Elena Ricart

Magnetic resonance for assessment of disease activity and severity in ileocolonic Crohn’s disease

Objective: Assessment of disease extension and activity is crucial to guide treatment in Crohn’s disease. The objective of the current cross-sectional study was to determine the accuracy of MR for this assessment. Design: 50 patients with clinically active (n = 35) or inactive (n = 15) Crohn’s disease underwent ileocolonoscopy (reference standard) and MR. T2-weighted and precontrast and postcontrast-enhanced T1-weighted sequences were acquired. Endoscopic activity was evaluated by CDEIS (Crohn’s Disease Endoscopic Index of Severity); in addition endoscopic lesions were classified as absent, mild (inflammation without ulcers) or severe (presence of ulceration). Results: The comparison of intestinal segments with absent, mild and severe inflammation demonstrated a progressive and significant (p<0.001) increase in the following MR parameters: wall thickness, postcontrast wall signal intensity, relative contrast enhancement, presence of oedema, ulcers, pseudopolyps and lymph node enlargement. Independent predictors for CDEIS in a segment were wall thickness (p = 0.007), relative contrast enhancement (p = 0.01), presence of oedema (p = 0.02) and presence of ulcers at MR (p = 0.003). There was a significant correlation (r = 0.82, p<0.001) between the CDEIS of the segment and the MR index calculated according to the logistic regression analysis coefficients. The MR index had a high accuracy for the detection of disease activity (area under the receiver operating characteristic (ROC) curve 0.891, sensitivity 0.81, specificity 0.89) and for the detection of ulcerative lesions (area under the ROC curve 0.978, sensitivity 0.95, specificity 0.91) in the colon and terminal ileum. Conclusion: The accuracy of MR for detecting disease activity and assessing severity brings about the possibility of using MR as an alternative to endoscopy in the evaluation of ileocolonic Crohn’s disease.

Magnetic resonance imaging for evaluation of Crohn's disease: validation of parameters of severity and quantitative index of activity.

Background: The use of magnetic resonance imaging (MRI) for assessment of Crohns disease (CD) is expanding. The aim of this study is to define and provide an external validation of the MRI predictors of active CD, severe CD, and a quantitative Magnetic Resonance Index of Activity (MaRIA). Methods: In all, 48 patients with clinically active (n = 29) or inactive (n = 19) CD underwent ileocolonoscopy (reference standard) and MRI. T2‐weighted and pre‐ and postcontrast‐enhanced T1‐weighted sequences were acquired. Endoscopic activity was evaluated by the Crohns Disease Endoscopic Index of Severity (CDEIS), and also classified as absent, mild (inflammation without ulcers), or severe (presence of ulceration). Results: In complete agreement with a previous derivation study, independent predictors of disease severity using CDEIS as a reference were wall thickness, relative contrast enhancement (RCE), presence of edema, and ulcers on MRI. Estimation of activity in each segment using this regression model, or another with simplified coefficients (MaRIAS = 1.5*wall thickness + 0.02*RCE + 5*edema + 10*ulceration) correlated with CDEIS (r = 0.798, P < 0.001; r = 0.80 P < 0.001, respectively). In the validation cohort both indexes had a high and equal accuracy for diagnosis of active disease: receiver operator characteristic (ROC) area 0.93, sensitivity 0.87, specificity 0.87 using a cutoff point ≥7, and for diagnosis of severe disease: ROC area 0.96, sensitivity 0.92, specificity 0.92 using a cutoff point ≥11. The total of segment values (MaRIAT) correlated with global CDEIS (r = 0.83, P < 0.001). Conclusions: The MRI variables that should be evaluated in clinical practice to diagnose active CD and severe CD are validated, as well as the quantitative index of activity for use in research studies. (Inflamm Bowel Dis 2010)

Infliximab for Crohn’s disease in clinical practice at the Mayo Clinic: the first 100 patients

OBJECTIVE:The aim of this study was to report the clinical outcome and adverse events in the first 100 patients with refractory inflammatory and/or fistulizing Crohns disease treated with infliximab at the Mayo Clinic.METHODS:Patient data was abstracted from medical records. Clinical response was classified as complete response, partial response, and nonresponse.RESULTS:Indications for infliximab therapy were: inflammatory disease (61 patients), fistulizing disease (26 patients), or both (13 patients). Patients received one to seven infusions of infliximab (5 mg/kg) for a total of 242 infusions. In all, 50 patients had complete response, 22 had partial response, and 28 had nonresponse. Median time to response was 7 days (range 1–21 days). Median duration of response was 10.3 weeks (range 3–25 wk). A total of 95 patients received concomitant treatment with immune modifiers. Steroid withdrawal was possible in 29/40 patients (73%). Median time of follow-up was 34 wk (range 14–48 wk). Clinically significant adverse events after infliximab included: abscess formation in two patients (perianal, peristomal), pneumonia in two patients, varicella zoster in three patients, candida esophagitis in one patient, and infusion-related reactions in 19 patients. A total of 23 patients were continued on infliximab as maintenance treatment.CONCLUSIONS:This study provides additional evidence that infliximab is safe and beneficial in clinical practice for refractory Crohns disease.

Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial

BACKGROUND Ciclosporin and infliximab are potential rescue treatments to avoid colectomy in patients with acute severe ulcerative colitis refractory to intravenous corticosteroids. We compared the efficacy and safety of these drugs for this indication. METHODS In this parallel, open-label, randomised controlled trial, patients were aged at least 18 years, had an acute severe flare of ulcerative colitis defined by a Lichtiger score greater than 10 points, and had been given an unsuccessful course of high-dose intravenous steroids. None of the patients had previously received ciclosporin or infliximab. Between June 1, 2007, and Aug 31, 2010, patients at 27 European centres were randomly assigned (via computer-derived permutation tables; 1:1) to receive either intravenous ciclosporin (2 mg/kg per day for 1 week, followed by oral drug until day 98) or infliximab (5 mg/kg on days 0, 14, and 42). In both groups, azathioprine was started at day 7 in patients with a clinical response. Neither patients nor investigators were masked to study treatment. The primary efficacy outcome was treatment failure defined by absence of a clinical response at day 7, a relapse between day 7 and day 98, absence of steroid-free remission at day 98, a severe adverse event leading to treatment interruption, colectomy, or death. Analysis was by intention to treat. This trial is registered with EudraCT (2006-005299-42) and ClinicalTrials.gov (NCT00542152). FINDINGS 115 patients were randomly assigned; 58 patients were allocated to receive ciclosporin and 57 to receive infliximab. Treatment failure occurred in 35 (60%) patients given ciclosporin and 31 (54%) given infliximab (absolute risk difference 6%; 95% CI -7 to 19; p=0·52). Nine (16%) patients in the ciclosporin group and 14 (25%) in the infliximab group had severe adverse events. INTERPRETATION Ciclosporin was not more effective than infliximab in patients with acute severe ulcerative colitis refractory to intravenous steroids. In clinical practice, treatment choice should be guided by physician and centre experience. FUNDING Association François Aupetit, Société Nationale Française de Gastroentérologie, and the International Organization for the study of Inflammatory Bowel Disease.

Accuracy of Magnetic Resonance Enterography in Assessing Response to Therapy and Mucosal Healing in Patients With Crohn's Disease

BACKGROUND & AIMS We assessed the accuracy of magnetic resonance enterography (MRE) in monitoring response to therapy in patients with Crohns disease (CD) using ileocolonoscopy as a reference standard. METHODS We performed a prospective multicenter study of 48 patients with active CD and ulcers in at least one ileocolonic segment. All patients underwent ileocolonoscopy and MRE at baseline and 12 weeks after completing treatment with corticosteroids (CS) or anti-tumor necrosis factor agents. Disease activity was quantified using Crohns Disease Endoscopic Index of Severity (CDEIS) and Magnetic Resonance Index of Activity (MaRIA). The primary analysis was to determine the accuracy of MRE in identification of healing, defined as the disappearance of ulcers in endoscopy examination. Additional analyses established the accuracy of MRE in determining endoscopic remission (a CDEIS score <3.5) and change in severity based on consideration of all segments. RESULTS MRE determined ulcer healing with 90% accuracy and endoscopic remission with 83% accuracy. The mean CDEIS and MaRIA scores significantly changed at week 12 in segments with ulcer healing, based on endoscopic examination (CDEIS: 21.28 ± 9.10 at baseline vs 2.73 ± 4.12 at 12 weeks; P < .001 and MaRIA: 18.86 ± 9.50 at baseline vs 8.73 ± 5.88 at 12 weeks; P < .001). The MaRIA score accurately detected changes in lesion severity (Guyatt score: 1.2 and standardized effect size: 1.07). MRE was as reliable as endoscopy in assessing healing; no significant changes in CDEIS or MaRIA scores were observed in segments with persistent ulcers, based on endoscopic examination (CDEIS: 26.43 ± 9.06 at baseline vs 20.77 ± 9.13 at 12 weeks; P = .18 and MaRIA: 22.13 ± 8.42 at baseline vs 20.77 ± 9.17 at 12 weeks; P = .42). The magnitude of change in CDEIS scores correlated with those in MaRIA scores (r = 0.51; P < .001). CONCLUSIONS MRE evaluates ulcer healing with a high level of accuracy when ileocolonoscopy is used as the reference standard. The MaRIA is a valid, responsive, and reliable index assessing response to therapy in patients with CD.

Management of Crohn's disease of the ileoanal pouch with infliximab☆

OBJECTIVES:The occurrence of Crohns disease (CD) in a patient with an ileal-pouch anstomosis (IPAA) often results in severe morbidity and significant chance of reservoir loss. We report our experience of the use of infliximab in these patients.METHODS:Medical records of 26 patients with an IPAA and CD-related complications were reviewed. The median time between the IPAA and the diagnosis of CD was 4.5 yr (range 0.1–16 yr). The main reasons for changing the original ulcerative colitis diagnosis to CD were complex perianal or pouch fistulizing disease in 14 patients (54%), prepouch ileitis in five (19%), and both prepouch ileitis and complex fistula in seven (27%). Patients received one to three doses of infliximab over 8 wk as induction therapy. Subsequently the patients received a variable number of maintenance infusions.RESULTS:At a short term follow-up, 16/26 patients (62%) had a complete response, six of 26 (23%) had a partial response, and four of 26 (15%) had no response. Information regarding long term follow-up was available in 24 patients. After a median follow-up of 21.5 months (range 3–44 months), eight patients (33%) either had their pouch resected or had a persistent diverting ileostomy. The pouch was functional in 16/24 (67%) patients, with either good (n = 7) or acceptable (n = 7) clinical results in 14/24 (58%). Of those 14 patients, 11 were under long term, on demand, or systematic maintenance treatment with infliximab.CONCLUSIONS:Infliximab is beneficial in both the short and long term treatment of patients with an IPAA performed for a presumed diagnosis of ulcerative colitis who subsequently develop CD-related complications. Good pouch function requires long term treatment with infliximab in most patients.

Narrow-band imaging as an alternative to chromoendoscopy for the detection of dysplasia in long-standing inflammatory bowel disease: a prospective, randomized, crossover study

BACKGROUND Narrow-band imaging (NBI) is a novel technique that may represent an alternative method to chromoendoscopy (CE) for the detection of colitis-associated intraepithelial neoplasia (IN) in patients with long-standing inflammatory bowel disease (IBD). OBJECTIVE To compare NBI with CE for the detection of IN. DESIGN Prospective, randomized, crossover study. SETTING Academic hospital. PATIENTS Patients with clinically inactive colonic IBD (≥8 years). INTERVENTION Patients underwent both CE and NBI in randomized order. Targeted biopsy specimens from abnormal areas were obtained. Pathological examination was regarded as the reference standard. MAIN OUTCOME MEASUREMENTS Number of false-positive and true-positive lesions in patients undergoing CE and NBI were compared as well as the proportion of patients with missed IN lesions. RESULTS Eighty patients were screened, of whom 20 were excluded. Mean ± standard deviation withdrawal time for CE was significantly longer than that for NBI (26.87 ± 9.89 minutes vs 15.74 ± 5.62 minutes, P < .01). Thirteen patients had at least 1 IN lesion on 1 of the examinations. In the per-lesion analysis, NBI resulted in a significantly inferior false-positive biopsy rate (P = .001) and a similar true-positive rate. The percentage of missed IN lesions and patients was superior with NBI, albeit without reaching statistical significance. LIMITATIONS Lesions were sampled immediately after detection, which precluded the possibility of paired analysis. CONCLUSIONS NBI appears to be a less time-consuming and equally effective alternative to CE for the detection of IN. However, given the NBI lesion and patient miss rates, it cannot be recommended as the standard technique.

Characterization of inflammation and fibrosis in Crohn's disease lesions by magnetic resonance imaging.

Objectives:Measurement of the component of fibrosis in Crohn’s disease (CD) may have important therapeutic implications. The aim of this study was to characterize the Magnetic Resonance Imaging (MRI) findings that are differentially associated with the presence of fibrosis and those associated with inflammatory activity, using the pathological analysis of surgically resected intestinal lesions as reference standard.Methods:MRI studies with identical imaging protocol of 41 CD patients who underwent elective bowel resection within 4 months before surgery were reviewed. MRI evaluated wall thickening, edema, ulcers, signal intensity at submucosa at 70 s and 7 min after gadolinium injection, stenosis, and pattern of enhancement in each phase of the dynamic study and changes on this pattern over time. Pathological inflammatory and fibrosis scores were classified into three grades of severity.Results:In all, 44 segments from 41 patients were analyzed. The pathological intensity of inflammation was associated with the following MRI parameters: hypersignal on T2 (P=0.02), mucosal enhancement (P=0.03), ulcerations (P=0.01), and blurred margins (P=0.05). The degree of fibrosis correlated with the percentage of enhancement gain (P<0.01), the pattern of enhancement at 7 min (P<0.01), and the presence of stenosis (P=0.05). Using percentage of enhancement gain, MRI is able to discriminate between mild–moderate and severe fibrosis deposition with a sensitivity of 0.94 and a specificity of 0.89.Conclusions:MRI is accurate for detecting the presence of severe fibrosis in CD lesions on the basis of the enhancement pattern.

Autoimmune disorders and extraintestinal manifestations in first-degree familial and sporadic inflammatory bowel disease: a case-control study.

Background:Genetic factors may play a role in determining the development of extraintestinal manifestations (EIMs) and autoimmune diseases (AD) in patients with inflammatory bowel disease (IBD). We sought to determine the association between EIMs and AD in patients with first-degree familial IBD and sporadic IBD. Methods:All patients evaluated in the IBD Clinic at the Mayo Clinic between January and September 1999 were offered enrollment. One clinic patient who was matched on age, gender, and geographic area of residence to each case served as controls. Information regarding EIMs and AD was obtained from a questionnaire completed by all IBD patients and controls. The adjusted odds ratios (95% CIs) for EIM as a function of first-degree familial IBD compared with sporadic IBD and AD as a function of first-degree familial IBD compared with sporadic IBD were estimated with a matched one-to-one conditional logistic regression model. Results:Two hundred forty-three patients with IBD (47 first-degree familial IBD, 196 sporadic IBD) were enrolled. Forty percent of IBD patients had one or more EIMs compared with 14% matched controls [p < 0.001; OR = 3.1 (95% CI: 1.8 to 5.2)]. A total of 259 of the 1122 IBD patients and their first-degree family members indicated one or more EIM diagnoses (23%). The association between “familial versus sporadic” status and any EIM diagnosis was not significant [p = 0.59, the odds for an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.2 (95% CI: 0.8 to 1.7)]. Ten percent of IBD patients had one or more AD diagnoses compared with 19% matched controls [p = 0.04; OR = 0.4 (95% CI: 0.1 to 0.96)]. A total of 153 of the 1122 IBD patients and their first-degree family members indicated one or more AD diagnoses (14%). The association between disease status (“familial or sporadic”) versus any AD diagnosis was not significant [p = 0.68, the odds for any AD in an individual from a familial IBD family relative to an individual from a sporadic IBD family was 1.4 (95% CI: 0.9 to 2.3)]. Conclusions:There was a positive association between IBD status (patient vs control) versus EIM, but not AD. A significant positive association between disease type (familial or sporadic) versus either EIM or AD was not detected.

Impact of Wide-Angle, High-Definition Endoscopy in the Diagnosis of Colorectal Neoplasia: A Randomized Controlled Trial

BACKGROUND & AIMS It is essential to optimize standard colonoscopy technique to be able to increase polyp detection. We sought to compare the performance of colonoscopy using a high-definition, wide-angle endoscope (HDE) versus a standard colonoscope (SC) for the detection of colorectal neoplasia. PATIENTS AND METHODS All consecutive consenting adult patients referred from primary care centers were included and randomly assigned at a 1:1 ratio to undergo HDE or SC. Times to reach and withdraw from the cecum were measured. Morphology, size, location, and pathologic diagnosis of each polyp were recorded. Sample size calculation resulted in a total of 682 patients needed. RESULTS A total of 693 consecutive patients fulfilled all inclusion criteria (73 excluded owing to insufficient bowel preparation). Each arm included 310 patients with no baseline characteristic differences. Time to reach the cecum was slightly superior for SC (8.9 +/- 4.8 minutes vs 8.2 +/- 4.5 minutes; P = .055). Pathology examination was feasible in 418 lesions (272 adenomas, 109 hyperplastic polyps, and 37 inflammatory lesions). Both techniques detected a similar number and type of lesions, and there were no differences in the distribution along the colon, in the degree of dysplasia, or morphology of adenomas. The per-patient basis analyses demonstrated that there were no differences between the 2 arms of the study in the detection rates of polyps (SC, 0.84 +/- 1.59; HDE, 0.83 +/- 1.30), adenomas (0.45 +/- 1.07 vs 0.43 +/- 0.87), small adenomas (0.22 +/- 0.71 vs 0.28 +/- 0.78), flat adenomas (0.30 +/- 0.91 vs 0.21 +/- 0.63), or hyperplastic polyps (0.16 +/- 0.50 vs 0.18 +/- 0.54). CONCLUSION HDE did not detect significantly more colorectal neoplasia than SC.