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-
Progress of Digestive Endoscopy 87(Suppl.) s80-s80 2015年6月
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GASTROINTESTINAL ENDOSCOPY 81(5) AB478-AB478 2015年5月
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消化器内視鏡 27(5) 828-834 2015年5月マントル細胞リンパ腫(mantle cell lymphoma:MCL)は、t(11;14)(q13;q32)の染色体転座によるcyclin D1高発現により発症する、CD5陽性のB細胞リンパ腫である。非Hodgkinリンパ腫の2〜3%を占め、20〜30%に消化管病変を認める。中悪性度リンパ腫(aggressive lymphoma)に分類されるが、寛解導入および寛解後療法が確立されておらず難治性である。現在、若年者の初発症例では、リツキシマブとシタラビン大量療法を含む寛解導入療法と、自家末梢血幹細胞移植併用大量化学療法により、生存率は改善傾向にある。一方、高齢者の初発症例では、R-CHOP療法後のリツキシマブ維持療法が生存率改善に寄与するとされている。再発・難治性MCLでは、ベンダムスチン、イブリツモマブ・チウキセタン、同種造血幹細胞移植などが施行されているが効果は限定的である。本稿では、MCLの症状、診断、治療などにつき、症例呈示も含めて述べた。(著者抄録)
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Gastroenterological Endoscopy 57(Suppl.1) 635-635 2015年4月
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Gastroenterological Endoscopy 57(Suppl.1) 665-665 2015年4月
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Gastroenterological Endoscopy 57(Suppl.1) 684-684 2015年4月
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Gastroenterological Endoscopy 57(Suppl.1) 732-732 2015年4月
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消化器内視鏡 27(4) 689-694 2015年4月第2世代の大腸用カプセル内視鏡(以下、PC2)は2014年1月に世界に先駆けて本邦で保険適用となり、今後は大腸癌スクリーニング検査の新たなモダリティーとして期待されている。ただし、PC2普及の課題として読影負担が大きいことがあげられる。日本カプセル内視鏡学会は、カプセル内視鏡読影支援技師認定制度を設立するとともに、大腸カプセル内視鏡eラーニングの運用を開始した。このシステムを用いれば読影支援体制の拡充および読影精度の向上につながることが期待される。また、PC2の読影ソフトウェアには画像強調機能であるFlexible spectral Imaging Color Enhancement(FICE)が搭載されているが、その有用性に関する報告はない。今回、少数例ながらPC2におけるFICEの有用性について検討したところ、通常光単独群とFICE単独群における大腸ポリープ検出感度に有意差はなかったが、ポリープそのものや周囲の血管が明瞭化され、カプセルの通過が速い部位でも拾い上げが可能であった。FICEは視認性を向上させ、読影支援ツールになりうる可能性が示唆された。(著者抄録)
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Journal of pediatric surgery 50(3) 377-81 2015年3月 査読有りBackground: To assess the diagnostic ability and safety of endoscopic retrograde cholangiopancreatography (ERCP) in in-depth preoperative examination of children patients with pancreaticobiliary maljunction (PBM). Methods: In 63 patients with a definite diagnosis of PBM, the ability to visualize the bile and main pancreatic ducts was compared between ERCP, which was performed in 63 patients with a definite diagnosis of PBM, and magnetic resonance cholangiopancreatography (MRCP), which was performed before ERCP in 29 patients. For ERCP, its complications were also evaluated. Results: The intrahepatic bile ducts could be visualized using ERCP in 44 patients (69.8%) and using MRCP in 18 (62.1%). The extrahepatic bile ducts could be visualized using ERCP in 59 patients (93.7%) and using MRCP in 29 (100%). The rates of the visualization of the main pancreatic duct and pancreaticobiliary ductal union were significantly higher in using ERCP than in using MRCP (96.8 vs. 41.4% and 90.5 vs. 37.9%, respectively; P < 0.0001). As complications, hyperamylasemia developed in 12 patients (19%), but no other severe complications such as pancreatitis were observed. Conclusions: ERCP as part of an in-depth preoperative examination of children with PBM is useful and safe. (C) 2015 Elsevier Inc. All rights reserved.
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難治性炎症性腸管障害に関する調査研究 平成26年度 総括・分担研究報告書 84-85 2015年
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Intestine 18(6) 599-602 2014年11月腸管ベーチェット病の病変は,定型的には回盲部に深い円形または類円形の境界明瞭な打ち抜き様潰瘍を認める.このような定型的病変のほかに,炎症性腸疾患類似の広範な腸病変を呈する非定型的病変も少なくない.本稿では,腸管ベーチェット病の非定型例につき,症例の画像を提示しながら解説する.(著者抄録)
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Gastroenterological Endoscopy 56(Suppl.2) 3014-3014 2014年9月
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European journal of radiology 83(8) 1324-31 2014年8月 査読有りBackground and aim: Transabdominal ultrasonography (US) is commonly used for the initial screening of bilio-pancreatic diseases in Asian countries due to its widespread availability, the non-invasiveness and the cost-effectiveness. However, it is considered that US has limits to observe the area, namely the blind area. The observation of the pancreatic tail is particularly difficult. The goal of this study was to examine the pancreatic tail region that cannot be visualized on transverse scanning of the upper abdomen using US with spatial positional information and factors related to visualization, and observation of the tail from the splenic hilum. Methods: Thirty-nine patients with pancreatic/biliary tract disease underwent CT and US with GPS-like technology and fusion imaging for measurement of the real pancreatic length and the predicted/real unobservable (PU and RU) length of the pancreatic tail. RU from US on transverse scanning and the real pancreatic length were used to determine the unobservable area (UA: RU/the real pancreatic length). Relationships of RU with physical and hematological variables that might influence visualization of the pancreatic tail were investigated. Results: The real pancreatic length was 160.9 +/- 16.4 mm, RU was 41.0 +/- 17.8 mm, and UA was 25.3 +/- 10.4%. RU was correlated with BMI (R = 0.446, P=0.004) and waist circumferences (R = 0.354, P = 0.027), and strongly correlated with PU (R = 0.788, P < 0.001). The pancreatic tail was visible from the splenic hilum in 22 (56%) subjects and was completely identified in 13 (33%) subjects. Conclusions: Combined GPS-like technology with fusion imaging was useful for the objective estimation of the pancreatic blind area. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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Journal of gastroenterology 49(7) 1183-92 2014年7月 査読有りAn accurate diagnosis of pancreatic fibrosis is clinically important and may have potential for staging chronic pancreatitis. The aim of this study was to diagnose the grade of pancreatic fibrosis through a quantitative analysis of endoscopic ultrasound elastography (EUS-EG). From September 2004 to October 2010, 58 consecutive patients examined by EUS-EG for both pancreatic tumors and their upstream pancreas before pancreatectomy were enrolled. Preoperative EUS-EG images in the upstream pancreas were statistically quantified, and the results were retrospectively compared with postoperative histological fibrosis in the same area. For the quantification of EUS-EG images, 4 parameters (mean, standard deviation, skewness, and kurtosis) were calculated using novel software. Histological fibrosis was graded into 4 categories (normal, mild fibrosis, marked fibrosis, and severe fibrosis) according to a previously reported scoring system. The fibrosis grade in the upstream pancreas was normal in 24 patients, mild fibrosis in 19, marked fibrosis in 6, and severe fibrosis in 9. Fibrosis grade was significantly correlated with all 4 quantification parameters (mean r = -0.75, standard deviation r = -0.54, skewness r = 0.69, kurtosis r = 0.67). According to the receiver operating characteristic analysis, the mean was the most useful parameter for diagnosing pancreatic fibrosis. Using the mean, the area under the ROC curves for the diagnosis of mild or higher-grade fibrosis, marked or higher-grade fibrosis and severe fibrosis were 0.90, 0.90, and 0.90, respectively. An accurate diagnosis of pancreatic fibrosis may be possible by analyzing EUS-EG images.
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Biomedical reports 2(4) 555-558 2014年7月 査読有りPrevious studies have demonstrated the protective role of inducible heat-shock protein (HSP) 70 in intestinal cells. The HSP70-2 gene has a PstI site due to an A-G transition at the 1,267 position and different genotypes are associated with various levels of mRNA expression. The present study aimed to clarify the effect of the HSP70-2 polymorphism on the risk of ulcerative colitis (UC), including its clinical phenotypes. A total of 121 patients with UC and 500 healthy control (HC) subjects participated in the study. To assess the polymorphisms at the 1,267 position of the HSP70-2 gene, restriction fragment length polymorphism analysis was performed. The subjects in the study were classified by disease behavior, severity and extent of disease. Although no significant difference of the HSP70-2 genotype distribution was identified between the HC and UC groups, the BB genotype exhibited a lower risk of the steroid-dependent phenotype [odds ratio (OR), 0.12; 95% confidence interval (CI), 0.02-0.95; P=0.02]. The same genotype was also associated with a lower risk of the refractory phenotype (OR, 0.16; 95% CI, 0.04-0.73; P=0.01). There was no direct correlation between the polymorphism of the HSP70-2 gene and UC susceptibility. However, there was an association between a reduced risk of the steroid-dependent and refractory phenotypes of UC and the BB genotype.
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Biomedical reports 2(4) 602-606 2014年7月 査読有りA complex interaction of genetic and environmental factors is closely associated with the development of inflammatory bowel disease. Previous studies reported that the expression of the regulated upon activation, normal T-cell expressed and secreted (RANTES) gene is enhanced in the colonic mucosa of ulcerative colitis (UC). Quantitative differences in RANTES gene expression among numerous promoter genotypes have also been reported. The aim of the present study was to clarify the effect of RANTES promoter polymorphism on the risk of UC, including its clinical phenotypes. A total of 150 UC patients and 372 healthy control (HC) subjects participated in the study. The UC patients were classified by disease behavior, severity and extent of disease. Restriction fragment length polymorphism analysis was performed for polymorphisms at -28 C/G in the RANTES gene promoter region. Although no significant difference of the RANTES promoter genotype distribution was observed between the HC and UC groups, the G/G genotype was significantly higher among female (OR=3.95, 95% CI=1.22-12.82, P=0.03), non-steroid dependent (OR=3.37, 95% CI=1.16-9.85, P=0.03) and non-refractory (OR=3.76, 95% CI=1.29-10.98, P=0.02) UC patients. The G carrier was also found to be associated with an increased risk of rectal colitis (OR=2.21, 95% CI=1.12-4.39, P=0.03). The data indicate that the polymorphism of the RANTES promoter is not directly associated with the susceptibility to UC, but the -28 G allele is associated with female UC patients and mild clinical phenotypes of UC, including non-steroid dependency, non-refractory and rectal colitis.
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GASTROENTEROLOGY 146(5) S332-S332 2014年5月
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胃と腸 49(5) 736-743 2014年5月小腸のびまん性大細胞型B細胞リンパ腫(DLBCL)の診断には,小腸X線造影,カプセル内視鏡(VCE),CTとバルーン内視鏡(BAE)などの検査が用いられる.小腸X線造影やVCE検査は存在診断と範囲診断の役割を果たすが,質的診断は不十分となる.VCEは滞留の危険性を有する.BEは腫瘍まで到達できれば,内視鏡診断と生検診断が可能である.当院におけるBAEによる病変への到達は13/14例(92.9%)であり,生検による正診率は13/14例(92.9%)であった.病変は単発で不整形の陥凹性病変が多く,腫瘍のボリュームに比べて腸管狭窄とそれによる症状は軽度な場合が多かった.大腸のDLBCLの診断には,注腸X線造影や大腸内視鏡検査が用いられる.病変は回盲部と直腸に多く認められる.(著者抄録)
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GASTROENTEROLOGY 146(5) S513-S513 2014年5月
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PloS one 9(8) e105565-S853 2014年5月BACKGROUND: The neurochemical serotonin (5-HT) is an important signaling molecule in the gastrointestinal motor and sensory functions. A key regulator of 5-HT levels is the transmembrane serotonin transporter (5-HTT; SLC6A4) that governs the reuptake of 5-HT. Recent studies have indicated 5-HTT expression may be regulated by epigenetic mechanisms. We investigated DNA methylation status of SLC6A4 gene in the gastric mucosa from functional dyspepsia (FD) because of their potential role in dyspeptic symptoms. METHODS: Endoscopic gastric biopsies were obtained from 78 subjects with no upper abdominal symptoms and 79 patients with FD. Bisulfite Pyrosequencing was carried out to determine the methylation status of promoter CpG islands (PCGIs), promoter non-CpG islands (PNCGIs) and gene body non-CpG islands (NPNCGIs) in the SLC6A4 gene. Gene expression was examined by real-time PCR. RESULTS: In overall, methylation level of PCGIs was significantly lower in FD compared to control subjects (p = 0.04). On the other hand, methylation level of NPNCGIs was significantly higher in FD compared to control subjects (p = 0.03). Lower methylation level in PNCGIs was highlighted in the patients with PDS (p = 0.01), while higher methylation level in NPNCGIs was more prominent in the patients with EPS (p = 0.017). Methylation levels of PCGIs and PNCGIs were inversely correlated, while methylation levels of NPNCGIs was positively correlated with SLC6A4 mRNA levels in FD patients. CONCLUSIONS: Our data suggest that change in DNA methylation pattern of SLC6A4 in the gastric mucosa may have a role for developing FD. A role of epigenetics for developing FD needs to be further evaluated.
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胃と腸 49(5) 795-809 2014年5月全身性悪性リンパ腫における消化管浸潤病変の肉眼形態は多彩であるが,びまん浸潤型の形態であるMLP型,腸炎類似型,巨大皺襞型を示すものが多い.MCLの消化管浸潤は,胃が最も多く,次いで結腸病変が多いが,食道病変は少ないとされている.胃病変は多彩であり,表層型,皺襞腫大型,腫瘤(隆起)型,MLP型などを呈する.一方,十二指腸から大腸にかけてはMLP型が大半を占めるが,一部に腫瘤(隆起)型も認められる.食道でもMLP型が大半を占める.FLは十二指腸から小腸に好発し,多くは多発する白色顆粒状隆起の集簇として認められるがMLPの肉眼形態を示すこともある.ATL/Lの消化管浸潤病変の肉眼形態はMLP以外に多発する表層型(0-IIc様)や肥厚型などが挙げられている.(著者抄録)
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JOURNAL OF CLINICAL GASTROENTEROLOGY 48(5) 463-464 2014年5月 査読有り
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Case reports in gastroenterology 8(2) 211-5 2014年5月 査読有りPlummer-Vinson syndrome (PVS) is a rare entity characterized by upper esophageal webs and iron deficiency anemia. We report a case of PVS whose esophageal web was rapidly improved by iron therapy. A 77-year-old woman was admitted to our hospital with complaints of dysphagia, vomiting, shortness of breath and weight loss for 1 month. Physical examination revealed conjunctival pallor, koilonychia, angular cheilitis and smooth tongue, and laboratory findings were consistent with microcytic hypochromic anemia with iron deficiency. Gastrointestinal endoscopy and barium-swallow esophagography detected a web that prevented passage of the endoscope into the upper portion of the esophagus. The patient received oral iron therapy daily the hemoglobin concentration rose to 8.9 g/dl and the complaints of dysphagia were dramatically improved after 2 weeks, with improvement of luminal stenosis confirmed by gastrointestinal endoscopy and barium-swallow esophagography. The PVS described in this report had a distinct clinical course, showing very rapid improvement of dysphagia and esophageal web after 2 weeks of oral iron therapy.
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Gastroenterological Endoscopy 56(Suppl.1) 1013-1013 2014年4月
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Hepatology (Baltimore, Md.) 59(4) 1591-9 2014年4月 査読有りAutophagy can degrade aggregate-prone proteins, but excessive autophagy can have adverse effects. It would be beneficial if autophagy could be enhanced in a cell type-specific manner, but this has been difficult because the basic mechanism of autophagy is common. In the present study we found that inhibition of Niemann-Pick-type C1-like 1 (NPC1L1) by ezetimibe activates autophagy only in hepatocytes and small intestinal epithelia, but not in other cells. Ezetimibe induced accumulation of free cholesterol in the late endosome/lysosome and increased partitioning of a Ragulator component, LAMTOR1, in rafts. The latter change led to down-regulation of mammalian target of rapamycin (mTOR)C1 activity by decreasing mTOR recruitment to the late endosome/lysosome and activated autophagy. A primary effect of ezetimibe was found to be a decrease of free cholesterol in the plasma membrane, because all the results caused by ezetimibe were suppressed by supplementation of cholesterol as a methyl-beta-cyclodextrin complex. By enhancing autophagy in human primary hepatocytes with ezetimibe, insoluble mutant alpha 1-antitrypsin Z was reduced significantly. Conclusion: Inhibition of NPC1L1 by ezetimibe activates autophagy in human hepatocytes by modulating cholesterol homeostasis. Ezetimibe may be used to ameliorate liver degeneration in alpha 1-antitrypsin deficiency. (Hepatology 2014;59:1591-1599)
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