Masakazu Nagahori

Comparison of magnetic resonance and balloon enteroscopic examination of the small intestine in patients with Crohn's disease.

BACKGROUND & AIMS Magnetic resonance (MR) enterography is a recommended imaging technique for detecting intestinal involvement in Crohns disease (CD). However, the diagnostic accuracy of MR enterography has not been compared directly what that of enteroscopy of the jejunum and proximal ileum. We evaluated the usefulness of MR enterocolonography (MREC) by comparing its findings with those from balloon-assisted enteroscopy. METHODS In a prospective study, MREC and enteroscopy were performed within 3 days of each other on 100 patients. Ulcerative lesions and all mucosal lesions were evaluated. Physicians and radiologists were blinded to results from other studies. Findings from MREC were compared directly with those from enteroscopy; the sensitivity and specificity with which MREC detected CD lesions were assessed. RESULTS MREC detected ulcerative lesions and all mucosal lesions in the small intestine with 82.4% sensitivity (95% confidence interval [CI], 75.4%-87.7%) and 67.5% sensitivity (95% CI, 63.1%-70.0%); specificity values were 87.6% (95% CI, 83.7%-90.6%) and 94.8% (95% CI, 90.1%-97.5%). MREC detected major stenosis with 58.8% sensitivity (95% CI, 37.6%-77.2%) and 90.0% specificity (95% CI, 88.4%-91.5%) and all stenoses with 40.8% sensitivity (95% CI, 30.8%-49.4%) and 93.7% specificity (95% CI, 91.1%-95.9%). CONCLUSIONS MREC is useful for detecting active lesions in the small intestine. However, MR imaging is less sensitive for detecting intestinal damage, such as stenoses. Enteroscopy is preferred for identifying intestinal damage. Suitable imaging approaches should be selected to assess CD lesions in deep small intestine.

The 2nd edition of consensus statements for the diagnosis and management of intestinal Behçet’s disease: indication of anti-TNFα monoclonal antibodies

BackgroundClinical evidence regarding intestinal Behçet’s disease (BD) management is lacking and intestinal lesions are a poor prognostic factor. In 2007, the Japan consensus statement for diagnosis and management of intestinal BD was developed. Recently, the efficacy of anti-tumor necrosis factor (TNF)α monoclonal antibodies (mAbs), and infliximab (IFX) was reported and adalimumab (ADA) was approved for intestinal BD in Japan. This study renewed consensus-based practice guidelines for diagnosis and treatment of intestinal BD focusing on the indication of anti-TNFα mAbs.MethodsAn expert panel of Japanese gastroenterology and rheumatology specialists was involved. Clinical statements for ratings were extracted from the literature, a professional group survey, and by an expert panel discussion, which rated clinical statements on a nine-point scale. After the first round of ratings, a panelist meeting discussed areas of disagreement and clarified areas of uncertainty. The list of clinical statements was revised after the panelist meeting and a second round of ratings was conducted.ResultsFifteen relevant articles were selected. Based on the first edition consensus statement, improved clinical statements regarding indications for anti-TNFα mAbs use were developed. After a two-round modified Delphi approach, the second edition of consensus statements was finalized.ConclusionsIn addition to standard therapies in the first edition, anti-TNFα mAbs (ADA and IFX) should be considered as a standard therapy for intestinal BD. Colchicines, thalidomide, other pharmacological therapy, endoscopic therapy, and leukocytapheresis were deemed experimental therapies.

Magnetic resonance enterocolonography is useful for simultaneous evaluation of small and large intestinal lesions in Crohn's disease

Background: We developed novel magnetic resonance enterocolonography (MREC) for simultaneously evaluating both small and large bowel lesions in patients with Crohns 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. Methods: 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. Results: 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. Conclusions: 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. (Inflamm Bowel Dis 2010;)

Adalimumab for the Treatment of Japanese Patients With Intestinal Behçet’s Disease

BACKGROUND & AIMS Behçets disease is a chronic, relapsing inflammatory disease that can involve the mouth, skin, eyes, genitals, and intestines. Active intestinal Behçets disease can be complicated by gastrointestinal (GI) bleeding and perforation. We performed a multicenter, open-label, uncontrolled study to evaluate the efficacy and safety of adalimumab, a fully human monoclonal antibody against tumor necrosis factor α, in patients with intestinal Behçets disease who were refractory to corticosteroid and/or immunomodulator therapies. METHODS The study was conducted at 12 sites in Japan, from November 2010 through October 2012. Twenty patients were given 160 mg adalimumab at the start of the study and 80 mg 2 weeks later, followed by 40 mg every other week for 52 weeks; for some patients, the dose was increased to 80 mg every other week. A composite efficacy index, combining GI symptom and endoscopic assessments, was used to evaluate efficacy. The primary efficacy end point was the percentage of patients with scores of 1 or lower for GI symptom and endoscopic assessments at week 24. Secondary end points included complete remission and resolution of non-GI Behçets-related symptoms. RESULTS Nine patients (45%) had GI symptom and endoscopic assessment scores of 1 or lower at week 24 of treatment, and 12 patients (60%) had these scores by week 52. Four patients (20%) achieved complete remission at weeks 24 and 52. Individual global GI symptom and endoscopic scores improved for most patients at weeks 24 and 52. Two thirds of patients with oral aphthous ulcers, skin symptoms, and genital ulcers, and 88% of patients with erythema nodosum had complete resolution of these conditions at week 52. A total of 9 of 13 patients (69%) taking steroids at baseline were able to taper (n = 1) or completely discontinue steroids (n = 8) during the study. No new safety signals were observed. CONCLUSIONS Adalimumab is a potentially effective treatment for intestinal Behçets disease in Japanese patients who are refractory to conventional treatments. ClinicalTrials.gov number: NCT01243671.

Conception and pregnancy outcome in women with inflammatory bowel disease: A multicentre study from Japan

BACKGROUND 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. METHODS 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. RESULTS 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 Crohns 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. CONCLUSION 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.

Advancing magnetic resonance imaging in crohn's disease

Crohns disease (CD) is a lifelong chronic inflammatory bowel disease associated with diarrhea, abdominal pain, bloody stool and often perianal fistulae. Inflammation in CD involves the entire gastrointestinal tract, especially including the small and large bowels, causing irreversible bowel damage. Frequent imaging examinations are necessary to monitor disease activity and to evaluate response to therapeutic interventions, and, furthermore, to predict recurrence in order to provide appropriate treatment. The suitable imaging modality should be reproducible, well tolerated, safe and free of ionizing radiation. In recent years, imaging used in CD has dramatically changed. Cross-sectional imaging techniques such as computed tomography and magnetic resonance imaging (MRI) are used to investigate not only extraluminal abnormalities, but also intraluminal changes. Recently, new techniques such as MR enteroclysis, enterography, colonography and enterocolonography have been developed. These recent advances enable the use of MRI to assess bowel disorders with high sensitivity, specificity and accuracy. MRI can evaluate simultaneously the bowel surface, bowel wall, abdominal abscesses and perianal lesions, such as perianal fistulae and perianal abscesses, without the problem of overlapping bowel loops. Therefore, MRI has the potential for evaluation of the overall disease activity of CD without radiation exposure. We believe that MRI is a suitable first choice imaging modality in the assessment of CD.

Correlation of the endoscopic and magnetic resonance scoring systems in the deep small intestine in Crohn's disease

Background:There are no widely accepted endoscopic or magnetic resonance scoring systems to evaluate deep small intestinal lesions in Crohns disease (CD). This study aimed to determine whether the simplified endoscopic activity score for Crohns 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.

Poor recall of prior exposure to varicella zoster, rubella, measles, or mumps in patients with IBD†

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.

Tacrolimus for the Treatment of Ulcerative Colitis

Tacrolimus is a calcineurin inhibitor used for the treatment of corticosteroid-refractory ulcerative colitis (UC). Two randomized controlled trials and a number of retrospective studies have assessed the therapeutic effect of tacrolimus in UC patients. These studies showed that tacrolimus has excellent short-term efficacy in corticosteroid-refractory patients, with the rates of clinical response ranging from 61% to 96%. However, the long-term prognosis of patients treated with tacrolimus is disappointing, and almost 50% of patients eventually underwent colectomy in long-term follow-up. Tacrolimus can achieve mucosal healing in 40-50% of patients, and this is associated with a favorable long-term prognosis. Anti-tumor necrosis factor (TNF)-α antibodies are another therapeutic option in corticosteroid-refractory patients. A prospective head-to-head comparative study of tacrolimus and infliximab is currently being performed to determine which treatment is more effective in corticosteroid-refractory patients. Several retrospective studies have demonstrated that switching between tacrolimus and anti-TNF-α antibody therapy was effective in patients who were refractory to one of the treatments. Most adverse events of tacrolimus are mild; however, opportunistic infections, especially pneumocystis pneumonia, are the most important adverse events, and these should be carefully considered during treatment. Several issues on tacrolimus treatment in UC patients remain unsolved (e.g., use of tacrolimus as remission maintenance therapy). Further controlled studies are needed to optimize the use of tacrolimus for the treatment of UC.

Efficacy of salvage therapy and its effect on operative outcomes in patients with ulcerative colitis.

Aims: To evaluate the efficacy and safety of salvage therapy, and to identify risk factors of operative complications among hospitalized ulcerative colitis (UC) patients. Patients and Methods: We evaluated 88 UC patients hospitalized at our center between April 2010 and November 2012. We compared characteristics of corticosteroid-refractory patients treated with calcineurin inhibitor and those with infliximab as second-line therapy. Furthermore, we compared the characteristics of operative and nonoperative patients. The association between perioperative treatments and complications was also investigated. Results: Calcineurin inhibitor and infliximab were used in 42 and 22 patients, respectively. We found no difference in the clinical background between them. Efficacy rates were 67 and 50%, respectively. Eight out of 10 nonresponders of each treatment were treated with the other drug as third-line therapy. The efficacy rates of calcineurin inhibitor and infliximab as the third-line therapy were 75 and 50%, respectively. Operative patients had more severe disease (87.5 vs. 31%, p < 0.01), higher Lichtiger score (14.1 vs. 11.5, p < 0.01), higher Rachmilewitz endoscopic index (10.5 vs. 8.4, p < 0.01), higher C-reactive protein (7.6 vs. 4.0, p = 0.015) and lower serum albumin (3.1 vs. 3.6, p = 0.014) than nonoperative patients. Complications were observed in 7 out of 16 (44 %) operative patients. Postoperative complications were not increased even when patients were treated with second- or third-line therapy. However, the complication rate in corticosteroid users was 54.5 (6/11) and 20% (1/5) in nonusers. Conclusions: Third-line salvage therapy is effective and tolerable in carefully selected UC patients. Perioperative use of corticosteroids may lead to more adverse outcomes.