Kento Takenaka

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.

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.

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.

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.

Magnetic resonance enterography for the evaluation of the deep small intestine in Crohn's disease.

For the control of Crohns disease (CD) a thorough assessment of the small intestine is essential; several modalities may be utilized, with cross-sectional imaging being important. Magnetic resonance (MR) enterography, i.e., MRE is recommended as a modality with the highest accuracy for CD lesions. MRE and MR enteroclysis are the two methods performed following distension of the small intestine. MRE has sensitivity and specificity comparable to computed tomography enterography (CTE); although images obtained using MRE are less clear compared with CTE, MRE does not expose the patient to radiation and is superior for soft-tissue contrast. Furthermore, it can assess not only static but also dynamic and functional imaging and reveals signs of CD, such as abscess, comb sign, fat edema, fistula, lymph node enhancement, less motility, mucosal lesions, stricture, and wall enhancement. Several indices of inflammatory changes and intestinal damage have been proposed for objective evaluation. Recently, diffusion-weighted imaging has been proposed, which does not need bowel preparation and contrast enhancement. Comprehension of the characteristics of MRE and other modalities is important for better management of CD.

Endoscopic features and genetic background of inflammatory bowel disease complicated with Takayasu arteritis

Takayasu arteritis (TA) is occasionally complicated with inflammatory bowel disease (IBD). This study assessed the endoscopic and genetic features of IBD complicated with TA (IBD‐TA).

Single cell analysis of Crohn’s disease patient-derived small intestinal organoids reveals disease activity-dependent modification of stem cell properties

BackgroundIntestinal stem cells (ISCs) play indispensable roles in the maintenance of homeostasis, and also in the regeneration of the damaged intestinal epithelia. However, whether the inflammatory environment of Crohn’s disease (CD) affects properties of resident small intestinal stem cells remain uncertain.MethodsCD patient-derived small intestinal organoids were established from enteroscopic biopsy specimens taken from active lesions (aCD-SIO), or from mucosa under remission (rCD-SIO). Expression of ISC-marker genes in those organoids was examined by immunohistochemistry, and also by microfluid-based single-cell multiplex gene expression analysis. The ISC-specific function of organoid cells was evaluated using a single-cell organoid reformation assay.ResultsISC-marker genes, OLFM4 and SLC12A2, were expressed by an increased number of small intestinal epithelial cells in the active lesion of CD. aCD-SIOs, rCD-SIOs or those of non-IBD controls (NI-SIOs) were successfully established from 9 patients. Immunohistochemistry showed a comparable level of OLFM4 and SLC12A2 expression in all organoids. Single-cell gene expression data of 12 ISC-markers were acquired from a total of 1215 cells. t-distributed stochastic neighbor embedding analysis identified clusters of candidate ISCs, and also revealed a distinct expression pattern of SMOC2 and LGR5 in ISC-cluster classified cells derived from aCD-SIOs. Single-cell organoid reformation assays showed significantly higher reformation efficiency by the cells of the aCD-SIOs compared with that of cells from NI-SIOs.ConclusionsaCD-SIOs harbor ISCs with modified marker expression profiles, and also with high organoid reformation ability. Results suggest modification of small intestinal stem cell properties by unidentified factors in the inflammatory environment of CD.

Laterally Spreading Tumor-like Early Cancer in Ileum

An 84-year-old man with continuing iron deficiency anemia was referred to our hospital. Esophagogastroduodenoscopy and ileocolonoscopy showed no significant hemorrhagic lesions. The patient underwent retrograde balloonassisted enteroscopy (BAE). A laterally spreading tumor (LST)-like tumor with an erythematous perimeter was detected in the ileum 60 cm from the ileocecal valve (Picture 1, 2). An analysis of the biopsy specimen revealed a neoplastic lesion, and the tumor was surgically resected. The definitive diagnosis according to a pathologic analysis was

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.

P-085 Adverse Effects on Renal Function in Long-Term Use of Tacrolimus for Ulcerative Colitis Patients

Background:Safety of long-term administration of tacrolimus for refractory ulcerative colitis (UC) is not well understood. Methods:Thirty-one UC patients who were refractory to conventional therapies were administered tacrolimus beyond 3 months and evaluated. Twelve patients were started with tacrolimus (0.1–0.15 mg/kg body weight per day) orally and 19 patients were started with tacrolimus (0.01–0.02 mg/kg body weight per day) intravenously, and then switched to with oral route. Serum trough levels of tacrolimus were aimed between 10 and 15 ng/mL to induce clinical remission and between 5 and 10 ng/mL to maintain it. After discharge, patients were evaluated biochemical values including renal function tests at least every 4 weeks. After tacrolimus had discontinued, the renal function was followed until 1 year. The primary endpoint of this study was the incidence rate of chronic kidney disease (CKD) at 1 year. The secondary endpoint was the improvement or recovery of renal function after tacrolimus discontinuation. Results:Four patients (12.9%) developed CKD within 1 year. Patients were classified into advent of CKD and non-advent of CKD groups. The median patient age was 37.0 ± 2.7 (median ± SE) in the non-CKD group and 62.5 ± 6.1 in the CKD group (P = 0.02). The average duration of tacrolimus treatment was 15.2 ± 1.9 months in the non-CKD group and 27.3 ± 7.0 months in the CKD group (P = 0.13). Twenty patients in the non-CKD group were evaluated regularly following the discontinuation of tacrolimus. The average eGFR when tacrolimus was started was 98.0 mL/min per 1.73 m2. However, when tacrolimus was discontinued, this value dropped to 79.4 mL/min per 1.73 m2 (P = 0.01); after 12 months it still remained as low as 81.3 mL/min per 1.73 m2 (P = 0.02). Conclusions:Careful monitoring of renal function is required to avoid chronic renal damage during the long-term administration of tacrolimus. Such monitoring is particularly relevant in patients with low eGFR values prior to treatment and the elderly.