Updated on 2025/04/17

Information

 

写真a

 
OGINO HARUEI
 
Organization
Faculty of Medical Sciences Lecturer
Title
Lecturer
Profile
九州大学大学院医学研究院 消化器代謝学講座(第三内科)にて消化管疾患の研究・診療・教育活動に従事している。 研究: 炎症性腸疾患はクローン病と潰瘍性大腸炎からなる、遺伝性素因・免疫学的素因・環境的素因が関与する難治性の疾患である。欧米で多い疾患とされてきたが、環境因子の影響もあり日本を含めたアジアでも患者数が激増している。免疫学的素因として、クローン病はTh1/Th17細胞、潰瘍性大腸炎はTh2/Th17が関与していると考えられており、炎症性腸疾患の患者様は、このエフェクターT細胞と免疫を制御するとされているT細胞のバランスが破綻していることや、環境因子としての腸内細菌叢の異常が病態に大きく関与している。我々は免疫学的機序や腸内細菌を含めた環境因子を基礎研究・臨床研究から解明し、炎症性腸疾患にて苦しんでいる患者様の助けになりたいと考えている。 診療: 炎症性腸疾患は大部分が軽症・中等症の患者様であるが、5%弱は非常に症状が重篤な重症や劇症症例が含まれている。この様な重篤な患者様や、軽症・中等症の患者様の中でも治療抵抗性・難治性の患者様の治療も積極的に行っている。 さらに、消化管癌に対する内視鏡治療として内視鏡粘膜下層剥離術を用いた侵襲の少ない治療を行っている。消化管癌は早期に発見することで内視鏡的に切除することが可能である。さらに下咽頭領域に対する内視鏡的治療も耳鼻科の先生と協力し積極的に行っている。 教育面では、上記内容を含めて大学院生・病棟医員・医学部生に対する指導・講義を行っている。
Homepage
  • http://www.intmed3.med.kyushu-u.ac.jp/

    第3内科は内分泌代謝糖尿病、血液、肝臓、膵臓、消化器の5つの研究室を有し、それぞれが専門的視点から診療にあたる一方、お互いに密接に連携して一人の患者さんを総合的に捉え、質の高い医療を提供します。特定の臓器に偏らず患者さん全体をみる伝統が根付いています。
    日本内科学会教育病院・教育関連病院はもちろんのこと、各専門学会の認定施設も多数関連病院に持ち、充実した施設と指導医の元で初期研修、後期研修、専門領域研修を行えます。北部九州に関連病院が集中し、お互いに連携しているのも大きな特徴です。電解質異常・高血糖への適切な対応、抗がん剤治療、エコー・内視鏡を駆使した処置など高度な知識・技術を系統的に習得することができます。
    当科には女医さんも多く所属しており、出産・子育て・仕事復帰を応援しています。子育てをしながらのキャリアアップが可能です。また、大学院進学者も多く、多数の医学博士を輩出しています。研究と臨床をバランス良く磨き、広い見方のできる医師を育てます。これらの強力な人材育成システムで教育された優秀な先輩たちは、大学教授、病院長などの重要なポストに入り、後輩の教育環境をさらに整えています。出身大学に関係なく個人の実力が優先される自由闊達な雰囲気がその源です。加えて、開業される先輩も多く、情報共有、診療連携など第3内科同門として頼りになるネットワークを形成します。

External link

Research Areas

  • Life Science / Gastroenterology

Degree

  • 博士 ( 2011.3 Kyushu University )

Research History

  • Kyushu University 消化器代謝学講座 Lecturer 

    2023.4 - Present

  • Kyushu University 病態制御内科学 肝臓・膵臓・胆道内科 Assistant Professor 

    2017.4 - 2023.3

Education

  • Kyushu University   医学部   医学科

    1995.4 - 2001.3

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    Country:Japan

Research Interests・Research Keywords

  • Research theme: Clarification of the pathology and examination of treatment policy in IBD

    Keyword: IBD

    Research period: 2017.4 - Present

Awards

  • 第121回 内科学会ことはじめ 専攻医指導医賞

    2024   日本内科学会  

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    Award type:Award from Japanese society, conference, symposium, etc. 

  • 第342回 日本内科学会九州支部例会 初期研修医指導医賞

    2023   日本内科学会  

Papers

  • Importance of rectal over colon status in ulcerative colitis remission: the role of microinflammation and mucosal barrier dysfunction in relapse Reviewed

    Nishioka, K; Ogino, H; Ihara, E; Chinen, T; Kimura, Y; Esaki, M; Bai, XP; Minoda, Y; Tanaka, Y; Wada, M; Hata, Y; Ambrosini, YM; Ogawa, Y

    JOURNAL OF GASTROENTEROLOGY   2024.12   ISSN:0944-1174 eISSN:1435-5922

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    Authorship:Lead author   Language:English   Publisher:Journal of Gastroenterology  

    Background: Ulcerative colitis (UC) is a refractory inflammatory disease that affects the rectum and colon, with pivotal involvement of the rectal environment in relapse initiation. This study was conducted in two phases to examine the differences in gene expression between the rectum and colon and to identify relapse factors. Methods: In ***Study 1, RNA sequencing was performed on biopsies from the colon and rectum of patients with active UC, those with remission UC, and controls. In Study 2, the mucosal impedance (MI) values reflecting mucosal barrier function and the mRNA expression of tight junction proteins and inflammatory cytokines were examined in 32 patients with remission UC and 22 controls. Relapse was monitored prospectively. Results: In Study 1, comprehensive genetic analysis using RNA sequencing revealed distinct gene profiles in the rectum and sigmoid colon of patients with remission UC. The rectum of these patients exhibited an enriched immune response and apical junction phenotype with persistent upregulation of CLDN2 gene expression. In Study 2, even in patients with remission UC, the MI values in the rectum, but not in the sigmoid colon, were significantly decreased, whereas they were negatively correlated with CLDN2, IL-1β, and IL-6 expressions. Conclusion: The status of the rectum in patients with remission UC differs from that of the colon, with microinflammation and impaired mucosal barrier function, which are associated with the upregulation of CLDN2, playing a role in relapse.

    DOI: 10.1007/s00535-024-02199-4

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  • Evidence-Based Clinical Guidelines for Chronic Diarrhea 2023. Reviewed International journal

    Eikichi Ihara, Noriaki Manabe, Hidenori Ohkubo, Naotaka Ogasawara, Haruei Ogino, Kazuki Kakimoto, Motoyori Kanazawa, Hidejiro Kawahara, Chika Kusano, Shiko Kuribayashi, Akinari Sawada, Tomohisa Takagi, Shota Takano, Toshihiko Tomita, Toshihiro Noake, Mariko Hojo, Ryota Hokari, Tatsuhiro Masaoka, Tomohiko Machida, Noboru Misawa, Yoshiyuki Mishima, Hiroshi Yajima, Sayuri Yamamoto, Hiroshi Yamawaki, Tatsuya Abe, Yasumi Araki, Kunio Kasugai, Takeshi Kamiya, Akira Torii, Atsushi Nakajima, Koji Nakada, Shin Fukudo, Yasuhiro Fujiwara, Hiroto Miwa, Hiromi Kataoka, Akihito Nagahara, Kazuhide Higuchi

    Digestion   105 ( 6 )   480 - 497   2024.12   ISSN:0012-2823 eISSN:1421-9867

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    The Japan Gastroenterological Association (JGA) published the first version of clinical guidelines for chronic diarrhea 2023. These guidelines describe the definition, classification, diagnostic criteria, diagnostic testing methods, epidemiology, pathophysiology, and treatment of chronic diarrhea, and provide flowcharts for the diagnosis and treatment of chronic diarrhea based on the latest evidence. Treatment for chronic diarrhea begins by distinguishing secondary chronic constipation with a clear etiology, such as drug-induced diarrhea, food-induced diarrhea, systemic disease-associated diarrhea, infection-associated diarrhea, organic disease-associated diarrhea, and bile acid diarrhea. The first line of treatment for chronic diarrhea in the narrow sense, defined in these guidelines as functional diarrhea in routine medical care, is lifestyle modification and dietary therapy. The first medicines to be considered for oral treatment are probiotics for regulating the gut microbiome and antidiarrheals. Other medications, such as 5HT3 receptor antagonists, anticholinergics, Kampo medicine, psychotherapy, antibiotics, bulking agents, adrenergic agonists, and somatostatin analogues, lack sufficient evidence for their use, highlighting a challenge for future research. This Clinical Guidelines for Chronic Diarrhea 2023, which provides the best clinical strategies for treating chronic diarrhea in Japan, will also be useful for medical treatment worldwide.

    DOI: 10.1159/000541121

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  • Validation of a claims-based algorithm to identify cases of ulcerative colitis in Japan Reviewed

    Ogino, H; Morikubo, H; Fukaura, K; Okui, T; Gardiner, S; Sugiyama, N; Yoshii, N; Kawaguchi, T; Chen, HQ; Nonnenmacher, E; Setoguchi, S; Nakashima, N; Kobayashi, T

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY   37 ( 3 )   499 - 506   2022.3   ISSN:0815-9319 eISSN:1440-1746

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    Authorship:Lead author   Language:English   Publisher:Journal of Gastroenterology and Hepatology (Australia)  

    Background and Aim: The prevalence of ulcerative colitis (UC) is increasing in Japan. Validated claims-based definitions are required to investigate the epidemiology of UC and its treatment and disease course in clinical practice. This study aimed to develop a claims-based algorithm for UC in Japan. Methods: A committee of epidemiologists, gastroenterologists, and internal medicine physicians developed a claims-based definition for UC, based on diagnostic codes and claims for UC treatments, procedures (cytapheresis), or surgery (postoperative claims). Claims data and medical records for a random sample of 200 cases per site at two large tertiary care academic centers in Japan were used to calculate the positive predictive value (PPV) of the algorithm for three gold standards of diagnosis, defined as physician diagnosis in the medical records, adjudicated cases, or registration in the Japanese Intractable Disease Registry (IDR). Results: Overall, 1139 claims-defined UC cases were identified. Among 393 randomly sampled cases (mean age 44; 48% female), 94% had received ≥ 1 systemic treatment (immunosuppressants, tumor necrosis factor inhibitors, corticosteroids, or antidiarrheals), 7% had cytapheresis, and 7% had postoperative claims. When physician diagnosis was used as a gold standard, PPV was 90.6% (95% confidence interval [CI]: 87.7–93.5). PPV with expert adjudication was also 90.6% (95% CI: 87.7–93.5). PPVs with enrollment in the IDR as gold standard were lower at 41.5% (95% CI: 36.6–46.3) due to incomplete case registration. Conclusions: The claims-based algorithm developed for use in Japan is likely to identify UC cases with high PPV for clinical studies using administrative claims databases.

    DOI: 10.1111/jgh.15732

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  • Mucosal IL23A expression predicts the response to Ustekinumab in inflammatory bowel disease. Reviewed

    Kei Nishioka, Haruei Ogino, Takatoshi Chinen, Eikichi Ihara, Yoshimasa Tanaka, Kazuhiko Nakamura, Yoshihiro Ogawa

    Journal of gastroenterology   56 ( 11 )   976 - 987   2021.8

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    BACKGROUND: Biologics against tumor necrosis factor-α (TNF) and the p40 subunit of interleukin (IL)-12 and IL-23 are increasingly used in inflammatory bowel disease (IBD) treatment. However, information on response prediction to these agents is limited. Thus, we aimed to identify factors for IBD treatment response prediction. METHODS: We conducted a retrospective study in 33 IBD subjects for anti-TNF and a prospective study of 23 IBD and 11 non-IBD subjects for ustekinumab (UST). Mucosal biopsy specimens were obtained before treatment with biologics. The expression of 18 immune-related genes encoding representative cytokines and transcription factors was analyzed by quantitative polymerase chain reaction. RESULTS: There was no difference between the treatment-resistant and -sensitive groups with regard to clinical characteristics. A higher expression of oncostatin M (OSM) and its receptor OSMR in the intestinal mucosa was most strongly associated with anti-TNF resistance, whereas lower IL23A expression was most strongly associated with UST resistance. In addition to the absolute expression levels of genes, concordant or discordant expression patterns of particular gene sets were associated with treatment sensitivity and resistance. CONCLUSIONS: The association of anti-TNF resistance and mucosal OSM and OSMR expression was consistent with the results of a previous study in a European cohort. Our observation that IBD subjects with higher mucosal IL23A expression were more likely to achieve remission by UST has not been previously reported. The response to biologics may thus be predicted in IBD patients through the analysis of mucosal gene expression levels and patterns.

    DOI: 10.1007/s00535-021-01819-7

  • Mucosa-associated gut microbiota reflects clinical course of ulcerative colitis. Reviewed International journal

    Yuichiro Nishihara, Haruei Ogino, Masaru Tanaka, Eikichi Ihara, Keita Fukaura, Kei Nishioka, Takatoshi Chinen, Yoshimasa Tanaka, Jiro Nakayama, Dongchon Kang, Yoshihiro Ogawa

    Scientific reports   11 ( 1 )   13743 - 13743   2021.7

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    Authorship:Corresponding author   Language:English   Publishing type:Research paper (scientific journal)  

    This longitudinal study was designed to elucidate whether gut microbiota is associated with relapse and treatment response in ulcerative colitis (UC) patients. Fifty-one patients with UC were enrolled between 2012 and 2017, and followed up through 2020. Colon mucosal biopsy were obtained at enrollment, and 16S ribosomal RNA sequencing was performed using extracted RNA. Of the 51 patients, 24 were in remission and 27 had active UC at enrollment. Of the 24 patients in remission, 17 maintained remission and 7 developed relapse during follow-up. The 7 patients with relapse showed lower diversity, with a lower proportion of Clostridiales (p = 0.0043), and a higher proportion of Bacteroides (p = 0.047) at enrollment than those without relapse. The 27 patients with active UC were classified into response (n = 6), refractory (n = 13), and non-response (n = 8) groups according to their treatment response in 6 months. The refractory and non-response groups showed lower diversity with a lower proportion of Prevotella (p = 0.048 and 0.043) at enrollment than the response group. This study is the first demonstration that reduced diversity and particular microbes are associated with the later clinical course of relapse events and treatment response in UC.

    DOI: 10.1038/s41598-021-92870-0

  • Role of the IL-23-T-bet/GATA3 Axis for the Pathogenesis of Ulcerative Colitis. Reviewed International journal

    Haruei Ogino, Keita Fukaura, Yoichiro Iboshi, Yousuke Nagamatsu, Hiroaki Okuno, Kei Nishioka, Yuichiro Nishihara, Yoshimasa Tanaka, Takatoshi Chinen, Eikich Ihara, Yoshihiro Ogawa

    Inflammation   2020.10

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    Ulcerative colitis (UC) has been considered a Th2- and Th17-related disease. However, anti-IL-12/23 p40 antibody, which blocks Th1 and Th17 cell induction and maintenance, has shown efficacy in treating UC, suggesting that UC might not be a prototypical Th2 and Th17 cell-mediated autoimmune disease. To verify how the immune responses in UC patients interact with each other, we analyzed the cytokine expression and transcription factors involved in the Th1, Th2, and Th17 responses. The mucosal expression of 19 cytokines and transcription factors related to Th1, Th2, and Th17 cells, as well as Tregs, were measured by quantitative polymerase chain reaction using endoscopic biopsy specimens from inflamed colons of UC patients. A correlation analysis between the cytokines and transcription factors was conducted. The characteristic cytokine profile in UC patients has two immune response clusters: Th17-related responses and Th1-/Th2-related responses. IL-23 showed a weaker association with Th17 cell-related cytokines and transcription factor RORC and a much stronger correlation with T-bet and GATA3. In the high-IL-23-expression group, the rate of chronic continuous type was higher and the remission rate lower than in the low-IL-23-expression group. IL-23 may be a very important cytokine for evaluating the UC disease condition, as the expression of IL-23 is associated with certain clinical characteristics of UC patients. A unique association between IL-23 and T-bet/GATA3 might play a key role in the pathogenesis of UC.

    DOI: 10.1007/s10753-020-01358-y

  • Interleukin-1β as a Predictor of Glucocorticoid Response in Ulcerative Colitis. Reviewed International journal

    Hiroaki Okuno, Haruei Ogino, Eikichi Ihara, Kei Nishioka, Yoichiro Iboshi, Takatoshi Chinen, Toshiaki Ochiai, Hirotada Akiho, Kazuhiko Nakamura, Takuji Gotoda, Yoshihiro Ogawa

    Digestion   1 - 11   2020.5

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    BACKGROUND/AIM: Currently, there are no established biomarkers to differentiate between glucocorticoid (GC)-resistant and GC-sensitive ulcerative colitis (UC); however, interleukin (IL)-1β could be one such candidate biomarker. The aim of this study was to investigate whether mucosally expressed IL-1β could predict the response to GC in patients with UC. METHODS: A total of 27 mucosal tissue samples from 10 patients with GC-resistant UC (GC-resistant group), 9 patients with GC-sensitive UC (GC-sensitive group), and 8 control patients (control group) were analyzed by qRT-PCR for the expression of IL-1β, GC receptor α (GRα), GRβ, and other inflammatory mediators. Rachmilewitz endoscopic index (REI) between the GC-resistant and GC-sensitive groups was matched to avoid any potential influence of inflammation. RESULTS: The REI did not significantly differ between the GC-resistant and GC-sensitive groups. Mucosally expressed IL-1β levels in the GC-resistant group were significantly higher than those in the GC-sensitive group. However, there were no significant differences in the expression levels of GRα, GRβ, and other inflammatory mediators between the 2 groups. We could distinguish between the GC-resistant and GC-sensitive groups with a sensitivity of 90.0% and specificity of 77.8% based on mucosally expressed IL-1β. CONCLUSIONS: Mucosally expressed IL-1β can be used as a predictor of GC response in patients with UC.

    DOI: 10.1159/000507435

  • Mucosal Profiles of Immune Molecules Related to T Helper and Regulatory T Cells Predict Future Relapse in Patients With Quiescent Ulcerative Colitis Reviewed International journal

    Keita Fukaura, Yoichiro Iboshi, Haruei Ogino, Eikichi Ihara, Kazuhiko Nakamura, Yuichiro Nishihara, Kei Nishioka, Takatoshi Chinen, Tsutomu Iwasa, Akira Aso, Ayako Goto, Kazuhiro Haraguchi, Hirotada Akiho, Naohiko Harada, Yoshihiro Ogawa

    Inflammatory bowel diseases   25 ( 6 )   1019 - 1027   2019.5

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    BACKGROUND: T helper (Th)- and regulatory T (Treg) cell-related immune molecules are implicated in ulcerative colitis (UC). However, the association between their mucosal expression during remission and the subsequent clinical course of UC is unknown. METHODS: The expression of cytokines and transcription factors related to Th1, Th2, Th17, and Treg in endoscopic mucosal biopsy specimens from 40 UC patients in clinical remission and 9 controls was measured by quantitative polymerase chain reaction. The relationship between their expression patterns, as stratified by Mayo Endoscopic Subscore (MES), and any future relapse was evaluated by univariate and multivariate analyses. RESULTS: Six of 40 patients (baseline MES 0/1/2, 22/14/4) experienced a relapse during the study period (median, 37 months). At baseline, even in the MES0 patients, the interleukin (IL)-17A of the patients was significantly upregulated in comparison with controls (P = 0.0351). Future relapse was associated with a higher baseline expression of IL-17A, IL-17F, and IL-21 in MES0/1, and the upregulation of IL-17F and IL-21 remained statistically significant when limited to MES0 patients. Kaplan-Meier analysis revealed that as a single marker, a higher IL-21 level best grouped patients with an increased risk of relapse (P = 0.0042). Furthermore, a multivariate model that consisted of IL-21 and T-bet showed an even greater value (P = 0.0001). CONCLUSIONS: The profiles of Th/Treg-related gene expression in the colonic mucosa are altered, even during clinical and endoscopic remission of UC, with a detectable Th17-predominant profile predicting future relapse. This association might represent latent immune dysregulation during disease quiescence and has the potential to be utilized to improve patient care.

    DOI: 10.1093/ibd/izy395

  • Regulatory T cells expanded by rapamycin in vitro suppress colitis in an experimental mouse model Reviewed

    OGINO Haruei, NAKAMURA Kazuhiko, IWASA Tsutomu, IHARA Eikich, AKIHO Hirotada, MOTOMURA Yasuaki, AKAHOSHI Kazuya, IGARASHI Hisato, KATO Masaki, KOTOH Kazuhiro, ITO Tetsuhide, TAKAYANAGI Ryoichi

    Journal of gastroenterology   47 ( 4 )   366 - 376   2012.4

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    Regulatory T cells expanded by rapamycin in vitro suppress colitis in an experimental mouse model
    Background: To provide rapid immunosuppression without side effects, we analyzed whether rapamycin alone, and regulatory T cells (Tregs) expanded ex vivo by rapamycin, suppressed colitis in a mouse model. Methods: Severe combined immunodeficiency (SCID) mice reconstituted with naive CD4+ T cells were treated with or without intraperitoneal rapamycin. Body weight was evaluated. CD4+ T cells were cultured inthe presence of rapamycin for three 7-day rounds of stimulation. The ratio of Tregs to CD4+T cells was analyzed by flow cytometry. NaiveCD4+T cells were transferred into SCID mice with CD4+ T cells expanded in the presence or absence of rapamycin. Clinical symptoms of colitis, histological changes, and cytokine expression were investigated. Results: Systemic rapamycin partially prevented the development of colonic inflammation in a transfer model of colitis, but decreased body weight in control mice. With rapamycin, stimulated CD4 +T cells expanded eightfold in 3 weeks in vitro, and the proportion of Tregs increased to about 40%. Without rapamycin, CD4+T cells expanded 20-fold in 3 weeks, but the proportion of Tregs remained at about 15%. CD4+ T cells expanded with rapamycin prevented the development of colitis in a naïve CD4+ T-cell transfer model, in association with the down regulation of Th1 and Th17 responses. Conclusions: We demonstrated, for the first time, that CD4+ T cells expanded with rapamycin in vitro suppressed colitis. Therefore, rapamycin-expanded Treg transfer therapy is expected to be efficacious for inflammatory bowel disease.

    DOI: 10.1007/s00535-011-0502-y

  • CD4(+)CD25(+) regulatory T cells suppress Th17-responses in an experimental colitis model Reviewed

    OGINO H

    Dig Dis Sci   56 ( 2 )   376 - 386   2011.2

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    CD4+CD25+ regulatory T cells suppress Th17-responses in an experimental colitis model
    Background: After the recent discovery of Th17 cells, it was proposed that Th17 responses are involved in the pathogenesis of inflammatory bowel diseases (IBD). CD4+CD25+ regulatory T cells (Treg) are considered to be an attractive tool for the treatment of IBD. Here, we investigated whether Treg are capable of suppressing Th17-mediated colitis. Methods: Naive CD4 + T cells were transferred into SCID mice with or without Treg. In some experiments, Treg were transferred into recipient mice with established colitis. Mice treated with Treg were injected with an anti-transforming growth factor (TGF)-β mAb or control IgG. Clinical symptoms of colitis, histological changes and cytokine expressions were investigated. Results: SCID mice transferred with naive CD4+ T cells developed chronic colitis with significant increases in Th1 and Th17 cytokine expressions in the colon. When Treg were co-transferred with naive CD4+ T cells, development of colitis was prevented, and Th17 cytokine expressions were markedly reduced. Similarly, when Treg were transferred into mice with established colitis, the colitis was significantly ameliorated in association with dramatic reductions in Th17 cytokine expressions. Injection of anti-TGF-β mAb abolished the Treg-mediated suppression with significant elevations in Th17 cytokine productions. Conclusion: This adoptive transfer model of colitis was associated with augmented Th1 and Th17 responses, and Treg were capable of suppressing colonic inflammation by downregulating Th17 responses as well as Th1 responses via TGF-β. Consequently, Treg transfer therapy is expected to be efficacious for IBD even if Th17 is involved in the pathogenesis.

    DOI: 10.1007/s10620-010-1286-2

  • Traction-assisted endoscopic ultrasound-guided fine-needle biopsy using the clip-with-thread method for small gastric subepithelial lesions: Randomized controlled trial (with video) Reviewed

    Minoda, Y; Suzuki, Y; Ogino, H; Nagatomo, S; Bai, XP; Esaki, M; Wada, M; Tanaka, Y; Hata, Y; Fujimori, N; Umekita, S; Tsurumaru, D; Ota, M; Oki, E; Ihara, E; Ogawa, Y

    DIGESTIVE ENDOSCOPY   2025.1   ISSN:0915-5635 eISSN:1443-1661

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    Objectives: Endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNA/B) is the gold standard for diagnosing gastric subepithelial lesions (SELs), but diagnosing lesions smaller than 20 mm remains challenging. We developed traction-assisted EUS-FNB (TA-EUS-FNB) using the clip-with-thread method to enhance diagnostic accuracy by stabilizing the lesion and providing counter-traction for easier needle access. This study evaluates the effectiveness of TA-EUS-FNB in diagnosing small gastric SELs. Methods: In this prospective, randomized, controlled cross-over trial (August 2019–November 2022), 30 patients with gastric SELs <20 mm were randomized to undergo TA-EUS-FNB or conventional EUS-FNB. Each patient underwent four punctures, two per method. The primary end-point was the adequate tissue sampling rate for both techniques. Secondary end-points included diagnostic yield and performance (sensitivity and specificity) in distinguishing gastrointestinal stromal tumors (GISTs) from non-GISTs. Results: The mean tumor size was 15.0 mm, with diagnoses comprising GISTs (n = 15, 50%), leiomyomas (n = 8, 26.7%), schwannomas (n = 2, 6.7%), aberrant pancreas (n = 3, 10%), and inflammation (n = 2, 6.7%). TA-EUS-FNB demonstrated a significantly higher adequate-tissue sampling rate (90% vs. 66.7%, P = 0.035) and diagnostic yield (86.7% vs. 63.3%, P = 0.037) than conventional EUS-FNB. Sensitivity (86.7%, 95% confidence interval [CI] 62.1–96.3% vs. 66.7%, 95% CI 41.7–84.8%; P = 0.20) and specificity (100%, 95% CI 79.6–100% vs. 100%, 95% CI 79.6–100%) were comparable between the methods. No adverse events were observed in the study. Conclusion: TA-EUS-FNB demonstrated superior tissue sampling rates and diagnostic yield for SELs <20 mm compared to conventional EUS-FNB, making it a viable option. Controlling lesion mobility is essential for successful EUS-FNB in small SELs.

    DOI: 10.1111/den.14977

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  • Effective hemostasis with a self-assembling peptide hemostatic gel to manage leaky hemorrhage at the ulcer closure site after gastric endoscopic submucosal dissection. Reviewed International journal

    Ryohei Maruoka, Mitsuru Esaki, Yosuke Minoda, Yoshihiro Otsuka, Kazuhiro Haraguchi, Haruei Ogino, Eikichi Ihara

    Endoscopy   56 ( S 01 )   E323-E324   2024.12

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    DOI: 10.1055/a-2291-9050

  • Antral early gastric neoplasm with severe oral scarring successfully treated by endoscopic submucosal dissection using retroflex approach and a novel, thin therapeutic endoscope. Reviewed International journal

    Ryohei Maruoka, Mitsuru Esaki, Yosuke Minoda, Mei Tadokoro, Kazuhiro Haraguchi, Haruei Ogino, Eikichi Ihara

    Endoscopy   56 ( S 01 )   E703 - E705   2024.12   ISSN:0013-726X eISSN:1438-8812

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    DOI: 10.1055/a-2371-0911

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  • Predicting the generalization of computer aided detection (CADe) models for colonoscopy Reviewed

    Shor J., McNeil C., Intrator Y., Ledsam J.R., Yamano H.O.O., Tsurumaru D., Kayama H., Hamabe A., Ando K., Ota M., Ogino H., Nakase H., Kobayashi K., Miyo M., Oki E., Takemasa I., Rivlin E., Goldenberg R.

    Discover Artificial Intelligence   4 ( 1 )   2024.12

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    Generalizability of AI colonoscopy algorithms is important for wider adoption in clinical practice. However, current techniques for evaluating performance on unseen data require expensive and time-intensive labels. We show that a "Masked Siamese Network" (MSN), trained to predict masked out regions of polyp images without labels, can predict the performance of Computer Aided Detection (CADe) of polyps on colonoscopies, without labels. This holds on Japanese colonoscopies even when MSN is only trained on Israeli colonoscopies, which differ in scoping hardware, endoscope software, screening guidelines, bowel preparation, patient demographics, and the use of techniques such as narrow-band imaging (NBI) and chromoendoscopy (CE). Since our technique uses neither colonoscopy-specific information nor labels, it has the potential to apply to more medical imaging domains.

    DOI: 10.1007/s44163-024-00187-4

    Scopus

  • Protective role of M3 muscarinic acetylcholine receptor in indomethacin-induced small intestinal injury. Reviewed International journal

    Yoko Igarashi-Hisayoshi, Eikichi Ihara, Xiaopeng Bai, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Yasushi Taguchi, Yoshihiro Ogawa

    Journal of molecular medicine (Berlin, Germany)   2024.8   ISSN:0946-2716

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    EP4 prostanoid receptor (EP4R) contributes to the intestinal epithelial Cl- secretion, and inhibition of prostaglandin E (PGE) production by non-steroidal anti-inflammatory drugs (NSAIDs) plays a central role in NSAID-induced enteropathy. Although M3 muscarinic acetylcholine receptor (M3R) also contributes to the intestinal epithelial Cl- secretion, it remains unclear whether M3R is involved in NSAID-induced enteropathy due to a lack of selective agents. The present study explored how M3R is involved in the regulation of the intestinal epithelial Cl- secretion and its pathophysiological role in NSAID-induced enteropathy. Using the novel highly-selective M3 positive allosteric modulator PAM-369 that we recently developed, we evaluated the role of M3R in the intestinal epithelial secretion ex vivo by measuring the short circuit current (Isc) of intestinal epithelium with a Ussing chamber system and examined whether or not M3R protects against small intestinal injury in indomethacin-treated mice. Both the PGE1 derivative misoprostol and carbachol similarly increased the Isc in a concentration-dependent manner. The Isc increases were abolished either by receptor antagonists (an EP4R antagonist and a M3R antagonist, respectively) or by removal of extracellular Cl-. PAM-369 enhanced the carbachol-induced Isc by potentiating M3R, which could contribute to enhanced intestinal epithelial secretion. Treatment with PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. Importantly, the M3R expression was significantly up-regulated, and PAM-369 potentiation of M3R was augmented in indomethacin-treated mice compared to untreated mice. These findings show that M3R plays a role in maintaining the intestinal epithelial secretion, which could contribute to protection against indomethacin-induced small intestinal injury. M3R is a promising target for treating or preventing NSAID-induced enteropathy. KEY MESSAGES: PAM-369, the M3 positive allosteric modulator, was used to potentiate M3R. PAM-369 enhanced carbachol-induced Isc in mouse ileum. PAM-369 ameliorated small intestinal injury in indomethacin-treated mice. M3R is a promising target for treating or preventing NSAID-induced enteropathy.

    DOI: 10.1007/s00109-024-02474-0

    PubMed

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  • Comparison of hemostatic ability between spray coagulation and forced coagulation modes in endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for multicenter randomized controlled trial (Spray-G trial). Reviewed International journal

    Kosuke Maehara, Mitsuru Esaki, Yorinobu Sumida, Daisuke Yamaguchi, Kei Nishioka, Hitoshi Homma, Taisuke Inada, Kazuo Shiotsuki, Shin-Ichiro Fukuda, Hirotada Akiho, Tadahiro Nomura, Yumi Mizuta, Satoshi Ishida, Shun Fujimoto, Shunichiro Kimura, Yuichiro Tanaka, Kaori Hata, Noriko Shiga, Tsutomu Iwasa, Yusuke Kimura, Norimoto Nakamura, Yusuke Suzuki, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Koshiro Tagawa, Eikichi Ihara, Yoshihiro Ogawa

    Trials   25 ( 1 )   53 - 53   2024.1

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    BACKGROUND: Endoscopic submucosal dissection (ESD) is the standard treatment for early gastric neoplasms (EGN). Controlling intraoperative bleeding is crucial for ensuring safe and reliable procedures. ESD using the spray coagulation mode (SCM-ESD) has been developed to control bleeding more effectively than ESD using the conventional forced coagulation mode (FCM-ESD). This study aims to compare the hemostatic efficacies of SCM-ESD and FCM-ESD. METHODS: This multicenter, prospective, parallel, randomized, open-label superiority trial will be conducted in five Japanese institutions. Patients with a preoperative diagnosis of intramucosal EGC will be randomized to undergo either SCM-ESD or FCM-ESD. The primary outcome measure is the completion of ESD with an electrosurgical knife alone, without the use of hemostatic forceps. Secondary outcomes include the number and duration of hemostasis using hemostatic forceps, procedure time, curability, and safety. A total of 130 patients will be enrolled in this study. DISCUSSION: This trial will provide evidence on the hemostatic efficacy of SCM-ESD compared with FCM-ESD in patients with intramucosal EGN, potentially improving the safety and reliability of ESD procedures. TRIAL REGISTRATION: The trial has been registered at the University Hospital Medical Information Network Clinical Trials Registration (UMIN-CTR) as UMIN000040518. The reception number is R000054009.

    DOI: 10.1186/s13063-023-07852-6

  • A Continuous Registry of Medical Record, Patient Input, and Epidemiological Data of Patients With Ulcerative Colitis: a Multicentre, Prospective, Observational Clinical Registry Study in Japan Reviewed

    Matsuoka Katsuyoshi, Hibiya Shuji, Ando Katsuyoshi, Tani Yuji, Torisu Takehiro, Ogino Haruei, Yamashita Takanori, Andoh Akira, Sugimoto Yoshihisa, Matsumoto Takayuki, Iwanaga Yusuke, Suda Takashi, Kobayashi Taku

    Annals of Clinical Epidemiology   6 ( 3 )   65 - 72   2024   eISSN:24344338

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    <p><b>BACKGROUND</b></p><p>This registry aims to allow for a prospective non-interventional observational study of ulcerative colitis. This will facilitate monitoring of the current state of ulcerative colitis in Japan and improving the long-term disease course and adverse events associated with current treatment options.</p><p><b>METHODS</b></p><p>Inclusion of patients from five centres in Japan is planned. The study is expected to take place from July 15, 2020, to November 30, 2024. Background, demographics, and medical history/information will be collected from electronic medical records at enrolment. Medical information including medications, laboratory data, and disease activity will be collected automatically from electronic medical records throughout the study. Patient-reported quality of life data will be collected directly from patients via smartphone. Efficacy endpoints (clinical remission rate, clinical improvement rate, and endoscopic healing rate) and safety endpoints (incidence of adverse events and specific ulcerative colitis-related events) will be collected according to treatment administered. Treatment categories include no treatment, 5-aminosalicylic acids, corticosteroids, immunomodulators, immunosuppressants, anti-tumour necrosis alpha agents, cytapheresis, Janus kinase inhibitors, anti-integrin antibodies, and anti-interleukin-12/23 antibodies.</p><p><b>CONCLUSIONS</b></p><p>The dataset will include cross-sectional and longitudinal data and is expected to capture the state of ulcerative colitis in Japan. Patients will be included on a large scale, and the registry will be established automatically from electronic medical records and direct patient input, facilitating the accurate recording of medical information for patients with ulcerative colitis in Japan and minimizing limitations intrinsic to databases that require manual data entry, such as the burden on participating investigators and entry of data with errors/typos.</p>

    DOI: 10.37737/ace.24010

    PubMed

    CiNii Research

  • Development of a new endoscopy system to visualize bilirubin for the diagnosis of duodenogastroesophageal reflux. Reviewed International journal

    Masafumi Wada, Yosuke Minoda, Eikichi Ihara, Hirotaka Tsuru, Yoshitaka Hata, Shuzaburo Nagatomo, Mitsuru Esaki, Xiaopeng Bai, Yoshimasa Tanaka, Takatoshi Chinen, Haruei Ogino, Yoshihiro Ogawa

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   2023.12

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    OBJECTIVES: Reflux hypersensitivity (RH) is a form of refractory gastroesophageal reflux disease in which duodenogastroesophageal reflux (DGER) plays a role. This study aimed to determine the usefulness of an endoscopy system equipped with image-enhanced technology for evaluating DGER and RH. METHODS: The image enhancement mode for detecting bilirubin and calculated values were defined as the Bil mode and Bil value, respectively. First, the visibility of the Bil mode was validated for a bilirubin solution and bile concentrations ranging from 0.01% to 100% (0.002-20 mg/dL). Second, visibility scores of the Bil mode, when applied to the porcine esophagus sprayed with a bilirubin solution, were compared to those of the blue laser imaging (BLI) and white light imaging (WLI) modes. Third, a clinical study was conducted to determine the correlations between esophageal Bil values and the number of nonacid reflux events (NNRE) during multichannel intraluminal impedance-pH monitoring as well as the utility of esophageal Bil values for the differential diagnosis of RH. RESULTS: Bilirubin solution and bile concentrations higher than 1% were visualized in red using the Bil mode. The visibility score was significantly higher with the Bil mode than with the BLI and WLI modes for 1% to 6% bilirubin solutions (P < 0.05). The esophageal Bil value and NNRE were significantly positively correlated (P = 0.031). The area under the receiver operating characteristic curve for the differential diagnosis of RH was 0.817. CONCLUSION: The Bil mode can detect bilirubin with high accuracy and could be used to evaluate DGER in clinical practice.

    DOI: 10.1111/den.14749

  • Two-step traction-assisted endoscopic submucosal dissection for a gastric neoplasm using a clip with a traction band and thread. Reviewed International journal

    Kei Nishioka, Mitsuru Esaki, Tsutomu Iwasa, Yosuke Minoda, Noriko Shiga, Haruei Ogino, Eikichi Ihara

    Endoscopy   55 ( S 01 )   E1041-E1042   2023.12

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    DOI: 10.1055/a-2155-7172

  • Two-point fixed pulley-traction method in endoscopic submucosal dissection for early gastric neoplasm. Reviewed International journal

    Tsubasa Takeuchi, Mitsuru Esaki, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa

    Endoscopy   55 ( S 01 )   E1087-E1088   2023.12

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    DOI: 10.1055/a-2173-8010

  • Circumferential suture delivery method of polyglycolic acid sheets for gastric postendoscopic submucosal dissection ulcers. Reviewed International journal

    Yusuke Suzuki, Takashi Osoegawa, Masaru Kubokawa, Mitsuru Esaki, Yosuke Minoda, Haruei Ogino, Eikichi Ihara

    Endoscopy   55 ( S 01 )   E68-E69   2023.12

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    DOI: 10.1055/a-1934-9752

  • Evaluating the efficacy and safety of acotiamide in patients with esophagogastric junction outflow obstruction: study protocol for an investigator-initiated, multi-center, randomized, double-blind, placebo-controlled phase II trial. Reviewed International journal

    Mitsuru Esaki, Eikichi Ihara, Noriaki Manabe, Noriyuki Kawami, Katsuhiko Iwakiri, Junichi Akiyama, Shiko Kuribayashi, Toshio Uraoka, Haruei Ogino, Takatoshi Chinen, Akiko Misumi, Hiroko Watanabe, Maya Suzuki, Junji Kishimoto, Yoshihiro Ogawa

    Trials   24 ( 1 )   459 - 459   2023.7

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    BACKGROUND: We have determined that the impaired accommodation of the lower esophageal sphincter (LES) underlies the pathogenesis of esophagogastric junction outflow obstruction (EGJOO). We have also found that acotiamide may treat EGJOO by improving impaired LES accommodation. The effects of acotiamide in patients with EGJOO need to be further confirmed in a prospective study. METHODS: This trial is a multicenter, randomized, double-blind, placebo-controlled study to compare the efficacy and safety of acotiamide (300 mg/day or 600 mg/day) with those of a placebo in the treatment of patients with EGJOO. The primary endpoint will be the proportion of patients who report an improvement in symptom of food sticking in the chest after 4 weeks of treatment period 1. The secondary endpoints will be the proportion of patients with normalized integrated relaxation pressure (IRP), the value of change from baseline in the distal contractile integral, basal LES pressure, EGJOO-quality of life score, Gastrointestinal Symptom Rating Scale, and the correlation between IRP and each symptom score. During the 2-year trial period, 42 patients from five institutions will be enrolled. DISCUSSION: This trial will provide evidence to clarify the efficacy and safety of acotiamide as a treatment for patients with EGJOO. Acotiamide might help improve the quality of life of patients with EGJOO and is expected to prevent the progression of EGJOO to achalasia. TRIAL REGISTRATION: This study was approved by the Institutional Review Board (IRB) of Kyushu University Hospital as well as the local IRBs of the participating sites for clinical trials and registered in the Japan Registry of Clinical Trials (jRCT: 2071210072). The registration date is on October 11, 2021.

    DOI: 10.1186/s13063-023-07468-w

  • Hybrid and Conventional Endoscopic Submucosal Dissection for Early Gastric Neoplasms: A Multi-Center Randomized Controlled Trial. Reviewed International journal

    Mitsuru Esaki, Eikichi Ihara, Yorinobu Sumida, Hiroyuki Fujii, Shunsuke Takahashi, Kazuhiro Haraguchi, Tsutomu Iwasa, Shinichi Somada, Yosuke Minoda, Haruei Ogino, Koshiro Tagawa, Yoshihiro Ogawa

    Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association   21 ( 7 )   1810 - 1818   2023.7

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    BACKGROUND & AIMS: Hybrid endoscopic submucosal dissection (H-ESD), which incorporates endoscopic submucosal dissection (ESD) with endoscopic mucosal resection, has been developed to make ESD technically easier. This study aimed to determine if H-ESD is superior to conventional ESD (C-ESD) for small early gastric neoplasms (EGNs). METHODS: We conducted a multi-center, prospective, open-label, randomized controlled trial to compare the treatment outcomes of H-ESD and C-ESD (Hybrid-G Trial). Patients with differentiated type intramucosal EGN ≤20 mm in diameter and without ulceration were randomly assigned (1:1) to groups that underwent H-ESD or C-ESD. A single multi-functional snare, SOUTEN (ST1850-20, Kaneka, Medix, Tokyo, Japan), was used for H-ESD. The primary outcome was procedure time. Secondary outcomes included mucosal incision time, time and speed of submucosal dissection, curability, and endoscopic procedural adverse events. RESULTS: A total of 39 and 40 patients underwent H-ESD and C-ESD, respectively. The procedure time of H-ESD was significantly shorter than that of C-ESD (33.16 min vs 62.46 min; H-ESD/C-ESD ratio: 0.53; 95% confidence interval, 0.41-0.69; P < .0001). There was no significant difference in mucosal incision time between the 2 groups; the time and speed of submucosal dissection of H-ESD were significantly shorter than those of C-ESD. No difference was observed between the 2 groups in other outcomes. CONCLUSIONS: H-ESD has significantly shorter procedure time than C-ESD, with high and comparable curability and safety for both H-ESD and C-ESD. H-ESD can be a good option for the endoscopic treatment of small EGNs. (UMIN Clinical Trials Registry, Numbers: UMIN000041244).

    DOI: 10.1016/j.cgh.2022.10.030

  • Auxiliary diagnosis of subepithelial lesions by impedance measurement during EUS-guided fine-needle biopsy. Invited Reviewed International journal

    Yosuke Minoda, Mitsuru Esaki, Eikichi Ihara, Shuzaburo Nagatomo, Kei Nishioka, Nao Fujimori, Haruei Ogino, Xiaopeng Bai, Yoshimasa Tanaka, Takatoshi Chinen, Qingjiang Hu, Mitsuhiko Ota, Shinya Umekita, Hidetaka Yamamoto, Yoshihiro Ogawa

    Gastrointestinal endoscopy   97 ( 5 )   977 - 984   2023.5

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    BACKGROUND AND AIMS: EUS-guided FNA/biopsy (EUS-FNA/B) is the citerion standard for diagnosing subepithelial lesions (SELs); however, its diagnostic ability for SELs <20 mm is low. We developed a new diagnostic method to differentiate between GI stromal tumor (GIST) and non-GIST by measuring high-frequency impedance (H-impedance) using an EUS-FNB needle. METHODS: The H-impedance of gastric epithelial neoplasms from 16 cases were measured with a conventional impedance probe to confirm whether H-impedance is clinically useful for assessing cell density (study 1). The H-impedance values of exposed SELs from 25 cases with use of the conventional probe (study 2) and nonexposed SELs from 20 cases with use of the EUS-FNB needle probe (study 3) were measured to determine the diagnostic ability of H-impedance for differentiating GISTs from non-GISTs. RESULTS: H-impedance significantly positively correlated with cell density (P = .030) (study 1). The H-impedance of GIST (99.5) measured with a conventional probe was significantly higher than with those of the muscular layer (82.4) and leiomyoma (89.2) (P < .01) (study 2). The H-impedance of GIST measured with the EUS-FNB needle was also significantly higher than that of leiomyoma (GIST: 80.2 vs leiomyoma, 71.8; P = .015). The diagnostic yield of the impedance method for differentiating GISTs from non-GISTs had 94.4% accuracy, 88.9% sensitivity, 100% specificity, and 0.95 area under the curve. Diagnostic ability was not affected by lesion size (P = .86) (study 3). CONCLUSION: Auxiliary differential diagnosis between gastric GISTs and non-GISTs by the H-impedance measurement during EUS-FNB could be a good option, especially when the lesion is <20 mm.

    DOI: 10.1016/j.gie.2022.11.022

  • Determination of Region-Specific Roles of the M3 Muscarinic Acetylcholine Receptor in Gastrointestinal Motility. Reviewed International journal

    Yoko Igarashi-Hisayoshi, Eikichi Ihara, Xiaopeng Bai, Chika Higashi, Hiroko Ikeda, Yoshimasa Tanaka, Mayumi Hirano, Haruei Ogino, Takatoshi Chinen, Yasushi Taguchi, Yoshihiro Ogawa

    Digestive diseases and sciences   68 ( 2 )   439 - 450   2023.2

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    BACKGROUND: The specific role of the M3 muscarinic acetylcholine receptor in gastrointestinal motility under physiological conditions is unclear, due to a lack of subtype-selective compounds. AIMS: The objective of this study was to determine the region-specific role of the M3 receptor in gastrointestinal motility. METHODS: We developed a novel positive allosteric modulator (PAM) for the M3 receptor, PAM-369. The effects of PAM-369 on the carbachol-induced contractile response of porcine esophageal smooth muscle and mouse colonic smooth muscle (ex vivo) and on the transit in mouse small intestine and rat colon (in vivo) were examined. RESULTS: PAM-369 selectively potentiated the M3 receptor under the stimulation of its orthosteric ligands without agonistic or antagonistic activity. Half-maximal effective concentrations of PAM activity for human, mouse, and rat M3 receptors were 0.253, 0.345, and 0.127 μM, respectively. PAM-369 enhanced carbachol-induced contraction in porcine esophageal smooth muscle and mouse colonic smooth muscle without causing any contractile responses by itself. The oral administration of 30 mg/kg PAM-369 increased the small intestinal transit in both normal motility and loperamide-induced intestinal dysmotility mice but had no effects on the colonic transit, although the M3 receptor mRNA expression is higher in the colon than in the small intestine. CONCLUSIONS: This study provided the first direct evidence that the M3 receptor has different region-specific roles in the motility function between the small intestine and colon in physiological and pathophysiological contexts. Selective PAMs designed for targeted subtypes of muscarinic receptors are useful for elucidating the subtype-specific function.

    DOI: 10.1007/s10620-022-07637-y

  • Negligible procedure-related dissemination risk of mucosal incision-assisted biopsy for gastrointestinal stromal tumors versus endoscopic ultrasound-guided fine-needle aspiration/biopsy. Reviewed International journal

    Yosuke Minoda, Eikichi Ihara, Soichi Itaba, Yorinobu Sumida, Kazuhiro Haraguchi, Akira Aso, Takahiro Mizutani, Takashi Osoegawa, Mitsuru Esaki, Shuzaburo Nagatomo, Kei Nishioka, Kazumasa Muta, Xiaopeng Bai, Haruei Ogino, Nao Fujimori, Daisuke Tsurumaru, Kenoki Ohuchida, Hu Qingjiang, Eiji Oki, Hidetaka Yamamoto, Yoshihiro Ogawa

    Surgical endoscopy   37 ( 1 )   101 - 108   2023.1

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    BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64% of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100%) and EUS-FNAB (97.1%) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

    DOI: 10.1007/s00464-022-09419-z

  • Gastric endoscopic submucosal dissection assisted by intralesional cross-traction using silicone bands. Reviewed International journal

    Yusuke Suzuki, Mitsuru Esaki, Taisuke Inada, Yosuke Minoda, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa

    Endoscopy   55 ( S 01 )   E324-E325   2022.12

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    DOI: 10.1055/a-1982-3875

  • Efficacy of ultrasound endoscopy with artificial intelligence for the differential diagnosis of non-gastric gastrointestinal stromal tumors. Reviewed International journal

    Yosuke Minoda, Eikichi Ihara, Nao Fujimori, Shuzaburo Nagatomo, Mitsuru Esaki, Yoshitaka Hata, Xiaopeng Bai, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Qingjiang Hu, Eiji Oki, Hidetaka Yamamoto, Yoshihiro Ogawa

    Scientific reports   12 ( 1 )   16640 - 16640   2022.10

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    Gastrointestinal stromal tumors (GISTs) are common subepithelial lesions (SELs) and require treatment considering their malignant potential. We recently developed an endoscopic ultrasound-based artificial intelligence (EUS-AI) system to differentiate GISTs from non-GISTs in gastric SELs, which were used to train the system. We assessed whether the EUS-AI system designed for diagnosing gastric GISTs could be applied to non-gastric GISTs. Between January 2015 and January 2021, 52 patients with non-gastric SELs (esophagus, n = 15; duodenum, n = 26; colon, n = 11) were enrolled. The ability of EUS-AI to differentiate GISTs from non-GISTs in non-gastric SELs was examined. The accuracy, sensitivity, and specificity of EUS-AI for discriminating GISTs from non-GISTs in non-gastric SELs were 94.4%, 100%, and 86.1%, respectively, with an area under the curve of 0.98 based on the cutoff value set using the Youden index. In the subanalysis, the accuracy, sensitivity, and specificity of EUS-AI were highest in the esophagus (100%, 100%, 100%; duodenum, 96.2%, 100%, 0%; colon, 90.9%, 100%, 0%); the cutoff values were determined using the Youden index or the value determined using stomach cases. The diagnostic accuracy of EUS-AI increased as lesion size increased, regardless of lesion location. EUS-AI based on gastric SELs had good diagnostic ability for non-gastric GISTs.

    DOI: 10.1038/s41598-022-20863-8

  • Improved esophagography screening for esophageal motility disorders using wave appearance and supra-junctional ballooning. Reviewed

    Yoshitaka Hata, Eikichi Ihara, Masafumi Wada, Hirotaka Tsuru, Kazumasa Muta, Yosuke Minoda, Xiaopeng Bai, Mitsuru Esaki, Yoshimasa Tanaka, Takatoshi Chinen, Haruei Ogino, Ryuichi Sakamoto, Yoshihiro Ogawa

    Journal of gastroenterology   57 ( 11 )   838 - 847   2022.8

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    BACKGROUND: High-resolution manometry (HRM) is the gold standard for diagnosing esophageal motility disorders (EMDs); however, it requires specialized equipment. The development of more accessible screening examinations is expected. We evaluated the utility of barium esophagography (BE) screening using two novel findings to diagnose EMDs. METHODS: Between January 2013 and October 2020, 244 patients with suspected EMDs who underwent both HRM and BE were analyzed. The EMD diagnosis was based on HRM findings using Chicago Classification version 3.0. BE was performed using sequential esophagography with barium sulfate. Three conventional BE findings (air-fluid level, rosary-bead/corkscrew appearance, and absent/weak peristalsis) and two novel BE findings (wave appearance and supra-junctional ballooning) were used for diagnosis. RESULTS: The sensitivity and specificity of BE screening using the two novel findings and conventional findings to diagnose EMDs were 79.4&#37; and 88&#37;, respectively [area under the receiver-operating characteristic curve (AUC) = 0.837]. Without these novel findings, they were 63.9&#37; and 96&#37;, respectively (AUC = 0.800), respectively. Achalasia was highly correlated with the air-fluid level (88.7&#37;). Absent contractility was highly correlated with absent/weak peristalsis (85.7&#37;). Relatively high correlations were observed between distal esophageal spasm and rosary-bead/corkscrew appearance (60&#37;), and between achalasia and wave appearance (59.7&#37;). The intra-observer reproducibility and inter-observer agreement for individual BE findings were 84.4&#37; and 75&#37;, respectively. Wave appearance was associated with higher integrated relaxation pressure (IRP) and shorter distal latency. Supra-junctional ballooning was associated with higher IRP. CONCLUSIONS: BE screening using two additional novel findings to diagnose EMDs could be useful in general practice.

    DOI: 10.1007/s00535-022-01913-4

  • Negligible procedure-related dissemination risk of mucosal incision-assisted biopsy for gastrointestinal stromal tumors versus endoscopic ultrasound-guided fine-needle aspiration/biopsy. Reviewed International journal

    Yosuke Minoda, Eikichi Ihara, Soichi Itaba, Yorinobu Sumida, Kazuhiro Haraguchi, Akira Aso, Takahiro Mizutani, Takashi Osoegawa, Mitsuru Esaki, Shuzaburo Nagatomo, Kei Nishioka, Kazumasa Muta, Xiaopeng Bai, Haruei Ogino, Nao Fujimori, Daisuke Tsurumaru, Kenoki Ohuchida, Hu Qingjiang, Eiji Oki, Hidetaka Yamamoto, Yoshihiro Ogawa

    Surgical endoscopy   37 ( 1 )   101 - 108   2022.7

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    BACKGROUND: Mucosal incision-assisted biopsy (MIAB) is a valuable alternative to endoscopic ultrasound-guided fine-needle aspiration/biopsy (EUS-FNAB) for sampling gastric subepithelial lesions (SELs). This study aimed to evaluate the potential risk of dissemination and impact on postoperative prognosis associated with MIAB, which has not yet been investigated. METHODS: Study 1: A prospective observational study was conducted to examine the presence or absence and growth rate of tumor cells in gastric juice before and after the procedure in patients with SELs who underwent MIAB (n = 25) or EUS-FNAB (n = 22) between September 2018 and August 2021. Study 2: A retrospective study was conducted to examine the impact of MIAB on postoperative prognosis in 107 patients with gastrointestinal stromal tumors diagnosed using MIAB (n = 39) or EUS-FNAB (n = 68) who underwent surgery between January 2001 and July 2020. RESULTS: In study 1, although no tumor cells were observed in gastric juice in MIAB before the procedure, they were observed in 64&#37; of patients after obtaining samples (P < 0.001). In contrast, no tumor cells were observed in the gastric juice in EUS-FNAB before and after the procedure. In study 2, there was no significant difference in 5-year disease-free survival between MIAB (100&#37;) and EUS-FNAB (97.1&#37;) (P = 0.27). CONCLUSION: MIAB is safe, with little impact on postoperative prognosis, although the procedure releases some tumor cells after damaging the SEL's pseudocapsule.

  • Innovative endoscopic submucosal dissection for early gastric neoplasm using intralesional traction and snaring techniques. Reviewed International journal

    Yoshihisa Shoguchi, Mitsuru Esaki, Yosuke Minoda, Xiaopeng Bai, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa

    Endoscopy   2022.6

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    DOI: 10.1055/a-1841-5907

  • Application of intralesional traction assistance with traction wire to endoscopic submucosal dissection for colorectal neoplasms. Reviewed International journal

    Takayuki Nasu, Mitsuru Esaki, Yoshihisa Shoguchi, Xiaopeng Bai, Yosuke Minoda, Haruei Ogino, Eikichi Ihara

    Endoscopy   2022.4

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    DOI: 10.1055/a-1809-4967

  • Comparisons of outcomes between ProKnife injection endoscopic submucosal dissection and conventional endoscopic submucosal dissection for large gastric lesions in ex vivo porcine model study: A randomized controlled trial. Reviewed International journal

    Mitsuru Esaki, Eikichi Ihara, Misato Esaki, Kei Nishioka, Yusuke Kimura, Yoshitaka Hata, Hirotaka Tsuru, Masafumi Wada, Yosuke Minoda, Xiaopeng Bai, Yoshihisa Shoguchi, Takayuki Nasu, Shuzaburo Nagatomo, Kazumasa Muta, Haruei Ogino, Yoshihiro Ogawa

    DEN open   2 ( 1 )   e91   2022.4

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    Objective: To compare treatment outcomes between injection endoscopic submucosal dissection using ProKnife (P-ESD) and conventional ESD (C-ESD) for gastric lesions. Methods: In this randomized controlled trial, we compared treatment outcomes of P-ESD and C-ESD for simulated gastric lesions ≥3 cm in resected porcine stomachs. Predictive factors associated with ESD difficulties were investigated using logistic regression analysis. Results: Seventy lesions were screened; however, two lesions were excluded. A total of 12 endoscopists performed 68 ESDs: 34 P-ESDs and 34 C-ESDs. The ESD procedure time of P-ESD (36.3 [28.4-46.8] min) was significantly shorter than that of C-ESD (46 [36.4-64.6] min; p = 0.0014). The technical success rates did not differ between the P-ESD and C-ESD groups (en bloc resection rate, 100% in both groups; complete resection rate, 94.1% and 85.3%, respectively; p = 0.23). The number of injections during P-ESD (7.5 [6-10] times) was significantly higher than during C-ESD (4 [3-5] times; p < 0.001), but the total volume of injected solution during P-ESD (20 [16-26.3] ml) was significantly smaller than during C-ESD (27.5 [20-31.5] ml; p = 0.0019). In multivariate analysis, less ESD experience (odds ratio [OR], 3.9) and selection of C-ESD as the ESD method (OR, 3.8) were independent predictive factors associated with ESD difficulties. Conclusions: Compared with C-ESD, P-ESD had a shorter procedure time but also allowed for notable technical success and safety.

    DOI: 10.1002/deo2.91

  • Comparison of the procedure time differences between hybrid endoscopic submucosal dissection and conventional endoscopic submucosal dissection in patients with early gastric neoplasms: a study protocol for a multi-center randomized controlled trial (Hybrid-G trial). Reviewed International journal

    Mitsuru Esaki, Eikichi Ihara, Hiroyuki Fujii, Yorinobu Sumida, Kazuhiro Haraguchi, Shunsuke Takahashi, Tsutomu Iwasa, Kayoko Nakano, Masafumi Wada, Shinichi Somada, Yosuke Minoda, Haruei Ogino, Koshiro Tagawa, Yoshihiro Ogawa

    Trials   23 ( 1 )   166 - 166   2022.2

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    BACKGROUND: Endoscopic submucosal dissection (ESD) is widely accepted as a local treatment for gastrointestinal tract tumors. As a simplified endoscopic procedure, hybrid ESD (H-ESD) has been performed for colorectal neoplasms in recent times. However, whether H-ESD is superior to conventional ESD (C-ESD) for patients with early gastric neoplasms (EGN) remains unclear. In this trial, we will compare the treatment outcomes of H-ESD and C-ESD. We hypothesize that the procedure time for H-ESD is shorter than that for C-ESD. METHODS: This is an investigator-initiated, multi-center, prospective, randomized, open-label, parallel-group trial to be conducted beginning in August 2020 at nine institutions in Japan. We will determine if H-ESD is superior to C-ESD in terms of procedure time in patients with EGN diagnosed as macroscopically intramucosal (T1a) differentiated carcinoma ≤ 20 mm in diameter without ulcerative findings according to current Japanese gastric cancer treatment guidelines. A total of 82 patients will be recruited and randomly assigned to either the C-ESD or the H-ESD group. The primary outcome is ESD procedure time. Secondary outcomes include mucosal incision, time and speed of submucosal dissection, en bloc resection, complete resection, curability, adverse events related to the ESD procedure, extent of dissection before snaring, volume of injection solution, number and time of hemostasis, thickness of the submucosal layer in the resected specimen, and handover to another operator. The stated sample size was determined based on the primary outcome. According to a previous report comparing the procedure times of C-ESD and H-ESD, we hypothesized that H-ESD would provide a 0.2 reduction in logarithmically concerted procedure time (-37%). We estimated that a total of 82 participants were needed to reach a power of 80% for a t-test with a significance level of 0.05 and considering a 10% dropout. DISCUSSION: This trial will provide high-quality data on the benefits and risks of H-ESD for EGN patients. The results of this study could lead to improved outcomes in patients with EGN undergoing ESD. The results will be presented at national and international meetings and published in peer-reviewed journals. TRIAL REGISTRATION: UMIN-CTR UMIN000041244 . Registered on July 29, 2020.

    DOI: 10.1186/s13063-022-06099-x

  • Is a small-caliber or large-caliber endoscope more suitable for colonic self-expandable metallic stent placement? A randomized controlled study. Reviewed International journal

    Yosuke Minoda, Haruei Ogino, Yorinobu Sumida, Takashi Osoegawa, Soichi Itaba, Norikazu Hashimoto, Mitsuru Esaki, Yusuke Kitagawa, Kentaro Yodoe, Yoichiro Iboshi, Takahiro Matsuguchi, Mei Tadokoro, Tomohito Chaen, Hiroaki Kubo, Masaru Kubokawa, Naohiko Harada, Kenichi Nishizima, Hiroyuki Fujii, Yoshitaka Hata, Yoshimasa Tanaka, Eikichi Ihara, Yoshihiro Ogawa

    Therapeutic advances in gastroenterology   15   17562848211065331 - 17562848211065331   2022.1   ISSN:1756-283X eISSN:1756-2848

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    Objectives: The colonic self-expandable metallic stent (C-SEMS) with a 9-French (Fr) delivery system allows for a small-caliber endoscope (SCE) to be used to treat malignant colonic obstruction. Despite the lack of evidence, the SCE has become popular because it is considered easier to insert than the large-caliber endoscope (LCE). We aimed to determine whether the SCE is more suitable than the LCE for C-SEMS placement. Methods: Between July 2018 and November 2019, 50 consecutive patients who were scheduled to undergo C-SEMS for colon obstruction were recruited in this study. Patients were randomized to the SCE or LCE group. The SCE and LCE were used with 9-Fr and 10-Fr delivery systems, respectively. The primary outcome was the total procedure time. Secondary outcomes were the technical success rate, complication rate, clinical success rate, insertion time, guidewire-passage time, stent-deployment time, and colonic obstruction-scoring-system score. Results: Forty-five patients (SCE group, n = 22; LCE group, n = 23) were analyzed. The procedure time in the LCE group (median, 20.5 min) was significantly (p = 0.024) shorter than that in the SCE group (median, 25.1 min). The insertion time in the LCE group (median, 2.0 min) was significantly (p = 0.0049) shorter than that in the SCE group (median, 6.0 min). A sub-analysis of the procedure difficulties showed that the insertion time in the LCE group (median, 5.0 min) was significantly shorter than that in the SCE group (median, 8.5 min). Conclusion: Both LCE and SCE can be used for C-SEMS; however, LCE is more suitable than SCE as it achieved a faster and equally efficacious C-SEMS placement as that of SCE. Clinical trial registration number: University Hospital Medical Information Network Clinical Trials Registry (UMIN 32748).

    DOI: 10.1177/17562848211065331

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  • Involvement of interstitial cells of Cajal in nicotinic acetylcholine receptor-induced relaxation of the porcine lower esophageal sphincter. Reviewed International journal

    Yoshihiro Otsuka, Xiaopeng Bai, Yoshimasa Tanaka, Eikichi Ihara, Takatoshi Chinen, Haruei Ogino, Yoshihiro Ogawa

    European journal of pharmacology   910   174491 - 174491   2021.11

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    The interstitial cells of Cajal (ICCs) play an important role in coordinated gastrointestinal motility. The present study aimed to elucidate whether or how ICCs are involved in the lower esophageal sphincter (LES) relaxation induced by stimulation of the nicotinic acetylcholine receptor. The application of 1,1-dimethyl-4-phenyl-piperazinium (DMPP; a nicotinic acetylcholine receptor agonist) induced a transient relaxation in the circular smooth muscle of the porcine LES. DMPP-induced relaxation was abolished by not only 1 μM tetrodotoxin but also the inhibition of ICC activity by pretreatment with 100 μM carbenoxolone (a gap junction inhibitor), pretreatment with 100 μM CaCCinh-A01 (an anoctamin-1 blocker acting as a calcium-activated chloride channel inhibitor), and pretreatment with Cl--free solution. However, pretreatment with 100 μM Nω-nitro-L-arginine methyl ester had little effect on DMPP-induced relaxation. Furthermore, DMPP-induced relaxation was inhibited by pretreatment with 1 mM suramin, a purinergic P2 receptor antagonist, but not by 1 μM VIP (6-28), a vasoactive intestinal peptide (VIP) receptor antagonist. Stimulation of the purinergic P2 receptor with adenosine triphosphate (ATP) induced relaxation, which was abolished by the inhibition of ICC activity by pretreatment with CaCCinh-A01. In conclusion, membrane hyperpolarization of the ICCs via the activation of anoctamin-1 plays a central role in DMPP-induced relaxation. ATP may be a neurotransmitter for inhibitory enteric neurons, which stimulate the ICCs. The ICCs act as the interface of neurotransmission of nicotinic acetylcholine receptor in order to induce LES relaxation.

    DOI: 10.1016/j.ejphar.2021.174491

  • Rubber band-assisted, one-person-operated cold snare polypectomy for colorectal polyps. Reviewed International journal

    Misato Esaki, Mitsuru Esaki, Kosuke Maehara, Yosuke Minoda, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa

    Endoscopy international open   9 ( 11 )   E1845-E1846   2021.11

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    DOI: 10.1055/a-1576-7673

  • Traction-assisted hybrid endoscopic submucosal dissection for small rectal neuroendocrine tumors. Reviewed International journal

    Takayuki Nasu, Mitsuru Esaki, Yoshihisa Shoguchi, Xiaopeng Bai, Yosuke Minoda, Haruei Ogino, Eikichi Ihara

    Endoscopy   2021.11

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    DOI: 10.1055/a-1662-4965

  • The treatment effects of acotiamide in esophagogastric outflow obstruction: a prospective longitudinal observational study. Reviewed

    Eikichi Ihara, Haruei Ogino, Kazumasa Muta, Shohei Hamada, Masafumi Wada, Yoshitaka Hata, Hiroko Ikeda, Xiaopeng Bai, Yosuke Minoda, Mitsuru Esaki, Yoshimasa Tanaka, Takatoshi Chinen, Yoshihiro Ogawa

    Esophagus : official journal of the Japan Esophageal Society   19 ( 2 )   332 - 342   2021.10

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    OBJECTIVES: We have found that an altered lower esophageal sphincter (LES) accommodation response is an underlying cause of esophagogastric junction outflow obstruction (EGJOO). The objective of this study was to examine the treatment effect of acotiamide, a prokinetic agent which improves impaired gastric accommodation in functional dyspepsia, in patients with EGJOO. METHODS: A prospective observational longitudinal study was conducted between October 2014 and March 2020. Acotiamide (100 mg, 3 times a day) was administered to 25 patients with EGJOO for 4 weeks. High-resolution manometry (HRM) was performed just before and after 4 weeks of treatment. RESULTS: As the primary outcome, the extent of integrated relaxation pressure (IRP) after treatment (14.6, 12.1-22.0 mmHg) was significantly lower than that before treatment (19.4, 17.1-27.4 mmHg). The extent of LES accommodation index after treatment (32.7, 21.0-40.0 mmHg) was also significantly lower than that before treatment (39.3, 31.2-50.2 mmHg). Acotiamide normalized the IRP (< 15 mmHg) in 13 of 25 patients with EGJOO (52&#37;), and the IRP was decreased in 20 of 25 patients with EGJOO (80&#37;). As the secondary outcome, the total FSSG score in 25 patients with EGJOO before and after acotiamide treatment showed no significant difference. In a sub-analysis of 13 patients in whom EGJOO was normalized by acotiamide, however, dysphagia was reported to be significantly improved by acotiamide. CONCLUSIONS: Acotiamide has a treatment effect on patients with EGJOO via a reduction in the IRP level through the lowering of both the basal LES pressure and LES accommodation response. Dysphagia is a key symptom to be evaluated and treated in patients with EGJOO.

    DOI: 10.1007/s10388-021-00887-1

  • Usefulness of a gel immersion-assisted EUS-guided fine-needle aspiration/biopsy for ampullary lesions (with videos). Reviewed International journal

    Yosuke Minoda, Shuzaburo Nagatomo, Nao Fujimori, Kei Nishioka, Shotaro Kakehashi, Katsuhito Teramatsu, Yu Takamatsu, Haruei Ogino, Eikichi Ihara

    Endoscopic ultrasound   2021.9

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    DOI: 10.4103/EUS-D-21-00043

  • Onigiri esophagography as a screening test for esophageal motility disorders. Reviewed International journal

    Shohei Hamada, Eikichi Ihara, Kazumasa Muta, Masafumi Wada, Yoshitaka Hata, Hiroko Ikeda, Yoshimasa Tanaka, Haruei Ogino, Takatoshi Chinen, Yoshihiro Ogawa

    Journal of neurogastroenterology and motility   28 ( 1 )   43 - 52   2021.7

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    Background/Aims: No screening test for esophageal motility disorder (EMD) has been established, the objective of this study is to examine the potential usefulness of our newly developed "Onigiri esophagography" combined with an obstruction level (OL) classification system in screening for EMD. Methods: A total of 102 patients with suspected EMDs who underwent both high-resolution manometry (HRM) and Onigiri esophagography between April 2017 and January 2019 were examined. The EMD diagnosis was performed based on the Chicago classification version 3.0 by HRM. Onigiri esophagography was performed using a liquid medium (barium sulfate) followed by a solid medium, which consisted of an Onigiri (a Japanese rice ball) with barium powder. The extent of medium obstruction was assessed by the OL classification, which was defined in a stepwise fashion from OL0 (no obstruction) to OL4 (severe obstruction). Results: Thirty-two percent of the patients with OL0 (32.3&#37;), OL1 (50.0&#37;), OL2 (88.0&#37;), OL3 (100.0&#37;), and OL4 (100.0&#37;) were diagnosed EMDs by HRM. The area under the curve, as determined by a receiver operating characteristic analysis, for the OL classification was 0.86. Using the cutoff value of OL1, the sensitivity and specificity were 87.3&#37; and 61.3&#37;, respectively, while using a cutoff value of OL2, the sensitivity and specificity were 73.2&#37; and 90.3&#37;, respectively. Conclusion: In conclusion, Onigiri esophagography combined with the OL classification system can be used as a screening test for EMDs with a cutoff value of OL1.

    DOI: 10.5056/jnm20138

  • Efficacy of hybrid endoscopic submucosal dissection with SOUTEN in gastric lesions: An ex vivo porcine model basic study. Reviewed International journal

    Mitsuru Esaki, Eikichi Ihara, Norikazu Hashimoto, Shuichi Abe, Chihoko Aratono, Noriko Shiga, Yorinobu Sumida, Hiroyuki Fujii, Kazuhiro Haraguchi, Shunsuke Takahashi, Tsutomu Iwasa, Kayoko Nakano, Masafumi Wada, Shinichi Somada, Kei Nishioka, Yosuke Minoda, Haruei Ogino, Yoshihiro Ogawa

    World journal of gastrointestinal surgery   13 ( 6 )   563 - 573   2021.6

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    BACKGROUND: Hybrid endoscopic submucosal dissection (ESD) that comprises mucosal incision and partial submucosal dissection followed by snaring in a planned manner, has been developed for endoscopic resection of gastrointestinal neoplasms to overcome the technical barrier of ESD. Although the superiority of hybrid ESD with SOUTEN, a single multifunctional device, over conventional ESD has been indicated, the actual effect of snaring itself remains unclear since SOUTEN could be applied to hybrid ESD group, but not to the conventional ESD group, due to ethical issue in clinical practice. AIM: To determine whether and how hybrid ESD was superior to conventional ESD in the endoscopic treatment of gastric lesions in an ex vivo porcine model basic study. METHODS: Sixteen endoscopists participated in this basic study in August 2020 at Kyushu University, performing 32 procedures each for hybrid ESD and conventional ESD. Mock lesions (10-15 mm, diameter) were created in the porcine stomach. The primary outcome was total procedure time and secondary outcomes were en bloc or complete resection, perforation, procedure time/speed for both, mucosal incision, and submucosal dissection. Factors associated with difficulty in ESD including longer procedure time, incomplete resection, and perforation, were also investigated. Categorical and continuous data were analyzed using the chi-square test or Fisher's exact test and the Mann-Whitney U test, respectively. RESULTS: The median total procedure time of hybrid ESD was significantly shorter than that of conventional ESD (median: 8.3 min vs 16.2 min, P < 0.001). Time, speed, and the amount of hyaluronic acid during submucosal dissection were more favorable in hybrid ESD than conventional ESD (time, 5.2 min vs 10.4 min, P < 0.001; speed, 43.7 mm2/min vs 23.8 mm2/min, P < 0.00; injection volume, 1.5 mL vs 3.0 mL, P < 0.001), although no significant differences in those factors were observed between both groups during mucosal incision. There was also no significant difference between both groups in the en bloc/complete resection rate and perforation rate (complete resection, 93.8% vs 87.5%, P = 0.67; perforation, 0% vs 3.1%, P = 1). Selection of conventional ESD as the treatment method was significantly associated with difficulties during ESD (odds ratio = 10.2; highest among factors). CONCLUSION: Hybrid ESD with SOUTEN improves the treatment outcomes of gastric lesions. It also has the potential to reduce medical costs since SOUTEN is a single multifunctional device that is inexpensive.

    DOI: 10.4240/wjgs.v13.i6.563

  • Application of traction-method to hybrid endoscopic submucosal dissection for gastrointestinal tumors. Reviewed International journal

    Mitsuru Esaki, Ryosuke Maehara, Shuzaburo Nagatomo, Kei Nishioka, Yosuke Minoda, Haruei Ogino, Eikichi Ihara

    Endoscopy   2021.4

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    DOI: 10.1055/a-1422-2902

  • Physiological and pathological roles of the accommodation response in lower esophageal sphincter relaxation during wet swallows. Reviewed International journal

    Kazumasa Muta, Eikichi Ihara, Shohei Hamada, Hiroko Ikeda, Masafumi Wada, Yoshitaka Hata, Xiaopeng Bai, Yuichiro Nishihara, Yoshimasa Tanaka, Haruei Ogino, Yoshihiro Ogawa

    Scientific reports   11 ( 1 )   7898 - 7898   2021.4

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    The preparatory accommodation response of lower esophageal sphincter (LES) before swallowing is one of the mechanisms involved in LES relaxation during wet swallows, however, the physiological and/or pathological roles of LES accommodation remain to be determined in humans. To address this problem, we conducted a prospective observational study of 38 patients with normal high-resolution manometry (HRM) and 23 patients with idiopathic esophagogastric junction outflow obstruction (EGJOO) to assess dry and wet swallows. The LES accommodation measurement was proposed for practical use in evaluating the LES accommodation response. Although swallow-induced LES relaxation was observed in both dry and wet swallows, LES accommodation (6.4, 3.1-11.1 mmHg) was only observed in wet swallows. The extent of LES accommodation was impaired in idiopathic EGJOO (0.6, - 0.6-6 mmHg), and the LES accommodation measurement of patients with idiopathic EGJOO (36.8, 29.5-44.3 mmHg) was significantly higher in comparison to those with normal HRM (23.8, 18-28.6 mmHg). Successful LES relaxation in wet swallowing can be achieved by LES accommodation in combination with swallow-induced LES relaxation. Impaired LES accommodation is characteristic of idiopathic EGJOO. In addition to the IRP value, the LES accommodation measurement may be useful for evaluating the LES relaxation function in clinical practice.

    DOI: 10.1038/s41598-021-87052-x

  • Discriminant equation using mucosally expressed cytokines and transcription factor for making definite diagnosis of inflammatory bowel disease unclassified. Reviewed International journal

    Hiroaki Okuno, Haruei Ogino, Eikichi Ihara, Kei Nishioka, Yoshimasa Tanaka, Takatoshi Chinen, Motoyuki Kohjima, Takamasa Oono, Masatake Tanaka, Takeshi Goya, Nao Fujimori, Yoichiro Iboshi, Takuji Gotoda, Yoshihiro Ogawa

    BMC gastroenterology   21 ( 1 )   73 - 73   2021.2

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    BACKGROUND: The pathological conditions of UC and CD involved in inflammatory bowel disease-unclassified (IBD-U), UC with primary sclerosing cholangitis (PSC-UC), and UC with autoimmune pancreatitis type 2 (AIP-UC) remain unclear. Therefore, it is difficult to decide the appropriate treatments for these subtypes of UC. Our aim was to examine whether the discriminant equation using the mucosally expressed mediators designed as our previous study for IBD, could characterize IBD-U, PSC-UC, or AIP-UC. METHODS: A total of 56 patients including UC (n = 24), CD (n = 15), IBD-U (n = 10), PSC-UC (n = 4), and AIP-UC (n = 3), along with 9 control patients were enrolled in this study. Mucosally expressed inflammatory mediators related to Th1, Th2, Th17, and Treg were measured using quantitative PCR in endoscopic biopsies from the inflamed intestines of the patients. The IBD-U, PSC-UC or AIP-UC were characterized using discriminant analysis and principle component analysis. RESULTS: Through discriminant analyses, combinations of 3 to 7 inflammatory mediators were used to discriminate between UC and CD. Moreover, the identified 3 markers could diagnose patients with IBD-U as UC or CD with high accuracy. The distribution graph of inflammatory mediators using the principal component analysis revealed that PSC-UC and AIP-UC exhibited CD-like and UC-like features, respectively. CONCLUSIONS: The discriminant equation using mucosally expressed mediators of IL-13, IL-21 and T-bet can be used as a universal diagnostic tool not only for IBD-U but also to assess pathological conditions in PSC-UC and AIP-UC.

    DOI: 10.1186/s12876-021-01656-1

  • Efficacy of endoscopic ultrasound with artificial intelligence for the diagnosis of gastrointestinal stromal tumors. Reviewed

    Yosuke Minoda, Eikichi Ihara, Keishi Komori, Haruei Ogino, Yoshihiro Otsuka, Takatoshi Chinen, Yasuo Tsuda, Koji Ando, Hidetaka Yamamoto, Yoshihiro Ogawa

    Journal of gastroenterology   55 ( 12 )   1119 - 1126   2020.12

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    BACKGROUND: Although endoscopic ultrasound (EUS) is reported to be suitable for determining the layer from which subepithelial lesions (SELs) originate, it is difficult to distinguish gastrointestinal stromal tumor (GIST) from non-GIST using only EUS images. If artificial intelligence (AI) can be used for the diagnosis of SELs, it should provide several benefits, including objectivity, simplicity, and quickness. In this pilot study, we propose an AI diagnostic system for SELs and evaluate its efficacy. METHODS: Thirty sets each of EUS images with SELs ≥ 20 mm or < 20 mm were prepared for diagnosis by an EUS diagnostic system with AI (EUS-AI) and three EUS experts. The EUS-AI and EUS experts diagnosed the SELs using solely the EUS images. The concordance rates of the EUS-AI and EUS experts' diagnoses were compared with the pathological findings of the SELs. RESULTS: The accuracy, sensitivity, and specificity for SELs < 20 mm were 86.3, 86.3, and 62.5%, respectively for the EUS-AI, and 73.3, 68.2, and 87.5%, respectively, for the EUS experts. In contrast, accuracy, sensitivity, and specificity for SELs ≥ 20 mm were 90.0, 91.7, and 83.3%, respectively, for the EUS-AI, and 53.3, 50.0, and 83.3%, respectively, for the EUS experts. The area under the curve for the diagnostic yield of the EUS-AI for SELs ≥ 20 mm (0.965) was significantly higher than that (0.684) of the EUS experts (P = 0.007). CONCLUSION: EUS-AI had a good diagnostic yield for SELs ≥ 20 mm. EUS-AI has potential as a good option for the diagnosis of SELs.

    DOI: 10.1007/s00535-020-01725-4

  • Endoscopic mucosal resection vs endoscopic submucosal dissection for superficial non-ampullary duodenal tumors. Reviewed International journal

    Mitsuru Esaki, Kazuhiro Haraguchi, Kazuya Akahoshi, Naru Tomoeda, Akira Aso, Soichi Itaba, Haruei Ogino, Yusuke Kitagawa, Hiroyuki Fujii, Kazuhiko Nakamura, Masaru Kubokawa, Naohiko Harada, Yosuke Minoda, Sho Suzuki, Eikichi Ihara, Yoshihiro Ogawa

    World journal of gastrointestinal oncology   12 ( 8 )   918 - 930   2020.8

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    BACKGROUND: The selection of endoscopic treatments for superficial non-ampullary duodenal epithelial tumors (SNADETs) is controversial. AIM: To compare the efficacy and safety of endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) for SNADETs. METHODS: We retrospectively analyzed the data of patients with SNADETs from a database of endoscopic treatment for SNADETs, which included eight hospitals in Fukuoka, Japan, between April 2001 and October 2017. A total of 142 patients with SNADETs treated with EMR or ESD were analyzed. Propensity score matching was performed to adjust for the differences in the patient characteristics between the two groups. We analyzed the treatment outcomes, including the rates of en bloc/complete resection, procedure time, adverse event rate, hospital stay, and local or metastatic recurrence. RESULTS: Twenty-eight pairs of patients were created. The characteristics of patients between the two groups were similar after matching. The EMR group had a significantly shorter procedure time and hospital stay than those of the ESD group [median procedure time (interquartile range): 6 (3-10.75) min vs 87.5 (68.5-136.5) min, P < 0.001, hospital stay: 8 (6-10.75) d vs 11 (8.25-14.75) d, P = 0.006]. Other outcomes were not significantly different between the two groups (en bloc resection rate: 82.1% vs 92.9%, P = 0.42; complete resection rate: 71.4% vs 89.3%, P = 0.18; and adverse event rate: 3.6% vs 17.9%, P = 0.19, local recurrence rate: 3.6% vs 0%, P = 1; metastatic recurrence rate: 0% in both). Only one patient in the ESD group underwent emergency surgery owing to intraoperative perforation. CONCLUSION: EMR has significantly shorter procedure time and hospital stay than ESD, and provides acceptable curability and safety compared to ESD. Accordingly, EMR for SNADETs is associated with lower medical costs.

    DOI: 10.4251/wjgo.v12.i8.918

  • The Efficacy and Safety of a Promising Single-Channel Endoscopic Closure Technique for Endoscopic Treatment-Related Artificial Ulcers: A Pilot Study. Reviewed International journal

    Yosuke Minoda, Eikichi Ihara, Haruei Ogino, Keishi Komori, Yoshihiro Otsuka, Hiroko Ikeda, Mitsuru Esaki, Takatoshi Chinen, Takahiro Matsuguchi, Shunsuke Takahashi, Noriko Shiga, Rie Yoshimura, Yoshihiro Ogawa

    Gastrointestinal tumors   7 ( 1-2 )   21 - 29   2020.4

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    Background/Aims: It is important to appropriately manage patients with procedure-related artificial mucosal ulcers or procedure-related complications. Many endoscopic closure techniques have been reported; however, they often require the use of special devices. We developed a single-channel endoscopic closure technique (SCCT) that can be performed with conventional devices. In the present study, we describe the technique and evaluate its efficacy. Methods: Twenty-five consecutive patients who underwent endoscopic treatment and whose artificial ulcer was closed using the SCCT were enrolled in this study. The technical success rate, number of clips for closure, procedure time, complication rate on the day of the procedure, clinical success rates on days 1 and 5, and incidence of severe stenosis of the gastrointestinal (GI) tract at 2 months after the procedure were evaluated. Results: The median ulcer diameter was 20 mm. The tumor locations were the stomach (n = 19), jejunum (n = 1), and colon (n = 5). The technical success rate was 100% (25/25), and the rate of incomplete closure was 0% (0/25). Eight clips were needed on average. The median procedure time was 18 min (range 5-49 min). The complication rate was 0% (25/25). The clinical success rates on days 1 and 5 were 100% (19/19) and 100% (9/9), respectively. No patients presented stenosis as a late complication at 2 months after the procedure (0/25). Conclusion: The SCCT could be applied in the treatment of artificial ulcers in several parts of the GI tract with a high clinical success rate and no complications. The SCCT appears to be a good option for closing artificial mucosal ulcers.

    DOI: 10.1159/000503994

  • Superiority of mucosal incision-assisted biopsy over ultrasound-guided fine needle aspiration biopsy in diagnosing small gastric subepithelial lesions: a propensity score matching analysis. Reviewed International journal

    Yosuke Minoda, Takatoshi Chinen, Takashi Osoegawa, Soichi Itaba, Kazuhiro Haraguchi, Hirotada Akiho, Akira Aso, Yorinobu Sumida, Keishi Komori, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa

    BMC gastroenterology   20 ( 1 )   19 - 19   2020.1

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    BACKGROUND: Gastric subepithelial lesions, including gastrointestinal stromal tumors, are often found during routine gastroscopy. While endoscopic ultrasound-guided fine-needle aspiration biopsy (EUS-FNAB) has been the gold standard for diagnosing gastric subepithelial lesions, alternative open biopsy procedures, such as mucosal incision-assisted biopsy (MIAB) has been reported useful. The aim of this study is to evaluate the efficacy of MIAB for the diagnosis of gastric SELs compared with EUS-FNAB. METHODS: We retrospectively analyzed medical records of 177 consecutive patients with gastric SELs who underwent either MIAB or EUS-FNAB at five hospitals in Japan between January 2010 and January 2018. Diagnostic yield, procedural time, and adverse event rates for the two procedures were evaluated before and after propensity-score matching. RESULTS: No major procedure-related adverse events were observed in either group. Both procedures yielded highly-accurate diagnoses once large enough samples were obtained; however, such successful sampling was more often accomplished by MIAB than by EUS-FNAB, especially for small SELs. As a result, MIAB provided better diagnostic yields for SELs smaller than 20-mm diameter. The diagnostic yields of both procedures were comparable for SELs larger than 20-mm diameter; however, MIAB required significantly longer procedural time (approximately 13 min) compared with EUS-FNAB. CONCLUSIONS: Although MIAB required longer procedural time, it outperformed EUS-FNAB when diagnosing gastric SELs smaller than 20-mm diameter.

    DOI: 10.1186/s12876-020-1170-2

  • Clinical Characterization of Vonoprazan-Refractory Gastroesophageal Reflux Disease. Reviewed International journal

    Shohei Hamada, Eikichi Ihara, Hiroko Ikeda, Kazumasa Muta, Haruei Ogino, Takatoshi Chinen, Yoshimasa Tanaka, Yoshihiro Ogawa

    Digestion   102 ( 2 )   1 - 8   2019.10

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    INTRODUCTION: The newly developed vonoprazan (a potassium-competitive acid blocker) has a greater ability to suppress gastric acid production than convention proton pump inhibitors (PPIs). The objective of the present study was to determine how vonoprazan influences the pathogenesis of refractory gastroesophageal reflux disease (GERD) in clinical practice. METHODS: Between March 2013 and November 2018, a total of 73 refractory GERD patients (34 in the conventional PPI group versus 39 in the vonoprazan group) were enrolled in this retrospective study. We then compared the underlying disease conditions between the 2 groups, examined by high-resolution manometry and multichannel intraluminal impedance/pH (MII-pH) monitoring. RESULTS: There was a significant difference in the proportion of underlying disease conditions, including erosive esophagitis, non-erosive reflux disease, reflux hypersensitivity, functional heartburn and oesophageal motility disorder (EMD), between the conventional PPI (6, 14, 23, 40 and 17&#37; respectively) and vonoprazan groups (0, 0, 10, 49, and 41&#37; respectively; p < 0.01). No cases of acid-related GERD were observed in the vonoprazan group. When the EMD patients were excluded, the lower oesophageal acid exposure time of the vonoprazan group (0.1&#37; [0.0-0.5&#37;], n = 23) was significantly lower than that of the conventional PPI group (0.35&#37; [0.1-3.9&#37;], n = 28; p < 0.05), and the gastric pH <4 holding time of the vonoprazan group (7.7&#37; [0.7-34.5&#37;]) was also significantly lower than that of the conventional PPI group (61.6&#37; [49.4-74.3&#37;], p < 0.01). CONCLUSIONS: Vonoprazan serves as a diagnostic tool to exclude acid-related GERD.

    DOI: 10.1159/000503340

  • Involvement of different receptor subtypes in prostaglandin E2-induced contraction and relaxation in the lower esophageal sphincter and esophageal body Reviewed

    Xiaopeng Bai, Eikichi Ihara, Yoshihihro Otsuka, Shinichi Tsuruta, Katsuya Hirano, Yoshimasa Tanaka, Haruei Ogino, Mayumi Hirano, Takatoshi Chinen, Hirotada Akiho, Kazuhiko Nakamura, Yoshinao Oda, Yoshihiro Ogawa

    European Journal of Pharmacology   857   2019.8

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    Prostaglandin E2 (PGE2) plays a role in the pathogenesis of gastro-esophageal reflux disease (GERD). There are 4 subtypes of PGE2, PGE2 receptor 1, 2, 3 and 4 (EP 1–4). In GERD patents, PGE2, EP2 and EP4 are upregulated. However, the effects of PGE2 on esophageal motility remain elusive. We examined how PGE2 regulates motility in the porcine circular smooth muscle of the lower esophageal sphincter (LES), and the circular and longitudinal smooth muscle of the esophagus body in organ bath. PGE2 induced tonic relaxation in the LES and circular smooth muscle, but transient contraction in longitudinal smooth muscle. The relaxation of the LES and circular smooth muscle was similar in pattern and mechanism, but was much larger in the LES. The relaxation was completely blocked by a voltage-gated K+ channel blocker or 40 mM K+ depolarization, indicating the involvement of K+ channel. Longitudinal smooth muscle contraction was completely blocked by an L-type Ca2+ channel blocker, showing the contribution of Ca2+ movement. The involvement of the EP receptor in motility was examined with selective receptor agonists and antagonists. Activation of EP2 and EP4 caused relaxation in the LES and circular smooth muscle. Compatible with PGE2, EP2 and EP4 agonists caused more significant relaxation in the LES than in circular smooth muscle. EP1 contributed to the longitudinal smooth muscle contraction. The different effects of PGE2 in the LES, circular and longitudinal smooth muscle contributes to esophageal motility, their impairment might increase the amount and frequency of esophageal reflux.

    DOI: 10.1016/j.ejphar.2019.172405

  • The Altered Mucosal Barrier Function in the Duodenum Plays a Role in the Pathogenesis of Functional Dyspepsia Reviewed International journal

    Keishi Komori, Eikichi Ihara, Yosuke Minoda, Haruei Ogino, Taisuke Sasaki, Minako Fujiwara, Yoshinao Oda, Yoshihiro Ogawa

    Digestive Diseases and Sciences   64 ( 11 )   3228 - 3239   2019.1

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    Background: An altered gastrointestinal barrier function is reportedly associated with the pathogenesis of functional dyspepsia (FD); however, the pathogenesis of FD has not yet been fully elucidated. Aims: The objective of the present study was to determine whether the mucosal barrier function is impaired in patients with FD and to investigate the mechanisms underlying FD. Methods: The present study included patients with FD (FD group, n = 24), non-FD patients with abdominal symptoms (symptomatic control group, n = 14), and patients with no abdominal symptoms (asymptomatic control group, n = 20). The groups were compared regarding the mucosal electrical impedance (MI) values of the stomach and duodenum, which were measured using a tissue conductance meter during esophagogastroduodenoscopy. Results: There were no significant differences between the three groups in the MI of the stomach. In contrast, the duodenal MI of the FD group (17.8 ± 4.3 Ω) was significantly lower than those of the symptomatic control group (27.2 ± 6.4 Ω, p < 0.0001) and asymptomatic control group (23.0 ± 7.4 Ω, p = 0.016). The expression of zonula occludens-1 (ZO-1) was significantly lower in the FD group than in the symptomatic control group (p = 0.011), where ZO-1 was positively correlated with the duodenal MI (β = 0.513, p = 0.017). The interleukin (IL)-1β expression was significantly higher in the FD group than in the symptomatic control group (p = 0.041), where IL-1β was inversely correlated with the duodenal MI (β = − 0.600, p = 0.004). Conclusions: The mucosal barrier function of the duodenum was altered in patients with FD. Both a decreased ZO-1 and increased IL-1β may play a role in the pathogenesis of FD.

    DOI: 10.1007/s10620-019-5470-8

  • Objective validity of the Japan Narrow-Band Imaging Expert Team classification system for the differential diagnosis of colorectal polyps Reviewed International journal

    Yosuke Minoda, Haruei Ogino, Takatoshi Chinen, Eikichi Ihara, Kazuhiro Haraguchi, Hirotada Akiho, Nobuyoshi Takizawa, Akira Aso, Yosuke Tomita, Mitsuru Esaki, Keishi Komori, Yoshihiro Otsuka, Tsutomu Iwasa, Yoshihiro Ogawa

    Digestive Endoscopy   31 ( 5 )   544 - 551   2019.1

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    Background and Aim: The Japan Narrow-Band Imaging (NBI) Expert Team (JNET) classification is a recently proposed NBI magnifying endoscopy-based classification system for colorectal tumors. Although the usefulness of this system has been reported by JNET experts, its objective validity remains unclear. We tested its validity and usefulness for the diagnosis of colorectal polyps by including colonoscopy experts and non-experts as test participants. Methods: Forty NBI images of polyps of various JNET types were shown to 22 doctors (11 experts and 11 non-gastrointestinal [GI] trainees) who had not examined the patients. The doctors diagnosed the polyps based solely on the surface and vessel patterns in the magnified images and the JNET classification system. Concordance rates of their diagnoses with the pathological findings of the polyps were determined, and the results for experts and non-GI trainees were compared. Results: Both for colonoscopy experts and non-GI trainees, the JNET classification system was particularly useful for classifying polyps as benign or malignant. Although the accuracy rates for classifying polyps into each JNET type varied among colonoscopy experts, those who were familiar with the JNET classification system were able to diagnose polyps with approximately 90&#37; accuracy. Common mistakes were attributable to misunderstandings of the wording in the JNET classification chart and lack of proper training. Conclusion: The JNET classification system is a practical approach for the diagnosis of colorectal polyps. Training is required even for experienced colonoscopists to adopt the system properly. Common pitfalls must be shared among colonoscopists to improve the accuracy of the diagnosis.

    DOI: 10.1111/den.13393

  • Mucosal incision-assisted biopsy versus endoscopic ultrasound-guided fine-needle aspiration with a rapid on-site evaluation for gastric subepithelial lesions A randomized cross-over study Reviewed International journal

    Takashi Osoegawa, Yosuke Minoda, Eikichi Ihara, Keishi Komori, Aso Akira, Ayako Goto, Soichi Itaba, Haruei Ogino, Kazuhiko Nakamura, Naohiko Harada, Kosuke Makihara, Shinichi Tsuruta, Hidetaka Yamamoto, Yoshihiro Ogawa

    Digestive Endoscopy   31 ( 4 )   413 - 421   2019.1

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    Objectives: This study aimed to compare the diagnostic yield of mucosal incision-assisted biopsy (MIAB) and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) with a rapid on-site evaluation (ROSE) for gastric subepithelial lesions (SEL) suspected of being gastrointestinal stromal tumors (GIST) with an intraluminal growth pattern. Methods: This was a prospective randomized, cross-over multicenter study. The primary outcome was the diagnostic yield of EUS-FNA and MIAB. The secondary outcomes were the technical success rate, complication rate, procedure time and biopsy frequency. Results: A total of 47 patients were randomized to the MIAB group (n = 23) and EUS-FNA group (n = 24). There was no significant difference in the diagnostic yield of MIAB and EUS-FNA (91.3&#37; vs 70.8&#37;, P = 0.0746). The complication rates of MIAB and EUS-FNA did not differ to a statistically significant extent. The mean procedure time in the MIAB group was significantly longer than that in the EUS-FNA group (34 vs 26 min, P = 0.0011). Conclusions: The diagnostic yield of MIAB was satisfactorily as high as EUS-FNA with ROSE for gastric SEL with an intraluminal growth pattern.

    DOI: 10.1111/den.13367

  • Clutch Cutter knife efficacy in endoscopic submucosal dissection for early gastric neoplasms Reviewed International journal

    Yasuyo Hayashi, Mitsuru Esaki, Sho Suzuki, Eikichi Ihara, Azusa Yokoyama, Seiichiro Sakisaka, Taizo Hosokawa, Yoshimasa Tanaka, Takahiro Mizutani, Shinichi Tsuruta, Aya Iwao, Shun Yamakawa, Akira Irie, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Hirotada Akiho, Yoshihiro Ogawa

    World Journal of Gastrointestinal Oncology   10 ( 12 )   487 - 495   2018.12

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    AIM To compare the outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms using Clutch Cutter (ESD-C) or other knives (ESD-O). METHODS This was a single-center retrospective study. Gastric neoplasms treated by ESD between April 2016 and October 2017 at Kitakyushu Municipal Medical Center were reviewed. Multivariate analyses and propensity score matching were used to reduce biases. Covariates included factors that might affect outcomes of ESD, including age, sex, underlying disease, anti-thrombotic drugs use, tumor location, tumor position, tumor size, tumor depth, tumor morphology, tumor histology, ulcer (scar), and operator skill. The treatment outcomes were compared among two groups. The primary outcome was ESD procedure time. Secondary outcomes were en bloc, complete, and curative resection rates, and adverse events rates including perforation and delayed bleeding. RESULTS A total of 155 patients were included in this study; 44 pairs were created by propensity score matching. Background characteristics were quite similar among two groups after matching. Procedure time was significantly shorter for ESD-C (median; 49 min) than for ESD-O (median; 88.5 min) (P < 0.01). However, there was no significant difference in treatment outcomes between ESD-C and ESD-O including en bloc resection rate (100&#37; in both groups), complete resection rate (100&#37; in both groups), curative resection rate (86.4&#37; vs 88.6&#37;, P = 0.730), delayed bleeding (2.3&#37; vs 6.8&#37;, P = 0.62) and perforation (0&#37; in both groups). CONCLUSION ESD-C achieved shorter procedure time without an increase in complication risk. Therefore, ESD-C could become an effective ESD option for gastric neoplasms.

    DOI: 10.4251/wjgo.v10.i12.487

  • Mucosally Expressed Cytokines are Associated with the Esophageal Motility Function Reviewed International journal

    Keita Fukaura, Eikichi Ihara, Haruei Ogino, Yoichiro Iboshi, Kazumasa Muta, Bai Xiaopeng, Shohei Hamada, Yoshitaka Hata, tsutomu iwasa, Akira Aso, Kazuhiko Nakamura, Yoshihiro Ogawa

    Digestion   98 ( 2 )   95 - 103   2018.8

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    Background and Aim: Although basic research has shown that certain cytokines affect gastrointestinal motility, the clinical evidence is lacking. The objective of this study was to explore the association between mucosally expressed cytokines and the esophageal motility function in humans. Methods: We enrolled a total of 57 patients with suspected esophageal motility disorders (EMDs) who underwent high-resolution manometry. Results: The diagnoses of the patients were as follows: normal esophageal motility (n = 25), ineffective esophageal motility (n = 5), esophagogastric junction outflow obstruction (EGJOO; n = 10), distal esophageal spasm (n = 5), achalasia (n = 10), absent contractility (n = 1), and jackhammer esophagus (n = 1). The expression of tumor necrosis factor (TNF)-α in the esophagogastric junction (EGJ) was significantly higher in EGJOO (14.6, 14.0-15.8, n = 10) than in normal esophageal motility (13.3, 12.8-14.1, n = 25); however, there was no difference in the expression of TNF-α between achalasia (13.4, 13.0-14.1, n = 10) and normal esophageal motility (13.3, 12.8-14.1, n = 25). EGJOO was discriminated from achalasia/normal by a linear discriminant analysis (AUC = 0.917). A multivariable regression analysis revealed that interleukin (IL)-13 and IL-23A were predictive of the distal contractile integral, whereas TNF-α and IL-6 were predictive of the basal EGJ pressure. Conclusions: The esophageal motility was associated with mucosally expressed cytokines in humans; these cytokines could be useful targets for the diagnosis and treatment of EMDs.

    DOI: 10.1159/000487708

  • Propensity score-matching analysis to compare clinical outcomes of endoscopic submucosal dissection for early gastric cancer in the postoperative and non-operative stomachs Reviewed International journal

    Mitsuru Esaki, Sho Suzuki, Yasuyo Hayashi, Azusa Yokoyama, Shuichi Abe, Taizo Hosokawa, Shinichi Tsuruta, Yosuke Minoda, Yoshitaka Hata, Haruei Ogino, Hirotada Akiho, Eikichi Ihara, Yoshihiro Ogawa

    BMC Gastroenterology   18 ( 1 )   125 - 125   2018.8

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    Background: Endoscopic submucosal dissection (ESD) of the postoperative stomach (ESD-P) for early gastric cancer (EGC) is considered a technically difficult procedure. However, it is difficult to compare the outcomes of ESD-P and ESD of the non-operative stomach (ESD-N) because their baseline characteristics are different. Therefore, we aimed to compare the technical outcomes of ESD-P with those of ESD-N using a propensity score-matching analysis to compensate for the differences. Methods: The chart records of 1046 patients with EGC who were treated with ESD between January 2004 and July 2016 at Kitakyushu Municipal Medical Center in Japan were reviewed in this retrospective study. Multivariate analyses and propensity score-matching were performed for age, sex, lesion location, lesion size, tumor invasion, tumor size, ulcer (scar), and operator skill. The primary outcome was procedure time. Secondary outcomes were percentages of en bloc, complete, and curative resections, and percentages of adverse events, which were evaluated between the two groups. Results: Forty-one patients were in the ESD-P group and 1005 patients were in the ESD-N group. Propensity score-matching created 41 matched pairs. According to the adjusted comparisons, ESD-P required a significantly longer procedure time (85 min vs 51 min, p < 0.001). Other treatment outcomes showed an en bloc resection rate of 100&#37; for both groups (p = 1) and complete resection rates of 95.1 and 97.6&#37; (p = 1), curative resection rates of 90.2 and 90.2&#37; (p = 1), perforation during ESD rates of 2.4 and 0&#37; (p = 1), and postprocedure bleeding rates of 2.4 and 2.4&#37; (p = 1) for the ESD-P and ESD-N groups, respectively. For the ESD-P group, lesions on the suture line or anastomotic site were significantly associated with longer procedure times (p = 0.038). Conclusions: ESD-P was a more time-consuming procedure than ESD-N. However, ESD-P and ESD-N achieved high rates of curative resection with a low rate of adverse events for the treatment of EGC. ESD could be selected as the treatment for EGC even in the postoperative stomach provided that careful attention is given to lesions on the suture line or anastomotic site.

    DOI: 10.1186/s12876-018-0855-2

  • A new robotic-assisted flexible endoscope with single-hand control endoscopic submucosal dissection in the ex vivo porcine stomach Reviewed International journal

    tsutomu iwasa, Ryu Nakadate, Shinya Onogi, Yasuharu Okamoto, Jumpei Arata, Susumu Oguri, Haruei Ogino, Eikichi Ihara, Kenoki Ouchida, Tomohiko Akahoshi, Tetsuo Ikeda, Yoshihiro Ogawa, Makoto Hashizume

    Surgical Endoscopy   32 ( 7 )   3386 - 3392   2018.7

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    Background: Difficulties in endoscopic operations and therapeutic procedures seem to occur due to the complexity of operating the endoscope dial as well as difficulty in performing synchronized movements with both hands. We developed a prototype robotic-assisted flexible endoscope that can be controlled with a single hand in order to simplify the operation of the endoscope. The aim of this study was to confirm the operability of the robotic-assisted flexible endoscope (RAFE) by performing endoscopic submucosal dissection (ESD). Methods: Study 1: ESD was performed manually or with RAFE by an expert endoscopist in ex vivo porcine stomachs; six operations manually and six were performed with RAFE. The procedure time per unit circumferential length/area was calculated, and the results were statistically analyzed. Study 2: We evaluated how smoothly a non-endoscopist can move a RAFE compared to a manual endoscope by assessing the designated movement of the endoscope. Results: Study 1: En bloc resection was achieved by ESD using the RAFE. The procedure time was gradually shortened with increasing experience, and the procedure time of ESD performed with the RAFE was not significantly different from that of ESD performed with a manual endoscope. Study 2: The time for the designated movement of the endoscope was significantly shorter with a RAFE than that with a manual endoscope as for a non-endoscopist. Conclusions: The RAFE that we developed enabled an expert endoscopist to perform the ESD procedure without any problems and allowed a non-endoscopist to control the endoscope more easily and quickly than a manual endoscope. The RAFE is expected to undergo further development.

    DOI: 10.1007/s00464-018-6188-y

  • Recovery technique using a double scope to rescue failed primary endoscopic ligation Reviewed

    Yosuke Minoda, Keishi Komori, Ryoko Naruo, tsutomu iwasa, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa

    Endoscopy   50 ( 9 )   E244 - E245   2018.6

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    DOI: 10.1055/a-0631-7760

  • Endogenous Hydrogen Sulfide Contributes to Tone Generation in Porcine Lower Esophageal Sphincter Via Na+/Ca2+ Exchanger Reviewed

    Xiaopeng Bai, Eikichi Ihara, Katsuya Hirano, Yoshimasa Tanaka, Kayoko Nakano, Satomi Kita, Takahiro Iwamoto, Haruei Ogino, Mayumi Hirano, Yoshinao Oda, Kazuhiko Nakamura, Yoshihiro Ogawa

    CMGH   5 ( 3 )   209 - 221   2018.3

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    Background and Aims: Hydrogen sulfide (H2S) is a major physiologic gastrotransmitter. Its role in the regulation of the lower esophageal sphincter (LES) function remains unknown. The present study addresses this question. Methods: Isometric contraction was monitored in circular smooth muscle strips of porcine LES. Changes in cytosolic Ca2+ concentration ([Ca2+]i) and force were simultaneously monitored in fura-2-loaded strips with front-surface fluorometry. The contribution of endogenous H2S to LES contractility was investigated by examining the effects of inhibitors of H2S-generating enzymes, including cystathionine-β-synthase, cystathionine-γ-lyase, and 3-mercaptopyruvate sulfurtransferase, on the LES function. Results: Porcine LES strips myogenically maintained a tetrodotoxin-resistant basal tone. Application of AOA (cystathionine-β-synthase inhibitor) or L-aspartic acid (L-Asp; 3-mercaptopyruvate sulfurtransferase inhibitor) but not DL-PAG (cystathionine-γ-lyase inhibitor), decreased this basal tone. The relaxant effects of AOA and L-Asp were additive. Maximum relaxation was obtained by combination of 1 mM AOA and 3 mM L-Asp. Immunohistochemical analyses revealed that cystathionine-β-synthase and 3-mercaptopyruvate sulfurtransferase, but not cystathionine-γ-lyase, were expressed in porcine LES. AOA+L-Asp–induced relaxation was accompanied by a decrease in [Ca2+]i and inversely correlated with the extracellular Na+ concentration ([Na+]o) (25-137.4 mM), indicating involvement of an Na+/Ca2+ exchanger. The reduction in the basal [Ca2+]i level by AOA was significantly augmented in the antral smooth muscle sheets of Na+/Ca2+ exchanger transgenic mice compared with wild-type mice. Conclusions: Endogenous H2S regulates the LES myogenic tone by maintaining the basal [Ca2+]i via Na+/Ca2+ exchanger. H2S-generating enzymes may be a potential therapeutic target for esophageal motility disorders, such as achalasia.

    DOI: 10.1016/j.jcmgh.2017.11.004

  • Splash M-knife versus Flush Knife BT in the technical outcomes of endoscopic submucosal dissection for early gastric cancer: a propensity score matching analysis. Reviewed International journal

    Esaki M, Suzuki S, Hayashi Y, Yokoyama A, Abe S, Hosokawa T, Ogino H, Akiho H, Ihara E, Ogawa Y.

    BMC gastroenterology   18 ( 1 )   35 - 35   2018.2

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    Abstract
    BACKGROUND:
    Endoscopic submucosal dissection (ESD) is a standard treatment for early gastric cancer. A new multi-functional ESD device was developed to achieve complete ESD with a single device. A metal plate attached to its distal sheath achieves better hemostasis during the procedure than the other needle-knife device, Flush Knife BT®, that has been conventionally used. The aim of this study was to compare the technical outcomes of ESD for early gastric cancer using the Splash M-Knife® with those using the Flush Knife BT.

    METHODS:
    We conducted a retrospective review of the case records of 149 patients with early gastric cancer treated with ESD using the needle-type ESD knives between January 2012 and August 2016 at Kitakyushu Municipal Medical Center. Lesions treated with ESD using the Splash M-knife (ESD-M) and the Flush Knife BT (ESD-F) were compared. Multivariate analyses and propensity score matching were used to compensate for the differences in age, gender, underlying disease, antithrombotic drug use, lesion location, lesion position, macroscopic type, tumor size, presence of ulceration, operator level and types of electrosurgical unit used. The primary endpoint was the requirement to use hemostatic forceps in the two groups. The secondary endpoints of procedure time, en bloc and complete resection rates, and adverse events rates were evaluated for the two groups.

    RESULTS:
    There were 73 patients in the ESD-M group, and 76 patients in the ESD-F group. Propensity score matching analysis created 45 matched pairs. Adjusted comparisons between the two groups showed a significantly lower usage rate of hemostatic forceps in the ESD-M group than in the ESD-F group (6.7&#37; vs 84.4&#37;, p < 0.001). Treatment outcomes showed an en bloc resection rate of 100&#37; in both groups; complete resection rate of 95.6&#37; vs 100&#37;, p = 0.49; median procedure time of 74.0 min vs 71.0 min, p = 0.90; post-procedure bleeding of 2.2&#37; vs 2.2&#37;, p = 1, in the ESD-M and ESD-F groups, respectively. There were no perforations in either group.

    CONCLUSIONS:
    ESD-M appeared to reduce the usage of hemostatic forceps during ESD for early gastric cancer without increasing the adverse effects. Thus, it may contribute to a reduction in the total ESD cost.

    DOI: 10.1186/s12876-018-0763-5

  • Increased IL-17A/IL-17F expression ratio represents the key mucosal T helper/regulatory cell-related gene signature paralleling disease activity in ulcerative colitis Reviewed

    Yoichiro Iboshi, Kazuhiko Nakamura, Keita Fukaura, tsutomu iwasa, Haruei Ogino, Yorinobu Sumida, Eikichi Ihara, Hirotada Akiho, Naohiko Harada, Makoto Nakamuta

    Journal of gastroenterology   52 ( 3 )   315 - 326   2017.3

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    Background: T helper (Th) and regulatory T (Treg) cell-related cytokines are implicated in inflammatory bowel diseases, including ulcerative colitis (UC). While these cytokines are generally upregulated in inflamed mucosae, the key cytokine profile explaining disease severity has not been determined. Methods: The Rachmilewitz endoscopic index (REI) was assessed in 61 UC patients undergoing colonoscopy. Biopsies obtained from inflamed (REI 3–12) and noninflamed (REI 0–2) areas were analyzed by quantitative PCR for expression of mRNAs encoding cytokines and transcription factors related to Th1 (TNF-α, IFN-γ, IL-12p35, IL-12p40, and T-bet), Th2 (IL-4, IL-13, IL-33, and GATA3), Th17 (IL-17A, IL-17F, IL-21, IL-22, IL-23p19, IL-6, and RORC), Th9 (IL-9, IRF4, and PU.1), and Treg (TGF-β and Foxp3). Expression patterns associated with higher REI were determined by univariate and multivariate analyses. Results: Despite general upregulation, none of these mRNAs showed univariate correlation with REI in inflamed samples. Multiple regression analysis, however, found that joint expression of IL-17A, IL-17F, IL-21, RORC, and TGF-β was significantly predictive of REI (P < 0.0002, R2 = 0.380), with major individual contributions by IL-17A (P < 0.0001) and IL-17F (P < 0.0001), which were associated with increased and decreased REI, respectively. Partial correlation analysis, validating this model, indicated differences between IL-17A and IL-17F in correlating with other targets. The IL-17A/IL-17F ratio showed a significant correlation with REI (r = 0.5124, P < 0.0001), whereas no other mRNAs were essentially predictive of REI. Conclusions: Mucosal IL-17A/IL-17F ratio significantly correlates with endoscopic score in UC patients, accompanied by their disparate interactions with other Th/Treg-related genes.

    DOI: 10.1007/s00535-016-1221-1

  • Limited effect of rebamipide in addition to proton pump inhibitor (PPI) in the treatment of post-endoscopic submucosal dissection gastric ulcers A randomized controlled trial comparing ppi plus rebamipide combination therapy with PPI monotherapy Reviewed

    Kazuhiko Nakamura, Eikichi Ihara, Hirotada Akiho, Kazuya Akahoshi, Naohiko Harada, Toshiaki Ochiai, Norimoto Nakamura, Haruei Ogino, tsutomu iwasa, Akira Aso, Yoichiro Iboshi, Ryoichi Takayanagi

    Gut and Liver   10 ( 6 )   2016.11

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    Background/Aims: The ability of endoscopic submucosal dissection (ESD) to resect large early gastric cancers (EGCs) results in the need to treat large artificial gastric ulcers. This study assessed whether the combination therapy of rebamipide plus a proton pump inhibitor (PPI) offered benefits over PPI monotherapy. Methods: In this prospective, randomized, multicenter, open-label, and comparative study, patients who had undergone ESD for EGC or gastric adenoma were randomized into groups receiving either rabeprazole monotherapy (10 mg/day, n=64) or a combination of rabeprazole plus rebamipide (300 mg/day, n=66). The Scar stage (S stage) ratio after treatment was compared, and factors independently associated with ulcer healing were identified by using multivariate analyses. Results: The S stage rates at 4 and 8 weeks were similar in the two groups, even in the subgroups of patients with large amounts of tissue resected and regardless of CYP2C19 genotype. Independent factors for ulcer healing were circumferential location of the tumor and resected tissue size; the type of treatment did not affect ulcer healing. Conclusions: Combination therapy with rebamipide and PPI had limited benefits compared with PPI monotherapy in the treatment of post-ESD gastric ulcer (UMIN Clinical Trials Registry, UMIN000007435).

    DOI: 10.5009/gnl15486

  • Characteristics of hemorrhagic peptic ulcers in patients receiving antithrombotic/nonsteroidal antiinflammatory drug therapy Reviewed

    Kazuhiko Nakamura, Kazuya Akahoshi, Toshiaki Ochiai, Keishi Komori, Kazuhiro Haraguchi, Munehiro Tanaka, Norimoto Nakamura, Yoshimasa Tanaka, Kana Kakigao, Haruei Ogino, Eikichi Ihara, Hirotada Akiho, Yasuaki Motomura, Teppei Kabemura, Naohiko Harada, Yoshiharu Chijiiwa, Tetsuhide Ito, Ryoichi Takayanagi

    Gut and Liver   6 ( 4 )   423 - 426   2012.10

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    Background/Aims: Antithrombotic/nonsteroidal antiinflammatory drug (NSAID) therapies increase the incidence of upper gastrointestinal bleeding. The features of hemorrhagic peptic ulcer disease in patients receiving antithrombotic/NSAID therapies were investigated. Methods: We investigated the medical records of 485 consecutive patients who underwent esophagogastroduodenoscopy and were diagnosed with hemorrhagic gastroduodenal ulcers. The patients treated with antithrombotic agents/NSAIDs were categorized as the antithrombotic therapy (AT) group (n=213). The patients who were not treated with antithrombotics/NSAIDs were categorized as the control (C) group (n=263). The clinical characteristics were compared between the groups. Results: The patients in the AT group were significantly older than those in the C group (p<0.0001). The hemoglobin levels before/without transfusion were significantly lower in the AT group (8.24±2.41 g/dL) than in the C group (9.44±2.95 g/dL) (p<0.0001). After adjusting for age, the difference in the hemoglobin levels between the two groups remained significant (p=0.0334). The transfusion rates were significantly higher in the AT group than in the C group (p=0.0002). However, the outcome of endoscopic hemostasis was similar in the AT and C groups. Conclusions: Patients with hemorrhagic peptic ulcers receiving antithrombotic/NSAID therapies were exposed to a greater risk of severe bleeding that required transfusion but were still treatable by endoscopy.

    DOI: 10.5009/gnl.2012.6.4.423

  • Feeding administration of daikenchuto suppresses colitis induced by naive CD4+ T cell transfer into SCID mice Reviewed

    tsutomu iwasa, Haruei Ogino, Kazuhiko Nakamura, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi

    Digestive Diseases and Sciences   57 ( 10 )   2571 - 2579   2012.10

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    Background and Aims Daikenchuto, a traditional Japanese herbal medicine, suppresses bacterial translocation by improvement of gastrointestinal motility and blood flow. As Daikenchuto reportedly reduces gastrointestinal inflammatory activity by these mechanisms, we analyzed whether Daikenchuto suppresses experimental colitis and reduces inflammatory cytokine expression in a mouse model. Methods Colitis was induced by transfer of naive CD4+ T cells of BALB/c mice into SCID mice, and mice were given either control or 2.7 &#37; Daikenchuto-containing feed. We investigated body weight, clinical symptoms, histological changes, and Th1- and Th17-cytokine expression. Cytokine mRNA expression was analyzed using real-time RT-PCR. The ratio of IL-17+ and IFN-c+ CD4+ T cells were analyzed by flow cytometry. Results Daikenchuto delayed the development of colitis and significantly reduced the histological inflammation scores. Analyses of cytokine mRNA revealed that Th17 cytokines were significantly decreased in colons of mice that received Daikenchuto. Absolute numbers of IL-17+ or IFN-c+ CD4+ T cells per colon were less in mice receiving Daikenchuto than in mice that received control feed, as both groups received naive CD4+ T cells to induce colitis. Conclusions We demonstrated that feeding administration of Daikenchuto suppresses colitis induced by naive CD4+ T cell transfer into SCID mice. Daikenchuto may show clinical benefit in the treatment of human inflammatory bowel disease and further studies are warranted.

    DOI: 10.1007/s10620-012-2218-0

  • Th1 responses are more susceptible to infliximab-mediated immunosuppression than Th17 responses Reviewed

    Kenji Kanayama, Kazuhiko Nakamura, Haruei Ogino, Yorinobu Sumida, Eikichi Ihara, Hirotada Akiho, Ryoichi Takayanagi

    Digestive Diseases and Sciences   56 ( 12 )   3525 - 3533   2011.12

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    Background Treatment with infliximab, a chimeric antitumor necrosis factor (TNF)-α antibody, is highly efficient in patients with inflammatory bowel disease (IBD). It neutralizes soluble TNF-α and induces the apoptosis of transmembrane TNF-α-positive macrophages and T cells in the gut. Recently, T helper (Th)17, as well as Th1, responses have been implicated in the pathogenesis of IBD. Aims To clarify the effects of infliximab on Th1 and Th17 responses in vitro. Methods Naive CD4 + T cells isolated from the peripheral blood of healthy volunteers were stimulated under Th1- or Th17-inducing conditions in the presence of 10 μg/ml of infliximab or control immunoglobulin (Ig)G1. The concentrations of interferon (IFN)-c, interleukin (IL)-17, and TNF-α in the culture supernatants were determined by enzyme-linked immunosorbent assay (ELISA). Th1 and Th17 cells were immunostained with infliximab or control IgG1 and transmembrane TNF-α-positive cells were analyzed by flow cytometry. Annexin V staining and terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) assays were conducted in order to analyze the percentage of apoptotic cells. Results Both Th1 and Th17 cells expressed soluble and transmembrane TNF-α abundantly. Although infliximab suppressed IFN-γ secretion by Th1 cells and IL-17 secretion by Th17 cells, the level of the former was more profound than the latter. Infliximab increased annexin V- and TUNEL-positive apoptotic cells under Th1-inducing conditions, but not under Th17-inducing conditions. Conclusions Infliximab suppressed Th1 and Th17 differentiation in vitro; however, IFN-γ production by Th1 cells was more profoundly suppressed than IL-17 secretion by Th17 cells. Th1 responses were more susceptible to infliximab-mediated apoptosis than Th17 responses. Our results clarify a new mechanism of action of infliximab.

    DOI: 10.1007/s10620-011-1780-1

  • Endoscopic ultrasound-guided transmural drainage of inflammatory peripancreatic fluid collections with a wire-guided triple-lumen needle knife Reviewed

    Soichi Itaba, Yorinobu Sumida, Akira Aso, Yoichiro Iboshi, Tsutomu Iwasa, Haruei Ogino, Hisato Igarashi, Hirotada Akiho, Kazuhiko Nakamura, Tetsuhide Ito, Ryoichi Takayanagi

    Digestive Endoscopy   23 ( 3 )   269   2011.7

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    DOI: 10.1111/j.1443-1661.2010.01089.x

  • LOW-FREQUENCY OF BACTEREMIA AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION OF THE STOMACH Reviewed

    ITABA SOICHI, IBOSHI YOICHIRO, NAKAMURA KAZUHIKO, OGINO HARUEI, SUMIDA YORINOBU, ASO AKIRA, YOSHINAGA SHIGETAKA, AKIHO HIROTADA, IGARASHI HISATO, KATO MASAKI, KOTOH KAZUHIRO, ITO TETSUHIDE, TAKAYANAGI RYOICHI

    Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society   23 ( 1 )   69 - 72   2011.1

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    Low-frequency of bacteremia after endoscopic submucosal dissection of the stomach.
    Mainstream therapy for early gastric cancer in Japan has now shifted from endoscopic mucosal resection (EMR) to endoscopic submucosal dissection (ESD). Although bacteremia is reported as being infrequent and transient in gastric EMR, there are no reports of it being investigated in gastric ESD. This study aimed to determine the frequency of bacteremia in gastric ESD. A prospective study, in 46 consecutive patients who underwent gastric ESD, investigated the frequency of bacteremia before and after the procedure. Results: The median time for the total ESD procedure was 105min (range 30-400). The median volume of the submucosal injection was 80ml (range 20-260). The mean size of the resected specimen was 40±9.7mm. Blood cultures obtained before ESD were positive in 4.4&#37; (2/45) of cases. Bacillus subtilis and Bacillus spp. were the isolated microorganisms. Blood cultures obtained 10min after ESD were positive in 4.3&#37; (2/46) of cases; with the same microorganisms being isolated. Blood cultures obtained 3h after ESD were all negative. No signs of sepsis were seen in the two patients with a positive blood culture 10min after ESD. The frequency of bacteremia after gastric ESD was low and transient. ESD for gastric lesions is thought to have a low risk of infectious complications; therefore, prophylactic administration of antibiotics may not be warranted.

    DOI: 10.1111/j.1443-1661.2010.01066.x

  • Multiple ulcers in the small and large intestines occurred during tocilizumab therapy for rheumatoid arthritis Reviewed

    T. Iwasa, K. Nakamura, Haruei Ogino, S. Itaba, H. Akiho, R. Okamoto, Y. Iboshi, A. Aso, H. Murao, K. Kanayama, T. Ito, R. Takayanagi

    Endoscopy   43 ( 1 )   70 - 72   2011

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    Tocilizumab is a monoclonal antibody against human interleukin-6 receptor which blocks the binding of interleukin-6 to its receptor. Tocilizumab is effective for the treatment of inflammatory disorders including rheumatoid arthritis. We report a case of multiple ulcers in the small and large intestines, which occurred during tocilizumab therapy. A 57-year-old woman started to use tocilizumab for rheumatoid arthritis. Three months later, she complained of hematochezia. Double-balloon endoscopy revealed multiple small aphthoid ulcers in the small and large intestines. One month after the woman had recovered, she was given tocilizumab again. The woman had hematochezia and abdominal pain again 2 weeks later. Colonoscopy revealed multiple round, discrete punched-out ulcers in the terminal ileum, and vast deep ulcers from the cecum to the descending colon. Bioptic histopathology and cultivation showed non-specific findings. Six weeks after discontinuation of tocilizumab, ulcers in the small and large intestine dramatically improved, leaving ulcer scars. This disease course and the results of examination made us strongly suspect that tocilizumab induced multiple ulcers in the small and large intestines. Interleukin-6 is a pleiotropic cytokine and involved in intestinal mucosal wound healing as well as in inflammatory processes. It is possible that tocilizumab inhibited tissue repair of the intestine and caused intestinal ulcers.

    DOI: 10.1055/s-0030-1255931

  • Persistent gut motor dysfunction in a murine model of T-cell-induced enteropathy Reviewed

    T. Mizutani, H. Akiho, W. I. Khan, H. Murao, Haruei Ogino, K. Kanayama, K. Nakamura, R. Takayanagi

    Neurogastroenterology and Motility   22 ( 2 )   2010.2

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    Background Inflammatory bowel disease (IBD) patients in remission often experience irritable bowel syndrome (IBS)-like symptoms. We investigated the mechanism for intestinal muscle hypercontractility seen in T-cell-induced enteropathy in recovery phase. Methods BALB/c mice were treated with an anti-CD3 antibody (100 μg per mouse) and euthanized at varying days post-treatment to investigate the histological changes, longitudinal smooth muscle cell contraction, cytokines (Th1, Th2 cytokines, TNF-α) and serotonin (5-HT)-expressing enterochromaffin cell numbers in the small intestine. The role of 5-HT in anti-CD3 antibody-induced intestinal muscle function in recovery phase was assessed by inhibiting 5-HT synthesis using 4-chloro-DL-phenylalanine (PCPA). Key Results Small intestinal tissue damage was observed from 24 h after the anti-CD3 antibody injection, but had resolved by day 5. Carbachol-induced smooth muscle cell contractility was significantly increased from 4 h after injection, and this muscle hypercontractility was evident in recovery phase (at day 7). Th2 cytokines (IL-4, IL-13) were significantly increased from 4 h to day 7. 5-HT-expressing cells in the intestine were increased from day 1 to day 7. The 5-HT synthesis inhibitor PCPA decreased the anti-CD3 antibody-induced muscle hypercontractility in recovery phase. Conclusions & Inferences Intestinal muscle hypercontractility in remission is maintained at the smooth muscle cell level. Th2 cytokines and 5-HT in the small intestine contribute to the maintenance of the altered muscle function in recovery phase.

    DOI: 10.1111/j.1365-2982.2009.01396.x

  • Impact of double-balloon endoscopy on the diagnosis of jejuoileal involvement in primary intestinal follicular lymphomas : a case series Reviewed

    HIGUCHI N

    Endoscopy   41 ( 2 )   175 - 178   2009.2

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    Impact of double-balloon endoscopy on the diagnosis of jejunoileal involvement in primary intestinal follicular lymphomas A case series
    In recent years, primary gastrointestinal follicular lymphoma has been increasingly detected in the duodenum on esophagogastroduodenoscopy (EGD). Primary gastrointestinal follicular lymphomas are frequently distributed to multiple sites in the gastrointestinal tract. Therefore, investigation into the spread of follicular lymphomas in the small bowel is important in order to determine the most appropriate treatment strategy. The performance of double-balloon endoscopy (DBE) in the diagnosis of jejunoileal follicular lymphoma lesions has not been fully evaluated. We aimed to investigate the value of DBE in addition to computed tomography (CT) and 18F- fluorodeoxyglucose positron emission tomography (18F-FDG-PET) in the diagnosis of jejunoileal follicular lymphoma. DBE with biopsy was performed in seven patients with primary duodenal follicular lymphoma diagnosed by EGD, in order to investigate jejunoileal involvement. Jejunoileal follicular lymphoma lesions were detected by DBE in six out of the seven patients (three in the jejunum and three in the jejunum and ileum), whereas CT and 18F-FDG- PET failed to detect the existence of these lesions. Endoscopic findings of the jejunoileal lesions revealed multiple white nodules and white villi, which were similar to those of duodenal lesions. DBE was more useful for the diagnosis of jejunoileal involvement in primary intestinal follicular lymphoma than CT and 18F-FDG-PET. The use of DBE will become important for determining the most appropriate treatment for gastrointestinal follicular lymphoma.

    DOI: 10.1055/s-0028-1119467

  • Duplication cyst of the small intestine found by double-balloon endoscopy A case report Reviewed

    Haruei Ogino, Toshiaki Ochiai, Norimoto Nakamura, Daisuke Yoshimura, Teppei Kabemura, Tetsuya Kusumoto, Hiroshi Matsuura, Akihiko Nakashima, Kuniomi Honda, Kazuhiko Nakamura

    World Journal of Gastroenterology   14 ( 24 )   3924 - 3926   2008.10

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    A 35-year-old man was admitted due to bloody stool and anemia. The bleeding source could not be detected by esophagogastroduodenoscopy or colonoscopy. Double balloon endoscopy (DBE) revealed a diverticulum-like hole in which coagula stuck in the ileum at 1 meter on the oral side from the ileocecal valve. The adjacent mucosa just to the oral side of the hole was elevated like a submucosal tumor. The lesion was considered the source of bleeding and removed surgically. It was determined to be a cyst with an ileal structure on the mesenteric aspect accompanying gastric mucosa. The diagnosis was a duplication cyst of the ileum, which is a rare entity that can cause gastrointestinal bleeding. In the present case, DBE was used to find the hemorrhagic duplication cyst in the ileum.

    DOI: 10.3748/wjg.14.3924

  • Gastric emptying in diabetic patients by the 13 C-octanoic acid breath test Role of insulin in gastric motility Reviewed

    Masahiro Matsumoto, Rie Yoshimura, Hirotada Akiho, Naomi Higuchi, Kunihisa Kobayashi, Noriaki Matsui, Kentaro Taki, Hiroyuki Murao, Haruei Ogino, Kenji Kanayama, Yorinobu Sumida, Takahiro Mizutani, Kuniomi Honda, Shigetaka Yoshinaga, Soichi Itaba, Hiromi Muta, Naohiko Harada, Kazuhiko Nakamura, Ryoichi Takayanagi

    Journal of gastroenterology   42 ( 6 )   469 - 474   2007.6

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    Background: Impairment of gastric emptying is well recognized in patients with diabetes mellitus (DM), especially long-standing insulin-dependent diabetes mellitus (IDDM). The aim of this study was to evaluate the cause of delayed gastric emptying in DM patients. Methods: In 16 controls, 16 non-insulin-dependent diabetes mellitus (NIDDM) patients and 23 IDDM patients, gastric emptying was studied using the
    13
    C octanoic acid breath test. Breath samples were taken before a test meal labeled with 100mg of
    13
    C octanoic acid, and at 15-min intervals over a 300-min period postprandially. Results: In all DM patients, the gastric emptying coefficient was lower than that in the controls (P < 0.05), and lag time and half-emptying time were significantly longer (P < 0.05). Both NIDDM and IDDM patients showed delayed
    13
    CO
    2
    excretion compared with the controls, but IDDM patients showed more delayed gastric emptying than NIDDM patients (P < 0.05). There were no significant differences in sex, HbA1c level, or the rate of neuropathy between the two groups. Conclusions: IDDM patients showed delayed gastric emptying compared with NIDDM patients, and the
    13
    C octanoic acid breath test is useful for evaluating DM patients with delayed gastric emptying.

    DOI: 10.1007/s00535-007-2031-2

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Presentations

  • UCにおけるオンボーのポジショニングを考える

    荻野 治栄

    オンボー発売1周年記念講演会in 長崎 

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    Event date: 2025.1

  • UCにおけるオンボーのポジショニングを考える

    荻野 治栄

    Voice of the Ulcerative Colitis Patients 

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    Event date: 2025.1

  • UCにおけるAdtのポジショニング

    荻野 治栄

    はりまIBD WEBフォーラム 

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    Event date: 2025.1

  • UCにおけるオンボーのポジショニングを考える

    荻野 治栄

    UC web Seminar 

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    Event date: 2024.12

  • 肝胆膵領域の疾患を合併した潰瘍性大腸炎の臨床的特徴の検討

    荻野 治栄

    第11回日本炎症性腸疾患学会 PD 

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    Event date: 2024.11

  • UCにおけるTNF阻害療法の意義と 病診連携について

    北九州IBD治療連携を考える会 

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    Event date: 2024.9

  • UCにおけるオンボーのポジショニングを考える

    荻野 治栄

    次世代UCスキルアップセミナー 

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    Event date: 2024.9

  • 便通異常症診療ガイドライン2023からひも解く慢性便秘症診療

    荻野 治栄

    慢性便秘症研究会 

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    Event date: 2024.8

  • クローン病の最新治療 炎症性腸疾患の病態に迫る

    荻野 治栄

    第45回 日本炎症・再生医学会 教育講演11   2024.7 

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    Event date: 2024.7

  • 潰瘍性大腸炎の病態について

    荻野 治栄

    沖縄IBD治療フォーラム 

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    Event date: 2024.7

  • 潰瘍性大腸炎治療におけるリンヴォックの有用性

    荻野 治栄

    UC Clinical Conference 

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    Event date: 2024.6

  • 各薬剤のUC治療ポジショニング

    荻野 治栄

    福岡UC治療ミーティング 

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    Event date: 2024.6

  • Mirikizumabへの期待と好適症例の検討 ~基礎・臨床の側面から~

    荻野 治栄

    Mirikizumab Discussion Seminar for All Kyushu University 

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    Event date: 2024.3

  • NON-TNF製剤の立場から

    荻野 治栄

    Ulcerative Colitis 全国WEB講演会 Multi-option時代のUC治療戦略 

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    Event date: 2024.3

  • 潰瘍性大腸炎における NON-TNF製剤の治療戦略

    荻野 治栄

    炎症性腸疾患の治療について考える会 

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    Event date: 2024.2

  • 潰瘍性大腸炎の治療について

    荻野 治栄

    潰瘍性大腸炎クリニカルカンファレンス in 沖縄 

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    Event date: 2024.1

  • クローン病診療について

    荻野 治栄

    飯塚 IBD Expert meeting 

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    Event date: 2023.12

  • 直腸粘膜バリア機能と潰瘍性大腸炎の関連について

    荻野 治栄

    第10回 日本炎症性腸疾患学会 ワークショップ 

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    Event date: 2023.12

  • 基礎から考える潰瘍性大腸炎の治療と課題

    荻野 治栄

    第116回 日本消化器内視鏡学会九州支部例会 ランチョンセミナー   2023.11 

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    Event date: 2023.11

  • 潰瘍性大腸炎治療における抗TNFα抗体を再考する

    荻野 治栄

    第54回日本吸収医学会 九州支部例会 ランチョンセミナー   2023.10 

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    Event date: 2023.10

  • 潰瘍性大腸炎の診断と治療、 生物学的製剤のポジショニングについて

    荻野 治栄

    潰瘍性大腸炎 Clinical Seminar in 福山 

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    Event date: 2023.1

  • IBD診療における内視鏡検査の意義

    荻野 治栄

    第36回 日本消化器内視鏡学会 九州セミナー   2023.1 

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    Event date: 2023.1

  • 潰瘍性大腸炎におけるインフリキシマブとウステキヌマブのポジショニングについて Invited

    荻野 治栄

    第120回 日本消化器病学会九州支部例会 ランチョンセミナー   2022.12 

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    Event date: 2022.12

  • 潰瘍性大腸炎の病態に関する免疫機序とUstekinumabについて

    Ulcerative Colitis Web Seminar 

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    Event date: 2021.9

  • 潰瘍性大腸炎における治療戦略 Invited

    荻野 治栄

    炎症性腸疾患の治療について考える会 

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    Event date: 2020.1

  • 診療報酬明細データベースにおける潰瘍性大腸炎抽出アルゴリズムの妥当性の検証

    荻野治栄、森久保拓、深浦啓太、奥井佑、Sean Gardiner 、杉山直伸 、吉井規敏、Haoqian Chen、Soko Setoguchi、中島直樹、小林拓

    JSIBD  2019.11 

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    Event date: 2019.11

    Language:Japanese  

    Venue:福岡市   Country:Japan  

  • Is the histological inflammation a predictor of future relapse in quiescent Ulcerative colitis?

    @Haruei Ogino, @Keita Fukaura, @Yuichiro Nishihara

    JGES  2019.5 

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    Event date: 2019.5 - 2019.6

    Language:Japanese   Presentation type:Symposium, workshop panel (public)  

    Venue:新高輪ホテル   Country:Japan  

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MISC

  • Usefulness of percutaneous endoscopic gastrostomy for supportive therapy of advanced aerodigestive cancer

    Haruei Ogino, Hirotada Akiho.

    World J Gastrointest Pathophysiol.   4 ( 4 )   119 - 125   2015

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    Authorship:Lead author  

  • Promising biological therapies for ulcerative colitis: A review of the literature

    Hirotada Akiho, Azusa Yokoyama, Shuichi Abe, Yuichi Nakazono, Masatoshi Murakami, Yoshihiro Otsuka, Kyoko Fukawa, Mitsuru Esaki, Yusuke Niina, Haruei Ogino.

    World J Gastrointest Pathophysiol   6 ( 4 )   219 - 227   2015

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    Authorship:Last author  

  • Hepatopancreatobiliary manifestations of inflammatory bowel disease

    Kazuhiko Nakamura, Tetsuhide Ito, Kazuhiro Kotoh, Eikichi Ihara, Haruei Ogino, Tsutomu Iwasa, Yoshimasa Tanaka, Yoichiro Iboshi, Ryoichi Takayanagi.

    Clinical Journal of Gastroenterology.   5 ( 1 )   1 - 8   2012

Professional Memberships

  • 日本炎症性腸疾患学会

  • 日本内科学会

  • 日本消化器病学会

  • 日本消化器内視鏡学会

  • 日本消化管学会

Committee Memberships

  • 内科学会   九州支部 事務局   Domestic

    2023.4 - 2025.3   

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    Committee type:Academic society

  • 日本炎症再生医学会   第45回 学会事務局補佐  

    2023 - 2024   

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    Committee type:Academic society

  • 日本消化管学会   便通異常症 ガイドライン作成委員   Domestic

    2022 - 2023   

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    Committee type:Academic society

Research Projects

  • 直腸環境の特殊性に着眼した潰瘍性大腸炎再燃機序の解明

    Grant number:23K07355  2023 - 2025

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Grant type:Scientific research funding

  • 直腸環境の特殊性からみる潰瘍性大腸炎の再燃機序

    Grant number:20K08389  2020 - 2022

    Japan Society for the Promotion of Science  Grants-in-Aid for Scientific Research  Grant-in-Aid for Scientific Research (C)

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    Authorship:Principal investigator  Grant type:Scientific research funding

Educational Activities

  • 九州大学医学部において、医学部3学年の「消化管・腹膜」の講義において、「食道疾患(1)」「胃・十二指腸腫瘍」を担当している。また、医学部4学年は臨床実習を始める前の臨床医学基本実習を受ける必要があるが、同学年に対して問診や腹部の診察を中心に実習指導を行っている。さらに、臨床の現場に出る前に必要な客観的臨床能力試験であるOSCEの腹部領域に対する試験監督を行っている。医学部6学年はクリニカルクラークシップとして病棟への実習を行うが、当科にローテーとする6学年に対してカリキュラムの作成を行い、臨床実習やレポート作成の指導を行っている。

Class subject

  • 消化管・腹膜

    2019.10 - Present   Second semester

Specialized clinical area

  • Biology / Medicine, Dentistry and Pharmacy / Internal Medicine / Gastroenterology

Clinician qualification

  • Preceptor

    日本内科学会

  • Preceptor

    The Japanese Society of Gastroenterology(JSGE)

  • Preceptor

    Japan Gastroenterological Endoscopy Society(JGES)

  • Preceptor

    日本消化管学会

  • Preceptor

    日本炎症性腸疾患学会

  • 癌治療認定医 指導責任者

    日本癌治療認定医機構

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Year of medical license acquisition

  • 2001

Notable Clinical Activities

  • 炎症性腸疾患の患者様の中には、治療抵抗性で難治の方や重症・劇症など重篤な方がいます。このような多くの患者さんを関連病院の先生からご紹介いただき治療にあたっている。もちろん、中には内科治療だけでは限界がある方もいるため、外科の先生と協力し適切な治療を提供できるように心がけている。また、消化管腫瘍(早期癌を含む)に対しても多くの関連病院の先生からご紹介いただき、内視鏡治療の適応がある場合には、非侵襲的な内視鏡治療である内視鏡的粘膜下層剥離術も積極的に行っている。