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ABSTRACT: The clinical management of ulcerative colitis (UC) involves first treating the acute symptoms to induce remission, and then successfully maintaining it. Oral 5-aminosalicylic acids are safe and useful for maintaining remission in patients with UC. In terms of adherence, a once-daily form of 5-aminosalicylic acid is superior in maintaining remission as compared with split dosing. Patients at high risk of relapse may be candidates for treatment with thiopurines and/or biologics in the early stages of UC. Calcineurin inhibitors, such as cyclosporine and tacrolimus, are effective for severe, steroid-refractory UC patients. It is suggested that these patients use thiopurines as their maintenance therapy once they achieve remission with calcineurin inhibitors. Recent studies have confirmed that biologics are effective for inducing clinical and endoscopic remission of UC, and thus they may improve long-term prognosis of UC.
Expert review of gastroenterology & hepatology 05/2013; 7(4):341-51.
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Naoki Hosoe,
Katsuyoshi Matsuoka, Makoto Naganuma,
Yosuke Ida,
Yuka Ishibashi,
Kayoko Kimura,
Kazuaki Yoneno,
Shingo Usui,
Kazuhiro Kashiwagi,
Tadakazu Hisamatsu,
Nagamu Inoue,
Takanori Kanai,
Hiroyuki Imaeda,
Haruhiko Ogata,
Toshifumi Hibi
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ABSTRACT: BACKGROUND AND AIM: Colon capsule endoscopy has already been used for colon visualization and detection of polyps but its applicability to inflammatory bowel disease is still unconfirmed. To assess the feasibility of evaluating the severity of mucosal inflammation in patients with ulcerative colitis (UC) using a second generation colon capsule endoscope (CCE-2). METHODS: Forty patients with histological confirmed diagnosis of UC were enrolled. Low volume (2L) polyethylene glycol solution (PEG) with prokinetics (mosapride citrate and metoclopramide) regimen were used for the bowel preparation. In Phase 1, consisting of 10 patients, to confirm appropriate CCE-2 bowel preparation for UC. In Phase 2, consisting of 30 patients, CCE-2 was performed with a fixed bowel preparation regimen. CCE-2 findings were recorded for 8 hours starting from capsule ingestion and conventional colonoscopy was subsequently performed on the same day. CCE-2 procedure completion rate and the colon cleansing level with a 4-point grading scale (poor, fair, good, and excellent) were evaluated in Phase 2. Correlations between Matts endoscopic scores as judged by CCE-2 and conventional colonoscopy were calculated. RESULTS: CCE-2 procedure was completed within 8 hours in 69% of the patients. The proportion of patients with good or excellent cleansing level was below 50%. However, Matts endoscopic scores determined by CCE-2 showed a strong correlation with scores obtained by conventional colonoscopy (average ρ = 0.797). CONCLUSIONS: Though modifications in bowel preparation are needed, CCE-2 might be feasible for assessing the severity of mucosal inflammation in patients with UC.
Journal of Gastroenterology and Hepatology 03/2013; · 2.87 Impact Factor
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ABSTRACT: BACKGROUND: Thirty to forty-five percent of ulcerative colitis (UC) patients show non-adherence to aminosalicylates, and non-adherence has been reported to increase the risk of clinical relapse. Because Japan differs from Western countries in terms of health care and drugs administered, adherence to aminosalicylates in Japan may differ from that elsewhere. Therefore, we examined aminosalicylate adherence and its relationship to the risk of clinical relapse of UC in Japan. METHODS: A 1-year, prospective cohort study was conducted in 104 outpatients with UC in remission who had taken aminosalicylates >6 months. Aminosalicylate adherence was evaluated using data from a self-administered questionnaire and medical records. Non-adherence was defined as taking <80 % of the prescribed dose of aminosalicylates. The primary outcome was the record of clinical relapse in medical charts. RESULTS: Twenty-nine patients (27.9 %) were evaluated as showing non-adherence. Among all subjects, 24 patients (23.1 %) relapsed. The non-adherence group had a higher rate of 1-year relapse than did the adherence group (41.3 vs. 16.0 %). Multiple Cox regression analysis showed that non-adherence increased the risk of clinical relapse 2.3-fold (hazard ratio 2.3, 95 % confidence interval 1.004-5.24, p = 0.04). CONCLUSIONS: Although the adherence rate in this study was slightly higher than that in previous studies, Japanese patients with UC who were not adherent to their medications had a twofold greater risk of relapse than those who were. These results indicate the importance of early identification of patients with non-adherence. A program to support medication taking behavior is needed to prevent UC relapse.
Journal of Gastroenterology 12/2012; · 4.16 Impact Factor
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ABSTRACT: BACKGROUND: Immunosuppressants lead to an increased risk of infection, but few prospective studies have assessed the incidence of opportunistic infections in inflammatory bowel disease (IBD) patients, a high proportion of whom are treated with immunosuppressants. The aim of this study was to assess the age distribution of Japanese IBD patients with opportunistic infections and the risk factors associated with these infections. METHODS: A multicenter, prospective study of 570 IBD patients was conducted. The patients were followed for up to 12 months to identify any new infections. The incidence of opportunistic infections and the age distribution of patients with these infections were analyzed. We carried out a case-control study in which 2 non-infected IBD patients were selected as controls for each case (infected IBD patient); the effect of medications on the infection rate was also examined. RESULTS: Fifty-two (9.1 %) of 570 IBD patients developed opportunistic infections. Herpes simplex virus and herpes zoster virus infections were observed in 29 and 16 patients, respectively. No cases of active tuberculosis were observed. The incidence of opportunistic infections in patients aged 50 years or over was significantly higher than that in the other age groups (p = 0.01). The use of steroids (p = 0.02), thiopurine (p < 0.01), and immunosuppressant combination therapy (p < 0.01) was associated with an increased rate of opportunistic infections. However, the use of infliximab was not associated with an increased rate of opportunistic infections (p = 0.62). Multivariate analysis indicated that the use of thiopurine was an independent risk factor for opportunistic infections (p < 0.01). CONCLUSIONS: Age ≥50 years and the use of immunosuppressants are risk factors for opportunistic infections in patients with IBD. In our cohort, tuberculosis was not seen as a complication of immunosuppressant therapy.
Journal of Gastroenterology 10/2012; · 4.16 Impact Factor
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Makoto Naganuma,
Toshimitsu Fujii,
Reiko Kunisaki,
Naoki Yoshimura,
Masakazu Takazoe,
Yoshiaki Takeuchi,
Eiko Saito,
Masakazu Nagahori,
Keiko Asakura,
Toru Takebayashi,
Mamoru Watanabe
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ABSTRACT: BACKGROUND: In 2009, influenza A (H1N1) infections spread worldwide. Because the use of immunomodulators is associated with an increased risk of infection, inflammatory bowel disease (IBD) patients who are on immunomodulators might be concerned about H1N1 influenza infections. The aim of this study was to investigate the age distribution and risk factors associated with H1N1 influenza of IBD patients in 2009-2010. METHODS: A multicenter, prospective study was conducted, and 570 IBD patients were enrolled. Patients were followed up for 10months to identify any new infections. The incidence and age distribution of the H1N1 influenza infections were analyzed. IBD patients with H1N1 influenza infections and 2 matched, noninfected IBD patients were selected to assess the effect of specifying the medication on the incidence of infections. RESULTS: A total of 38 patients (6.7%) developed H1N1 influenza infections. The incidence of H1N1 influenza infections in patients aged less than 20years was significantly higher than that among patients in other age groups (p<0.01). The age distribution for H1N1 influenza infections in IBD patients was comparable to those in the general population. No patients needed hospitalization due to influenza infection. A total of 29 patients (76%) recovered from the H1N1 influenza symptoms within 7days and 20 patients (53%) received antiviral treatment. The percentage of patients who used steroids or thiopurine was comparable between the cases of H1N1 influenza infection and the control group. CONCLUSION: Our prospective study showed that younger IBD patients were frequently infected with the influenza A (H1N1) virus as well as general population. Admission and fatal cases due to H1N1 influenza infections were not observed.
Journal of Crohn s and Colitis 07/2012; · 2.57 Impact Factor
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ABSTRACT: In capsule endoscopy (CE), the capsule does not always reach the cecum within its battery life, which may reduce its diagnostic yield. We evaluated the effect of mosapride citrate, a 5-hydroxytryptamine-4 agonist that increases gastrointestinal motility, on CE completion.
In a retrospective study, we performed univariate and multivariate analyses for 232 CE procedures performed at our hospital. To identify factors that affect CE completion, the following data were systematically collected: gender, age, gastric transit time (GTT), nonsteroidal anti-inflammatory drug administration, previous abdominal surgery, hospitalization, use of a polyethylene glycol solution, use of mosapride citrate (10 mg), body mass index (BMI), and total recording time.
The univariate analysis showed that oral mosapride citrate, GTT, and BMI were associated with improved CE completion. Multivariate analyses showed that oral mosapride citrate (odds ratio [OR], 1.99; 95% confidence interval [CI], 1.01 to 3.91) and GTT (OR, 2.34; 95% CI, 1.13 to 4.87) were significant factors for improving the CE completion. Oral mosapride citrate significantly shortened the GTT and small bowel transit time (SBTT).
Oral mosapride citrate reduced the GTT and SBTT during CE and improved the CE completion rate.
Gut and liver 07/2012; 6(3):339-43. · 0.83 Impact Factor
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Digestive Diseases and Sciences 06/2012; · 2.12 Impact Factor
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ABSTRACT: BACKGROUND: Few studies have measured the levels of antibodies specific for measles, mumps, rubella, and varicella zoster/chickenpox viruses in inflammatory bowel disease (IBD) patients undergoing treatment with immunomodulators/biologics. METHODS: We prospectively recruited 139 IBD outpatients. Enzyme-linked immunosorbent assays were used as the serological tests for measles, mumps, rubella, and varicella zoster. We defined anti-rubella IgG <10 IU/mL, anti-measles IgG <16 IU/mL, and anti-mumps/varicella zoster IgG <4 IU/mL as seronegative for viruses. We also asked participants about past immunizations against or infections with measles, mumps, rubella, and varicella zoster viruses. RESULTS: The proportion of patients with seronegative levels of antibodies specific for varicella zoster, rubella, measles, and mumps viruses was 5%, 30%, 34%, and 37%, respectively. Approximately 40% of the IBD patients did not remember whether they had previously been infected with any of the viruses, and almost one-third of the patients could not remember whether they had previously been vaccinated. Almost 30% of the patients with a past history of rubella or measles did not have seropositive antibody levels. A total of 54% of the patients being treated with immunosuppressant displayed seronegative levels of antibodies specific for at least one of the viruses. CONCLUSIONS: Many IBD patients were unaware of whether they had previously been vaccinated against or infected with the viruses causing varicella zoster, rubella, measles, or mumps. Therefore, measuring the current levels of antibodies specific for such viruses is useful for determining whether patients have seropositive antibody levels before immunomodulators/biologics are used for therapy. (Inflamm Bowel Dis 2012;).
Inflammatory Bowel Diseases 05/2012; · 4.86 Impact Factor
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ABSTRACT: We encountered a case of reactivation of hepatitis B virus after administration of infliximab for Crohn’s disease. The use
of infliximab was considered because the patient displayed abdominal symptoms and perianal lesions. Transaminases were normal,
and hepatitis B virus (HBV) DNA was undetectable before treatment, so no antiviral treatment was used, and infliximab and
low-dose 6-mercaptopurine were administered. This treatment was effective, but liver dysfunction and reactivation of HBV were
observed after the fourth injection of infliximab. This is the first report of Crohn’s disease for which infliximab use was
continued even after reactivation of HBV was observed. However, liver dysfunction was not improved by lamivudine. Antiviral
treatment should be considered before administration of infliximab for patients with HBV.
Journal of Gastroenterology 04/2012; 43(5):397-401. · 4.16 Impact Factor
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Nippon rinsho. Japanese journal of clinical medicine 02/2012; 70 Suppl 1:286-93.
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ABSTRACT: Behçet's disease is a chronic relapsing disease with multiple organ system involvement, including the gastrointestinal tract, which is known as intestinal Behçet's disease. Intestinal Behçet's disease is often resistant to empirical treatments such as 5-aminosalicylic acid, immunomodulators and steroids and often causes a perforation, requiring surgical resection. Therefore, intestinal lesions are considered to be a poor prognostic factor in Behçet's disease. Recently, several reports have demonstrated the efficacy of anti-TNFα monoclonal antibodies, such as infliximab, against intestinal Behçet's disease, however, it remains unknown whether anti-TNFα therapy can improve the prognosis of patients with intestinal Behçet's disease. We herein report the case of an adult female patient with intestinal Behçet's disease who responded well to the induction therapy with infliximab, and has been maintained in remission by scheduled administration of infliximab. Her C-reactive protein level has been sustained at a negative level, and endoscopic findings revealed complete mucosal healing. Therefore, infliximab may have the potential to induce "sustained deep remission" in patients with intestinal Behçet's disease.
Internal Medicine 01/2012; 51(16):2125-9. · 0.94 Impact Factor
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ABSTRACT: Ulcerative colitis (UC) and Crohn's disease (CD) is an inflammatory bowel disease of unknown aetiology characterized by periods of remission and acute episodes of relapse with severe inflammation in the colonic mucosa. Conventional treatments for UC and CD include 5-aminosalicylate, corticosteroid, elemental dietary treatment, corticosteroid, and thiopurine (azathioprine). Recently, new immunomodulators and anti-TNFa agents, such as tacrolimus, infliximab, and adalimumab have been developed and these treatments are available to be treated for patients with refractory UC and CD. Conventional step-up treatment has been replaced by top-down treatment using biologics. Infliximab and adalimumab induce not only clinical remission but also improve relapse rates and surgical rates. Endoscopic mucosal healing predicts short- and long-prognosis for both of these diseases, thus recent treatment strategy should be aimed for endoscopic remission. Although biologics is useful for patients with UC/CD, secondary loss of responses (LOR) for biologics has been partly observed in CD patients. Measuring anti-infliximab antibodies and concentration of infliximab trough level may help considering treatment strategy for patients with LOR.
Japanese Journal of Clinical Immunology 01/2012; 35(2):99-106.
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ABSTRACT: Aminosalicylates are effective in inducing remission and are also useful in preventing relapse of ulcerative colitis (UC); however, previous studies have reported a 30%-45% rate of nonadherence to prescribed medication among UC patients. Enumerating and conceptualizing the difficulties in taking aminosalicylates enable us to assess and support patients more effectively. The aim of this study was to investigate the difficulties in taking aminosalicylates among Japanese UC patients and explore factors related to these difficulties. Outpatients with UC (n = 242) completed a questionnaire supported by a semistructured interview on the basis of a literature review. Twelve items about difficulties in taking aminosalicylates were processed by factor analysis and the related factors regarding difficulties were analyzed. The following three independent domains were identified: Domain 1: diminished sense of priority for medication; Domain 2: concern about side effects; and Domain 3: burden of taking the prescribed drug. Factors related to the difficulties in taking aminosalicylates included the disease state, psychosocial factors, and demographic characteristic variables. On the basis of the results, we recommend the creation and validation of a program aimed at decreasing the difficulties in taking aminosalicylates.
Gastroenterology nursing: the official journal of the Society of Gastroenterology Nurses and Associates 01/2012; 35(1):24-31. · 0.47 Impact Factor
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ABSTRACT: Capsule endoscopy (CE) is a comfortable for the patients; however, CE review is time-consuming. The aim of this study was (1) to evaluate the effectiveness of the CE software in reducing the CE reading time and the number of false negatives by beginners, and (2) to determine the learning curve for reading CE images.
Capsule endoscopic images were captured by Pillcam SB (Given Imaging Ltd, Tokyo, Japan), and analyzed using the proprietary RAPID 5 software. Comparison of CE reading using different software modes: manual mode, automatic mode, and QuickView (QV) mode. Three trainee endoscopists participated as CE readers. Each participant watched CE videos in which positive findings had been predefined by trained endoscopists. Each participant read the same CE record by using one of three different software modes. These were blinded on clinical history of patients. CE reading time was recorded, and the number of false negatives was counted. Each trainee endoscopist read a total of 45 CE videos, in five steps divided into nine videos per step.
There was no significant reader associated difference between the results for the different modes. The QV software did miss some positive findings. Therefore, the total number of instances of FN by the software plus the reader in the QV mode was significantly higher than the others. The reading times in the automatic mode and the QV mode were significantly shorter than that in the manual mode. After the second step, the number of instances of false negatives significantly decreased.
CE software is useful for reducing the reading time. Experience of approximately 20 CE readings can be considered as the first step to becoming an expert.
Gastroentérologie Clinique et Biologique 11/2011; 36(1):66-71. · 0.80 Impact Factor
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Makoto Naganuma,
Reiko Kunisaki,
Naoki Yoshimura,
Masakazu Nagahori,
Hisae Yamamoto,
Hideaki Kimura,
Minako Sako,
Takaaki Kawaguchi,
Masakazu Takazoe,
Shojiro Yamamoto,
Toshiyuki Matsui,
Toshifumi Hibi,
Mamoru Watanabe
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ABSTRACT: Neither conceptions and pregnancy outcomes nor the safety of medications for childbearing inflammatory bowel disease (IBD) patients has been investigated in Asia. The aim of this study is to analyse conception and pregnancy outcomes of Japanese female IBD patients.
We conducted a retrospective cohort study of pregnant IBD patients at 6 institutions. The incidences of abortion, Caesarean delivery, low birth weight (LBW) (<2500g), and congenital malformation were analysed in these patients. Risk factors associated with adverse outcomes in IBD patients were also assessed.
A total of 325 patients experienced 534 conceptions. Among these, 303 conceptions (57%) were observed during/after disease onset. Although conceptions and pregnancy outcomes after disease onset were comparable to the observed levels prior to disease onset in UC patients, the incidences of spontaneous abortion (OR 5.3; 95%CI 1.1-25.0) and Caesarean delivery (OR 4.8; 95%CI 1.5-15.0) were significantly higher in Crohn's disease (CD) patients whose conceptions occurred after disease onset compared to CD patients whose conceptions occurred before disease onset. The incidences of spontaneous abortion, LBW, and Caesarean delivery were higher in CD patients who had a history of surgery for perianal lesions than in those who did not have perianal lesions or who had ulcerative colitis (UC). In the IBD patients studied after disease onset, independent risk factors for spontaneous abortions included a history of previous treatment for sterility (OR 2.9; 95%CI 1.2-7.0). Independent risk factors for Caesarean operation (OR 4.1, 95% CI: 1.7-10.1) and LBW (OR 3.5, 95% CI: 1.3-9.1) included a history of bowel resection for the treatment of IBD. Congenital malformation was not associated with the factors of type of disease, smoking, and previous surgery.
In Japanese UC patients, conception and pregnancy outcomes after disease onset were comparable to the outcomes observed prior to disease onset, whereas CD appeared to be associated with adverse outcomes. Caesarean operation and LBW were more frequently observed in CD patients who had a history of surgery for perianal lesions and bowel resection.
Journal of Crohn s and Colitis 09/2011; 5(4):317-23. · 2.57 Impact Factor
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Sea Bong Hyun,
Yoshio Kitazume,
Masakazu Nagahori,
Akira Toriihara,
Toshimitsu Fujii,
Kiichiro Tsuchiya,
Shinji Suzuki,
Eriko Okada,
Akihiro Araki, Makoto Naganuma,
Mamoru Watanabe
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ABSTRACT: We developed novel magnetic resonance enterocolonography (MREC) for simultaneously evaluating both small and large bowel lesions in patients with Crohn's disease (CD). The aim of this study was to evaluate the diagnostic performance of MREC by comparing results of this procedure to those of endoscopies for evaluating the small and large bowel lesions of patients with CD.
Thirty patients with established CD were prospectively examined by newly developed MREC. Patients underwent ileocolonoscopy (ICS) (24 procedures) or double-balloon endoscopy (DBE) (10 procedures) after MREC on the same day. Two gastroenterologists and two radiologists who were blinded to the results of another study evaluated endoscopy and MREC findings, respectively.
In colonic lesions the sensitivities of the MREC for deep mucosal lesions (DML), all CD lesions, and stenosis were 88.2, 61.8, and 71.4%, respectively, while the specificities were 98.1, 95.3, and 97.7%, respectively. In small intestinal lesions, MREC sensitivities for DML, all CD lesions, and stenosis were 100, 85.7, and 100%, respectively, while specificities were 100, 90.5, and 93.1%, respectively. Endoscopic scores were significantly correlated with MREC scores. Eleven (46%) of the 24 patients who were clinically not suspected to show stricture were observed to demonstrate stricture by radiologists.
Our results demonstrated that MREC can simultaneously detect the CD lesions of the small and large intestine. MREC can be performed without radiation exposure, the use of enema, or the placement of a naso-jejunal catheter. MREC and endoscopy have comparable abilities for evaluating mucosal lesions of patients with CD.
Inflammatory Bowel Diseases 05/2011; 17(5):1063-72. · 4.86 Impact Factor
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Nippon Shokakibyo Gakkai zasshi The Japanese journal of gastro-enterology 03/2011; 108(3):388-400.
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Journal of Crohn s and Colitis 02/2011; 5(1):73-4. · 2.57 Impact Factor
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ABSTRACT: Intravenous cyclosporine A (CsA) is an effective treatment for patients with severe, steroid-refractory ulcerative colitis (UC). Like the response to CsA, clinical trials have shown that two-thirds of patients with refractory UC respond to tacrolimus therapy. However, it is unclear how/when this agent should be used for patients with active UC.
We reviewed the results of previous studies regarding calcineurin inhibitors in UC patients. We examined the best way to use tacrolimus to obtain maximum efficacy by comparing the results from clinical trials with those from a recent survey in Japan.
Calcineurin inhibitors are useful to induce remission in patients with refractory UC; however, the long-term prognosis has not been shown to be improved by CsA. Early intervention with CsA/tacrolimus may improve the long-term prognosis of UC patients just as infliximab does for Crohn's disease patients. Recent studies have indicated that a fasting state and administration of a higher dosage of tacrolimus at the beginning of therapy are critical in ensuring that the target trough concentration of the agent is reached.
The use of higher initial doses of tacrolimus ensured that patients achieved their target levels. Further studies will be needed to elucidate the efficacy of top-down therapy with tacrolimus in patients with UC. Physicians must know how to use calcineurin inhibitors to obtain maximum efficacy.
Journal of Gastroenterology 02/2011; 46(2):129-37. · 4.16 Impact Factor
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Shoko Nakamura,
Hiroyuki Imaeda,
Tomohisa Sujino,
Naoki Hosoe, Makoto Naganuma,
Hirotoshi Ebinuma,
Susumu Okamoto,
Toshihiro Nishizawa,
Masahiko Takahashi,
Yasushi Iwao,
Kaori Kameyama,
Makio Mukai,
Haruhiko Ogata,
Toshifumi Hibi
Gastrointestinal endoscopy 12/2010; 73(5):1041-2. · 6.71 Impact Factor
