi, T., Goto, M., Takenaka, M., Miyakawa, H., Otsuka, Y., Nishi, M., Suwa, K., Sakagami, J., Satoh, M., Koga, H., Takagi, T., Nagahama, M., Hatayama, K., Kaneko, N., Mori, M., Nakai, Y., Iwashita, Y., Iwatsuka, K., Hayashi, K., Terai, S., Kaneto, H., Nishikawa, T., Uchi, M., Honjo, M., Takagi, T., Mizukami, K., Tamura, T., Gushima, T., Sato, A., Shimizu, K., Aruga, Y., Nonogaki, K., Kaino, M., Iwashita, T., Tsuruoka, M., Miura, M., Hasegawa, H., Takai, T., Yokota, H., Fujisawa, T., Uetsuki, K., Kobayashi, T., yamaji, N., Itoi, T., Muraki, T., Watanabe, T., Inatomi, O., Ushijima, T., Takehara, Y., Kawamura, H., Fukasawa, M., Hagiwara, H., Tamura, H., Moriya, T., Kuwatani, M., Kawaji, Y., Kamisawa, T., Abue, M., Fukunishi, M., Onoyama, H., Mochizuki, S., Sumimoto, K., Koyabu, M., Nishio, A., Sakao, M., Imamura, Y., Ohta, H., Nishimura, N., Shiihara, M., Anan, H., Motoya, M., Chiba, M., Deguchi, T., Kofunato, Y., Sawada, N., Katada, K., Matsumoto, S., Higashide, S., Okano, H., Ishida, M., Yamazaki, M., Tamura, N., Muraoka, T., Uza, N., Kodama, Y., Muro, S., Fujimori, N., Ikeda, T., Shimokawahara, N., Otsu, N., Yano, Y., Sugawara, S., Takaura, K., Ogura, Y., Furuuchi, T., Shibasaki, M., Kishimoto, M.

Pancreatology 20 ( 4 ) 2020年

A case of primary hepatic actinomycosis difficult to distinguish from malignant hepatic tumors

Honda, H., Nozawa, Y., Takamura, M., Kamimura, H., Tsuchiya, A., Terai, S.

Kanzo/Acta Hepatologica Japonica 61 ( 3 ) 2020年

Rare Mesenteric Arterial Diseases: Fibromuscular Dysplasia and Segmental Arterial Mediolysis and Literature Review. 査読

Masayoshi Ko, Kenya Kamimura, Akira Sakamaki, Yusuke Niwa, Kentaro Tominaga, Kenichi Mizuno, Shuji Terai

Internal medicine (Tokyo, Japan) 58 ( 23 ) 3393 - 3400 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Fibromuscular dysplasia (FMD) and segmental arterial mediolysis (SAM) are noninflammatory, nonatherosclerotic arterial diseases that cause aneurysm, occlusion, and thromboses. These diseases are rarely seen in mesenteric arterial lesions; however, as they can be lethal if appropriate management is not provided, the accumulation of clinical information from cases is essential. We herein report the cases of a 57-year-old man diagnosed with FMD and a 63-year-old man diagnosed with SAM. We conclude that an early diagnosis with imaging modalities and clinical information followed by the appropriate treatment improves the prognosis of these arterial diseases.

DOI： 10.2169/internalmedicine.3094-19

Pulmonary tumor thrombotic microangiopathy of hepatocellular carcinoma: A case report and review of literature. 査読国際誌

Morita S, Kamimura K, Abe H, Watanabe-Mori Y, Oda C, Kobayashi T, Arao Y, Tani Y, Ohashi R, Ajioka Y, Terai S

World journal of gastroenterology 25 ( 48 ) 6949 - 6958 2019年12月

Efficacy of gelatin hydrogels incorporating triamcinolone acetonide for prevention of fibrosis in a mouse model. 査読国際誌

Nao Nakajima, Satoru Hashimoto, Hiroki Sato, Kazuya Takahashi, Takuro Nagoya, Kenya Kamimura, Atsunori Tsuchiya, Junji Yokoyama, Yuichi Sato, Hanako Wakatsuki, Masayuki Miyata, Yusuke Akashi, Ryusuke Tanaka, Ken Matsuda, Yasuhiko Tabata, Shuji Terai

Regenerative therapy 11 41 - 46 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Introduction: Triamcinolone acetonide (TA), a steroid, is often used clinically to prevent dysfunctions associated with fibrosis. The objective of this study was to examine whether TA can be suspended in a gelatin sheet for tissue engineering using a mouse skin wound model. Methods: TA was suspended in biodegradable gelatin and freeze-dried in a sheet form. The sheet was analyzed for homogeneity and controlled release of TA by high-performance liquid chromatography. We made two skin wounds on the dorsal side of mice. Gelatin sheets with TA (TA sheet) and without TA (control sheet) were attached to each skin wound. To determine the efficacy of the prepared TA sheet on the skin wounds, TA-sheet versus TA-injection experiments were conducted. Hematoxylin and eosin staining was performed to assess the grade of epithelialization and alpha smooth muscle actin (α-SMA) immunohistochemical staining was conducted to evaluate myofibroblast infiltration. Results: In the TA-release test in vitro, 7.7 ± 2.3% of TA was released from the sheet by 24 h. After replacing the initial phosphate-buffered saline (PBS) with collagenase PBS, the amount of released TA increased over time. The wound area/original skin wound area after 15 days with the TA sheet was significantly larger than that with the control sheet (26.9 ± 5.5% vs 10.7 ± 2.6%, p = 0.023). The α-SMA positive area/whole area with the TA sheet was significantly lower than that with the control sheet (4.65 ± 0.66% vs 7.24 ± 0.7%, p = 0.023). Furthermore, the α-SMA positive area/whole area with the TA sheet was significantly lower than that with TA injection (5.32 ± 0.45% vs 7.93 ± 0.75%, p = 0.013). Conclusions: We developed a TA sheet and confirmed both the homogeneity of the suspended TA and controlled-release of the TA in the presence of collagenase in vitro. The TA sheet caused less myofibroblast infiltration into the tissue than the control sheet or TA injection did.

DOI： 10.1016/j.reth.2019.04.001

心窩部痛、肝障害を契機に発見されたcholedochoceleの一例

Rare case of systemic scleroderma showing full-layer histologic features of an ileal lesion. 査読国際誌

Hiroki Sato, Terasu Honma, Saki Yamada, Takashi Owaki, Shuji Terai

Gastrointestinal endoscopy 90 ( 6 ) 991 - 993 2019年12月

表在型食道癌患者における禁酒後の体組成変化の検討

水澤健, 橋本哲, 上村博輝, 高村昌昭, 寺井崇二

アルコールと医学生物学 38 54 - 54 2019年12月

岩澤貴宏, 五十嵐聡, 林和直, 大脇崇史, 上村博輝, 橋本哲, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 35 ( 2 ) 152 - 152 2019年12月

A case of pancreatic pseudocysts accompanied by infection, pseudoaneurysm ruptures, and pseudocystocolonic fistulae.

Kosuke Sato, Kazuya Takahashi, Yukio Aruga, Fusako Yamazaki, Daisuke Kumaki, Masashi Yamakawa, Masaaki Hirano, Kazuhiro Funakoshi, Shuji Terai

Clinical journal of gastroenterology 12 ( 6 ) 615 - 620 2019年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Pancreatic pseudocysts (PPs) can be accompanied by infection, pseudoaneurysm ruptures, and fistulae to other organs, which can be fatal without appropriate treatment. Herein, we present the case of an 82-year-old man with PPs accompanied by infection, pseudoaneurysm rupture, and pseudocystocolonic fistula that were managed via multidisciplinary treatment. Computed tomography (CT) revealed two inflamed PPs, one each in the pancreatic head and tail. He was, therefore, diagnosed with infectious PPs. The pancreatic head PP shrunk on endoscopic nasopancreatic drainage (ENPD), but the pancreatic tail PP did not. Endoscopic ultrasound (EUS)-guided transluminal drainage was performed to treat the pancreatic tail PP; his symptoms improved. However, he vomited blood at 14 day post-drainage. Angiography revealed pseudoaneurysm rupture in a left gastric artery branch. After successful angioembolization, he developed hematochezia 2 days later. We suspected re-bleeding of the pseudoaneurysm. The bleeding stopped spontaneously, but CT and radiography revealed the presence of a pseudocystocolonic fistula. Careful follow-up was performed, and he has not had any symptoms at 9 month post-discharge. We managed PP-related complications via ENPD, EUS-guided transluminal drainage, angioembolization, and careful follow-up. Infection, pseudoaneurysm rupture, and pseudocystocolonic fistula are rare, but can occur simultaneously. Therefore, clinicians should consider these complications when treating patients with PPs.

DOI： 10.1007/s12328-019-00986-8

Gene Therapy for Liver Cancers: Current Status from Basic to Clinics. 査読国際誌

Kamimura K, Yokoo T, Abe H, Terai AS

Cancers 11 ( 12 ) 2019年11月

Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review. 査読国際誌

Takeshi Mizusawa, Kenya Kamimura, Hiroki Sato, Takeshi Suda, Hiroyuki Fukunari, Go Hasegawa, Osamu Shibata, Shinichi Morita, Akira Sakamaki, Junji Yokoyama, Yu Saito, Yoshihisa Hori, Yuduru Maruyama, Fumitoshi Yoshimine, Takahiro Hoshi, Shinichi Morita, Tsutomu Kanefuji, Masaaki Kobayashi, Shuji Terai

World journal of clinical cases 7 ( 21 ) 3553 - 3561 2019年11月

記述言語：英語

BACKGROUND: Immunosuppression is effective in treating a number of diseases, but adverse effects such as bone marrow suppression, infection, and oncogenesis are of concern. Methotrexate is a key immunosuppressant used to treat rheumatoid arthritis. Although it is effective for many patients, various side effects have been reported, one of the most serious being methotrexate-related lymphoproliferative disorder. While this may occur in various organs, liver involvement is rare. Information on these liver lesions, including clinical characteristics, course, and imaging studies, has not been summarized to date. CASE SUMMARY: We present a case of 70-year-old woman presented with a 2-wk history of fever and abdominal pain. She had had rheumatoid arthritis for 5 years and was being treated with medication including methotrexate. Contrast-enhanced computed tomography revealed multiple low density tumors in the liver and the histological analyses showed significant proliferation of lymphocytes in masses that were positive on immunohistochemical staining for CD3, CD4, CD8, and CD79a but negative for CD20 and CD56. Staining for Epstein-Barr virus-encoded RNA was negative. And based on these findings, the liver tumors were diagnosed as Methotrexate-related lymphoproliferative disorders. A time-dependent disappearance of the liver tumors after stopping methotrexate supported the diagnoses. CONCLUSION: The information obtained from our case and a review of 9 additional cases reported thus far assist physicians who may face the challenge of diagnosing and managing this disorder.

DOI： 10.12998/wjcc.v7.i21.3553

高齢者表在型食道癌患者における内視鏡的粘膜下層剥離術後の体組成変化の検討

肝硬度測定を用いたICG検査の代替の試み

熊谷優, 横尾健, 佐藤毅昂, 茂木聡子, 川田雄三, 薛徹, 水野研一, 木村成宏, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増大会 ) A849 - A849 2019年11月

水澤健, 橋本哲, 上村博輝, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増大会 ) A811 - A811 2019年11月

IgG4関連硬化性胆管炎の一例

中村涼太, 田中裕登, 大越麻里奈, 小関洋平, 水澤健, 五十嵐聡, 林和直, 佐藤裕樹, 坂牧僚, 上村顕也, 横山純二, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 65回 81 - 81 2019年11月

複合型免疫不全症を合併する遷延性黄疸が免疫グロブリン療法により改善した一例

小田知友美, 土屋淳紀, 木村淳史, 冨永顕太郎, 林和直, 寺井崇二

肝臓 60 ( Suppl.3 ) A1000 - A1000 2019年11月

胃瘻造設によりS状結腸間膜穿孔をきたした一例

吉田悠紀, 川田雄三, 永山逸夫, 野澤良祐, 冨永顕太郎, 薛徹, 横尾健, 水野研一, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 65回・87回 47 - 47 2019年11月

肝癌の局所制御及び集学的治療法としての放射線治療の検討

上村顕也, 柴田理, 寺井崇二

肝臓 60 ( Suppl.3 ) A875 - A875 2019年11月

有腹水肝硬変症例に対するtolvaptan投与前後のM2BPGiの経時的変化とその臨床的意義

高村昌昭, 坂牧僚, 寺井崇二, 上村博輝, 土屋淳紀, 薛徹, 上村顕也, 横尾健

肝臓 60 ( Suppl.3 ) A936 - A936 2019年11月

NASHの病態への臓器間ネットワークの関与

高昌良, 上村顕也, 名古屋拓郎, 井上良介, 酒井規裕, 丹羽祐輔, 坂牧僚, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増大会 ) A846 - A846 2019年11月

Eosinophilic esophagitis after total gastrectomy treated with proton pump inhibitors: a case report. 査読

Takashi Owaki, Hiroki Sato, Ryoko Horigome, Satoru Hashimoto, Terasu Honma, Shuji Terai

Clinical journal of gastroenterology 12 ( 5 ) 420 - 423 2019年10月

記述言語：英語

Eosinophilic esophagitis (EoE) is a chronic, immune-mediated disorder in the esophagus characterized by symptoms related to esophageal dysfunction and eosinophil-predominant inflammation. EoE and Gastro Esophageal Reflux Disease (GERD) are known not to be mutually exclusive and share a complex relationship. Proton pump inhibitors (PPIs), which are generally used in the treatment of GERD, could be used to treat esophageal eosinophilia in suspected EoE. We report a rare case of EoE after total gastrectomy that responded to PPIs. Our case indicates that the onset of EoE does not necessarily require an acid reflux-induced antigen-mediated drive, and the action of PPIs in patients with active EoE is unrelated to gastric acid suppression.

DOI： 10.1007/s12328-019-00960-4

アルコール性肝硬変の予後における、るいそうおよび肥満の影響

A rare case of Paneth cell-rich depressed adenoma in the terminal ileum. 査読国際誌

Kentaro Tominaga, Atsunori Tsuchiya, Hiroki Sato, Shuji Terai

Gastrointestinal endoscopy 90 ( 4 ) 694 - 695 2019年10月

Endoscopic retrieval of a button battery using the tip of a magnetic tube. 査読国際誌

Morita S, Yagi K, Terai S

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 31 ( 6 ) e116-e117 2019年10月

肝臓病理の臨床への貢献と次世代への飛躍を目指して小児NAFLD患者の臨床スコアの動態とSerial Biopsyによる知見

上村博輝, 上村顕也, 寺井崇二

肝臓 60 ( Suppl.2 ) A607 - A607 2019年10月

急性膵炎後の諸問題に対する内視鏡の役割重症急性膵炎後Walled-off necrosisに対するLumen apposing metal stentの有効性

五十嵐聡, 林和直, 寺井崇二

Gastroenterological Endoscopy 61 ( Suppl.2 ) 2066 - 2066 2019年10月

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) 当科における副乳頭アプローチカニュレーションの工夫

林和直, 五十嵐聡, 寺井崇二

Gastroenterological Endoscopy 61 ( Suppl.2 ) 2055 - 2055 2019年10月

IFN-γ刺激下採取エクソソームは抗炎症マクロファージを誘導し、肝線維化改善に寄与する

竹内卓, 土屋淳紀, 寺井崇二

肝臓 60 ( Suppl.2 ) A681 - A681 2019年10月

消化器疾患での間葉系幹細胞を用いた治療法開発

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 60 ( Suppl.2 ) A570 - A570 2019年10月

間葉系幹細胞を"指揮細胞"として用いた肝硬変に対する再生医療の治療戦略

寺井崇二, 土屋淳紀, 竹内卓

肝臓 60 ( Suppl.2 ) A561 - A561 2019年10月

非ウイルス性肝炎・肝硬変増加時代の効果的な肝細胞癌リスク患者の拾い上げと専門医による評価

土屋淳紀, 高村昌昭, 寺井崇二

肝臓 60 ( Suppl.2 ) A696 - A696 2019年10月

高齢者におけるFIB-4 indexの特徴

横尾健, 薛徹, 上村博輝, 坂牧僚, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

肝臓 60 ( Suppl.2 ) A696 - A696 2019年10月

肝癌に対する分子標的治療中のヒスチジンによる肝予備能維持効果と副作用予防

上村顕也, 寺井崇二

肝臓 60 ( Suppl.2 ) A674 - A674 2019年10月

坂牧僚, 横山邦彦, 上村顕也, 高村昌昭, 寺井崇二

肥満研究 25 ( Suppl. ) 304 - 304 2019年10月

マウス肝線維化進展予防薬の探索及びレトロゾールによる線維化進展予防効果の検証

酒井規裕, 上村顕也, 名古屋拓郎, 丹羽佑輔, 高昌良, 薛徹, 横尾健, 坂牧僚, 榎本初音, 立木秀尚, 寺井崇二

肝臓 60 ( Suppl.2 ) A680 - A680 2019年10月

NASHモデルマウスにおける自律神経系を介したグレリンの関与

名古屋拓郎, 上村顕也, 井上良介, 酒井規裕, 後藤諒, 高昌良, 丹羽佑輔, 坂牧僚, 寺井崇二

肝臓 60 ( Suppl.2 ) A682 - A682 2019年10月

Wavy mucosal tear in the sigmoid colon. 査読国際誌

Kentaro Tominaga, Junji Yokoyama, Kazunao Hayashi, Atsunori Tsuchiya, Shuji Terai

Clinical case reports 7 ( 9 ) 1825 - 1826 2019年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Although linear mucosal tears have been reported, we found a relatively rare case of wavy mucosal tear in collagenous colitis. This may be related to the mutual weak adhesiveness between the epithelium and collagen band. This complication necessitates great care to be taken while performing colonoscopy in patients suspected of collagenous colitis.

DOI： 10.1002/ccr3.2275

Inhibition of sodium-glucose cotransporter 2 ameliorated renal injury in a novel medaka model of nonalcoholic steatohepatitis-related kidney disease. 査読国際誌

Nagoya T, Kamimura K, Goto R, Shinagawa-Kobayashi Y, Niwa Y, Kimura A, Sakai N, Ko M, Nishina H, Terai S

FEBS open bio 9 ( 12 ) 2016 - 2024 2019年9月

NSTによる消化器内科病変の発見により自宅退院まで改善した症例

小師優子, 村山稔子, 上村博輝, 小山諭, 寺井崇二

学会誌JSPEN 1 ( Suppl. ) 1331 - 1331 2019年9月

非ウイルス性肝硬変時代の門亢症〜ウイルス性との共通点・相違点を中心に〜原発性胆汁性胆管炎における食道・胃静脈瘤の検討

薛徹, 横山純二, 高綱将史, 荒生祥尚, 上村輝博, 坂牧僚, 横尾健, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

日本門脈圧亢進症学会雑誌 25 ( 3 ) 110 - 110 2019年9月

門亢症に伴う慢性肝不全の臓器関連〜脳・腎・腸〜 NASHの病態進行との自律神経を介した臓器間ネットワークの関与

高昌良, 上村顕也, 名古屋拓郎, 大脇崇史, 井上良介, 酒井規裕, 丹羽祐輔, 坂牧僚, 横尾健, 寺井崇二

日本門脈圧亢進症学会雑誌 25 ( 3 ) 77 - 77 2019年9月

Change in body composition in patients with achalasia before and after peroral endoscopic myotomy. 査読国際誌

Takeshi Mizusawa, Hiroki Sato, Kenya Kamimura, Satoru Hashimoto, Ken-Ichi Mizuno, Hiroteru Kamimura, Satoshi Ikarashi, Kazunao Hayashi, Masaaki Takamura, Junji Yokoyama, Shuji Terai

Journal of gastroenterology and hepatology 35 ( 4 ) 601 - 608 2019年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Patients with achalasia experience weight loss because of dysphagia caused by impaired relaxation of the lower esophageal sphincter. This study aimed to use dual bioelectrical impedance analysis (BIA) to determine the change in bodyweight and body composition in patients with achalasia before and after peroral endoscopic myotomy (POEM). METHODS: Patients with achalasia who underwent POEM from 2013 to 2018 (n = 72) were retrospectively analyzed for change in bodyweight before and after 3 months. Additionally, change in body composition was prospectively investigated in the final 10 of 72 patients using non-radiation dual BIA. RESULTS: Twenty patients (27.8%) were underweight (body mass index < 18.5) before undergoing POEM. No clinical parameters were identified to be associated with the underweight condition before POEM and be predictive of an increase in bodyweight after POEM. Low visceral fat volume observed on dual BIA correlated closely with the result obtained using computed tomography (Pearson correlation coefficient: r = 0.850, P < 0.01). Patients with achalasia had a statistically significant increase in visceral (P < 0.01) and subcutaneous fat volumes (P < 0.01) after POEM. Skeletal muscle mass index slightly increased (P = 0.02), although the value after POEM was still low. No blood biomarkers were indicators for low bodyweight or low visceral fat volume. CONCLUSIONS: Dual BIA is an effective non-invasive tool to evaluate the change in body composition of underweight patients with achalasia. Skeletal muscle volume was not enough after POEM, although a rapid increase in the intra-abdominal fat volume was observed. Additional studies are warranted to understand the pathological implications.

DOI： 10.1111/jgh.14847

Epidemiological analysis of achalasia in Japan using a large-scale claims database 査読

Methotrexate-Associated Lymphoproliferative Disorder: A Rare Case of Large Liver Tumors. 国際誌

Saori Watanabe, Kazuya Takahashi, Kazuhiro Funakoshi, Shuji Terai

Hepatology (Baltimore, Md.) 70 ( 2 ) 748 - 750 2019年8月

Sato, H., Yokomichi, H., Takahashi, K., Tominaga, K., Mizusawa, T., Kimura, N., Kawata, Y., Terai, S.

Journal of Gastroenterology 54 ( 7 ) 621 - 627 2019年7月

Case of early-stage gastric cancer identified in the gastric mucosa with lanthanum phosphate deposition. 査読

Takatsuna M, Takeuchi M, Usuda H, Terai S

Endoscopy international open 7 ( 7 ) E893 - E895 2019年7月

Colorectal neuroendocrine carcinoma: A case report and review of the literature. 査読国際誌

Yoshida T, Kamimura K, Hosaka K, Doumori K, Oka H, Sato A, Fukuhara Y, Watanabe S, Sato T, Yoshikawa A, Tomidokoro T, Terai S

World journal of clinical cases 7 ( 14 ) 1865 - 1875 2019年7月

Delayed pancreatic ductal leakage after EUS-FNA for autoimmune pancreatitis. 査読

Ikarashi S, Tsuchiya A, Hayashi K, Terai S

Endoscopic ultrasound 8 ( 4 ) 277 - 278 2019年7月

肝癌薬剤耐性におけるエクソソームの有用性および課題

松田康伸, 寺井崇二

BIO Clinica 34 ( 7 ) 737 - 740 2019年7月

A case report of psychiatric symptoms following direct-acting antiviral and ribavirin combination therapy for chronic hepatitis C in a patient with innate anxiety. 査読国際誌

Akira Sakamaki, Kenya Kamimura, Naoki Fukui, Haruka Watanabe, Norihiro Sakai, Kentaro Tominaga, Kenichi Mizuno, Masaaki Takamura, Hirokazu Kawai, Takuro Sugai, Satoshi Yamagiwa, Toshiyuki Someya, Shuji Terai

BMC gastroenterology 19 ( 1 ) 85 - 85 2019年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Direct-acting antivirals (DAAs) result in a highly sustained virological response rate and better patient tolerance. However, this therapeutic approach may, on rare occasions, give rise to psychiatric symptoms. We describe a case requiring discontinuation of DAA and ribavirin combination therapy due to psychiatric symptoms in a patient with congenital anxious personality traits. The information summarized here will be helpful to physicians treating chronic hepatitis C virus (HCV) infection in patients with underlying psychiatric problems. CASE PRESENTATION: A 57-year-old Japanese woman diagnosed with chronic HCV infection was prescribed DAA and ribavirin combination therapy. She had a history of mild innate anxiety and development of psychiatric symptoms due to interferon (IFN) therapy 8 years prior, which subsided with discontinuation of the therapy. Similar psychiatric symptoms such as enervation, palpitations, an episode of hyperventilation, and consciousness disturbances with myotonia were observed after the administration of the antiviral agents. No abnormal findings related to her symptoms were observed on laboratory or imaging results. Psychiatrists diagnosed the patient as having a somatization disorder induced by the antiviral agents on the basis of innate anxiety. After the discontinuation of therapy, her symptoms gradually improved. CONCLUSIONS: Although DAAs were not causative factors for psychiatric symptoms in phase 3 studies, a post-marketing study reported psychiatric symptoms such as depression in patients with underlying psychiatric problems. Our case suggests psychiatric symptoms might worsen after DAA and ribavirin administration in patients with underlying psychiatric disorders, and therefore, close monitoring is necessary for these patients, especially if they have a history of psychiatric symptoms after IFN.

DOI： 10.1186/s12876-019-1013-1

Evaluating the effect of injecting triamcinolone acetonide in two sessions for preventing esophageal stricture after endoscopic submucosal dissection. 査読国際誌

Satoru Hashimoto, Ken-Ichi Mizuno, Kazuya Takahashi, Hiroki Sato, Junji Yokoyama, Manabu Takeuchi, Yuichi Sato, Masaaki Kobayashi, Shuji Terai

Endoscopy international open 7 ( 6 ) E764-E770 - E770 2019年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background and study aims Several previous reports indicate that endoscopic injection of triamcinolone acetonide (TA) after widespread endoscopic submucosal dissection (ESD) is effective for preventing esophageal stricture. We investigated the efficacy of injecting TA in two sessions for preventing stricture formation post-ESD. Patients and methods Sixty-six consecutive patients with widespread mucosal defects that affected more than three-fourths of the circumference of the esophagus were included. The study group (n = 40) received TA injections over two sessions: immediately after and 14 days after ESD. The control group (n = 26) did not receive a TA injection. This study was performed retrospectively against historical controls. The primary endpoint of this study was frequency of stricture after TA injection. The secondary endpoint was number of required endoscopic balloon dilations (EBDs) after TA injection. Results The post-ESD stricture rate among patients who had subcircumferential mucosal defects was 45.7 % in the study group (16/35 patients), which was significantly lower than the rate of 73.9 % in the control group (17/23 patients; P = 0.031). The number of EBD procedures required was significantly lower in the study group (median 0, range 0 - 7) than in the control group (median 4, range 0 - 20; P < 0.001). There was no significant difference between the study and control groups among the patients who had full circumferential mucosal defects. Conclusion This study showed that performing two sessions of TA injection is an effective and safe treatment for prevention of esophageal stricture following subcircumferential ESD.

DOI： 10.1055/a-0894-4374

医学・医療におけるシミュレータの進歩と普及(Vol.23) 消化器領域超音波のシミュレータ腹部超音波/超音波内視鏡

林和直, 五十嵐聡, 寺井崇二

医学のあゆみ 269 ( 12 ) 945 - 948 2019年6月

ダブルバルーン内視鏡で診断に至った消化管重複症の成人例

丹羽佑輔, 上村顕也, 小林隆昌, 高橋一也, 冨永顕太郎, 河久順志, 阿部聡司, 川合弘一, 横山純二, 杉野英明, 梅津哉, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 35 ( 1 ) 44 - 44 2019年6月

FDG-PETが重粒子線治療の効果判定に有用であった、若年者切除不能肝内胆管癌の1例

渡邉緑, 柴田理, 上村顕也, 安住里映, 渋谷圭, 大野達也, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 64回 34 - 34 2019年6月

Rational arrangement of measuring shear wave speed in the liver. 査読国際誌

Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Itsuo Nagayama, Takahiro Hoshi, Satoshi Abe, Shinichi Morita, Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Kazuyoshi Yagi, Shuji Terai

World journal of gastroenterology 25 ( 20 ) 2503 - 2513 2019年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Shear wave speed has been widely applied to quantify a degree of liver fibrosis. However, there is no standardized procedure, which makes it difficult to utilize the speed universally. AIM: To provide procedural standardization of shear wave speed measurement. METHODS: Point shear wave elastography (pSWE) was measured in 781 patients, and two-dimensional shear wave elastography (2dSWE) was measured on the same day in 18 cases. Regions-of-interest were placed at 12 sites, and the median and robust coefficient-of-variation (CVR) were calculated. A residual sum-of-square (Σdi2) was computed for bootstrap values of 1000 iterations in 18 cases with each assumption of 1 to 12 measurements. The proportion of the Σdi2 (%Σdi2) was calculated as the ratio of Σdi2 to pSWE after converting it based on the correlation between pSWE and 2dSWE. RESULTS: The CVR showed a significantly broader distribution in the left lobe (P < 0.0001), and the smallest CVR in the right anterior segment that covered 95% cases was 40.4%. pSWE was significantly higher in the left lobe than in the right lobe (1.63 ± 0.78 m/s vs 1.61 ± 0.78 m/s, P = 0.0004), and the difference between the lobes became further discrete when the subjects were limited to the cases with a CVR less than 40.4% in any segment (1.76 ± 0.80 m/s vs 1.70 ± 0.82 m/s, P < 0.0001). The highest values of the CVR in every 0.1 m/s interval were plotted in convex upward along pSWE and peaked at 1.93 m/s. pSWE and 2dSWE were significantly correlated (P < 0.0001, r = 0.95). In 216000 resamples from 18 cases, the %Σdi2 of 12 sites was 8.0% and gradually increased as the acquisition sites decreased to reach a significant difference with a %Σdi2 of 7 sites (P = 0.027). CONCLUSION: These data suggest that shear wave speed should be measured at 8 or more sites of spreading in both lobes.

DOI： 10.3748/wjg.v25.i20.2503

Utility of measuring paraesophageal varices using computed tomography to select endoscopic treatment for patients with esophageal varices 査読

Kimura, N., Yokoyama, J., Terai, S.

Digestive Endoscopy 31 ( 3 ) 335 - 335 2019年5月

Efficacy and safety of ribavirin therapy for chronic hepatitis E after kidney transplantation. 査読国際誌

Yoshida T, Takamura M, Goto R, Takeuchi S, Tsuchiya A, Kamimura K, Tasaki M, Nakagawa Y, Saito K, Tomita Y, Terai S

Hepatology research : the official journal of the Japan Society of Hepatology 49 ( 10 ) 1244 - 1248 2019年5月

Multiple Endocrine Neoplasia Type 1-Related Acute Pancreatitis. 査読

Takahashi S, Kamimura K, Abe H, Watanabe Y, Hayashi K, Mizuno K, Yamamoto T, Takeuchi M, Natsui M, Terai S

Pancreas 48 ( 5 ) e35 - e38 2019年5月

A rare duodenal carcinosarcoma: A case report and literature review 査読

Arao, Y., Kamimura, K., Ikemi, M., Takaki, M., Takahashi, S., Seino, S., Abe, H., Kohisa, J., Kato, T., Ajioka, Y., Terai, S.

Internal Medicine 58 ( 9 ) 1273 - 1278 2019年5月

Endoscopic ultrasound-guided hepaticogastrostomy using a novel covered metallic stent with a fine-diameter delivery system 査読

Morita, S., Yagi, K., Terai, S.

Digestive Endoscopy 31 ( 3 ) e60 - e61 2019年5月

Submucosal painting for gastroduodenal stent placement. 査読国際誌

Morita S, Suda T, Terai S

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 31 ( 3 ) e64 - e65 2019年5月

膵癌術前胆道ドレナージにおける大口径プラスチックステントの役割

五十嵐聡, 林和直, 寺井崇二, 水澤健, 川田雄三, 冨永顕太郎, 佐藤裕樹, 水野研一, 橋本哲, 横山純二, 高村昌昭

Gastroenterological Endoscopy 61 ( Suppl.1 ) 981 - 981 2019年5月

慢性膵炎による膵管狭窄に対するステント治療の現状と課題

林和直, 五十嵐聡, 寺井崇二, 水澤健, 冨永顕太郎, 佐藤裕樹, 水野研一, 橋本哲, 横山純二

Gastroenterological Endoscopy 61 ( Suppl.1 ) 1000 - 1000 2019年5月

当院における小腸カルチノイド7例の臨床的検討

冨永顕太郎, 川田雄三, 本田穣, 上村顕也, 横山純二, 寺井崇二, 田島陽介, 中野雅人, 島田能史, 亀山仁史, 若井俊文, アネコフ・アレクセイ, 味岡洋一, 阿部達也, 梅津哉, 岩渕三哉

日本大腸肛門病学会雑誌 72 ( 5 ) 348 - 348 2019年5月

A Rare Case Involving the Inability to Belch. 査読

Hiroki Sato, Shunzo Ikarashi, Shuji Terai

Internal medicine (Tokyo, Japan) 58 ( 7 ) 929 - 931 2019年4月

記述言語：英語

A 17-year-old girl was referred to our hospital with an inability to belch, while experiencing chest gurgling noises, and severe abdominal bloating. She reported having these symptoms all her life. A timed barium esophagogram revealed a moderate amount of bubbles in the esophagus and gastric fundus, which significantly increased after the examination. High resolution manometry revealed that the basal upper esophageal sphincter pressure increased with a rise in the cervical esophageal pressure. A pathological inability to belch is rare; at present, no specific name exists to describe the disorder. Further research is needed in this unexplored field.

DOI： 10.2169/internalmedicine.1908-18

Duodenal lymphangiectasia distinguished from follicular lymphoma by narrow-band imaging magnification endoscopy 査読

Considerations of elderly factors to manage the complication of liver cirrhosis in elderly patients. 査読国際誌

Kamimura K, Sakamaki A, Kamimura H, Setsu T, Yokoo T, Takamura M, Terai S

World journal of gastroenterology 25 ( 15 ) 1817 - 1827 2019年4月

Inhibition of sodium glucose cotransporter 2 (SGLT2) delays liver fibrosis in a medaka model of nonalcoholic steatohepatitis (NASH). 査読国際誌

Goto R, Kamimura K, Shinagawa-Kobayashi Y, Sakai N, Nagoya T, Niwa Y, Ko M, Ogawa K, Inoue R, Yokoo T, Sakamaki A, Kamimura H, Abe S, Nishina H, Terai S

FEBS open bio 9 ( 4 ) 643 - 652 2019年4月

Esophageal Stenosis by Prostate Cancer Metastasis 査読

Kamimura, K., Shinagawa-Kobayashi, Y., Mizuno, K., Terai, S.

American Journal of Gastroenterology 114 ( 4 ) 685 - 687 2019年4月

Tominaga, K., Tsuchiya, A., Mizuno, K.-I., Terai, S.

Gastrointestinal Endoscopy 90 ( 3 ) 2019年4月

Overlap in disease concept of functional esophageal disorders and minor esophageal motility disorders. 査読

Sato H, Takahashi K, Mizuno KI, Hashimoto S, Kawata Y, Mizusawa T, Tominaga K, Yokoyama J, Terai S

Journal of gastroenterology and hepatology 34 ( 11 ) 1940 - 1945 2019年4月

Usefulness of CCR7- PD-1+ follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis. 査読

Kimura N, Yamagiwa S, Sugano T, Horigome R, Setsu T, Tominaga K, Kamimura H, Takamura M, Terai S

Hepatology research : the official journal of the Japan Society of Hepatology 49 ( 9 ) 1026 - 1033 2019年4月

当院における高齢発症原発性胆汁性胆管炎患者の予後予測マーカーについて

高村昌昭, 木村成宏, 薛徹, 上村博輝, 坂牧僚, 横尾健, 土屋淳紀, 上村顕也, 松田康伸, 寺井崇二

肝臓 60 ( Suppl.1 ) A407 - A407 2019年4月

Management of endoscopic submucosal dissection for ulcerative colitis‐associated neoplasia: Tips and pitfalls

Ken‐ichi Mizuno, Junji Yokoyama, Shuji Terai

Digestive Endoscopy 31 ( S1 ) 44 - 45 2019年4月

急性肝不全:救命率の向上を目指した取り組み本県における急性肝不全診療ネットワーク構築の取り組み

薛徹, 高村昌昭, 寺井崇二

肝臓 60 ( Suppl.1 ) A211 - A211 2019年4月

肝癌診療ガイドライン2017を再検証する肝癌に対する放射線治療の検討

上村顕也, 柴田理, 寺井崇二

肝臓 60 ( Suppl.1 ) A132 - A132 2019年4月

NASH/NAFLDの病態解明に向けた基礎的検討 NASH/NAFLDの病態における自律神経を介した消化管ホルモンの関与

上村顕也, 名古屋拓郎, 寺井崇二

肝臓 60 ( Suppl.1 ) A146 - A146 2019年4月

肝癌に対する分子標的薬の有害事象の発症予測

上村顕也, 寺井崇二

肝臓 60 ( Suppl.1 ) A487 - A487 2019年4月

免疫チェックポイント阻害薬による免疫関連有害事象と考えられる肝障害を呈した2例

坂牧僚, 上村顕也, 寺井崇二

肝臓 60 ( Suppl.1 ) A488 - A488 2019年4月

メダカを用いた食品・医薬品の機能性評価基盤の構築メダカモデルを用いた薬物スクリーニングと医学研究応用

寺井崇二, 上村顕也

日本栄養・食糧学会大会講演要旨集 73回 174 - 174 2019年4月

Esophageal diverticulum: New perspectives in the era of minimally invasive endoscopic treatment. 査読国際誌

Hiroki Sato, Manabu Takeuchi, Satoru Hashimoto, Ken-Ichi Mizuno, Koichi Furukawa, Akito Sato, Junji Yokoyama, Shuji Terai

World journal of gastroenterology 25 ( 12 ) 1457 - 1464 2019年3月

記述言語：英語

Esophageal diverticula are rare conditions that cause esophageal symptoms, such as dysphagia, regurgitation, and chest pain. They are classified according to their location and characteristic pathophysiology into three types: epiphrenic diverticulum, Zenker's diverticulum, and Rokitansky diverticulum. The former two disorders take the form of protrusions, and symptomatic cases require interventional treatment. However, the esophageal anatomy presents distinct challenges to surgical resection of the diverticulum, particularly when it is located closer to the oral orifice. Since the condition itself is not malignant, minimally invasive endoscopic approaches have been developed with a focus on alleviation of symptoms. Several types of endoscopic devices and techniques are currently employed, including peroral endoscopic myotomy (POEM). However, the use of minimally invasive endoscopic approaches, like POEM, has allowed the development of new disorder called iatrogenic esophageal diverticula. In this paper, we review the pathophysiology of each type of diverticulum and the current state-of-the-art treatment based on our experience.

DOI： 10.3748/wjg.v25.i12.1457

M2-polarized macrophages relate the clearance of gastric lanthanum deposition 査読

Nakamura, T., Tsuchiya, A., Kobayashi, M., Naito, M., Terai, S.

Clinical Case Reports 7 ( 3 ) 570 - 572 2019年3月

Diverse perspectives to address for the future treatment of heterogeneous hepatocellular carcinoma. 査読国際誌

Tsuchiya A, Ogawa M, Watanabe T, Takeuchi S, Kojima Y, Watanabe Y, Kimura N, Hayashi K, Yokoyama J, Terai S

Heliyon 5 ( 3 ) e01325 2019年3月

当院における切除不能局所進行膵癌の治療の現況

林和直, 五十嵐聡, 水澤健, 川田雄三, 冨永顕太郎, 佐藤裕樹, 水野研一, 橋本哲, 横山純二, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A468 - A468 2019年3月

術後再建腸管例におけるEUS-FNAの現状と工夫

五十嵐聡, 林和直, 水澤健, 川田雄三, 冨永顕太郎, 佐藤裕樹, 水野研一, 橋本哲, 横山純二, 高村昌昭, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A299 - A299 2019年3月

当院における肝癌に対する放射線治療の検討

柴田理, 上村顕也, 木村成宏, 薛徹, 横尾健, 坂牧僚, 上村博輝, 土屋淳紀, 高村昌昭, 丸山克也, 太田篤, 海津元樹, 青山英史, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A456 - A456 2019年3月

難治性潰瘍性大腸炎の治療戦略における外科と内科のコラボレーション難治性潰瘍性大腸炎に対する治療と今後の課題

横山純二, 冨永顕太郎, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A53 - A53 2019年3月

消化器領域における腸内細菌研究と臨床応用空置腸炎に対宇る自家糞便移植の有用性と腸内細菌叢への影響の解明

冨永顕太郎, 横山純二, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A161 - A161 2019年3月

メタボリックシンドロームとしての脂肪肝 SGLT2阻害薬によるNASH進展抑制効果の検証メダカNASHモデルを用いて

上村顕也, 後藤諒, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A142 - A142 2019年3月

Radial incision and cutting for refractory benign esophageal stricture. 国際誌

Takeshi Mizusawa, Masaaki Kobayashi, Shuji Terai

Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society 31 ( 2 ) e46-e47 2019年3月

肝線維化研究の展開と臨床応用マウス肝線維化進展予防薬の探索及びレトロゾールによる線維化進展予防効果の検証

酒井規裕, 上村顕也, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A214 - A214 2019年3月

高齢肝癌症例におけるソラフェニブの効果と有用性

横尾健, 森田真一, 木村成宏, 薛徹, 坂牧僚, 上村博輝, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

日本消化器病学会雑誌 116 ( 臨増総会 ) A413 - A413 2019年3月

Clinical and pathological profile of eosinophilic gastroenteritis. 査読国際誌

Hiroki Sato, Terasu Honma, Takashi Owaki, Kentaro Tominaga, Junji Yokoyama, Shuji Terai

European journal of gastroenterology & hepatology 31 ( 2 ) 157 - 162 2019年2月

記述言語：英語

BACKGROUND: Eosinophilic gastroenteritis (EoGE) can be diagnosed on the basis of histologic criteria; however, the pathology is considered to be heterogeneous. There is no consensus on the management of this enigmatic disorder with an unknown etiology. PATIENTS AND METHODS: Data for patients diagnosed with EoGE and followed up over a 1-year period were analyzed. Their symptoms, patterns of flares, and type of treatment were documented. The shift in peripheral blood eosinophil levels was also examined. RESULTS: A total of 10 (mean age, 44 years; range: 31-70 years; women, 5) patients were diagnosed with EoGE. The most frequent presenting symptom was abdominal pain, and eight patients were classified with mucosal type of EoGE. Chronic disease or multiple flares were observed in seven out of 10 (70.0%) patients, and all of them had a history of allergy. Four were corticosteroid dependent (three relapsed during corticosteroid tapering and one following corticosteroid withdrawal). One of them received anti-IL5 monoclonal antibody that enabled corticosteroid dose tapering. In four patients with highly elevated initial eosinophil levels at diagnosis, the peripheral eosinophil level correlated with the amelioration and deterioration of their symptoms. The remaining three patients had a single flare without relapse. Two had no history of allergy. CONCLUSION: EoGE is a unique disorder with a variable clinical course. Although further studies are required to confirm our observations, the presence of other allergic disorders is associated with chronicity or multiple flares. Peripheral eosinophil level may be an effective biomarker for recurrence in patients with severe systemic disorders at diagnosis.

DOI： 10.1097/MEG.0000000000001241

A cut-off value of shear wave speed to distinguish nonalcoholic steatohepatitis candidates 査読

Co-existent ulcerative colitis and Guillain-Barré syndrome: a case report and literature review. 査読

Tominaga K, Tsuchiya A, Sato H, Kimura A, Oda C, Hosaka K, Kawata Y, Kimura N, Hayashi K, Yokoyama J, Terai S

Clinical journal of gastroenterology 12 ( 3 ) 243 - 246 2019年2月

Suda, T., Kanefuji, T., Abe, A., Nagayama, I., Hoshi, T., Morita, S., Yagi, K., Hatakeyama, S., Hayatsu, M., Hasegawa, N., Terai, S.

Medicine (United States) 98 ( 2 ) e13958 2019年1月

Early injection of human adipose tissue-derived mesenchymal stem cell after inflammation ameliorates dextran sulfate sodium-induced colitis in mice through the induction of M2 macrophages and regulatory T cells. 査読

Kawata Y, Tsuchiya A, Seino S, Watanabe Y, Kojima Y, Ikarashi S, Tominaga K, Yokoyama J, Yamagiwa S, Terai S

Cell and tissue research 376 ( 2 ) 257 - 271 2019年1月

EpCAM- and/or NCAM-Expressing Hepatocellular Carcinoma in Which Behavior of Hepatic Progenitor Cell Marker-Positive Cells Are Followed. 査読

Tsuchiya A, Suda T, Oda C, Kimura A, Hosaka K, Kimura N, Tominaga K, Hayashi K, Takamura M, Terai S

Case reports in gastroenterology 13 ( 1 ) 118 - 124 2019年1月

Re-examination using newly proposed diagnostic criteria of acute-on-chronic liver failure in Japan 査読

Nojiri, S., Tsuchiya, A., Terai, S.

Hepatology Research 49 ( 1 ) 2019年

Effective prevention of sorafenib-related vascular damage induced adverse events and maintenance of hepatic function by dried bonito broth and histidine. 査読国際誌

Sakai N, Kamimura K, Shinagawa-Kobayashi Y, Nagoya T, Niwa Y, Ko M, Setsu T, Sakamaki A, Yokoo T, Abe S, Kamimura H, Sugitani S, Yanagi M, Terai S

Cancer management and research 11 4437 - 4448 2019年

A First Ileus Event in an Elderly Man With Malrotation 査読

Tominaga, K., Tsuchiya, A., Terai, S.

Gastroenterology 156 ( 3 ) 35026 - 1 2019年

Dynamic changes in basal lamina fenestrations in rat intestinal villous epithelium under high-fat diet condition 査読

Morita Keisuke, Azumi Rie, Sato Masatoshi, Mizutani Yusuke, Hayatsu Manabu, Terai Shuji, Ushiki Tatsuo

BIOMEDICAL RESEARCH-TOKYO 40 ( 2 ) 57 - 66 2019年

Different distribution of mucosal-associated invariant T cells within the human cecum and colon. 査読

Hama I, Tominaga K, Yamagiwa S, Setsu T, Kimura N, Kamimura H, Wakai T, Terai S

Central-European journal of immunology 44 ( 1 ) 75 - 83 2019年

Correction to: The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection (Gastric Cancer, (2019), 22, 3, (567-575), 10.1007/s10120-018-0878-y)

Azumi, M., Takeuchi, M., Koseki, Y., Kumagai, M., Kobayashi, Y., Takatsuna, M., Yoshioka, A., Yoshikawa, S., Miura, T., Terai, S.

Gastric Cancer 22 ( 3 ) 576 - 576 2019年

Microbiome in Liver Cirrhosis

Sakamaki, A., Takamura, M., Terai, S.

The Evolving Landscape of Liver Cirrhosis Management 2019年

A case of early-stage gastric mixed adenoneuroendocrine carcinoma (MANEC),早期胃 mixed adenoneuroendocrine carcinoma（MANEC）の例

Koseki, Y., Takatsuna, M., Kumagai, M., Kobayashi, Y., Azumi, M., Yoshioka, A., Yoshikawa, S., Usuda, H., Takeuchi, M., Terai, S.

Gastroenterological Endoscopy 61 ( 12 ) 2019年

The search, coagulation, and clipping (SCC) method prevents delayed bleeding after gastric endoscopic submucosal dissection

Azumi, M., Takeuchi, M., Koseki, Y., Kumagai, M., Kobayashi, Y., Takatsuna, M., Yoshioka, A., Yoshikawa, S., Miura, T., Terai, S.

Gastric Cancer 22 ( 3 ) 2019年

Gastrointestinal: Endoscopic diverticulectomy for the treatment of Zenker's diverticulum with a unique “tip”: A first case report in Japan

Sato, H., Takeuchi, M., Terai, S.

Journal of Gastroenterology and Hepatology (Australia) 34 ( 8 ) 1272 - 1272 2019年

Long-Term Culture of Mouse Fetal Hepatic Stem/Progenitor Cells

Tsuchiya, A., Terai, S.

Methods in molecular biology (Clifton, N.J.) 1905 2019年

Mesenchymal stem cell therapies for liver cirrhosis: MSCs as "conducting cells" for improvement of liver fibrosis and regeneration

Tsuchiya, A., Takeuchi, S., Watanabe, T., Yoshida, T., Nojiri, S., Ogawa, M., Terai, S.

Inflammation and Regeneration 39 ( 1 ) 2019年

Hepatobiliary and Pancreatic: AL amyloidosis presented as a hematoma in the hepatoduodenal ligament

Kobayashi, T., Yoshikawa, S., Takeuchi, M., Terai, S.

Journal of Gastroenterology and Hepatology (Australia) 34 ( 11 ) 1897 - 1897 2019年

肝胆膵疾患に対する低侵襲治療の工夫当院におけるWalled-off necrosis(WON)に対する内視鏡治療成績の検討

林和直, 五十嵐聡, 河久順志, 横山純二, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 34 ( 2 ) 189 - 189 2018年12月

Gastrointestinal: A case of hypereosinophilic syndrome with esophageal involvement 査読

Takahashi, K., Sato, H., Tominaga, K., Kohisa, J., Ikarashi, S., Hayashi, K., Miuzno, K., Hashimoto, S., Yokoyama, J., Terai, S.

Journal of Gastroenterology and Hepatology (Australia) 33 ( 11 ) 1817 - 1817 2018年11月

Novel Magnified Single-Balloon Enteroscopy Enables Observation of Jejunal White Spots Associated with Lymphangiectasia. 査読

Tominaga K, Tsuchiya A, Kawata Y, Yokoyama J, Terai S

Digestive diseases (Basel, Switzerland) 37 ( 2 ) 1 - 5 2018年11月

Mesenchymal Stem Cells and Induced Bone Marrow-Derived Macrophages Synergistically Improve Liver Fibrosis in Mice. 査読国際誌

Watanabe Y, Tsuchiya A, Seino S, Kawata Y, Kojima Y, Ikarashi S, Starkey Lewis PJ, Lu WY, Kikuta J, Kawai H, Yamagiwa S, Forbes SJ, Ishii M, Terai S

Stem cells translational medicine 8 ( 3 ) 271 - 284 2018年11月

高齢者消化器疾患に対する治療方針高齢者の術後再建腸管に対するERCPの検討

水澤健, 五十嵐聡, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 63回 47 - 47 2018年11月

腹部大動脈瘤増大により初めての腸閉塞をきたした腸回転異常症の高齢者の1例

村松夏季, 土屋敦紀, 小田知友美, 木村淳史, 保坂和徳, 木村成宏, 冨永顕太郎, 林和直, 寺井崇二

日本消化器病学会甲信越支部例会抄録集 63回 74 - 74 2018年11月

画像診断の新しいモダリティを用いた診断 MRエラストグラフィーを用いたリスクに応じた肝細胞癌及び門脈大循環シャントのマネージメントの確立に向けて

薛徹, 土屋淳紀, 寺井崇二

肝臓 59 ( Suppl.3 ) A850 - A850 2018年11月

原発巣とは真逆なMRI T2所見を呈したぶどう膜悪性黒色腫の多発肝転移の1例

薛徹, 土屋淳紀, 寺井崇二

肝臓 59 ( Suppl.3 ) A893 - A893 2018年11月

ダブルバルーン内視鏡で診断に至った消化管重複症の成人例

丹羽佑輔, 上村顕也, 小林隆昌, 高橋一也, 冨永顕太郎, 河久順志, 阿部聡司, 川合弘一, 横山純二, 杉野英明, 梅津哉, 寺井崇二

日本消化器病学会甲信越支部例会・日本消化器内視鏡学会甲信越支部例会抄録集 63回・85回 59 - 59 2018年11月

肝疾患と臓器相関肝疾患における自律神経による臓器間ネットワークの関与

上村顕也, 名古屋拓郎, 寺井崇二

肝臓 59 ( Suppl.3 ) A862 - A862 2018年11月

Green epithelium revealed by narrow-band imaging (NBI): a feature for practical assessment of extent of gastric cancer after H. pylori eradication. 査読

Yagi K, Nagayama I, Hoshi T, Abe S, Morita SI, Suda T, Hasegawa G, Sato YI, Terai S

Endoscopy international open 6 ( 11 ) E1289 - E1295 2018年11月

Usefulness of Capsule Endoscopy and Double-balloon Enteroscopy for the Diagnosis of Multiple Carcinoid Tumors in the Small Intestine: Case Reports and a Literature Review. 査読

Tominaga K, Kamimura K, Yokoyama J, Terai S

Internal medicine (Tokyo, Japan) 58 ( 5 ) 655 - 659 2018年10月

Gene therapy for pancreatic diseases: Current status 査読

Kamimura, K., Yokoo, T., Terai, S.

International Journal of Molecular Sciences 19 ( 11 ) 2018年10月

超高齢者における肝硬変診療査読

上村顕也, 坂牧僚, 木村成広, 薛徹, 上村博輝, 横尾健, 阿部聡司, 寺井崇二

消化器・肝臓内科 4 ( 4 ) 344 - 347 2018年10月

フレイルとサルコペニアについて進行消化器癌における体組成と予後との関連

川合弘一, 小林隆昌, 中野応央樹, 五十嵐聡, 河久順志, 阿部聡司, 上村博輝, 坂牧僚, 林和直, 上村顕也, 土屋淳紀, 高村昌昭, 寺井崇二

新潟医学会雑誌 132 ( 10 ) 350 - 352 2018年10月

超音波内視鏡における音速補正モードの有用性

林和直, 五十嵐聡, 河久順志, 高橋一也, 冨永顕太郎, 水野研一, 橋本哲, 横山純二, 山際訓, 寺井崇二

Gastroenterological Endoscopy 60 ( Suppl.2 ) 2110 - 2110 2018年10月

ステロイド使用例における胆管結石治療の現状

五十嵐聡, 林和直, 河久順志, 冨永顕太郎, 高橋一也, 水野研一, 橋本哲, 横山純二, 山際訓, 寺井崇二

Gastroenterological Endoscopy 60 ( Suppl.2 ) 2086 - 2086 2018年10月

重篤な基礎疾患を持たないサイトメガロウイルス小腸炎の特徴と小腸内視鏡の有用性

横山純二, 冨永顕太郎, 寺井崇二

日本消化器病学会雑誌 115 ( 臨増大会 ) A760 - A760 2018年10月

炎症性腸疾患患者における血清IgAの検討

冨永顕太郎, 横山純二, 寺井崇二

Gastroenterological Endoscopy 60 ( Suppl.2 ) 2121 - 2121 2018年10月

NASHモデルマウスにおける自律神経系を介した消化管ホルモンの関与

名古屋拓郎, 上村顕也, 井上良介, 酒井規裕, 後藤諒, 高昌良, 丹羽佑輔, 坂牧僚, 中村由香, 上野将紀, 寺井崇二

日本消化器病学会雑誌 115 ( 臨増大会 ) A732 - A732 2018年10月

Peroral cholangioscopy of nivolumab-related (induced) ulcerative cholangitis in a patient with non-small cell lung cancer 査読

Kuraoka, N., Hara, K., Terai, S., Yatabe, Y., Horio, Y.

Endoscopy 50 ( 9 ) E259 - E261 2018年9月

Listeria meningitis during infliximab-based treatment for ulcerative colitis 査読

Tsuchiya, A., Terai, S.

Internal Medicine 57 ( 17 ) 2603 - 2603 2018年9月

Disappearance of multiple pancreatic cysts after prednisolone treatment in a patient with autoimmune pancreatitis 査読

Kohisa, J., Tsuchiya, A., Ikemi, M., Terai, S.

Clinical Case Reports 6 ( 9 ) 1898 - 1900 2018年9月

マウス肝線維化進展予防薬の探索及び効果の検証

酒井規裕, 上村顕也, 後藤諒, 小川光平, 坂牧僚, 阿部聡司, 榎本初音, 立木秀尚, 寺井崇二

肝臓 59 ( Suppl.2 ) A723 - A723 2018年9月

消化管疾患と肝疾患の関連-消化管・肝臓間の相互の影響- 自律神経線維による肝,脳,腸の臓器間ネットワークを介した肝切除後の肝再生メカニズムの検討

上村顕也, 寺井崇二

肝臓 59 ( Suppl.2 ) A609 - A609 2018年9月

Diagnosis and management of fibromuscular dysplasia and segmental arterial mediolysis in gastroenterology field: A mini-review. 査読国際誌

Ko M, Kamimura K, Ogawa K, Tominaga K, Sakamaki A, Kamimura H, Abe S, Mizuno K, Terai S

World journal of gastroenterology 24 ( 32 ) 3637 - 3649 2018年8月

Potential role of extracellular vesicle-mediated antigen presentation in Helicobacter pylori hypersensitivity during eradication therapy. 査読国際誌

Takamasa Ito, Takashi Shiromizu, Shunsuke Ohnishi, Shotaro Suzuki, Katsuhiro Mabe, Akito Hasegawa, Hideyuki Ujiie, Yasuyuki Fujita, Yuichi Sato, Shuji Terai, Mototsugu Kato, Masahiro Asaka, Takeshi Tomonaga, Hiroshi Shimizu, Riichiro Abe

The Journal of allergy and clinical immunology 142 ( 2 ) 672 - 676 2018年8月

Gastric Cavernous Hemangioma Resected by Endoscopic Submucosal Dissection. 査読

Watanabe Y, Takahashi K, Yokoyama J, Terai S

Internal medicine (Tokyo, Japan) 57 ( 15 ) 2269 - 2270 2018年8月

The Value of 18F-FDG PET in the Diagnosis of Intertrabecular Vertebral Metastasis in a Small Cell Lung Cancer Patient with a High Serum CEA Level. 査読

Morita S, Suda T, Oda C, Kobayashi M, Hoshi T, Kanefuji T, Yagi K, Hasegawa G, Terai S

Internal medicine (Tokyo, Japan) 58 ( 3 ) 415 - 418 2018年8月

Successful treatment of aortic dissection during sorafenib therapy for hepatocellular carcinoma. 査読国際誌

Tsuchiya A, Ogawa M, Watanabe Y, Kimura N, Hayashi K, Suda T, Terai S

Clinical case reports 6 ( 8 ) 1643 - 1644 2018年8月

Rapidly declining skeletal muscle mass predicts poor prognosis of hepatocellular carcinoma treated with transcatheter intra-arterial therapies. 査読国際誌

Takamasa Kobayashi, Hirokazu Kawai, Oki Nakano, Satoshi Abe, Hiroteru Kamimura, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Satoshi Yamagiwa, Shuji Terai

BMC cancer 18 ( 1 ) 756 - 756 2018年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The impact of sarcopenia on the prognosis of patients with hepatocellular carcinoma (HCC) who receive transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, remains unclear. We investigated the prognostic value of skeletal muscle loss (SML) stratified by cutoffs for sarcopenia and rate of change in skeletal muscle mass over 6 months. METHODS: We retrospectively evaluated 102 patients with HCC treated with transcatheter intra-arterial therapies between 2005 and 2015. Computed tomography images of the third lumbar vertebra (L3) were analyzed to obtain the skeletal muscle area normalized for the height squared, defined as the skeletal muscle index at L3 (L3 SMI), before and 6 months after treatment. Low or high SMI was defined using cutoff values of 42 cm2/m2 in men and 38 cm2/m2 in women. The rate of change in skeletal muscle mass (ΔL3 SMI) over 6 months was calculated. Overall survival (OS) was compared in groups classified by baseline L3 SMI and ΔL3 SMI; prognostic significance was assessed with univariate and multivariate analyses, using Cox proportional hazards models. RESULTS: OS did not differ significantly between groups with low (n = 31) and high (n = 71) SMI at baseline (P = 0.172), but OS was significantly poorer in patients with SML (n = 41), defined as ΔL3 SMI < - 4.6% over 6 months than in those without SML (n = 61, P = 0.018). On multivariate analysis, SML (hazard ratio [HR], 1.675; 95% confidence interval [CI], 1.031-2.721; P = 0.037), serum alpha-fetoprotein ≥20 ng/mL (HR, 2.550; 95% CI, 1.440-4.515; P = 0.001), and maximum tumor diameter ≥ 30 mm (HR, 1.925; 95% CI, 1.166-3.179; P = 0.010) were independent predictors of poor OS. Baseline L3 SMI was not significantly associated with OS (HR, 1.405; 95% CI, 0.861-2.293; P = 0.174). CONCLUSIONS: ΔL3 SMI was an independent prognostic factor in patients with HCC treated with transcatheter intra-arterial therapies. Further study is required to reveal whether prevention of skeletal muscle depletion might be a new therapeutic strategy to contribute to improved clinical outcomes in patients with HCC.

DOI： 10.1186/s12885-018-4673-2

Management decision based on lymphovascular involvement leads to favorable outcomes after endoscopic treatment of esophageal squamous cell carcinoma 査読

Kazuya Takahashi, Satoru Hashimoto, Ken-Ichi Mizuno, Takamasa Kobayashi, Kentaro Tominaga, Hiroki Sato, Junji Kohisa, Satoshi Ikarashi, Kazunao Hayashi, Manabu Takeuchi, Junji Yokoyama, Hirokazu Kawai, Yuichi Sato, Masaaki Kobayashi, Shuji Terai

Endoscopy 50 ( 7 ) 662 - 670 2018年7月

A case of inferior vena cava thrombosis caused by compression due to growing giant liver cyst. 査読

Kimura N, Tsuchiya A, Ogawa M, Watanabe Y, Hayashi K, Yokoyama J, Umezu H, Terai S

Clinical journal of gastroenterology 12 ( 1 ) 71 - 75 2018年7月

Anti-Programmed Cell Death-1 Immunotherapy-Related Secondary Sclerosing Cholangitis. 査読国際誌

Ogawa K, Kamimura K, Terai S

Hepatology (Baltimore, Md.) 69 ( 2 ) 914 - 916 2018年7月

Renal Impairment in Chronic Hepatitis B: A Review. 査読国際誌

Hiroteru Kamimura, Toru Setsu, Naruhiro Kimura, Takeshi Yokoo, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Satoshi Yamagiwa, Shuji Terai

Diseases (Basel, Switzerland) 6 ( 2 ) 2018年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

The liver plays a key role in the metabolism of proteins. Liver dysfunction affects many organs because it communicates with the spleen and all digestive organs through the portal vein. Additionally, the kidney is an organ that is closely related to the liver and is involved in liver diseases. Glomerulonephritis is an important extrahepatic manifestation of chronic hepatitis B virus (HBV) infection. Nucleos(t)ide analog (NA) therapy effectively suppresses HBV replication by inhibiting HBV polymerase, thus decreasing the levels of serum HBV-DNA and delaying the progression of cirrhosis. Although NA therapy is recommended for all patients with chronic HBV infection, regardless of the level of renal dysfunction, there is limited information on NA use in patients with chronic kidney disease. In addition, in patients with end-stage liver cirrhosis, hepatorenal syndrome can be fatal. Hence, we should take into account the stage of impaired renal function in patients with cirrhosis. The aims of this article are to review the epidemiology, clinical presentation, treatment, and prevention of HBV-associated nephropathy.

DOI： 10.3390/diseases6020052

Eosinophilic Esophageal Myositis (EoEM) Causes Jackhammer Esophagus, Rarely Posing a Problem in the Differential Diagnosis of Eosinophilic Esophagitis 査読

Hiroki Sato, Shuji Terai

American Journal of Gastroenterology 113 ( 8 ) 1 - 2 2018年6月

Reply to the letter to the editor: Lymph node metastasis of adenocarcinoma and different definitions of sm1 cancer in the esophagus 査読

Ryu Ishihara, Tsuneo Oyama, Seiichiro Abe, Hiroaki Takahashi, Hiroyuki Ono, Junko Fujisaki, Mitsuru Kaise, Kenichi Goda, Kenro Kawada, Tomoyuki Koike, Manabu Takeuchi, Rie Matsuda, Dai Hirasawa, Masayoshi Yamada, Junichi Kodaira, Masaki Tanaka, Masami Omae, Akira Matsui, Takashi Kanesaka, Akiko Takahashi, Shinichi Hirooka, Masahiro Saito, Yosuke Tsuji, Yuki Maeda, Hiroharu Yamashita, Ichiro Oda, Yasuhiko Tomita, Takashi Matsunaga, Shuji Terai, Soji Ozawa, Tatsuyuki Kawano, Yasuyuki Seto

Journal of Gastroenterology 53 ( 6 ) 804 - 805 2018年6月

Nationwide survey for acute liver failure and late-onset hepatic failure in Japan 査読

Masamitsu Nakao, Nobuaki Nakayama, Yoshihito Uchida, Tomoaki Tomiya, Akio Ido, Isao Sakaida, Osamu Yokosuka, Yasuhiro Takikawa, Kazuaki Inoue, Takuya Genda, Masahito Shimizu, Shuji Terai, Hirohito Tsubouchi, Hajime Takikawa, Satoshi Mochida

Journal of Gastroenterology 53 ( 6 ) 752 - 769 2018年6月

IS ENDOSCOPIC SUBMUCOSAL DISSECTION VALUABLE FOR ELDERLY PATIENTS WITH SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA? 査読

Hashimoto Satoru, Mizuno Kenichi, Takahashi Kazuya, Sato Hiroki, Tominaga Kentaro, Kohisa Junji, Ikarashi Satoshi, Hayashi Kazunao, Yokoyama Junji, Terai Shuji

GASTROINTESTINAL ENDOSCOPY 87 ( 6 ) AB287 - AB287 2018年6月

Persistent reduction of mucosal-associated invariant T cells in primary biliary cholangitis. 査読国際誌

Toru Setsu, Satoshi Yamagiwa, Kentaro Tominaga, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shuji Terai

Journal of gastroenterology and hepatology 33 ( 6 ) 1286 - 1294 2018年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIM: Mucosal-associated invariant T (MAIT) cells constitute a novel subset of innate-like T lymphocytes characterized by a semi-invariant T-cell receptor repertoire capable of recognizing bacterial products. Considering the abundance of MAIT cells in the liver and the possible association between bacterial infections and primary biliary cholangitis (PBC), we aimed to analyze the involvement of MAIT cells in the immunopathogenesis of PBC. METHODS: Peripheral blood and liver biopsy specimens were collected from 25 patients with PBC and 19 patients with chronic viral hepatitis. Surgically removed liver tissues distant from tumors in patients with metastatic liver tumors were used as controls. Mononuclear cells were separated using Ficoll gradient, and the expression of various markers was investigated by flow cytometry. Cytokine production was investigated using blood MAIT cells after stimulation by anti-CD3/CD28-coupled beads with/without interleukin-7 (IL-7). RESULTS: Mucosal-associated invariant T cells were significantly reduced in both the blood and liver of PBC patients compared with those in controls. MAIT cells in the blood of PBC patients expressed significantly lower levels of activation markers and IL-7 receptor. Moreover, MAIT cells in the blood of PBC patients showed impaired production of cytokines, especially tumor necrosis factor alpha, after in vitro stimulation with IL-7. Interestingly, even after biochemical responses were achieved by ursodeoxycholic acid treatment, the frequencies of MAIT cells did not fully recover to normal levels. CONCLUSIONS: These findings suggested that MAIT cells were activated, exhausted, and persistently depleted in PBC patients even after ursodeoxycholic acid treatment, possibly as a consequence of persistent liver inflammation.

DOI： 10.1111/jgh.14076

フランシーン形状針を用いたEUS-FNAの有用性についての検討

ENDOSCOPIC MANAGEMENT OF UNRESECTABLE MALIGNANT HILAR STRICTURES USING THREADED INSIDE STENTS VERSUS METALLIC STENTS 査読

Hayashi Kazunao, Ikarashi Satoshi, Kohisa Junji, Takahashi Kazuya, Tominaga Kentaro, Mizuno Ken-ichi, Hashimoto Satoru, Yokoyama Junji, Yamagiwa Satoshi, Terai Shuji

GASTROINTESTINAL ENDOSCOPY 87 ( 6 ) AB208 - AB208 2018年6月

IS ENDOSCOPIC SUBMUCOSAL DISSECTION A FEASIBLE TREATMENT FOR ESOPHAGOGASTRIC JUNCTION CANCER? 査読

Takahashi Kazuya, Hashimoto Satoru, Mizuno Kenichi, Sato Hiroki, Tominaga Kentaro, Kohisa Junji, Ikarashi Satoshi, Hayashi Kazunao, Yokoyama Junji, Terai Shuji

GASTROINTESTINAL ENDOSCOPY 87 ( 6 ) AB396 - AB397 2018年6月

SAFETY AND EFFICACY OF PROPOFOL-BASED SEDATION FOR BALLOON ENTEROSCOPE-ASSISTED ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN ELDERLY PATIENTS 査読

Kohisa Junji, Ikarashi Satoshi, Hayashi Kazunao, Takahashi Kazuya, Tominaga Kentaro, Mizuno Kenichi, Hashimoto Satoru, Yokoyama Junji, Yamagiwa Satoshi, Terai Shuji

GASTROINTESTINAL ENDOSCOPY 87 ( 6 ) AB229 - AB229 2018年6月

河久順志, 林和直, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 34 ( 1 ) 73 - 73 2018年6月

How do you treat this diversion ileitis and pouchitis? 査読

Kentaro Tominaga, Atsunori Tsuchiya, Junji Yokoyama, Shuji Terai

Gut 2018年5月

Efficacy and safety of rifaximin in Japanese patients with hepatic encephalopathy: A phase II/III, multicenter, randomized, evaluator-blinded, active-controlled trial and a phase III, multicenter, open trial 査読

Kazuyuki Suzuki, Ryujin Endo, Yasuhiro Takikawa, Fuminori Moriyasu, Yutaka Aoyagi, Hisataka Moriwaki, Shuji Terai, Isao Sakaida, Yoshiyuki Sakai, Shuhei Nishiguchi, Toru Ishikawa, Hitoshi Takagi, Atsushi Naganuma, Takuya Genda, Takafumi Ichida, Koichi Takaguchi, Katsuhiko Miyazawa, Kiwamu Okita

Hepatology Research 48 ( 6 ) 411 - 423 2018年5月

Cost-effectiveness of combined serum anti-Helicobacter pylori IgG antibody and serum pepsinogen concentrations for screening for gastric cancer risk in Japan 査読

Shota Saito, Motoi Azumi, Yusuke Muneoka, Katsuhiko Nishino, Takashi Ishikawa, Yuichi Sato, Shuji Terai, Kouhei Akazawa

European Journal of Health Economics 19 ( 4 ) 545 - 555 2018年5月

Diversion colitis and pouchitis: A mini-review 査読

Kentaro Tominaga, Kenya Kamimura, Kazuya Takahashi, Junji Yokoyama, Satoshi Yamagiwa, Shuji Terai

World Journal of Gastroenterology 24 ( 16 ) 1734 - 1747 2018年4月

Endoscopic ultrasound-guided transmural drainage for subphrenic abscess: Report of two cases and a literature review 査読

Shinichi Morita, Kenya Kamimura, Takeshi Suda, Chiyumi Oda, Takahiro Hoshi, Tsutomu Kanefuji, Kazuyoshi Yagi, Shuji Terai

BMC Gastroenterology 18 ( 1 ) 55 2018年4月

Clinical outcome of hepatocellular carcinoma can be predicted by the expression of hepatic progenitor cell markers and serum tumour markers. 査読国際誌

Satoshi Seino, Atsunori Tsuchiya, Yusuke Watanabe, Yuzo Kawata, Yuichi Kojima, Shunzo Ikarashi, Hiroyuki Yanai, Koji Nakamura, Daisuke Kumaki, Masaaki Hirano, Kazuhiro Funakoshi, Takashi Aono, Takeshi Sakai, Jun Sakata, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Toshifumi Wakai, Shuji Terai

Oncotarget 9 ( 31 ) 21844 - 21860 2018年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The high heterogeneity of hepatocellular carcinomas (HCCs) complicates stratification of HCC patients for treatment. Therefore, it is necessary to establish a comprehensive panel of HCC biomarkers related to tumour behaviour and cancer prognosis. Resected HCCs from 251 patients were stained for hepatic progenitor cell (HPC) markers epithelial cell adhesion molecule (EpCAM), neural cell adhesion molecule (NCAM), delta-like 1 homolog (DLK1), and cytokeratin 19 (CK19). Staining patterns were analysed for their prognostic association with relapse-free survival and overall survival. α-Fetoprotein (AFP), lectin-reactive α-fetoprotein (AFP-L3), and des-γ-carboxy prothrombin (DCP) were assessed as indicators of HPC protein expression. Expression pattern of HPC markers correlated with tumour malignancy indicated by high AFP/AFP-L3 serum levels, more frequent vascular invasion, and poorer tumour differentiation. EpCAM expression, DCP ≥300 mAU/ml, age ≥60, and Child-Pugh score grade B or C were independent prognostic factors of poor outcome and were used in a new scoring system for HCC prognosis after operation. Expression of two or more HPC markers was a significant predictor of poor HCC outcome and serum levels of AFP/AFP-L3 correlated with the expression of HPC proteins. Our study paved the way for further elucidation of the association among HPC markers, serum tumour markers, and HCC clinical outcome for precision medicine.

DOI： 10.18632/oncotarget.25074

Autonomic nervous system network and liver regeneration 査読

Kenya Kamimura, Ryosuke Inoue, Takuro Nagoya, Norihiro Sakai, Ryo Goto, Masayoshi Ko, Yusuke Niwa, Shuji Terai

World Journal of Gastroenterology 24 ( 15 ) 1616 - 1621 2018年4月

A case of Behçet's disease with various gastrointestinal findings. 査読

Tominaga K, Kamimura K, Takahashi K, Yokoyama J, Terai S

Clinical journal of gastroenterology 11 ( 5 ) 1 - 5 2018年4月

Efficacy of EUS for detection of a buried fish bone in the esophagus. 査読

Kohisa J, Mizuno KI, Takahashi K, Yokoyama J, Terai S

VideoGIE : an official video journal of the American Society for Gastrointestinal Endoscopy 3 ( 4 ) 125 - 126 2018年4月

A clinical study of peroral endoscopic myotomy reveals that impaired lower esophageal sphincter relaxation in Achalasia is not only defined by high-resolution manometry 査読

Hiroki Sato, Kazuya Takahashi, Ken-Ichi Mizuno, Satoru Hashimoto, Junji Yokoyama, Shuji Terai

PLoS ONE 13 ( 4 ) e0195423 2018年4月

Esophageal motility disorders: new perspectives from high-resolution manometry and histopathology 査読

Hiroki Sato, Kazuya Takahashi, Ken-ichi Mizuno, Satoru Hashimoto, Junji Yokoyama, Go Hasegawa, Shuji Terai

Journal of Gastroenterology 53 ( 4 ) 484 - 493 2018年4月

Ombitasvir–Paritaprevir–Ritonavir Therapy in a Kidney Transplant Recipient With Chronic Hepatitis C Virus Genotype 1 Infection: A Case Report on the Importance of Considering Drug–Drug Interactions and Monitoring Cyclosporine Levels 査読

S. Takeuchi, M. Takamura, T. Yoshida, K. Takahashi, K. Hayashi, S. Hashimoto, S. Yamagiwa, M. Tasaki, Y. Nakagawa, K. Saito, Y. Tanabe, Y. Tomita, S. Terai

Transplantation Proceedings 50 ( 3 ) 884 - 886 2018年4月

当院における非切除悪性肝門部胆管狭窄に対する内視鏡的ステント留置術の現状と課題

林和直, 五十嵐聡, 河久順志, 水野研一, 橋本哲, 横山純二, 山際訓, 寺井崇二

Gastroenterological Endoscopy 60 ( Suppl.1 ) 797 - 797 2018年4月

Bleeding from a Small-Intestinal Ulcer Associated with Chronic Hepatitis C. 査読国際誌

Hiroteru Kamimura, Satoshi Yamagiwa, Iwasaki Tomohiro, Wataru Higuchi, Norio Ogata, Atsunori Tsuchiya, Kenya Kamimura, Masaaki Takamura, Hirokazu Kawai, Shuji Terai

The American journal of case reports 19 234 - 237 2018年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND Hepatitis C virus infection is probably the most common chronic viral infection and affects an estimated 180 million people worldwide. Extrahepatic manifestations are well recognized among patients with chronic HCV infection. CASE REPORT We report a case of melena occurring in a 69-year-old Japanese man who had been diagnosed with CHC and who was treated with antiviral therapy. CONCLUSIONS Finally, he was diagnosed with multiple small intestine ulcers in a short time. We herein report the case of HCV with rapidly developing small intestine ulcers.

Full-layer mucosal histology in achalasia: Histological epithelial wave is characteristic in "pinstripe pattern"-positive achalasia. 査読

Proposed diagnostic criteria for acute-on-chronic liver failure in Japan 査読

Satoshi Mochida, Nobuaki Nakayama, Akio Ido, Kazuaki Inoue, Takuya Genda, Yasuhiro Takikawa, Isao Sakaida, Shuji Terai, Osamu Yokosuka, Masahito Shimizu, Hajime Takikawa

Hepatology Research 48 ( 4 ) 219 - 224 2018年3月

Effect of a neural relay on liver regeneration in mice: activation of serotonin release from the gastrointestinal tract 査読

Ryosuke Inoue, Kenya Kamimura, Takuro Nagoya, Norihiro Sakai, Takeshi Yokoo, Ryo Goto, Kohei Ogawa, Yoko Shinagawa-Kobayashi, Yukari Watanabe-Mori, Akira Sakamaki, Satoshi Abe, Hiroteru Kamimura, Norio Miyamura, Hiroshi Nishina, Shuji Terai

FEBS Open Bio 8 ( 3 ) 449 - 460 2018年3月

A multicenter pilot survey to clarify the clinical features of patients with acute-on-chronic liver failure in Japan 査読

Nobuaki Nakayama, Hayato Uemura, Yoshihito Uchida, Tomoaki Tomiya, Akio Ido, Kazuaki Inoue, Takuya Genda, Yasuhiro Takikawa, Isao Sakaida, Shuji Terai, Osamu Yokosuka, Masahito Shimizu, Hajime Takikawa, Satoshi Mochida

Hepatology Research 48 ( 4 ) 303 - 312 2018年3月

Gastric Metastasis From Uveal Melanoma. 査読国際誌

Morita S, Suda T, Terai S

Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association 17 ( 7 ) A20 2018年3月

急性膵炎診療Up-to-date 重症急性膵炎におけるwalled-off necrosis合併のリスク因子に関する多施設共同後方視的研究

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 115 ( 臨増総会 ) A176 - A176 2018年3月

切除不能膵癌における好中球リンパ球比と他の炎症・栄養指標による予後予測能の比較検討

中野応央樹, 川合弘一, 小林隆昌, 河久順志, 五十嵐聡, 林和直, 横山順二, 寺井崇二

日本消化器病学会雑誌 115 ( 臨増総会 ) A373 - A373 2018年3月

Effect of histidine on sorafenib-induced vascular damage: Analysis using novel medaka fish model 査読

Yoko Shinagawa-Kobayashi, Kenya Kamimura, Ryo Goto, Kohei Ogawa, Ryosuke Inoue, Takeshi Yokoo, Norihiro Sakai, Takuro Nagoya, Akira Sakamaki, Satoshi Abe, Soichi Sugitani, Masahiko Yanagi, Koichi Fujisawa, Yoshizu Nozawa, Naoto Koyama, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida, Shuji Terai

Biochemical and Biophysical Research Communications 496 ( 2 ) 556 - 561 2018年2月

A case of panenteritis with massive IgG4-positive plasma cell infiltration developed 26 years after total proctocolectomy for ulcerative colitis 査読

Kentaro Tominaga, Atsunori Tsuchiya, Yutaka Honda, Tatsuya Abe, Junji Yokoyama, Hajime Umezu, Shuji Terai

American Journal of Gastroenterology 113 ( 2 ) 173 2018年2月

Response criteria of tolvaptan for the treatment of hepatic edema 査読

Yasunari Hiramine, Haruki Uojima, Hiroyuki Nakanishi, Akira Hiramatsu, Takuya Iwamoto, Mutsuumi Kimura, Hideto Kawaratani, Shuji Terai, Hitoshi Yoshiji, Hirofumi Uto, Isao Sakaida, Namiki Izumi, Kiwamu Okita, Kazuhiko Koike

Journal of Gastroenterology 53 ( 2 ) 258 - 268 2018年2月

The factors influencing long-term outcomes of stenting for malignant colorectal obstruction in elderly group in community medicine 査読

Michitaka Imai, Kenya Kamimura, Yoshifumi Takahashi, Toshihiro Sato, Osamu Isokawa, Masaki Maruyama, Takamasa Kobayashi, Kazunao Hayashi, Shuji Terai

International Journal of Colorectal Disease 33 ( 2 ) 189 - 197 2018年2月

Possible involvement of chemokine C-C receptor 7−programmed cell death-1+ follicular helper T-cell subset in the pathogenesis of autoimmune hepatitis 査読

Naruhiro Kimura, Satoshi Yamagiwa, Tomoyuki Sugano, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Masaaki Takamura, Shuji Terai

Journal of Gastroenterology and Hepatology (Australia) 33 ( 1 ) 298 - 306 2018年1月

Sato H, Takahashi K, Nakajima N, Hasegawa G, Mizuno K, Hashimoto S, Ikarashi S, Hayashi K, Honda Y, Yokoyama J, Sato Y, Terai S

Neurogastroenterology and motility : the official journal of the European Gastrointestinal Motility Society 30 ( 1 ) e13168 - e13168 2018年1月

臨床応用可能な肝臓選択的核酸医薬送達法の確立招待査読

上村顕也, 横尾健, 寺井崇二

BIO Clinica 33 ( 1 ) 34 - 38 2018年1月

Opinion

Terai, S.

Drug Delivery System 33 ( 5 ) 2018年

Gastrointestinal: A rare case of concomitant type III achalasia and chronic idiopathic intestinal pseudo-obstruction

Sato, H., Abe, H., Nagashima, A., Yokoyama, J., Terai, S.

Journal of Gastroenterology and Hepatology (Australia) 33 ( 3 ) 559 - 559 2018年

Exploration for cell sources for liver regenerative medicine: “CLiP” as a dawn of cell transplantation therapy

Hosaka, K., Katsuda, T., Terai, S., Ochiya, T.

Stem Cells and Cancer in Hepatology: From the Essentials to Application 2018年

Successful closure with over-the-scope clip of an iatrogenic duodenal perforation due to endoscopic ultrasonography

Morita, S., Suda, T., Oda, C., Hoshi, T., Kanefuji, T., Yagi, K., Terai, S.

Endoscopic Forum for Digestive Disease 34 ( 1 ) 2018年

Effective prevention of sorafenib-induced hand-foot syndrome by dried-bonito broth. 査読国際誌

Kenya Kamimura, Yoko Shinagawa-Kobayashi, Ryo Goto, Kohei Ogawa, Takeshi Yokoo, Akira Sakamaki, Satoshi Abe, Hiroteru Kamimura, Takeshi Suda, Hiroshi Baba, Takayuki Tanaka, Yoshizu Nozawa, Naoto Koyama, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Yutaka Aoyagi, Shuji Terai

Cancer management and research 10 805 - 813 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Sorafenib (SOR) is a molecular medicine that prolongs the survival of patients with hepatocellular carcinoma (HCC). Therefore, the management of side effects is essential for the longer period of continuous medication. Among the various side effects, hand-foot syndrome (HFS) is the most common, occurring in 30%-50% of patients, and often results in discontinuation of the SOR medication. However, its mechanism has not been clarified, and no effective prevention method has been reported for the symptoms. Therefore, this study aimed to analyze its mechanism and to develop an effective prevention regimen for the symptoms. Materials and methods: To assess the mechanism of SOR-induced HFS, the peripheral blood flow in the hand and foot was carefully monitored by Doppler ultrasound, thermography, and laser speckle flowgraphy in the cases treated with SOR and its contribution was assessed. Then, the effect of dried-bonito broth (DBB), which was reported to improve peripheral blood flow, on the prevention of the symptom was examined by monitoring its occurrence and the peripheral blood flow. Results: A total of 25 patients were enrolled in this study. In all, eight patients developed HFS, and all cases showed a significant decrease in the peripheral blood flow. DBB contributed to an increase in the flow (p = 0.009) and significantly decreased occurrence of HFS (p = 0.005) than control. Multivariable analysis showed that the ingestion of DBB is a significant independent contributor to HFS-free survival period (p = 0.035). Conclusion: The mechanism of SOR-induced HFS involves a decrease in the peripheral blood flow, and the ingestion of DBB effectively prevents the development of the syndrome by maintaining the flow.

DOI： 10.2147/CMAR.S159370

Antireflux Metal Stent for Initial Treatment of Malignant Distal Biliary Obstruction 査読

Shinichi Morita, Yasuaki Arai, Shunsuke Sugawara, Miyuki Sone, Yasunari Sakamoto, Takuji Okusaka, Shigetaka Yoshinaga, Yutaka Saito, Shuji Terai

Gastroenterology Research and Practice 2018 3805173 2018年

A Case of Enteritis Induced by Nivolumab 査読

Takamasa Kobayashi, Kazuya Takahashi, Shuji Terai

Clinical Gastroenterology and Hepatology 2018年

Specific gastric blood vessels in sinistral portal hypertension 査読

Hiroteru Kamimura, Toru Ishikawa, Noriko Ishihara, Shuji Terai

Internal Medicine 57 ( 7 ) 1053 - 1054 2018年

Prognostic value of subcutaneous adipose tissue volume in hepatocellular carcinoma treated with transcatheter intra-arterial therapy. 査読国際誌

Takamasa Kobayashi, Hirokazu Kawai, Oki Nakano, Satoshi Abe, Hiroteru Kamimura, Akira Sakamaki, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Satoshi Yamagiwa, Shuji Terai

Cancer management and research 10 2231 - 2239 2018年

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Prognosis of patients with hepatocellular carcinoma (HCC) who undergo transcatheter intra-arterial therapies, including transcatheter arterial chemoembolization and transcatheter arterial infusion chemotherapy, is affected by many clinical factors including liver function and tumor progression. However, the effect of body composition such as skeletal muscle and visceral and subcutaneous adipose tissues (VAT and SAT, respectively) on the prognosis of these patients remains unclear. We investigated the prognostic value of body composition in HCC patients treated with transcatheter intra-arterial therapies. Patients and methods: This study retrospectively evaluated 100 HCC patients treated with transcatheter intra-arterial therapies between 2005 and 2015. Areas of skeletal muscle, VAT, and SAT were measured on computed tomography images at third lumbar vertebra level and normalized by the height squared to calculate the skeletal muscle index, VAT index, and SAT index (SATI). The visceral to subcutaneous adipose tissue area ratio was also calculated. Overall survival (OS) was compared between high- and low-index groups for each body composition. Furthermore, prognostic significance was assessed by univariate and multivariate analyses using Cox proportional hazards models. Results: Among the body composition indexes, only SATI could significantly differentiate OS (p=0.012). Multivariate analysis showed that SATI (low- vs. high-SATI: HR, 2.065; 95% CI, 1.187-3.593; p=0.010), serum albumin (<3.5 vs. ≥3.5 g/dL; HR, 2.007; 95% CI, 1.037-3.886; p=0.039), serum alpha-fetoprotein (<20 vs. ≥20 ng/mL; HR, 0.311; 95% CI, 0.179-0.540; p<0.001), and Modified Response Evaluation Criteria in Solid Tumors assessment (complete response+partial response+stable disease vs. progressive disease; HR, 0.392; 95% CI, 0.221-0.696; p=0.001) were indicated as independent prognostic factors for OS. Conclusion: High SAT volume is associated with better survival outcomes in HCC patients treated with transcatheter intra-arterial therapies. Elucidation of the mechanisms regulating SAT volume may offer a new therapeutic strategy for these patients.

DOI： 10.2147/CMAR.S167417

Dynamics of basal lamina fenestrations in the rat intestinal villous epithelium in response to dietary conditions 査読

Rie Azumi, Keisuke Morita, Yusuke Mizutani, Manabu Hayatsu, Shuji Terai, Tatsuo Ushiki

Biomedical Research (Japan) 39 ( 2 ) 65 - 74 2018年

A rare case of concomitant type III achalasia and chronic idiopathic intestinal pseudo-obstruction. 査読

Sato H, Abe H, Nagashima A, Yokoyama J, Terai S

J Gastroenterol Hepatol 33 ( 3 ) 559 2018年

Jackhammer esophagus accompanied by esophageal intramural pseudodiverticulosis 査読

Kazuya Takahashi, Satoshi Ikarashi, Junji Yokoyama, Shuji Terai

Internal Medicine 57 ( 7 ) 1051 - 1052 2018年

Gastric Cancer after H. pylori Eradication therapy develops in the Intermediate Zone. Relationship to Spasmolytic Polypeptide-Expressing Metaplasia 査読

Kazuyoshi Yagi, Itsuo Nagayama, Takahiro Hoshi, Satoshi Abe, Shinichi Morita, Takeshi Suda, Yu-ichi Sato, Shuji Terai

Open Access J Surg 9 1 - 6 2018年

Eosinophilic esophagitis in Japanese patients: A mild and slow-progressing disorder. 査読国際誌

Hiroki Sato, Terasu Honma, Yujiro Nozawa, Takashi Owaki, Michitaka Imai, Tomoe Sano, Akito Iwanaga, Keiichi Seki, Toru Ishikawa, Toshiaki Yoshida, Shuji Terai

PloS one 13 ( 11 ) e0206621 2018年

記述言語：英語

BACKGROUND AND AIM: Awareness of eosinophilic esophagitis (EoE) has gradually increased in Japan, therefore the characteristics of this disease in the Japanese patient population need to be elucidated. This study aimed to investigate the features of EoE in the Japanese population. METHODS: During a 2-year period, all gastrointestinal endoscopies were performed with maximum attention being paid to identify EoE through endoscopic findings. Clinical features and findings were analyzed among this population. RESULTS: Among a total of 8589 patients (general gastrointestinal endoscopy, performed for evaluation of symptoms or disease follow-up: 3669; medical check-up endoscopy, routinely performed in asymptomatic patients: 4920), 17 patients (0.20%) were diagnosed with esophageal eosinophilia (mean age ± standard deviation: 44±11.9 years; 1 female). Only 6 patients with esophageal eosinophilia were diagnosed by general gastrointestinal endoscopy; among them, 3 patients had dysphagia and 3 were asymptomatic. The remaining 11 patients were diagnosed by medical check-up endoscopy. All patients were treated with a proton pump inhibitor (PPI); 5 were diagnosed with EoE and 12 with PPI responsive esophageal eosinophilia. Chronological endoscopy analysis showed that EoE findings could be observed for a mean of 6.1 years prior to diagnosis, and the disease did not significantly progress in severity. CONCLUSIONS: Most Japanese patients with EoE have mild and slowly progressing disease, which can be diagnosed when close attention is paid to the endoscopic findings. Medical check-up endoscopy in Japan could be a great opportunity for the early diagnosis of EoE.

DOI： 10.1371/journal.pone.0206621

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study. 査読

A Case of Pancreatic Schwannoma Diagnosed Preoperatively by Endoscopic Ultrasonography-Guided Fine Needle Aspiration and Treated with Laparoscopic Surgery. 査読国際誌

Hayashi K, Tsuchiya A, Ikarashi S, Takizawa K, Terai S

Journal of pancreatic cancer 4 ( 1 ) 7 - 10 2018年

Effect of Helicobacter pylori eradication on elder cases: Observational study in community-based medicine 査読

Masaki Maruyama, Kenya Kamimura, Ayako Hoshiyama, Koki Hoshiyama, Mari Hoshiyama, Yoshihiro Hoshiyama, Shuji Terai

WORLD JOURNAL OF CLINICAL CASES 5 ( 12 ) 412 - 418 2017年12月

Endoscopic ultrasound-guided fine-needle aspiration for diagnosing a rare extraluminal duodenal gastrointestinal tumor. 査読国際誌

Hayashi K, Kamimura K, Hosaka K, Ikarashi S, Kohisa J, Takahashi K, Tominaga K, Mizuno K, Hashimoto S, Yokoyama J, Yamagiwa S, Takizawa K, Wakai T, Umezu H, Terai S

World journal of gastrointestinal endoscopy 9 ( 12 ) 583 - 589 2017年12月

Efficacy and Safety of Pancreas-Targeted Hydrodynamic Gene Delivery in Rats 査読

Kohei Ogawa, Kenya Kamimura, Yuji Kobayashi, Hiroyuki Abe, Takeshi Yokoo, Norihiro Sakai, Takuro Nagoya, Akira Sakamaki, Satoshi Abe, Kazunao Hayashi, Satoshi Ikarashi, Junji Kohisa, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

MOLECULAR THERAPY-NUCLEIC ACIDS 9 80 - 88 2017年12月

Changes in esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer: a high-resolution manometry study 査読

K. Takahashi, Y. Sato, M. Takeuchi, H. Sato, N. Nakajima, S. Ikarashi, K. Hayashi, K. -I. Mizuno, Y. Honda, S. Hashimoto, J. Yokoyama, S. Terai

DISEASES OF THE ESOPHAGUS 30 ( 11 ) 2017年11月

【臓器間ネットワークからみた肝胆膵の恒常性とその破綻】臓器間ネットワークの破綻による疾患自律神経線維が肝再生に与えるインパクト

上村顕也, 井上良介, 名古屋拓郎, 酒井規裕, 寺井崇二

肝・胆・膵 75 ( 5 ) 967 - 972 2017年11月

Takahashi K, Sato Y, Takeuchi M, Sato H, Nakajima N, Ikarashi S, Hayashi K, Mizuno KI, Honda Y, Hashimoto S, Yokoyama J, Terai S

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus 30 ( 11 ) 1 - 8 2017年11月

Overexpression of a disintegrin and metalloproteinase 21 is associated with motility, metastasis, and poor prognosis in hepatocellular carcinoma 査読

Hiroki Honda, Masaaki Takamura, Satoshi Yamagiwa, Takuya Genda, Ryoko Horigome, Naruhiro Kimura, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Yasunobu Matsuda, Toshifumi Wakai, Yutaka Aoyagi, Shuji Terai

SCIENTIFIC REPORTS 7 ( 1 ) 15485 2017年11月

Intraductal Papillary Neoplasm of the Bile Duct: A Rare Liver Tumor Complicated by Malignancy 査読

Kentaro Tominaga, Kenya Kamimura, Akira Sakamaki, Shuji Terai

HEPATOLOGY 66 ( 5 ) 1695 - 1697 2017年11月

Magnifying image-enhanced endoscopy for collagenous colitis. 査読

Kobayashi M, Hoshi T, Morita SI, Kanefuji T, Suda T, Hasegawa G, Terai S

Endoscopy international open 5 ( 11 ) E1069 - E1073 2017年11月

Live image and mechanistic analysis of Mesenchymal stem cells (MSCs) and induced bone marrow derived macrophages (id-BMMs) combination therapy for liver cirrhosis in mice 査読

Yusuke Watanabe, Atsunori Tsuchiya, Satoshi Seino, Syunzou Ikarashi, Suguru Takeuchi, Takayuki Watanabe, Kenya Kamimura, Masaaki Takamura, Satoshi Yamagiwa, Shuji Terai

HEPATOLOGY 66 76A - 76A 2017年10月

Effectiveness and safety of tolvaptan in liver cirrhosis patients with edema: Interim results of post-marketing surveillance of tolvaptan in liver cirrhosis (START study) 査読

Isao Sakaida, Shuji Terai, Masayuki Kurosaki, Moriyoshi Yasuda, Mitsuru Okada, Kosuke Bando, Yasuhiko Fukuta

HEPATOLOGY RESEARCH 47 ( 11 ) 1137 - 1146 2017年10月

Usefulness of follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis 査読

Naruhiro Kimura, Satoshi Yamagiwa, Ryoko Horigome, Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Shuji Terai

HEPATOLOGY 66 687A - 688A 2017年10月

Persistent reduction of mucosal-associated invariant T cells in primary biliary cholangitis 査読

Toru Setsu, Satoshi Yamagiwa, Naruhiro Kimura, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Shuji Terai

HEPATOLOGY 66 166A - 166A 2017年10月

A Case of Hepatorenal Syndrome and Abdominal Compartment Syndrome with High Renal Congestion. 査読国際誌

Hiroteru Kamimura, Takayuki Watanabe, Tomoyuki Sugano, Nao Nakajima, Junji Yokoyama, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Takashi Kato, Gen Watanabe, Satoshi Yamagiwa, Shuji Terai

The American journal of case reports 18 1000 - 1004 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND Hepatorenal syndrome (HRS) is a reversible renal impairment that occurs in patients with acute liver failure and advanced liver cirrhosis. HRS is due to a renal vasoconstriction that results from extreme vasodilatation. It is therefore a functional disorder, not associated with structural kidney damage. On the other hand, end-stage liver diseases are often complicated by massive ascites. Massive ascites may cause abdominal compartment syndrome (ACS), which includes impairment of renal blood flow, but there are no reports indicating that kidney lesions caused by ACS may pathologically contribute to end-stage liver diseases. CASE REPORT A 40-year-old man with acute liver failure was admitted to our hospital. He was diagnosed with type 1 HRS and showed ACS at the same time. He died 30 days after admission. There were signs of congestion in the kidneys upon dissection and advanced erythroid fullness in the renal tubules. CONCLUSIONS We report an autopsy case with HRS and ACS diagnosed with a clinical and histopathological consideration of liver and kidney. Further clinical studies are needed to improve management of renal failure in patients with acute liver failure and advanced liver cirrhosis.

A canine liver fibrosis model to develop a therapy for liver cirrhosis using cultured bone marrow-derived cells. 査読国際誌

Takashi Matsuda, Taro Takami, Ryo Sasaki, Tatsuro Nishimura, Yuki Aibe, Bruno Diaz Paredes, Luiz Fernando Quintanilha, Toshihiko Matsumoto, Tsuyoshi Ishikawa, Naoki Yamamoto, Kenji Tani, Shuji Terai, Yasuho Taura, Isao Sakaida

Hepatology communications 1 ( 7 ) 691 - 703 2017年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

We have been developing a therapy for liver cirrhosis using cultured autologous bone marrow-derived mesenchymal stem cells (BMSCs). Before human clinical trials can be considered, the safety and efficacy of BMSC infusion in medium to large animals must be confirmed; thus, we developed a canine liver fibrosis model. A small amount of bone marrow fluid was aspirated from the canine humerus to assess the characteristics of BMSCs. We implanted a venous catheter in the stomach and a subcutaneous infusion port in the back of the neck of each canine. Repeated injection of CCl4 through the catheter was performed to induce liver cirrhosis. After 10 weeks of CCl4 injection, eight canines were equally divided into two groups: no cell infusion (control group) and autologous BMSC infusion through the peripheral vein (BMSC group). A variety of assays were carried out before and 4 weeks after the infusion. The area of liver fibrosis stained with sirius red was significantly reduced in the BMSC group 4 weeks after BMSC infusion, consistent with a significantly shortened half-life of indocyanine green and improved liver function. Conclusion: We established a useful canine liver fibrosis model and confirmed that cultured autologous BMSC infusion improved liver fibrosis without adverse effects. (Hepatology Communications 2017;1:691-703).

DOI： 10.1002/hep4.1071

Training sample selection based on self-training for liver cirrhosis classification using ultrasound images 査読

A Huge Abdominal Tumor Abdominal Abscess 査読

Norihiro Sakai, Kenya Kamimura, Shuji Terai

GASTROENTEROLOGY 153 ( 3 ) E5 - E6 2017年9月

HHMの肝発癌における分子生物学的メカニズムの解明

小川光平, 上村顕也, 後藤諒, 井上良介, 品川陽子, 酒井規裕, 名古屋拓郎, 小林雄司, 阿部寛幸, 阿部聡司, 坂牧僚, 横尾健, 川合弘一, 山際訓, 高見太郎, 山本直樹, 坂井田功, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増大会 ) A732 - A732 2017年9月

Innovative therapeutic endoscopy 膵仮性嚢胞・感染性WONに対する内視鏡的治療重症急性膵炎後Walled-off necrosisの自然軽快に関連する因子

五十嵐聡, 林和直, 寺井崇二

Gastroenterological Endoscopy 59 ( Suppl.2 ) 2103 - 2103 2017年9月

Innovative therapeutic endoscopy 膵仮性嚢胞・感染性WONに対する内視鏡的治療重症急性膵炎後Walled-off necrosisの自然軽快に関連する因子

五十嵐聡, 林和直, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増大会 ) A689 - A689 2017年9月

当院におけるBordeline resectable膵癌の治療の現況

林和直, 五十嵐聡, 水野研一, 橋本哲, 横山純二, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増大会 ) A832 - A832 2017年9月

YAP determines the cell fate of injured mouse hepatocytes in vivo (vol 8, 16017, 2017) 査読

Norio Miyamura, Shoji Hata, Tohru Itoh, Minoru Tanaka, Miki Nishio, Michiko Itoh, Yoshihiro Ogawa, Shuji Terai, Isao Sakaida, Akira Suzuki, Atsushi Miyajima, Hiroshi Nishina

NATURE COMMUNICATIONS 8 16146 2017年8月

An Automated Self-Learning Quantification System to Identify Visible Areas in Capsule Endoscopy Images 査読

Shinichi Hashimoto, Hiroyuki Ogihara, Masato Suenaga, Yusuke Fujita, Shuji Terai, Yoshihiko Hamamoto, Isao Sakaida

JOURNAL OF MEDICAL SYSTEMS 41 ( 8 ) 119 2017年8月

YAP determines the cell fate of injured mouse hepatocytes in vivo 査読

Norio Miyamura, Shoji Hata, Tohru Itoh, Minoru Tanaka, Miki Nishio, Michiko Itoh, Yoshihiro Ogawa, Shuji Terai, Isao Sakaida, Akira Suzuki, Atsushi Miyajima, Hiroshi Nishina

NATURE COMMUNICATIONS 8 1 - 9 2017年7月

The use of clip anchoring to ensure safe transgastric puncture during endoscopic ultrasound-guided transmural drainage 査読

Shinichi Morita, Kazuo Hara, Takeshi Suda, Susumu Hijioka, Nozomi Okuno, Masaaki Kobayashi, Shuji Terai

ENDOSCOPY 49 ( 7 ) E186 - E187 2017年7月

Risk of metastasis in adenocarcinoma of the esophagus: a multicenter retrospective study in a Japanese population 査読

JOURNAL OF GASTROENTEROLOGY 52 ( 7 ) 800 - 808 2017年7月

Lusutrombopag increases hematocytes in a compensated liver cirrhosis patient 査読

Akira Sakamaki, Takayuki Watanabe, Satoshi Abe, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

Clinical Journal of Gastroenterology 10 ( 3 ) 261 - 264 2017年6月

Spontaneous regression of hepatocellular carcinoma: A mini-review 査読

Akira Sakamaki, Kenya Kamimura, Satoshi Abe, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 23 ( 21 ) 3797 - 3804 2017年6月

Effect of double platinum agents, combination of miriplatintransarterial oily chemoembolization and cisplatinhepatic arterial infusion chemotherapy, in patients with hepatocellular carcinoma: Report of two cases 査読

Kohei Ogawa, Kenya Kamimura, Yukari Watanabe, Yosuke Motai, Daisuke Kumaki, Ryoya Seki, Akira Sakamaki, Satoshi Abe, Hirokazu Kawai, Takeshi Suda, Satoshi Yamagiwa, Shuji Terai

WORLD JOURNAL OF CLINICAL CASES 5 ( 6 ) 238 - 246 2017年6月

Long-term efficacy and safety of nalfurafine hydrochloride on pruritus in chronic liver disease patients: Patient-reported outcome based analyses 査読

Kenya Kamimura, Takeshi Yokoo, Hiroteru Kamimura, Akira Sakamaki, Satoshi Abe, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

PLOS ONE 12 ( 6 ) e0178991 2017年6月

Evaluation of the effects of L-carnitine on medaka (Oryzias latipes) fatty liver 査読

Koichi Fujisawa, Taro Takami, Aya Matsuzaki, Toshihiko Matsumoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida

SCIENTIFIC REPORTS 7 ( 1 ) 2749 2017年6月

Prevention of esophageal stricture after endoscopic submucosal dissection using RNA-based silencing of carbohydrate sulfo-transferase 15 in a porcine model 査読

Hiroki Sato, Seiji Sagara, Nao Nakajima, Teppei Akimoto, Kenji Suzuki, Hiroyuki Yoneyama, Shuji Terai, Naohisa Yahagi

ENDOSCOPY 49 ( 5 ) 491 - 497 2017年5月

Transhepatic arterial infusion chemotherapy using a combination of miriplatin and CDDP powder versus miriplatin alone in the treatment of hepatocellular carcinoma: a randomized controlled trial 査読

Kenya Kamimura, Takeshi Suda, Takeshi Yokoo, Hiroteru Kamimura, Tsutomu Kanefuji, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Nobuo Waguri, Satoshi Yamagiwa, Shuji Terai

BMC CANCER 17 ( 1 ) 322 2017年5月

Development and use of a non-biomaterial model for hands-on training of endoscopic procedures 査読

Hiroki Sato, Ken-Ichi Mizuno, Yuichi Sato, Satoru Hashimoto, Kazunao Hayashi, Satoshi Ikarashi, Yutaka Honda, Junji Yokoyama, Shuji Terai

Annals of Translational Medicine 5 ( 8 ) 182 2017年4月

Herpes virus reactivation during and after direct-acting antiviral therapy for hepatitis C virus infection 査読

Takeshi Yokoo, Atsunori Tsuchiya, Soichi Sugitani, Shuji Terai

DIGESTIVE AND LIVER DISEASE 49 ( 4 ) 453 - 454 2017年4月

Long-term outcomes of colorectal endoscopic submucosal dissection in elderly patients 査読

Yoshifumi Takahashi, Ken-ichi Mizuno, Kazuya Takahashi, Hiroki Sato, Satoru Hashimoto, Manabu Takeuchi, Masaaki Kobayashi, Junji Yokoyama, Yuichi Sato, Shuji Terai

INTERNATIONAL JOURNAL OF COLORECTAL DISEASE 32 ( 4 ) 567 - 573 2017年4月

Proposed criteria to differentiate heterogeneous eosinophilic gastrointestinal disorders of the esophagus, including eosinophilic esophageal myositis 査読

Hiroki Sato, Nao Nakajima, Kazuya Takahashi, Go Hasegawa, Ken-ichi Mizuno, Satoru Hashimoto, Satoshi Ikarashi, Kazunao Hayashi, Yutaka Honda, Junji Yokoyama, Yuichi Sato, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 23 ( 13 ) 2414 - 2423 2017年4月

HHMはDNA損傷ストレスに対する応答機構を介して肝発癌抑制に寄与する

小川光平, 上村顕也, 後藤諒, 井上良介, 品川陽子, 阿部寛幸, 阿部聡司, 坂牧僚, 横尾健, 川合弘一, 山際訓, 高見太郎, 山本直樹, 坂井田功, 寺井崇二

肝臓 58 ( Suppl.1 ) A448 - A448 2017年4月

術後再建腸管例に対するERCP関連手技における偶発症の現状と対策

五十嵐聡, 林和直, 水野研一, 本田穣, 橋本哲, 横山純二, 佐藤祐一, 山際訓, 寺井崇二

Gastroenterological Endoscopy 59 ( Suppl.1 ) 1035 - 1035 2017年4月

当科における術後再建腸管の胆管結石症に対する内視鏡治療の検討

林和直, 五十嵐聡, 水野研一, 本田穣, 橋本哲, 横山純二, 佐藤祐一, 山際訓, 寺井崇二

Gastroenterological Endoscopy 59 ( Suppl.1 ) 1036 - 1036 2017年4月

ソラフェニブ投与時の手足症候群の発症における血流減少の関与臨床データ、メダカモデルを用いた血管面積の解析

品川陽子, 上村顕也, 後藤諒, 小川光平, 井上良介, 阿部寛幸, 横尾健, 坂牧僚, 阿部聡司, 川合弘一, 山際訓, 杉谷想一, 柳雅彦, 藤澤浩一, 坂井田功, 寺井崇二

肝臓 58 ( Suppl.1 ) A275 - A275 2017年4月

Muscle layer histopathology and manometry pattern of primary esophageal motility disorders including achalasia 査読

N. Nakajima, H. Sato, K. Takahashi, G. Hasegawa, K. Mizuno, S. Hashimoto, Y. Sato, S. Terai

NEUROGASTROENTEROLOGY AND MOTILITY 29 ( 3 ) 2017年3月

Drug-eluting beads in hepatocellular carcinoma 査読

Hiroyuki Abe, Kenya Kamimura, Shuji Terai

THERAPEUTIC ADVANCES IN GASTROENTEROLOGY 10 ( 3 ) 337 - 338 2017年3月

Re-evaluation of phenotypic expression in differentiated-type early adenocarcinoma of the stomach 査読

Masato Hayakawa, Ken Nishikura, Yoichi Ajioka, Yutaka Aoyagi, Shuji Terai

PATHOLOGY INTERNATIONAL 67 ( 3 ) 131 - 140 2017年3月

当科におけるCrohn病に合併した胆石症の検討

林和直, 五十嵐聡, 水野研一, 本田穣, 橋本哲, 横山純二, 佐藤祐一, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A335 - A335 2017年3月

他臓器癌合併IPMNの臨床像

五十嵐聡, 林和直, 水野研一, 本田穣, 橋本哲, 横山純二, 佐藤祐一, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A372 - A372 2017年3月

膵癌非切除例における骨格筋量と体脂肪組成の評価による予後解析

中野応央樹, 川合弘一, 小林隆昌, 五十嵐聡, 林和直, 佐藤祐一, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A271 - A271 2017年3月

自己免疫性肝疾患のパラダイムシフト原発性胆汁性胆管炎におけるMucosal-associated invariant T細胞の検討

薛徹, 山際訓, 寺井崇二

日本消化器病学会雑誌 114 ( 臨増総会 ) A135 - A135 2017年3月

Predictive factors of the pharmacological action of tolvaptan in patients with liver cirrhosis: a post hoc analysis 査読

Isao Sakaida, Shuji Terai, Koji Nakajima, Yoshiyuki Shibasaki, Sayaka Tachikawa, Hidetsugu Tsubouchi

JOURNAL OF GASTROENTEROLOGY 52 ( 2 ) 229 - 236 2017年2月

A novel technique for biliary biopsy using the sheath of a plastic stent and a non-return valve 査読

Shinichi Morita, Tsutomu Kanefuji, Takahiro Hoshi, Masaaki Kobayashi, Takeshi Suda, Takeshi Mizusawa, Shuji Terai

ENDOSCOPY 49 ( S 01 ) E9 - E10 2017年2月

Loss of peristalsis of the esophagus due to diffuse esophageal leiomyomatosis 査読

Kazuya Takahashi, Yui Ishii, Kazunao Hayashi, Satoshi Ikarashi, Hirokazu Kawai, Yuichi Sato, Shuji Terai

ENDOSCOPY 49 ( S 01 ) E95 - E96 2017年2月

lStatus of and candidates for cell therapy in liver cirrhosis: overcoming the "point of no return'' in advanced liver cirrhosis 査読

Shuji Terai, Atsunori Tsuchiya

JOURNAL OF GASTROENTEROLOGY 52 ( 2 ) 129 - 140 2017年2月

Phase 1 Clinical Study of siRNA Targeting Carbohydrate Sulphotransferase 15 in Crohn's Disease Patients with Active Mucosal Lesions 査読

Kenji Suzuki, Junji Yokoyama, Yusuke Kawauchi, Yutaka Honda, Hiroki Sato, Yutaka Aoyagi, Shuji Terai, Kazuichi Okazaki, Yasuo Suzuki, Yukinori Sameshima, Tsuneo Fukushima, Kazuyuki Sugahara, Raja Atreya, Markus F. Neurath, Kenichi Watanabe, Hiroyuki Yoneyama, Hitoshi Asakura

JOURNAL OF CROHNS & COLITIS 11 ( 2 ) 221 - 228 2017年2月

Lipoprotein-X in cholestatic patients causes xanthomas and promotes foam cell formation in human macrophages 査読

Luka Suzuki, Satoshi Hirayama, Mariko Fukui, Makoto Sasaki, Sadayuki Hiroi, Makoto Ayaori, Shuji Terai, Minoru Tozuka, Hirotaka Watada, Takashi Miida

JOURNAL OF CLINICAL LIPIDOLOGY 11 ( 1 ) 110 - 118 2017年2月

Early Detection of Hepatocellular Carcinoma Recurrence Using the Highly Sensitive Fucosylated Fraction of Alpha-Fetoprotein 査読

Toru Setsu, Atsunori Tsuchiya, Takayuki Watanabe, Takuro Nagoya, Satoshi Ikarashi, Kazunao Hayashi, Junji Yokoyama, Satoshi Yamagiwa, Shuji Terai

Case Reports in Gastroenterology 11 ( 1 ) 142 - 147 2017年1月

Immunohistochemical differentiation of eosinophilic esophageal myositis from eosinophilic esophagitis 査読

Hiroki Sato, Nao Nakajima, Go Hasegawa, Yuzo Kawata, Yuichi Sato, Kenji Suzuki, Terasu Honma, Shuji Terai

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 32 ( 1 ) 106 - 113 2017年1月

Yusuke Fujita, Yoshihiro Mitani, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

THIRTEENTH INTERNATIONAL CONFERENCE ON QUALITY CONTROL BY ARTIFICIAL VISION 2017 10338 103380J 2017年

Two cases of cholangiocellular carcinoma complicated with Trousseau’s syndrome

Shinagawa, Y., Kamimura, K., Sakai, N., Kumaki, D., Ogawa, K., Azumi, R., Tominaga, K., Sakamaki, A., Ikarashi, S., Hayashi, K., Yamamoto, T., Mizuno, K., Yamagiwa, S., Terai, S.

Kanzo/Acta Hepatologica Japonica 58 ( 9 ) 2017年

Invasive Liver Abscess Syndrome Caused by Klebsiella pneumoniae 査読

Toru Setsu, Atsunori Tsuchiya, Satoshi Yamagiwa, Shuji Terai

INTERNAL MEDICINE 56 ( 22 ) 3121 - 3122 2017年

Clinical trials using mesenchymal stem cells in liver diseases and inflammatory bowel diseases. 査読国際誌

Tsuchiya A, Kojima Y, Ikarashi S, Seino S, Watanabe Y, Kawata Y, Terai S

Inflammation and regeneration 37 16 - 16 2017年

Tumor markers for early diagnosis for brain metastasis of hepatocellular carcinoma: A case series and literature review for effective loco-regional treatment 査読

Kenya Kamimura, Yuji Kobayashi, Yoshifumi Takahashi, Hiroyuki Abe, Daisuke Kumaki, Takeshi Yokoo, Hiroteru Kamimura, Norihiro Sakai, Akira Sakamaki, Satoshi Abe, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

CANCER BIOLOGY & THERAPY 18 ( 2 ) 79 - 84 2017年

Increase of Soluble Programmed Cell Death Ligand 1 in Patients with Chronic Hepatitis C 査読

Satoshi Yamagiwa, Toru Ishikawa, Nobuo Waguri, Soichi Sugitani, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Shuji Terai

INTERNATIONAL JOURNAL OF MEDICAL SCIENCES 14 ( 5 ) 403 - 411 2017年

Prognostic Impact of Indocyanine Green Plasma Disappearance Rate in Hepatocellular Carcinoma Patients after Radiofrequency Ablation: A Prognostic Nomogram Study 査読

Motoi Azumi, Takeshi Suda, Shuji Terai, Kouhei Akazawa

INTERNAL MEDICINE 56 ( 9 ) 1001 - 1007 2017年

Possible involvement of mucosal-associated invariant T cells in the progression of inflammatory bowel diseases 査読

Kentaro Tominaga, Satoshi Yamagiwa, Toru Setsu, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Yutaka Honda, Masaaki Takamura, Junji Yokoyama, Kenji Suzuki, Toshifumi Wakai, Shuji Terai

BIOMEDICAL RESEARCH-TOKYO 38 ( 2 ) 111 - 121 2017年

A Mesenteric Desmoid Tumor with Rapid Progression 査読

Kazunao Hayashi, Masaaki Takamura, Hisashi Yokoyama, Yuichi Sato, Satoshi Yamagiwa, Hitoshi Nogami, Toshifumi Wakai, Go Hasegawa, Shuji Terai

INTERNAL MEDICINE 56 ( 5 ) 505 - 508 2017年

Efficacy and safety of telaprevir- and simeprevir-based triple therapies for older patients with chronic hepatitis C 査読

Satoshi Yamagiwa, Toru Ishikawa, Nobuo Waguri, Soichi Sugitani, Hiroto Wakabayashi, Shogo Ohkoshi, Takashi Tsukishiro, Toru Takahashi, Toshiaki Watanabe, Shuji Terai

World Journal of Hepatology 9 ( 5 ) 252 - 262 2017年

An Unusual Case of an Extremely Large α-Fetoprotein-Producing Tumor. 査読

Takahashi K, Tsuchiya A, Terai S

Gastroenterology 151 ( 6 ) 1077 - 1080 2016年12月

Myofibroblast distribution is associated with invasive growth types of colorectal cancer 査読

Masafumi Takatsuna, Satoko Morohashi, Tadashi Yoshizawa, Hideaki Hirai, Toshihiro Haga, Rie Ota, Kensuke Saito, Yunyan Wu, Hiroko Seino, Yutaka Aoyagi, Shuji Terai, Hiroshi Kijima

ONCOLOGY REPORTS 36 ( 6 ) 3154 - 3160 2016年12月

Transhepatic arterial chemotherapy using a combination of miriplatin and CDDP powder in patients with hepatocellular carcinoma 査読

Kenya Kamimura, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Nobuo Waguri, Toru Ishikawa, Takeshi Suda, Satoshi Yamagiwa, Shuji Terai

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 31 361 - 361 2016年11月

Vonoprazan 20 mg vs lansoprazole 30 mg for endoscopic submucosal dissection-induced gastric ulcers. 査読国際誌

Takahashi K, Sato Y, Kohisa J, Watanabe J, Sato H, Mizuno K, Hashimoto S, Terai S

World journal of gastrointestinal endoscopy 8 ( 19 ) 716 - 722 2016年11月

Case of severe alcoholic hepatitis treated with granulocytapheresis 査読

Yukari Watanabe, Kenya Kamimura, Tomohiro Iwasaki, Hiroyuki Abe, Shunsaku Takahashi, Ken-ichi Mizuno, Manabu Takeuchi, Atsushi Eino, Ichiei Narita, Shuji Terai

WORLD JOURNAL OF CLINICAL CASES 4 ( 11 ) 369 - 374 2016年11月

[Series: Diagnosis at a Glance]. 査読

Kobayashi T, Tsuchiya A, Kuraoka N, Yamamoto T, Honda Y, Yokoyama J, Kawai H, Yamagiwa S, Suda T, Terai S

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 105 ( 11 ) 2263 - 2267 2016年11月

Significance of hepatic progenitor cell marker-positive hepatocellular carcinoma and its possible prediction by AFP-L3 査読

Atsunori Tsuchiya, Yuichi Kojima, Satoshi Seino, Yusuke Watanabe, Kenya Kamimura, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

HEPATOLOGY 64 669A - 670A 2016年10月

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique 査読

Takeshi Yokoo, Kenya Kamimura, Hiroyuki Abe, Yuji Kobayashi, Tsutomu Kanefuji, Kohei Ogawa, Ryo Goto, Masafumi Oda, Takeshi Suda, Shuji Terai, Masafumi Oda

WORLD JOURNAL OF GASTROENTEROLOGY 22 ( 40 ) 8862 - 8868 2016年10月

Platinum-based transhepatic arterial chemotherapy using a combination of miriplatin and CDDP powder in patients with hepatocellular carcinoma 査読

Kohei Ogawa, Kenya Kamimura, Takeshi Suda, Takeshi Yokoo, Akira Sakamaki, Satoshi Abe, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Nobuo Waguri, Toru Ishikawa, Satoshi Yamagiwa, Shuji Terai

HEPATOLOGY 64 652A - 652A 2016年10月

Biological significance of a disintegrin and metalloproteinase 21 expression in hepatocellular carcinoma 査読

Masaaki Takamura, Hiroki Honda, Satoshi Yamagiwa, Naruhiro Kimura, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Takuya Genda, Yasunobu Matsuda, Toshifumi Wakai, Shuji Terai

HEPATOLOGY 64 639A - 639A 2016年10月

Myofibroblasts of the muscle layer stimulate the malignant potential of colorectal cancer 査読

Masafumi Takatsuna, Satoko Morohashi, Tadashi Yoshizawa, Hideaki Hirai, Toshihiro Haga, Rie Ota, Yunyan Wu, Hajime Morohashi, Kenichi Hakamada, Shuji Terai, Hiroshi Kijima

ONCOLOGY REPORTS 36 ( 3 ) 1251 - 1257 2016年9月

Assessments of histologic changes after peroral endoscopic myotomy. 査読

Sato H, Sagara S, Suzuki K, Terai S, Yahagi N

Gastrointestinal endoscopy 84 ( 2 ) 377 - 378 2016年8月

Management of gastric and duodenal neuroendocrine tumors 査読

Yuichi Sato, Satoru Hashimoto, Ken-ichi Mizuno, Manabu Takeuchi, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 22 ( 30 ) 6817 - 6828 2016年8月

Effects of Fibrotic Tissue on Liver-targeted Hydrodynamic Gene Delivery 査読

Yuji Kobayashi, Kenya Kamimura, Hiroyuki Abe, Takeshi Yokoo, Kohei Ogawa, Yoko Shinagawa-Kobayashi, Ryo Goto, Ryosuke Inoue, Masato Ohtsuka, Hiromi Miura, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

MOLECULAR THERAPY-NUCLEIC ACIDS 5 ( 8 ) e359 2016年8月

A novel training model composed of nonbiological materials for endoscopic submucosal dissection. 査読

Mizuno K, Sato H, Hashimoto S, Sato Y, Terai S

Gastrointestinal endoscopy 84 ( 2 ) 373 - 374 2016年8月

Novel ex-vivo training model for peroral endoscopic myotomy using hydrogel 査読

Hiroki Sato, Ken-ichi Mizuno, Shuji Terai

DIGESTIVE ENDOSCOPY 28 ( 5 ) 620 - 620 2016年7月

Pivotal Role of Carbohydrate Sulfotransferase 15 in Fibrosis and Mucosal Healing in Mouse Colitis 査読

Kenji Suzuki, Somasundaram Arumugam, Junji Yokoyama, Yusuke Kawauchi, Yutaka Honda, Hiroki Sato, Yutaka Aoyagi, Shuji Terai, Kazuichi Okazaki, Yasuo Suzuki, Shuji Mizumoto, Kazuyuki Sugahara, Raja Atreya, Markus F. Neurath, Kenichi Watanabe, Taishi Hashiguchi, Hiroyuki Yoneyama, Hitoshi Asakura

PLOS ONE 11 ( 7 ) e0158967 2016年7月

Therapeutic or spontaneous Helicobacter pylori eradication can obscure magnifying narrow-band imaging of gastric tumors. 査読

Kobayashi M, Hashimoto S, Mizuno K, Takeuchi M, Sato Y, Watanabe G, Ajioka Y, Azumi M, Akazawa K, Terai S

Endoscopy international open 4 ( 6 ) E665 - 72 2016年6月

Deferasirox, an oral iron chelator, prevents hepatocarcinogenesis and adverse effects of sorafenib 査読

Naoki Yamamoto, Takahiro Yamasaki, Taro Takami, Koichi Uchida, Koichi Fujisawa, Toshihiko Matsumoto, Issei Saeki, Shuji Terai, Isao Sakaida

JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 58 ( 3 ) 202 - 209 2016年5月

Effective prevention of hand-foot syndrome by the consumption of dried bonito broth 査読

Kenya Kamimura, Yoko Shinagawa, Kohei Ogawa, Yuji Kobayashi, Hiroyuki Abe, Takeshi Yokoo, Hiroteru Kamimura, Hirokazu Kawai, Takeshi Suda, Satoshi Yamagiwa, Hiroshi Baba, Shuji Terai

Japanese Journal of Cancer and Chemotherapy 43 ( 4 ) 463 - 465 2016年4月

当院における悪性胃十二指腸狭窄に対する内視鏡的ステント留置術の有用性の検討

林和直, 山本幹, 水野研一, 本田穣, 橋本哲, 横山純二, 竹内学, 佐藤祐一, 寺井崇二

Gastroenterological Endoscopy 58 ( Suppl.1 ) 790 - 790 2016年4月

Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4 査読国際誌

Fujisawa Koichi, Terai Shuji, Takami Taro, Yamamoto Naoki, Yamasaki Takahiro, Matsumoto Toshihiko, Yamaguch Kazuhito, Owada Yuji, Nishina Hiroshi, Takafumi Noma, Sakaida Isao

Journal of Experimental & Clinical Cancer Research Vol.35 ( No.1 ) 48 - 48 2016年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: Adenylate kinase is a key enzyme in the high-energy phosphoryl transfer reaction in living cells. Anisoform of this enzyme, adenylate kinase 4 (AK4), is localized in the mitochondrial matrix and is believed to beinvolved in stress, drug resistance, malignant transformation in cancer, and ATP regulation. However, the molecularbasis for the AK4 functions remained to be determined.Methods: HeLa cells were transiently transfected with an AK4 small interfering RNA (siRNA), an AK4 short hairpinRNA (shRNA) plasmid, a control shRNA plasmid, an AK4 expression vector, and a control expression vector toexamine the effect of the AK4 expression on cell proliferation, sensitivity to anti-cancer drug, metabolome, geneexpression, and mitochondrial activity.Results: AK4 knockdown cells treated with short hairpin RNA increased ATP production and showed greatersensitivity to hypoxia and anti-cancer drug, cis-diamminedichloro-platinum (II) (CDDP). Subcutaneous grafting AK4knockdown cells into nude mice revealed that the grafted cells exhibited both slower proliferation and reduced thetumor sizes in response to CDDP. AK4 knockdown cell showed a increased oxygen consumption rate with FCCPtreatment, while AK4 overexpression lowered it. Metabolome analysis showed the increased levels of thetricarboxylic acid cycle intermediates, fumarate and malate in AK4 knockdown cells, while AK4 overexpressionlowered them. Electron microscopy detected the increased mitochondrial numbers in AK4 knockdown cells.Microarray analysis detected the increased gene expression of two key enzymes in TCA cycle, succinatedehydrogenase A (SDHA) and oxoglutarate dehydrogenease L (OGDHL), which are components of SDH complexand OGDH complex, supporting the metabolomic results.Conclusions: We found that AK4 was involved in hypoxia tolerance, resistance to anti-tumor drug, and theregulation of mitochondrial activity. These findings provide a new potential target for efficient anticancer therapiesby controlling AK4 expression.

DOI： 10.1186/s13046-016-0322-2

Training ROI selection based on MILBoost for liver cirrhosis classification using ultrasound images 査読

Modulation of anti-cancer drug sensitivity through the regulation of mitochondrial activity by adenylate kinase 4. 査読国際誌

Fujisawa K, Terai S, Takami T, Yamamoto N, Yamasaki T, Matsumoto T, Yamaguchi K, Owada Y, Nishina H, Noma T, Sakaida I

Journal of experimental & clinical cancer research : CR 35 48 - 48 2016年3月

Advanced diagnostic endoscopy for gastric cancers discovered after H. Pylori eradication 査読

Masaaki Kobayashi, Takahiro Hoshi, Shin-Ichi Morita, Tsutomu Kanefuji, Takeshi Suda, Ken-Ichi Mizuno, Satoru Hashimoto, Manabu Takeuchi, Yuichi Sato, Shuji Terai

Journal of Japanese Society of Gastroenterology 113 ( 2 ) 235 - 244 2016年2月

Human T-cell leukemia virus type 1 (HTLV-1) Tax1 oncoprotein but not HTLV-2 Tax2 induces the expression of OX40 ligand by interacting with p52/p100 and RelB 査読

Yosuke Motai, Masahiko Takahashi, Takayuki Takachi, Masaya Higuchi, Toshifumi Hara, Mariko Mizuguchi, Yutaka Aoyagi, Shuji Terai, Yuetsu Tanaka, Masahiro Fujii

VIRUS GENES 52 ( 1 ) 4 - 13 2016年2月

Circadian variations in the liver metabolites of medaka (Oryzias latipes) 査読

Koichi Fujisawa, Taro Takami, Yoshitaka Kimoto, Toshihiko Matsumoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida

SCIENTIFIC REPORTS 6 20916 2016年2月

Percutaneous transhepatic obliteration for hepatic encephalopathy accompanied with chronic renal failure in a super-elderly patient: A case report 査読

Yusuke Watanabe, Toru Ishikawa, Satoshi Abe, Ryousuke Inoue, Tomoyuki Sugano, Akito Iwanaga, Keiichi Seki, Terasu Honma, Toshiaki Yoshida, Takeo Nemoto, Keiko Takeda, Shuji Terai

Acta Hepatologica Japonica 56 ( 12 ) 668 - 674 2016年1月

Liver regeneration therapy using autologous bone marrow-derived cells for cirrhotic patients 査読

Taro Takami, Isao Sakaida, Shuji Terai

Gene Therapy and Cell Therapy Through the Liver: Current Aspects and Future Prospects 25 - 34 2016年1月

Effective Prevention of Liver Fibrosis by Liver-targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in a Rat Liver Fibrosis Model 査読

Hiroyuki Abe, Kenya Kamimura, Yuji Kobayashi, Masato Ohtsuka, Hiromi Miura, Riuko Ohashi, Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Masanori Tsuchida, Yutaka Aoyagi, Guisheng Zhang, Dexi Liu, Shuji Terai

MOLECULAR THERAPY-NUCLEIC ACIDS 5 e276 2016年1月

Fujita, Y., Mitani, Y., Hamamoto, Y., Segawa, M., Terai, S., Sakaida, I.

Lecture Notes in Computer Science (including subseries Lecture Notes in Artificial Intelligence and Lecture Notes in Bioinformatics) 9799 451 - 459 2016年

Improvement of Pancreatic Tumor-induced NAFLD with Pancrelipase 査読

Naosuke Kuraoka, Atsunori Tsuchiya, Takeshi Suda, Shuji Terai

INTERNAL MEDICINE 55 ( 1 ) 89 - 90 2016年

Stomach Dysfunction Is a Potential Risk Factor for Wernicke's Encephalopathy 査読

Oki Nakano, Atsunori Tsuchiya, Satoshi Yamagiwa, Shuji Terai

INTERNAL MEDICINE 55 ( 24 ) 3679 - 3680 2016年

The Combination Therapy of Dissolution Using Carbonated Liquid and Endoscopic Procedure for Bezoars: Pragmatical and Clinical Review 査読

Kohei Ogawa, Kenya Kamimura, Ken-ichi Mizuno, Yoko Shinagawa, Yuji Kobayashi, Hiroyuki Abe, Yukari Watanabe, Shunsaku Takahashi, Kazunao Hayashi, Junji Yokoyama, Manabu Takeuchi, Masaaki Kobayashi, Satoshi Yamagiwa, Yuichi Sato, Shuji Terai

GASTROENTEROLOGY RESEARCH AND PRACTICE 2016 7456242 2016年

Endoscopic Removal of Ingested Dentures and Dental Instruments: A Retrospective Analysis 査読

Ken-ichi Mizuno, Kazuya Takahashi, Kentaro Tominaga, Yuki Nishigaki, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Takashi Yamamoto, Yutaka Honda, Satoru Hashimoto, Kenya Kamimura, Manabu Takeuchi, Junji Yokoyama, Yuichi Sato, Masaaki Kobayashi, Shuji Terai

GASTROENTEROLOGY RESEARCH AND PRACTICE 2016 3537147 2016年

Three Times Repeated Portal Venous Gas after Meals 査読

Takamasa Kobayashi, Atsunori Tsuchiya, Takeshi Suda, Shuji Terai

INTERNAL MEDICINE 55 ( 7 ) 843 - 845 2016年

Formulation for Effective Screening and Management of Nonalcoholic Steatohepatitis: Noninvasive NAFLD Management Strategy 査読

Kanae Hirose, Tsutomu Kanefuji, Takeshi Suda, Souichi Sugitani, Keisuke Nagasaki, Tomoyuki Kubota, Masato Igarashi, Shuji Terai

GASTROENTEROLOGY RESEARCH AND PRACTICE 2016 6343656 2016年

フルカバー金属ステントが有用であった胆管空腸吻合部良性胆道狭窄の１例

森田慎一, 薛徹, 星隆洋, 兼藤努, 小林正明, 須田剛士, 寺井崇二

日本消化器内視鏡学会雑誌 58 ( 11 ) 2279 - 2286 2016年

記述言語：日本語出版者・発行元：一般社団法人日本消化器内視鏡学会

70歳女性．膵胆管合流異常にて肝外胆管切除，胆管空腸吻合術施行．１年後に急性胆管炎を発症し経皮経肝胆道ドレナージを施行した．その後に内瘻化を企図したが高度の吻合部狭窄にて通過困難であった．経皮経路より気管支内視鏡を用いた観察にて吻合部にpin hole状の瘢痕狭窄を認め，同部をガイドワイヤーで通過し内外瘻チューブを留置しえた．その後，狭窄部にフルカバー金属ステントを留置した．拡張は良好であり，留置４カ月後に抜去した．造影検査でも吻合部は良好に開存しており外瘻チューブも抜去した．フルカバー金属ステントは持続的に狭窄部を拡張し抜去も可能である．本法は良性胆道狭窄に対し有効で実行可能な治療法と考える．

DOI： 10.11280/gee.58.2279

【再生医療-新たな医療を求めて-】再生医療の臨床研究・治験 C型肝炎ウイルス起因肝硬変に対する自己骨髄細胞投与療法

Enhanced survival of mice infused with bone marrow-derived as compared with adipose-derived mesenchymal stem cells 査読

Shogo Shiratsuki, Shuji Terai, Yasuhiko Murata, Taro Takami, Naoki Yamamoto, Koichi Fujisawa, Guzel Burganova, Luiz Fernando Quintanilha, Isao Sakaida

HEPATOLOGY RESEARCH 45 ( 13 ) 1353 - 1359 2015年12月

First case of bacteremia caused by Helicobacter cinaedi in a patient with liver cirrhosis: a case report and literature review 査読

Kenya Kamimura, Daisuke Kumaki, Masashi Arita, Yuji Kobayashi, Ken-ichi Mizuno, Fumiko Kusama, Megumi Kobayashi, Hiroyuki Abe, Yoshifumi Takahashi, Kohei Ogawa, Yoko Shinagawa, Manabu Takeuchi, Yuichi Sato, Hirokazu Kawai, Satoshi Yamagiwa, Shuji Terai

Clinical Journal of Gastroenterology 8 ( 5 ) 306 - 317 2015年10月

Evaluation of esophageal motility after endoscopic submucosal dissection for superficial esophageal cancer 査読

Kazuya Takahashi, Manabu Takeuchi, Yuichi Sato, Hiroki Sato, Kenichi Mizuno, Satoru Hashimoto, Masaaki Kobayashi, Shuji Terai

EUROPEAN JOURNAL OF GASTROENTEROLOGY & HEPATOLOGY 27 ( 10 ) 1187 - 1192 2015年10月

Histological and Transcriptomic Analysis of Adult Japanese Medaka Sampled Onboard the International Space Station 査読

Yasuhiko Murata, Takako Yasuda, Tomomi Watanabe-Asaka, Shoji Oda, Akiko Mantoku, Kazuhiro Takeyama, Masahiro Chatani, Akira Kudo, Satoko Uchida, Hiromi Suzuki, Fumiaki Tanigaki, Masaki Shirakawa, Koichi Fujisawa, Yoshihiko Hamamoto, Shuji Terai, Hiroshi Mitani

PLOS ONE 10 ( 10 ) e0138799 2015年10月

Endoscopic surveillance of gastric cancers after Helicobacter pylori eradication 査読

Masaaki Kobayashi, Yuichi Sato, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 21 ( 37 ) 10553 - 10562 2015年10月

Possible involvement of activating follicular helper T cells in autoimmune hepatitis 査読

Kimura Naruhiro, Yamagiwa Satoshi, Honda Hiroki, Setsu Toru, Tominaga Kentaro, Kamimura Hiroteru, Takamura Masaaki, Terai Shuji

HEPATOLOGY 62 369A - 369A 2015年10月

Site-specific impact of a regional hydrodynamic injection: Computed tomography study during hydrodynamic injection targeting the swine liver 査読

Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Kenya Kamimura, Dexi Liu, Shuji Terai

Pharmaceutics 7 ( 3 ) 334 - 343 2015年9月

Nutcracker and jackhammer esophagus treatment: a three-case survey, including two novel cases of eosinophilic infiltration into the muscularis propria 査読

Hiroki Sato, Manabu Takeuchi, Kazuya Takahashi, Yuichi Sato, Satoru Hashimoto, Kenichi Mizuno, Kenji Suzuki, Masaaki Kobayashi, Terasu Honma, Haruhiro Inoue, Shuji Terai

ENDOSCOPY 47 ( 9 ) 855 - 857 2015年9月

Image-guided hydrodynamic gene delivery: Current status and future directions 査読

Kenya Kamimura, Takeshi Yokoo, Hiroyuki Abe, Yuji Kobayashi, Kohei Ogawa, Yoko Shinagawa, Ryosuke Inoue, Shuji Terai

Pharmaceutics 7 ( 3 ) 213 - 223 2015年8月

Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging (vol 10, e0129950, 2015) 査読

Koichi Fujisawa, Shuji Terai, Toshihiko Matsumoto, Taro Takami, Naoki Yamamoto, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida

PLOS ONE 10 ( 8 ) e0137156 2015年8月

臨床応用の現状非代償性肝硬変症に対する再生療法

寺井崇二, 高見太郎, 坂井田功

メディカル朝日 44 ( 8 ) 36 - 37 2015年8月

抗結核薬による昏睡型急性肝不全の一例

松田崇史, 石川剛, 岩本拓也, 佐伯一成, 日高勲, 高見太郎, 寺井崇二, 坂井田功

肝臓 56 ( 7 ) 387 - 388 2015年7月

Evidence for a Role of the Transcriptional Regulator Maid in Tumorigenesis and Aging 査読

Koichi Fujisawa, Shuji Terai, Toshihiko Matsumoto, Taro Takami, Naoki Yamamoto, Hiroshi Nishina, Makoto Furutani-Seiki, Isao Sakaida

PLOS ONE 10 ( 6 ) e0129950 2015年6月

Autologous bone marrow cell infusion therapy for hepatitis C virus infected liver cirrhosis. 査読

Aibe Y, Takami T, Terai S, Sakaida I

Nihon rinsho. Japanese journal of clinical medicine 73 Suppl 5 499 - 503 2015年6月

相部祐希, 高見太郎, 寺井崇二, 坂井田功

日本臨床 73 ( 増刊5 再生医療 ) 499 - 503 2015年6月

特発性血小板減少性紫斑病を合併した原発性胆汁性肝硬変自己免疫性肝炎オーバーラップ症候群に部分的脾動脈塞栓術を施行した1例

仁志麻衣子, 石川剛, 相部祐希, 白築祥吾, 松田崇史, 岩本拓也, 高見太郎, 寺井崇二, 坂井田功

日本門脈圧亢進症学会雑誌 21 ( 2 ) 122 - 127 2015年6月

記述言語：日本語出版者・発行元：(一社)日本門脈圧亢進症学会

症例は50歳代女性で、吐血で近医にて食道静脈瘤破裂と診断され、内視鏡的静脈瘤結紮術が行われた。肝硬変症(LC)の精査に前医を紹介され、原発性胆汁性肝硬変症-自己免疫性肝炎のオーバーラップ症候群に起因するLCの診断でウルソデオキシコール酸とプレドニゾロン(PSL)が開始されたが、肝障害の持続と血小板減少を認め、特発性血小板減少性紫斑病(ITP)と診断され、静脈瘤再発で精査目的に当院へ入院した。検査で中等度の脾腫、門脈・脾動静脈の拡張、食道静脈瘤を認め、静脈瘤に対し内視鏡的静脈瘤硬化結紮療法(EISL)を行い、その後にLC・ITPに起因する血小板減少症に対し部分的脾動脈塞栓術(PSE)を行った。1週間後の造影CTで80.6%の脾梗塞を確認し、肺動脈楔入圧、肝静脈圧較差の改善を認め、2週間後に血小板数の上昇で軽快退院した。PSLの漸減・中止後も血小板減少・肝障害の再燃はなく、EISL後18ヵ月、PSE後16ヵ月経過で食道静脈瘤の再発は認めていない。

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2015&ichushi_jid=J03767&link_issn=&doc_id=20150721240003&doc_link_id=10.11423%2Fjsph.21.122&url=https%3A%2F%2Fdoi.org%2F10.11423%2Fjsph.21.122&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Rheological modification of hydrodynamic gene delivery

Takeshi Yokoo, Tsutomu Kanefuji, Takeshi Suda, Akiomi Ushida, Tomiichi Hasegawa, Kenya Kamimura, Dexi Liu, Shuji Terai

Proceedings of The 18th Annual Meeting of the American Society of Gene and Cell Therapy ( 350594 ) 140 - 141 2015年5月

早期胃癌に対するESD後に発生した遅発性穿孔の検討査読

荒生祥尚, 小林正明, 橋本哲, 水野研一, 竹内学, 本田博樹, 影向一美, 高村昌昭, 佐藤祐一, 寺井崇二

ENDOSCOPIC FORUM for digestive disease 31 ( 1 ) 27 - 32 2015年5月

Effective Prevention of Liver Fibrosis by Liver-Targeted Hydrodynamic Gene Delivery of Matrix Metalloproteinase-13 in Rat Liver Fibrosis Model 査読

Abe Hiroyuki, Kamimura Kenya, Kobayashi Yuji, Ohtsuka Masato, Miura Hiromi, Ohashi Riuko, Yokoo Takeshi, Kanefuji Tsutomu, Suda Takeshi, Tsuchida Masanori, Aoyagi Yutaka, Zhang Guisheng, Liu Dexi, Terai Shuji

MOLECULAR THERAPY 23 S234 2015年5月

A New Therapeutic Assessment Score for Advanced Hepatocellular Carcinoma Patients Receiving Hepatic Arterial Infusion Chemotherapy 査読

Issei Saeki, Takahiro Yamasaki, Norikazu Tanabe, Takuya Iwamoto, Toshihiko Matsumoto, Yohei Urata, Isao Hidaka, Tsuyoshi Ishikawa, Taro Takami, Naoki Yamamoto, Koichi Uchida, Shuji Terai, Isao Sakaida

PLOS ONE 10 ( 5 ) e0126649 2015年5月

Advances in understanding and treating liver diseases during pregnancy: A review 査読

Kenya Kamimura, Hiroyuki Abe, Hirokazu Kawai, Hiroteru Kamimura, Yuji Kobayashi, Minoru Nomoto, Yutaka Aoyagi, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 21 ( 17 ) 5183 - 5190 2015年5月

Effect of Fibrotic Tissue on Liver-Targeted Hydrodynamic Gene Delivery 査読

Kobayashi Yuji, Kamimura Kenya, Abe Hiroyuki, Ohtsuka Masato, Miura Hiromi, Yokoo Takeshi, Kanefuji Tsutomu, Suda Takeshi, Zhang Guisheng, Tsuchida Masanori, Aoyagi Yutaka, Liu Dexi, Terai Shuji

MOLECULAR THERAPY 23 S141 2015年5月

Factors predicting aggressiveness of non-hypervascular hepatic nodules detected on hepatobiliary phase of gadolinium ethoxybenzyl diethylene-triamine-pentaacetic-acid magnetic resonance imaging 査読

Tsutomu Kanefuji, Toru Takano, Takeshi Suda, Kouhei Akazawa, Takeshi Yokoo, Hiroteru Kamimura, Kenya Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Hirokazu Kawai, Satoshi Yamagiwa, Hidefumi Aoyama, Minoru Nomoto, Shuji Terai

WORLD JOURNAL OF GASTROENTEROLOGY 21 ( 15 ) 4583 - 4591 2015年4月

【炎症と線維化】肝線維化に対する骨髄由来細胞を用いた治療戦略

寺井崇二, 高見太郎, 土屋淳紀, 坂井田功

細胞 47 ( 4 ) 176 - 179 2015年4月

臨床応用の基盤形成を目指した肝再生研究の新展開自己骨髄細胞による肝臓再生療法の臨床実施とそのメカニズム解析

高見太郎, 寺井崇二, 坂井田功

肝臓 56 ( Suppl.1 ) A146 - A146 2015年4月

定圧炭酸ガス送気システムを用いた大腸内視鏡下腸管内送気圧と検査時の苦痛、最適な内視鏡視野との関連について

高橋祥史, 水野研一, 小林正明, 高橋一也, 西垣祐紀, 林和直, 山本幹, 本田穣, 橋本哲, 横山純二, 竹内学, 佐藤祐一, 寺井崇二

Gastroenterological Endoscopy 57 ( Suppl.1 ) 927 - 927 2015年4月

膵漿液性嚢胞腺腫(SCA)の外科切除例の検討

林和直, 山本幹, 塩路和彦, 小林正明, 若井俊文, 寺井崇二

Gastroenterological Endoscopy 57 ( Suppl.1 ) 985 - 985 2015年4月

Modern Immunologyからみた肝病態原発性胆汁性肝硬変におけるMucosal associated invariant T cellsの検討

薛徹, 山際訓, 寺井崇二

肝臓 56 ( Suppl.1 ) A62 - A62 2015年4月

C型肝炎の肝線維化経時的評価におけるReal-time Tissue Elastography(RTE)の有用性

花園忠相, 日高勲, 佐伯一成, 岩本拓也, 石川剛, 寺井崇二, 坂井田功

肝臓 56 ( Suppl.1 ) A538 - A538 2015年4月

Collagenous gastritis: Review. 査読

Kamimura K, Kobayashi M, Sato Y, Aoyagi Y, Terai S

World journal of gastrointestinal endoscopy 7 ( 3 ) 265 - 273 2015年3月

低侵襲肝臓再生療法

坂井田功, 寺井崇二, 高見太郎

日本消化器病学会雑誌 112 ( 臨増総会 ) A22 - A22 2015年3月

消化器疾患における線維化の病態と診療骨髄細胞を用いた線維化と発癌を標的とした肝臓再生療法の開発と展望

高見太郎, 寺井崇二, 坂井田功

日本消化器病学会雑誌 112 ( 臨増総会 ) A104 - A104 2015年3月

DEB-TACE有効症例の検討 TACE後CT値に注目して

佐伯一成, 相部祐希, 中島崇雄, 田邉規和, 白築祥吾, 花園忠相, 岩本拓也, 日高勲, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功

日本消化器病学会雑誌 112 ( 臨増総会 ) A451 - A451 2015年3月

当科における急性肝不全及び薬物性肝障害の現況

花園忠相, 日高勲, 佐伯一成, 岩本拓也, 石川剛, 寺井崇二, 坂井田功

日本消化器病学会雑誌 112 ( 臨増総会 ) A504 - A504 2015年3月

癌幹細胞を標的とした消化器癌治療の最前線エネルギー代謝に関わるアデニル酸キナーゼ(AK4)はミトコンドリア活性を抑制することで低酸素耐性、薬剤耐性を制御する

藤澤浩一, 寺井崇二, 坂井田功

日本消化器病学会雑誌 112 ( 臨増総会 ) A185 - A185 2015年3月

Interferon β+ribavirin併用療法によりsustained virological responseが得られたCharcot-Marie-Tooth病合併C型慢性肝炎の一例

松浦桂司, 日高勲, 花園忠相, 佐伯一成, 岩本拓也, 石川剛, 高見太郎, 川井元晴, 寺井崇二, 神田隆, 坂井田功

山口医学 64 ( 1 ) 53 - 57 2015年2月

【肥満症診療最前線】肥満に起因する疾患の検査、治療のポイントは? 体重減少の効果を主に非アルコール性肝疾患(脂肪肝)

寺井崇二, 佐伯一成, 日高勲, 丸本芳雄, 橋本真一, 岡本健志, 坂井田功

Modern Physician 35 ( 2 ) 191 - 194 2015年2月

肝細胞癌に対する肝動脈化学塞栓療法施行直後に腫瘍破裂を来した一例

福井悠美, 佐伯一成, 花園忠相, 田邉規和, 浦田洋平, 日高勲, 寺井崇二, 坂井田功

山口医学 64 ( 1 ) 35 - 40 2015年2月

Delayed perforation after endoscopic submucosal dissection for early gastric cancer

Arao, Y., Kobayashi, M., Hashimoto, S., Mizuno, K., Takeuchi, M., Honda, H., Yoko, K., Takamura, M., Sato, Y., Terai, S.

Endoscopic Forum for Digestive Disease 31 ( 1 ) 2015年

Three cases of Meckel's diverticulum in adult patients diagnosed using transanal balloon enteroscopy

Azumi, R., Yokoyama, J., Honda, Y., Yamagiwa, S., Terai, S., Komukai, S., Ohashi, Y., Matsuzawa, N., Kobayashi, K., Hashidate, H., Shibuya, H.

Endoscopic Forum for Digestive Disease 31 ( 1 ) 2015年

Epiphrenic diverticulum of the esophagus after peroral endoscopic myotomy 査読

Hiroki Sato, Kazuya Takahashi, Manabu Takeuchi, Yuichi Sato, Satoru Hashimoto, Kenichi Mizuno, Shuji Terai

ENDOSCOPY 47 E509 - E510 2015年

当院で経験した十二指腸静脈瘤破裂の４症例

佐々木嶺, 松田崇史, 相部祐希, 中島崇雄, 白築祥吾, 岩本拓也, 石川剛, 寺井崇二, 坂井田功

山口医学 64 ( 2 ) 145 - 152 2015年

記述言語：日本語出版者・発行元：山口大学医学会

十二指腸静脈瘤（Duodenal varices：DV）は，その豊富な血流のために一旦出血を来すと止血処置が困難で致死的状況となることがある．その治療方法や適応に関しては未だ一定の見解が得られていない．今回，我々はDV破裂の４症例を経験したので，当院のDV破裂に対する治療のフローチャートと文献的考察を加えて報告する．【症例１】C型肝硬変，胃癌術後の80歳代男性．黒色便精査後に十二指腸輸入脚深部のDV破裂の診断に至った．同病変に対して，シングルバルーン内視鏡を用いて67% N-butyl-2-cyanoacrylate（NBCA）による内視鏡的硬化療法（Endoscopic injection sclerotherapy with Cyanoacrylate：CA-EIS）を施行し止血を得た．【症例２】原発性胆汁性肝硬変の40歳代女性．貧血と黒色便精査のため上部消化管内視鏡検査を施行した．十二指腸水平脚に結節状のDVを認め，同部位より湧出性出血が認められたためCA-EISを施行し止血を得た．【症例３】B型肝硬変の50歳代男性．下血精査のため施行した腹部血管造影下CTと上部消化管内視鏡検査でDV破裂と診断した．内視鏡的静脈瘤結紮術（Endoscopic variceal ligation：EVL）で緊急止血を行い，根治目的でバルーン閉塞下逆行性経静脈的塞栓術（Balloon-occluded retrograde transvenous obliteration：B-RTO）を施行した．【症例４】アルコール性肝硬変の60歳代男性．黒色便精査の上部消化管内視鏡検査にて十二指腸下行脚に連珠状DVが認められた．CA-EIS後も滲出性出血が続き，EVLやアルゴンプラズマ凝固を追加し止血に至った．【結語】我々が経験した十二指腸静脈瘤破裂の４症例を報告した．食道胃静脈瘤の治療普及に伴って，今後十二指腸静脈瘤をはじめとした異所性静脈瘤が増加してくることが予想され，症例の蓄積と治療指針の確立が必要と考えられる．

DOI： 10.2342/ymj.64.145

CiNii Books

【肝胆膵診療のNew Horizon】肝臓疾患肝硬変肝性浮腫に対するバソプレシンV2受容体拮抗剤トルバプタンの使用法の提案肝性浮腫の発生機序から考える

その他リンク： http://www.lib.yamaguchi-u.ac.jp/yunoca/handle/B030064000210

寺井崇二, 田邊規和, 五嶋敦史, 坂井田功

肝胆膵 69 ( 6 ) 955 - 960 2014年12月

造影エコーにて評価した回腸NETの1例

佐伯一成, 高見太郎, 寺井崇二, 坂井田功

超音波医学 41 ( 6 ) 908 - 908 2014年11月

Association of tyrosine with insulin resistance in hepatitis C virus-related chronic liver disease 査読

Takashi Oono, Takahiro Yamasaki, Junichi Zaitsu, Issei Saeki, Takuya Iwamoto, Yumiko Harima, Yoshio Marumoto, Isao Hidaka, Yohei Urata, Tsuyoshi Ishikawa, Taro Takami, Makoto Segawa, Koichi Uchida, Shuji Terai, Ichiro Kunitugu, Tsuyoshi Tanabe, Isao Sakaida

HEPATOLOGY RESEARCH 44 ( 10 ) E54 - E62 2014年10月

Canine mesenchymal stem cells show antioxidant properties against thioacetamide-induced liver injury in vitro and in vivo 査読

Luiz Fernando Quintanilha, Taro Takami, Yoshikazu Hirose, Koichi Fujisawa, Yasuhiko Murata, Naoki Yamamoto, Regina Coeli dos Santos Goldenberg, Shuji Terai, Isao Sakaida

HEPATOLOGY RESEARCH 44 ( 10 ) E206 - E217 2014年10月

Occlusion of portosystemic shunts improves hyperinsulinemia due to insulin resistance in cirrhotic patients with portal hypertension 査読

Tsuyoshi Ishikawa, Shogo Shiratsuki, Takashi Matsuda, Takuya Iwamoto, Taro Takami, Koichi Uchida, Shuji Terai, Takahiro Yamasaki, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 49 ( 9 ) 1333 - 1341 2014年9月

Fatty Acid Binding Protein 7 Regulates Phagocytosis and Cytokine Production in Kupffer Cells during Liver Injury 査読

Hirofumi Miyazaki, Tomoo Sawada, Miwa Kiyohira, Zhiqian Yu, Keiji Nakamura, Yuki Yasumoto, Yoshiteru Kagawa, Majid Ebrahimi, Ariful Islam, Kazem Sharifi, Saki Kawamura, Takanori Kodama, Yui Yamamoto, Yasuhiro Adachi, Nobuko Tokuda, Shuji Terai, Isao Sakaida, Toshizo Ishikawa, Yuji Owada

AMERICAN JOURNAL OF PATHOLOGY 184 ( 9 ) 2505 - 2515 2014年9月

急性肝不全予後向上を目指す新規治療法の展望他家骨髄由来の間葉系幹細胞を用いた急性肝不全に対する肝臓再生療法の可能性

寺井崇二, 高見太郎, 坂井田功

肝臓 55 ( Suppl.2 ) A560 - A560 2014年9月

当科における肝硬変による体液貯留に対するトルバプタン投与症例の検討

田邉規和, 寺井崇二, 浦田洋平, 内田耕一, 坂井田功

肝臓 55 ( Suppl.2 ) A670 - A670 2014年9月

高齢C型慢性患者における抗ウイルス療法の効果と肝発癌について

花園忠相, 日高勲, 大野高嗣, 岩本拓也, 佐伯一成, 石川剛, 寺井崇二, 坂井田功

肝臓 55 ( Suppl.2 ) A665 - A665 2014年9月

肝細胞癌(HCC)に対し肝動脈化学塞栓術(TACE)施行後に腫瘍破裂を来した1例

福井悠美, 佐伯一成, 花園忠相, 田邊規和, 浦田洋平, 日高勲, 寺井崇二, 山崎隆弘, 坂井田功

山口医学 63 ( 3 ) 228 - 228 2014年8月

田邉規和, 高見太郎, 寺井崇二, 坂井田功

最新医学 69 ( 7月増刊 ) 1438 - 1445 2014年7月

【単球・マクロファージの多様性と病態】骨髄由来細胞を用いた肝線維化改善療法

寺井崇二, 高見太郎, 谷本治子, 岩本拓也, 坂井田功

血管医学 15 ( 2 ) 157 - 160 2014年7月

高齢者肝・胆・膵疾患の治療における諸問題当科における高齢者肝細胞癌患者の現状と治療成績についての検討

田邉規和, 佐伯一成, 浦田洋平, 寺井崇二, 坂井田功

日本高齢消化器病学会誌 17 ( 1 ) 45 - 45 2014年7月

当科における高齢C型慢性肝炎患者に対する抗ウイルス療法の特性

花園忠相, 日高勲, 佐伯一成, 岩本拓也, 石川剛, 寺井崇二, 坂井田功

日本高齢消化器病学会誌 17 ( 1 ) 79 - 79 2014年7月

Veno-occlusive diseaseを呈した薬物性肝障害の一例

石川剛, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 55 ( 7 ) 441 - 441 2014年7月

Status and Prospects of Liver Cirrhosis Treatment by Using Bone Marrow-Derived Cells and Mesenchymal Cells 査読

Shuji Terai, Taro Takami, Naoki Yamamoto, Koichi Fujisawa, Tsuyoshi Ishikawa, Yohei Urata, Haruko Tanimoto, Takuya Iwamoto, Yuko Mizunaga, Takashi Matsuda, Takashi Oono, Miho Marumoto, Guzel Burganova, Luiz Fernando Quintanilha, Isao Hidaka, Yoshio Marumoto, Issei Saeki, Koichi Uchida, Takahiro Yamasaki, Kenji Tani, Yasuho Taura, Yasuhiko Fujii, Hiroshi Nishina, Kiwamu Okita, Isao Sakaida

TISSUE ENGINEERING PART B-REVIEWS 20 ( 3 ) 206 - 210 2014年6月

Serum transferrin as a predictor of prognosis for hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma 査読

Junichi Zaitsu, Takahiro Yamasaki, Issei Saeki, Yohei Harima, Takuya Iwamoto, Yumiko Harima, Toshihiko Matsumoto, Yohei Urata, Isao Hidaka, Yoshio Marumoto, Tsuyoshi Ishikawa, Taro Takami, Naoki Yamamoto, Seiji Kaino, Koichi Uchida, Shuji Terai, Isao Sakaida

HEPATOLOGY RESEARCH 44 ( 5 ) 481 - 490 2014年5月

造影エコーによる部分的脾動脈塞栓術の評価

佐伯一成, 石川剛, 日高勲, 高見太郎, 寺井崇二, 坂井田功

超音波医学 41 ( Suppl. ) S596 - S596 2014年4月

Sorafenibに対する徐放化DFOの血管新生に関する検討

大野高嗣, 寺井崇二, 藤澤浩一, 高見太郎, 齊藤高志, 田畑泰彦, 坂井田功

肝臓 55 ( Suppl.1 ) A467 - A467 2014年4月

当科外来に受診している肝硬変の成因別実態

田邉規和, 寺井崇二, 岩本拓也, 佐伯一成, 浦田洋平, 日高勲, 石川剛, 高見太郎, 瀬川誠, 内田耕一, 坂井田功

肝臓 55 ( Suppl.1 ) A429 - A429 2014年4月

臨床応用を視野に入れた肝再生研究の新たな展開肝硬変に対する培養自己骨髄間葉系幹細胞投与による肝臓再生療法

高見太郎, 寺井崇二, 坂井田功

肝臓 55 ( Suppl.1 ) A76 - A76 2014年4月

C型慢性肝炎に対するIFN治療前後での肝線維化の改善とElastographyによる肝硬度の変化

日高勲, 花園忠相, 大野高嗣, 佐伯一成, 高見太郎, 寺井崇二, 坂井田功

超音波医学 41 ( Suppl. ) S601 - S601 2014年4月

【再生医療技術の新展開】現在実現化に最も近い、外科領域における再生医療研究骨髄細胞を用いた低侵襲な肝臓再生療法の開発

松田崇史, 高見太郎, 寺井崇二, 坂井田功

Surgery Frontier 21 ( 1 ) 19 - 23 2014年3月

【肝硬変-診断と治療の進歩】肝硬変治療の進歩骨髄由来細胞を用いた肝再生治療の現状と展望

白築祥吾, 高見太郎, 寺井崇二, 坂井田功

臨床消化器内科 29 ( 4 ) 479 - 484 2014年3月

生活習慣病と消化器疾患・病態生理学の新たな展開メダカモデルを用いた概日リズムの変化による非アルコール性脂肪肝炎の誘導に与える影響の解析

寺井崇二, 藤澤浩一, 坂井田功

日本消化器病学会雑誌 111 ( 臨増総会 ) A88 - A88 2014年3月

エゼチミブのNASHメダカへの作用とヒトNAFLD症例に対する使用経験の検討

大野高嗣, 寺井崇二, 大石俊之, 桑代紳哉, 藤澤浩一, 坂井田功

日本消化器病学会雑誌 111 ( 臨増総会 ) A402 - A402 2014年3月

Systemic Gemcitabine Combined with Hepatic Arterial Infusion Chemotherapy with Cisplatin, 5-Fluorouracil, and Isovorin for the Treatment of Advanced Intrahepatic Cholangiocarcinoma: A Pilot Study 査読

Miho Marumoto, Takahiro Yamasaki, Yoshio Marumoto, Issei Saeki, Yohei Harima, Yohei Urata, Isao Hidaka, Tsuyoshi Ishikawa, Taro Takami, Makoto Segawa, Yuhki Yamaguchi, Koichi Uchida, Shuji Terai, Isao Sakaida

HEPATO-GASTROENTEROLOGY 61 ( 129 ) 162 - 167 2014年1月

肝臓肝臓の再生療法

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2014 187 - 193 2014年1月

胃がんを対象とした内視鏡教育のための動画像を用いたシミュレーション型教材の開発（第2報）:医学生へのeラーニングによる教育の実践とその評価-

小柏香穂理, 浜本義彦, 藤田悠介, 西川潤, 寺井崇二, 坂井田功

ITヘルスケア誌 9 ( 2 ) 22 - 33 2014年

記述言語：日本語出版者・発行元：Japan Association of Applied IT Healthcare

本稿は，2009年にITヘルスケア誌に掲載された「胃がんを対象とした内視鏡教育のための動画像を用いたシミュレーション型教材」の続報で，開発した教材の有効性を学生に対する評価から検証したものである．本研究の目的は，先行論文で開発した内視鏡教育のためのシミュレーション型教材を活用して，医学生を対象とした教育実践とその評価について得られた知見を報告することである．本研究では，医学生82名（6年生31名，5年生51名）を対象に教育実践を行い，学生の学習履歴データを分析・評価した．その結果，主成分分析により教材中の8つの問題が，画像に関係する問題と画像に関係しない問題に類別されることがわかった．また，病変の範囲診断の評価では，「検出率－過検出率」という評価量を使って定量的に評価した結果，NBI（色素）画像が通常画像よりも読影に適していることがわかった．今回の調査結果から得られた知見として，内視鏡教育には，画像に関係する問題と画像に関係しない問題の両方を学習する必要性が明らかにされた．画像に関係する問題は従来のテキストによる学習だけでは限界があり，特に読影能力を高めるためには動画像を活用する問題を効果的に学習することが期待できるeラーニングが内視鏡教育に有効であると考えられる．

DOI： 10.11204/ithc.9.22

A Method of Bubble Removal for Computer-Assisted Diagnosis of Capsule Endoscopic Images. 査読

Masato Suenaga, Yusuke Fujita, Shinichi Hashimoto, Shuji Terai, Isao Sakaida, Yoshihiko Hamamoto

Modern Advances in Applied Intelligence - 27th International Conference on Industrial Engineering and Other Applications of Applied Intelligent Systems, IEA/AIE 2014, Kaohsiung, Taiwan, June 3-6, 2014, Proceedings, Part II 228 - 233 2014年

Tolvaptan for improvement of hepatic edema: A phase 3, multicenter, randomized, double-blind, placebo-controlled trial

Sakaida, I., Kawazoe, S., Kajimura, K., Saito, T., Okuse, C., Takaguchi, K., Okada, M., Okita, K., Masumoto, A., Kaneko, A., Inoue, A., Hasebe, C., Takesaki, E., Hayashi, E., Ohta, H., Morimoto, H., Yoshihara, H., Nishimura, H., Tsuruta, H., Ario, K., Iwase, H., Tanimura, H., Kumada, H., Hasegawa, H., Kohno, H., Hidaka, H., Moriwaki, H., Kobayashi, I., Shimoda, K., Tsuji, K., Yamamoto, K., Yokota, K., Yamauchi, M., Takahashi, M., Inada, M., Kawaguchi, M., Kudo, M., Tanaka, M., Mihara, M., Suzuki, M., Kato, M., Kitamoto, M., Murata, M., Higashi, N., Chida, N., Mano, Y., Inoue, O., Takano, S., Nakayama, S., Hayashi, S., Fujiyama, S., Fujioka, S., Shimizu, S., Katsushima, S., Kitamura, S., Kira, S., Nagaoka, S., Terai, S., Watanabe, S., Takahashi, S., Inoue, S., Yamaguchi, T., Satoh, T., Azuma, T., Igura, T., Komatsu, T., Tamura, T., Ito, T., Ueki, T., Muro, T., Morita, T., Nishigaki, Y., Ohnishi, Y., Karino, Y., Narahara, Y., Osaki, Y.

Hepatology Research 44 ( 1 ) 2014年

Dose-finding trial of tolvaptan in liver cirrhosis patients with hepatic edema: A randomized, double-blind, placebo-controlled trial

Okita, K., Kawazoe, S., Hasebe, C., Kajimura, K., Kaneko, A., Okada, M., Sakaida, I., Inoue, A., Yoshihara, H., Kumada, H., Ikeda, K., Kohno, H., Hidaka, H., Moriwaki, H., Inoue, J., Nakatsuka, K., Chayama, K., Katayama, K., Fujimura, K., Tsuji, K., Kumamoto, M., Yamazaki, M., Kawaguchi, M., Yoneda, M., Tanaka, M., Kato, M., Kitamoto, M., Endo, R., Suzuki, S., Watanabe, S., Kaneda, S., Yamashita, S., Nakayama, S., Kokubu, S., Tanaka, S., Katsushima, S., Aimitsu, S., Terai, S., Kawata, S., Saito, T., Ueki, T., Nouchi, T., Ohnishi, Y., Nishigaki, Y.

Hepatology Research 44 ( 1 ) 2014年

Re-response to tolvaptan after furosemide dose reduction in a patient with refractory ascites 査読

Atsushi Goto, Shuji Terai, Munetaka Nakamura, Masaharu Matsumoto, Isao Sakaida

Clinical Journal of Gastroenterology 8 ( 1 ) 47 - 51 2014年

Hepatic Crown-Like Structure: A Unique Histological Feature in Non-Alcoholic Steatohepatitis in Mice and Humans 査読

Michiko Itoh, Hideaki Kato, Takayoshi Suganami, Kuniha Konuma, Yoshio Marumoto, Shuji Terai, Hiroshi Sakugawa, Sayaka Kanai, Miho Hamaguchi, Takahiro Fukaishi, Seiichiro Aoe, Kazunari Akiyoshi, Yoshihiro Komohara, Motohiro Takeya, Isao Sakaida, Yoshihiro Ogawa

PLOS ONE 8 ( 12 ) e82163 2013年12月

Improvement of liver fibrosis by infusion of cultured cells derived from human bone marrow 査読

Haruko Tanimoto, Shuji Terai, Takami Taro, Yasuhiko Murata, Kouichi Fujisawa, Naoki Yamamoto, Isao Sakaida

CELL AND TISSUE RESEARCH 354 ( 3 ) 717 - 728 2013年12月

ソラフェニブの関与が疑われたネフローゼ症候群の2例

田邉規和, 浦田洋平, 白築祥吾, 岩本拓也, 佐伯一成, 播磨夕美子, 日高勲, 丸本芳雄, 石川剛, 高見太郎, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 54 ( Suppl.3 ) A857 - A857 2013年11月

限局性結節性過形成と鑑別困難であった巨大肝細胞癌の一例

佐伯一成, 大野高嗣, 浦田洋平, 高見太郎, 寺井崇二, 山崎隆弘, 徳久善弘, 為佐卓夫, 坂井田功

超音波医学 40 ( 6 ) 667 - 667 2013年11月

肝移植と再生医療のクロストーク自己骨髄細胞による肝臓再生療法の取り組み

高見太郎, 寺井崇二, 坂井田功

肝臓 54 ( Suppl.3 ) A666 - A666 2013年11月

エゼチミブのNASHに対する作用機序および臨床使用経験についての検討

大野高嗣, 寺井崇二, 大石俊之, 桑代紳哉, 藤澤浩一, 丸本芳雄, 坂井田功

肝臓 54 ( Suppl.3 ) A799 - A799 2013年11月

A study of liver cirrhosis classification on m-mode ultrasound images by higher-order local auto-correlation features

K. Fujino, Y. Mitani, T. Hayashi, Y. Fujita, Y. Hamamoto, M. Segawa, S. Terai, I. Sakaida

Proceedings of the SICE Annual Conference 1403 - 1404 2013年9月

再生医療の最前線肝硬変症に対する骨髄由来細胞を用いた再生療法

寺井崇二, 高見太郎, 坂井田功

日本内分泌学会雑誌 89 ( 2 ) 723 - 723 2013年9月

NASH発症におけるhepatic crown-like structureの意義

伊藤美智子, 菅波孝祥, 小沼邦葉, 丸本芳雄, 寺井崇二, 佐久川廣, 坂井田功, 小川佳宏

肥満研究 19 ( Suppl. ) 156 - 156 2013年9月

当科における肝細胞癌に対するソラフェニブ(SF)治療の検証

花園忠相, 浦田洋平, 岩本拓也, 佐伯一成, 日高勲, 丸本芳雄, 石川剛, 高見太郎, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

山口医学 62 ( 3 ) 175 - 175 2013年8月

The expanding role of fish models in understanding non-alcoholic fatty liver disease 査読

Yoichi Asaoka, Shuji Terai, Isao Sakaida, Hiroshi Nishina

DISEASE MODELS & MECHANISMS 6 ( 4 ) 905 - 914 2013年7月

【細胞移植】肝硬変症に対する自己骨髄由来培養髄細胞を用いた再生細胞療法

寺井崇二, 高見太郎, 坂井田功

細胞 45 ( 7 ) 327 - 329 2013年7月

Correlations between Obesity/Metabolic Syndrome-Related Factors and Risk of Developing Colorectal Tumors 査読

Satoko Harima, Shinichi Hashimoto, Hiroaki Shibata, Takaharu Matsunaga, Ryo Tanabe, Shuji Terai, Isao Sakaida

HEPATO-GASTROENTEROLOGY 60 ( 124 ) 733 - 737 2013年6月

Bortezomib induces tumor-specific cell death and growth inhibition in hepatocellular carcinoma and improves liver fibrosis 査読

Issei Saeki, Shuji Terai, Koichi Fujisawa, Taro Takami, Naoki Yamamoto, Toshihiko Matsumoto, Yoshikazu Hirose, Yasuhiko Murata, Takahiro Yamasaki, Isao Sakaida

Journal of Gastroenterology 48 ( 6 ) 738 - 750 2013年6月

チロシンは、C型慢性肝障害におけるインスリン抵抗性の新たなバイオマーカーとなり得る

在津潤一, 山崎隆弘, 佐伯一成, 岩本拓也, 播磨夕美子, 丸本芳雄, 日高勲, 浦田洋平, 石川剛, 高見太郎, 瀬川誠, 内田耕一, 寺井崇二, 坂井田功

肝臓 54 ( Suppl.1 ) A238 - A238 2013年4月

短期間で興味深いエコー像変化を呈した肝細胞癌の一例

佐伯一成, 日高勲, 松永一仁, 高見太郎, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 40 ( Suppl. ) S534 - S534 2013年4月

当科における肝細胞癌に対するソラフェニブ治療の検証とくに肝予備能と病勢制御に着目して

浦田洋平, 山崎隆弘, 佐伯一成, 岩本拓也, 播磨夕美子, 日高勲, 石川剛, 高見太郎, 内田耕一, 寺井崇二, 坂井田功

肝臓 54 ( Suppl.1 ) A284 - A284 2013年4月

Bone-marrow-derived cells cultured in serum-free medium reduce liver fibrosis and improve liver function in carbon-tetrachloride-treated cirrhotic mice 査読

Takuya Iwamoto, Shuji Terai, Takuro Hisanaga, Taro Takami, Naoki Yamamoto, Shoko Watanabe, Isao Sakaida

CELL AND TISSUE RESEARCH 351 ( 3 ) 487 - 495 2013年3月

【肝疾患と幹細胞をめぐる進歩】骨髄細胞投与による肝硬変症に対する肝再生・発癌抑制療法

高見太郎, 前田雅喜, 寺井崇二, 坂井田功

消化器内科 56 ( 3 ) 324 - 330 2013年3月

Crohn 病の経過中に非アルコール性脂肪性肝炎(NASH)から非代償性肝硬変へと進展した一例

田邉規和, 播磨夕美子, 橋本真一, 寺井崇二, 山崎隆弘, 坂井田功

山口医学 62 ( 1 ) 33 - 37 2013年2月

記述言語：日本語出版者・発行元：山口大学医学会

症例は31歳の女性.18歳時にCrohn病と診断され,当科での治療を開始された.経腸栄養療法や5-ASA製剤,ステロイドや抗TNFα抗体製剤等の内科的治療を行うも効果不十分であり,消化管合併症の悪化から24歳時に回腸部分切除術,26歳時に回盲部切除術,28歳時に回腸および上行結腸切除術を施行し,残存小腸は約280cmとなった.その後も症状は安定せず,成分栄養剤による経腸栄養療法を勧めるも患者の理解が得られず,長期の絶食および中心静脈栄養を施行していた.31歳時頃より,見当識障害および活動性低下が認められたため当科入院となった.腹部骨盤単純CT検査上,肝萎縮を伴う肝硬変の状態と考えられ,血液生化学検査にて著明な肝機能障害およびアンモニア値の上昇を認めたため,非代償性肝硬変症による肝性脳症と診断された.血液検査上HBVおよびHCV感染は否定され,飲酒歴もなく,以前より脂肪肝が認められ,肝胆道系酵素の上昇も認められていたことから,非アルコール性脂肪性肝炎(NASH)による非代償性肝硬変と診断した.年齢と肝機能から肝移植を考慮したが,適したドナーがいなかったことと,患者が肝移植を希望しなかったことから対症療法を継続した.その後もCrohn病や肝硬変の加療で入退院を繰り返し肝不全により死亡した.重症Crohn病の経過中に複数の要因からNASHを併発し非代償性肝硬変症へ進展した,極めてまれな症例を経験したため報告する.The patient was a 31-year-old woman who had been diagnosed with Crohn's disease at age 18 years. Enteral nutrition and medical treatment were given, but their effect was insufficient. Gastrointestinal complications worsened, and ileocecal resection was performed three times. The remaining small intestine was 280 cm. But, her symptoms were unstable. Thus long-term fasting and central venous nutrition were adopted. At 31 years old, she was hospitalized with cognitive dysfunction and decreased activity. CT scan showed liver cirrhosis(LC),and hepatic dysfunction and an elevated ammonia level were seen on blood tests. Therefore, she was diagnosed as hepatic encephalopathy from decompensated LC. Blood tests were negative for HBV and HCV infections, she had no history of drinking alcohol, fatty liver had been presented for some time, and elevated transaminase were seen. This led to a diagnosis of LC resulting from non-alcoholic steatohepatitis(NASH).Liver transplantation was considered, but there was no appropriate donor, and the patient did not desire. Therefore, symptomatic therapy was continued. She was repeatedly hospitalized and finally died from liver failure. We report that the rare case in which NASH occurred due to multiple factors during the course of severe Crohn's disease and progressed to decompensated LC.

DOI： 10.2342/ymj.62.33

J-GLOBAL

【再生医療の実現化に向けて】肝硬変症に対する自己骨髄細胞投与療法

Medaka fish, Oryzias latipes, as a model for human obesity-related glomerulopathy 査読

Koichiro Ichimura, Yusuke Kawashima, Tomomi Nakamura, Rebecca Powell, Yuya Hidoh, Shuji Terai, Isao Sakaida, Yoshio Kodera, Takashi Tsuji, Jian-Xing Ma, Tatsuo Sakai, Hiroyuki Matsumoto, Tomoko Obara

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 431 ( 4 ) 712 - 717 2013年2月

消化器領域における幹細胞研究の進歩培養骨髄由来細胞を用いた肝硬変症に対する修復療法の開発へのProof of Concept

寺井崇二, 高見太郎, 坂井田功

日本消化器病学会雑誌 110 ( 臨増総会 ) A83 - A83 2013年2月

丸本美穂, 寺井崇二, 丸本芳雄, 高見太郎, 坂井田功

炎症と免疫 21 ( 2 ) 142 - 147 2013年2月

肝線維化の診断と臨床自己骨髄細胞による肝硬変に対する再生修復療法の現状と展望

高見太郎, 寺井崇二, 坂井田功

Japanese Journal of Diagnostic Imaging 31 ( 1 ) 30 - 30 2013年2月

An improvement of liver cirrhosis classification using ultrasonic images

Hayashi, T., Fujita, Y., Mitani, Y., Hamamoto, Y., Segawa, M., Terai, S., Sakaida, I.

IEEJ Transactions on Electronics, Information and Systems 133 ( 2 ) 289 - 296 2013年1月

肝臓肝臓の再生療法

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2013 196 - 202 2013年1月

A liver cirrhosis detection method using probabilistic ROI combination 査読

Y. Fujita, T. Goto, Y. Mitani, Y. Hamamoto, M. Segawa, S. Terai, I. Sakaida

Proceedings of 11th International Conference on Quality Control by Artificial Vision 81 - 85 2013年

超音波画像を用いた肝硬変識別の高精度化査読

林孝哉, 藤田悠介, 三谷芳弘, 浜本義彦, 瀬川誠, 寺井崇二, 坂井田功

電気学会論文誌C 133 ( 2 ) 289 - 296 2013年

A note of liver cirrhosis classification on M-mode ultrasound images by higher-order local auto-correlation features. 査読

K. Fujino, Yoshihiro Mitani, T. Hayashi, Yusuke Fujita, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

2013 International Conference on Soft Computing and Pattern Recognition, SoCPaR 2013, Hanoi, Vietnam, December 15-18, 2013 50 - 53 2013年

Liver Resident Stem Cell 査読

Christina M. Takiya, Bruno Diaz Paredes, Luiz Fernando Quintanilha de Mesquita, Grazielle Suhett Dias, Lanuza Alaby Pinheiro Faccioli, Taro Takami, Shuji Terai, Isao Sakaida, Regina Coeli dos Santos Goldenberg

Resident Stem Cells and Regenerative Therapy 177 - 203 2013年

肝疾患に対する先端医療骨髄由来培養細胞を用いた肝臓修復再生療法の実現化準備ヒト幹細胞を用いた臨床指針を踏まえて

寺井崇二, 高見太郎, 坂井田功

日本消化器病学会雑誌 109 ( 臨増大会 ) A424 - A424 2012年9月

骨髄細胞投与による酸化ストレス制御を介した肝発癌抑制メカニズムの解明

高見太郎, 寺井崇二, 前田雅喜, 坂井田功

日本消化器病学会雑誌 109 ( 臨増大会 ) A721 - A721 2012年9月

肝発癌・進展機序研究に与える幹細胞学のインパクトゼブラフィッシュ肝発癌モデルを用いた肝細胞幼若化、老化に関する検討

藤澤浩一, 寺井崇二, 坂井田功

肝臓 53 ( Suppl.2 ) A591 - A591 2012年9月

Advanced Therapies Using Autologous Bone Marrow Cells for Chronic Liver Disease 査読

Taro Takami, Shuji Terai, Isao Sakaida

DISCOVERY MEDICINE 14 ( 74 ) 7 - 12 2012年7月

【肝硬変update より良き診療のために】肝硬変診療のトピックス自己骨髄細胞を用いた肝修復再生療法の現状

高見太郎, 寺井崇二, 坂井田功

Medicina 49 ( 7 ) 1238 - 1239 2012年7月

Effect of transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma 査読

Takahiro Yamasaki, Issei Saeki, Yohei Harima, Junichi Zaitsu, Masaki Maeda, Haruko Tanimoto, Takuya Iwamoto, Isao Hidaka, Yohei Urata, Tsuyoshi Ishikawa, Taro Takami, Yuhki Yamaguchi, Koichi Uchida, Shuji Terai, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 47 ( 6 ) 715 - 722 2012年6月

Therapeutic Potential of Canine Bone Marrow Stromal Cells (BMSCs) in the Carbon Tetrachloride (CCl4) Induced Chronic Liver Dysfunction Mouse Model 査読

Tomoya Haraguchi, Kenji Tani, Ryo Takagishi, Yasutaka Oda, Kazuhito Itamoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida, Hiroshi Nakazawa, Yasuho Taura

JOURNAL OF VETERINARY MEDICAL SCIENCE 74 ( 5 ) 607 - 611 2012年5月

Stem cell therapy in chronic liver disease 査読

Taro Takami, Shuji Terai, Isao Sakaida

CURRENT OPINION IN GASTROENTEROLOGY 28 ( 3 ) 203 - 208 2012年5月

Timeline for development of autologous bone marrow infusion (ABMi) therapy and perspective for future stem cell therapy 査読

Shuji Terai, Haruko Tanimoto, Masaki Maeda, Junichi Zaitsu, Takuro Hisanaga, Takuya Iwamoto, Koichi Fujisawa, Yuko Mizunaga, Toshihiko Matsumoto, Yohei Urata, Yoshio Marumoto, Isao Hidaka, Tsuyoshi Ishikawa, Yuichiro Yokoyama, Koji Aoyama, Masako Tsuchiya, Taro Takami, Kaoru Omori, Naoki Yamamoto, Makoto Segawa, Koichi Uchida, Takahiro Yamasaki, Kiwamu Okita, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 47 ( 5 ) 491 - 497 2012年5月

Ezetimibe reduces fatty acid quantity in liver and decreased inflammatory cell infiltration and improved NASH in medaka model 査読

Toshiyuki Oishi, Shuji Terai, Shinya Kuwashiro, Koichi Fujisawa, Toshihiko Matsumoto, Hiroshi Nishina, Isao Sakaida

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 422 ( 1 ) 22 - 27 2012年5月

Matrix Metalloproteinases (MMPs) Activity in Cultured Canine Bone Marrow Stromal Cells (BMSCs) 査読

Tomoya Haraguchi, Kenji Tani, Masato Koga, Yasutaka Oda, Kazuhito Itamoto, Naoki Yamamoto, Shuji Terai, Isao Sakaida, Hiroshi Nakazawa, Yasuho Taura

JOURNAL OF VETERINARY MEDICAL SCIENCE 74 ( 5 ) 633 - 636 2012年5月

Clear cell typeの肝細胞癌の一例

土屋昌子, 石川剛, 高見太郎, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 39 ( Suppl. ) S408 - S408 2012年4月

Splenectomy enhances the anti-fibrotic effect of bone marrow cell infusion and improves liver function in cirrhotic mice and patients 査読

Takuya Iwamoto, Shuji Terai, Yuko Mizunaga, Naoki Yamamoto, Kaoru Omori, Koichi Uchida, Takahiro Yamasaki, Yasuhiko Fujii, Hiroshi Nishina, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 47 ( 3 ) 300 - 312 2012年3月

Autologous bone marrow cell infusions suppress tumor initiation in hepatocarcinogenic mice with liver cirrhosis 査読

Masaki Maeda, Taro Takami, Shuji Terai, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 27 104 - 111 2012年3月

Hepatic arterial infusion chemotherapy in combination with pegylated interferon-α-2b for advanced hepatocellular carcinoma. 査読

Okita K, Yamasaki T, Hamabe S, Saeki I, Harima Y, Terai S, Sakaida I

Hepato-gastroenterology 59 ( 114 ) 533 - 537 2012年3月

当科における肝細胞癌に対するsorafenibの治療成績

浦田洋平, 山崎隆弘, 在津潤一, 日高勲, 石川剛, 土屋昌子, 内田耕一, 寺井崇二, 坂井田功

日本消化器病学会雑誌 109 ( 臨増総会 ) A281 - A281 2012年3月

肝臓肝臓の再生治療

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2012 192 - 197 2012年1月

Advanced therapies using autologous bone marrow cells for chronic liver disease.

Takami, T., Terai, S., Sakaida, I.

Discovery medicine 14 ( 74 ) 2012年

Granulocyte colony-stimulating factor and interleukin-1β are important cytokines in repair of the cirrhotic liver after bone marrow cell infusion: comparison of humans and model mice. 査読

Mizunaga Y, Terai S, Yamamoto N, Uchida K, Yamasaki T, Nishina H, Fujita Y, Shinoda K, Hamamoto Y, Sakaida I

Cell transplantation 21 ( 11 ) 2363 - 2375 2012年

Autologous bone marrow cell infusion therapy to repair and regenerate liver 査読

Shuji Terai, Isao Sakaida

Seikagaku 84 ( 8 ) 707 - 711 2012年

内視鏡的静脈瘤結紫術・バルーン閉塞下逆行性経静脈的塞栓術併用療法で止血し得た十二指腸静脈瘤破裂の1例

松田崇史, 石川剛, 末永成之, 五嶋敦史, 浜辺功一, 岩本拓也, 橋本真一, 中島好晃, 岡田宗正, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

山口医学 60 ( 6 ) 237 - 242 2011年12月

記述言語：日本語出版者・発行元：山口大学医学会

57歳の男性.B型肝硬変・肝細胞癌に対して外来経過観察中,下血に対する精査加療目的で当科に緊急入院した.上部消化管内視鏡検査(EGD)で十二指腸下行脚に静脈瘤が認められたものの活動性出血および血液貯留の所見はなく,下部消化管内視鏡検査･カプセル内視鏡検査･経肛門的ダブルバルーン内視鏡検査においても回腸~結腸内に凝血塊の貯留が認められたのみで出血源の同定には至らなかった.腹部血管造影検査では十二指腸周辺に著明な門脈系-大循環系短絡路の発達が認められ,血管造影下CTで十二指腸下行脚付近に造影剤の血管外漏出が疑われた.直後の緊急EGDにより十二指腸静脈瘤破裂と診断し,内視鏡的静脈瘤結紮術(EVL)にて一次止血に成功した.しかしその2日後に出血性ショックに陥ったため,EVLで止血した上で引き続きバルーン閉塞下逆行性経静脈的塞栓術(B-RTO)を施行して完全止血を得た.十二指腸静脈瘤破裂は非常に稀な難治性消化管出血であるが,今回我々はEVL･B-RTO併用療法で止血し救命し得た症例を経験したので報告する.A 57-year-old male with hepatitis B virus-related liver cirrhosis, who had undergone right lobectomy and radiofrequency ablation for hepatocellular carcinoma, was admitted to our department for the purpose of examination and treatment of melena. Esophagogastroduodenoscopy (EGD) on admission showed duodenal varices without active bleeding in the 2nd portion of duodenum. In addition, total colonoscopy, capsule endoscopy, and double-balloon endoscopy via the anal demonstrated massive dark-red clot in the ileum and colon, but not pointed out a source of bleeding. Thereafter, the angiography via superior mesenteric artery revealed large portalsystemic shunts around the duodenum and computed tomography during arteriography showed extravasation at the 2nd portion of duodenum. Urgent EGD enabled us to diagnose as ruptured duodenal varices and endoscopic variceal ligation (EVL) was successfully performed. However, two days later, he suffered from hemorrhagic shock because of rebleeding of duodenal varices and balloon-occluded retrograde transvenous obliteration (B-RTO) after second EVL finally led to complete hemostasis. We report this rare case of ruptured duodenal varices treated by combination therapy of EVL and BRTO in a cirrhotic patient.

DOI： 10.2342/ymj.60.237

多発性肝転移に対し, Degradable starch microspheres (DSM) とリピオドールによる肝動脈化学塞栓療法を施行後, オクトレオチド酢酸塩を継続投与した回腸原発神経内分泌腫瘍肝転移の一例

大野高嗣, 瀬川誠, 橋本真一, 内田耕一, 寺井崇二, 山崎隆弘, 星井嘉信, 坂井田功

山口医学 60 ( 6 ) 255 - 261 2011年12月

記述言語：日本語出版者・発行元：山口大学医学会

症例は50歳代女性．健診の腹部超音波検査で多発肝腫瘤を指摘され当院を受診．ダブルバルーン小腸内視鏡で回腸に多発する腫瘤性病変を認め，生検により，回腸原発神経内分泌腫瘍の多発肝転移と診断された．肝転移病巣に対し，微小デンプン球（degradable starch microspheres：DSM）とリピオドールを用いた肝動脈化学塞栓療法を施行し，良好な腫瘍縮小効果を認めた．さらに，術後に持続性ソマトスタチンアナログマイクロスフェア型徐放性製剤（オクトレオチド酢酸塩徐放性製剤：商品名：サンドスタチンLAR筋注用）を継続投与し，長期間にわたる腫瘍の増殖抑制効果を維持し得た．切除不能の消化管神経内分泌腫瘍の肝転移症例に対する治療法として有用であると考えられた．

DOI： 10.2342/ymj.60.255

Melanocortin 4 Receptor-Deficient Mice as a Novel Mouse Model of Nonalcoholic Steatohepatitis 査読

Michiko Itoh, Takayoshi Suganami, Nobutaka Nakagawa, Miyako Tanaka, Yukio Yamamoto, Yasutomi Kamei, Shuji Terai, Isao Sakaida, Yoshihiro Ogawa

AMERICAN JOURNAL OF PATHOLOGY 179 ( 5 ) 2454 - 2463 2011年11月

肝細胞癌・慢性関節リウマチの加療中に悪性リンパ腫を発症した一例

播磨博文, 石川剛, 土屋昌子, 内田耕一, 星井嘉信, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 52 ( Suppl.3 ) A954 - A954 2011年11月

TNFR1-mediated signaling is important to induce the improvement of liver fibrosis by bone marrow cell infusion 査読

Takuro Hisanaga, Shuji Terai, Takuya Iwamoto, Taro Takami, Naoki Yamamoto, Tomoaki Murata, Toshifumi Matsuyama, Hiroshi Nishina, Isao Sakaida

CELL AND TISSUE RESEARCH 346 ( 1 ) 79 - 88 2011年10月

Senescence marker protein 30 (SMP30)/regucalcin (RGN) expression decreases with aging, acute liver injuries and tumors in zebrafish 査読

Koichi Fujisawa, Shuji Terai, Yoshikazu Hirose, Taro Takami, Naoki Yamamoto, Isao Sakaida

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 414 ( 2 ) 331 - 336 2011年10月

Potential Therapeutic Application of Intravenous Autologous Bone Marrow Infusion in Patients with Alcoholic Liver Cirrhosis 査読

Takafumi Saito, Kazuo Okumoto, Hiroaki Haga, Yuko Nishise, Rika Ishii, Chikako Sato, Hisayoshi Watanabe, Akio Okada, Motoki Ikeda, Hitoshi Togashi, Tsuyoshi Ishikawa, Shuji Terai, Isao Sakaida, Sumio Kawata

STEM CELLS AND DEVELOPMENT 20 ( 9 ) 1504 - 1511 2011年9月

肝疾患と幹細胞炎症、再生、発癌まで骨髄細胞頻回投与による肝細胞がん合併肝硬変症に対する修復再生・抗腫瘍療法開発のための基礎研究

高見太郎, 寺井崇二, 坂井田功

日本消化器病学会雑誌 108 ( 臨増大会 ) A687 - A687 2011年9月

肝疾患動物モデルとtranslational research 肝硬変症に対する骨髄由来培養細胞を用いた修復再生療法開発のために橋渡し研究

寺井崇二, 高見太郎, 坂井田功

日本消化器病学会雑誌 108 ( 臨増大会 ) A566 - A566 2011年9月

Deferoxamine for Advanced Hepatocellular Carcinoma 査読

Takahiro Yamasaki, Shuji Terai, Isao Sakaida

NEW ENGLAND JOURNAL OF MEDICINE 365 ( 6 ) 576 - 578 2011年8月

内視鏡的静脈瘤硬化結紮療法後におけるAT3製剤投与による門脈血栓予防効果

浜辺功一, 石川剛, 岩本拓也, 瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

日本門脈圧亢進症学会雑誌 17 ( 3 ) 111 - 111 2011年8月

肝細胞癌との鑑別に苦慮した脈絡膜悪性黒色腫肝転移の1例

在津潤一, 石川剛, 播磨陽平, 土屋昌子, 高見太郎, 山口裕樹, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 52 ( 7 ) 468 - 476 2011年7月

記述言語：日本語出版者・発行元：一般社団法人日本肝臓学会

左脈絡膜悪性黒色腫に対する手術歴（2004年4月，左眼球摘出術）を有する79歳の男性患者が2009年10月に右季肋部痛を主訴に当院外来を受診した．血液検査にて軽度の肝機能障害と高度の凝固系異常が認められたため精査加療目的で同日当科に緊急入院となった．HBs抗原・抗HBs抗体・抗HBc-IgG抗体・抗HCV抗体はいずれも陰性であり，腹部超音波検査・CT検査・MRI検査・血管造影検査で肝両葉に多血性腫瘤が多数認められた．悪性黒色腫に特異的な腫瘍マーカーである5-S-cysteinyldopaが異常高値を呈したがPIVKA IIも著明に上昇していたため画像・血液検査所見からは悪性黒色腫肝転移と肝細胞癌の鑑別には至らなかった．超音波下肝腫瘍生検にて悪性黒色腫の確定診断を得た上で同病変に対してシスプラチンを用いた肝動脈化学塞栓療法を施行した．今回我々は「脈絡膜悪性黒色腫肝転移」という非常に稀な一例を経験したので報告する．

DOI： 10.2957/kanzo.52.468

An abdominal aorta wall extraction for liver cirrhosis classification using ultrasonic images

Takaya Hayashi, Yusuke Fujita, Yoshihiro Mitani, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

AIP Conference Proceedings 1371 343 - 344 2011年7月

Splenectomy reduces fibrosis and preneoplastic lesions with increased triglycerides and essential fatty acids in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet 査読

Toshiyuki Oishi, Shuji Terai, Takuya Iwamoto, Taro Takami, Naoki Yamamoto, Isao Sakaida

HEPATOLOGY RESEARCH 41 ( 5 ) 463 - 474 2011年5月

Telmisartan improves nonalcoholic steatohepatitis in medaka (Oryzias latipes) by reducing macrophage infiltration and fat accumulation 査読

Shinya Kuwashiro, Shuji Terai, Toshiyuki Oishi, Koichi Fujisawa, Toshihiko Matsumoto, Hiroshi Nishina, Isao Sakaida

CELL AND TISSUE RESEARCH 344 ( 1 ) 125 - 134 2011年4月

Imaging mass spectrometry reveals characteristic changes in triglyceride and phospholipid species in regenerating mouse liver 査読

Norio Miyamura, Takashi Nakamura, Naoko Goto-Inoue, Nobuhiro Zaima, Takahiro Hayasaka, Tokiwa Yamasaki, Shuji Terai, Isao Sakaida, Mitsutoshi Setou, Hiroshi Nishina

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 408 ( 1 ) 120 - 125 2011年4月

HHMは肝細胞増殖を抑制する

藤澤浩一, 寺井崇二, 桑代紳哉, 松本俊彦, 高見太郎, 山本直樹, 坂井田功

肝臓 52 ( Suppl.1 ) A198 - A198 2011年4月

肝再生医学研究の新展開効率的な肝硬変症に対する骨髄細胞を用いた修復再生療法の開発のための基礎的検討

寺井崇二, 高見太郎, 坂井田功

肝臓 52 ( Suppl.1 ) A117 - A117 2011年4月

A novel transcatheter arterial infusion chemotherapy using iodized oil and degradable starch microspheres for hepatocellular carcinoma: a prospective randomized trial 査読

Takahiro Yamasaki, Satoe Hamabe, Issei Saeki, Yohei Harima, Yuhki Yamaguchi, Koichi Uchida, Shuji Terai, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 46 ( 3 ) 359 - 366 2011年3月

Current State and Future Prospects for Our Liver Regeneration Therapy Using Autologous Bone Marrow Cells for Decompensated Liver Cirrhosis Patients 査読

Taro Takami, Shuji Terai, Isao Sakaida

JOURNAL OF PHARMACOLOGICAL SCIENCES 115 ( 3 ) 274 - 278 2011年3月

非代償性肝硬変の合併症とその対策肝硬変症に対する次世代型骨髄由来培養細胞を用いた修復再生療法の開発

寺井崇二, 高見太郎, 坂井田功

日本消化器病学会雑誌 108 ( 臨増総会 ) A147 - A147 2011年3月

当科で経験したHBVキャリア急性増悪を来たした二例

内田耕一, 瀬川誠, 柴田大明, 植木谷俊之, 播磨陽平, 土屋昌子, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功, 加藤彰, 木村輝明, 山下智省, 沖田極

肝臓 52 ( 3 ) 222 - 222 2011年3月

Autologous bone marrow cell infusion therapy for liver cirrhosis patients 査読

Shuji Terai, Isao Sakaida

JOURNAL OF HEPATO-BILIARY-PANCREATIC SCIENCES 18 ( 1 ) 23 - 25 2011年1月

Efficient detection of hepatocellular carcinoma by a hybrid blood test of epigenetic and classical protein markers 査読

Norio Iizuka, Masaaki Oka, Isao Sakaida, Toyoki Moribe, Toshiaki Miura, Naoki Kimura, Shigeru Tamatsukuri, Hideo Ishitsuka, Koichi Uchida, Shuji Terai, Satoyoshi Yamashita, Kiwamu Okita, Koichiro Sakata, Yoshiyasu Karino, Joji Toyota, Eiji Ando, Tatsuya Ide, Michio Sata, Ryoichi Tsunedomi, Masahito Tsutsui, Michihisa Iida, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Takao Tamesa, Yusuke Fujita, Yoshihiko Hamamoto

CLINICA CHIMICA ACTA 412 ( 1-2 ) 152 - 158 2011年1月

肝臓肝疾患の再生治療

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2011 223 - 228 2011年1月

C型慢性肝炎におけるエラストグラフィの有用性

江角智子, 高見太郎, 岸田由香里, 堤寛子, 松尾亜矢, 石川剛, 瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 37 ( 6 ) 679 - 679 2010年11月

Sonazoid造影エコー検査では肝細胞癌との鑑別が困難であった脈絡膜悪性黒色腫肝転移の一例

大石俊之, 石川剛, 土屋昌子, 高見太郎, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 37 ( 6 ) 676 - 677 2010年11月

門脈圧亢進症における病態進行度の指標としての肝弾性値の有用性

瀬川誠, 浜辺功一, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 37 ( 6 ) 679 - 679 2010年11月

再生医療臨床研究の現状各シーズの臨床研究進捗状況肝臓骨髄由来liver repair cell(LR細胞)の開発

坂井田功, 宮島篤, 小川佳宏, 松山晃文, 佐々木功典, 寺井崇二

臨床評価 38 ( 3 ) 589 - 592 2010年10月

Helicobacter pylori CagA inhibits endocytosis of cytotoxin VacA in host cells 査読

Junko K. Akada, Hiroki Aoki, Yuji Torigoe, Takao Kitagawa, Hisao Kurazono, Hisashi Hoshida, Jun Nishikawa, Shuji Terai, Masunori Matsuzaki, Toshiya Hirayama, Teruko Nakazawa, Rinji Akada, Kazuyuki Nakamura

DISEASE MODELS & MECHANISMS 3 ( 9-10 ) 605 - 617 2010年9月

肝臓の再生機構を考える今後の肝再生医療への展望骨髄由来Liver Repair cell(LR細胞)を用いた肝臓再生修復療法の開発について

寺井崇二, 高見太郎, 坂井田功

肝臓 51 ( Suppl.2 ) A450 - A450 2010年9月

メダカNASHモデルを用いた薬物スクリーニングについて

寺井崇二, 大石俊之, 桑代紳哉, 松本俊彦, 坂井田功

肥満研究 16 ( Suppl. ) 144 - 144 2010年9月

肝胆膵疾患と組織幹細胞/progenitor cell 病態解析と治療戦略 Oval cellの活性化に伴う肝再生・修復過程におけるHGF/c-Metシグナリングの役割

石川剛, 寺井崇二, 坂井田功

肝臓 51 ( Suppl.2 ) A511 - A511 2010年9月

Ezetimibeは肝臓の脂肪酸構成と脂肪沈着を改善する

大石俊之, 寺井崇二, 桑代紳哉, 藤澤浩一, 坂井田功

肥満研究 16 ( Suppl. ) 144 - 144 2010年9月

門脈圧亢進症に対するPSEと脾摘の有用性部分的脾動脈塞栓術における血小板増加予測因子と肝予備能改善効果

石川剛, 浜辺功一, 大森薫, 高見太郎, 瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

日本門脈圧亢進症学会雑誌 16 ( 2 ) 69 - 69 2010年8月

食道・胃静脈瘤の予防的治療バルーン閉塞下逆行性経静脈的塞栓術の肝機能改善効果

石川剛, 浜辺功一, 大森薫, 高見太郎, 瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

日本門脈圧亢進症学会雑誌 16 ( 2 ) 57 - 57 2010年8月

バルーン閉塞下逆行性経静脈的塞栓術(B-RTO)前後での食道静脈瘤増悪の有無別の検討

浜辺功一, 瀬川誠, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功

日本門脈圧亢進症学会雑誌 16 ( 2 ) 97 - 97 2010年8月

門脈圧亢進症の血行動態門脈圧亢進症における病態進行度の指標としての肝弾性値の有用性

瀬川誠, 浜辺功一, 石川剛, 寺井崇二, 山崎隆弘, 坂井田功

日本門脈圧亢進症学会雑誌 16 ( 2 ) 50 - 50 2010年8月

Medaka as a model for human nonalcoholic steatohepatitis 査読

Toshihiko Matsumoto, Shuji Terai, Toshiyuki Oishi, Shinya Kuwashiro, Koichi Fujisawa, Naoki Yamamoto, Yusuke Fujita, Yoshihiko Hamamoto, Makoto Furutani-Seiki, Hiroshi Nishina, Isao Sakaida

DISEASE MODELS & MECHANISMS 3 ( 7-8 ) 431 - 440 2010年7月

【NASH】基礎的メカニズムの解明ヒト類似のメダカ非アルコール性脂肪肝炎(NASH)モデルの開発

寺井崇二, 松本俊彦, 大石俊之, 桑代紳哉, 坂井田功

The Lipid 21 ( 3 ) 235 - 246 2010年7月

Effect of a late evening snack using branched-chain amino acid-enriched nutrients in patients undergoing hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma 査読

Yohei Harima, Takahiro Yamasaki, Satoe Hamabe, Issei Saeki, Kohsuke Okita, Shuji Terai, Isao Sakaida

HEPATOLOGY RESEARCH 40 ( 6 ) 574 - 584 2010年6月

肝細胞癌との鑑別に苦慮した悪性黒色腫肝転移の一例

在津潤一, 石川剛, 播磨陽平, 土屋昌子, 高見太郎, 山口裕樹, 内田耕一, 寺井崇二, 山崎隆弘, 坂井田功

山口医学 59 ( 3 ) 146 - 146 2010年6月

肝病態形成における酸化ストレスの意義メダカNASHモデルの病態にERストレス、酸化ストレス及び炎症細胞浸潤が関わりテルミサルタンは脂肪酸酸化の増加によりその病態進展を抑制する

桑代紳哉, 寺井崇二, 大石俊之, 藤澤浩一, 松本俊彦, 坂井田功

肝臓 51 ( Suppl.1 ) A91 - A91 2010年4月

肝弾性値と門脈圧との関連性についての検討

瀬川誠, 浜辺功一, 石川剛, 大森薫, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 51 ( Suppl.1 ) A349 - A349 2010年4月

HGF/c-Metシグナリングはoval cell由来肝再生に必須である

石川剛, 寺井崇二, 坂井田功

肝臓 51 ( Suppl.1 ) A257 - A257 2010年4月

後天的脂肪肝メダカと先天的脂肪肝メダカを用いたNASH病態解析

大石俊之, 寺井崇二, 桑代紳哉, 藤澤浩一, 坂井田功

肝臓 51 ( Suppl.1 ) A384 - A384 2010年4月

Retinoic acid signaling positively regulates liver specification by inducing wnt2bb gene expression in medaka

Negishi, T, Nagai, Y, Asaoka, Y, Ohno, M, Namae, M, Mitani, H, Sasaki, T, Shimizu, N, Terai, S, Sakaida, I, Kondoh, H, Katada, T, Furutani-Seiki, M, Nishina, H

Hepatology 51 ( 3 ) 1037 - 45 2010年3月

UNLABELLED: During vertebrate embryogenesis, the liver develops at a precise location along the endodermal primitive gut tube because of signaling delivered by adjacent mesodermal tissues. Although several signaling molecules have been associated with liver formation, the molecular mechanism that regulates liver specification is still unclear. We previously performed a screen in medaka to isolate mutants with impaired liver development. The medaka hio mutants exhibit a profound (but transient) defect in liver specification that resembles the liver formation defect found in zebrafish prometheus (prt) mutants, whose mutation occurs in the wnt2bb gene. In addition to their liver abnormality, hio mutants lack pectoral fins and die after hatching. Positional cloning indicated that the hio mutation affects the raldh2 gene encoding retinaldehyde dehydrogenase type2 (RALDH2), the enzyme principally responsible for retinoic acid (RA) biosynthesis. Mutations of raldh2 in zebrafish preclude the development of pectoral fins. Interestingly, in hio mutants, expression of wnt2bb in the lateral plate mesoderm (LPM) directly adjacent to the liver-forming endoderm was completely lost. CONCLUSION: Ou

DOI： 10.1002/hep.23387

細胞操作技術の最前線(第7回) 細胞治療技術肝硬変も治る時代へ、自己細胞で肝炎治療

Retinoic Acid Signaling Positively Regulates Liver Specification by Inducing wnt2bb Gene Expression in Medaka 査読

Takahiro Negishi, Yoko Nagai, Yoichi Asaoka, Mami Ohno, Misako Namae, Hiroshi Mitani, Takashi Sasaki, Nobuyoshi Shimizu, Shuji Terai, Isao Sakajda, Hisato Kondoh, Toshiaki Katada, Makoto Furutani-Seiki, Hiroshi Nishina

HEPATOLOGY 51 ( 3 ) 1037 - 1045 2010年3月

高見太郎, 寺井崇二, 坂井田功

Medical Bio 7 ( 2 ) 54 - 57 2010年3月

HGF/c-Metシグナリングはoval cell由来肝再生に必須である

石川剛, 寺井崇二, 坂井田功

日本消化器病学会雑誌 107 ( 臨増総会 ) A261 - A261 2010年3月

Fish model leads to new findings in liver disease 査読

Shuji Terai

HEPATOLOGY RESEARCH 40 ( 1 ) 111 - 113 2010年1月

肝臓肝疾患における再生治療・細胞療法の展望

高見太郎, 寺井崇二, 坂井田功

Annual Review消化器 2010 201 - 206 2010年1月

An Improved Method for Cirrhosis Detection Using Liver's Ultrasound Images. 査読

Yusuke Fujita, Yoshihiko Hamamoto, Makoto Segawa, Shuji Terai, Isao Sakaida

20th International Conference on Pattern Recognition, ICPR 2010, Istanbul, Turkey, 23-26 August 2010 2294 - 2297 2010年

Autologous Bone Marrow Infusion Activates the Progenitor Cell Compartment in Patients With Advanced Liver Cirrhosis 査読

Ja Kyung Kim, Young Nyun Park, Jin Seok Kim, Mi-Suk Park, Yong Han Paik, Jae-Yeon Seok, Yong Eun Chung, Hyun Ok Kim, Kyung Sik Kim, Sang Hoon Ahn, Do Young Kim, Myeong-Jin Kim, Kwan Sik Lee, Chae Yoon Chon, Soo Jeong Kim, Shuji Terai, Isao Sakaida, Kwang-Hyub Han

CELL TRANSPLANTATION 19 ( 10 ) 1237 - 1246 2010年

【幹細胞を用いた消化器再生医療の展望】肝硬変症は幹細胞再生医療で治せるか

高見太郎, 寺井崇二, 坂井田功

分子消化器病 6 ( 4 ) 359 - 364 2009年12月

経皮的ドレナージ術と経過観察に Sonazoid^【○!R】造影超音波検査が有用であった, 肝膿瘍の1例

大森薫, 谷本治子, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 50 ( 11 ) 657 - 664 2009年11月

記述言語：日本語出版者・発行元：一般社団法人日本肝臓学会

症例は60代男性．主訴は発熱と右季肋部痛．CTで肝右葉に60&times;40 mmの膿瘍を指摘された．腹部超音波検査Bモードでは，膿瘍と背景肝の境界が不明瞭で，安全かつ確実な穿刺ドレナージが困難であった．Sonazoid&reg;造影超音波検査のKupffer imageでは50 mmの膿瘍腔・壊死部が明瞭に描出され，経皮経肝膿瘍ドレナージ術を施行した．その後もSonazoid&reg;造影超音波検査により，治癒経過を観察しえた．肝膿瘍の経皮的ドレナージ術と経過観察に，造影超音波検査が有用であった肝膿瘍の1例を経験した．

DOI： 10.2957/kanzo.50.657

CiNii Books

【NASH 非アルコール性脂肪肝炎治療の現状と課題】NASHの治療瀉血療法の可能性

Sonazoid造影超音波検査が治療と評価に有用であった肝膿瘍の一例

高見太郎, 大森薫, 谷本治子, 土屋昌子, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 36 ( 6 ) 701 - 701 2009年11月

Sonazoid造影超音波検査が診断に有用であった肝細胞癌の一例

土屋昌子, 高見太郎, 寺井崇二, 山崎隆弘, 坂井田功

超音波医学 36 ( 6 ) 701 - 701 2009年11月

【肝細胞癌の予防】肝発癌制御におけるMaidシグナルの重要性について

寺井崇二, 藤澤浩一, 坂井田功

消化器科 49 ( 5 ) 444 - 448 2009年11月

肝硬変の対策原因療法から合併症の対策非代償性肝硬変症に対する自己骨髄細胞投与療法の現状と今後の展開

高見太郎, 寺井崇二, 坂井田功

肝臓 50 ( Suppl.3 ) A626 - A626 2009年10月

寺井崇二, 松本俊彦, 坂井田功

治療学 43 ( 10 ) 1107 - 1110 2009年10月

NASH研究の最前線メダカNASHモデルの特性を生かした薬物スクリーニングについて

寺井崇二, 松本俊彦, 坂井田功

肝臓 50 ( Suppl.3 ) A606 - A606 2009年10月

門脈圧亢進症に対する総合的なアプローチ B-RTOとPSE

大森薫, 浜辺功一, 石川剛, 瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

肝臓 50 ( Suppl.3 ) A721 - A721 2009年10月

Telmisartanの投与によるマクロファージ浸潤抑制を含めたNASHの改善効果検討

桑代紳哉, 寺井崇二, 大石俊之, 藤澤浩一, 松本俊彦, 坂井田功

肥満研究 15 ( Suppl. ) 185 - 185 2009年9月

Ezetimibは肝マクロファージの肝臓への遊走を低下させNASH病態を改善する

大石俊之, 寺井崇二, 有吉平, 桑代紳哉, 藤澤浩一, 坂井田功

肥満研究 15 ( Suppl. ) 185 - 185 2009年9月

肝癌発生・進展の分子機構と臨床への還元 HHM(Maid)の肝発癌の制御分子としての重要性について

寺井崇二, 藤澤浩一, 高見太郎, 山崎隆弘, 坂井田功

肝臓 50 ( Suppl.1 ) A97 - A97 2009年4月

TelmisartanはメダカNASHモデルにおいてER stressを改善し炎症細胞浸潤を抑制し病態を改善する

桑代紳哉, 寺井崇二, 大石俊之, 藤澤浩一, 松本俊彦, 坂井田功

肝臓 50 ( Suppl.1 ) A384 - A384 2009年4月

Ezetimibeは小腸に作用することで、肝脂肪沈着、炎症細胞浸潤を低下させNASH病態を改善させる

大石俊之, 寺井崇二, 有吉平, 桑代紳哉, 藤澤浩一, 坂井田功

肝臓 50 ( Suppl.1 ) A384 - A384 2009年4月

Hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma: Is the addition of subcutaneous interferon-alpha-2b beneficial? 査読

Satoe Takaki-Hamabe, Takahiro Yamasaki, Issei Saeki, Yohei Harima, Kohsuke Okita, Shuji Terai, Isao Sakaida

HEPATOLOGY RESEARCH 39 ( 3 ) 223 - 230 2009年3月

Hematopoiesis-dependent expression of CD44 in murine hepatic progenitor cells 査読

Shinya Ohata, Makiko Nawa, Takeshi Kasama, Tokiwa Yamasaki, Kenji Sawanobori, Shoji Hata, Takashi Nakamura, Yoichi Asaoka, Toshio Watanabe, Hitoshi Okamoto, Takahiko Hara, Shuji Terai, Isao Sakaida, Toshiaki Katada, Hiroshi Nishina

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 379 ( 4 ) 817 - 823 2009年2月

On a diagnostic imaging teaching system for endoscopic education 査読

K. Ogashiwa, Y. Hamamoto, Y. Fujita, K. Murokawa, H. Yoneda, M. Saito, S. Terai, I. Sakaida

Proceedings of 1st Asia Pacific Conference on Health Promotion and Education 2009年1月

Continuos intravenous infusion of atrial natriuretic peptide(ANP) prevented liver fibrosis in rat 査読

Noriko Ishigaki, Naold Yamamoto, Haiyan Jin, Kouichi Uchida, Shuji Terai, Isao Sakaida

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 378 ( 3 ) 354 - 359 2009年1月

肝硬変症に対する自己骨髄細胞投与療法の現状と今後の展望

寺井崇二, 坂井田功

日本医科大学医学会雑誌 5 ( 1 ) 27 - 32 2009年

Current status of autologous bone marrow cell infusion therapy for liver cirrhosis patients 査読

Shuji Terai, Isao Sakaida

HEPATOLOGY RESEARCH 38 S72 - S75 2008年11月

Relation between serum levels of cell-free DNA and inflammation status in hepatitis C virus-related hepatocellular carcinoma 査読

Michihisa Iida, Norio Iizuka, Isao Sakaida, Toyoki Moribe, Nozomi Fujita, Toshiaki Miura, Shigeru Tamatsukuri, Hideo Ishitsuka, Koichi Uchida, Shuji Terai, Yoshihiro Tokuhisa, Kazuhiko Sakamoto, Takao Tamesa, Takanobu Miyamoto, Yoshihiko Hamamoto, Masaaki Oka

ONCOLOGY REPORTS 20 ( 4 ) 761 - 765 2008年10月

消化器疾患の分子遺伝学的病態 HGF/c-Met signalingによるredox homeostasisの維持が肝発癌増殖を抑制する

高見太郎, 寺井崇二, 坂井田功

日本消化器病学会雑誌 105 ( 臨増大会 ) A672 - A672 2008年9月

Hepatocyte growth factor/c-met signaling pathwayの欠損はDEN誘発肝発癌早期段階を促進させる(Loss of hepatocyte growth factor/c-met signaling pathway accelerates early stages of DEN-induced hepatocarcinogenesis)

高見太郎, 内田耕一, 寺井崇二, 坂井田功

日本癌学会総会記事 67回 179 - 179 2008年9月

生活習慣病合併肝癌患者におけるHeat shock proteinおよび小胞体ストレス関連分子の発現の検討

大石俊之, 寺井崇二, 桑代紳哉, 松本俊彦, 坂井田功

肥満研究 14 ( Suppl. ) 202 - 202 2008年9月

メダカNASHモデルを用いた治療剤開発のストラテジー

寺井崇二, 桑代紳哉, 大石俊之, 松本俊彦, 坂井田功

肥満研究 14 ( Suppl. ) 189 - 189 2008年9月

メダカNASHモデルを用いたTelmisartanの効果検討

桑代紳哉, 寺井崇二, 大石俊之, 松本俊彦, 坂井田功

肥満研究 14 ( Suppl. ) 235 - 235 2008年9月

Hepatic stem cellとcancer stem cell Maid分子からみた幹細胞の分化と癌化の接点に関する検討

寺井崇二, 藤澤浩一, 坂井田功

肝臓 49 ( Suppl.2 ) A427 - A427 2008年9月

Pilot study of combination therapy with transcatheter arterial infusion chemotherapy using iodized oil and percutaneous radiofrequency ablation during occlusion of hepatic blood flow for hepatocellular carcinoma 査読

Ryt Shiraishi, Takahiro Yamasaki, Issei Saeki, Kohsuke Ok-Ita, Ytthki Yamaguchi, Koichi Uchida, Shuji Terai, Isao Salfaida

AMERICAN JOURNAL OF CLINICAL ONCOLOGY-CANCER CLINICAL TRIALS 31 ( 4 ) 311 - 316 2008年8月

c-Metシグナル伝達経路はredox制御機構の安定化から肝発癌増殖抑制作用を有する

高見太郎, 内田耕一, 寺井崇二, 坂井田功

G.I.Research 16 ( 4 ) 372 - 373 2008年8月

肝の発癌と進展における分子代謝学的研究 Hepatocyte growth factor(HGF)/c-met signaling pathwayの肝発癌機構における意義

高見太郎, 内田耕一, 寺井崇二, 坂井田功

肝臓 49 ( Suppl.1 ) A44 - A44 2008年4月

非アルコール性脂肪性肝疾患の病態と治療メダカモデルから人へ NASH治療剤の開発の新ストラテジー

寺井崇二, 松本俊彦, 坂井田功

肝臓 49 ( Suppl.1 ) A36 - A36 2008年4月

Increased expression of heat shock protein-binding protein 1 and heat shock protein 70 in human hepatocellular carcinoma tissues 査読

Yuichiro Yokoyama, Yasuhiro Kuramitsu, Motonari Takashima, Masanori Fujimoto, Norio Iizuka, Shuji Terai, Kiwamu Okita, Isao Sakaida, Masaaki Oka, Deborah A. Raynes, Vince Guerriero, Kazuyuki Nakamura

MOLECULAR MEDICINE REPORTS 1 ( 2 ) 197 - 201 2008年3月

Continuous high expression of XBP1 and GRP78 is important for the survival of bone marrow cells in CCl4-treated cirrhotic liver 査読

Yoshio Marumoto, Shuji Tera, Yohei Urata, Toshihiko Matsumoto, Yuko Mizunaga, Naoki Yamamoto, Haiyan Jina, Koichi Fujisawa, Tomoaki Murata, Koh Shinoda, Hiroshi Nishina, Isao Sakaida

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 367 ( 3 ) 546 - 552 2008年3月

A new hepatic encephalopathy model to monitor the change of neural amino acids and astrocytes with behaviour disorder 査読

Yumiko Isobe-Harima, Shuji Terai, Izumi Miura, Makoto Segawa, Tomoaki Murata, Kazuhito Itamoto, Yasuho Taura, Koh Shinoda, Isao Sakaida

LIVER INTERNATIONAL 28 ( 1 ) 117 - 125 2008年1月

Serum S100b (astrocyte-specific protein) is a useful marker of hepatic encephalopathy in patients with fulminant hepatitis 査読

Yumiko Isobe-Harima, Shuji Terai, Makoto Segawa, Koichi Uchida, Takahiro Yamasaki, Isao Sakaida

LIVER INTERNATIONAL 28 ( 1 ) 146 - 147 2008年1月

FibroScanを用いた食道静脈瘤の存在診断の現状

瀬川誠, 寺井崇二, 山崎隆弘, 坂井田功

日本門脈圧亢進症学会雑誌 14 ( 4 ) 313 - 316 2008年

記述言語：日本語出版者・発行元：日本門脈圧亢進症学会

肝硬変の診断方法として, 肝臓の硬さの診断は, 主として触診によってなされてきたが, 最近の技術の進歩により, 超音波を用いて非侵襲的に肝臓の硬さ (肝硬度, 肝弾性値) を測定する機器 (FibroScan) が臨床応用され, 肝線維化の進行と肝弾性値が相関することが明らかとなり, 肝線維化の非侵襲的な評価方法として確立しつつある.一方で, 肝弾性値は, 肝線維化などの静的因子に加え, 血流, 炎症, 胆汁鬱滞などの動的因子も関与していることが明らかになってきた.肝弾性値と門脈圧との関連性が検討されつつあり, 肝弾性値測定による門脈圧亢進症診断への応用が試みられている.肝弾性値測定により, 門脈圧亢進症の合併症である食道静脈瘤の存在診断が可能となれば, 現在肝硬変患者に対しての非侵襲的な定期検査の実施も期待できる.本総説では, 肝弾性値測定による門脈圧亢進症診断に関する現状を述べる.

DOI： 10.11423/jsph1999.14.4_313

治療薬シリーズ高脂血症非アルコール性脂肪性肝疾患、肝炎に対する薬物療法について

その他リンク： http://search.jamas.or.jp/link/ui/2009287768

Telmisartan prevents hepatic fibrosis and enzyme-altered lesions in liver cirrhosis rat induced by a choline-deficient L-amino acid-defined diet 査読

Haiyan Jin, Naoki Yamamoto, Koichi Uchida, Shuji Terai, Isao Sakaida

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 364 ( 4 ) 801 - 807 2007年12月

強皮症に肝細胞癌と乳癌を合併した一例

佐伯一成, 是永匡紹, 岩本拓也, 松本俊彦, 瀬川誠, 山口裕樹, 是永圭子, 内田耕一, 寺井崇二, 山崎隆弘, 為佐卓夫, 岡正朗, 坂井田功

肝臓 48 ( Suppl3 ) A622 - A622 2007年11月

NASHにおける肝線維化と発癌をめぐって耐糖能異常は脂肪肝症例における肝線維化・発癌のリスクファクターの可能性がある

松本俊彦, 寺井崇二, 坂井田功

肝臓 48 ( Suppl3 ) A514 - A514 2007年11月

The development of new drug screening system using steatohepatitis medaka fish model induced by high-fat diet 査読

Matsumoto Toshihiko, Terai Shuji, Kuwashiro Shinya, Fujisawa Koichi, Yamamoto Naoki, Hamamoto Yoshihiko, Sakaida Isao

HEPATOLOGY 46 ( 4 ) 756A 2007年10月

Is an arterial infusion chemotherapy with pegylated interferon-alpha-2b effective for advanced hepatocellular carcinoma? 査読

Yamasaki Takahiro, Saeki Issei, Okita Kousuke, Yamaguchi Yuhki, Uchida Koichi, Terai Shuji, Sakaida Isao

JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY 22 A193 2007年10月

肝の再生医学・医療/人工肝臓の現状と展望肝硬変症に対する自己骨髄細胞投与療法(ABMI療法)の現状および今後の工夫について

寺井崇二, 丸本芳雄, 坂井田功

肝臓 48 ( Suppl.2 ) A357 - A357 2007年9月

メダカNASHモデルにおける病態解析

松本俊彦, 寺井崇二, 坂井田功

肝臓 48 ( Suppl.2 ) A474 - A474 2007年9月

Importance of inhibitor of DNA binding/differentiation 2 in hepatic stellate cell differentiation and proliferation 査読

Kunihiko Tajima, Shuji Terai, Taro Takami, Kotaro Kawaguchi, Kiwamu Okita, Isao Sakaida

HEPATOLOGY RESEARCH 37 ( 8 ) 647 - 655 2007年8月

The iron chelator deferoxamine causes activated hepatic stellate cells to become quiescent and to undergo apoptosis 査読

Haiyan Jin, Shuii Terai, Isao Sakaida

JOURNAL OF GASTROENTEROLOGY 42 ( 6 ) 475 - 484 2007年6月

[Candidate drugs for non-alcoholic steatohepatitis (NASH)]. 査読

Terai S, Matsumoto T, Sakaida I

Nihon yakurigaku zasshi. Folia pharmacologica Japonica 129 ( 4 ) 271 - 275 2007年4月

記述言語：日本語出版者・発行元：公益社団法人日本薬理学会

非アルコール性脂肪性肝炎（NASH）は肝硬変症に進行する病態であり，その病態としてFree fatty acid（FFA），Tumor necrosis factor-α（TNF-α），レプチン，レジスチンの上昇とアディポネクチンの低下が報告されている．これらの変化は体重の減量によって可逆的で，NASHの改善につながることが知られているが，実際には生活習慣の改善が難しい症例が多く，NASHの病態から考えた薬物療法が必要とされている．薬物療法は4つの方向性が考えられる．(1)インスリン抵抗性の改善（インスリン抵抗性改善薬），(2)脂肪酸生合成の抑制と肝内に蓄積した脂肪酸の燃焼（高脂血症薬），(3)脂肪酸の代謝過程で生じた酸化ストレスからの保護（抗酸化剤や肝庇護剤）である．(4)さらに抗NASH作用を持つアディポネクチンのレセプターに対するアゴニストや抗TNF-α剤なども，今後，検討すべきだろう．また，肝線維化抑制の側面より，アンジオテンシンIIレセプター拮抗薬が，NASHにおける肝線維化抑制薬として作用する可能性が期待される．

DOI： 10.1254/fpj.129.271

その他リンク： https://jlc.jst.go.jp/DN/JALC/00291948050?from=CiNii

寺井崇二, 松本俊彦, 坂井田功

日本薬理学雑誌 129 ( 4 ) 271 - 275 2007年4月

Administration of fibroblast growth factor 2 in combination with bone marrow transplantation synergistically improves carbon-tetrachloride-induced liver fibrosis in mice 査読

Tsuyoshi Ishikawa, Shuji Terai, Yohei Urata, Yoshio Marumoto, Koji Aoyama, Tomoaki Murata, Yuko Mizunaga, Naoki Yamamoto, Hiroshi Nishina, Koh Shinoda, Isao Sakaida

CELL AND TISSUE RESEARCH 327 ( 3 ) 463 - 470 2007年3月

Circulating cell-free DNA as a predictive marker for distant metastasis of hepatitis C virus-related hepatocellular carcinoma 査読

Tokuhisa, Y., Iizuka, N., Sakaida, I., Moribe, T., Fujita, N., Miura, T., Tamatsukuri, S., Ishitsuka, H., Uchida, K., Terai, S., Sakamoto, K., Tamesa, T., Oka, M.

British Journal of Cancer 97 ( 10 ) 1399 - 1403 2007年

Elevated levels of circulating cell-free DNA in the blood of patients with hepatitis C virus-associated hepatocellular carcinoma 査読

Norio Iizuka, Isao Sakaida, Toyoki Moribe, Nozomi Fujita, Toshiaki Miura, Markus Stark, Shigeru Tamatsukuri, Hideo Ishitsuka, Koichi Uchida, Shuji Terai, Kazuhiko Sakamoto, Takao Tamesa, Masaaki Oka

ANTICANCER RESEARCH 26 ( 6C ) 4713 - 4719 2006年11月

Improved liver function in patients with liver cirrhosis after autologous bone marrow cell infusion therapy 査読

Shuji Terai, Tsuyoshi Ishikawa, Kaoru Omori, Koji Aoyama, Yoshio Marumoto, Yohei Urata, Yuichirou Yokoyama, Koichi Uchida, Takahiro Yamasaki, Yasuhiko Fujii, Kiwamu Okita, Isao Sakaida

STEM CELLS 24 ( 10 ) 2292 - 2298 2006年10月

【消化器疾患 state of arts II.肝・胆・膵】治療法をめぐる最近の進歩肝再生医療の現況と展望細胞療法を用いた肝再生医療自己骨髄細胞を用いた肝再生療法の開発

丸本芳雄, 寺井崇二, 坂井田功

医学のあゆみ別冊 ( 消化器疾患Ver.3 ) 495 - 498 2006年10月

rFGF2併用骨髄移植の肝線維化改善効果とその分子制御機構

石川剛, 寺井崇二, 坂井田功

肝臓 47 ( Suppl.2 ) A477 - A477 2006年9月

消化器疾患の再生医療自己骨髄細胞を用いた肝臓再生療法の現状と今後の展開

寺井崇二, 石川剛, 坂井田功

日本消化器病学会雑誌 103 ( 臨増大会 ) A413 - A413 2006年9月

Proteomic analysis of serum marker proteins in recipient mice with liver cirrhosis after bone marrow cell transplantation 査読

Y Yokoyama, S Terai, T Ishikawa, K Aoyama, Y Urata, Y Marumoto, N Hiroshi, K Nakamura, K Okita, Sakaida, I

PROTEOMICS 6 ( 8 ) 2564 - 2570 2006年4月

XBP-1は骨髄細胞から肝細胞への分化に関与する

丸本芳雄, 寺井崇二, 水永裕子, 松本俊彦, 浦田洋平, 青山浩司, 石川剛, 坂井田功

肝臓 47 ( Suppl.1 ) A292 - A292 2006年4月

メダカを用いた新規脂肪肝モデルの作成と,脂肪肝形成過程における遺伝子発現の検討

松本俊彦, 寺井崇二, 丸本芳雄, 仁科博史, 坂井田功

肝臓 47 ( Suppl.1 ) A97 - A97 2006年4月

肝線維化の分子機構と治療 rFGF2併用骨髄移植の肝線維化改善効果とその分子制御機構

石川剛, 寺井崇二, 坂井田功

肝臓 47 ( Suppl.1 ) A41 - A41 2006年4月

Protein level of apolipoprotein E increased in human hepatocellular carcinoma 査読

Y Yokoyama, Y Kuramitsu, M Takashima, N Iizuka, S Terai, M Oka, K Nakamura, K Okita, Sakaida, I

INTERNATIONAL JOURNAL OF ONCOLOGY 28 ( 3 ) 625 - 631 2006年3月

炎症と発癌肝持続炎症環境下における小胞体ストレス関連分子XBP-1とHSPの発現についての解析

丸本芳雄, 寺井崇二, 坂井田功

日本消化器病学会雑誌 103 ( 臨増総会 ) A127 - A127 2006年3月

Fibroblast growth factor 2 facilitates the differentiation of transplanted bone marrow cells into hepatocytes 査読

T Ishikawa, S Terai, Y Urata, Y Marumoto, K Aoyama, Sakaida, I, T Murata, H Nishina, K Shinoda, S Uchimura, Y Hamamoto, K Okita

CELL AND TISSUE RESEARCH 323 ( 2 ) 221 - 231 2006年2月

【ここまで進んだ幹細胞研究と再生医療2006 幹細胞の分化を運命づけるメカニズムから臨床応用の取り組み,産業化の展望まで】幹細胞の臨床応用ここまで来ている再生医療自己骨髄細胞を用いた肝臓再生療法の開発基礎研究から臨床研究へ

石川剛, 寺井崇二, 坂井田功

実験医学 24 ( 2 ) 268 - 273 2006年1月

脂肪肝に対するイコサペント酸エチル(エパデールS)の有用性の検討

松本俊彦, 寺井崇二, 坂井田功

肝臓 46 ( Suppl.3 ) A562 - A562 2005年11月

急性肝不全における肝再生療法の現状 rFGF2併用骨髄移植による肝障害改善効果とその分子制御機構

石川剛, 寺井崇二, 坂井田功, 沖田極

肝臓 46 ( 11 ) 678 - 678 2005年11月

肝病変進展抑制をめざす新しい視点基礎と臨床 rFGF2併用骨髄移植による肝病変改善効果とその分子制御機構

石川剛, 寺井崇二, 沖田極

日本消化器病学会雑誌 102 ( 臨増大会 ) A574 - A574 2005年9月

肝病変進展抑制をめざす新しい視点基礎と臨床 rFGF2併用骨髄移植による肝病変改善効果とその分子制御機構

石川剛, 寺井崇二, 沖田極

肝臓 46 ( Suppl.2 ) A374 - A374 2005年9月

Leptin enhances TNF-alpha production via p38 and JNK MAPK in LPS-stimulated Kupffer cells 査読

JH Shen, Sakaida, I, K Uchida, S Terai, K Okita

LIFE SCIENCES 77 ( 13 ) 1502 - 1515 2005年8月

Human homologue of maid is a useful marker protein in hepatocarcinogenesis 査読

T Takami, S Terai, Y Yokoyama, H Tanimoto, K Tajima, K Uchida, T Yamasaki, Sakaida, I, H Nishina, SS Thorgeirsson, K Okita

GASTROENTEROLOGY 128 ( 5 ) 1369 - 1380 2005年5月

レトロウイルスベクターを用いたId2持続強制発現HSc-T6での線維化抑制の検討

田島邦彦, 寺井崇二, 金海燕, 磯部夕美子, 松本俊彦, 浦田洋平, 丸本芳雄, 川口浩太郎, 高見太郎, 土屋昌子, 内田耕一, 坂井田功, 沖田極

肝臓 46 ( Suppl.1 ) A68 - A68 2005年5月

骨髄細胞から肝細胞への分化過程における線維芽細胞増殖因子の促進効果

石川剛, 寺井崇二, 磯部夕美子, 松本俊彦, 浦田洋平, 丸本芳雄, 青山浩司, 大森薫, 坂井田功, 沖田極

肝臓 46 ( Suppl.1 ) A157 - A157 2005年5月

Liv-8陰性分画骨髄細胞移植による肝線維化改善時における,ECM関連遺伝子群の経時的発現変化の検討

青山浩司, 坂井田功, 磯部夕美子, 松本俊彦, 浦田洋平, 丸本芳雄, 石川剛, 大森薫, 寺井崇二, 沖田極

肝臓 46 ( Suppl.1 ) A71 - A71 2005年5月

PCR-selected cDNA subtractionシステムを用いた骨髄細胞から肝細胞への分化制御遺伝子の検索

丸本芳雄, 寺井崇二, 松本俊彦, 浦田洋平, 青山浩司, 石川剛, 大森薫, 坂井田功, 仁科博史, 沖田極

肝臓 46 ( Suppl.1 ) A101 - A101 2005年5月

臨床研究(自己骨髄細胞を用いた肝臓再生療法)の途中経過と頻回骨髄細胞の投与法への工夫

寺井崇二, 大森薫, 石川剛, 青山浩司, 浦田洋平, 丸本芳雄, 坂井田功, 沖田極

肝臓 46 ( Suppl.1 ) A57 - A57 2005年5月

骨髄幹細胞移植による肝疾患の治療

沖田極, 寺井崇二, 坂井田功

日本内科学会雑誌 94 ( 4 ) 769 - 774 2005年4月

記述言語：日本語出版者・発行元：The Japanese Society of Internal Medicine

骨髄には造血幹細胞が存在し白血病患者に対する骨髄移植によって患者の体内で一生に渡り血球細胞を供給することが可能である.骨髄移植は既に20年以上の実績を積んだ体性幹細胞を用いた再生医療である.最近になり男女間での骨髄移植の結果,骨髄由来の肝細胞,小腸細胞への分化が確認され,骨髄中に多分化能を持つ"骨髄由来幹細胞"の存在が考えられるようになった.すでに循環器領域では虚血性疾患に対して臨床応用として血管新生を誘導するために自己の骨髄細胞を患部に自家移植する試みがすでに行われてきた.我々は自己骨髄細胞を用いた肝臓再生療法を開発するため,どんな状況で骨髄細胞移植が有効であるかを検討し,持続肝障害が続く状態において骨髄細胞が肝再生誘導,肝線維化制御に役立つことを見出した.さらにそれらの基礎研究の結果を基盤とし,国内最初の臨床研究:自己骨髄細胞を用いた肝臓再生療法のPhasel研究を平成15年11月より開始し現在進行中である.

DOI： 10.2169/naika.94.769

CiNii Books

Treatment of hepatic diseases with bone marrow stem cell transplantation 査読

その他リンク： https://jlc.jst.go.jp/DN/JALC/00249900949?from=CiNii

Use of bone marrow cells for the development of cellular therapy in liver diseases 査読

Sakaida, I, S Terai, K Okita

HEPATOLOGY RESEARCH 31 ( 4 ) 195 - 196 2005年4月

Okita, K., Terai, S., Sakaida, I.

Nihon Naika Gakkai zasshi. The Journal of the Japanese Society of Internal Medicine 94 ( 4 ) 769 - 774 2005年4月

消化器領域における細胞増殖因子と組織再生療法を目指したニューフロンティア基礎から臨床へ骨髄細胞から肝細胞への分化過程における線維芽細胞増殖因子の促進効果

石川剛, 寺井崇二, 沖田極

日本消化器病学会雑誌 102 ( 臨増総会 ) A156 - A156 2005年3月

Percutaneous radiofrequency ablation with cooled electrodes combined with hepatic arterial balloon occlusion in hepatocellular carcinoma 査読

T Yamasaki, T Kimura, F Kurokawa, KJ Aoyama, T Ishikawa, K Tajima, Y Yokoyama, T Takami, K Omori, K Kawaguchi, M Tsuchiya, S Terai, Sakaida, I, K Okita

JOURNAL OF GASTROENTEROLOGY 40 ( 2 ) 171 - 178 2005年2月

Prognostic factors in patients with advanced hepatocellular carcinoma receiving hepatic arterial infusion chemotherapy 査読

T Yamasaki, T Kimura, F Kurokawa, K Aoyama, T Ishikawa, K Tajima, Y Yokoyama, T Takami, K Omori, K Kawaguchi, M Tsuchiya, S Terai, Sakaida, I, K Okita

JOURNAL OF GASTROENTEROLOGY 40 ( 1 ) 70 - 78 2005年1月

Development of New Therapy in Fulminant Hepatitis from Glucagon-Insulin Therapy to Bone Marrow Cell Transplantation

Kiwamu Okita, Isao Sakaida, Shuji Terai, Naoki Yamamoto, Kaoru Omori, Tsuyoshi Ishikawa, Kouji Aoyama, Koh Shinoda, Yoshihiko Hamamoto

International Journal of Oncology 52 ( 3-4 ) 25 - 31 2005年

Development of cell therapy using autologous bone marrow cells for liver cirrhosis 査読

Isao Sakaida, Shuji Terai, Hiroshi Nishina, Kiwamu Okita

Medical Molecular Morphology 38 ( 4 ) 197 - 202 2005年

Lesson from the GFP/CCl4 model - Translational Research Project: the development of cell therapy using autologous bone marrow cells in patients with liver cirrhosis 査読

S Terai, Sakaida, I, H Nishina, K Okita

JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY 12 ( 3 ) 203 - 207 2005年

Molecular signature associated with plasticity of bone marrow cell under persistent liver damage by self-organizing-map-based gene expression 査読

K Omori, S Terai, T Ishikawa, K Aoyama, Sakaida, I, H Nishina, K Shinoda, S Uchimura, Y Hamamoto, K Okita

FEBS LETTERS 578 ( 1-2 ) 10 - 20 2004年12月

Transplantation of bone marrow cells reduces CCl4-induced liver fibrosis in mice 査読

Sakaida, I, S Terai, N Yamamoto, K Aoyama, T Ishikawa, H Nishina, K Okita

HEPATOLOGY 40 ( 6 ) 1304 - 1311 2004年12月

自己骨髄細胞を用いた肝硬変症に対する肝臓再生療法

寺井崇二, 大森薫, 石川剛, 青山浩司, 高見太郎, 横山雄一郎, 田島邦彦, 坂井田功, 沖田極

治療学 38 ( 10 ) 1158 - 1159 2004年10月

肝発癌機構におけるhelix-loop-helix(HLH)型転写制御分子の発現とその制御

高見太郎, 寺井崇二, 沖田極

肝臓 45 ( Suppl.2 ) A486 - A486 2004年9月

骨髄細胞の肝細胞への分化過程において変動する血清蛋白質の解析

横山雄一郎, 寺井崇二, 大森薫, 青山浩司, 石川剛, 高見太郎, 坂井田功, 沖田極

日本癌学会総会記事 63回 505 - 506 2004年9月

肝発癌早期に高発現するHHM(Human Homologue of Maid)のプロモーター解析と,肝疾患患者血清中の抗HHM抗体の検出

高見太郎, 寺井崇二, 横山雄一郎, 田島邦彦, 谷本治子, 仁科博史, 坂井田功, 沖田極

日本癌学会総会記事 63回 295 - 295 2004年9月

肝細胞癌に対する新しいバルーンマイクロカテーテルを用いたリピオドール併用肝動脈バルーン閉塞下ラジオ波凝固療法

山崎隆弘, 木村輝昭, 浦田洋平, 丸本芳雄, 青山浩司, 石川剛, 田島邦彦, 横山雄一郎, 大森薫, 川口浩太郎, 高見太郎, 土屋昌子, 山口裕樹, 寺井崇二, 黒川典枝, 坂井田功, 沖田極

肝臓 45 ( 9 ) 505 - 506 2004年9月

記述言語：日本語出版者・発行元：(一社)日本肝臓学会

肝細胞癌4例を対象に,新しいバルーンマイクロカテーテルを用いたリピオドール併用肝動脈バルーン閉塞下ラジオ波凝固療法を施行した.通常の腹部血管造影の手技にて,5Frカテーテルを用い,精査を行い,マイクロカテーテルにてTranscatheter arterial chemoembolizationを施行し,腫瘍内にリピオドールをpoolingさせた後,Equinox occlusion balloon catheterを胆癌領域の肝動脈に留置し,バルーン閉塞後に経皮的ラジオ波凝固療法を施行した.治療効果判定として1週間後の造影CTで凝固範囲を測定した.12分間1回穿刺での凝固範囲が検討できたのは2例で,各々50×47mm,55×44mmであった.1週間後の造影CTでは,全例で治療部位の早期濃染像は認めなかったが,1例で脈管近傍のsafety marginが不足していたため,経皮的エタノール注入療法を追加した.合併症として発熱の遷延1例,肝梗塞1例を認めたが保存的に改善し,その他は全例に発熱と疼痛を認めたが対処療法で改善した.また一時的に肝機能悪化を認めたが,1週間後に前値に復した

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2004&ichushi_jid=J00263&link_issn=&doc_id=20041005370008&doc_link_id=10.2957%2Fkanzo.45.505&url=https%3A%2F%2Fdoi.org%2F10.2957%2Fkanzo.45.505&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

骨髄細胞から肝細胞への分化転換における線維芽細胞増殖因子の関与

石川剛, 寺井崇二, 浦田洋平, 丸本芳雄, 青山浩司, 大森薫, 坂井田功, 沖田極

肝臓 45 ( Suppl.2 ) A509 - A509 2004年9月

Proteomic profiling of proteins decreased in hepatocellular carcinoma from patients infected with hepatitis C virus 査読

Y Yokoyama, Y Kuramitsu, M Takashima, N Iizuka, T Toda, S Terai, Sakaida, I, M Oka, K Nakamura, K Okita

PROTEOMICS 4 ( 7 ) 2111 - 2116 2004年7月

Helix-loop-helix(HLH)型転写制御分子Human homologue of Maid(HHM)からみた肝発癌

高見太郎, 寺井崇二, 谷本治子, 坂井田功, 沖田極

山口医学 53 ( 3 ) 185 - 185 2004年6月

肝発癌におけるHuman homologue of Maid(HHM)の機能とその発現制御

高見太郎, 寺井崇二, 沖田極

肝臓 45 ( Suppl.1 ) A96 - A96 2004年4月

肝硬変患者の就寝前肝不全経口栄養剤投与についての検討

土屋昌子, 坂井田功, 青山浩司, 石川剛, 田島邦彦, 横山雄一郎, 大森薫, 川口浩太郎, 高見太郎, 木村輝昭, 寺井崇二, 山崎隆弘, 黒川典枝, 沖田極

肝臓 45 ( Suppl.1 ) A258 - A258 2004年4月

骨髄細胞による肝再生モデルマウスにおける血清プロテオミクス

横山雄一郎, 寺井崇二, 大森薫, 青山浩司, 石川剛, 高見太郎, 坂井田功, 沖田極

肝臓 45 ( Suppl.1 ) A225 - A225 2004年4月

骨髄細胞移植による肝線維化治療の検討

坂井田功, 山浩司, 石川剛, 大森薫, 寺井崇二, 仁科博史, 沖田極

マトリックス研究会大会 ( 51 ) 52 - 52 2004年4月

【幹細胞と消化器疾患】骨髄細胞から肝細胞への分化転換の制御機構の解析とその臨床応用自己骨髄細胞を用いた肝臓再生療法の基礎的検討

寺井崇二, 石川剛, 大森薫, 青山浩司, 坂井田功, 沖田極

G.I.Research 12 ( 2 ) 117 - 125 2004年4月

線維芽細胞増殖因子は骨髄細胞から肝細胞への分化転換を促進する

石川剛, 寺井崇二, 浦田洋平, 丸本芳雄, 青山浩司, 大森薫, 坂井田功, 沖田極

肝臓 45 ( Suppl.1 ) A43 - A43 2004年4月

骨髄細胞から肝細胞への分化転換の素過程に関与する遺伝子群の抽出及び可視化

大森薫, 寺井崇二, 浦田洋平, 丸本芳雄, 石川剛, 青山浩司, 坂井田功, 仁科博史, 内村俊二, 浜本義彦, 沖田極

肝臓 45 ( Suppl.1 ) A84 - A84 2004年4月

Liv-8陰性分画骨髄細胞の移植による肝線維化改善の検討

青山浩司, 坂井田功, 浦田洋平, 丸本芳雄, 石川剛, 大森薫, 寺井崇二, 沖田極

肝臓 45 ( Suppl.1 ) A89 - A89 2004年4月

Herbal medicine Sho-saiko-to (TJ-9) increases expression matrix metalloproteinases (MMPs) with reduced expression of tissue inhibitor of metalloproteinases (TIMPs) in rat stellate cell 査読

Sakaida, I, K Hironaka, T Kimura, S Terai, T Yamasaki, K Okita

LIFE SCIENCES 74 ( 18 ) 2251 - 2263 2004年3月

A subpopulation of bone marrow cells depleted by a novel antibody, anti-Liv8, is useful for cell therapy to repair damaged liver 査読

N Yamamoto, S Terai, S Ohata, T Watanabe, K Omori, K Shinoda, K Miyamoto, T Katada, Sakaida, I, H Nishina, K Okita

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 313 ( 4 ) 1110 - 1118 2004年1月

肝臓肝細胞癌の病態と診断

高見太郎, 寺井崇二, 沖田極

Annual Review消化器 2004 303 - 307 2004年1月

Strategy for the development of cell therapy using bone marrow cells to repair damaged liver 査読

S Terai, Sakaida, I, N Yamamoto, K Omori, K Okita

STEM CELL AND LIVER REGENERATION 51 - 56 2004年

An in vivo model for monitoring trans-differentiation of bone marrow cells into functional hepatocytes 査読

S Terai, Sakaida, I, N Yamamoto, K Omori, T Watanabe, S Ohata, T Katada, K Miyamoto, K Shinoda, H Nishina, K Okita

JOURNAL OF BIOCHEMISTRY 134 ( 4 ) 551 - 558 2003年10月

Arterial infusion chemotherapy using cisplatin, 5-fluorouracil, and isovorin for patients with advanced hepatocellular carcinoma, pilot study: Is a high dose of the biochemical modulator effective? 査読

T Yamasaki, F Kurokawa, T Takami, K Omori, K Kawaguchi, M Tsuchiya, N Yamamoto, M Okamoto, K Hironaka, T Kimura, S Terai, Sakaida, I, K Okita

HEPATOLOGY RESEARCH 27 ( 1 ) 36 - 44 2003年9月

Leptin receptor-deficient Zucker (fa/fa) rat retards the development of pig serum-induced liver fibrosis with Kupffer cell dysfunction 査読

Sakaida, I, S Jinhua, K Uchida, S Terai, K Okita

LIFE SCIENCES 73 ( 19 ) 2491 - 2501 2003年9月

【コンセンサス肝細胞癌の治療】肝細胞癌治療後のフォローアップと補助療法

山崎隆弘, 高見太郎, 大森薫, 川口浩太郎, 土屋昌子, 木村輝昭, 寺井崇二, 黒川典枝, 坂井田功, 沖田極

コンセンサス癌治療 2 ( 3 ) 162 - 163 2003年8月

肝臓の発生分化再生過程におけるHLH型転写制御分子の解析

谷本治子, 寺井崇二, 高見太郎, 横山雄一郎, 田島邦彦, 仁科博史, 沖田極

日本癌学会総会記事 62回 324 - 324 2003年8月

HHM(Human Homologue of Maid)は肝発癌をinitiateする

高見太郎, 寺井崇二, 横山雄一郎, 田島邦彦, 谷本治子, 内田耕一, 木村輝昭, 宮本康嗣, 黒川典枝, 仁科博史, 坂井田功, 沖田極

日本癌学会総会記事 62回 284 - 284 2003年8月

Herbal medicine inchin-ko-to (TJ-135) prevents liver fibrosis and enzyme-altered lesions in rat liver cirrhosis induced by a cholinedeficient (L)-amino acid-defined diet 査読

Sakaida, I, M Tsuchiya, K Kawaguchi, T Kimura, S Terai, K Okita

JOURNAL OF HEPATOLOGY 38 ( 6 ) 762 - 769 2003年6月

【肝細胞癌の治療方針最近の進歩】肝細胞癌に対する経皮的局所治療

山崎隆弘, 木村輝昭, 高見太郎, 大森薫, 川口浩太郎, 土屋昌子, 山本直樹, 岡本真理子, 寺井崇二, 黒川典枝, 坂井田功, 沖田極

消化器外科 26 ( 5 ) 563 - 569 2003年5月

記述言語：日本語出版者・発行元：(株)へるす出版

肝細胞癌の経皮的局所治療は,経皮的エタノール注入療法(PEI)に始まり,マイクロ波凝固療法(MCT)を経由して,ラジオ波凝固療法(RFA)へと発展してきた.現在,RFAは1回あたりの獲得しうる壊死範囲が広いことから,局所療法の主流となっている.著者等の施設でもRFA導入後,MCTは施行していない.しかし大きな脈管や胆嚢に接する腫瘍に対しては,安全性を考えて,PEIを選択している.またPEIとRFAの使い分けとしては,肝予備能の点を考える必要がある.現時点で経皮的局所療法の主流はRFAであるが,PEIもなくてはならない治療法の一つと考えている

Gadolinium chloride reverses dimethylnitrosamine (DMN)-induced rat liver fibrosis with increased matrix metalloproteinases (MMPs) of Kupffer cells 査読

ラット肝星細胞のMAPKシグナル伝達経路におけるMMPsの制御

土屋昌子, 坂井田功, 青山浩司, 石川剛, 田島邦彦, 横山雄一郎, 大森薫, 川口浩太郎, 高見太郎, 寺井崇二, 沖田極

肝臓 44 ( Suppl.1 ) A142 - A142 2003年4月

骨髄細胞移植による肝繊維化治療の検討

青山浩司, 坂井田功, 石川剛, 田島邦彦, 横山雄一郎, 大森薫, 川口浩太郎, 高見太郎, 土屋昌子, 山本直樹, 寺井崇二, 沖田極

肝臓 44 ( Suppl.1 ) A103 - A103 2003年4月

Sakaida, I., Hironaka, K., Terai, S., Okita, K.

Life Sciences 72 ( 8 ) 943 - 959 2003年

劇症肝炎時におけるアポトーシス誘導因子であるチトクロムc血清中濃度の臨床的検討について

木村輝昭, 坂井田功, 大森薫, 川口浩太郎, 土屋昌子, 高見太郎, 岡本真理子, 山本直己, 坂口栄樹, 瀬川誠, 寺井崇二, 萱野幸三, 山崎隆弘, 沖田極

肝臓 43 ( 12 ) 600 - 601 2002年12月

Ubiquitin is a possible new predictive marker for the recurrence of human hepatocellular carcinoma 査読

H Shirahashi, Sakaida, I, S Terai, K Hironaka, N Kusano, K Okita

LIVER 22 ( 5 ) 413 - 418 2002年10月

骨髄細胞から肝細胞への分化制御に関する遺伝子群の検索

大森薫, 寺井崇二, 山本直樹, 川口浩太郎, 高見太郎, 土屋昌子, 内田耕一, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

日本消化吸収学会総会プログラム・講演抄録集 33回 107 - 107 2002年10月

骨髄細胞を用いた肝臓再生療法の開発を目指して GFP/CCI4モデルの開発と解析及び骨髄中の幹細胞の同定法

寺井崇二, 山本直樹, 大森薫, 川口浩太郎, 高見太郎, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

日本癌学会総会記事 61回 464 - 465 2002年10月

肝幹細胞の発生分化と肝発癌に関与するHLH型転写制御分子Human Homologue of Maid(HHM)

高見太郎, 寺井崇二, 内田耕一, 川口浩太郎, 大森薫, 土屋昌子, 山本直樹, 木村輝昭, 黒川典枝, 宮本康嗣, 坂井田功, 沖田極

日本癌学会総会記事 61回 78 - 78 2002年10月

骨髄細胞から肝細胞への分化制御に関する遺伝子群の検索

大森薫, 寺井崇二, 山本直樹, 川口浩太郎, 高見太郎, 土屋昌子, 内田耕一, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

Gastroenterological Endoscopy 44 ( Suppl.2 ) 1476 - 1476 2002年9月

骨髄細胞から肝細胞への分化制御に関する遺伝子群の検索

大森薫, 寺井崇二, 山本直樹, 川口浩太郎, 高見太郎, 土屋昌子, 内田耕一, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

日本消化器集団検診学会雑誌 40 ( 5 ) 106 - 106 2002年9月

Liv8抗体を用いた臨床応用可能な骨髄中の肝幹細胞群の同定への試み

山本直樹, 寺井崇二, 大森薫, 高見太郎, 川口浩太郎, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

肝臓 43 ( Suppl.2 ) A369 - A369 2002年9月

骨髄細胞から肝細胞への分化制御に関する遺伝子群の検索

大森薫, 寺井崇二, 山本直樹, 川口浩太郎, 高見太郎, 土屋昌子, 内田耕一, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

肝臓 43 ( Suppl.2 ) A337 - A337 2002年9月

肝細胞癌破裂における肝動脈塞栓術(TAE)の意義

山本直樹, 山崎隆弘, 高見太郎, 大森薫, 川口浩太郎, 木村輝昭, 寺井崇二, 黒川典枝, 坂井田功, 沖田極

山口医学 51 ( 3 ) 89 - 90 2002年6月

星細胞活性化に伴う新規転写制御因子HHM(Human homologue of Maid)とMyoDの発現動態についての検討

川口浩太郎, 坂井田功, 寺井崇二, 高見太郎, 大森薫, 山本直樹, 木村輝昭, 萱野幸三, 沖田極

肝臓 43 ( Suppl.1 ) A43 - A43 2002年5月

【これからの肝発癌研究をどう考えるか】遺伝子「DNAチップを用いた遺伝子発現パターン」肝発癌に関与する転写制御分子HHM

寺井崇二, 坂井田功, 高見太郎, 内田耕一, 白橋斉, 山本直樹, 大森薫, 川口浩太郎, 宮本康嗣, 沖田極

医学と薬学 47 ( Suppl. ) 4 - 10 2002年5月

記述言語：日本語出版者・発行元：(株)自然科学社

肝臓の発生・分化・増殖の制御機構に関与するMyoDと同様な肝臓のMaster geneの存在を推測し,その同定を目的とし以下の実験を行った.1)Yeast Two Hybrid Screen,2)5' Rapid Amplification of cDNA,3)遺伝子発現プロファイリング,4)実験モデル,5)Luciferase Assay,6)細胞周期に対する影響の解析,7)ヒト肝癌組織におけるHHM蛋白の発現の検討.その結果肝再生時での発現上昇はあまり顕著でなく,むしろ肝幹細胞を誘導する肝細胞への分化モデルにおいて,foci部に一致し発現量が増加していた.又,化学発癌モデルのコリン欠乏アミノ酸置換食ラットモデルでのfoci部及び実際にヒト肝細胞癌症例に対する染色にて高率に陽性細胞の存在を確認し得た.これらの結果は,肝発癌過程におけるHHMの重要な意味を示した

生体部分肝移植で救命し得たB型劇症肝炎急性型の成人例

新規マウスモノクローナル抗体Liv抗体群及びMaid抗体を用いた肝幹細胞同定への試み

山本直樹, 寺井崇二, 大森薫, 高見太郎, 川口浩太郎, 内田耕一, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

肝臓 43 ( Suppl.1 ) A102 - A102 2002年5月

骨髄細胞から肝細胞への分化制御に関する遺伝子群の検索

大森薫, 寺井崇二, 山本直樹, 川口浩太郎, 高見太郎, 内田耕一, 宮本康嗣, 坂井田功, 仁科博史, 沖田極

肝臓 43 ( Suppl.1 ) A100 - A100 2002年5月

肝発癌に関与する転写制御分子HHMの機能解析

高見太郎, 寺井崇二, 内田耕一, 川口浩太郎, 大森薫, 山本直樹, 瀬川誠, 木村輝昭, 萱野幸三, 山崎隆弘

肝臓 43 ( Suppl.1 ) A35 - A35 2002年5月

HHM: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression and liver stem cells 査読

S Terai, SS Thorgeirsson, K Okita

GROWTH, PROLIFERATION, AND APOPTOSIS IN HEPATOCYTES 1 - 9 2002年

A new cell therapy using bone marrow cells to repair damaged liver 査読

S Terai, N Yamamoto, K Omori, Sakaida, I, K Okita

JOURNAL OF GASTROENTEROLOGY 37 162 - 163 2002年

Herbal medicine Inchin-ko-to (TJ-135) prevents liver fibrosis in rat liver cirrhosis induced by a choline-deficient L-amino acid-defined diet 査読

Sakaida, I, T Yamasaki, S Terai, K Okita

ASIAN PACIFIC ASSOCIATION FOR THE STUDY OF THE LIVER MEETING 2002 153 - 158 2002年

大森薫, 木村輝昭, 丸本芳雄, 川口浩太郎, 高見太郎, 岡本真理子, 瀬川誠, 坂口栄樹, 岡崎宗子, 寺井崇二

山口医学 50 ( 6 ) 829 - 829 2001年12月

近未来医療移植から再生医療 GFP transgenic mouseを用いた肝臓再生療法の基礎的検討

山本直樹, 寺井崇二, 坂井田功, 大森薫, 川口浩太郎, 高見太郎, 坂口栄樹, 宮本康嗣, 沖田極

肝臓 42 ( Suppl.3 ) A479 - A479 2001年11月

肝細胞癌に対するバルーンマイクロカテーテルを用いた肝動脈バルーン閉塞下ラジオ波凝固療法

山崎隆弘, 黒川典枝, 高見太郎, 山本直樹, 是永匡紹, 木村輝昭, 寺井崇二, 萱野幸三, 坂井田功, 沖田極

肝臓 42 688 - 689 2001年

Human homologue of maid: A dominant inhibitory helix-loop-helix protein associated with liver-specific gene expression 査読

S Terai, H Aoki, K Ashida, SS Thorgeirsson

HEPATOLOGY 32 ( 2 ) 357 - 366 2000年8月

Does cytoplasmic cyclin D1 regulate the cell cycle directly? 査読

Terai S, Okita K

J Gastroenterol. 32 ( 2 ) 357 - 66 2000年8月

Antitumor effect of vesnarinone on human hepatocellular carcinoma cell lines 査読

K Kubo, Y Matsuzaki, A Kato, S Terai, K Okita

INTERNATIONAL JOURNAL OF ONCOLOGY 14 ( 1 ) 41 - 46 1999年1月

肝細胞癌に対する経皮的熱湯局注療法併用下マイクロ波凝固治療

山崎隆弘, 加藤彰, 草野倫好, 弘中孝治, 久保圭子, 寺井崇二, 黒川典枝, 藪下芳子, 森健治, 水町宗治, 沖田極

Journal of Microwave Surgery 16 37 - 41 1998年

出版者・発行元：Study Group of Microwave Surgery

We compared the usefulness of percutaneous hot water injection and microwave coagulation therapy (PHMCT) and percutaneous microwave coagulation therapy (PMCT) in patients with hepatocellular carcinomas (HCCs). We performed PHMCT in 18 patients with HCCs (23 nodules) measuring less than 30 mm in diameter and PMCT in 5 patients with HCCs (7 nodules). After 1 week of treatment, we performed a dynamic computed tomography (CT) scan to examine the maximum area of necrosis. There was significant difference in long and short axes diameter of the necrotic area between the PHMCT group injected hot water with more than 15 ml and the PMCT group. Our findings indicate that PHMCT is an effective treatment for small HCCs.

DOI： 10.3380/jmicrowavesurg.16.37