研究者業績
基本情報
- 所属
- 藤田医科大学 医学部 医学科 先端光学診療学講座
- 学位
- 博士(医学）
- J-GLOBAL ID
- 200901011108502975
- researchmap会員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。
研究キーワード
8研究分野
1委員歴
28-
2024年2月 - 現在
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2023年2月 - 現在
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2022年9月 - 現在
受賞
4-
2022年10月
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2019年10月
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2015年10月
論文
270-
The Journal of dermatology 2024年9月30日 査読有り
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JAMA 2024年7月22日 査読有りImportance 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 < .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 < .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 2024年6月29日 査読有りBACKGROUND 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 2024年5月 査読有りBACKGROUND: 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 2024年3月
MISC
1258-
INNERVISION 22(10) 31-36 2007年9月2007年1月に、超音波造影剤Sonazoid(ソナゾイド)(第一三共社製)が販売開始となった。Levovist(バイエル薬品社製)が、1999年9月に販売開始されて以来わが国で新規の超音波造影剤が発売されたのは8年ぶりのことである。ソナゾイドを用いた造影エコー法が、胆・膵疾患の診断においてどのような有用性を有するかは今後の検討を待つ必要があり、結論めいたことを述べる段階ではないと考える。したがって、本稿では、ソナゾイドを胆・膵疾患の診断に用いた現段階での印象を述べることになる。また当科(筆者)では、超音波内視鏡(EUS)を用いた診断が大部分を占めることから、主に造影EUS(CE-EUS)について言及する。ソナゾイドの添付文書によると、効能・効果は"超音波検査における肝腫瘤性病変の造影"とされている。したがって、本稿で述べる胆・膵疾患の診断に対してソナゾイドを使用することは、"適応外使用"に当たる。適応外使用に関しては、各施設におけるIRB(institutional review board)などの承認が必要であることは当然のことである。(著者抄録)
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日本消化器病学会雑誌 104(臨増大会) A336-A336 2007年9月
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日本消化器病学会雑誌 104(臨増大会) A412-A412 2007年9月
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Journal of gastroenterology and hepatology 22(9) 1435-42 2007年9月 査読有りBackground and Aim: In Japan, screening examination with photofluorography is widely performed to reduce the mortality due to gastric cancer. The possibility of a future decline in gastric cancer cases and changes in its characteristics is suggested. The aim of this study was to examine the usefulness of direct radiology as a general health screening technique and the historical changes of gastric cancer in Japan. Methods: This study involved 936 patients with gastric cancer whose carcinomas were detected by direct radiology as part of a general health screening at the Aichi Prefectural Center for Health Care from 1970 to 2000. We studied the prevalence of gastric carcinoma, its prognosis, differences between the two histological types of carcinoma and historical changes. Results: The age-adjusted cancer detection rate slightly decreased. Comparing two histological types, diffuse-type carcinoma cases relatively increased. Intestinal-type carcinomas increased in the lower portion of the stomach, whereas diffuse-type increased in the upper portion. The 5-year survival rate was 92.7% for intestinal-type carcinoma and 84.8% for diffuse-type. Diffuse-type carcinomas were further progressed than intestinal-type when detected by direct radiology; however, detection of diffuse-type improved, so the percentage of early gastric cancer of diffuse type significantly increased, and the survival rate significantly improved, from 70.4% to 90.5%. Conclusion:The prevalence of gastric cancer has been decreasing, but the proportion of diffuse-type carcinoma localized in the upper portion of the stomach has been increasing in Japan.
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European journal of immunology 37(8) 2309-16 2007年8月 査読有りAcetate is a principal short chain fatty acid produced by bacterial fermentation in the colon and a major end product of alcohol metabolism. In the present study, we assessed the effects of acetate on T cell activation and found that acetate inhibited NFAT activation but not NF-kappa B activation. Moreover, acetate impaired the nuclear translocation of NFAT but not that of NF-kappa B. Unlike cyclosporin A (CsA), acetate did not affect the dephosphorylation of NFAT and calcineurin activity. Acetate impaired the binding of NFAT to importin beta 1, which is involved in NFAT nuclear translocation. NEAT is a critical transcription factor in cytokine and early response gene expression in activated T cells. Agents targeting NFAT such as CsA are used to suppress harmful immune responses in inflammatory diseases. Therefore, we also evaluated the efficacy of acetate in murine models of inflammatory diseases, and found that acetate administration (as well as administration of dexamethasone) attenuated trinitrobenzenesulfonic acid-induced colitis and dinitrofluorobenzene-induced dermatitis. These findings indicate for the first time that acetate inhibits NFAT activation by interfering with the interaction between NFAT and importin beta 1 in T cells and that acetate can potentially act as an anti-inflammatory agent.
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European journal of gastroenterology & hepatology 19(7) 595-8 2007年7月 査読有りSmall bowel tuberculosis is sometimes encountered in oriental countries, and because its symptoms are vague and present a nonspecific pattern, confirmative diagnosis is difficult to achieve. In 2001, two new innovative endoscopic techniques for the small bowel, video capsule endoscopy and double balloon enteroscopy, were introduced, thus advancing the diagnostic technology for small bowel disorders. Our asymptomatic patient with small bowel tuberculosis was diagnosed definitively using the combination of video capsule endoscopy and double balloon enteroscopy. The number of such cases will increase when those procedures become more widely used. At present, the endoscopic view of small bowel tuberculosis is difficult to differentiate from Crohn's disease and drug-induced enteropathy, but from now on it will be possible to distinguish them utilizing endoscopic and fluoroscopic images. On the basis of the characteristics of small bowel tuberculosis with its endoscopic images, referring to our case report and previous literature, we report a topical diagnostic procedure, the combination of video capsule endoscopy and double balloon enteroscopy.
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European journal of gastroenterology & hepatology 19(7) 561-6 2007年7月OBJECTIVES: Infection with Helicobacter pylori has been linked to chronic gastritis with atrophy or hyperrugosity. The development of noncardia gastric carcinoma, especially the intestinal type in Lauren's classification, has been associated with severe atrophic gastritis and p53 mutations. The objective of this study was to determine the association between hyperrugosity and gastric carcinogenesis, including p53 mutations. PARTICIPANTS AND METHODS: Barium meal roentgenograms were performed in 395 control participants and 132 gastric carcinoma patients. The fold width was measured at the greater curvature of the middle portion of the gastric body. Serum pepsinogens I and II were determined along with gastrin levels. Complete coding sequences and splice junctions for exons 5-8 of p53 gene were screened for mutations by polymerase chain reaction-based single-strand conformational polymorphism analysis. RESULTS: Rugal hyperplastic gastritis (gastric body fold width ≥ 5 mm) increased the risk of gastric carcinoma [odds ratio, 2.60 95% confidence interval, 1.69-4.01] as compared with the control group, especially diffuse-type gastric carcinoma (odds ratio, 4.13 95% confidence interval, 2.36-7.24). The p53 mutational rate was significantly lower in gastric carcinoma patients with rugal hyperplastic gastritis. In intestinal-type gastric carcinoma with hyperrugosity, the incidence of p53 gene mutations decreased, but no association was found in diffuse-type gastric carcinoma between p53 mutations and rugal hyperplastic gastritis. CONCLUSIONS: Rugal hyperplastic gastritis was associated with an elevated risk of gastric carcinoma, especially diffuse-type, and a lower frequency of p53 mutations. © 2007 Lippincott Williams & Wilkins, Inc.
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Inflammopharmacology 15(3) 101-104 2007年6月The predominant histopathologic feature of inflammatory bowel disease is the infiltration of acute and chronic inflammatory cells, including polymorphonuclear neutrophils, macrophages and lymphocytes, in the affected intestine. Helicobacter pylori is recognized as the most common cause of upper gastrointestinal lesions, and Helicobacter pylori-associated gastritis is characterized by increased numbers of acute and chronic inflammatory cells. The pathogenesis of inflammatory bowel disease or Helicobacter pylori-associated gastritis involves immunological abnormalities, including the deficient or excessive expression of cytokines. The chronic inflammatory process in patients with Crohn's disease may affect any part of the gastrointestinal tract, whereas ulcerative colitis affects mainly the colon and rectum. Here, we discuss abnormalities in the upper gastrointestinal tract in inflammatory bowel disease. Although the prevalence rate of Helicobacter pylori infection is low in Crohn's disease, these patients often have abnormalities in the upper gastrointestinal tract. © 2007 Birkhäuser Verlag.
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IBD Research 1(2) 109-113 2007年6月ダブルバルーン小腸内視鏡(double-balloon endoscopy:DBE)を施行したクローン病(Crohn's disease:CD)29例において、およそ96%に小腸病変が観察できた。そのうち小腸狭窄を呈した11例にDBE下バルーン拡張術を施行し、これまで8例(73%)で手術が回避されている。DBEはクローン病の診断および治療において非常に有用であると考えられた。またカプセル内視鏡は小腸型クローン病4例におこない、施行した全例でクローン病を示唆する病変が認められたが、盲腸到達は1例のみで、小腸内滞留が1例で認められた。(著者抄録)
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World journal of gastroenterology 13(18) 2523-8 2007年5月14日 査読有りUlcerative colitis (UC) is a chronic inflammatory bowel disorder characterized by exacerbations and remissions. The degree of inflammation as assessed by conventional colonoscopy is a reliable parameter of disease activity. However, even when conventional colonoscopy suggests remission and normal mucosal findings, microscopic abnormalities may persist, and relapse may occur later. Patients with long-standing, extensive ulcerative colitis have an increased risk of developing colorectal cancer. Ulcerative colitis-associated colorectal cancer is characterized by an early age at onset, poorly differentiated tumor cells, mucinous carcinoma, and multiple lesions. Early detection of dysplasia and colitic cancer is thus a prerequisite for survival. A relatively new method, magnifying chromoscopy, is thought to be useful for the early detection and diagnosis of dysplasia and colitic cancer, as well as the prediction of relapse. (C) 2007 The WJG Press. All rights reserved.
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Scandinavian journal of gastroenterology 42(5) 633-41 2007年5月 査読有りObjective. The usefulness of F-18-fluoro-2-deoxyglucose positron emission tomography ((18)FDG-PET), whose high rate of FDG accumulation indicates high metabolism and malignant potential, has already been reported. The aims of this study were to evaluate the malignancy of primary gastrointestinal stromal tumour (GIST) in the stomach by (18)FDG-PET and to correlate the FDG uptake values with known risk factors as determined by histology after EUS-guided fine needle aspiration (EUS-FNA) or endoscopic biopsy. Material and Methods. Of 29 patients with histologically proven GI-mesenchymal tumours, 21 with gastric GISTs underwent (18)FDG-PET. Tumour size, mitotic index, Ki-67 labelling index (LI) and cellularity of the tumour tissue were compared with the standardized uptake value (SUV) of FDG. Results. Strong correlations were found between the SUV of FDG and EUS size, and mitotic index of EUS-FNA specimens (tumour size versus SUV, p = 0.004, r = 0.542; number of mitotic cells versus SUV, p = 0.0078; n = 21). Moreover, we examined the association between SUV and risk categories based on EUS-FNA findings using ROC curves. The cut-off values of FDG SUV were 2.2, 4.2 and 6.5 for the very low-, low-, intermediate- and high-risk groups, respectively. Conclusions. (18)FDG-PET may be used to assess malignancy of GISTs. This image modality helps us determine the management strategy for these patients and complements the information on the biological behaviour and cellular proliferation of the tumours.
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GASTROENTEROLOGY 132(4) A351-A351 2007年4月
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Endoscopic ultrasound elastography: Preliminary results for gastro-intestinal masses and lymph nodesGASTROINTESTINAL ENDOSCOPY 65(5) AB201-AB201 2007年4月
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GASTROINTESTINAL ENDOSCOPY 65(5) AB186-AB186 2007年4月
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GASTROINTESTINAL ENDOSCOPY 65(5) AB186-AB186 2007年4月
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GASTROINTESTINAL ENDOSCOPY 65(5) AB247-AB247 2007年4月
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GASTROINTESTINAL ENDOSCOPY 65(5) AB297-AB297 2007年4月
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GASTROENTEROLOGY 132(4) A357-A357 2007年4月
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GASTROINTESTINAL ENDOSCOPY 65(5) AB165-AB165 2007年4月
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GASTROINTESTINAL ENDOSCOPY 65(5) AB207-AB207 2007年4月
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Gastroenterological Endoscopy 49(Suppl.1) 688-688 2007年4月
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Gastroenterological Endoscopy 49(Suppl.1) 826-826 2007年4月
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Gastroenterological Endoscopy 49(Suppl.1) 1003-1003 2007年4月
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Progress in Medicine 27(4) 941-945 2007年4月
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膵臓 22(2) 95-109 2007年4月膵疾患診断における超音波内視鏡(EUS)の有用性は既に確立されており、必須の検査法であるといえる。基本となるB-mode画像において、電子走査方式EUSはメカニカルラジアル走査方式に比して同等以上の画質が得られることが証明されたことで、EUSの主流がメカニカルラジアル走査方式から電子走査方式(電子ラジアル型、電子コンベックス型)に変化することは必然的なものとなる。電子走査方式になることで、ティッシュハーモニックイメージング法、カラードプラ断層法・パワードプラ断層法、造影ハーモニックイメージング法、三次元画像、real time tissue elastographyなどすでに体外式超音波検査(US)では広く臨床応用されている技術がEUSで行えるようになった。このように多方面からのtissue characterizationが可能になったことは膵疾患診断に関する有用性がさらに向上したことを意味する。今後はさらに症例を蓄積し明確な臨床的有用性を証明してゆく必要がある。本稿では、電子走査型EUSで可能になった種々の画像診断法に関して概説する。(著者抄録)
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日本消化器病学会雑誌 104(臨増総会) A75-A75 2007年3月
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World journal of gastroenterology 13(5) 754-60 2007年2月7日 査読有りAIM: To investigate active cytornegalovirus (CMV) infection following the cyclosporine A (CyA) treatment of steroid- refractory ulcerative colitis (UC). METHODS: Twenty-three patients with severe UC not responding to steroid therapy (male 14, and female 9) enrolled at Nagoya University Hospital from 1999 to 2005. They received continuous intravenous infusion of CyA (average 4 mg/kg per day) for 1 mo. Serum and colonic biopsy samples were collected before CyA treatment and 4 d, 10 d, 20 d, and 30 d after treatment. Patients were evaluated for CMV by using serology (IgM antibody by ELISA), quantitative real-time PCR for CMV DNA, and histopathological assessment of hematoxylin and eosin (HE)-stained colonic biopsies. CMV infection was indicated by positive results in any test, RESULTS: No patients had active CMV infection before CyA treatment. Eighteen of 23 UC patients treated with CyA were infected with active CMV (IgM antibody in 16/23 patients, 69.6%; CMV DNA in 18/23 patients, 78.2%; and inclusion bodies in 4/23 patients, 17.3%). There was no difference in the active CMV-infection rate between males and females. Active CMV infection was observed after approximately 8 d of CyA treatment, leading to an exacerbation of colitis. Fifteen of these 18 patients with active CMV infection (83.3%) required surgical treatment because of severe deteriorating colitis. Treatment with ganciclovir rendered surgery avoidable in three patients. CONCLUSION: Our results suggest that active CMV infection in severe UC patients treated with CyA is associated with poor outcome. Further, ganciclovir is useful for treatment of CMV-associated UC after immunosuppressive therapy. (c) 2007 The WJG Press. All rights reserved.
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Inflammopharmacology 15(1) 10-14 2007年2月Helicobacter pylori plays an important role in the development of atrophic gastritis that represents the most recognized pathway in multistep gastric carcinogenesis. Recent studies suggest that a combination of host genetic factors, bacterial virulence factors, and environmental and lifestyle factors determine the severity of gastric damage and the eventual clinical outcome of Helicobacter pylori infection. As to bacterial virulence factors, a high proportion of Japanese strains are cagA+vacAs1. The CagA protein is injected from attached Helicobacter pylori into gastric epithelial cells and the CagA-SHP-2 interactions elicit cellular changes that increase the risk of carcinogenesis. Host cytokine gene polymorphisms and a frequent single nucleotide polymorphism in the PTPN11 gene that encodes SHP-2 may associate with gastric atrophy among Helicobacter pylori-infected subjects. Prevention of gastric cancer requires the development of better screening strategies for determining eradication candidates and further improvement of treatments of Helicobacter pylori infection. © 2007 Birkhäuser Verlag.
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ENDOSCOPY 39(Suppl 1) E7-E8 2007年2月 査読有り
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Inflammopharmacology 15(1) 15-17 2007年2月 査読有りCrohn's disease is a chronic relapsing disease for which no complete cure is available. Although drug therapy with agents such as corticosteroids and azathiopurine is useful, the long-term side effects of these drugs are problematic. The advent of infliximab has recently brought a change in treatment, but the long-term side effects of this agent remain uncertain. In contrast, nutritional therapy produces no druginduced side effects and is effective in inducing and maintaining remission. However, sufficient efficacy cannot be expected in patients in whom compliance with nutritional regimens gradually decreases owing to unpalatability. In these cases, combination therapy with agents such as immunosuppressors and infliximab may be useful. © 2007 Birkhäuser Verlag.
書籍等出版物
46講演・口頭発表等
430-
JDDW2024 第108回日本消化器内視鏡学会 2024年11月1日
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第62回日本小腸学会学術集会 2024年10月19日
担当経験のある科目(授業)
7所属学協会
12共同研究・競争的資金等の研究課題
31-
日本学術振興会 科学研究費助成事業 2022年4月 - 2025年3月
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日本学術振興会 科学研究費助成事業 基盤研究(C) 2022年4月 - 2025年3月
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厚生労働省 先進医療B 2021年2月 - 2024年6月
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国立研究開発法人日本医療研究開発機構（AMED) 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） 2024年6月
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国立研究開発法人日本医療研究開発機構（AMED) 令和３年度難治性疾患実用化研究事業 2021年5月 - 2024年3月