Curriculum Vitaes
Profile Information
- Affiliation
- School of Medicine Faculty of Medicine, Department of Advanced Endoscopy (formerly Department of Gastroenterology), Fujita Health University
- Degree
- 博士(医学）
- J-GLOBAL ID
- 200901011108502975
- researchmap Member ID
- 6000005568
患者さんの立場にたって、安全かつ最高の医療を提供できるよう努力します。
Research Interests
10Research Areas
1Committee Memberships
28-
Jul, 2023 - Present
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- Present
Awards
4-
May, 2000
Papers
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Journal of gastroenterology, Nov 18, 2025BACKGROUND: Owing to the rarity of metastatic tumors in the small bowel, their clinicopathological features, and prognostic factors remain poorly understood. This study aimed to clarify the clinicopathological features and factors associated with the prognosis of patients with small bowel metastasis from other organs in Japan. METHODS: We retrospectively examined 253 patients who were histopathologically diagnosed with small bowel metastases between January 2008 and December 2017 at multiple institutions in Japan. We identified the clinicopathological features of the condition and determined the factors associated with the prognosis of these patients. RESULTS: Obstructive symptoms were the most frequent clinical presentations (39% abdominal pain and 18% vomiting), while gastrointestinal bleeding was observed in 27% of patients. The diagnostic modalities included enteroscopy (33%), balloon-assisted enteroscopy (30%), and capsule endoscopy (13%). The most common primary tumor was lung cancer (38%), followed by colorectal cancer (18%), gastric cancer (9%), and malignant melanoma (6%). Surgical intervention, including tumor resection or bypass surgery, was performed in 79% of patients. The cumulative survival rates of patients at 12, 24, and 60 months were 49%, 36%, and 22%, respectively. Multivariate analysis identified surgery as a significant factor for improving overall survival (HR = 0.56, 95% CI 0.35-0.89, p = 0.01). CONCLUSIONS: The lung cancer is the most frequent primary tumor of metastatic tumors in the small bowel. Surgical intervention was associated with improved survival outcomes.
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Journal of gastroenterology, Oct 22, 2025BACKGROUND: Peutz-Jeghers syndrome (PJS), a rare genetic disorder characterized by hamartomatous gastrointestinal polyps, poses increased risks of various cancers. Despite the importance of early intervention, the optimal timing for jejunal-ileal polypectomy remains unclear owing to the limited number of comparative studies. METHODS: Herein, we conducted a nationwide survey in Japan and analyzed data from 184 patients with PJS identified through a two-stage sampling process. The initial screening of 2912 medical institutions yielded 1748 facilities, of which 1077 responded to the survey. Time-dependent Cox proportional hazards models and logistic regression analyses were used to examine the association between the timing of jejunal-ileal polypectomy and the risk of surgery for intussusception. RESULTS: Among 184 patients (47.0% women; mean age, 33.5 years), intussusception was the most common complication (67.7%). In the Cox proportional hazards analysis excluding surgeries within 1 year of diagnosis, early jejunal-ileal polypectomy was associated with a reduced risk of surgery for intussusception (adjusted hazard ratio, 0.17; 95% confidence interval [CI] 0.04-0.74, p = 0.018). Logistic regression analysis showed higher odds of surgery in the late treatment group compared with the early treatment group (adjusted odds ratio, 4.26; 95% CI 1.38-13.16, p = 0.012). CONCLUSIONS: Early jejunal-ileal polypectomy may reduce the risk of intussusception in patients with PJS. However, the need for frequent endoscopic procedures must be balanced considering patient burden. These findings support the importance of early intervention and highlight the need for optimized surveillance strategies that consider clinical effectiveness and patients' quality of life.
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Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 23(11) 1991-2000, Oct, 2025BACKGROUND & AIMS: Although biologic therapy has revolutionized the treatment of Crohn's disease (CD), surgery remains unavoidable in cases involving ileal complications. We aimed to evaluate the efficacy of biologics on proximal ileal lesions using balloon-assisted enteroscopy (BAE). METHODS: This open-label multicenter prospective study was conducted at tertiary referral centers in Japan. We enrolled 253 patients with active ileal CD who were treated with biologics (infliximab/adalimumab/ustekinumab/vedolizumab). BAE was performed at week 0 and week 26, and endoscopic findings were centrally assessed. We evaluated the rate of endoscopic remission (defined as having a maximum modified Simple Endoscopic Score for Crohn's disease <4) at week 26 and patient prognosis (CD-related hospitalization and surgery). RESULTS: At baseline, 74 patients (29.2%) had proximal ileal ulcerations without terminal ileal ulcerations. The second BAE showed that endoscopic remission was achieved in 91 patients (36.0%). Of the patients with complete ulcer healing of the terminal ileum, 28.6% (22/77) had residual ulcers in the proximal ileum. The rate of endoscopic remission in the proximal ileum (50.9%) was relatively lower compared with the colon (63.4%) and terminal ileum (56.7%), a trend consistently observed across all treatment agents. After a median follow-up of 134 weeks, residual ulcerations in the proximal ileum were associated with a poorer prognosis (P = .0126 for hospitalization and P = .0014 for surgery). CONCLUSIONS: A substantial proportion of patients with CD exhibited ulcerations in the proximal ileum, which correlated with a poorer prognosis. These lesions proved challenging to heal, regardless of the type of biologic used.
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Journal of gastrointestinal and liver diseases : JGLD, 34(3) 407-408, Sep 26, 2025
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JGH open : an open access journal of gastroenterology and hepatology, 9(7) e70209, Jul, 2025AIMS: The Japan COVID-19 Survey and the Questionnaire for Inflammatory Bowel Disease (J-DESIRE) identified multiple factors associated with anxiety regarding the novel coronavirus disease 2019 (COVID-19). However, no regional differences in anxiety were observed. In this post hoc analysis of J-DESIRE, we investigated the relationship between the municipal population size at the place of residence (MPSPR) and anxiety among patients with IBD in Japan during the COVID-19 pandemic. METHODS AND RESULTS: We analyzed 2958 questionnaires collected from patients with IBD aged ≥ 16 years between March 2020 and June 2021. The primary endpoint was the association between the visual analogue scale (VAS) scores of anxiety and MPSPR during the COVID-19 pandemic. The mean VAS score for anxiety was higher than the overall mean VAS score in municipalities with large and small populations, while it was lower in municipalities with medium populations. Therefore, we categorized the population into three groups based on MPSPR: ≤ 150 000, 150 001-1 000 000, and ≥ 1 000 001. The three groups had different background factors, contents of anxiety, and sources of information regarding therapeutic drugs. These differences may have led to differences in the degree and content of anxiety. CONCLUSIONS: We investigated the association between anxiety in Japanese patients with IBD and MPSPR nationwide during the COVID-19 pandemic in Japan. The results obtained in this analysis are useful not only in special situations such as the COVID-19 pandemic but also for considering regional differences in medical care.
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Addiction biology, 30(6) e70052, Jun, 2025In Japan, the establishment of diagnostic criteria for acute-on-chronic liver failure (ACLF) in 2022 has increased the focus on alcoholic hepatitis. Most hospitals in Japan lack specialized treatment units or psychiatrists for managing alcohol use disorders, leaving hepatologists to handle various aspects of the disease-a challenging task. This study retrospectively investigated the outcomes of alcoholic hepatitis in a typical Japanese hospital setting, stratified by ACLF diagnosis and other features, with the aim of identifying areas for possible improvement. We conducted a retrospective analysis of 88 patients hospitalized with alcoholic hepatitis, reviewing records for the diagnosis of ACLF or related conditions, development of delirium tremens (DT), risk factors, and patient outcomes. Patients meeting the Japanese criteria for ACLF or related conditions had significantly worse survival outcomes. DT developed in 13 patients, with low platelet counts and elevated γ-glutamyl transpeptidase levels identified as risk factors. Prophylactic oral benzodiazepines were found safe and significantly associated with preventing DT. Onset of DT during hospitalization did not measurably impact survival prognosis, but DT patients showed a tendency to break contact with our hospital and critical events may have been missed. While under hepatologist care, patients typically maintained sobriety, but relapse into alcohol-related health problems frequently occurred after follow-up was discontinued. In Japan, hepatologists may be missing important events with alcoholic hepatitis after follow-up discontinuation, especially in patients with DT. Therefore, integrated and collaborative care, particularly a psychosocial approach providing behavioural support, may reduce risk of relapse and improve patient prognosis. TRIAL REGISTRATION: All study protocols were reviewed and approved by the ethics committee at Fujita Health University School of Medicine (approval no. HM23-213).
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Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 37(6) 680-694, Jun, 2025OBJECTIVES: We aimed to determine the compliance, safety, and acceptance of colon capsule endoscopy (CCE) and small bowel capsule endoscopy (SBCE) in an out-of-clinic setting remotely supported by medical staff. METHODS: We enrolled 30 examinees (24 with CCE and six with SBCE) who had not undergone CE at six gastroenterological centers. All examinees were provided with instructions on equipment and bowel preparations. RESULTS: CCE was performed at home (n = 16) or at the workplace (n = 8). Compliance with data-recorder alerts was 100% for bowel preparation and 79% for equipment operation. Total capsule colonoscopy was achieved in 83.3%. The overall adequate endoscopic cleansing rate was 83.3%, and abnormalities, including colorectal polyps, were detected in 37.5%. CCE malfunction, such as the inability to automatically detect the small bowel mucosa occurred in one (4.2%). One experienced mild abdominal pain that required no treatment. Inquiries were present from half of the examinees. The proportions of examinees who desired and refused CCE at the next examination were 67% and 4%, respectively. SBCE was performed at home (n = 4) or at the workplace (n = 2). Compliance with the procedures was 100%. Whole small bowel images were recorded for all examinees. The overall adequate endoscopic clearness rate was 100%. One abnormality was detected. Inquiries were present from half of the examinees. There were no adverse events or malfunctions. The proportion of examinees who reported "quite easy" and "fairly easy" was 66%. CONCLUSION: CCE and SBCE with all procedures in the out-of-clinic setting supported by remote consultations were feasible. A multicenter prospective study of the safety and acceptance of capsule endoscopy examinations at home (HomeCam-J study) (jRCTs042220163).
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Gastrointestinal endoscopy, 101(5) 1051-1063, May, 2025BACKGROUND AND AIMS: We determined the factors influencing total capsule colonoscopy, adequate cleansing, and detectability of second-generation colon capsule endoscopy (CCE) for colorectal polyps or tumors (CRTs), adverse events, and acceptability. METHODS: Among 44 Japanese hospitals, 1,006 patients with suspected or documented colorectal diseases who underwent CCE were enrolled prospectively. RESULTS: The total capsule colonoscopy rate was 86.1%. Age younger than 63 years (adjusted odds ratio [aOR], 1.525), male sex (aOR, 1.496), inflammatory bowel disease (aOR, 1.889), lavage intake on Day -1 (aOR, 1.625), ≥1800 mL lavage intake on Day 0 (aOR, 0.595), prokinetics on Day 0 (aOR, 0.608), and ≥30 mL castor oil booster on Day 0 (aOR, 1.734) were significant independent predictors. The overall adequate cleansing rate was 65.5%. Constipation (aOR, 0.527), lavage intake on Day -1 (aOR, 1.822), laxative intake on Day -1 (aOR, 2.616), and ≥1900 mL lavage intake on Day 0 (aOR, 1.449) were significant independent predictors. The detection rates (95% confidence intervals) for patients with CRTs ≥6 mm and ≥10 mm were 92 (84-97) % and 89 (78-96) %, respectively. Inadequate cleansing in the ascending colon (aOR, 0.184), ≥6 mm CRT in the transverse colon (aOR, 4.703), and ≥6 mm CRT in the left-sided colon (aOR, 32.013) were significant independent predictors. CCE retention occurred in two patients (0.20%) requiring endoscopic and surgical interventions. In total, 63% of patients desired CCE for their next colonoscopy. CONCLUSIONS: CCE was relatively safe, well tolerated, and useful for detecting colorectal lesions when adequate bowel preparation was made.
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Journal of gastroenterology, 60(2) 263-264, Feb, 2025
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The Journal of dermatology, 52(2) e182-e183, Feb, 2025 Peer-reviewed
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Journal of gastroenterology, 60(1) 86-95, Jan, 2025BACKGROUND: A serum biomarker for diagnosing ulcerative colitis (UC) remains to be established. Although we recently reported an anti-integrin αvβ6 antibody (V6 Ab) for diagnosing UC with high sensitivity and specificity, no large-scale validation study exists. This study aimed to validate the diagnostic value of V6 Ab for UC using a nationwide multicenter cohort study. METHODS: We measured V6 Ab titers in patients definitively diagnosed with UC, Crohn's disease (CD), or other gastrointestinal disorders (OGDs). The primary outcome was the diagnostic value of V6 Ab. Secondary outcomes were factors associated with false-negative results in patients with UC and false-positive results in patients without UC and the heterogeneity of the diagnostic value of V6 Ab among the participating facilities. RESULTS: We enrolled 1241, 796, and 206 patients with UC, CD, and OGD, respectively, from 28 Japanese high-volume referral centers. The diagnostic sensitivity of V6 Ab for UC was 87.7%, and its specificities for CD and OGDs were 82.0% and 87.4%, respectively. Multivariable logistic regression analysis showed that false-negative results were associated with older age at the time of sample collection, current smokers, lower partial Mayo score, and not receiving advanced therapies in patients with UC, and false-positive results were associated with colonic CD in patients with CD. No factor was associated with false-positive results in patients with OGDs. There were no significant differences in the diagnostic value of V6 Ab among the centers. CONCLUSIONS: The diagnostic value of V6 Ab for UC was validated in the large-scale nationwide multicenter study.
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JAMA, Jul 22, 2024 Peer-reviewedImportance The clinical effects of risankizumab (a monoclonal antibody that selectively targets the p19 subunit of IL-23) for the treatment of ulcerative colitis are unknown. Objective To evaluate the efficacy and safety of risankizumab when administered as an induction and a maintenance therapy for patients with ulcerative colitis. Design, Setting, and Participants Two phase 3 randomized clinical trials were conducted. The induction trial was conducted at 261 clinical centers (in 41 countries) and enrolled 977 patients from November 5, 2020, to August 4, 2022 (final follow-up on May 16, 2023). The maintenance trial was conducted at 238 clinical centers (in 37 countries) and enrolled 754 patients from August 28, 2018, to March 30, 2022 (final follow-up on April 11, 2023). Eligible patients had moderately to severely active ulcerative colitis; a history of intolerance or inadequate response to 1 or more conventional therapies, advanced therapies, or both types of therapies; and no prior exposure to risankizumab. Interventions For the induction trial, patients were randomized 2:1 to receive 1200 mg of risankizumab or placebo administered intravenously at weeks 0, 4, and 8. For the maintenance trial, patients with a clinical response (determined using the adapted Mayo score) after intravenous treatment with risankizumab were randomized 1:1:1 to receive subcutaneous treatment with 180 mg or 360 mg of risankizumab or placebo (no longer receiving risankizumab) every 8 weeks for 52 weeks. Main Outcomes and Measures The primary outcome was clinical remission (stool frequency score ≤1 and not greater than baseline, rectal bleeding score of 0, and endoscopic subscore ≤1 without friability) at week 12 for the induction trial and at week 52 for the maintenance trial. Results Among the 975 patients analyzed in the induction trial (aged 42.1 [SD, 13.8] years; 586/973 [60.1%] were male; and 677 [69.6%] were White), the clinical remission rates at week 12 were 132/650 (20.3%) for 1200 mg of risankizumab and 20/325 (6.2%) for placebo (adjusted between-group difference, 14.0% [95% CI, 10.0%-18.0%], P &amp;lt; .001). Among the 548 patients analyzed in the maintenance trial (aged 40.9 [SD, 14.0] years; 313 [57.1%] were male; and 407 [74.3%] were White), the clinical remission rates at week 52 were 72/179 (40.2%) for 180 mg of risankizumab, 70/186 (37.6%) for 360 mg of risankizumab, and 46/183 (25.1%) for placebo (adjusted between-group difference for 180 mg of risankizumab vs placebo, 16.3% [97.5% CI, 6.1%-26.6%], P &amp;lt; .001; adjusted between-group difference for 360 mg of risankizumab vs placebo, 14.2% [97.5% CI, 4.0%-24.5%], P = .002). No adverse event signals were detected in the treatment groups. Conclusion and Relevance Compared with placebo, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis. Further study is needed to identify benefits beyond the 52-week follow-up. Trial Registration ClinicalTrials.gov Identifiers: NCT03398148 and NCT03398135
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Journal of gastrointestinal and liver diseases : JGLD, 33(2) 164-169, Jun 29, 2024 Peer-reviewedBACKGROUND AND AIMS: Early gastric cancers (EGCs) after Helicobacter pylori (H. pylori) eradication often appear as reddish depressed lesions (RDLs); the same features are also appeared in benign stomachs after eradication. We compared clinic-pathological and endoscopic features of benign and neoplastic RDLs after H. pylori eradication. METHODS: 228 neoplastic RDLs after H. pylori eradication were studied. All lesions were divided into neoplastic RDLs (differentiated carcinoma or adenoma, n=114) and benign RDLs (n=114) according to the histology. Clinical and pathological characteristics were compared in neoplastic and benign groups. Endoscopic diagnostic yields using the white light (WL) endoscopy, chromoendoscopy (CE) using indigo carmine dye and the magnifying endoscopy with narrow-band imaging (ME-NBI) were also evaluated in relation to the pathological diagnosis. RESULTS: Size of neoplastic RDLs was larger than that of benign RDLs (p<0.01). Sensitivity, specificity and accuracy for predicting pathological types of RDLs was 70.1%, 52.6% and 61.4% for the WL, 65.8%, 63.1% and 65.4% for the CE, while the ME-NBI scored better with the 88.6%, 88.6%, 99.1% and 93.9% of sensitivity, specificity and accuracy. The accuracy of the ME-NBI was 99.9% (113/114) in the benign RDLs and 89.4% (101/114) for the neoplastic RDLs. Undiagnosed neoplastic RDLs using the ME-NBI were associated with more differentiated tumors such as adenoma and well-differentiated adenocarcinoma (tub1) and the presence of an unclear demarcation line. CONCLUSIONS: ME-NBI is useful to diagnose RDLs after H. pylori eradiation, while some of neoplastic lesions are difficult to diagnose using the ME-NBI.
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Journal of gastroenterology, 59(5) 376-388, May, 2024 Peer-reviewedBACKGROUND: The clinicopathological features and prognosis of primary small bowel adenocarcinoma (PSBA), excluding duodenal cancer, remain undetermined due to its rarity in Japan. METHODS: We analyzed 354 patients with 358 PSBAs, between January 2008 and December 2017, at 44 institutions affiliated with the Japanese Society for Cancer of the Colon and Rectum. RESULTS: The median age was 67 years (218 males, 61.6%). The average tumor size was 49.9 (7-100) mm. PSBA sites consisted of jejunum (66.2%) and ileum (30.4%). A total of 219 patients (61.9%) underwent diagnostic small bowel endoscopy, including single-balloon endoscopy, double-balloon endoscopy, and capsule endoscopy before treatment. Nineteen patients (5.4%) had Lynch syndrome, and 272 patients (76.8%) had symptoms at the initial diagnosis. The rates for stages 0, I, II, III, and IV were 5.4%, 2.5%, 27.1%, 26.0%, and 35.6%, respectively. The 5-year overall survival rates at each stage were 92.3%, 60.0%, 75.9%, 61.4%, and 25.5%, respectively, and the 5-year disease-specific survival (DSS) rates were 100%, 75.0%, 84.1%, 59.3%, and 25.6%, respectively. Patients with the PSBA located in the jejunum, with symptoms at the initial diagnosis or advanced clinical stage had a worse prognosis. However, multivariate analysis using Cox-hazard model revealed that clinical stage was the only significant predictor of DSS for patients with PSBA. CONCLUSIONS: Of the patients with PSBA, 76.8% had symptoms at the initial diagnosis, which were often detected at an advanced stage. Detection during the early stages of PSBA is important to ensure a good prognosis.
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日本消化器病学会雑誌, 121(臨増総会) A190-A190, Mar, 2024
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JCO global oncology, 10 e2300392, Feb, 2024PURPOSE: Limited information is available regarding the characteristics and outcomes of stage IV small bowel adenocarcinoma (SBA) in Japan. This study examined the clinical and pathological characteristics and outcomes according to the treatment strategies in patients with stage IV SBA. METHODS: This retrospective observational study used the data of patients with jejunal or ileal adenocarcinoma collected by the Small Bowel Malignant Tumor Project of the Japanese Society for Cancer of the Colon and Rectum. Descriptive statistics were expressed as the mean (standard deviation) or median (range). Survival analysis was performed using Kaplan-Meier curves and pairwise log-rank tests. RESULTS: Data from 128 patients were analyzed. The treatment strategies were chemotherapy alone (26 of 128, 20.3%), surgery alone (including palliative surgery; 21 of 128, 16.4%), surgery + chemotherapy (74 of 128, 57.8%), and best supportive care (7 of 128, 5.5%). The median (range) overall survival was 16 (0-125) months overall, and 11 (1-38) months, 8 (0-80) months, 18 (0-125) months, and 0 (0-1) months for the chemotherapy, surgery, surgery + chemotherapy, and best supportive care groups, respectively. Three main categories of chemotherapeutic regimen were used: a combination of fluoropyrimidine and oxaliplatin (F + Ox), fluoropyrimidine and irinotecan (F + Iri), and single-agent fluoropyrimidine. Among patients treated with chemotherapy, the median (range) OS was 16 (1-106) months overall, and 17 (1-87) months, 29 (7-39) months, and 16 (1-106) months in patients treated with fluoropyrimidine, F + Iri, and F + Ox, respectively. CONCLUSION: Patients treated with surgery, chemotherapy, or both had a better prognosis than those who received best supportive care. Among patients who received chemotherapy, survival did not differ according to the chemotherapeutic regimen.
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Gastrointestinal endoscopy, 99(2) 245-253, Feb, 2024BACKGROUND AND AIMS: We prospectively determined the efficacy of flexible spectral imaging color enhancement (FICE) used with second-generation colon capsule endoscopy (CCE) for colorectal polyps and tumors (CRTs). METHODS: This study included optical colonoscopy within 4 months after CCE. Two colonoscopists independently reviewed CCE using white-light images (CCE-WL) and CCE using FICE images (CCE-FICE), respectively. Based on colonoscopic findings as the criterion standard, the diagnostic accuracy for CRTs was compared between CCE-WL and CCE-FICE. RESULTS: Of 89 enrolled patients (65 men and 24 women; 75 with CRTs including 36 with serrated lesions, 63 with adenomas, and 9 with adenocarcinomas), the per-patient detectability of CCE-FICE for the representative CRTs was significantly higher than that of CCE-WL: overall CRTs (CCE-WL, 79%; CCE-FICE, 88%; P = .0001), 6- to 9-mm CRTs (CCE-WL, 63%; CCE-FICE, 94%; P = .0055), and ≥6-mm CRTs (CCE-WL, 78%; CCE-FICE, 93%; P = .0159). The per-lesion sensitivity of CCE-FICE was significantly higher than that of CCE-WL for CRTs: overall (CCE-WL, 61%; CCE-FICE, 79%; P < .0001), <6 mm (CCE-WL, 53%; CCE-FICE, 69%; P < .0001), 6- to 9-mm CRTs (CCE-WL, 65%; CCE-FICE, 93%; P = .0007), slightly elevated CRTs (CCE-WL, 53%; CCE-FICE, 75%; P < .0001), tubular adenomas (CCE-WL, 61%; CCE-FICE, 79%; P < .0001), and serrated polyps (CCE-WL, 57%; CCE-FICE, 74%; P = .0022). Both modes detected all adenocarcinomas. No significant differences were found between CCE-WL and CCE-FICE of the per-lesion sensitivity for ≥10-mm CRTs (CCE-WL, 81%; CCE-FICE, 94%; P = .1138) or protruding CRTs (CCE-WL, 77%; CCE-FICE, 86%; P = .0614). Kappa coefficients for overall CRTs for CCE-WL and CCE-FICE were .66 and .64, respectively, which indicated substantial agreement. CONCLUSIONS: CCE-FICE improved the detection rates for all CRTs except adenocarcinomas, ≥10-mm polyps, and protruding polyps when compared with CCE-WL. (Clinical trial registration number: UMIN 000021125.).
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Journal of gastroenterology and hepatology, 39(2) 337-345, Feb, 2024BACKGROUND AND AIM: The PillCam patency capsule (PC) without a radio frequency identification tag was released to preclude retention of the small bowel capsule endoscope (CE) in Japan in 2012. We conducted a multicenter study to determine tag-less PC-related adverse events (AEs). METHODS: We first conducted a retrospective survey using a standardized data collection sheet for the clinical characteristics of PC-related AEs among 1096 patients collected in a prospective survey conducted between January 2013 and May 2014 (Cohort 1). Next, we retrospectively investigated additional AEs that occurred before and after Cohort 1 within the period June 2012 and December 2014 among 1482 patients (Cohort 2). RESULTS: Of the 2578 patients who underwent PC examinations from both cohorts, 74 AEs occurred among 61 patients (2.37%). The main AEs were residual parylene coating in 25 events (0.97%), PC-induced small bowel obstruction, suspicious of impaction, in 23 events (0.89%), and CE retention even after patency confirmation in 10 events (0.39%). Residual parylene coating was significantly associated with Crohn's disease (P < 0.01). Small bowel obstruction was significantly associated with physicians with less than 1 year of experience handling the PC and previous history of postprandial abdominal pain (P < 0.01 and P < 0.03, respectively). CE retention was ascribed to erroneous judgment of PC localization in all cases. CONCLUSIONS: This large-scale multicenter study provides evidence supporting the safety and efficiency of a PC to preclude CE retention. Accurate PC localization in patients without excretion and confirmation of previous history of postprandial abdominal pain before PC examinations is warranted (UMIN000010513).
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Molecular carcinogenesis, 63(2) 266-274, Feb, 2024Helicobacter pylori induces DNA methylation in gastric mucosa, which links to gastric cancer (GC) risk. In contrast, CpG island methylator phenotype (CIMP) is defined as high levels of cancer-specific methylation and provides distinct molecular and clinicopathological features of GC. The association between those two types of methylation in GC remains unclear. We examined DNA methylation of well-validated H. pylori infection associated genes in GC and its adjacent mucosa and investigated its association with CIMP, various molecular subtypes and clinical features. We studied 50 candidate loci in 24 gastric samples to identify H. pylori infection associated genes. Identified loci were further examined in 624 gastric tissue from 217 primary GC, 217 adjacent mucosa, and 190 mucosae from cancer-free subjects. We identified five genes (IGF2, SLC16A2, SOX11, P2RX7, and MYOD1) as hypermethylated in H. pylori infected gastric mucosa. In non-neoplastic mucosa, methylation of H. pylori infection associated genes was higher in patients with GC than those without. In primary GC tissues, higher methylation of H. pylori infection associated genes correlated with CIMP-positive and its related features, such as MLH1 methylated cases. On the other hand, GC with lower methylation of these genes presented aggressive clinicopathological features including undifferentiated histopathology, advanced stage at diagnosis. H. pylori infection associated DNA methylation is correlated with CIMP, specific molecular and clinicopathological features in GC, supporting its utility as promising biomarker in this tumor type.
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Journal of Gastroenterology, Jan 26, 2024
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Journal of Gastroenterology, Oct 13, 2023
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Journal of gastroenterology, 58(10) 1015-1029, Oct, 2023BACKGROUND: The degree of immune response to COVID-19 vaccination in inflammatory bowel disease (IBD) patients based on actual changes in anti-SARS-CoV-2 antibody titres over time is unknown. METHODS: Data were prospectively acquired at four predetermined time points before and after two vaccine doses in a multicentre observational controlled study. The primary outcome was humoral immune response and vaccination safety in IBD patients. We performed trajectory analysis to identify the degree of immune response and associated factors in IBD patients compared with controls. RESULTS: Overall, 645 IBD patients and 199 control participants were analysed. At 3 months after the second vaccination, the seronegative proportions were 20.3% (combination of anti-tumour necrosis factor [TNF]α and thiopurine) and 70.0% (triple combination including steroids), despite that 80.0% receiving the triple combination therapy were seropositive at 4 weeks after the second vaccination. Trajectory analyses indicated three degrees of change in immune response over time in IBD patients: high (57.7%), medium (35.6%), and persistently low (6.7%). In the control group, there was only one degree, which corresponded with IBD high responders. Older age, combined anti-TNFα and thiopurine (odds ratio [OR], 37.68; 95% confidence interval [CI], 5.64-251.54), steroids (OR, 21.47; 95%CI, 5.47-84.26), and tofacitinib (OR, 10.66; 95%CI, 1.49-76.31) were factors associated with persistently low response. Allergy history (OR, 0.17; 95%CI, 0.04-0.68) was a negatively associated factor. Adverse reactions after the second vaccination were significantly fewer in IBD than controls (31.0% vs 59.8%; p < 0.001). CONCLUSIONS: Most IBD patients showed a sufficient immune response to COVID-19 vaccination regardless of clinical factors. Assessment of changes over time is essential to optimize COVID-19 vaccination, especially in persistently low responders.
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日本大腸肛門病学会雑誌, 76(9) A86-A86, Sep, 2023
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Journal of Crohn's & colitis, 17(8) 1193-1206, Aug 21, 2023BACKGROUND AND AIMS: Perianal lesion is a refractory phenotype of Crohn's disease (CD) with significantly diminished quality of life. We evaluated the clinical characteristics of perianal lesions in newly diagnosed CD patients and the impact of perianal lesions on the quality of life in Japanese patients with CD. METHODS: Patients newly diagnosed with CD after June 2016 were included between December 2018 and June 2020 from the Inception Cohort Registry Study of Patients with CD (iCREST-CD). RESULTS: Perianal lesions were present in 324 (48.2%) of 672 patients with newly diagnosed CD. 71.9% (233/324) were male. The prevalence of perianal lesions was higher in patients aged <40 years versus ≥40 years, and it decreased with age. Perianal fistula (59.9%) and abscess (30.6%) were the most common perianal lesions. In multivariate analyses, male sex, age <40 years, and ileocolonic disease location were significantly associated with a high prevalence of perianal lesions, whereas stricturing behaviour and alcohol intake were associated with low prevalence. Fatigue was more frequent (33.3% vs 21.6%) and, work productivity and activity impairment-work time missed (36.3% vs 29.5%) and activity impairment (51.9% vs 41.1%) were numerically higher in patients with than those without perianal lesions. CONCLUSIONS: At the time of CD diagnosis, approximately half of the patients had perianal lesions; perianal abscesses and perianal fistulas were the most common. Young age, male sex, disease location, and behaviour are significantly associated with the presence of perianal lesions. The presence of perianal lesion was associated with fatigue and impairment of daily activities.
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New England Journal of Medicine, 388(26) 2444-2455, Jun 29, 2023 Peer-reviewed
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Journal of gastroenterology, 58(6) 602-603, Jun, 2023
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Fujita medical journal, 9(2) 163-169, May, 2023BACKGROUND: Anisakiasis is a parasitic disease caused by the consumption of raw or undercooked fish that is infected with Anisakis third-stage larvae. In countries, such as Japan, Italy, and Spain, where people have a custom of eating raw or marinated fish, anisakiasis is a common infection. Although anisakiasis has been reported in the gastrointestinal tract in several countries, reports of anisakiasis accompanied by cancer are rare. CASE PRESENTATION: We present the rare case of a 40-year-old male patient with anisakiasis coexisting with mucosal gastric cancer. Submucosal gastric cancer was suspected on gastric endoscopy and endoscopic ultrasonography. After laparoscopic distal gastrectomy, granulomatous inflammation with Anisakis larvae in the submucosa was pathologically revealed beneath mucosal tubular adenocarcinoma. Histological and immunohistochemical investigation showed cancer cells as intestinal absorptive-type cells that did not produce mucin. CONCLUSION: Anisakis larvae could have invaded the cancer cells selectively because of the lack of mucin in the cancerous epithelium. Anisakiasis coexisting with cancer is considered reasonable rather than coincidental. In cancer with anisakiasis, preoperative diagnosis may be difficult because anisakiasis leads to morphological changes in the cancer.
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Gastroenterological Endoscopy, 65(Suppl.1) 770-770, Apr, 2023
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Gastroenterological Endoscopy, 65(Suppl.1) 820-820, Apr, 2023
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Journal of gastroenterology, 58(3) 205-216, Mar, 2023BACKGROUND: Given the increasing health concerns for patients with inflammatory bowel disease (IBD), amidst the COVID-19 pandemic, we investigated the impact of the pandemic on the anxiety and behavioral changes in Japanese patients with IBD. METHODS: We analyzed 3032 questionnaires from patients with IBD, aged 16 years or older visiting 30 hospitals and 1 clinic between March 2020 and June 2021. The primary outcome was the score of the anxiety experienced by patients with IBD during the pandemic. RESULTS: Participants reported a median age of 44 years; 43.3% of the patients were women. Moreover, 60.6% and 39.4% were diagnosed with ulcerative colitis and Crohn's disease, respectively, with a median disease duration of 10 years. Participants indicated an average of disease-related anxiety score of 5.1 ± 2.5 on a ten-point scale, with a tendency to increase, 1 month after the number of infected persons per population increased. The top three causes for anxiety were the risk of contracting COVID-19 during hospital visits, SARS-CoV-2 infection due to IBD, and infection by IBD medication. Factors associated with anxiety were gender (women), being a homemaker, hospital visit timings, mode of transportation (train), use of immunosuppressive drugs, and nutritional therapy. Most patients continued attending their scheduled hospital visits, taking their medications, experienced the need for a family doctor, and sought guidance and information regarding COVID-19 from primary doctors, television, and Internet news. CONCLUSIONS: Patients with IBD experienced moderate disease-related anxiety due to the pandemic and should be proactively informed about infectious diseases to relieve their anxiety.
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Gastro hep advances, 2(8) 1056-1065, 2023BACKGROUND AND AIMS: Japan has experienced 8 waves of the coronavirus disease 2019 (COVID-19) outbreak over the past 3 years, resulting in an increasing number of deaths and incidence of severe infections. This study aimed to analyze the data from the Japanese inflammatory bowel disease (IBD) patients with COVID-19 registry (J-COSMOS) up to the eighth wave to investigate the clinical course of IBD patients with COVID-19 and factors contributing to disease severity. METHODS: In this multicenter, observational, cohort study, we analyzed a cohort of 1308 IBD patients diagnosed with COVID-19, enrolled across 77 participating facilities in the J-COSMOS registry from June 2020 to December 2022. Data on age, sex, IBD (classification, treatment, and activity), and COVID-19 (symptoms, severity, and treatment) were analyzed. RESULTS: The majority of patients (76%) were in clinical remission. According to the World Health Organization classification of COVID-19 severity, 98.4% of IBD patients had nonsevere disease, while 1.6% of patients had severe or critical disease. COVID-19 did not affect disease activity in most IBD patients. Stepwise logistic regression analysis revealed that high body mass index, and cerebrovascular disease were risk factors for severe COVID-19. Corticosteroids could affect COVID-19 severity, whereas anti-tumor necrosis factor α antibodies and thiopurines were associated with a reduced risk of severe COVID-19. No deaths were observed among IBD patients with COVID-19 registered in this cohort. CONCLUSION: The impact of COVID-19 on IBD disease activity and factors associated with COVID-19 severity were consistent with findings of previous reports. No deaths in Japanese patients with IBD were observed.
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PloS one, 18(5) e0286300, 2023BACKGROUND/AIM: Lymphoid follicles hyperplasia (LH) is sometimes observed in the normal colon as small, round, yellowish-white nodules. LH is associated with food hypersensitivity and bowel symptoms and histologically characterized as intense infiltration of lymphocytes or plasmacytes. It is suggested that LH represents inflammatory immune response in the colonic mucosa. We investigated the presence of LH in the normal colonic mucosa and its association with incidence of colorectal lesions including colorectal cancer, adenoma and hyperplastic polyp. PATIENTS/METHODS: 605 participants undergoing colonoscopy for various indications were enrolled. Presence of LH in the proximal colon (appendix, cecum and the ascending colon) was observed using the blue laser imaging (BLI) endoscopy, a new generation image enhanced endoscopy (IEE) system. LH was defined as well demarcated white nodules. Elevated LH with erythema was distinguished as LH severe. Association between presence of LH and occurrence of colorectal lesions was investigated. RESULTS: Prevalence of all colorectal lesions and adenoma were significantly lower in LH severe group compared to the LH negative group (P = 0.0008, 0.0009, respectively). Mean number of all colorectal lesions and adenoma were also lower in LH severe group compared to the LH negative group (P = 0.005, 0.003 respectively). The logistic regression with adjustment for gender and age demonstrated that presence of LH severe held significantly lower risk of all colorectal lesions (OR = 0.48, 95%CI = 0.27-0.86) and adenoma (OR = 0.47, 95%CI = 0.26-0.86). CONCLUSION: LH in the colonic mucosa visualized by IEE is useful endoscopic finding to predict risk of colorectal adenoma.
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Journal of gastroenterology and hepatology, 38(1) 87-93, Jan, 2023BACKGROUND AND AIM: In colorectal endoscopic submucosal dissection (ESD), post-ESD electrocoagulation syndrome (PECS) has been recognized as one of the major complications. There are no reports on the relationships between ESD findings and PECS. This study aims to evaluate the risk factors for PECS, including ESD findings such as muscularis propria exposure. METHODS: We performed a retrospective cohort study of patients who underwent colorectal ESD between January 2017 and December 2021 in Japan. The grade of injury to the muscle layer caused by ESD was categorized as follows: Grade 0, no exposure of muscularis propria; Grade 1, muscularis propria exposure; Grade 2, torn muscularis propria; and Grade 3, colon perforation. The risk factors for PECS, including injury to the muscle layer, were analyzed by univariate and multivariate analyses. RESULTS: Out of 314 patients who underwent colorectal ESD, PECS occurred in 28 patients (8.9%). The multivariate analysis showed that female sex (odds ratio [OR] 3.233; 95% confidence interval [95% CI]: 1.264-8.265, P = 0.014), large specimen size (≥ 40 mm) (OR 6.138; 95% CI: 1.317-28.596, P = 0.021), long procedure time (≥ 90 min) (OR 2.664; 95% CI: 1.053-6.742, P = 0.039), and Grade 1 or 2 injury to the muscle layer (OR 3.850; 95% CI: 1.090-13.61, P = 0.036) were independent risk factors for PECS. CONCLUSIONS: Injury to the muscle layer, such as exposure or tear, was identified as a novel independent risk factor for PECS. We should perform colorectal ESD carefully to avoid injuring the muscle layers.
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Journal of gastroenterology, 57(11) 867-878, Nov, 2022BACKGROUND: The Inception Cohort Registry Study of Patients with Crohn's Disease aimed to clarify clinical characteristics and disease course of newly diagnosed Crohn's disease patients in Japan throughout a 4-year period. Results from an interim analysis of the largest nation-wide registry study that covers approximately 1% of Crohn's disease patient population in Japan are reported. METHODS: This prospective, observational registry study was conducted at 19 tertiary centers in Japan. Patients newly diagnosed with Crohn's disease after June 2016 (age ≥ 16 years at informed consent) were enrolled between December 17, 2018 and June 30, 2020. Patient demographics, diagnostic procedures and categories, disease location and lesion behavior (Montreal classification) at the time of diagnosis were recorded. RESULTS: Of 673 patients enrolled, 672 (99.9%) were analyzed (458: men, 214: women), male-to-female ratio: 2.1, median age at diagnosis 25 (range 13-86) years; peak age of disease diagnosis: 20-24 years. Most common disease location was L3 (ileocolonic; 60.1%). Non-stricturing, non-penetrating (B1) disease was most common behavior (62.8%); 48.9% reported perianal lesions. Notably, age-wise analysis revealed disease phenotypes varied between patients aged < 40 and ≥ 40 years in terms of male-to-female ratio (2.5/1.3)/disease location (L3: 66.3%/37.0%)/disease behavior (B1: 66.4%/50.0%)/perianal lesion: (55.7%/20.5%) at Crohn's disease diagnosis, respectively. CONCLUSIONS: Interim analysis of this nation-wide Inception Cohort Registry Study of Patients with Crohn's Disease revealed the demographics and disease characteristics of newly diagnosed Crohn's disease patients in Japan and demonstrated that disease phenotype varied between patients aged < 40 and ≥ 40 years, serving as important information for management of individual patients.
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Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 34(7) 1278-1296, Nov, 2022
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Journal of gastroenterology and hepatology, 37(11) 2051-2059, Jul 15, 2022BACKGROUND AND AIM: Adrenomedullin is a bioactive peptide with many pleiotropic effects, including mucosal healing and immunomodulation. Adrenomedullin has shown beneficial effects in rodent models of inflammatory bowel disease and, more importantly, in clinical trials including patients with ulcerative colitis. We performed a successive clinical trial to investigate the efficacy and safety of adrenomedullin in patients with Crohn's disease (CD). METHODS: This was a multicenter, double-blind, placebo-controlled phase 2a trial that evaluated 24 patients with biologic-resistant CD in Japan. Patients were randomly assigned to three groups and were given an infusion of 10 or 15 ng/kg/min of adrenomedullin or placebo for 8 h per day for 7 days. The primary endpoint was the change in the CD activity index (CDAI) at 8 weeks. The main secondary endpoints included changes in CDAI from week 4 to week 24. RESULTS: No differences in the primary or secondary endpoints were observed between the three groups by the 8th week. Changes in CDAI in the placebo group gradually decreased and disappeared at 24 weeks, but those in the adrenomedullin-treated groups (10 or 15 ng/kg/min group) remained at steady levels for 24 weeks. Therefore, a significant difference was observed between the placebo and adrenomedullin-treated groups at 24 weeks (P = 0.043) in the mixed-effects model. We noted mild adverse events caused by the vasodilatory effect of adrenomedullin. CONCLUSION: In this trial, we observed a long-lasting (24 weeks) decrease in CDAI in the adrenomedullin-treated groups. Adrenomedullin might be beneficial for biologic-resistant CD, but further research is needed.
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Medicine, 101(28) e29386, Jul 15, 2022Gastric endoscopic submucosal dissection (ESD) is increasingly performed in patients receiving antithrombotic therapy. Second-look endoscopy (SLE) has been performed empirically in several clinical settings. We investigated whether SLE omission was associated with an increased risk of postESD bleeding in all patients, including those administered antithrombotic agents. Between July 2016 and June 2018, 229 patients were treated with a clinical pathway for gastric ESD that involved SLE on the day after ESD (SLE group). Between September 2018 and May 2020, 215 patients were treated using a clinical pathway that did not include SLE (nonSLE group). We retrospectively compared the incidence of postESD bleeding among the propensity score-matched cohorts and determined the risk factors for postESD bleeding using multivariate analysis. The propensity score-matched cohorts showed no significant differences in the incidence of postESD bleeding between the SLE (3.2%) and nonSLE (5.1%) groups. Multivariate analysis revealed that the presence of lesions in the lower gastric body (adjusted odds ratio [OR] 2.17, 95% confidence interval [CI] 1.06-4.35, P.03) was a significant risk factor for postESD bleeding during admission, whereas resected specimen size ≥ 40 mm (adjusted OR 3.21, 95% CI 1.19-8.19, P.02) and antiplatelet therapy (adjusted OR 4.16, 95% CI 1.47-11.80, P.007) were significant risk factors after discharge. Complete omission of SLE after gastric ESD does not increase postESD bleeding in clinical practice.
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Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society, 34(5) 1075-1075, Jul, 2022
Misc.
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Gastroenterological Endoscopy, 67(Suppl.1) 754-754, Apr, 2025
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日本消化器病学会雑誌, 122(臨増総会) A80-A80, Mar, 2025
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日本消化器病学会雑誌, 122(臨増総会) A82-A82, Mar, 2025
Books and Other Publications
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羊土社, Oct 15, 2024 (ISBN: 9784758110853)
Presentations
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第16回日本炎症性腸疾患学会学術集会, Aug 22, 2025
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第109回日本消化器内視鏡学会総会, May 9, 2025
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第111回日本消化器病学会総会, Apr 25, 2025
Teaching Experience
7Professional Memberships
12Research Projects
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Grants-in-Aid for Scientific Research, Japan Society for the Promotion of Science, Apr, 2022 - Mar, 2025
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Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C), Japan Society for the Promotion of Science, Apr, 2022 - Mar, 2025
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Advanced medical care B, Ministry of Health, Labour and Welfare, Feb, 2021 - Jun, 2024
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令和6年度 医療機器等研究成果展開事業（開発実践タイプ）, 国立研究開発法人日本医療研究開発機構（AMED), Jun, 2024
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令和３年度難治性疾患実用化研究事業, 国立研究開発法人日本医療研究開発機構（AMED), May, 2021 - Mar, 2024