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
266-
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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JCO global oncology 10 e2300392 2024年2月PURPOSE: 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 2024年2月BACKGROUND 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.).
MISC
1256-
GUT 47(1) 120-125 2000年7月 査読有りBackground/aims-For pretherapeutic staging of squamous cell carcinoma of the oesophagus, endoscopic ultrasonography (EUS) is considered the most profitable modality because it can provide cross sectional imaging of the tumour. The aim of this study was to evaluate the relation between prognosis and BUS findings, especially tumour area, in squamous cell carcinoma of the oesophagus. Patients/methods-A total of 113 patients with squamous cell carcinoma of the oesophagus underwent EUS for pretherapeutic examination at Nagoya University Hospital. We compared EUS findings, histological results, and outcome. In addition, we measured the area of the tumour on EUS images (n=113) and evaluated if EUS area correlated with volume of the tumour on histological findings (n=50). Results-The overall accuracy rate of EUS was 83.2% (94/113) for depth of tumour invasion and 67.6% (69/102) for perioesophageal lymph node metastasis. The EUS area increased in proportion to the development of tumour infiltration, and patients with lymph node metastasis had a larger EUS area than patients without lymph node metastasis. There was a close correlation between EUS area and volume of the tumour on histological findings. If EUS area of the tumour was less than 50 mm(2)? the five year survival rate was 100%. As EUS area increased, the survival rate decreased. Conclusions Measurement of EUS area of the tumour is reliable for quantification of the tumour and prediction of prognosis in patients with squamous cell carcinoma of the oesophagus.
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実験潰瘍 = ULCER RESEARCH 27(1) 76-78 2000年5月20日
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実験潰瘍 27(1) 76-78 2000年5月MKN45においてIFNγは単独でアポトーシスを誘導したが,TNFとの併用による相乗的な作用は認められなかった.又,IFNγはsTNFRを放出することによりTNFの細胞傷害作用を制御している可能性が示唆された
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Gastroenterological Endoscopy 42(Suppl.1) 613-613 2000年4月
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日本消化器病学会雑誌 97(臨増総会) A188-A188 2000年3月
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JOURNAL OF CLINICAL BIOCHEMISTRY AND NUTRITION 29 29-36 2000年 査読有りIt has been established that there are two isoforms of mammalian branched-chain aminotransferases, cytosolic (BCATc) and mitochondrial (BCATm). Since the BCATc was reported to be a direct target for c-Myc regulation, we investigated expression of mRNAs for c-myc, BCATc, and BCATm in human gastric cancer cells and tissues. MKN45 and KATOIII were used as human gastric cancer cell lines. Human gastric mucosal tissues with cancer were obtained from 9 patients and those with non-ulcer dyspepsia (NUD) were from 8 patients by endoscopic biopsy. Expression of mRNA was measured by the method of polymerase-chain reaction coupled with reverse transcription. Expression of c-myc mRNA was detected in both cell lines but was greater in MKN45. Expression of BCATc mRNA was detected in KATOIII, but not in MKN45, whereas expression of BCATm mRNA was detected only in MKN45. In the analyses of human gastric tissues, it was found that c-myc mRNA was expressed in all of the tissues examined, but overexpression of the mRNA was detected in the 5 tissues with cancer. On the other hand, expression of BCATc mRNA was detected in 4 tissues with gastric cancer, in which only one tissue had the overexpression of c-myc mRNA. Expression of BCATc mRNA was not detected in all tissues with NUD. BCATm mRNA expression was detected in all tissues with cancer or NUD. These results suggest that there is no correlation between expression of mRNAs for c-myc and BCATc in these tissues and that expression of BCATc in gastric cancer cells and tissues is regulated in a manner independent of c-myc expression.
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Therapeutic Research 19(1) 35-40 1998年消化性潰瘍の難治,再発にmatrix metalloproteinase I陽性好酸球の関与が示唆された
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HISTOCHEMISTRY AND CELL BIOLOGY 108(1) 27-34 1997年7月 査読有りAn association between eosinophils and tissue damage has been observed in numerous disorders. However, few reports have addressed the role of infiltrating eosinophils in gastric ulcer healing. The aim of this study was to investigate the kinetics and role of eosinophils infiltrating experimental chronic gastric ulcers in the rat. We developed a monoclonal antibody against human matrix metalloproteinase 1 (MMPI) purified from conditioned culture medium of human skin fibroblasts. Acetic acid-induced gastric ulcers were resected from rats on days 1, 3, 5, 10, 20, 40, and 180 after the days of induction (day 0). Tissue specimens were immunostained with this antibody and examined with an electron microscope. Few eosinophils were observed in the granulation tissue until day 20. By days 40 and 180, MMP1-positive eosinophils had increased in the granulation tissue of open ulcers. Azan staining revealed dispersed collagen fibers around infiltrating eosinophils. In contrast, scars demonstrated few eosinophils in fibrous tissue on days 40 and 180. Eosinophils which express MMP1 infiltrate granulation tissue at the chronic stage of gastric ulceration. The results suggest that eosinophils may play a role in tissue remodeling and deterioration of ulceration.
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Progress in Medicine 17(8) 2221-2226 1997年慢性潰瘍では肉芽の中に好酸球が多数浸潤するのに対し,scarでは好酸球は非常に少ない.20日目からopen ulcerになるか,或いはscarになるかという点への好酸球の関わりは二次的なものだと思われるが,その二次的な変化に好酸球が増悪因子として働いているのではないかと考えられる.好酸球はMMP-1をもっており,そのMMP-1が組織のremodellingと潰瘍の増悪に働いていると考えられた
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PATHOLOGY INTERNATIONAL 46(6) 399-407 1996年6月 査読有りImmunohistochemistry was used to study the kinetics of B lymphocytes (B-lys) in the early stages of the localized inflammatory response induced in SMA mice by the subcutaneous injection of lipopolysaccharide (LPS), At the injection sites, medium-sized B-lys formed early inflammatory lesions with neutrophils and activated macrophages on days 1 and 2, The B-lys were morphologically similar to monocytes, but were not stained with Mac1 antibody, Remarkably the B-lys showed the phenotypes of B220(+), IgM(+), IgD (slight to negative), Ly-1(-) and CD23(-) by double immunohistochemical staining, The B-lys were also positive for alkaline phosphatase. Consequently the B-lys could be identified as monocytoid B-lys or marginal zone B-lys, Plasmacytic B-lys and plasma cells were first observed on days 3 and 4, but no lymphoid follicles were found at the injection sites, In the inguinal lymph nodes, the same B-lys responses were mainly induced in the paracortical lesions (T cell areas) preceding the formation of activated germinal centers (GC), These findings suggested that the B-lys, induced by injections of LPS, matured into plasma cells in the localized inflammatory lesions independent of GC, and that they were different from follicular B-lys.
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消化器科 22(5) 478-486 1996年ヒトMMP-1に対するモノクローナル抗体(NE9)を作製し,胃潰瘍マウスにおける好酸球のMMP-1発現を検討したところ,40日目以降で肉芽組織全体にMMP-1陽性好酸球の浸潤がみられた.又,ラット血管内皮細胞に対する2種類の抗体(REC4-1, REC16-11)を用いて組織染色を行ったところ,肉芽組織の深層部から表層部までREC16-11陽性血管がみられた.更にREC4-1及びICAM-1陽性の血管が肉芽組織の深層部から中層部にかけて認められた.以上より,ラット潰瘍肉芽組織に多数の好酸球が浸潤し,ヒトMMP-1様のcollagenaseを有していることが明らかになった
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CLINICAL AND EXPERIMENTAL IMMUNOLOGY 100(1) 151-156 1995年4月 査読有りWe determined the kinetics and phenotypes of infiltrating B cells in gastric ulcer in the rat induced by gastric injection of acetic acid (day 0). Few B cells were found in the lesion in the early stages of ulceration. On day 40, two kinds of B cells with phenotypes of IgM(high)IgD(low)OX33 (CD45)(+)OX19 (CD5)(-) and IgM(low)IgD(high)OX33(CD45)(+)OX19(CD5)(-) were scattered in the granulation tissue of open ulcers, but not in the healed scar tissue. On day 180, those two kinds of B cells formed primary follicles in the granulation tissue of open ulcers, but were absent from the healed scar tissue. The IgM(high)IgD(low)OX33(CD45)(+)OX19(CD5)(-) B cell was considered to be identical to the marginal zone B cell of rat spleen. This phenotype of B cell might be associated with inflammatory process in chronic gastric ulcer.
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AMERICAN JOURNAL OF GASTROENTEROLOGY 90(3) 399-402 1995年3月 査読有りObjective: To study the role of autonomic nervous innervation in the etiology of peptic ulcer, we investigated the blood pressure in patients with peptic ulcer. Methods: In 100,085 Japanese adults who were undergoing health screening examinations, including barium meal study, there were endoscopic evaluation-confirmed diagnoses of gastric ulcer in 769 cases and of duodenal ulcer in 344 cases. The blood pressure in those patients was compared with that in 57,208 normal Japanese controls with no gastrointestinal abnormalities, as confirmed by barium meal study. Results: The blood pressure of younger and middle-aged men with gastric and duodenal ulcer were lower than those of normal control men. In women, except for the diastolic pressure of those in their 50s, the blood pressure in patients with peptic ulcer and normal controls did not differ significantly. The incidence of duodenal ulcer or of gastric ulcer in men was inversely related to the systolic and diastolic pressure. No definite relationship in this respect was seen in women. Conclusions: An inverse relationship was observed between the occurrence of peptic ulcer and the blood pressure level in Japanese men, but not in women. The relationship may be mediated by an inhibitory effect of the sympathetic nervous system on ulcer formation in hypertensive subjects. The reason for the sex difference in this respect is unknown.
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Progress in Medicine 14(10) 2713-2716 1994年好酸球は炎症の慢性化に関与し,肉芽内の膠原線維の一つであるtype 1collagen再構築を促し,胃潰瘍の難治化,再発に関係している可能性が示唆された。異物除去にも関与している可能性が考えられた
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Digestive Endoscopy 5(1) 62-66 1993年 査読有りAbstract: To study reflux esophagitis in the general population, we reviewed the records of 64,171 apparently healthy Japanese adults, 48, 706 men and 15,465 women, who had undergone automated multiphasic health testing and services (AMHTS), a comprehensive routine medical health check, that includes double‐contrast upper gastrointestinal roentgenograms. All subjects suspected of having gastrointestinal disease underwent a flexible fiberscopy as indicated. Reflux esophagitis was thus confirmed in 101 subjects. The prevalence of refla esophugitis was 0.20% among men and 0.04% among women (men vs. women p< 0.001) and its frequency increased with age in both men (p< 0.001) and women (p< 0.05). Endoscopic classification according to the Savary‐Miller criteria yielded 48, 27, 23, and patients in Stage I, II, III and IV, respectively. In this series, 49/101 (48.5%) of the esophagitis patients had concurrent upper gastrointestinal abnormalities. The incidence of heavy smoking and excessive drinking of alcohol was significantly higher in the patients with reflux esophagitis (p< 0.001 and p< 0.005, respectively) as compared with the normal population. Copyright © 1993, Wiley Blackwell. All rights reserved
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Therapeutic Research 14(1) 144-148 1993年ヒスタミンは血管内皮細胞の増殖能,管腔形成能を促進させた。また,この増殖促進作用はH1受容体を介する可能性がある
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AMERICAN JOURNAL OF GASTROENTEROLOGY 87(5) 630-633 1992年5月 査読有りThe prevalence of gallbladder polyps was investigated in apparently healthy Japanese who underwent abdominal ultrasonography as part of their health screening examination. The Polyps found were differentiated from gallstones, adenomas, or carcinomas as much as possible, and were considered to be cholesterol polyps. The prevalence of such gallbladder polyps was higher among males in every decade of age evaluated. The subjects with gallbladder polyps were more obese than the control group without gallbladder polyps, on abdominal ultrasonograms. The prevalence of gallbladder polyps rose in accordance with a rise in obesity index. At each range of obesity index, the prevalence of gallbladder Polyps was higher among males. The prevalence of gallbladder polyps was highest among the middle-aged (40- and 50-yr-old) males, similar to the curve of the obesity index. In females, the obesity index increased with age, with no accompanying rise in the prevalence of gallbladder Polyps. These data suggest that obesity contributes to the formation of cholesterol Polyps of the gallbladder.
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DIGESTION 51(4) 198-202 1992年 査読有りTo investigate the role of duodenal mucosal blood flow (DMBF) in the regulation of duodenal alkaline secretion (DAS), both parameters were measured before and after the administration of various drugs in rats. The DMBF was determined using an electrolytically generated hydrogen gas clearance technique, and the DAS was measured by the perfusion method. The administration of dulcerozine, a potent duodenal ulcerogenic agent, at a dose of 250 mg/kg and serotonin at a dose of 20 mg/kg, which produces duodenal ulcerations with an acid load, decreased both DMBF and DAS. On the other hand, the administration of secretin at a dose of 10 U/kg increased both parameters. There were parallel changes in DMBF and DAS. It is concluded, therefore, that DAS may be regulated by DMBF and that both parameters may be involved in the defense mechanism of duodenal mucosa.
書籍等出版物
44講演・口頭発表等
426-
第110回日本消化器病学会総会 ワークショップ5 消化器腫瘍の分子イメージング診断と治療の展望 2024年5月11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
27-
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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公益財団法人 日本対がん協会 2023年度がん検診研究助成事業研究助成 2024年1月
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日本学術振興会 科学研究費助成事業 2019年4月 - 2022年3月
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一般財団法人 愛知健康増進財団 医学研究・健康増進活動等助成金 2020年1月