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Crohn Disease: HELP
Articles by Katsuyoshi Matsuoka
Based on 24 articles published since 2010
(Why 24 articles?)
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Between 2010 and 2020, Katsuyoshi Matsuoka wrote the following 24 articles about Crohn Disease.
 
+ Citations + Abstracts
1 Guideline Evidence-based clinical practice guidelines for inflammatory bowel disease. 2018

Matsuoka, Katsuyoshi / Kobayashi, Taku / Ueno, Fumiaki / Matsui, Toshiyuki / Hirai, Fumihito / Inoue, Nagamu / Kato, Jun / Kobayashi, Kenji / Kobayashi, Kiyonori / Koganei, Kazutaka / Kunisaki, Reiko / Motoya, Satoshi / Nagahori, Masakazu / Nakase, Hiroshi / Omata, Fumio / Saruta, Masayuki / Watanabe, Toshiaki / Tanaka, Toshiaki / Kanai, Takanori / Noguchi, Yoshinori / Takahashi, Ken-Ichi / Watanabe, Kenji / Hibi, Toshifumi / Suzuki, Yasuo / Watanabe, Mamoru / Sugano, Kentaro / Shimosegawa, Tooru. ·Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan. · Guidelines Committee for Creating and Evaluating the ''Evidence-Based Clinical Practice Guidelines for Inflammatory Bowel Disease in Japan'', The Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Building, 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan. tiger44@wa2.so-net.ne.jp. · Ofuna Central Hospital, 6-2-24 Ofuna, Kamakura-shi, Kanagawa, 247-0056, Japan. tiger44@wa2.so-net.ne.jp. ·J Gastroenterol · Pubmed #29429045.

ABSTRACT: Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn's disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.

2 Guideline Evidence-based clinical practice guidelines for Crohn's disease, integrated with formal consensus of experts in Japan. 2013

Ueno, Fumiaki / Matsui, Toshiyuki / Matsumoto, Takayuki / Matsuoka, Katsuyoshi / Watanabe, Mamoru / Hibi, Toshifumi / Anonymous2100740. ·Ofuna Chuo Hospital, Kanagawa, Japan. ·J Gastroenterol · Pubmed #23090001.

ABSTRACT: Crohn's disease is a disorder of unknown etiology and complicated pathogenesis. A substantial amount of evidence has accumulated recently and has been applied to clinical practice. The present guidelines were developed based on recent evidence and the formal consensus of experts relevant to this disease. Here we provide an overview of these guidelines, as follows. Target disease: Crohn's disease Users: Clinical practitioners in internal medicine, surgery, gastroenterology, and general practice Purpose: To provide appropriate clinical indicators to practitioners Scope of clinical indicators: Concept of Crohn's disease, epidemiology, classifications, diagnosis, treatment, follow up, and special situations Intervention: Diagnosis (interview, physical examination, clinical laboratory tests, imaging, and pathology) and treatment (lifestyle guidance, drug therapy, nutritional therapy, surgery, etc.) Outcome assessment: Attenuation of symptoms, induction and maintenance of remission, imaging findings, quality of life (QOL), prevention of complications and harm of therapy Methods for developing these guidelines: Described in the text Basis of recommendations: Integration of evidence level and consensus of experts Cost-benefit analysis: Not implemented Evaluation of effectiveness: Yet to be confirmed Status of guidelines: Updated version of the first Guidelines published in 2010 Publication sources: Printed publication available and electronic information in preparation Patient information: Not available Date of publication: October 2011 These guidelines were intended primarily to be used by practitioners in Japan, and the goal of these guidelines is to improve the outcomes of patients with Crohn's disease.

3 Review Mechanism and therapeutic strategy of secondary failure to anti-tumor necrosis factor-α monoclonal antibody treatment for Crohn's disease. 2013

Matsuoka, Katsuyoshi / Kanai, Takanori. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. ·Digestion · Pubmed #23797247.

ABSTRACT: It is not too much to say that infliximab has revolutionized the treatment of Crohn's disease. However, there is the problem of 'secondary failure' wherein the effect may diminish during treatment. This is a much-discussed topic. For example, not all patients with secondary failure can maintain remission with dose intensification to 10 mg/kg. It is also important to make the appropriate drug selection and to clarify the optimal timing of dose intensification for achieving long-term maintenance of remission, including discussion of the first priority use of adalimumab.

4 Review [Mechanism and therapeutic strategy of second failure of infliximab treatment for Crohn's disease]. 2012

Kanai, Takanori / Matsuoka, Katsuyoshi / Hisamatsu, Tadakazu / Iwao, Yasushi / Ogata, Haruhiko / Hibi, Toshifumi. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan. ·Nihon Shokakibyo Gakkai Zasshi · Pubmed #22398900.

ABSTRACT: -- No abstract --

5 Clinical Trial TGR5 signalling inhibits the production of pro-inflammatory cytokines by in vitro differentiated inflammatory and intestinal macrophages in Crohn's disease. 2013

Yoneno, Kazuaki / Hisamatsu, Tadakazu / Shimamura, Katsuyoshi / Kamada, Nobuhiko / Ichikawa, Riko / Kitazume, Mina T / Mori, Maiko / Uo, Michihide / Namikawa, Yuka / Matsuoka, Katsuyoshi / Sato, Toshiro / Koganei, Kazutaka / Sugita, Akira / Kanai, Takanori / Hibi, Toshifumi. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. ·Immunology · Pubmed #23566200.

ABSTRACT: Bile acids (BAs) play important roles not only in lipid metabolism, but also in signal transduction. TGR5, a transmembrane receptor of BAs, is an immunomodulative factor, but its detailed mechanism remains unclear. Here, we aimed to delineate how BAs operate in immunological responses via the TGR5 pathway in human mononuclear cell lineages. We examined TGR5 expression in human peripheral blood monocytes, several types of in vitro differentiated macrophages (Mϕs) and dendritic cells. Mϕs differentiated with macrophage colony-stimulating factor and interferon-γ (Mγ-Mϕs), which are similar to the human intestinal lamina propria CD14(+) Mϕs that contribute to Crohn's disease (CD) pathogenesis by production of pro-inflammatory cytokines, highly expressed TGR5 compared with any other type of differentiated Mϕ and dendritic cells. We also showed that a TGR5 agonist and two types of BAs, deoxycholic acid and lithocholic acid, could inhibit tumour necrosis factor-α production in Mγ-Mϕs stimulated by commensal bacterial antigen or lipopolysaccharide. This inhibitory effect was mediated by the TGR5-cAMP pathway to induce phosphorylation of c-Fos that regulated nuclear factor-κB p65 activation. Next, we analysed TGR5 levels in lamina propria mononuclear cells (LPMCs) obtained from the intestinal mucosa of patients with CD. Compared with non-inflammatory bowel disease, inflamed CD LPMCs contained more TGR5 transcripts. Among LPMCs, isolated CD14(+) intestinal Mϕs from patients with CD expressed TGR5. In isolated intestinal CD14(+) Mϕs, a TGR5 agonist could inhibit tumour necrosis factor-α production. These results indicate that TGR5 signalling may have the potential to modulate immune responses in inflammatory bowel disease.

6 Article Certolizumab pegol for induction of remission in Crohn's disease. 2019

Yamazaki, Hajime / So, Ryuhei / Matsuoka, Katsuyoshi / Kobayashi, Taku / Shinzaki, Shinichiro / Matsuura, Minoru / Okabayashi, Shinji / Kataoka, Yuki / Tsujimoto, Yasushi / Furukawa, Toshi A / Watanabe, Norio. ·Department of Healthcare Epidemiology, School of Public Health in the Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto, Japan, 606-8501. ·Cochrane Database Syst Rev · Pubmed #31476018.

ABSTRACT: BACKGROUND: Crohn's disease (CD) is a chronic inflammatory disease of the gastrointestinal tract, and immune response modulation is the main treatment strategy to induce remission in active CD. Certolizumab pegol (CZP) is a tumor necrosis factor-alfa (TNF-α) inhibitor which regulates impaired immune response. OBJECTIVES: The primary objectives were to evaluate the efficacy and safety of CZP for the induction of remission in CD. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, the Cochrane IBD group specialized register, trials registers and other sources from inception to 28 January 2019. Moreover, we contacted the pharmaceutical company that manufactures CZP. SELECTION CRITERIA: We included randomized controlled trials comparing CZP with placebo or no treatment in active CD patients. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. The main outcomes selected for GRADE analysis were clinical remission at week 8 (Crohn's Disease Activity Index [CDAI] ≤150), clinical response at week 8 (CDAI reduction ≥ 100 or clinical remission), and serious adverse events. The Mantel-Haenszel random-effects method was applied for the statistical analyses. For dichotomous outcomes, we calculated the risk ratio (RR) and corresponding 95% confidence interval (95% CI). MAIN RESULTS: Four studies involving 1485 participants with moderate to severe CD met the inclusion criteria and were used in the meta-analyses. All studies included active CD patients with CDAI ranging from 220 to 450. Most patients were adults over 18 years of age. One study was identified as high risk of bias due to a non-identical placebo while the other studies were judged to be at low risk of bias.CZP (100 mg to 400 mg every 2 to 4 weeks) was shown to be superior to placebo for achieving clinical remission at week 8 (RR 1.36, 95% CI 1.11 to 1.66; moderate certainty evidence). The raw numbers of participants achieving clinical remission at week 8 were 26.9% (225/835) and 19.8% (129/650) in the CZP and the placebo groups, respectively.CZP was shown to be superior to placebo for achieving clinical response at week 8 (RR 1.29, 95% CI 1.09 to 1.53; moderate certainty evidence). In raw numbers, clinical response at week 8 was achieved in 40.2% (336/835) and 30.9% (201/650) of participants in the CZP and the placebo groups, respectively.In raw numbers, serious adverse events were observed in 8.7% (73/835) and 6.2% (40/650) of participants in the CZP and the placebo groups, respectively (RR 1.35, 95% CI 0.93 to 1.97; moderate certainty evidence). Serious adverse events included worsening Crohn's disease, infections, and malignancy. AUTHORS' CONCLUSIONS: Moderate certainty evidence suggests that CZP is effective for induction of clinical remission and clinical response in participants with active CD patients. It is uncertain whether the risk of serious adverse events differs between CZP and placebo as the 95% CI includes the possibility of a small decrease or doubling of events. Future studies are needed to evaluate the long-term efficacy and safety of CZP in CD patients.

7 Article Factors predicting the therapeutic response to infliximab during maintenance therapy in Japanese patients with Crohn's disease. 2018

Matsuoka, Katsuyoshi / Hamada, Shunsuke / Shimizu, Mikiko / Nanki, Kosaku / Mizuno, Shinta / Kiyohara, Hiroki / Arai, Mari / Sugimoto, Shinya / Iwao, Yasushi / Ogata, Haruhiko / Hisamatsu, Tadakazu / Naganuma, Makoto / Kanai, Takanori / Mochizuki, Mayumi / Hashiguchi, Masayuki. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan. · Division for Evaluation and Analysis of Drug Information, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan. · Department of Hygienic Chemistry, Faculty of Pharmacy, Keio University, Shibakoen, Minato-ku, Tokyo, Japan. · Center for Preventive Medicine, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan. · Center for Diagnostic and Therapeutic Endoscopy, Keio University School of Medicine, Shinanomachi, Shinjuku-ku, Tokyo, Japan. ·PLoS One · Pubmed #30286108.

ABSTRACT: Since anti-tumor necrosis factor (TNF)-α agents (TNF-α inhibitors) induce both clinical response and remission in patients with moderate to severe inflammatory bowel disease (IBD), the use of anti-TNF therapies has fundamentally changed the approach to treatment for patients with IBD. Infliximab (IFX) is a TNF-α inhibitor approved for the induction and remission of Crohn's disease (CD). However, even among patients who initially demonstrate a clinical response to IFX therapy, secondary loss of response occurs, although the reason remains unknown. We therefore investigated predictive factors associated with the response to IFX in long-term maintenance treatment in Japanese CD patients. Eight types of single-nucleotide polymorphisms (SNPs) were investigated using the real-time PCR method, and patient characteristics were collected from the electronic medical records. The Crohn's Disease Activity Index criteria were used as the response to IFX therapy. The observation period was 1 year after IFX had been administered for more than 1 year. Associations between the IFX response and patient characteristics were evaluated using the multivariate logistic regression model. We studied 121 unrelated adult Japanese with CD treated for more than 1 year with IFX as outpatients at Keio University Hospital from November 1, 2014 to November 30, 2015. Among them, 71 were classified as in remisson. In multivariate analysis, patients with the TNF-α 857C>T C/C genotype, shorter disease duration, without double dosing, and combination treatment with an immunomodulator had higher remisson rates than those with the C/T or T/T genotype, longer disease duration, with double dosing, and no combination treatment with an immunomodulator. The response to IFX in Japanese CD patients may therefore be predicted by these 4 characteristics in actual clinical practice.

8 Article β-(1,3)-Glucan derived from 2018

Mori, Kiyoto / Naganuma, Makoto / Mizuno, Shinta / Suzuki, Hiroaki / Kitazume, Mina T / Shimamura, Katsuyoshi / Chiba, Sayako / Sugita, Akira / Matsuoka, Katsuyoshi / Hisamatsu, Tadakazu / Kanai, Takanori. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. · Department of Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Japan. · The Third Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan. ·Intest Res · Pubmed #30090037.

ABSTRACT: Background/Aims: Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. Methods: CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these Results: Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. Conclusions: These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.

9 Article Prediction of disease activity of Crohn's disease through fecal calprotectin evaluated by balloon-assisted endoscopy. 2018

Iwamoto, Fumihiko / Matsuoka, Katsuyoshi / Motobayashi, Maiko / Takenaka, Kento / Kuno, Toru / Tanaka, Keisuke / Tsukui, Yuya / Kobayashi, Shoji / Yoshida, Takashi / Fujii, Toshimitsu / Saito, Eiko / Yamaguchi, Tatsuya / Nagahori, Masakazu / Sato, Tadashi / Ohtsuka, Kazuo / Enomoto, Nobuyuki / Watanabe, Mamoru. ·Department of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. · First Department of Internal Medicine, University of Yamanashi, Yamanashi, Japan. ·J Gastroenterol Hepatol · Pubmed #29889986.

ABSTRACT: BACKGROUND AND AIM: Fecal calprotectin (FC) is a useful marker for assessing the activity of intestinal inflammation. However, most studies have used ileocolonoscopy to evaluate the association of FC with intestinal inflammation, and it is not clear whether FC is useful for the evaluation of small-bowel Crohn's disease (CD). This study aimed to determine the usefulness of FC for predicting intestinal inflammation evaluated by balloon-assisted endoscopy (BAE), which can visualize the deep small intestine. METHODS: This was a cross-sectional, observational study involving 69 CD patients, 39 of whom had only small-bowel disease. The extended simplified endoscopic activity score for Crohn's disease (eSES-CD) was calculated based on the findings of BAE. Mucosal healing was defined as an eSES-CD of 0. RESULTS: In all CD patients, FC levels were correlated with the eSES-CD (r = 0.663, P < 0.001). The cutoff value to predict mucosal healing was 92 mg/kg, with a sensitivity of 94%, specificity of 88%, positive predictive value of 98%, negative predictive value of 64%, and the area under the curve of 0.91. Even in small-bowel CD patients, FC levels were correlated with the eSES-CD (r = 0.607, P < 0.001). The cutoff value was 92 mg/kg, with a sensitivity of 87%, specificity of 88%, positive predictive value of 96%, negative predictive value of 64%, and area under the curve of 0.85. CONCLUSIONS: Fecal calprotectin showed a significant correlation with the intestinal inflammation evaluated with BAE even in patients with only small intestinal disease. FC is useful for the evaluation of CD including both the small and large intestines.

10 Article Utility of Magnetic Resonance Enterography For Small Bowel Endoscopic Healing in Patients With Crohn's Disease. 2018

Takenaka, Kento / Ohtsuka, Kazuo / Kitazume, Yoshio / Matsuoka, Katsuyoshi / Nagahori, Masakazu / Fujii, Toshimitsu / Saito, Eiko / Kimura, Maiko / Fujioka, Tomoyuki / Watanabe, Mamoru. ·Department of Gastroenterology and Hepatology, Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan. · Department of Radiology, Tokyo Medical and Dental University, Tokyo, Japan. ·Am J Gastroenterol · Pubmed #29257147.

ABSTRACT: OBJECTIVES: Small bowel (SB) endoscopic healing has not been well studied in patients with Crohn's disease (CD). This study aims to evaluate the utility of magnetic resonance (MR) enterography (MRE) for SB lesions in comparison with balloon-assisted enteroscopy (BAE) findings. METHODS: In total, 139 patients with CD in clinical-serological remission were prospectively followed after BAE and MRE procedures. We applied a modified version of the Simple Endoscopic Score for CD (SES-CD) for an endoscopic evaluation of the SB, called the Simple Endoscopic Active Score for CD (SES-CDa). We also used the MR index of activity (MaRIA) for MR evaluations. The primary end points were time to clinical relapse (CD activity index of >150 with an increase of >70 points) and serological relapse (abnormal elevation of C-reactive protein). RESULTS: Clinical and serological relapses occurred in 30 (21.6%) and 62 (44.6%) patients, respectively. SB endoscopic healing (SES-CDa<5) was observed in 76 (54.7%) patients. A multiple regression analysis showed that the lack of SB endoscopic healing was an independent risk factor for clinical relapses (hazard ratio (HR): 5.34; 95% confidence interval (CI): 2.06-13.81) and serological relapses (HR: 3.02; 95% CI: 1.65-5.51), respectively. MR ulcer healing (MaRIA score <11) demonstrated a high diagnostic accuracy (90.9%; 95% CI: 87.9-93.2%) for endoscopic healing. The kappa coefficient between BAE and MRE for longitudinal responsiveness was 0.754 (95% CI: 0.658-0.850) for clinical relapse and 0.783 (95% CI: 0.701-0.865) for serological relapse. CONCLUSIONS: SB inflammation was associated with a poor prognosis in patients with clinical-serological remission. MRE is a valid and reliable examination for SB inflammatory activity both for cross-sectional evaluations and prognostic prediction.

11 Article Magnetic resonance evaluation for small bowel strictures in Crohn's disease: comparison with balloon enteroscopy. 2017

Takenaka, Kento / Ohtsuka, Kazuo / Kitazume, Yoshio / Matsuoka, Katsuyoshi / Fujii, Toshimitsu / Nagahori, Masakazu / Kimura, Maiko / Fujioka, Tomoyuki / Araki, Akihiro / Watanabe, Mamoru. ·Department of Gastroenterology and Hepatology, Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. · Department of Radiology, Tokyo Medical and Dental University, Tokyo, Japan. · Department of Gastroenterology and Hepatology, Internal Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo, 113-8519, Japan. mamoru.gast@tmd.ac.jp. ·J Gastroenterol · Pubmed #27848026.

ABSTRACT: BACKGROUND: Magnetic resonance (MR) imaging is the recommended technique for detection of small bowel lesions in Crohn's disease. We aimed to evaluate the impact of stricture findings obtained by MR imaging on patient outcomes using balloon-assisted enteroscopy (BAE) as a reference. METHODS: Two hundred Crohn's disease patients undergoing both MR enterocolonography and BAE were prospectively followed up for at least 1 year. The presence of strictures detected by MR enterocolonography was compared with endoscopic findings. Moreover, the relationship between MR findings and surgery was evaluated. RESULTS: The accuracy of MR imaging for detection of small bowel strictures was defined by a sensitivity of 60.6% and a specificity of 93.4%. Major strictures (diameter less than 10 mm or with internal fistula), long strictures (length 10 mm or greater), and prestenotic dilatation were predictors of stricture detection by MR imaging (P = 0.001, 0.017, and 0.002 respectively). Surgery was performed in 31.6% of patients (18 of 57) in the MR-positive-BAE-positive stricture group and in 10.8% of patients (4 of 37) in the MR-negative-BAE-positive stricture group. Multiple regression analysis showed MR-positive-BAE-positive strictures were an independent risk factor for surgery (P = 0.002 at 6 months and P < 0.001 at 1 year). The surgery-free rate in the MR-negative-BAE-positive stricture group was significantly lower than that in nonstricture group at 1 year (P = 0.001). CONCLUSIONS: The specificity of MR imaging for detection of small bowel strictures was clinically sufficient, and the MR procedure could detect critical strictures, which was a predictive factor for surgery. But MR-negative-BAE-positive strictures were also associated with an increased risk compared with no strictures after 1 year of follow-up.

12 Article Findings of ulceration and severe stricture on MRE can predict prognosis of Crohn's disease in patients treated with anti-TNF treatment. 2017

Naganuma, Makoto / Okuda, Shigeo / Hisamatsu, Tadakazu / Matsuoka, Katsuyoshi / Mori, Kiyoto / Hosoe, Naoki / Nakazato, Yoshihiro / Ogata, Haruhiko / Kanai, Takanori. ·Department of Gastroenterology and Hepatology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. maknaganuma@gmail.com. · Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan. maknaganuma@gmail.com. · Department of Radiology, School of Medicine, Keio University, Tokyo, Japan. · Department of Gastroenterology and Hepatology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo, 160-8582, Japan. · Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan. ·Abdom Radiol (NY) · Pubmed #27549100.

ABSTRACT: BACKGROUND: MR enterography (MRE) is useful for evaluating transmural lesions and extra-intestinal complications of Crohn's disease (CD). The aim of this study was to prospectively evaluate whether MRE could detect severe strictures and inflammatory lesions in patients who lost the responsiveness to anti-TNF treatment and whether MRE could predict prognosis of CD patients with clinical remission. PATIENTS AND METHODS: MRE were conducted in 50 patients who were treated with infliximab or adalimumab. The main aims of this study were as follows; (1) to compare the rates of CD lesions of the patients with clinical remission and active disease at the baseline and (2) to assess the MRE findings that were predictors of clinical recurrence among patients with clinical remission at the baseline. RESULTS: The MRE detection rates of markedly increased contrast uptake, severe strictures, and the presence of ulcers were significantly higher in patients with Crohn Disease Activity Index ≥150 than in patients with clinical remission. Over a mean follow-up of 18.2 months, the absence of ulceration (p = 0.001) or severe stricture (p = 0.01) prolonged clinical recurrence among patients with clinical remission at baseline. Expected duration of recurrence significantly prolonged in patients with total magnetic resonance index of activity (MaRIA) <36.3 [29.8 months (95% CI 23.7-35.9)] than in patients with total MaRIA ≥36.3 (13.9 months (95% CI 7.7-20.1). A cut-off value of total MaRIA score of 36.3 had a sensitivity of 75% and specificity of 70% for predicting recurrence. CONCLUSION: Findings of ulceration and severe stricture on MRE predict prognosis of CD patients who were treated with anti-TNF treatment. MRE might be useful for making treatment decisions in patients who lost the effectiveness of medical treatments.

13 Article Endoscopic Severity Predicts Long-Term Prognosis in Crohn's Disease Patients with Clinical Remission. 2016

Naganuma, Makoto / Hisamatsu, Tadakazu / Matsuoka, Katsuyoshi / Kiyohara, Hiroki / Arai, Mari / Sugimoto, Shinya / Mori, Kiyoto / Nanki, Kosaku / Ohno, Keiko / Mutaguchi, Makoto / Mizuno, Shinta / Bessho, Rieko / Nakazato, Yoshihiro / Hosoe, Naoki / Inoue, Nagamu / Iwao, Yasushi / Ogata, Haruhiko / Kanai, Takanori. ·Department of Gastroenterology and Hepatology, School of Medicine, Keio University, Tokyo, Japan. ·Digestion · Pubmed #26789838.

ABSTRACT: INTRODUCTION: Mucosal healing has emerged as a desirable treatment goal in clinical practice for patients with Crohn's disease (CD). The aim of this study was to assess the relationship between endoscopic activity and the long-term prognosis of CD using simple endoscopic score for Crohn's disease (SESCD) and Rutgeerts' score. METHODS: We conducted a cohort study in clinical practice at a single center. Among CD patients who underwent colonoscopy between July 2008 and June 2011 at our hospital, 131 patients with clinical remission were selected, and the patients were divided into 2 groups: a non-surgical group (n = 84) and a surgical group (n = 47). The primary endpoint of this study was to assess the associations between variables and clinical relapse after endoscopic procedures. The cut-off levels of SESCD or Rutgeerts' score for the prediction of relapse were also assessed in patients with clinical remission. RESULTS: In the non-surgical group, SESCD and C-reactive protein at baseline were significantly higher in patients who had clinical recurrence than in patients who maintained remission. A factor of SESCD ≤2 was independently associated with sustained remission, even in patients with clinical remission. In the surgical group, patients with Rutgeerts' scores ≤1 had significantly prolonged clinical remission compared to patients with Rutgeerts' scores ≥3. CONCLUSION: A cut-off value of SESCD ≤2 and a Rutgeerts' score ≤1 enabled the prediction of long-term prognosis. These cut-off values could be used in clinical trials of endoscopic remission from the point of view of the clinical outcomes of CD.

14 Article An open-label prospective randomized multicenter study of intensive versus weekly granulocyte and monocyte apheresis in active crohn's disease. 2015

Yoshimura, Naoki / Yokoyama, Yoko / Matsuoka, Katsuyoshi / Takahashi, Hiroki / Iwakiri, Ryuichi / Yamamoto, Takayuki / Nakagawa, Tomoo / Fukuchi, Takumi / Motoya, Satoshi / Kunisaki, Reiko / Kato, Shingo / Hirai, Fumihito / Ishiguro, Yoh / Tanida, Satoshi / Hiraoka, Sakiko / Mitsuyama, Keiichi / Ishihara, Shunji / Tanaka, Shinji / Otaka, Michiro / Osada, Taro / Kagaya, Takashi / Suzuki, Yasuo / Nakase, Hiroshi / Hanai, Hiroyuki / Watanabe, Kenji / Kashiwagi, Nobuhito / Hibi, Toshifumi. ·Department of internal medicine, Division of IBD, Tokyo Yamate Medical Centre, Tokyo, Japan. ynaokun@yahoo.co.jp. · Division of Internal Medicine, Department of Inflammatory Bowel Disease, Hyogo College of Medicine, Hyogo, Japan. yoko0502@hyo-med.ac.jp. · Department of Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo, Japan. matsuoka@z2.keio.jp. · Department of General Medicine, National Hospital Organization, Sendai Medical Centre, Miyagi, Japan. hiro-ki@snh.go.jp. · Division of Gastroenterology, Department of Internal Medicine, Saga Medical School, Saga, Japan. iwakiri@cc.saga-u.ac.jp. · Inflammatory Bowel Disease Centre, Yokkaichi Hazu Medical Centre, Mie, Japan. nao-taka@sannet.ne.jp. · Department of Gastroenterology and Hepatology, Chiba University Hospital, Chiba, Japan. tom20852@yahoo.co.jp. · Department of Gastroenterology and Hepatology, Osakafu Saiseikai Nakatsu Hospital, Osaka, Japan. takuleotakuleo@yahoo.co.jp. · IBD Center, Sapporo Kosei General Hospital, Hokkaido, Japan. sa-motoya@nifty.com. · Inflammatory Bowel Centre, Yokohama City University Medical Centre, Kanagawa, Japan. reikok@urahp.yokohama-cu.ac.jp. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Saitama Medical Centre, Saitama Medical University, Saitama, Japan. skato@saitama-med.ac.jp. · Department of Gastroenterology Fukuoka University Chikushi Hospital, Fukuoka, Japan. fuhirai@yahoo.co.jp. · Department of Gastroenterology and Hematology, Hirosaki National Hospital, Aomori, Japan. yishihki@gmail.com. · Department of Gastroenterology and Metabolism, Nagoya City University, Graduate School of Medical Sciences, Nagoya, Japan. stanida@med.nagoya-cu.ac.jp. · Department of Gastroenterology and Hepatology, Dentistry and Pharmaceutical Sciences, Okayama University Graduate School of Medicine, Okayama, Japan. sakikoh@cc.okayama-u.ac.jp. · Division of Gastroenterology, Department of Medicine, Inflammatory Bowel Disease Centre, Kurume University School of Medicine, Fukuoka, Japan. ibd@med.kurume-u.ac.jp. · Department of Internal Medicine II, Faculty of Medicine, Shimane University, Izumo, Japan. si360405@med.shimane-u.ac.jp. · Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan. colon@hiroshima-u.ac.jp. · Division of Gastroenterology, Kobari General Hospital & Juntendo University, Chiba, Japan. mootaka@juntendo.ac.jp. · Department of Gastroenterology, Juntendo University School of Medicine, Tokyo, Japan. otaro@juntendo.ac.jp. · Department of Gastroenterology, Kanazawa University Hospital, Ishikawa, Japan. kagaya@m-kanazawa.jp. · Internal Medicine, Toho University Sakura Medical Centre, Chiba, Japan. yasuo-suzuki@sakura.med.toho-u.ac.jp. · Department of Gastroenterology and Endoscopic Medicine, Kyoto University Hospital, Kyoto, Japan. hiropy_n@kuhp.kyoto-u.ac.jp. · Centre for Gastroenterology and Inflammatory Bowel Disease Research, Hamamatsu South Hospital, Shizuoka, Japan. hanai@hamamatsu-minami.com. · Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan. kenjiw@med.osaka-cu.ac.jp. · Research division, JIMRO Co., Ltd, Gunma, Japan. kashiwagin@jimro.co.jp. · Kitasato Institute Hospital, Centre for Advanced IBD Research and Treatment, Kitasato University, 108-8642 Minato-ku, Tokyo, Japan. thibi@insti.kitasato-u.ac.jp. ·BMC Gastroenterol · Pubmed #26585569.

ABSTRACT: BACKGROUND: Granulocyte and monocyte adsorptive apheresis (GMA) has shown efficacy in patients with active Crohn's disease (CD). However, with routine weekly therapy, it may take several weeks to achieve remission. This study was performed to assess clinical efficacy and safety of intensive GMA in patients with active CD. METHODS: In an open-label, prospective, randomized multicentre setting, 104 patients with CD activity index (CDAI) of 200 to 450 received intensive GMA, at two sessions per week (n = 55) or one session per week (n = 49). Clinical remission was defined as a CDAI score <150. Patients in each arm could receive up to 10 GMA sessions. However, GMA treatment could be discontinued when CDAI decreased to <150 (clinical remission level). RESULTS: Of the 104 patients, 99 were available for efficacy evaluation as per protocol, 45 in the weekly GMA group, and 54 in the intensive GMA group. Remission was achieved in 16 of 45 patients (35.6 %) in the weekly GMA and in 19 of 54 (35.2 %) in the intensive GMA (NS). Further, the mean time to remission was 35.4 ± 5.3 days in the weekly GMA and 21.7 ± 2.7 days in the intensive GMA (P = 0.0373). Elevated leucocytes and erythrocyte sedimentation rate were significantly improved by intensive GMA, from 8005/μL to 6950/μL (P = 0.0461) and from 54.5 mm/hr to 30.0 mm/hr (P = 0.0059), respectively. In both arms, GMA was well tolerated and was without safety concern. CONCLUSIONS: In this study, with respect to remission rate, intensive GMA was not superior to weekly GMA, but the time to remission was significantly shorter in the former without increasing the incidence of side effects. UMIN registration # 000003666.

15 Article Crohn's Disease in which the Patient Developed Aortitis during Treatment with Adalimumab. 2015

Kiyohara, Hiroki / Hisamatsu, Tadakazu / Matsuoka, Katsuyoshi / Naganuma, Makoto / Kameda, Hideto / Seta, Noriyuki / Takeuchi, Tsutomu / Kanai, Takanori. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Japan. ·Intern Med · Pubmed #26179525.

ABSTRACT: A 23-year-old woman developed aortitis during treatment with adalimumab (ADA) for ileocolic Crohn's disease (CD). The patient complained of a high fever, abdominal pain, diarrhea, hematochezia and arthralgia. Although the ADA therapy resulted in immediate symptom improvement, after six weeks, she again complained of a low-grade fever and abdominal pain, whereas the CD-related symptoms did not worsen. Contrast-enhanced computed tomography revealed thoracoabdominal aortitis, and we therefore started treatment with prednisolone, which immediately improved the fever and abdominal pain. We subsequently tapered the dose of prednisolone and resumed the administration of ADA in order to maintain the CD remission. No further episodes of aortitis relapse were noted after restarting ADA, and the CD currently remains in remission. This is the first report of the onset of aortitis during ADA therapy for CD.

16 Article Correlation of the Endoscopic and Magnetic Resonance Scoring Systems in the Deep Small Intestine in Crohn's Disease. 2015

Takenaka, Kento / Ohtsuka, Kazuo / Kitazume, Yoshio / Nagahori, Masakazu / Fujii, Toshimitsu / Saito, Eiko / Fujioka, Tomoyuki / Matsuoka, Katsuyoshi / Naganuma, Makoto / Watanabe, Mamoru. ·Departments of *Gastroenterology and Hepatology, and †Radiology, Tokyo Medical and Dental University, Tokyo, Japan. ·Inflamm Bowel Dis · Pubmed #26020602.

ABSTRACT: BACKGROUND: There are no widely accepted endoscopic or magnetic resonance scoring systems to evaluate deep small intestinal lesions in Crohn's disease (CD). This study aimed to determine whether the simplified endoscopic activity score for Crohn's disease (SES-CD) and the Magnetic Resonance Index of Activity (MaRIA) could be adapted for assessing CD lesions in the deep small intestine. METHODS: Magnetic resonance enterocolonography and single-balloon enteroscopy were prospectively performed in 125 patients with CD. SES-CD and MaRIA were applied to the deep small intestine. The correlation between the SES-CD and MaRIA was evaluated. RESULTS: Endoscopic and magnetic resonance active lesions were detected in the terminal and proximal ileal segments at a similar rate. The total MaRIA scores correlated well with the total SES-CD scores (R = 0.808, P < 0.001). A MaRIA score of ≥11 had a high sensitivity, specificity, and diagnostic accuracy for ulcerative lesions that were defined by enteroscopy (sensitivity: 78.3%; specificity: 98.0%). Similarly, an MaRIA score of ≥7 had a high sensitivity, specificity, and diagnostic accuracy for all mucosal lesions defined by enteroscopy (sensitivity: 87.0%; specificity: 86.0%). CONCLUSIONS: The MaRIA closely correlates with the SES-CD in the deep small intestine, indicating these scoring systems can be used to assess deep small intestinal lesions. We also showed the validity of MaRIA to evaluate the active lesions in the deep small intestine.

17 Article Combination therapy with infliximab and thiopurine compared to infliximab monotherapy in maintaining remission of postoperative Crohn's disease. 2015

Sakuraba, Atsushi / Okamoto, Susumu / Matsuoka, Katsuyoshi / Sato, Toshiro / Naganuma, Makoto / Hisamatsu, Tadakazu / Iwao, Yasushi / Ogata, Haruhiko / Kanai, Takanori / Hibi, Toshifumi. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. ·Digestion · Pubmed #25823572.

ABSTRACT: BACKGROUND AND AIMS: Infliximab is an efficacious agent used for the induction and maintenance of remission in Crohn's disease (CD), and recent studies suggested that it may also prevent the recurrence of this disease after surgery. The present study was performed to assess the efficacy and safety of infliximab in the postoperative setting, and to identify whether combination treatment with thiopurines had any additional beneficial effect as compared to mono-therapy. METHODS: We performed a retrospective cohort study to compare the efficacy of infliximab mono-therapy and combination treatment with a thiopurine in preventing recurrence after surgery. RESULTS: Forty-one patients who received infliximab as maintenance treatment following surgery from May 2002 to April 2010 were identified. Twenty-four were naive to infliximab, and 17 who underwent surgery during infliximab treatment were continued on it following surgery. The median follow-up period was 27 months (range 12-66 months). All patients continued infliximab as maintenance treatment, but 10 required dose intensification due to clinical recurrence. Kaplan-Meier analysis demonstrated that the use of concomitant thiopurine was correlated with the continuation of infliximab treatment at an 8-week interval (log-rank test p = 0.018). The rate of adverse event was 9.8% with no patient experiencing severe adverse reactions. CONCLUSION: Infliximab appears to be safe and it prevented clinical recurrence after surgery. Concomitant thiopurine use predicted response toward continuation of therapy at an 8-week interval. Prospective controlled studies to assess the efficacy of combination treatment in the postoperative setting are warranted.

18 Article Risk factors for decreased bone mineral density in inflammatory bowel disease: A cross-sectional study. 2015

Wada, Yasuyo / Hisamatsu, Tadakazu / Naganuma, Makoto / Matsuoka, Katsuyoshi / Okamoto, Susumu / Inoue, Nagamu / Yajima, Tomoharu / Kouyama, Keisuke / Iwao, Yasushi / Ogata, Haruhiko / Hibi, Toshifumi / Abe, Takayuki / Kanai, Takanori. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan; Center for Human Nutrition, The University of Texas Southwestern Medical Center, Dallas, TX, USA. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. Electronic address: hisamachi@a7.keio.jp. · Center for Diagnostic and Therapeutic Endoscopy, School of Medicine, Keio University, Tokyo, Japan. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. · Center for Clinical Research, School of Medicine, Keio University, Tokyo, Japan. · Center for Preventive Medicine, School of Medicine, Keio University, Tokyo, Japan. · Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan. ·Clin Nutr · Pubmed #25618799.

ABSTRACT: BACKGROUND & AIM: Although inflammatory bowel disease (IBD) patients are at risk for metabolic bone disease, studies analyzing this correlation have identified various risk factors, including disease phenotype, age, sex and steroid therapy. Furthermore, few studies have assessed risk factors for bone loss in Japanese IBD patients. This study analyzed risk factors for metabolic bone disease in Japanese IBD patients. METHODS: This cross-sectional study assessed 388 patients with IBD aged 20-50 years, including 232 with ulcerative colitis (UC) and 156 with Crohn's disease (CD). Bone mineral density of the femoral neck, total femur and lumbar spine was quantified by dual-energy X-ray absorptiometry. The blood concentrations of bone metabolism markers were measured. History of smoking and bone fracture, and nutritional intake were assessed using questionnaires. RESULTS: Of the 388 patients with IBD, 78 (20.1%; UC, 17.2%; CD, 24.4%) had osteopenia and 17 (4.4%; UC, 3.4%; CD, 5.8%) had osteoporosis, as assessed by T-score. Bone mineral density of the lumbar vertebrae was lower in males than in females. Multivariate regression analysis showed that risk factors for bone loss in UC patients were male sex, low body mass index (BMI), high steroid dose and disease location. Risk factors for bone loss in CD patients were male sex and low BMI. CONCLUSION: Among Japanese patients with IBD, male sex and low BMI were associated with increased risk for metabolic bone disease. In addition, Steroid therapy shouldn't be indiscriminate in UC patients. These findings may help identify patients at particularly high risk of metabolic bone disease and may help implement appropriate therapies in a timely manner and improve long-term quality of life.

19 Article Early intervention with adalimumab may contribute to favorable clinical efficacy in patients with Crohn's disease. 2014

Miyoshi, Jun / Hisamatsu, Tadakazu / Matsuoka, Katsuyoshi / Naganuma, Makoto / Maruyama, Yuriko / Yoneno, Kazuaki / Mori, Kiyoto / Kiyohara, Hiroki / Nanki, Kosaku / Okamoto, Susumu / Yajima, Tomoharu / Iwao, Yasushi / Ogata, Haruhiko / Hibi, Toshifumi / Kanai, Takanori. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. ·Digestion · Pubmed #25323803.

ABSTRACT: BACKGROUND: We evaluated the clinical efficacy of adalimumab (ADA) for Crohn's disease (CD) and analyzed predictive factors for clinical remission and long-term prognosis. METHODS: We retrospectively reviewed the medical records of 45 patients treated with ADA for CD at Keio University Hospital between October 2010 and March 2014. Clinical remission was defined as a Harvey-Bradshaw index of ≤4. RESULTS: Twenty-eight of 45 patients (62.2%) achieved clinical remission at week 4. Among these 28 patients, 18 patients (64.3%) maintained clinical remission at week 26, and among these, 16 patients (88.9%) maintained clinical remission at week 52. Absence of a history of bowel resection and absence of prior anti-tumor necrosis factor (anti-TNF) therapy were significant predictive factors for clinical remission at week 4 upon multivariate logistic regression analyses. Younger age and a disease duration of ≤3 years correlated with clinical remission at week 26 upon univariate analyses. Patients without a history of bowel resection showed significantly better long-term prognosis than those with a history of bowel resection (p = 0.01). None of the patients contracted a serious infectious disease. CONCLUSIONS: Younger age, shorter duration of disease, being naive to anti-TNF antagonists, and absence of a history of bowel resection were associated with the efficacy of ADA in CD patients.

20 Article Cross-talk between RORγt+ innate lymphoid cells and intestinal macrophages induces mucosal IL-22 production in Crohn's disease. 2014

Mizuno, Shinta / Mikami, Yohei / Kamada, Nobuhiko / Handa, Tango / Hayashi, Atsushi / Sato, Toshiro / Matsuoka, Katsuyoshi / Matano, Mami / Ohta, Yuki / Sugita, Akira / Koganei, Kazutaka / Sahara, Rikisaburo / Takazoe, Masakazu / Hisamatsu, Tadakazu / Kanai, Takanori. ·*Department of Gastroenterology and Hepatology, and †Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan; ‡Division of Gastroenterology, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan; §Life Science of Medical Bio Science, Waseda University School of Advanced Science and Engineering, Tokyo, Japan; ‖Department of Surgery, Yokohama Municipal Citizen's Hospital, Yokohama, Japan; and ¶Coloproctology Center of Social Health Insurance Medical Center, Tokyo, Japan. ·Inflamm Bowel Dis · Pubmed #24991784.

ABSTRACT: BACKGROUND: Interleukin (IL)-22-producing RORγt innate lymphoid cells (ILCs) play a pivotal role in intestinal immunity. Recent reports demonstrated that ILCs contribute to mucosal protection and intestinal inflammation in mice. In humans, numbers of RORγt ILCs are significantly increased in the intestine of patients with Crohn's disease (CD), suggesting that ILCs may be associated with intestinal inflammation in CD. However, the mechanism by which ILCs are regulated in the intestine of patients with CD is poorly understood. This study aimed to determine the activation mechanism of intestinal ILCs in patients with CD. METHODS: CD45 lineage marker ILCs were isolated from intestinal lamina propria of patients with CD. ILCs were then subdivided into 4 distinct populations based on the expression of CD56 and CD127. Purified ILC subsets were cocultured with intestinal CD14 macrophages, and IL-22 production was evaluated. RESULTS: CD127CD56 and CD127CD56 ILC, but not CD127CD56 or CD127CD56 ILC, subsets expressed RORγt and produced IL-22. IL-22 production by these ILC subsets was enhanced when ILCs were cocultured with intestinal macrophages. IL-23 or cell-to-cell contact was required for macrophage-mediated activation of ILCs. IL-22 production by ILCs was perturbed in inflamed mucosa compared with noninflamed mucosa. IL-22 induced the expression of Reg1α and Claudin-1 in human intestinal epithelial organoids. CONCLUSIONS: RORγt ILCs might enhance mucosal barrier function through the upregulation of Reg1α through production of IL-22. Although CD14 macrophages augment intestinal inflammation in patients with CD, macrophages also promote a negative feedback pathway through the activation of IL-22 production by RORγt ILCs.

21 Article Risk and management of intra-abdominal abscess in Crohn's disease treated with infliximab. 2014

Yoneno, Kazuaki / Hisamatsu, Tadakazu / Matsuoka, Katsuyoshi / Okamoto, Susumu / Takayama, Tetsuro / Ichikawa, Riko / Sujino, Tomohisa / Miyoshi, Jun / Takabayashi, Kaoru / Mikami, Yohei / Mizuno, Shinta / Wada, Yasuyo / Yajima, Tomoharu / Naganuma, Makoto / Inoue, Nagamu / Iwao, Yasushi / Ogata, Haruhiko / Hasegawa, Hirotoshi / Kitagawa, Yuko / Hibi, Toshifumi / Kanai, Takanori. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. ·Digestion · Pubmed #24803137.

ABSTRACT: BACKGROUND AND AIMS: Infliximab (IFX) is a monoclonal antibody used to treat patients with Crohn's disease (CD). Intra-abdominal abscess formation is a major complication of CD with negative effects on patient prognosis. We have analyzed risk factors for abscess formation in CD patients treated with IFX. METHODS: CD patients who received IFX between January 2000 and April 2011 at Keio University Hospital were analyzed retrospectively. Risk factors for abscess formation were assessed by univariate and multivariate logistic regression analyses. RESULTS: Intra-abdominal abscess was seen in 15 of 258 patients. Univariate analyses showed serum C-reactive protein (CRP) concentration at 14 weeks after initiation of IFX (p = 0.021), serum albumin concentration at week 0 (p = 0.022) and week 14 (p = 0.004), the presence of anal lesions (p = 0.036), progression of intestine deformation (p = 0.015) and early loss of response to IFX (p < 0.0001) to be risk factors. Multivariate analysis showed that CRP concentration at 14 weeks [odds ratio (OR) 1.361] and loss of IFX response within 6 months (OR 5.361) were independent risk factors. CONCLUSIONS: Abscess formation should be suspected in patients with symptoms of CD recurrence during IFX therapy. Uncontrolled CRP concentration and early loss of response to IFX are risk factors.

22 Article Endoscopic and pathologic changes of the upper gastrointestinal tract in Crohn's disease. 2014

Sakuraba, Atsushi / Iwao, Yasushi / Matsuoka, Katsuyoshi / Naganuma, Makoto / Ogata, Haruhiko / Kanai, Takanori / Hibi, Toshifumi. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan ; Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago, 5841 S. Maryland Avenue, MC 4076, Chicago, IL 60615, USA. · Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, 35 Shinanomachi, Shinjyuku-ku, Tokyo 160-8582, Japan. ·Biomed Res Int · Pubmed #24672792.

ABSTRACT: BACKGROUND: Crohn's disease (CD) may involve any part of the gastrointestinal tract. We assessed the prevalence and features of upper gastrointestinal (UGI) lesions in CD. METHODS: This was a retrospective study that included 138 CD patients that underwent esophagogastroduodenoscopy (EGD). The rate of Crohn's specific endoscopic lesions in the esophagus, stomach, and duodenum was assessed, and immunohistochemical analysis was performed. Changes in the UGI lesions were assessed in those who had two or more EGD. RESULTS: Of 138 patients, 51.3% had Crohn's specific UGI lesions. The rates of Crohn's specific lesion in the esophagus, upper-to-middle stomach, lower stomach, duodenal bulb, and 2nd portion of the duodenum were 6.5%, 47.8%, 24.6%, 31.9%, and 18.1%, respectively. Granulomas were detected in 6.1%, 25.0%, and 11.4% in the upper-to-middle stomach, lower stomach, and duodenal bulb, respectively, but none in the esophagus and 2nd portion of the duodenum. Thirty-seven were analyzed for Helicobacter pylori and 4 were positive (10.8%). Improvements of UGI lesions were seen in 14 out of 49 (28.5%) and were unchanged in 59.2% and worsened in 12.2%. CONCLUSIONS: The prevalence of Crohn's specific UGI lesions was common in our case series, and immunohistochemical studies suggested that the majority was unrelated to Helicobacter pylori infection. Worsening of UGI lesions over the course was rare.

23 Article Novel, objective, multivariate biomarkers composed of plasma amino acid profiles for the diagnosis and assessment of inflammatory bowel disease. 2012

Hisamatsu, Tadakazu / Okamoto, Susumu / Hashimoto, Masaki / Muramatsu, Takahiko / Andou, Ayatoshi / Uo, Michihide / Kitazume, Mina T / Matsuoka, Katsuyoshi / Yajima, Tomoharu / Inoue, Nagamu / Kanai, Takanori / Ogata, Haruhiko / Iwao, Yasushi / Yamakado, Minoru / Sakai, Ryosei / Ono, Nobukazu / Ando, Toshihiko / Suzuki, Manabu / Hibi, Toshifumi. ·Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan. hisamachi@a7.keio.jp ·PLoS One · Pubmed #22303484.

ABSTRACT: BACKGROUND: Inflammatory bowel disease (IBD) is a chronic intestinal disorder that is associated with a limited number of clinical biomarkers. In order to facilitate the diagnosis of IBD and assess its disease activity, we investigated the potential of novel multivariate indexes using statistical modeling of plasma amino acid concentrations (aminogram). METHODOLOGY AND PRINCIPAL FINDINGS: We measured fasting plasma aminograms in 387 IBD patients (Crohn's disease (CD), n = 165; ulcerative colitis (UC), n = 222) and 210 healthy controls. Based on Fisher linear classifiers, multivariate indexes were developed from the aminogram in discovery samples (CD, n = 102; UC, n = 102; age and sex-matched healthy controls, n = 102) and internally validated. The indexes were used to discriminate between CD or UC patients and healthy controls, as well as between patients with active disease and those in remission. We assessed index performances using the area under the curve of the receiver operating characteristic (ROC AUC). We observed significant alterations to the plasma aminogram, including histidine and tryptophan. The multivariate indexes established from plasma aminograms were able to distinguish CD or UC patients from healthy controls with ROC AUCs of 0.940 (95% confidence interval (CI): 0.898-0.983) and 0.894 (95%CI: 0.853-0.935), respectively in validation samples (CD, n = 63; UC, n = 120; healthy controls, n = 108). In addition, other indexes appeared to be a measure of disease activity. These indexes distinguished active CD or UC patients from each remission patients with ROC AUCs of 0.894 (95%CI: 0.853-0.935) and 0.849 (95%CI: 0.770-0.928), and correlated with clinical disease activity indexes for CD (r(s) = 0.592, 95%CI: 0.385-0.742, p<0.001) or UC (r(s) = 0.598, 95%CI: 0.452-0.713, p<0.001), respectively. CONCLUSIONS AND SIGNIFICANCE: In this study, we demonstrated that established multivariate indexes composed of plasma amino acid profiles can serve as novel, non-invasive, objective biomarkers for the diagnosis and monitoring of IBD, providing us with new insights into the pathophysiology of the disease.

24 Article Ectopic expression of blood type antigens in inflamed mucosa with higher incidence of FUT2 secretor status in colonic Crohn's disease. 2011

Miyoshi, Jun / Yajima, Tomoharu / Okamoto, Susumu / Matsuoka, Katsuyoshi / Inoue, Nagamu / Hisamatsu, Tadakazu / Shimamura, Katsuyoshi / Nakazawa, Atsushi / Kanai, Takanori / Ogata, Haruhiko / Iwao, Yasushi / Mukai, Makio / Hibi, Toshifumi. ·Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japan. ·J Gastroenterol · Pubmed #21725903.

ABSTRACT: BACKGROUND: Host-intestinal microbial interaction plays an important role in the pathogenesis of inflammatory bowel diseases (IBDs). The surface molecules of the intestinal epithelium act as receptors for bacterial adhesion and regulate the intestinal bacteria. Some known receptors are the mucosal blood type antigens, which are regulated by the fucosyltransferase2 (FUT2) gene, and individuals who express these antigens in the gastrointestinal tract are called secretors. Recent research has revealed that the FUT2 gene is associated with Crohn's disease (CD) in western populations. METHODS: To clarify the contribution of mucosal blood type antigens in IBD, we determined the incidence of five previously reported single-nucleotide polymorphisms of the FUT2 gene in Japanese patients. We also used immunohistochemistry to investigate the antigen expression in mucosal specimens from IBD patients and animal models. RESULTS: Genetic analysis revealed that all of the patients with colonic CD were secretors, whereas the incidence of secretors was 80, 80, 67, and 80%, respectively, for the control, ileocolonic CD, ileal CD, and ulcerative colitis groups (P = 0.036). Abnormal expression of blood type antigens was observed only in colonic CD. Interleukin-10⁻/⁻ mice, but not dextran sulfate sodium colitis mice, had enhanced colonic expression of blood type antigens, and the expression of these antigens preceded the development of colitis in the interleukin-10⁻/⁻ mice. CONCLUSIONS: FUT2 secretor status was associated with colonic-type CD. This finding, taken together with the immunohistochemistry data, suggests that the abnormal expression of blood type antigens in the colon may be a unique and essential factor for colonic CD.