Toshifumi Hibi

Kitasato University, Edo, Tōkyō, Japan

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Publications (765)3817.54 Total impact

  • Gastroenterology 08/2015; DOI:10.1053/j.gastro.2015.08.044 · 13.93 Impact Factor
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    ABSTRACT: Background and AimWe recently conducted a randomized placebo-controlled trial on the efficacy and safety of rikkunshito, a standardized Japanese herbal medicine, for the treatment of functional dyspepsia (FD). The present post-hoc study aimed to evaluate the differences in clinical characteristics between responders and non-responders among FD patients who received rikkunshito for 8 weeks.Methods Rikkunshito responders were defined by using a global patient assessment. Candidate predictors included age, gender, smoking, alcohol consumption, body mass index, comorbidity, Helicobacter pylori infection, plasma levels of acyl ghrelin and des-acyl ghrelin, severity of dyspeptic symptoms, FD subgroup, previous medication, and the type of recruiting institution (clinic or hospital). We calculated hazard ratios (HRs) by using Cox regression analysis with the factors that were indicated to be associated with responders.ResultsWe assigned 83 and 42 patients to responder and non-responder categories, respectively. Lack of alcohol consumption (HR, 2.04; 95% confidence interval [CI], 1.08–3.88) and low plasma des-acyl ghrelin levels (<177 fmol/mL; HR, 2.42; 95% CI, 1.24–4.73) were significantly associated with the efficacy of rikkunshito. Lack of alcohol consumption was associated with the efficacy of rikkunshito especially among H. pylori-infected participants. On the other hand, the low plasma des-acyl ghrelin was associated with the efficacy of rikkunshito especially among H. pylori-negative participants.ConclusionsA low baseline level of plasma des-acyl ghrelin was associated with an increased treatment efficacy of rikkunshito against FD. Lack of alcohol consumption was also clinically useful for predicting the response to rikkunshito. This article is protected by copyright. All rights reserved.
    Journal of Gastroenterology and Hepatology 08/2015; DOI:10.1111/jgh.13074 · 3.63 Impact Factor
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    ABSTRACT: First reported in 1955, Cronkhite-Canada syndrome (CCS), a rare syndrome characterized by ectodermal abnormalities and inflammatory changes of the gastrointestinal tract mucosa, has been associated with a poor prognosis and life-threatening malignant complications. In a large population survey, we endeavored to characterize the course and treatment outcome of CCS through clinical and endoscopic assessment, and to explore its optimal treatment and surveillance strategy. A retrospective analysis of 210 patients with CCS was conducted via a questionnaire-based nationwide survey of 983 teaching hospitals located throughout Japan. We assessed clinical features, endoscopic findings, treatments used, and short- and long-term outcomes. The average age at diagnosis was 63.5 years. In all cases, upper or lower gastrointestinal tract polyposis was confirmed, accompanied by characteristic ectodermal abnormalities. Of the treatments used, oral corticosteroids (30-49 mg/day) were the most effective treatment for active disease, with adjunctive nutritional support considered beneficial. With corticosteroid treatment, abdominal symptoms were relieved within a few months, whereas polyp regression often required more than 6 months. Maintenance of endoscopic remission with or without steroids for 3 years significantly lowered the development of CCS-related cancer, compared with relapsers or nonresponders, underscoring the importance of sustained endoscopic remission for cancer prevention. The prognosis of CCS has greatly improved through the use of improved medical treatment. Although CCS continues to be relentlessly progressive, carrying a high cancer risk, a sufficient dose and duration of corticosteroid therapy accompanied by nutritional support and periodic endoscopic surveillance appears to improve its natural history.
    Journal of Gastroenterology 07/2015; DOI:10.1007/s00535-015-1107-7 · 4.02 Impact Factor
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    ABSTRACT: We aimed to clarify the efficacy, safety, and factors associated with remission on dose escalation in patients with Crohn's disease showing loss of response (LOR) to infliximab treatment of 5 mg/kg at 8-week intervals in a clinical trial. Thirty-nine patients with LOR to 5 mg/kg infliximab therapy started treatment with 10 mg/kg per 8 weeks. LOR was defined as both a Crohn's Disease Activity Index of ≥175 at 8 weeks after infusion of 5 mg/kg infliximab and a Crohn's Disease Activity Index increase of ≥50 from 4 to 8 weeks after infusion. At week 8 after the first infusion of 10 mg/kg, median (95% confidence interval) reduction in Crohn's Disease Activity Index of 33 patients evaluated was 95.0 (70.0-134.0), meeting the primary endpoint. Remission rate at week 40 was 41% (16 of 39), with correlation noted between remission achievement and serum infliximab level (P = 0.036). Univariate analysis revealed that "infliximab trough level ≥1 µg/mL," "interleukin 6 level ≤2.41 pg/mL," and "albumin level ≥3.8 g/dL" before dose escalation were significantly associated with remission at week 40 (P = 0.017, P = 0.011, and P = 0.019, respectively), and these variables were correlated with each other (all: P < 0.001). The cutoff infliximab level for remission was 0.42 µg/mL in receiver operating characteristic curve analysis. No adverse events related to dose escalation were observed. Doubling the infliximab dose safely led to remission in patients with Crohn's disease with LOR to 5 mg/kg treatment. Remission was associated with pre-escalation levels of infliximab, interleukin 6, and albumin. Our findings suggest that dose escalation while maintaining a certain level of infliximab is important in achieving remission.
    Inflammatory Bowel Diseases 07/2015; DOI:10.1097/MIB.0000000000000475 · 5.48 Impact Factor
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    ABSTRACT: Infliximab (IFX) is one of the treatments of choice for corticosteroid-refractory and corticosteroid-dependent ulcerative colitis (UC). A high serum trough level of IFX (TL) is reported to be associated with sustained efficacy during maintenance treatment. As part of a phase 3 randomized controlled trial of IFX in UC, we assessed the predictive value of the first TL at week 2 for short- and long-term response. Patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients with evidence of a response by week 8 continued treatment at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Post hoc analysis was then performed for TL and clinical outcomes. Clinical response rate at week 8, the primary end point, was significantly higher in the IFX group than placebo (p = 0.005). The incidence of adverse events between groups was similar. Week 2 TL was significantly associated with a 14-week clinical activity index (CAI) remission. In multiple logistic regression analysis, the week 2 TL-to-CAI ratio (TL/CAI, odds ratio 8.07; 95 % confidence interval 2.84-27.07, p < 0.001) was an independent factor correlating with 14-week CAI remission. The week 2 TL and TL/CAI were also significantly associated with 30-week mucosal healing. IFX was confirmed to be effective and safe in this population. Our results suggest that the first TL at week 2, in combination with clinical evaluation, is useful for predicting both short- and long-term outcomes, allowing an earlier decision between continuing IFX or switching to other options.
    Journal of Gastroenterology 07/2015; DOI:10.1007/s00535-015-1102-z · 4.02 Impact Factor
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    ABSTRACT: Cytoapheresis (CAP) therapy is widely used in ulcerative colitis (UC) patients with moderate to severe activity in Japan. The aim of this study is to predict the need of operation after CAP therapy of UC patients on an individual level using an artificial neural network system (ANN). Ninety UC patients with moderate to severe activity were treated with CAP. Data on the patients' demographics, medication, clinical activity index (CAI) and efficacy of CAP were collected. Clinical data were divided into training data group and validation data group and analyzed using ANN to predict individual outcomes. The sensitivity and specificity of predictive expression by ANN were 0.96 and 0.97, respectively. Events of admission, operation, and use of immunomodulator, and efficacy of CAP were significantly correlated to the outcome. Requirement of operation after CAP therapy was successfully predicted by using ANN. This newly established ANN strategy would be used as powerful support of physicians in the clinical practice.
    PLoS ONE 06/2015; 10(6):e0131197. DOI:10.1371/journal.pone.0131197 · 3.23 Impact Factor
  • Annals of Oncology 06/2015; 26(suppl 4). DOI:10.1093/annonc/mdv233.136 · 6.58 Impact Factor
  • PLoS ONE 05/2015; 10(5):e0125664. DOI:10.1371/journal.pone.0125664 · 3.23 Impact Factor
  • Journal of Hepatology 04/2015; 62:S299. DOI:10.1016/S0168-8278(15)30230-0 · 10.40 Impact Factor
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    ABSTRACT: Infliximab is an efficacious agent used for the induction and maintenance of remission in Crohn's disease (CD), and recent studies suggested that it may also prevent the recurrence of this disease after surgery. The present study was performed to assess the efficacy and safety of infliximab in the postoperative setting, and to identify whether combination treatment with thiopurines had any additional beneficial effect as compared to mono-therapy. We performed a retrospective cohort study to compare the efficacy of infliximab mono-therapy and combination treatment with a thiopurine in preventing recurrence after surgery. Forty-one patients who received infliximab as maintenance treatment following surgery from May 2002 to April 2010 were identified. Twenty-four were naive to infliximab, and 17 who underwent surgery during infliximab treatment were continued on it following surgery. The median follow-up period was 27 months (range 12-66 months). All patients continued infliximab as maintenance treatment, but 10 required dose intensification due to clinical recurrence. Kaplan-Meier analysis demonstrated that the use of concomitant thiopurine was correlated with the continuation of infliximab treatment at an 8-week interval (log-rank test p = 0.018). The rate of adverse event was 9.8% with no patient experiencing severe adverse reactions. Infliximab appears to be safe and it prevented clinical recurrence after surgery. Concomitant thiopurine use predicted response toward continuation of therapy at an 8-week interval. Prospective controlled studies to assess the efficacy of combination treatment in the postoperative setting are warranted. © 2015 S. Karger AG, Basel.
    Digestion 03/2015; 91(3):233-238. DOI:10.1159/000375302 · 2.03 Impact Factor
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    ABSTRACT: Inflammatory bowel disease (IBD) was previously thought to be rare in Asia, but emerging data indicate rising incidence and prevalence of IBD in the region. The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region.(1) The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field. This article is protected by copyright. All rights reserved.
    Journal of Gastroenterology and Hepatology 03/2015; DOI:10.1111/jgh.12956 · 3.63 Impact Factor
  • Journal of Gastroenterology and Hepatology 03/2015; DOI:10.1111/jgh.12958 · 3.63 Impact Factor
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    ABSTRACT: Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life. Copyright © 2015 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
    Clinical nutrition (Edinburgh, Scotland) 01/2015; DOI:10.1016/j.clnu.2015.01.003 · 3.94 Impact Factor
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    ABSTRACT: The hepatocyte growth factor (HGF)/c-Met pathway has attracted attention in the formation of malignant tumors, as HGF secreted from the microcirculatory components as well as residing macrophages has been suggested to act on the c-Met receptors of cancer cells to decrease apoptosis and increase proliferation, invasion, and metastasis. The present study was undertaken to elucidate the interaction of the gastric, hepatic, and pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma induced by Helicobacter heilmannii infection with c-Met and HGF. C57BL/6 female mice, infected with H. heilmannii for 3 months were used. The localization of the HGF, c-Met, and HGF activator immunoreactivities was observed by the indirect immunohistochemical methods. In addition, the effect of c-Met antibody and c-Met inhibitor, PHA-665752, was also investigated. c-Met immunoreactivity was found in the lymphocytes composing the MALT lymphoma, and HGF immunoreactivity was recognized mostly in the endothelial cells and macrophages in the MALT lymphoma. HGFA was localized on mesenchymal cells other than the lymphocytes. The administration of the antibody against c-Met or the c-Met inhibitor to the infected mice induced the significant suppression of hepatic and pulmonary MALT lymphoma, while the gastric MALT lymphoma showed only a tendency to decrease in size, while the active caspase 3 positive cells markedly decreased in the gastric, hepatic, and pulmonary MALT lymphoma after the treatment with the c-Met antibody or the c-Met antagonist. HGF and c-Met pathway were suggested to contribute to the lymphomagenesis in the MALT lymphoma after H. heilmannii infection. © 2014 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.
    Journal of Gastroenterology and Hepatology 12/2014; 29 Suppl S4(S4):70-76. DOI:10.1111/jgh.12776 · 3.63 Impact Factor
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    ABSTRACT: Previous studies have suggested that the human leukocyte antigen (HLA) is involved in the etiology of Crohn's disease (CD); however, few reports are available on the association between HLA class I antigens and CD in Japan. In this study, we performed association analysis of HLA class I antigens in CD using 208 Japanese patients and 384 healthy controls. We identified novel positive associations between CD and HLA-A*02:01 (odds ratio (OR)=1.64, P=0.016) and HLA-A*02:07 (OR=2.31, P=0.0067) and confirmed previously reported positive associations between CD and HLA-Cw*14:02 (OR=2.18, P=0.0021) and HLA-B*51:01 (OR=1.70, P=0.033). We also identified novel negative associations between CD and HLA-A*24:02 (OR=0.60, P=0.0047) and HLA-B*07:02 (OR=0.38, P=0.0041). Although the associations were not significant after full Bonferroni correction, we suggested that HLA class I genes have dual functions, susceptibility and resistance in controlling the development of CD.Genes and Immunity advance online publication, 6 November 2014; doi:10.1038/gene.2014.61.
    Genes and Immunity 11/2014; 16(1). DOI:10.1038/gene.2014.61 · 3.79 Impact Factor
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    ABSTRACT: Background: We evaluated the clinical efficacy of adalimumab (ADA) for Crohn's disease (CD) and analyzed predictive factors for clinical remission and long-term prognosis. Methods: We retrospectively reviewed the medical records of 45 patients treated with ADA for CD at Keio University Hospital between October 2010 and March 2014. Clinical remission was defined as a Harvey-Bradshaw index of <= 4. Results: Twenty-eight of 45 patients (62.2%) achieved clinical remission at week 4. Among these 28 patients, 18 patients (64.3%) maintained clinical remission at week 26, and among these, 16 patients (88.9%) maintained clinical remission at week 52. Absence of a history of bowel resection and absence of prior anti-tumor necrosis factor (anti-TNF) therapy were significant predictive factors for clinical remission at week 4 upon multivariate logistic regression analyses. Younger age and a disease duration of <= 3 years correlated with clinical remission at week 26 upon univariate analyses. Patients without a history of bowel resection showed significantly better long-term prognosis than those with a history of bowel resection (p = 0.01). None of the patients contracted a serious infectious disease. Conclusions: Younger age, shorter duration of disease, being naive to anti-TNF antagonists, and absence of a history of bowel resection were associated with the efficacy of ADA in CD patients. (C) 2014 S. Karger AG, Basel
    Digestion 10/2014; 90(2):130-6. DOI:10.1159/000365783 · 2.03 Impact Factor
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    ABSTRACT: Background & Aims: Behçet’s disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçet’s disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor ɑ, in patients with intestinal Behçet’s disease who were refractory to corticosteroid and/or immunomodulator therapies. Methods The study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy endpoint was the percentage of patients with scores of ≤1 for GI symptom and endoscopic assessments at week 24. Secondary endpoints included complete remission and resolution of non-GI Behçet’s-related symptoms. Results Nine patients (45%) had GI symptom and endoscopic assessment scores ≤1 at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two-thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9/13 patients (69%) taking steroids at baseline were able to taper (n=1) or completely discontinue steroids (n=8) during the study. No new safety signals were observed. Conclusions Adalimumab is a potentially effective treatment for intestinal Behçet’s disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671.
    Clinical Gastroenterology and Hepatology 09/2014; 13(5). DOI:10.1016/j.cgh.2014.08.042 · 6.53 Impact Factor
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    ABSTRACT: Background and aims Leukocytapheresis is an extracorporeal therapy for ulcerative colitis. However, no large-scale study on leukocytapheresis has been reported. This large-scale, prospective, observational study aimed to evaluate the treatment outcomes of leukocytapheresis for active ulcerative colitis in clinical practice. Methods Patients with active ulcerative colitis treated with leukocytapheresis using a Cellsorba E column between May 2010 and December 2012 were enrolled from 116 medical facilities in Japan. Results A total of 847 patients were enrolled, and 623 were available for efficacy analysis. Out of 847 patients, 80.3% of the patients had moderate to severe disease activity, and 67.6% were steroid refractory. As concomitant medications, 5-aminosalicylic acids, corticosteroids, and thiopurines were administered to 94.8%, 63.8%, and 32.8% of the patients, respectively. In addition, infliximab and tacrolimus were concomitantly used in 5.8% and 12.3%, respectively. Intensive leukocytapheresis (≥ 4 leukocytapheresis sessions within the first 2 weeks) was used in > 70% of the patients. Adverse events were seen in 10.3% (87/847), which were severe in only 5 patients (0.6%). Any concomitant medications did not increase the incidence of adverse events. Intensive leukocytapheresis was as safe as the conventional weekly procedure. The overall clinical remission rate was 68.9% (429/623), and the mucosal healing rate was 62.5% (145/232). Clinical remission was achieved more frequently and rapidly in the intensive group than in the weekly group. Conclusions This large-scale study indicates that leukocytapheresis, including intensive procedure, is a safe and effective therapeutic option for active ulcerative colitis.
    Journal of Crohn s and Colitis 09/2014; 8(9). DOI:10.1016/j.crohns.2014.01.027 · 3.56 Impact Factor
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    ABSTRACT: Background and aims: Adalimumab has been shown to be effective and well tolerated in patients with Crohn’s disease. This analysis reports the results of a cohort of Japanese patients with moderate to severe Crohn’s disease who were evaluated for up to 3 years to assess the long-term use of adalimumab. Methods: The study consisted of a double-blind part and an open-label part. Patients were included either in the 52-week double-blind, placebo-controlled part of the study followed by a 96-week open-label extension or in the open-label part from the beginning or in the event of a flare. Patients were treated with adalimumab and evaluated for up to 148 weeks as 3 data cohorts: the all-adalimumab cohort (patients receiving ≥1 injection of adalimumab), the 148-week follow-up subcohort (patients who completed 148 weeks of follow-up after the first adalimumab dose), and the dose-escalation subcohort (patients receiving adalimumab doses that increased to 80 mg every other week). Results: In the all-adalimumab cohort (n = 79), clinical remission rates were approximately 30% after 36 weeks of exposure to adalimumab and for the remainder of the study (35%, 33%, and 28% for weeks 48, 108, and 144, respectively). An improvement in quality of life was also maintained over the same period. In the dose-escalation subcohort (n = 40), the clinical remission rate was 75% (6/8) 48 weeks after dose escalation. Adalimumab was tolerated, and no deaths were reported. Conclusions: Adalimumab is effective for maintaining long-term clinical remission in Japanese patients with moderate to severe Crohn’s disease (NCT00445432).
    Journal of Crohn s and Colitis 05/2014; 8(11). DOI:10.1016/j.crohns.2014.04.012 · 3.56 Impact Factor
  • Gastrointestinal Endoscopy 05/2014; 79(5):AB401. DOI:10.1016/j.gie.2014.02.1016 · 4.90 Impact Factor

Publication Stats

10k Citations
3,817.54 Total Impact Points

Institutions

  • 2009–2015
    • Kitasato University
      • Center for Advanced IBD Research and Treatment
      Edo, Tōkyō, Japan
    • Tokyo Medical and Dental University
      • Department of Gastroenterology and Hepatology
      Edo, Tōkyō, Japan
  • 1970–2015
    • Keio University
      • • Department of Internal Medicine
      • • School of Medicine
      Edo, Tōkyō, Japan
  • 2013
    • Keiyu Hospital
      Yokohama, Kanagawa, Japan
  • 2012
    • University of Washington Seattle
      • Division of Gastroenterology
      Seattle, Washington, United States
    • Kumamoto Municipal Citizens Hospital
      Kumamoto, Kumamoto Prefecture, Japan
    • Nihon Institute of Medical Science
      Saitama, Saitama, Japan
  • 2004–2012
    • Tokyo Dental College
      • Department of Internal Medicine
      Tiba, Chiba, Japan
  • 2005–2009
    • Eiju General Hospital
      Edo, Tōkyō, Japan
  • 2008
    • JCR Pharmaceuticals Co., Ltd.
      Ashiya, Hyōgo, Japan
    • Hosei University
      • Faculty of Bioscience and Applied Chemistry
      Edo, Tōkyō, Japan
  • 2006–2007
    • Tachikawa Hospital
      Edo, Tōkyō, Japan
    • Tokai University
      • School of Medicine
      Hiratuka, Kanagawa, Japan
  • 2003
    • Juntendo University
      Edo, Tōkyō, Japan
    • Hyogo College of Medicine
      • Department of Gastroenterology
      Nishinomiya, Hyogo-ken, Japan