Eiko Saito

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.

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.

Incidence and characteristics of the 2009 influenza (H1N1) infections in inflammatory bowel disease patients

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 10 months 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 20 years 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 7 days 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.

Utility of Magnetic Resonance Enterography For Small Bowel Endoscopic Healing in Patients With Crohn’s Disease

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.

Histologically Confirmed IgG4-Related Small Intestinal Lesions Diagnosed via Double Balloon Enteroscopy

Immunoglobulin G4 (IgG4)-related disease is a systemic disease characterized by chronic inflammation with abundant IgG4-positive cells and elevated serum IgG4. Previous reports describe infiltration of IgG4-positive cells in multiple organs [1]. In the gastrointestinal (GI) tract, previous reports indicate that inflammation was observed in the esophagus, stomach, and colon [1–6]. However, there have been few reports regarding small intestinal lesions. We report a case of IgG4-related disease with small and large intestinal lesions. A 55-year-old man presented to our hospital with 4 months of general fatigue and lower abdominal pain. He had the past history of cholecystectomy and did not take any non-steroidal anti-inflammatory drugs. He was admitted because his abdominal pain was worsening. The findings of abdominal computed tomography (CT) scan indicated that his pancreas was swollen; however, he did not have any ocular, salivary gland, and retroperitoneal lesions. Blood tests revealed high levels of C-reactive protein (4.1 mg/dL), elevated IgG (5,636 mg/dL), and IgG4 (2,480 mg/dl) levels. Nephritis was suspected because urinary tests revealed elevated beta-2 microglobulin and N-acetyl-b-D-glucosaminidase although renal biopsy was not done. Histological findings from cervical lymph node indicated infiltration of IgG4-positive cells while malignant lymphoma and Castleman’s disease were excluded. Esophagogastroduodenoscopy (EGD) and colonoscopic findings revealed multiple erosions and ulcerations in the stomach and colon (Fig. 1a,b). The abdominal CT also indicated increased bowel wall thickness of the proximal small intestine, therefore we performed double balloon enteroscopy (DBE). Small erosions and irregular ulcerations were observed at the jejunum (Fig. 1c,d) while inflammation was not observed in the ileum. These lesions included neither longitudinal nor circular ulcerations. Membranous strictures were not observed. Histological findings from biopsy specimens revealed infiltration of inflammatory cells, including plasma cells (Fig. 2a,b) in the jejunum. The percentage of IgG4-positive cells among IgG-positive plasma cells was approximately 70 % (Fig. 2c,d). IgG4-positive cells were detected not only from specimens containing erosions but also from endoscopically normal mucosa in the ileum (Fig. 2e,f). A total of 40 mg daily of oral prednisolone was given and his symptoms rapidly improved. At 3 months after administration of corticosteroids, the colonoscopy indicated colonic ulceration was improved (Fig. 3). However, IgG4positive cells remained even after clinical remission was obtained by the use of corticosteroids. Thus, dose of steroid has been gradually decreased to avoid relapsing remission. On the basis of the elevated serum IgG4 level and histological analysis (ratio of IgG4/IgG [ 50 % in the cervical lymph node and GI tracts), this patient was diagnosed K. Fujita M. Naganuma (&) E. Saito S. Suzuki A. Araki M. Watanabe Departments of Gastroenterology and Hepatology, School of Medicine, Tokyo Medical and Dental University, 1-5-45, Yushima, Bunkyo-ku, Tokyo 113-8519, Japan e-mail: mnaganuma.gast@tmd.ac.jp

Prediction of disease activity of Crohn's disease through fecal calprotectin evaluated by balloon-assisted endoscopy: Fecal calprotectin and Crohn's disease

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 Crohns 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.