Elena Dubcenco

Given capsule endoscopy in celiac disease: evaluation of diagnostic accuracy and interobserver agreement.

BACKGROUND AND AIMS:Capsule endoscopy (CE) has been increasingly used for diagnosing diseases of the small bowel. It is an attractive technique for assessing celiac disease (CD) because it is noninvasive and provides a close and magnified view of the mucosa of the entire small bowel. In this study, we evaluated the accuracy of CE and interobserver agreement in recognizing villous atrophy (VA) using histopathology as the reference. We also explored the extent of small bowel involvement with CD and the relationship between the length of the affected bowel and the clinical presentation.METHODS:Ten CD patients with histologically proven VA and the same number of controls were subjected to CE. Four, blinded to histology findings, investigators (two with and two without prestudy CE experience) were asked to diagnose VA on CE images.RESULTS:Based on assessment of all four investigators, the overall sensitivity, specificity, PPV, and NPV of CE in diagnosing VA were 70%, 100%, 100%, and 77%, respectively. The sensitivity and the specificity of the test was 100% when the reports of experienced capsule endoscopists only were analyzed. The interobserver agreement was perfect (κ= 1.0) between investigators with prestudy CE experience and poor (κ= 0.2) between the investigators who had limited prestudy exposure to CE. Celiac patients with extensive small bowel involvement had typical symptoms of malabsorption (diarrhea, weight loss) as opposed to mild and nonspecific symptoms in patients whose disease was limited to the proximal small bowel. CE was tolerated well by all study participants with 95% reporting absence of any discomfort.CONCLUSIONS:Although based on a small sample size, the study suggests that CE may be useful in assessing patients with CD. Familiarity with CE technology appears to be a critical factor affecting the accuracy of the test. Larger studies are warranted to more precisely define the advantages and limitations of CE in CD.

A Systematic Review of the Measurement of Endoscopic Healing in Ulcerative Colitis Clinical Trials: Recommendations and Implications for Future Research

Background:Assessment of endoscopic disease activity, as measured by various endoscopic evaluative instruments, is an essential part of quantifying disease activity in clinical trials in patients with ulcerative colitis (UC). Evaluative instruments have specific definitions and operating properties that influence the interpretation of clinical trial results. Our objective was to systematically review all endoscopic evaluative instruments that measure endoscopic disease activity in UC and to describe their definitions and operating characteristics (reliability, responsiveness, and predictive validity). Methods:We performed a systematic review of evaluative instruments assessing endoscopic disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week abstracts of clinical trials were searched from inception to January 2013. Results:In total, 5885 studies were identified and screened for inclusion criteria. Four hundred twenty-two studies involving 31 evaluative instruments were identified. Two types of indices were found, numerical scoring systems and stepwise grading scales. Conclusions:Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for UC. Currently, the sigmoidoscopic component of the Mayo Score and the ulcerative colitis endoscopic index of severity show the most promise as reliable evaluative instruments of endoscopic disease activity. However, further validation is required.

Reliability among central readers in the evaluation of endoscopic findings from patients with Crohn's disease

Objective The Crohns Disease Endoscopic Index of Severity (CDEIS) and Simple Endoscopic Score for Crohns Disease (SES-CD) are commonly used to assess Crohns disease (CD) activity; however, neither instrument has been fully validated. We assessed intra-rater and inter-rater reliability of these indices. Design Video recordings of colonoscopies obtained from 50 patients with CD who participated in an induction trial of a biological therapy were triplicated and reviewed in random order by four central readers. Data were used to assess intra-rater and inter-rater reliability for CDEIS, SES-CD and a global evaluation of lesion severity (GELS). Subsequently, readers participated in a consensus process that identified common sources of disagreement. Results Intraclass correlation coefficients (ICCs) for intra-rater reliability for CDEIS, SES-CD and GELS (95% CIs) were 0.89 (0.86 to 0.93), 0.91 (0.89 to 0.95) and 0.81 (0.77 to 0.89), respectively, with standard error of measurement (SEM) of 2.10, 2.42 and 1.15. The corresponding ICCs for inter-rater reliability were 0.71 (0.63 to 0.76), 0.83 (0.75 to 0.88) and 0.62 (0.52 to 0.70), with SEM of 3.42, 3.07 and 1.63, respectively. Correlation between CDEIS and GELS was 0.75, between SES-CD and GELS was 0.74 and between CDEIS and SES-CD was 0.92. The most common sources of disagreement were interpretation of superficial ulceration, definition of disease site at the ileocolonic anastomosis, assessment of anorectal lesions and grading severity of stenosis. Conclusions Central reading of CDEIS and SES-CD had ‘substantial’ to ‘almost perfect’ intra-rater and inter-rater reliability; however, the responsiveness of these instruments is yet to be determined. Trial registration number Clinicaltrials.gov NCT01466374.

A systematic review of measurement of endoscopic disease activity and mucosal healing in Crohn's disease: recommendations for clinical trial design.

Background:Crohns disease (CD) is a chronic idiopathic inflammatory disorder of the gastrointestinal tract. Recently, mucosal healing has been proposed as a goal of therapy because clinical symptoms are subjective. Evaluative indices that measure endoscopic disease activity are required to define mucosal healing for clinical trials. The primary objective of this systematic review was to assess the existing evaluative indices that measure disease activity in CD and evaluate their role as outcome measures in clinical trials. Methods:A systematic literature review was performed using MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and DDW abstracts to identify randomized controlled trials and controlled clinical trials that used a relevant evaluative index from inception to February 2013. The data obtained from these trials were reviewed and summarized. Results:The initial literature searches identified 2300 citations. After duplicates were removed, 1454 studies remained. After application of the apriori inclusion and exclusion criteria, 109 articles were included and 3 were identified with handsearches. In total, 9 evaluative indices for CD were identified and reviewed. The Crohns Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score in Crohns Disease (SES-CD) are indices with the most extensively described operating properties. Conclusions:Both the endoscopic evaluative instrument selected and the definition chosen for mucosal healing affect the validity of assessing endoscopic disease activity during a clinical trial for CD. Currently, the CDEIS and SES-CD have the most data regarding operating properties; however, further validation is required.

Neurological symptoms suggestive of demyelination in Crohn's disease after infliximab therapy

Anti-TNFalpha drugs are currently used in the treatment of patients with Crohns disease. Studies have reported neurological side effects occurring after anti-TNFalpha treatment, including infliximab-induced complications.

The development of a novel intracolonic occlusion balloon for transcolonic natural orifice transluminal endoscopic surgery: description of the technique and early experience in a porcine model (with videos)

BACKGROUND Transgastric and transvaginal approaches in natural orifice transluminal endoscopic surgery (NOTES) are the most commonly used, although the transcolonic approach may have some advantages. OBJECTIVE To develop a workable technique for transcolonic NOTES. DESIGN A nonsurvival study followed by a survival study in a porcine model. Transcolonic peritoneoscopy was performed with the use of a novel intracolonic occlusion balloon. The colotomy was closed with endoclips. A necropsy and histologic evaluation were performed 2 weeks after surgery. SETTING Academic hospital, health science research center. SUBJECTS Fifteen female Yorkshire pigs (5 nonsurvival, 10 survival). INTERVENTIONS A balloon-tipped catheter was placed proximal to the colotomy site. The balloon was inflated to occlude the colonic lumen. An endoscope was inserted through the anus. Colonic incision was created with an endoscopic needle-knife at 15 to 20 cm from the anal verge. Peritoneoscopy was performed. The colotomy was closed with endoclips. MAIN OUTCOME MEASUREMENTS Rates of complications, survival, healing, and adhesions. RESULTS Two initial experiments were complicated by bowel distension and contamination of the incision area by colonic content. In the remaining 13 pigs, the experiments were performed with the use of the intracolonic occlusion balloon. No complications were documented. Necropsies were performed 2 weeks after surgery. Gross and histologic evaluations demonstrated near complete healing. Minimal adhesions were identified in 4 of 10 pigs. LIMITATION Imperfection of the prototype balloon. CONCLUSIONS Excessive bowel distension and fecal contamination because of spillage from the proximal bowel may be barriers to performing transcolonic NOTES. Isolation of the operative area by splitting the bowel and sealing the colonic lumen with the balloon above the colonic incision may overcome these problems and optimize the technique.

Assessment of histologic disease activity in Crohn's disease: a systematic review.

Background:Crohns disease (CD) is an idiopathic, chronic, transmural inflammatory disorder of the gastrointestinal tract. Because mucosal involvement is near-universal, endoscopic healing has emerged as an important aspect in improving outcome. However, resolution of histologic disease activity has potential to convey additional benefit beyond that attained with endoscopic healing alone. Validated scoring systems of histologic disease activity are required to further assess this possibility. The aim of this study was to systematically review the existing histologic disease activity indices (HDAI) for CD and to assess their operating properties and potential use as outcome measures in clinical trials. Methods:MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Disease Week (DDW) abstracts were searched from 1981 to April 2013 for applicable studies to identify relevant studies for review and analysis. Results:In total, 3732 citations were screened to obtain 89 articles for inclusion. Sixty-six HDAIs were characterized as either stepwise or numerical instruments. These HDAIs were used for either assessment of response to medical therapy or for comparison with biomarkers or imaging tests. None of the HDAIs identified was developed according to currently accepted methods for developing evaluative instruments, and none have been formally validated. Conclusions:Measurement of histologic disease activity has potential value in CD; however, no validated measures are available. Additional research is needed to develop a methodologically rigorous instrument for use in clinical investigation and potentially for clinical practice.

Sa1198 Agreement Among Experts in the Endoscopic Evaluation of Postoperative Recurrence in Crohn's Disease Using the Rutgeerts Score

Geboes-Structural 0.70 (0.60 0.79) 0.80 (0.74 0.86) Geboes-Chronic inflammatory infiltrate 0.64 (0.54 0.74) 0.81 (0.75 0.86) Geboes-Lamina propria eosinophils 0.26 (0.18 0.37) 0.59 (0.52 0.66) Geboes & Modified Riley-Lamina propria neutrophils 0.37 (0.27 0.49) 0.59 (0.51 0.68) Modified Riley-Neutrophils in epithelium 0.47 (0.37 0.59) 0.71 (0.64 0.78) Geboes-Crypt destruction 0.34 (0.24 0.47) 0.61 (0.54 0.69) Geboes-Erosion or ulceration 0.56 (0.45 0.67) 0.78 (0.73 0.84)

Responsiveness of Endoscopic Indices of Disease Activity for Crohn’s Disease

Objectives:The Crohn’s Disease Endoscopic Index of Severity (CDEIS) and the Simple Endoscopic Score for Crohn’s Disease (SES-CD) are commonly used to assess Crohn’s disease (CD) activity; however neither instrument is fully validated. We evaluated the responsiveness to change of the SES-CD and CDEIS using data from a trial of adalimumab, a drug therapy of known efficacy.Methods:Paired video recordings (N=112) of colonoscopies (baseline and week 8–12) obtained from patients with CD who participated in a trial of adalimumab therapy were reviewed in random order, in duplicate, by four central readers (56 pairs of videos by 2 groups of readers). Responsiveness of the SES-CD and the CDEIS was evaluated by comparing correlations between the observed and pre-specified predictions of change scores for these endoscopic indices with a global endoscopic evaluation of severity (GELS), a patient reported outcome (PRO2), and the Crohn’s disease activity index (CDAI), and by calculation of the standardized effect size, and Guyatt’s Responsiveness statistic (GRS) using 2 definitions of change; (1) treatment assignment and (2) an absolute change in total PRO2 of 50. The potential application of effect size estimates was demonstrated by calculating hypothetical sample sizes for comparing two independent groups. The impact of removing stenosis as an index item and adjusting for the number of segments observed was also assessed.Results:Changes in both endoscopic instruments and the GELS were highly correlated. The SES-CD displayed numerically higher effect sizes for both definitions of change. The standardized effect size and GRS estimates (95% confidence interval) for the SES-CD based on treatment assignment were 0.84 (0.53, 1.15) and 0.79 (0.48, 1.09). Corresponding values for the CDEIS were 0.72 (0.42, 1.02) and 0.75 (0.45, 1.06). The standardized effect size and GRS estimates for the SES-CD based on an absolute change in total PRO2 of 50 points or greater were 0.76 (0.49, 1.02) and 0.93 (0.64, 1.21). Corresponding values for CDEIS were 0.70 (0.44, 0.97), 0.83 (0.55, 1.10). Removal of stenosis as an index item and adjusting for observed segments did not improve responsiveness estimates.Conclusions:Although both the SES-CD and CDEIS are valid measures of endoscopic disease activity that are moderately responsive to changes in endoscopic disease activity, the SES-CD displayed numerically greater responsiveness in this data set.

OP024 Agreement among central readers in the evaluation of endoscopic disease activity in Crohn's disease

of a biomarker test that can identify and stratify young IBD patients. Methods Samples from well-characterized patients were collected from 15 North American GI centers. Median age was 15 (IQR: 13-16). Samples from 251 patients were used: 147 Crohns disease (CD), 47 ulcerative colitis (UC) and 57 non-IBD disease controls. A combination of serological markers (ASCA-IgA, ASCA-IgG, ANCA, pANCA, anti-OmpC, anti-Fla2, anti-FlaX and anti-CBir1), four gene variants (ATG16L1, NKX2-3, ECM1, and STAT3) and five inflammatory markers (CRP, SAA, ICAM, VCAM, and VEGF) were used in this evaluation. Identification of IBD, CD, and UC and was made with the aid of a machine learning model. Sensitivity, specificity, NPV, PPV and accuracy statistics were calculated for both the IBD vs. Non-IBD component of the diagnostic model, and separately for the CD vs. UC component (for patients called IBD by the model). Results The multi-marker biomarker diagnostic model performed in classifying IBD, CD and UC in pediatric patients as reported in Table 1. We observed a sensitivity of 86.1% and a specificity of 86% for identifying young adults with IBD. The sensitivity and specificity for classifying CD in patients called IBD by the model was 91.9% and 75.8%, respectively. UC sensitivity and specificity was 82.1% and 90.5%, respectively. Diagnostic accuracy of the biomarkers was 86.1% for IBD vs. non-IBD, 88.2% for CD and 88.9% for UC. The IBD NPV and PPV were 64.5% and 95.4% respectively. CD NPV and PPV were 73.5% and 92.7%, respectively. UC NPV and PPV were and 95.5% and 67.6%, respectively. Conclusion Our results demonstrate that a combination of serological, genetic, and inflammatory markers may be utilized for classifying non-IBD, CD, and UC in the young adult patient population. Further studies are required to further investigate the clinical utility of this biomarker test. Table 1