2024/12/26 更新

写真a

トミナガ ケンタロウ
冨永 顕太郎
TOMINAGA Kentaro
所属
教育研究院 医歯学系 医学系列 助教
医歯学総合研究科 分子細胞医学専攻 細胞機能 助教
職名
助教
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外部リンク

学位

  • 新潟大学大学院医歯学総合研究科博士課程修了(医学博士) ( 2017年3月   新潟大学 )

研究分野

  • ライフサイエンス / 消化器内科学

経歴

  • 新潟大学   医歯学総合研究科 分子細胞医学専攻 細胞機能   助教

    2023年4月 - 現在

  • 新潟大学   教育研究院 医歯学系 医学系列   助教

    2023年4月 - 現在

  • 新潟大学   医歯学総合研究科   特任助教

    2018年7月 - 2020年3月

 

論文

  • 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

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    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

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  • Deriving human intestinal organoids with functional tissue-resident macrophages all from pluripotent stem cells. 国際誌

    Kentaro Tominaga, Daniel O Kechele, J Guillermo Sanchez, Simon Vales, Ingrid Jurickova, Lizza Roman, Akihiro Asai, Jacob R Enriquez, Heather A McCauley, Keishi Kishimoto, Kentaro Iwasawa, Akaljot Singh, Yuko Horio, Jorge O Múnera, Takanori Takebe, Aaron M Zorn, Michael A Helmrath, Lee A Denson, James M Wells

    Cellular and molecular gastroenterology and hepatology   101444 - 101444   2024年12月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND & AIMS: Organs of the gastrointestinal tract contain tissue-resident immune cells that function during tissue development, homeostasis, and disease. However, most published human organoid model systems lack resident immune cells, thus limiting their potential as disease avatars. For example, human intestinal organoids (HIOs) derived from pluripotent stem cells contain epithelial and various mesenchymal cell types but lack immune cells. In this study, we aimed to develop an HIO model with functional tissue-resident macrophages. METHODS: HIOs and macrophages were generated separately through the directed differentiation of human pluripotent stem cells and combined in vitro. Following two weeks of co-culture, the organoids were used for transcriptional profiling, functional analysis of macrophages, or transplanted into immunocompromised mice and matured in vivo for an additional 10-12 weeks. RESULTS: Macrophages were incorporated into developing HIOs and persisted for 2 weeks in vitro HIOs and for at least 12 weeks in HIOs in vivo. These co-cultured macrophages had a transcriptional signature that resembled those in the human fetal intestine, indicating that they were acquiring the features of tissue-resident macrophages. HIO macrophages could phagocytose bacteria and produced inflammatory cytokines in response to proinflammatory signals such as lipopolysaccharide, which could be reversed with IL-10. CONCLUSIONS: We generated an HIO system containing functional tissue-resident macrophages for an extended period. This new organoid system can be used to investigate the molecular mechanisms involved in inflammatory bowel disease.

    DOI: 10.1016/j.jcmgh.2024.101444

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  • 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

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    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

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  • 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

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    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

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  • Eicosatetraynoic Acid Regulates Pro-Fibrotic Pathways in an Induced Pluripotent Stem Cell Derived Macrophage:Human Intestinal Organoid Model of Crohn's Disease. 国際誌

    Ingrid Jurickova, Benjamin W Dreskin, Elizabeth Angerman, Erin Bonkowski, Jack Nguyen, Richard Villarreal, Kentaro Tominaga, Kentaro Iwasawa, Tzipi Braun, Takanori Takebe, Michael A Helmrath, Yael Haberman, James M Wells, Lee A Denson

    Journal of Crohn's & colitis   2024年8月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIMS: We previously identified small molecules predicted to reverse an ileal gene signature for future Crohn's Disease (CD) strictures. Here we used a new human intestinal organoid (HIO) model system containing macrophages to test a lead candidate, eicosatetraynoic acid (ETYA). METHODS: Induced pluripotent stem cell lines (iPSC) were derived from CD patients and differentiated into macrophages and HIOs. Macrophages and macrophage:HIO co-cultures were exposed to lipopolysaccharide (LPS) with and without ETYA pre-treatment. Cytospin and flow cytometry characterized macrophage morphology and activation markers, and RNA sequencing defined the global pattern of macrophage gene expression. TaqMan Low Density Array, Luminex multiplex assay, immunohistologic staining, and sirius red polarized light microscopy were performed to measure macrophage cytokine production and HIO pro-fibrotic gene expression and collagen content. RESULTS: iPSC-derived macrophages exhibited morphology similar to primary macrophages and expressed inflammatory macrophage cell surface markers including CD64 and CD68. LPS-stimulated macrophages expressed a global pattern of gene expression enriched in CD ileal inflammatory macrophages and matrisome secreted products, and produced cytokines and chemokines including CCL2, IL1B, and OSM implicated in refractory disease. ETYA suppressed CD64 abundance and pro-fibrotic gene expression pathways in LPS stimulated macrophages. Co-culture of LPS-primed macrophages with HIO led to up-regulation of fibroblast activation genes including ACTA2 and COL1A1, and an increase in HIO collagen content. ETYA pre-treatment prevented pro-fibrotic effects of LPS-primed macrophages. CONCLUSIONS: ETYA inhibits pro-fibrotic effects of LPS-primed macrophages upon co-cultured HIO. This model may be used in future untargeted screens for small molecules to treat refractory CD.

    DOI: 10.1093/ecco-jcc/jjae139

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  • 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

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    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

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  • 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

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    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

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  • 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

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    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

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  • Development of functional resident macrophages in human pluripotent stem cell-derived colonic organoids and human fetal colon. 国際誌

    Jorge O Múnera, Daniel O Kechele, Carine Bouffi, Na Qu, Ran Jing, Pritiprasanna Maity, Jacob R Enriquez, Lu Han, Ian Campbell, Maxime M Mahe, Heather A McCauley, Xinghao Zhang, Nambirajan Sundaram, Jonathan R Hudson, Adrian Zarsozo-Lacoste, Suman Pradhan, Kentaro Tominaga, J Guillermo Sanchez, Alison A Weiss, Praneet Chatuvedi, Jason R Spence, Mariam Hachimi, Trista North, George Q Daley, Christopher N Mayhew, Yueh-Chiang Hu, Takanori Takebe, Michael A Helmrath, James M Wells

    Cell stem cell   30 ( 11 )   1434 - 1451   2023年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Most organs have tissue-resident immune cells. Human organoids lack these immune cells, which limits their utility in modeling many normal and disease processes. Here, we describe that pluripotent stem cell-derived human colonic organoids (HCOs) co-develop a diverse population of immune cells, including hemogenic endothelium (HE)-like cells and erythromyeloid progenitors that undergo stereotypical steps in differentiation, resulting in the generation of functional macrophages. HCO macrophages acquired a transcriptional signature resembling human fetal small and large intestine tissue-resident macrophages. HCO macrophages modulate cytokine secretion in response to pro- and anti-inflammatory signals and were able to phagocytose and mount a robust response to pathogenic bacteria. When transplanted into mice, HCO macrophages were maintained within the colonic organoid tissue, established a close association with the colonic epithelium, and were not displaced by the host bone-marrow-derived macrophages. These studies suggest that HE in HCOs gives rise to multipotent hematopoietic progenitors and functional tissue-resident macrophages.

    DOI: 10.1016/j.stem.2023.10.002

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  • 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

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    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

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  • Gas Leak in the Port: Portal Venous Gas Associated With Congenital Cytomegalovirus Colitis. 国際誌

    Kentaro Tominaga, David Haslam, Akihiro Asai

    JPGN reports   3 ( 4 )   e267   2022年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1097/PG9.0000000000000267

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  • 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

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    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

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  • 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

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    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

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  • GENERATION OF HUMAN INTESTINAL ORGANOIDS CONTAINING TISSUE-RESIDENT IMMUNE CELLS

    Kentaro Tominaga, Dan Kechele, Guillermo Sanchez, Heather McCauley, Jacob Enriquez, Simon Vales, Ingrid Jurickova, Lee Denson, Takanori Takebe, Michael Helmrath, Aaron Zorn, James Wells

    GASTROENTEROLOGY   162 ( 3 )   S57 - S57   2022年2月

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    記述言語:英語   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • GENERATION OF HUMAN INTESTINAL ORGANOIDS CONTAINING TISSUE-RESIDENT IMMUNE CELLS

    Kentaro Tominaga, Dan Kechele, Guillermo Sanchez, Heather McCauley, Jacob Enriquez, Simon Vales, Ingrid Jurickova, Lee Denson, Takanori Takebe, Michael Helmrath, Aaron Zorn, James Wells

    INFLAMMATORY BOWEL DISEASES   28   S57 - S57   2022年1月

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    記述言語:英語   出版者・発行元:OXFORD UNIV PRESS INC  

    DOI: 10.1093/ibd/izac015.090

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  • 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

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    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

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  • 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

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    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

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  • 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8月

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    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

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  • 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

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    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

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  • 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

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    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

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  • 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

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    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

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Focal nodular hyperplasia (FNH) is the second most frequent benign liver tumor, and it is a fiber-rich stiff lesion. Typically, FNH can be diagnosed by imaging without biopsy. However, liver biopsy and diagnostic resection may be required to differentiate atypical FNH from other liver tumors, such as hepatocellular adenoma (HCA). Therefore, improved noninvasive diagnostic methods are needed. We experienced 2 cases where combination of magnetic resonance elastography (MRE) and gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) helped diagnose FNH. A 36-year-old woman and 17-year-old boy with liver tumors measuring 40 mm in diameter each showed hypointense nodule centers, indicating a central scar, surrounded by hyperintense signals during the hepatobiliary phase of Gd-EOB-DTPA-enhanced MRI. To rule out HCA, we performed MRE and liver biopsy. On MRE, the mean stiffness of the mass was 11.6 kPa (mean stiffness of the background liver was 1.7 kPa) and 11.1 kPa (mean stiffness of the background liver was 2.4 kPa) in the first and second patients, respectively. Histological examination of both specimens showed CK7-positive bile-ductular proliferations, abundant fibrous tissue, and few Ki-67-positive cells. Based on these results, we diagnosed these tumors as FNH. Combination of Gd-EOB-DTPA-enhanced MRI and MRE can evaluate the character and stiffness of lesion and help in the diagnosis of FNH.

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:KARGER  

    Pancreatic pseudocyst-portal vein (PP-PV) fistula, mostly occurring after pseudocyst formation following acute/chronic pancreatitis, is a rare but life-threatening condition. The majority of treatments are based on conservative or surgical interventions. We report the case of a 70-year-old man with a PP-PV fistula and PV thrombosis. We adopted conservative treatment at first due to his mild symptoms. However, after resuming food intake, the patient had severe abdominal pain. Following endoscopic retrograde cholangiopancreatography, we found that the pseudocyst was connected with the PV through the fistula. Subsequently, an endoscopic nasopancreatic drainage (ENPD) catheter was inserted into the main pancreatic duct to establish pancreatic drainage, which resulted in a decrease in the abdominal pain. After the ENPD tube had been exchanged for endoscopic pancreatic stenting, his abdominal pain did not recur. Therefore, this case demonstrated endoscopic treatment as an effective treatment option for PP-PV fistula.

    DOI: 10.1159/000510331

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    This report highlights the easy peeling of the esophageal epithelium with Nikolsky phenomenon after swallowing the foreign body and the healing status of the esophagus only 3 days later in a patient of pemphigus vulgaris.

    DOI: 10.1002/ccr3.2846

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  • 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

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    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

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  • 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   2020年5月

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    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 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 post-treatment and that during initial treatment were significantly positively correlated with VATI (r = 0.326, P = 0.027). Patients with high VSR had a significantly higher frequency of HCC after EV treatment by Kaplan-Meier analysis (P = 0.024). 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

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  • 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5月

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    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

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  • 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5月

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    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

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  • 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

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    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

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  • Variation in small bowel transit time on capsule endoscopy. 査読 国際誌

    Kentaro Tominaga, Hiroki Sato, Hiroshi Yokomichi, Atsunori Tsuchiya, Tomoaki Yoshida, Yuzo Kawata, Takeshi Mizusawa, Junji Yokoyama, Shuji Terai

    Annals of translational medicine   8 ( 6 )   348 - 348   2020年3月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:AME Publ Co  

    Background: Small bowel motility remains inadequately understood because of the complex and various functions as well as its anatomical position. The aimed of the study was to investigate the small bowel transit time (SBTT) of capsule endoscopy (CE) and to analyze the clinical factors affecting SBTT. Methods: SBTT was analyzed in patients who underwent small bowel CE. Factors contributing to SBTT and CE retention were investigated. Results: Among 397 patients enrolled in this study, 336 (84.6%) completed CE. The mean SBTT (± standard deviation) was 282.1±132.2 min. According to the univariate and multivariate analyses, aging and small bowel stenosis extended SBTT. In 38 patients who underwent multiple CE studies, considerable variation in SBTT were observed [mean of standard deviations (SDs) =97.97 min, SD of the SDs =81.99 min]. CE retention was observed in 61 patients (13.3%), and it was statistically associated to small bowel lesion. Conclusions: Aging and small bowel stenosis were associated with longer SBTT. Furthermore, SBTT analyzed by CE should be interpreted carefully considering the intra-individual differences in SBTT.

    DOI: 10.21037/atm.2020.02.40

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  • 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

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    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

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  • 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

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    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

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  • Overlap in disease concept of functional esophageal disorders and minor esophageal motility disorders. 査読 国際誌

    Hiroki Sato, Kazuya Takahashi, Ken-Ichi Mizuno, Satoru Hashimoto, Yuzo Kawata, Takeshi Mizusawa, Kentaro Tominaga, Junji Yokoyama, Shuji Terai

    Journal of gastroenterology and hepatology   34 ( 11 )   1940 - 1945   2019年11月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND AND AIM: Functional gastrointestinal disorders are the most common disorders in gastroenterology and are currently considered as gut-brain interaction disorders with multiple related factors including motility disturbance. However, high-resolution manometry (HRM) had revealed a new disease concept known as minor esophageal motility disorders. This study aimed to investigate the correlation between functional esophageal disorders (FEDs) and minor esophageal motility disorders. METHODS: Functional esophageal disorders were diagnosed using upper endoscopy, pH monitoring, and HRM, to exclude achalasia, esophago-gastric junction outflow obstruction, and other major esophageal motility disorders. FEDs with or without minor esophageal motility disorders were compared using the Chicago classification. RESULTS: Twelve healthy volunteers also subjected to HRM showed no minor esophageal motility disorders. Of the 40 patients with FEDs, 15 (37.5%) were diagnosed with minor esophageal motility disorders. Characteristics were not different between patients with and without minor esophageal motility disorders (sex: P = 0.609, age: P = 0.054, body mass index: P = 0.137, and presence of psychiatric disorders: P = 0.404). The type and location of symptoms were not related to the comorbidity rate of minor esophageal motility disorders (P = 0.744 and 0.094). No patients with FEDs developed major esophageal motility disorders. CONCLUSIONS: Minor esophageal motility disorders were frequently observed in FEDs, but the causal relationship between esophageal symptoms remains unclear. The disease concepts of FEDs and minor esophageal motility disorders are considered to overlap and are both independent of major esophageal motility disorders.

    DOI: 10.1111/jgh.14691

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.gie.2019.05.040

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  • 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

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    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

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  • Duodenal lymphangiectasia distinguished from follicular lymphoma by narrow-band imaging magnification endoscopy. 査読 国際誌

    Kentaro Tominaga, Atsunori Tsuchiya, Ken-Ichi Mizuno, Shuji Terai

    Gastrointestinal endoscopy   90 ( 3 )   528 - 529   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1016/j.gie.2019.04.220

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  • Usefulness of chemokine C-C receptor 7- /programmed cell death-1+ follicular helper T cell subset frequencies in the diagnosis of autoimmune hepatitis. 査読 国際誌

    Naruhiro Kimura, Satoshi Yamagiwa, Tomoyuki Sugano, Ryoko Horigome, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Masaaki Takamura, Shuji Terai

    Hepatology research : the official journal of the Japan Society of Hepatology   49 ( 9 )   1026 - 1033   2019年9月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    AIM: A significant concern for autoimmune hepatitis (AIH) patients is diagnostic specificity. Delayed treatment due to delayed diagnosis leads to poor survival. We recently reported that chemokine C-C receptor 7 (CCR7)- /programmed cell death-1 (PD-1)+ follicular helper T (Tfh) cells could be involved in AIH pathogenesis. We hypothesized that Tfh cell frequencies might contribute to AIH diagnosis. METHODS: Peripheral blood was collected from 12 patients with AIH from April 2013 to March 2016, as well as 24 patients with hepatitis B virus (HBV) infection and 44 healthy controls (HC). Mononuclear cells were separated using a Ficoll gradient, and surface markers were investigated using flow cytometry. RESULTS: The frequency of CCR7- PD-1+ Tfh cells was significantly higher in AIH patients (39.1 ± 8.6) compared to that in HC (25.1 ± 7.9%, P < 0.01) and HBV patients (22.7 ± 7.8, P < 0.01). The area under the receiver operating characteristic curve for the frequency of the CCR7- PD-1+ Tfh cell subset for AIH and HC and AIH and HBV was 0.905 and 0.927, respectively. The frequency of the CCR7- PD-1+ Tfh cell subset was not correlated with International Autoimmune Hepatitis Group (IAIHG) scoring, Simplified AIH scoring, or Japanese diagnostic guidelines (R = 0.10, 0.947; R = 0.0008, 0.180; and R = 0.348, 0.558, respectively). Therefore, these frequencies could diagnose AIH patients who were not diagnosed with the IAIHG or simplified AIH scores. CONCLUSIONS: The frequency of the peripheral CCR7- PD-1+ Tfh cell subset could be useful for diagnosing AIH even in patients who were not diagnosed with IAIHG or simplified AIH scores.

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  • Epidemiological analysis of achalasia in Japan using a large-scale claims database. 査読

    Hiroki Sato, Hiroshi Yokomichi, Kazuya Takahashi, Kentaro Tominaga, Takeshi Mizusawa, Naruhiro Kimura, Yuzo Kawata, Shuji Terai

    Journal of gastroenterology   54 ( 7 )   621 - 627   2019年7月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    BACKGROUND: Achalasia is a well-known esophageal motility disorder, but epidemiological studies in Japan are lacking. We investigated the incidence and period prevalence of achalasia in Japan, including the rate of coexistence of esophageal carcinoma, and evaluated treatment trends. METHODS: To estimate the nationwide number of patients with achalasia, a large-scale insurance claims database from 2005 to 2017 were used for our analyses. Patients with achalasia and coexistence of esophageal carcinoma were identified based on the diagnosis code registered. Interventional treatment was also evaluated. RESULTS: Of the total 5,493,650 populations, 385 were diagnosed with primary achalasia. The incidence was calculated as 0.81-1.37 per 100,000 person-years (male-to-female ratio was almost 1; mean age at diagnosis was 43.3 ± 14.4 years). The period prevalence was 7.0 per 100,000 persons. There were statistically significant trends of increase in the incidence and period prevalence over age groups (all p values < 0.0001). Four men with achalasia developed esophageal carcinoma, and the incidence of esophageal carcinoma with achalasia was estimated as 0.25 per 100 person-years. With regard to intervention, esophageal dilation was performed as a first treatment in 64.7% of patients, with repeat intervention required in 56.9% of these. The proportion of patients treated using peroral endoscopic myotomy (POEM) increased annually to 41.1% in 2017. CONCLUSIONS: In Japan, the incidence and period prevalence of achalasia is comparable to that in other countries. The absolute risk of esophageal carcinoma is rather low. Esophageal dilation has been the mainstay of achalasia treatment, and the role of POEM has increased annually.

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  • 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

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    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.

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  • 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6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • OUTCOME OF ENDOSCOPIC BALLOON DILATATION FOR INTESTINAL DILATATION IN PATIENTS WITH CROHN'S DISEASE

    Yuzo Kawata, Junji Yokoyama, Kentaro Tominaga, Shuji Terai

    GASTROINTESTINAL ENDOSCOPY   89 ( 6 )   AB344 - AB344   2019年6月

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    記述言語:英語   出版者・発行元:MOSBY-ELSEVIER  

    DOI: 10.1016/j.gie.2019.03.483

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  • 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 国際誌

    Yuzo Kawata, Atsunori Tsuchiya, Satoshi Seino, Yusuke Watanabe, Yuichi Kojima, Shunzo Ikarashi, Kentaro Tominaga, Junji Yokoyama, Satoshi Yamagiwa, Shuji Terai

    Cell and tissue research   376 ( 2 )   257 - 271   2019年5月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Inflammatory bowel diseases (IBDs) are sometimes refractory to current therapy or associated with severe adverse events during immunosuppressive therapy; thus, new therapies are urgently needed. Recently, mesenchymal stem cells (MSCs) have attracted attention based on their multitude of functions including anti-inflammatory effects. However, proper timing of MSC therapy and the mechanisms underlying the therapeutic effects of MSCs on colitis are not fully elucidated. Human adipose tissue-derived mesenchymal stem cells (hAdMSCs; 1 × 106) were administrated via the tail vein on day 3 (early) or 11 (delayed) using a 7-day dextran sulfate sodium (DSS)-induced mouse model of colitis. The effects were evaluated based on colon length, disease activity index (DAI) and histological score. Cytokine-encoding mRNA levels T cells and macrophages were evaluated by real-time PCR and flow cytometry. Regarding the timing of administration, early (day 3) injection significantly ameliorated DSS-induced colitis in terms of both DAI and histological score, compared to those parameters with delayed (day 11) injection. With early cell injection, the tissue mRNA levels of anti-inflammatory cytokine genes (Il10, Tgfb) increased, whereas those of inflammatory cytokine genes (Il6, Tnfa and Il17a) decreased significantly. Regarding the associated mechanism, hAdMSCs suppressed T cell proliferation and activation in vitro, increased the number of regulatory T cells in vivo and changed the polarity of macrophages (into the anti-inflammatory M2 phenotype) in vitro. Timing of injection is critical for the effective therapeutic effects of hAdMSCs. Furthermore, part of the associated mechanism includes T cell activation and expansion and altered macrophage polarization.

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  • 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

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    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.

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1159/000498913

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  • Novel Magnified Single-Balloon Enteroscopy Enables Observation of Jejunal White Spots Associated with Lymphangiectasia. 査読 国際誌

    Kentaro Tominaga, Atsunori Tsuchiya, Yuzo Kawata, Junji Yokoyama, Shuji Terai

    Digestive diseases (Basel, Switzerland)   37 ( 2 )   170 - 174   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    A 59-year-old woman was diagnosed with primary intestinal lymphangiectasia (PIL), with characteristic findings on capsule enteroscopy and confirmation by histopathological examination of biopsy specimens. We viewed the abnormal jejunal mucosa using a newly developed magnifying single-balloon enteroscope (SIF-Y0007). Conventional observation showed leakage of chyle. However, using this new scope, we could see scattered white villi, representing dilated lymphatic vessels within the intestinal villi protruding from the dilated submucosal lymphoid vessels (D2-40 positive) within an edematous jejunal lesion. This report is the first to describe the white villi in a patient with PIL observed clearly using a newly developed magnifying enteroscope. Technological advancements and the accumulation of reported pathological data would further improve our understanding of the pathophysiological aspects of this disease entity, even in the jejunum.

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  • Different distribution of mucosal-associated invariant T cells within the human cecum and colon. 査読 国際誌

    Isamu Hama, Kentaro Tominaga, Satoshi Yamagiwa, Toru Setsu, Naruhiro Kimura, Hiroteru Kamimura, Toshifumi Wakai, Shuji Terai

    Central-European journal of immunology   44 ( 1 )   75 - 83   2019年

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    Introduction: Mucosal-associated invariant T (MAIT) cells are innate-like T cells that are involved in anti-bacterial immunity. MAIT cells are found in the intestines, but their role and distribution within the large intestine have not been fully elucidated. Therefore, we investigated the distribution of MAIT cells within the cecum and colon. Material and methods: Surgically resected tissues of the cecum and colon were obtained from 4 patients with cecal appendix cancer and 8 patients with colorectal cancer, respectively. Lymphocytes were isolated from the intestinal epithelium (intraepithelial lymphocytes - IELs) and the underlying lamina propria (lamina propria lymphocytes - LPLs), and then, MAIT cells were analyzed by flow cytometry. Results: Compared with the colon, the cecum showed a significantly increased frequency of MAIT cells among IELs (p < 0.01). CD69 expression on MAIT cells was significantly increased in the cecum and colon compared with that in the blood, and the frequency of natural killer group 2, member A+ cells among MAIT cells was significantly increased in the cecum. Conclusions: These results suggest that the distribution of MAIT cells was different between the cecum and colon and that MAIT cells were more likely to be activated, especially in the intestinal epithelium of the cecum than in the colon and blood.

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  • 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   33 ( 11 )   1817   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

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  • A first ileus event in an elderly man with malrotation. 査読

    Tominaga K, Tsuchiya A, Terai S

    Gastroenterology   156 ( 3 )   E9 - E11   2018年9月

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Georg Thieme Verlag  

    Background Esophageal squamous cell carcinoma (ESCC) invading the muscularis mucosae (MM) and submucosa up to 200μm (SM1) has a risk of metastasis. The aims of this study were to investigate the long-term outcome of endoscopic submucosal dissection (ESD) for MM/SM1 ESCC and to assess the management after ESD in our hospital. Methods This was a retrospective cohort study conducted at a single institution. Patients with MM or SM1 ESCC who were treated with ESD were included. Additional prophylactic therapy was added if lymphovascular involvement (LVI) was noted in the ESD specimens. Results A total of 102 patients were analyzed. The median length of follow-up was 71.5 months (range 9-144 months) and the median number of CTs was 6 (range 0-24). LVI was found in 21 patients (20.6%), and 12 patients underwent additional prophylactic therapy. The 5-year overall survival, disease-specific survival, and tumor-free survival rates were 84.1%, 97.5%, and 82.1%, respectively. A total of 26 patients died, but only 2 of them died from ESCC. The cumulative metastasis rate was 11.8%, and LVI was a significant predictor of metastasis (hazard ratio 5.42, 95% confidence interval 1.39-21.18
    P =0.02). There were no differences between patients with MM ESCC and those with SM1 ESCC. Conclusions The long-term outcome after ESD for MM/SM1 ESCC was favorable with additional prophylactic therapy and strict adherence to follow-up.These results indicate that our management decision based on LVI is a valid approach and that ESD can be offered as a therapeutic option to MM/SM1 ESCCs.

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  • 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

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    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.

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  • 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

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    記述言語:英語  

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  • 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

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    記述言語:英語  

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  • 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

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  • 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

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  • How do you treat this diversion ileitis and pouchitis? 査読

    Kentaro Tominaga, Atsunori Tsuchiya, Junji Yokoyama, Shuji Terai

    Gut   2018年5月

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

    DOI: 10.1136/gutjnl-2017-315591

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  • 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

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    記述言語:英語   出版者・発行元:Baishideng Publishing Group Co., Limited  

    Diversion colitis is characterized by inflammation of the mucosa in the defunctioned segment of the colon after colostomy or ileostomy. Similar to diversion colitis, diversion pouchitis is an inflammatory disorder occurring in the ileal pouch, resulting from the exclusion of the fecal stream and a subsequent lack of nutrients from luminal bacteria. Although the vast majority of patients with surgically-diverted gastrointestinal tracts remain asymptomatic, it has been reported that diversion colitis and pouchitis might occur in almost all patients with diversion. Surgical closure of the stoma, with reestablishment of gut continuity, is the only curative intervention available for patients with diversion disease. Pharmacologic treatments using short-chain fatty acids, mesalamine, or corticosteroids are reportedly effective for those who are not candidates for surgical reestablishment
    however, there are no established assessment criteria for determining the severity of diversion colitis, and no management strategies to date. Therefore, in this mini-review, we summarize and review various recently-reported treatments for diversion disease. We are hopeful that the information summarized here will assist physicians who treat patients with diversion colitis and pouchitis, leading to better case management.

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)  

    DOI: 10.1007/s12328-018-0860-6

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  • 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

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    記述言語:英語   出版者・発行元:Nature Publishing Group  

    DOI: 10.1038/ajg.2017.481

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:Blackwell Publishing  

    Background and Aim: Recent studies have demonstrated that B cells and follicular helper T (Tfh) cells, which are central regulators of humoral immune response, contribute to the development and progression of autoimmune diseases. Because Tfh cells can be divided into several subsets with distinct functional properties, this study aimed to examine the roles of different subsets of circulating Tfh cells in the immune pathogenesis of autoimmune hepatitis (AIH). Methods: Thirty-five patients with AIH, 28 patients with primary biliary cholangitis, 22 patients with chronic hepatitis B (CHB), and 44 health controls (HC) were enrolled. The frequencies of different Tfh subsets in the blood and liver were examined by flow cytometry and immunohistochemical staining. The function of circulating Tfh subsets was examined after in vitro stimulation. Results: In newly diagnosed AIH patients, the frequency of circulating chemokine C-C receptor 7−programmed cell death-1+ Tfh subset was significantly increased compared with that in CHB patients and HC, significantly correlated with clinical parameters, including serum IgG, prothrombin time and albumin levels, and significantly decreased after corticosteroid treatment. In the liver of AIH patients, the frequencies of activated Tfh subsets were significantly increased and positively correlated with those in the blood. Moreover, the ability to produce interleukin-21 and interleukin-17 from circulating Tfh cells was significantly increased in AIH patients compared with HC. Conclusions: These results significantly extend our understanding of Tfh subsets in AIH and suggest a potential role of dysregulated chemokine C-C receptor 7−programmed cell death-1+ Tfh subset in the pathogenesis and disease progression of AIH.

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  • 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

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  • 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

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1002/hep.29266

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:NATURE PUBLISHING GROUP  

    Cell motility plays an important role in intrahepatic metastasis of hepatocellular carcinoma (HCC), and predicts poor prognosis in patients. The present study investigated the role of a disintegrin and metalloproteinases (ADAMs) in HCC, since these proteins are known to be associated with cell motility. We confirmed the expression of 12 ADAMs with putative metalloproteinase activity in HCC cells, and established a KYN-2 HCC cell line stably expressing short interfering RNA against ADAM21 to investigate the effect of ADAM21 deficiency on HCC cell motility and metastasis in vitro and in vivo. We also examined ADAM21 expression in a cohort of 119 HCC patients by immunohistochemistry. ADAM21 was overexpressed in KYN-2 cells, and its knockdown reduced invasion, migration, proliferation, and metastasis relative to controls. In clinical specimens, ADAM21 positivity was associated with vascular invasion, large tumor size, high histological grade, and lower overall and recurrence-free survival as compared to cases that were negative for ADAM21 expression. A multivariate analysis revealed that ADAM21 positivity was an independent risk factor for overall (P = 0.003) and recurrence-free (P = 0.001) survival. These results suggest that ADAM21 plays a role in HCC metastasis and can serve as a prognostic marker for disease progression.

    DOI: 10.1038/s41598-017-15800-z

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  • Intraductal Papillary Neoplasm of the Bile Duct: A Rare Liver Tumor Complicated by Malignancy

    Kentaro Tominaga, Kenya Kamimura, Akira Sakamaki, Shuji Terai

    HEPATOLOGY   66 ( 5 )   1695 - 1697   2017年11月

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    記述言語:英語   出版者・発行元:WILEY  

    DOI: 10.1002/hep.29266

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    munity. Recent studies have demonstrated that MAIT cells might be implicated in inflammatory bowel diseases (IBDs), but their precise function in IBD remains to be elucidated. We investigated the possible involvement of MAIT cells in the immunopathogenesis of IBDs. Heparinized peripheral blood and biopsy specimens of the colon were collected from 25 patients with ulcerative colitis (UC), 15 patients with Crohn's disease (CD), and 19 heathy individuals. Lymphocytes were isolated from the blood and colon, and then MAIT cells were analyzed by flow cytometry. The frequency of MAIT cells was significantly lower in the blood of IBD patients compared to healthy donors and significantly higher in the inflamed colons compared to healthy colons (P = 0.001). Among the IBD patients, the frequency of MAIT cells in the blood and colon was correlated with disease activities. In vitro activated MAIT cells from IBD patients secreted significantly more tumor necrosis factor-alpha and interleukin-17 than those from healthy donors. These findings indicate that MAIT cells are activated in IBD patients, and their accumulation in the inflamed mucosa is correlated with disease activities.

    DOI: 10.2220/biomedres.38.111

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  • 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

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    記述言語:英語   出版者・発行元:WILEY  

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  • 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

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:HINDAWI PUBLISHING CORP  

    Background. Dentures and dental instruments are frequently encountered ingested foreign bodies. The aim of the present study was to assess the safety and efficacy of endoscopically removing ingested dental objects. Methods. Twenty-nine consecutive patients with 29 dental objects who were treated at the Niigata University Medical and Dental Hospital from August 2009 to December 2015 were retrospectively reviewed. Characteristics of the patients and the ingested dental objects, the clinical features and findings of radiological imaging tests, and outcomes of endoscopic removal were analyzed. Results. Patients' mean age was 62.9 + 21.0 years. The ingested dental objects included 23 dentures (13 crowns, 4 bridges, 4 partial dentures, and 2 other dentures) and 6 dental instruments. Twenty-seven upper gastrointestinal endoscopies and 2 colonoscopies were performed, and their success rates were 92.6% and 100%, respectively. There were 2 cases of removal failure; one case involved an impacted partial denture in the cervical esophagus, and this case required surgical removal. Conclusions. Endoscopic removal of ingested dentures and dental instruments is associated with a favorable success rate and acceptable complications. The immediate intervention and appropriate selection of devices are essential for managing ingested dental objects.

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  • 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

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  • Imbalance between CD56(+bright) and CD56(+dim) natural killer cell subsets in the liver of patients with recurrent hepatitis C after liver transplantation 査読

    Satoshi Yamagiwa, Yoshinobu Sato, Takafumi Ichida, Toru Setsu, Kentaro Tominaga, Hiroteru Kamimura, Atsunori Tsuchiya, Masaaki Takamura, Yasunobu Matsuda, Yutaka Aoyagi

    BIOMEDICAL RESEARCH-TOKYO   35 ( 3 )   177 - 184   2014年6月

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    記述言語:英語   掲載種別:研究論文(学術雑誌)   出版者・発行元:BIOMEDICAL RESEARCH PRESS LTD  

    Progressive liver fibrosis remains a major problem for patients with recurrent chronic hepatitis C (CHC) after liver transplantation (LT). However, the involvement of natural killer (NK) and natural killer T (NKT) cells, which predominate in the liver, in recurrent CHC after LT remains unclear. In the present study, we investigated the status of NK and NKT cells in the liver and peripheral blood obtained from 10 patients with recurrent CHC after LT (LT-C), 15 patients with CHC, and 7 normal donors for living donor LT. CD56(+) NK cells were separated into two subsets: CD56(+bright) subset, which is identified as major NK cytokine producer, and CD56(+dim) subset, which has greater spontaneous cytotoxicity. We found a significant decrease in the CD56(+bright) subset in the liver of patients with LT-C compared to patients with CHC (P &lt; 0.01) and normal donors (P = 0.03). The expression of inhibitory NK cell receptor NKG2A was significantly increased on intrahepatic CD56(+bright) subset in LT-C patients, and activated CD69(+)CD56(+dim) NK cell subset was significantly increased. in the liver of LT-C patients. Our results suggest that a significant imbalance between CD56(+bright) and CD56(+dim) NK cell subsets in the liver may contribute to the progression of recurrent CHC after LT.

    DOI: 10.2220/biomedres.35.177

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  • Distinctive phenotypic features of human mucosal-associated invariant T cells in the liver 査読

    Kentaro Tominaga, Toru Setsu, Satoshi Yamagiwa, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Masaaki Takamura, Minoru Nomoto

    HEPATOLOGY   60   506A - 506A   2014年

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    記述言語:英語   出版者・発行元:WILEY-BLACKWELL  

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  • Possible impairment of mucosal-associated invariant T cells in the liver of patients with primary biliary cirrhosis 査読

    Toru Setsu, Satoshi Yamagiwa, Kentaro Tominaga, Naruhiro Kimura, Hiroki Honda, Hiroteru Kamimura, Masaaki Takamura, Minoru Nomoto

    HEPATOLOGY   60   357A - 358A   2014年

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  • 空置腸炎における自家糞便移植の有用性と腸内細菌叢の評価

    冨永 顕太郎

    腸内細菌学雑誌   38 ( 2 )   85 - 86   2024年4月

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    記述言語:日本語   出版者・発行元:(公財)腸内細菌学会  

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  • 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

    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

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 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

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    記述言語:日本語   出版者・発行元:日本消化器病学会-甲信越支部  

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  • 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

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    記述言語:日本語   出版者・発行元:日本消化器病学会-甲信越支部  

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 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

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    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  

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  • 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

    肝臓   62 ( Supplement 2 )   2021年

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 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 (Web)   62 ( Supplement1 )   2020年

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 十二指腸狭窄により発症した前下膵十二指腸動脈瘤破裂の1例

    渡部 はるか, 石井 結唯, 武田 信峻, 夏井 一輝, 荒生 祥尚, 冨永 顕太郎, 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   65回   59 - 59   2019年11月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-甲信越支部  

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  • 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

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    記述言語:日本語   出版者・発行元:日本消化器病学会-甲信越支部  

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  • 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

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

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  • CONSIDERATION OF SERUM IGA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

    Kentaro Tominaga, Yuzo Kawata, Naruhiro Kimura, Takeshi Mizusawa, Hiroki Sato, Satoshi Ikarashi, Kazunao Hayashi, Kenichi Mizuno, Satoru Hashimoto, Atsunori Tsuchiya, Junji Yokoyama, Shuji Terai

    GASTROENTEROLOGY   156 ( 6 )   S847 - S847   2019年5月

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    記述言語:英語   掲載種別:研究発表ペーパー・要旨(国際会議)   出版者・発行元:W B SAUNDERS CO-ELSEVIER INC  

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本消化器内視鏡学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一社)日本大腸肛門病学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 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

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 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

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    消化器・肝臓内科 = Gastroenterology & hepatology   5 ( 1 )   120 - 126   2019年1月

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    日本消化器病学会雑誌(Web)   116   2019年

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    日本大腸肛門病学会雑誌(Web)   72 ( 5 )   2019年

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    日本消化器病学会雑誌(Web)   116   2019年

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    日本消化器病学会雑誌(Web)   116   2019年

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    Endoscopic Forum for Digestive Disease   34 ( 2 )   195 - 195   2018年12月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

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    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

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    記述言語:日本語   出版者・発行元:日本消化器病学会-甲信越支部  

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    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   74 - 74   2018年11月

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    記述言語:日本語   出版者・発行元:日本消化器病学会-甲信越支部  

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  • 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

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  • 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

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  • 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

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  • 超音波内視鏡における音速補正モードの有用性

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    Gastroenterological Endoscopy   60 ( Suppl.2 )   2110 - 2110   2018年10月

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  • 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

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  • 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

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  • 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

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    日本消化器病学会雑誌   115 ( 臨増総会 )   A393 - A393   2018年4月

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    林 和直, 五十嵐 聡, 木村 成宏, 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

    日本消化器病学会雑誌   115 ( 臨増総会 )   A299 - A299   2018年4月

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  • 消化管機能検査 最新技術とその応用 消化管運動機能検査としての小腸カプセル内視鏡の有用性の検討

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    日本消化器病学会雑誌   115 ( 臨増総会 )   A136 - A136   2018年4月

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    Gastroenterological Endoscopy   60 ( Suppl.1 )   762 - 762   2018年4月

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  • IPMNの悪性診断における膵液細胞診の役割

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    Gastroenterological Endoscopy   60 ( Suppl.1 )   671 - 671   2018年4月

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    日本消化器病学会雑誌   115 ( 臨増総会 )   A393 - A393   2018年4月

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    日本消化管学会雑誌   2 ( Supplement )   135 - 135   2018年2月

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    日本消化管学会雑誌   2 ( Suppl. )   135 - 135   2018年2月

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    日本消化器病学会雑誌(Web)   115   2018年

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    Gastroenterological Endoscopy (Web)   60 ( Supplement1 )   762(J‐STAGE)   2018年

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    Gastroenterological Endoscopy (Web)   60 ( Supplement1 )   671(J‐STAGE)   2018年

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  • 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

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  • Trousseau症候群を合併した胆管細胞癌の2例

    品川 陽子, 上村 顕也, 酒井 規裕, 熊木 大輔, 小川 光平, 安住 里英, 冨永 顕太郎, 坂牧 僚, 五十嵐 聡, 林 和直, 山本 幹, 水野 研一, 山際 訓, 寺井 崇二

    肝臓   58 ( 9 )   528 - 535   2017年9月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    Trousseau症候群は、Trousseauによって1865年に報告された、悪性腫瘍に合併する血栓症である。その脳卒中症状は、重篤な神経症状を呈し、直接的に生命予後に関与しうる傍悪性腫瘍症候群の一つとして認識されている。今回、胆管細胞癌に脳卒中症状を呈するTrousseau症候群を合併し死亡した2例を経験したので報告する。症例1は90歳、男性、症例2は58歳、女性でいずれの症例も生活習慣病の危険因子を有し、40mm前後の肝腫瘍で初診、各種画像検査、胆汁細胞診、組織診にて胆管細胞癌の診断となった。経過中、腫瘍の急激な増大、胆道出血を合併し、本症候群を発症しやすい状況であった。担癌患者では、病態が急速に進行する場合、凝固線溶系の異常値などに留意し、抗凝固療法の開始を含む対応が本症候群の発症を予防し、原病に対する治療介入の機会を増やしうる方法論であると考え、報告する。(著者抄録)

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    その他リンク: https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J00263&link_issn=&doc_id=20171003140007&doc_link_id=130006106557&url=http%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130006106557&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

  • Crohn病診療におけるMR enterographyの役割

    本田 穣, 横山 純二, 冨永 顕太郎, 高橋 一也, 西垣 佑紀, 五十嵐 聡, 林 和直, 水野 研一, 橋本 哲, 佐藤 祐一, 寺井 崇二

    日本消化器病学会雑誌   114 ( 臨増総会 )   A275 - A275   2017年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • Trousseau症候群を合併した胆管細胞癌の2例

    品川陽子, 上村顕也, 酒井規裕, 熊木大輔, 小川光平, 安住里英, 冨永顕太郎, 坂牧僚, 五十嵐聡, 林和直, 山本幹, 水野研一, 山際訓, 寺井崇二

    肝臓   58 ( 9 )   528‐535(J‐STAGE) - 535   2017年

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

    Trousseau症候群は、Trousseauによって1865年に報告された、悪性腫瘍に合併する血栓症である。その脳卒中症状は、重篤な神経症状を呈し、直接的に生命予後に関与しうる傍悪性腫瘍症候群の一つとして認識されている。今回、胆管細胞癌に脳卒中症状を呈するTrousseau症候群を合併し死亡した2例を経験したので報告する。症例1は90歳、男性、症例2は58歳、女性でいずれの症例も生活習慣病の危険因子を有し、40mm前後の肝腫瘍で初診、各種画像検査、胆汁細胞診、組織診にて胆管細胞癌の診断となった。経過中、腫瘍の急激な増大、胆道出血を合併し、本症候群を発症しやすい状況であった。担癌患者では、病態が急速に進行する場合、凝固線溶系の異常値などに留意し、抗凝固療法の開始を含む対応が本症候群の発症を予防し、原病に対する治療介入の機会を増やしうる方法論であると考え、報告する。(著者抄録)

    DOI: 10.2957/kanzo.58.528

    J-GLOBAL

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  • IFN関連精神症状と診断された既往があり,DAA治療中にも精神症状を呈したC型慢性肝炎の1例

    坂牧僚, 上村顕也, 酒井規裕, 冨永顕太郎, 阿部聡司, 水野研一, 土屋淳紀, 高村昌昭, 川合弘一, 山際訓, 寺井崇二

    肝臓   57 ( Supplement 3 )   A772   2016年10月

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    記述言語:日本語  

    J-GLOBAL

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  • IFN関連精神症状と診断された既往があり、DAA治療中にも精神症状を呈したC型慢性肝炎の1例

    坂牧 僚, 上村 顕也, 酒井 規裕, 冨永 顕太郎, 阿部 聡司, 水野 研一, 土屋 淳紀, 高村 昌昭, 川合 弘一, 山際 訓, 寺井 崇二

    肝臓   57 ( Suppl.3 )   A772 - A772   2016年10月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 肝細胞癌におけるa disintegrin and metalloprotease 21発現の生物学的意義に関する検討

    本田 博樹, 高村 昌昭, 山際 訓, 玄田 拓哉, 木村 成宏, 薛 徹, 冨永 顕太郎, 上村 博輝, 松田 康伸, 若井 俊文, 寺井 崇二

    肝臓   57 ( Suppl.1 )   A247 - A247   2016年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 自己免疫性肝炎における肝内および末梢血中濾胞性ヘルパーT細胞の検討

    木村 成宏, 山際 訓, 本田 博樹, 薛 徹, 冨永 顕太郎, 上村 博輝, 高村 昌昭, 寺井 崇二

    肝臓   56 ( Suppl.1 )   A295 - A295   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • メチオニン・コリン欠乏食(MCD)誘発性脂肪肝炎に対するDPP-4阻害薬の効果

    山際 訓, 木村 成宏, 本田 博樹, 薛 徹, 冨永 顕太郎, 上村 博輝, 高村 昌昭, 寺井 崇二

    肝臓   56 ( Suppl.1 )   A549 - A549   2015年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • 炎症性腸疾患患者の末梢血および大腸粘膜におけるMAIT細胞に関する検討

    冨永 顕太郎, 山際 訓, 薛 徹, 木村 成宏, 鈴木 健司, 寺井 崇二

    日本消化器病学会雑誌   112 ( 臨増総会 )   A345 - A345   2015年3月

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    記述言語:日本語   出版者・発行元:(一財)日本消化器病学会  

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  • 自己免疫性肝炎と胆汁性肝硬変のオーバーラップの検討

    冨永 顕太郎, 栗田 聡, 佐々木 俊哉, 船越 和博, 本山 展隆, 加藤 俊幸

    新潟医学会雑誌   126 ( 11 )   645 - 645   2012年11月

  • 47 自己免疫性肝炎と胆汁性肝硬変のオーバーラップの検討(I.一般演題, 第36回リバーカンファレンス)

    冨永 顕太郎, 栗田 聡, 佐々木 俊哉, 船越 和博, 本山 展隆, 加藤 俊幸

    新潟医学会雑誌   126 ( 11 )   645 - 645   2012年11月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    CiNii Article

    CiNii Books

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  • 4 十二指腸主乳頭病変をともなったIgG4関連膵・胆管炎の1例(I.一般演題, 第95回新潟消化器病研究会)

    冨永 顕太郎, 船越 和博, 本山 展隆, 栗田 聡, 佐々木 俊哉, 加藤 俊幸, 野村 達也, 土屋 嘉昭

    新潟医学会雑誌   126 ( 10 )   561 - 561   2012年10月

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    記述言語:日本語   出版者・発行元:新潟医学会  

    CiNii Article

    CiNii Books

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  • 十二指腸主乳頭病変をともなったIgG4関連膵・胆管炎の1例

    冨永 顕太郎, 船越 和博, 本山 展隆, 栗田 聡, 佐々木 俊哉, 加藤 俊幸, 野村 達也, 土屋 嘉昭

    新潟医学会雑誌   126 ( 10 )   561 - 561   2012年10月

  • 肝疾患臨床 BCG免疫療法による肉芽腫性肝炎の2例

    栗田 聡, 加藤 俊幸, 冨永 顕太郎, 佐々木 俊哉, 船越 和博, 本山 展隆

    肝臓   53 ( Suppl.1 )   A267 - A267   2012年4月

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    記述言語:日本語   出版者・発行元:(一社)日本肝臓学会  

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  • EUS-FNAが治療方針決定に有用であった膵癌の2例

    塩路 和彦, 小林 正明, 成澤 林太郎, 冨永 顕太郎, 林 和直, 瀧澤 一休, 冨樫 忠之, 青柳 豊

    ENDOSCOPIC FORUM for digestive disease   27 ( 2 )   159 - 159   2011年11月

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    記述言語:日本語   出版者・発行元:(株)癌と化学療法社  

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▶ 全件表示

共同研究・競争的資金等の研究

  • ヒト、マウスモデルを用いた空置腸炎に対する自家糞便移植の病態改善機序解明

    研究課題/領域番号:19K17393

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 若手研究

    研究種目:若手研究

    提供機関:日本学術振興会

    冨永 顕太郎

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    本研究の目的は、空置腸炎における自家糞便移植(FMT)の有用性の検討と、空置腸管の免疫グロブリンA(IgA)・短鎖脂肪酸濃度の測定および腸内細菌叢の評価を行い、空置腸炎の発症のメカニズムを調査することである。
    研究実績①:第 105 回日本消化器病学会総会(2019)において、「空置腸炎に対する自家糞便移植の有用性と腸内細菌叢に与える影響の検討」と題してワークショップセッションで学会発表を行った。対象は、当院で人工肛門造設に伴う空置腸炎と診断された6症例、FMT前後で内視鏡検査および糞便採取を行い、次世代シーケンサーMiSeqを用いた16SrRNAメタゲノム解析により腸内細菌叢の解析を行うと共に、糞便中のIgA、脂肪酸の濃度測定を行った。FMTによって全症例で内視鏡上の腸炎の悪化は抑制された。また、FMTによる空置腸管内の腸内細菌叢の変化(Proteobacteria門の減少とFirmicutes門の増加)が観察された。本発表では、空置腸炎における自家糞便移植の有用性と腸内細菌叢の変化を提示し、今後の腸内細菌叢をターゲットする新しい治療法・予防法への応用の可能性を示した。
    研究実績②:米国消化器病学会(2019)において、「Consideration of serum IgA in patients with Inflammatory Bowel Disease」と題してポスター発表を行った。免疫グロブリンA(IgA)は腸管粘膜から分泌され、感染防御と腸内細菌叢制御、腸管免疫において重要な役割をはたす抗体である。今回、炎症性腸疾患患者において、病勢や病型、腸管切除歴等が血清IgA値に影響している可能性を示した。今後、腸管免疫制御に重要な役割を担うIgAをターゲットとした炎症性腸疾患に対する新たな内科的治療も期待される。

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  • 小腸絨毛基底膜における「窓」の脂肪吸収に対する調節機能の解明

    研究課題/領域番号:19K08462

    2019年4月 - 2022年3月

    制度名:科学研究費助成事業 基盤研究(C)

    研究種目:基盤研究(C)

    提供機関:日本学術振興会

    横山 純二, 寺井 崇二, 牛木 辰男, 高村 昌昭, 八木 一芳, 冨永 顕太郎

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    配分額:4290000円 ( 直接経費:3300000円 、 間接経費:990000円 )

    肥満者にみられる十二指腸絨毛の白色変化を光学顕微鏡で観察すると、リンパ管拡張所見はみられず、細胞内や細胞間隙に蓄積したカイロミクロンを反映しているものと思われた。電子顕微鏡での観察結果と合わせ、小腸絨毛基底膜にみられる窓は、カイロミクロンの中心乳糜管への運搬を調整しており、肥満者においては、カイロミクロンの通過を厳しく制限している可能性が示唆された。すなわち、基底膜の窓は、高脂血症、肥満の抑制に寄与する方向に働いていると推察された。また、脂肪吸収の効率と基底膜の窓との相関については、腸管壁バリア機能の破綻や、小腸内細菌増殖症との関連も含め総合的に検討する必要があると考えられた。

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