2.Treatment and outcomes: medical and surgical treatment for intestinal Behçet's disease.
Tadakazu HISAMATSU ; Mari HAYASHIDA
Intestinal Research 2017;15(3):318-327
Behçet's disease (BD) is a chronic relapsing disease involving multiple organ systems. BD is characterized clinically by oral and genital aphthae, cutaneous lesions, and ophthalmological, neurological, and/or gastrointestinal manifestations. It is widely recognized that the presence of intestinal lesions may be a poor prognostic factor in intestinal BD, increasing the risk of surgery and decreasing the quality of life. Despite this, the management of intestinal BD has not been standardized. Empirical therapies including 5-aminosalicylic acid and corticosteroids have been used anecdotally to treat intestinal BD, but recent studies have provided evidence for the efficacy of anti-tumor necrosis factor α monoclonal antibodies. The development of agents targeting tumor necrosis factor α continues, it seems likely that they will change the therapeutic strategy and clinical outcomes of intestinal BD and inflammatory bowel disease. Monitoring disease activity such as endoscopic evaluation will become more important to obtain better outcomes. Here, we review current and future perspectives in the treatment and outcomes of intestinal BD.
Adrenal Cortex Hormones
;
Antibodies, Monoclonal
;
Inflammatory Bowel Diseases
;
Mesalamine
;
Necrosis
;
Quality of Life
;
Stomatitis, Aphthous
;
Tumor Necrosis Factor-alpha
3.First aid with color atlas for the use of intestinal ultrasound for inflammatory bowel disease in daily clinical practice
Jun MIYOSHI ; Hiromu MORIKUBO ; Hiromi YONEZAWA ; Hideaki MORI ; Tadakazu HISAMATSU
Intestinal Research 2023;21(2):177-188
Intestinal ultrasound (IUS) is a promising modality for the management of inflammatory bowel disease (IBD) and has the potential to particularly contribute in monitoring disease activity, an advantage crucial for optimizing the therapeutic strategy. While many IBD physicians appreciate and are interested in the use of IUS for IBD, currently only a limited number of facilities can employ this examination in daily clinical practice. A lack of guidance is one of the major barriers to introducing this procedure. Standardized protocols and assessment criteria are needed such that IUS for IBD can be considered a feasible, reliable examination in clinical practice, and multicenter clinical studies can be conducted for further clinical evidence of the application of IUS in IBD for best patient care. In this article, we provide an overview of how to start IUS for IBD and introduce basic procedures. Furthermore, IUS images from our practice are provided as a color atlas for understanding sonographic findings and scoring systems. We anticipate this “first aid” article will be helpful to promote IUS for IBD in daily practice.
4.Diet, microbiota, and inflammatory bowel disease: lessons from Japanese foods.
Takanori KANAI ; Katsuyoshi MATSUOKA ; Makoto NAGANUMA ; Atsushi HAYASHI ; Tadakazu HISAMATSU
The Korean Journal of Internal Medicine 2014;29(4):409-415
The incidence and prevalence of inflammatory bowel diseases (IBDs) including ulcerative colitis and Crohn disease are rapidly increasing in Western countries and in developed Asian countries. Although biologic agents targeting the immune system have been effective in patients with IBD, cessation of treatment leads to relapse in the majority of patients, suggesting that intrinsic immune dysregulation is an effect, not a cause, of IBD. Dramatic changes in the environment, resulting in the dysregulated composition of intestinal microbiota or dysbiosis, may be associated with the fundamental causes of IBD. Japan now has upgraded water supply and sewerage systems, as well as dietary habits and antibiotic overuse that are similar to such features found in developed Western countries. The purpose of this review article was to describe the association of diet, particularly Japanese food and microbiota, with IBD.
Animals
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*Asian Continental Ancestry Group
;
Diet/*ethnology
;
Evidence-Based Medicine
;
Food Habits/ethnology
;
Humans
;
Incidence
;
Inflammatory Bowel Diseases/diagnosis/diet therapy/*ethnology/immunology/*microbiology
;
Intestines/immunology/*microbiology
;
Japan/epidemiology
;
*Microbiota
;
Prevalence
;
Probiotics/therapeutic use
;
Prognosis
;
Risk Factors
5.Immunological Abnormalities in the Pathogenesis of Inflammatory Bowel Disease.
Tadakazu HISAMATSU ; Yohei MIKAMI ; Katsuyoshi MATSUOKA ; Takanori KANAI ; Toshifumi HIBI
Intestinal Research 2012;10(4):317-323
Crohn's disease and ulcerative colitis represent two distinct forms of inflammatory bowel diseases (IBD). In this paper, we discuss how immunological mechanisms contribute to the pathogenesis of IBD. Intestinal homeostasis is sustained by various kinds of cells, such as epithelial cells, lymphocytes, antigen presenting cells, and other innate immune cells. We pay special attention to intestinal CD14+ macrophages. Intestinal macrophages play a central role in the regulation of immune responses against commensal bacteria. In the physiological condition, intestinal macrophages lack the expression of innate-immune receptor CD14 and do not produce proinflammatory cytokines. We identified a unique macrophage subset of IBD in the human intestine, which expressed both macrophage (CD14, CD33, CD68) and dendritic cell (DC) markers (CD205, CD209) and produced larger amounts of proinflammatory cytokines, such as interleukin (IL)-23 and tumor necrosis factor (TNF)-alpha. In addition, the CD14+ macrophages contributed to interferon (IFN)-gamma production rather than IL-17 production by lamina propria mononuclear cells dependent on IL-23. We discuss herein this IL-23/IFN-gamma-positive feedback loop in IBD patients. We also discuss IFN-gamma and IL-17 production from mucosal T cells and natural killer (NK) cells. Here, we show our recent findings about the plasticity of T helper cells in colitis. Th 17 cells express T-bet, and finally lose the expression of retinoic acid-related orphan receptor (ROR)gammat, the master regulator of Th 17 cells, and are differentiated 'alternative Th 1 cells.' In addition to Th 1 cells, mucosal NK cells are also important sources of IFN-gamma. Some of our ideas may be provocative, but we hope this review paper will provide new and firm understanding of the pathogenesis of IBD.
Antigen-Presenting Cells
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Bacteria
;
Child
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Child, Orphaned
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Colitis
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Colitis, Ulcerative
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Crohn Disease
;
Cytokines
;
Dendritic Cells
;
Epithelial Cells
;
Homeostasis
;
Humans
;
Inflammatory Bowel Diseases
;
Interferons
;
Interleukin-17
;
Interleukin-23
;
Interleukins
;
Intestines
;
Killer Cells, Natural
;
Lymphocytes
;
Macrophages
;
Mucous Membrane
;
Plastics
;
T-Lymphocytes
;
T-Lymphocytes, Helper-Inducer
;
Tumor Necrosis Factor-alpha
6.Long-term safety and effectiveness of adalimumab in Japanese patients with Crohn’s disease: 3-year results from a real-world study
Tadakazu HISAMATSU ; Yasuo SUZUKI ; Mariko KOBAYASHI ; Takashi HAGIWARA ; Takeshi KAWABERI ; Haruhiko OGATA ; Toshiyuki MATSUI ; Mamoru WATANABE ; Toshifumi HIBI
Intestinal Research 2021;19(4):408-418
Background/Aims:
Crohn’s disease is a chronic disorder; therefore, it is essential to investigate long-term safety and efficacy of treatments. This study assessed the safety and effectiveness of adalimumab for up to 3 years in Japanese patients with Crohn’s disease in real-world settings.
Methods:
This was a multicenter, single-cohort, observational study of patients with Crohn’s disease. Safety assessments included incidence of adverse drug reactions. Effectiveness assessments included clinical remission, mucosal healing, and Work Productivity and Activity Impairment (WPAI).
Results:
The safety and effectiveness analysis populations comprised 389 and 310 patients, respectively. Mean (standard deviation) exposure to adalimumab in the safety analysis population was 793.4 (402.8) days, with a 58.1% retention rate. A total of 105 patients (27.0%) and 43 patients (11.1%) experienced adverse drug reactions and serious adverse drug reactions, respectively, with no patient reporting tuberculosis or hepatitis B. Infections and serious infections were reported in 37 patients (9.5%) and 17 patients (4.4%), respectively. Malignancy was reported as an adverse drug reaction in 2 patients (0.5%). Remission rate increased from 37.8% (98/259) at baseline to 73.9% (167/226) at week 4 and remained > 70% over 3 years. Proportion of patients without mucosal ulcerations increased from 2.7% (2/73) at baseline to 42.3% (11/26) between years > 2 to ≤ 3. WPAI improvement started at 4 weeks, with the overall work impairment score improving from 42.7 (n = 102) at baseline to 26.9 (n = 84) at 4 weeks.
Conclusions
Results from this study confirm the long-term safety and effectiveness of adalimumab treatment in Japanese patients with Crohn’s disease in the real-world setting.
7.Treatment of inflammatory bowel disease–Asian perspectives: the results of a multinational web-based survey in the 8th Asian Organization for Crohn’s and Colitis meeting
Eun Mi SONG ; Soo-Young NA ; Sung Noh HONG ; Siew Chien NG ; Tadakazu HISAMATSU ; Byong Duk YE
Intestinal Research 2023;21(3):339-352
Background/Aims:
As the characteristics of inflammatory bowel disease (IBD) differ between Asians and Westerners, it is necessary to determine adequate therapeutic strategy for Asian IBD patients. We evaluated the current treatment of IBD in Asian countries/regions using a web-based survey.
Methods:
The Korean Association for the Study of Intestinal Diseases conducted a multinational web-based survey for current IBD care in Asia between September 16, 2020, and November 13, 2020.
Results:
A total of 384 doctors treating IBD patients from 24 Asian countries/regions responded to the survey. Anti-tumor necrosis factor (TNF) agents, anti-integrins, and anti-interleukin-12/23 agents were available for use by 93.8%, 72.1%, and 70.1% of respondents in Asian countries/regions. Compared with a previous survey performed in 2014, an increased tendency for treatment with biologics, including anti-TNF agents, was observed. In the treatment of corticosteroid-refractory acute severe ulcerative colitis, 72.1% of respondents chose anti-TNF agents, followed by tacrolimus (11.7%). In the treatment of corticosteroid-refractory Crohn’s disease, 90.4% chose anti-TNF agents, followed by thiopurines (53.1%), anti-interleukin-12/23 agents (39.3%), and anti-integrin agents (35.7%). In the treatment of Crohn’s disease patients refractory to anti-TNF agents, the most preferred strategy was to measure serum levels of anti-TNF and anti-drug antibodies (40.9%), followed by empiric dose escalation or shortening of dosing intervals (25.3%).
Conclusions
Although there were some differences, treatment strategies for patients with IBD were mostly similar among Asian doctors. Based on the therapeutic outcomes, it is necessary to identify the most appropriate therapeutic strategy for Asian IBD patients.
8.Ileal Mucosa-Associated Lymphoid Tissue (MALT) Lymphoma with a Large-Cell Component That Regressed Spontaneously.
Yohsuke MAKINO ; Hidekazu SUZUKI ; Toshihiro NISHIZAWA ; Kaori KAMEYAMA ; Tadakazu HISAMATSU ; Hiroyuki IMAEDA ; Makio MUKAI ; Toshifumi HIBI
Gut and Liver 2010;4(1):117-121
Reported herein is a case of mucosa-associated lymphoid tissue (MALT) lymphoma of the terminal ileum with a large-cell component, which regressed spontaneously. To the best of our knowledge, only five cases of spontaneously regressing MALT lymphoma have been reported in the English-language literature, and all of these cases were low-grade lymphomas. Spontaneous regression of a MALT lymphoma with a high-grade component is very rare. The present case suggests that MALT lymphoma cells have a reversible nature, even in the presence of a high-grade component.
Ileum
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Lymphoid Tissue
;
Lymphoma
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Lymphoma, B-Cell, Marginal Zone
;
Lymphoma, Non-Hodgkin
9.Randomized, crossover questionnaire survey of acceptabilities of controlled-release mesalazine tablets and granules in ulcerative colitis patients
Keiji YAGISAWA ; Taku KOBAYASHI ; Ryo OZAKI ; Shinji OKABAYASHI ; Takahiko TOYONAGA ; Miki MIURA ; Mari HAYASHIDA ; Eiko SAITO ; Masaru NAKANO ; Hajime MATSUBARA ; Tadakazu HISAMATSU ; Toshifumi HIBI
Intestinal Research 2019;17(1):87-93
BACKGROUND/AIMS: Oral mesalazine is an important treatment for ulcerative colitis (UC), and non-adherence to mesalazine increases the risk of relapse. Controlled-release (CR) mesalazine has 2 formulations: tablets and granules. The relative acceptabilities of these formulations may influence patient adherence; however, they have not been compared to date. This study aimed to evaluate the acceptabilities of the 2 formulations of CR mesalazine in relation to patient adherence using a crossover questionnaire survey. METHODS: UC patients were randomly assigned to 2 groups in a 1:1 ratio. Patients in each group took either 4 g of CR mesalazine tablets or granules for 6 to 9 weeks, and then switched to 4 g of the other formulation for a further 6 to 9 weeks. The acceptability and efficacy were evaluated by questionnaires, and adherence was assessed using a visual analog scale. The difference in acceptabilities between the 2 formulations and its impact on adherence were assessed. RESULTS: A total of 49 patients were prospectively enrolled and 33 patients were included in the analysis. Significantly more patients found the tablets to be less acceptable than the granules (76% vs. 33%, P=0.0005). The granules were preferable to the tablets when the 2 formulations were compared directly (73% vs. 21%, P=0.004), for their portability, size, and numbers of pills. The adherence rate was slightly better among patients taking the granules (94% vs. 91%) during the observation period, but the difference was not significant (P=0.139). CONCLUSIONS: CR mesalazine granules are more acceptable than tablets, and may therefore be a better option for long-term medication.
Colitis, Ulcerative
;
Drug Compounding
;
Humans
;
Medication Adherence
;
Mesalamine
;
Patient Acceptance of Health Care
;
Patient Compliance
;
Prospective Studies
;
Recurrence
;
Tablets
;
Ulcer
;
Visual Analog Scale
10.Evaluation of the drug-induced lymphocyte stimulation test for diagnosing mesalazine allergy.
Daisuke SAITO ; Mari HAYASHIDA ; Taro SATO ; Shintaro MINOWA ; Osamu IKEZAKI ; Tatsuya MITSUI ; Miki MIURA ; Akihito SAKURABA ; Tadakazu HISAMATSU
Intestinal Research 2018;16(2):273-281
BACKGROUND/AIMS: Mesalazine is an effective drug for treating ulcerative colitis (UC), but causes allergic symptoms in a few cases. Therefore, the objective of this study was to evaluate the usefulness of the drug-induced lymphocyte stimulation test (DLST) for the diagnosis of mesalazine allergy. METHODS: Patients with UC treated with mesalazine with or without a history of associated adverse events (AEs) were enrolled at Kyorin University Hospital from July 2016 to April 2017. RESULTS: The DLST was performed in 104 patients with UC, of which 24 had a history of AEs due to mesalazine treatment. The control value of DLST was 337.4±296.3 counts per minute (cpm) in the AE+ group and 408.0±371.9 cpm in the AE− group. The measured value of DLST was 578.8±424.7 cpm in the AE+ group and 476.5±471.8 cpm in the AE− group. The stimulation index (SI) was 243.9%±291.1% in the AE+ group and 119.8%±53.0% in the AE− group. The SI value and DLST positivity were significantly higher in the AE+ group than in the AE− group (P=0.030 and P=0.029, respectively). The test sensitivity and specificity were 0.240 and 0.805, respectively, and the false-positive and false-negative rate was 0.195 and 0.760, respectively. CONCLUSIONS: The DLST for mesalazine showed low sensitivity and high specificity, suggesting that it may be useful for the definitive diagnosis of allergy to mesalazine.
Colitis, Ulcerative
;
Diagnosis
;
Humans
;
Hypersensitivity*
;
Lymphocyte Activation*
;
Lymphocytes*
;
Mesalamine*
;
Sensitivity and Specificity