Kanai, Takanori

写真a

Affiliation

School of Medicine, Department of Internal Medicine (Gastroenterology and Hepatology) （Shinanomachi）

Position

Professor

E-mail Address

E-mail address

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Other Affiliation 【 Display / hide 】

  • School of Medicine, School of Medicine, Professor and Chairman

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Licenses and Qualifications 【 Display / hide 】

  • 日本がん治療認定機構暫定教育医

  • 日本肝臓学会認定肝臓専門医

  • 日本消化器内視鏡学会専門医

  • 日本消化器病学会指導医

  • 日本消化器病学会認定医

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Research Keywords 【 Display / hide 】

  • ディスバイオーシス

  • プロバイオティクス

  • 炎症性腸疾患

  • 腸内細菌

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Papers 【 Display / hide 】

  • Intramucosal poorly differentiated and signet-ring cell components in patients with ulcerative colitis-associated high-grade dysplasia

    Sugimoto S., Shimoda M., Iwao Y., Mutaguchi M., Nanki K., Mizuno S., Kameyama K., Ogata H., Naganuma M., Kanai T.

    Digestive Endoscopy （Digestive Endoscopy)  31 （ 6 ） 706 - 711 2019.11

    ISSN  09155635

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    © 2019 Japan Gastroenterological Endoscopy Society Despite the rarity of colorectal poorly differentiated adenocarcinoma (Por) and signet-ring cell carcinoma (Sig), they are more frequent in patients with ulcerative colitis (UC). However, little is known about these components of early colitis-associated cancer due to the difficulty of detection at an early stage. Here, we reviewed colitis-associated high-grade dysplasia/cancer with Por/Sig components within the submucosa among 103 lesions of 79 UC patients who presented between 1997 and 2017. In total, one Sig in situ, three intramucosal and two submucosal carcinomas (8.7%) were identified among 69 lesions within the submucosa. Depressed appearance, loss of crypt architecture and amorphous surface pattern suggested the presence of Por/Sig, rather than submucosal infiltration. All lesions were located in the rectosigmoid colon and included high-grade dysplasia. While the surrounding noncancerous mucosa expressed E-cadherin and MUC5AC, the expression of E-cadherin was reduced and the expression of MUC5AC was negative in all of the carcinomas except for the Sig in situ. The gastric type metaplasia associated with altered MUC5AC profiles may be a sign of the stepwise accumulation of molecular alterations, including TP53 defects and a reduced expression level of E-cadherin.

  • Pancreatic fat content may increase the risk of imaging progression in low-risk branch duct intraductal papillary mucinous neoplasm

    Kashiwagi K., Minami K., Seino T., Hirata K., Iwasaki E., Inoue N., Iwao Y., Kanai T.

    Journal of Digestive Diseases （Journal of Digestive Diseases)  20 （ 10 ） 557 - 562 2019.10

    ISSN  17512972

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    © 2019 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd Objective: To identify risk factors of imaging progression (increase in cyst size or main pancreatic duct size, or a new mural nodule) in low-risk branch duct intraductal papillary mucinous neoplasm (BD-IPMN), including obesity-related factors such as pancreatic fat content. Methods: Our hospital databases were searched for patients who had completed health checkup, including upper abdominal magnetic resonance imaging (MRI) over 48 months (August 2012 to July 2016). Individuals with BD-IPMN without worrisome features and high-risk stigmata who underwent surveillance with at least one follow-up MRI, irrespective of the follow-up period, were included. Pancreatic computed tomography attenuation indexes were defined as the difference between the pancreas and spleen attenuation (P - S) and the pancreas to spleen attenuation ratio (P/S). Results: Among 75 patients diagnosed as having low-risk BD-IPMN, during a median follow-up of 36 months, 11 (15%) had imaging progression in cyst size, including two with worrisome features. A multivariate logistic analysis showed that the initial cyst size and both indexes (P - S, or P/S) were significantly associated with imaging progression in IPMN, respectively (Model 1: odds ratio [OR] 1.188, 95% confidence interval [CI] 1.060-1.331, P = 0.003; OR 0.871, 95% CI 0.776-0.977, P = 0.019; Model 2: OR 1.186, 95% CI 1.064-1.322, P = 0.002; OR 0.002, 95% CI 0.000-0.970, P = 0.049). Conclusions: Pancreatic fat content and initial cyst size were significantly associated with imaging progression in low-risk BD-IPMN. Revisions of international consensus Fukuoka guidelines might be customized based on initial cyst size and pancreatic fat content.

  • Concerns and Side Effects of Azathioprine During Adalimumab Induction and Maintenance Therapy for Japanese Patients With Crohn's Disease: A Subanalysis of a Prospective Randomised Clinical Trial [DIAMOND Study

    Hisamatsu T., Matsumoto T., Watanabe K., Nakase H., Motoya S., Yoshimura N., Ishida T., Kato S., Nakagawa T., Esaki M., Nagahori M., Matsui T., Naito Y., Kanai T., Suzuki Y., Nojima M., Watanabe M., Hibi T.

    Journal of Crohn's & colitis （Journal of Crohn's & colitis)  13 （ 9 ） 1097 - 1104 2019.09

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    Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com. BACKGROUND: Combining a thiopurine with the human anti-tumour necrosis factor-α monoclonal antibody adalimumab for Crohn's disease [CD] treatment is controversial with regard to efficacy and safety. By conducting a subanalysis of a multicentre, randomised, prospective, open-label trial [the DIAMOND study, UMIN registration number 000005146], we studied the risk of discontinuation of thiopurine in combination with adalimumab. METHODS: In the preceding DIAMOND study, we analysed the: [i] timing and reasons for dropout in the monotherapy group and combination group; [ii] risk factors for dropout in the combination group. RESULTS: There was no significant difference in the dropout rate up to Week 52 between the monotherapy group and combination group [p = 0.325]. The main reason for study dropout was active CD in the monotherapy group, whereas it was adverse effects in the combination group [Fisher's exact test, p <0.001]. Kaplan-Meier analyses revealed significantly earlier dropout in the combination group [log-rank test, p = 0.001]. Multivariable analysis revealed low body weight to be a risk for dropout due to adverse effects in the combination group. CONCLUSIONS: Combination of azathioprine with adalimumab resulted in dropout in the early stage of the study due to side effects of azathioprine, in comparison with late dropout due to active CD in the adalimumab monotherapy group.

  • Difference in the clinical characteristic and prognosis of colitis-associated cancer and sporadic neoplasia in ulcerative colitis patients

    Mutaguchi M., Naganuma M., Sugimoto S., Fukuda T., Nanki K., Mizuno S., Hosoe N., Shimoda M., Ogata H., Iwao Y., Kanai T.

    Digestive and Liver Disease （Digestive and Liver Disease)  51 （ 9 ） 1257 - 1264 2019.09

    ISSN  15908658

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    © 2019 Editrice Gastroenterologica Italiana S.r.l. Background: Although various studies have been conducted on colitis-associated cancer (CAC), few have assessed the differences in the clinical and endoscopic features, treatment, and prognosis of CAC and sporadic neoplasia (SN) in the inflamed mucosa of ulcerative colitis (UC) patients. Aims: To compare the characteristics of CAC and SN within the previously or currently inflamed mucosa. Methods: Between 1997 and 2017, we retrospectively analyzed the endoscopic chart data of 348 colonic lesions from 266 UC patients. Non-dysplastic lesions and lesions located outside the inflamed mucosa were excluded. The diagnosis of CAC or SN was confirmed by conventional histopathological and immunohistochemical evaluation of p53 and Ki67. Results: In total, 74 patients with CAC (97 lesions) and 46 with SN (58) were enrolled. The proportions of patients with a younger age of onset of UC, with chronic persistent UC, and with severe inflamed mucosa were significantly higher in the CAC group. In the SN group, no flat lesions were found, whereas 26% of the lesions in the CAC group were flat. Sixteen patients died during a median follow-up of 6.1 years (interquartile range (IQR) 1.8–11.1)in the CAC group, whereas 1 patient died during a median follow-up 3.2 years(IQR 1.4–4.6) in the SN group. Mortality from colorectal cancer was significantly higher (P = 0.015) in the CAC group (12/68; 17.6%) than in the SN group (1/44; 2.3%). The 5-year survival rate was 100% in the SN group and 97% in the CAC group for lesions located in the mucosa or submucosa. Conclusion: Recognizing differences in the characteristics of CAC and SN within the inflamed mucosa is critical to avoid unnecessary total colectomy in patients with SN.

  • Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis

    Ji F., Yeo Y., Wei M., Ogawa E., Enomoto M., Lee D., Iio E., Lubel J., Wang W., Wei B., Ide T., Preda C., Conti F., Minami T., Bielen R., Sezaki H., Barone M., Kolly P., Chu P., Virlogeux V., Eurich D., Henry L., Bass M., Kanai T., Dang S., Li Z., Dufour J., Zoulim F., Andreone P., Cheung R., Tanaka Y., Furusyo N., Toyoda H., Tamori A., Nguyen M.

    Journal of Hepatology （Journal of Hepatology)  71 （ 3 ） 473 - 485 2019.09

    ISSN  01688278

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    © 2019 European Association for the Study of the Liver Background & Aims: The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. Methods: PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. Results: We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8–92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9–94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2–7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). Conclusion: Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. Lay summary: There are now medications (direct-acting antivirals or “DAAs”) that can “cure” hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

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Papers, etc., Registered in KOARA 【 Display / hide 】

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Reviews, Commentaries, etc. 【 Display / hide 】

  • How Can We Assess "Complete Healing" Beyond Endoscopic Remission?

    Fukuda T., Naganuma M., Kanai T.

    Inflammatory bowel diseases (Inflammatory bowel diseases)  25 ( 6 )  2019.05

  • Correction: Vedolizumab in Japanese patients with ulcerative colitis: A Phase 3, randomized, double-blind, placebo-controlled study (PLoS ONE (2019) 14:2 (e0212989) DOI: 10.1371/journal.pone.0212989)

    Motoya S., Watanabe K., Ogata H., Kanai T., Matsui T., Suzuki Y., Shikamura M., Sugiura K., Oda K., Hori T., Araki T., Watanabe M., Hibi T.

    PLoS ONE (PLoS ONE)  14 ( 4 )  2019.04

    　View Summary

    © 2019 Motoya et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. An incorrect version of S2 File was published in error. This article was republished on April 2, 2019 to correct for this error. Please download this article again to view the correct version.

  • Correction: Clinical utility of novel ultrathin single-balloon enteroscopy: A feasibility study (Endoscopy (2018) (50) DOI: 10.1055/a-0656-5622)

    Takabayashi K., Hosoe N., Miyanaga R., Fukuhara S., Kimura K., Mizuno S., Naganuma M., Yahagi N., Ogata H., Kanai T.

    Endoscopy (Endoscopy)  51 ( 5 )  2019

    ISSN  0013726X

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    © Georg Thieme Verlag KG, Stuttgart - New York. In the above-mentioned article, the name of the author Kaoru Takabayashi has been corrected. This was corrected in the online version on August 24, 2018.

  • Innate lymphoid cells in organ fibrosis

    Mikami Y., Takada Y., Hagihara Y., Kanai T.

    Cytokine and Growth Factor Reviews (Cytokine and Growth Factor Reviews)  42   27 - 36 2018.08

    ISSN  13596101

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    © 2018 Elsevier Ltd Innate lymphoid cells (ILCs) are a recently identified family of lymphoid effector cells. ILCs are mainly clustered into 3 groups based on their unique cytokine profiles and transcription factors typically attributed to the subsets of T helper cells. ILCs have a critical role in the mucosal immune response through promptly responding to pathogens and producing large amount of effector cytokines of type 1, 2, or 3 responses. In addition to the role of early immune responses against infections, ILCs, particularly group 2 ILCs (ILC2), have recently gained attention for modulating remodeling and fibrosis especially in the mucosal tissues. Herein, we overview the current knowledge in this area, highlighting roles of ILCs on fibrosis in the mucosal tissues, especially focusing on the gut and lung. We also discuss some new directions for future research by extrapolating from knowledge derived from studies on Th cells.

  • Reply

    Kanai T., Naganuma M.

    Gastroenterology (Gastroenterology)  155 ( 2 ) 578 - 579 2018.08

    ISSN  00165085

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Presentations 【 Display / hide 】

  • 粘膜下層深部への浸潤を認めたバレット腺癌の一例

    KANAI Takanori

    第106回日本消化器内視鏡学会関東支部例会, 2018.06

  • ガストリン著明上昇を伴わない自己免疫性胃炎を背景とした神経内分泌腫瘍の1例

    KANAI Takanori

    第106回日本消化器内視鏡学会関東支部例会, 2018.06

  • 肝移植待機における門脈血栓治療と静脈瘤治療

    KANAI Takanori

    第54回日本肝臓学会総会, 2018.06

  • Mayo内視鏡スコア1を有する臨床的寛解潰瘍性大腸炎患者に対する治療介入の意 義に関する検討

    KANAI Takanori

    第95回日本消化器内視鏡学会総会, 2018.05

  • 潰瘍性大腸炎における青黛の副作用に関する検討

    KANAI Takanori

    第104回日本消化器病学会総会, 2018.04

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Research Projects of Competitive Funds, etc. 【 Display / hide 】

  • 腸管AhRワールドの解明

    2019.02
    -
    2021.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金井　隆典, Fund for the Promotion of Joint International Research (Home-Returning Researcher Development Research (B)), Principal Investigator

  • 難治性クローン病に対する神経難病治療薬OCH-NCNPの有用性および安全性を検証する医師主導治験

    2015.04
    -
    2018.03

    国立研究開発法人　日本医療研究開発機構, 金井　隆典, No Setting, Principal Investigator

  • To identify the mechanism of inflammatory bowel disease by using human microbe mono-associated mouse

    2015.04
    -
    2018.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金井　隆典, Grant-in-Aid for Scientific Research (A) , Principal Investigator

  • Development of new vaccine therapy to promote the symbiotic bacteria in gut.

    2015.04
    -
    2017.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, 金井　隆典, Grant-in-Aid for Challenging Exploratory Research, Principal Investigator

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    Regarding the onset of inflammatory bowel disease, it is important to reduce the diversity of intestinal microbiota. We generated the mice inoculated with healthy human feces (HC mice) or primary sclerosis cholangitis-associated ulcerative colitis (PSC / UC) patient feces (PSC/UC mice) and analysed a week after transplantation. In PSC / UC mice, Th17 cells was accumulated in liver compare to the HC mice. Next, we isolated 3 dominant microbiota in mesenteric lymph node of PSC/UC mice. Klebsiella pneumonia, Proteus mirabilis and Enterococcus gallinarum were isolated.We also analysed fecal microbiota in Healthy controls and PSC/UC patients. Analysis by the Q-PCR method confirmed that these intestinal bacteria were detected more frequently in PSC / UC patients than in HC control. We demonstrated that certain intestinal microbiota are involved in extraintestinal lesions. We will further promote vaccine therapy with the analysis of these bacteria.

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Awards 【 Display / hide 】

  • 慶應義塾大学医学部坂口洋光記念医学研究助成賞

    2009

  • 三越医学研究助成賞

    2008

  • 慶應義塾大学医学部三師会　北島賞

    2008

  • 日本応用酵素協会研究奨励賞

    2005

  • 全米生理学会カンファレンス　Travel Award

    2004

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Courses Taught 【 Display / hide 】

  • ADVANCED CLINICAL AND SOCIAL MEDICINE

    2019

  • ADVANCED CLINICAL CLERKSHIP IN INTERNAL MEDICINE

    2019

  • ADVANCED CLINICAL ONCOLOGY

    2019

  • ADVANCED INTERNAL MEDICINE

    2019

  • CASE STUDIES OF INTERNAL MEDICINE

    2019

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Memberships in Academic Societies 【 Display / hide 】

  • 日本内科学会

    　

  • 日本消化器病学会

    　

  • 日本消化器内視鏡学会

    　

  • 日本消化管学会

    　

  • 日本大腸肛門病学会

    　

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Committee Experiences 【 Display / hide 】

  • 2015
    -
    Present

    評議員, 日本門脈亢進症学会

  • 2015
    -
    Present

    理事, 日本無菌生物ノートバイオロジー学会

  • 2014
    -
    Present

    評議員, 日本臨床腸内微生物学会

  • 2014
    -
    Present

    特定疾患事業 「神経難病治療薬OCH-NCNPの炎症性腸疾患を対象とした医師主導治験へ向けた製剤確保、治験プロトコール作成、治験相談の実施」, 厚生労働省

  • 2013
    -
    Present

    財団評議員, 日本消化器病学会

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