Su1305 Clinical, Endoscopic, and Histologic Features With Utilization of Ki67 Staining in Serrated Polyps in Patients With Inflammatory Bowel Disease

revealed an AUC of 0.78 (CI 0.68-0.89). A NNET model also differentiated between B1and B3 phenotypes (sensitivity-78%, specificity-77% on the testing population). Differentiating between B2 and B3 phenotypes, was not possible using morphometric variables. Multivariate analysis also predicted surgery (sensitivity-67%, specificity-72.5%, accuracy on cross validation- 69%). ROC analysis of the DS for surgery revealed an AUC of 0.72 (CI 0.61-0.82,). A NNET model predicted surgery with a sensitivity of 80% and a specificity of 91% on the testing population. Conclusions: This study validates our previous "proof of concept study" and suggests that morphometric analysis of early biopsies from patients with Crohn's colitis may contribute to the prediction of future outcomes such as clinical phenotype and surgery, thus potentially improving the patient management. Prospective validation on larger cohorts is still needed. Su1304 Is Fecal Calprotectin Really Useful for Diagnostic Decision Making in the Inpatient Setting? Edwin K. McDonald, Tiffany Chua, Navdeep S. Chehl, Amoah Yeboah-Korang, Arthur Kastl, Rana R. Abraham, Garth Swanson Background & AIMS: Patients hospitalized for abdominal pain and diarrhea are commonly assessed for active inflammatory bowel disease (IBD) with imaging and/or endoscopy. Fecal calprotectin (FC) is a useful, non-invasive biomarker of intestinal inflammation. Prior studies highlight its potential for reducing endoscopies, but clinical algorithms for its effective use in hospitalized patients are lacking. We aimed to evaluate the inpatient use of FC in diagnostic decision-making. Methods: A retrospective chart review was performed including patients with FC levels done during hospitalizations at an academic medical center from July 2012 to July 2013. FC levels (Quest Diagnostics, San Juan Capsitrano, Ca) were measured and the manufacturer's validated reference of <163.0 mcg/g was used. Other clinical variables of interest were demographic data, length of stay, history of IBD, gastrointestinal symptoms, serum markers of inflammation, C. difficile testing, abdominal imaging, and endoscopic findings. Temporal relationships between the timing of ordering FC, obtaining the FC results, endoscopy, abdominal imaging, and discharge were assessed. Endoscopic evidence of inflammation was defined by the presence of erythema, ulceration, pseudo-polyps, and loss of vascularity. Correlation of FC levels with serum markers of inflammation, history of IBD, endoscopic findings, and imaging were estimated with Pearson (r). Analysis of variance (ANOVA) and independent t-tests were used for comparisons between groups. Results: Forty-two patients were identified (21 male, 21 female). Of the 42 patients, 23 (54.8%) had IBD. Of these 23 patients, 17 (73.9%) had Crohn's disease and 6 (14.3%) had ulcerative colitis. The mean FC level was 739.8 mcg/g (+/-883.1 mcg/g). Twenty-four patients (57.1%) had FC levels > 163 mcg/g. An average of 7.7 days (range 3-12 days) lapsed after ordering FC and obtaining results. Of the 19 patients (45.2%) who underwent endoscopies, all were performed prior to obtaining the FC results. Abdominal imaging (CT or MRI) was performed in 17 patients (40.5 %) of which 82.4% had imaging done prior to ordering FC and 58.8% showed intestinal thickening suggestive of an inflammatory process. FC positivity was associated with having diagnosed IBD (P=0.024). Positive FC correlated significantly with inflammatory changes on imaging (Pearson's r 0.648, P=0.005), endoscopic findings suggestive of inflammation (Pearson's r 0.535, P=0.018), and CRP levels (Pearson's r 0.365, P=0.031). Conclusions: The inpatient utility of FC for urgent medical decision-making is limited by its turnaround time. Endoscopy was routinely performed prior to obtaining FC results. The yield of ordering FC after imaging demonstrates inflammatory changes may be low. Improving the turnaround time for FC or point of care testing may improve its inpatient value and cost effectiveness.

Figure 1. PLSDA analysis of urine

Su1305 Clinical, Endoscopic, and Histologic Features With Utilization of Ki67 Staining in Serrated Polyps in Patients With Inflammatory Bowel Disease Yaman Tarabishy, ILKe Nalbantoglu Background: Colorectal serrated polyps (SP) include hyperplastic polyps (HP) and sessile serrated adenomas (SSA). SPs in normal subjects were classified based on histologic features and dual Ki67 and keratin 20 staining characteristics by Torlakovic et al in 2008. Regular extension of Ki67 proliferative zone (PZ) up to ½ of the crypt was designated as HP-like pattern; and irregular Ki67 staining expansion/reduction of PZ with skip areas as SSA-like pattern. Classification, biological behavior, and clinical follow up of SPs in the setting of inflammatory bowel disease (IBD) are of continuous debate. We describe the clinical, endoscopic, histologic and Ki67 staining pattern of SPs in screening IBD biopsies. Design: IBD biopsies with a diagnosis of HP or SSA from 2004 to 2013 were reviewed, with the exclusion of rectal and histologically poorly oriented polyps. Ki67 immunohistochemistry (IHC) was performed, and staining pattern was compared to a control group of SPs (10 HPs, 10 SSAs) in non-IBD patients. Results: 30 polyps from 23 IBD patients (pts) [15 Ulcerative colitis (UC), 8 Crohn's disease (CD)] were classified as SSA (n=8) or HP (n=22) by blinded H& E review. Average disease duration (DD) was 13.1 years (available in 21 pts). Follow up data was available for 11 pts [mean=30 months (mos)]. Of the 8 pts with an SSA diagnosis, 5 had UC and 3 had CD. Their average DD was 13.4 years. 5 polyps were located in the ascending and 3 in the left colon. Endoscopically, 7 appeared as sessile polyps, and 1 presented as granular mucosa. Average polyp size was 7 mm. Background mucosa showed chronic active colitis (1 pt), focal active colitis (1 pt), and quiescent colitis (2 pts). It was normal in 2 pts; and no background mucosa was present in 1 pt. Ki67 IHC showed SSAlike pattern in 62.5% of cases (n=5; 2 ascending, 1 descending and 2 sigmoid), with the remainder showing HP-like pattern (n=3, all ascending). In the control group, 50% had SSAlike, and 50% HP-like Ki67 staining pattern. On follow up, 1 pt developed adenocarcinoma in the same location of the previous SSA 42 mos later, 1 had a HP in the same location 24 mos later, and 1 had a normal biopsy. 86% of the 22 HPs (12 left, 10 right colon) showed HP-like pattern by Ki67 IHC, with similar findings to the control group (80% HP-pattern, 20% SSA-like pattern). On follow up, 1 study pt developed recurrent HPs in the same location (sigmoid) 10 months later. No follow-up data was available in the control group. Conclusions: SPs in IBD patients have similar histologic and endoscopic features to those in non-IBD patients, as well as similar Ki67 staining pattern, suggesting that these are likely

Figure 2. PLSDA analysis of serum Su1303 Early Histological Findings May Predict the Clinical Phenotype in Crohn's Colitis Amir Klein, Amir Karban, Yoav Mazor, Ofer Ben-Izhak, Yehuda Chowers, Edmond Sabo Background: The clinical course of Crohn's disease (CD) is variable and relevant for treatment selection. Early aggressive treatment may change disease course, but should be balanced with safety considerations. Currently, diagnostic tools for prediction of disease phenotype and complications are lacking. Histomorphometric analysis allows for quantitative measurements of size, shapes and orientation of cells and structures in tissues. In a previous pilot study, we were able to show that morphometric analysis may contribute to the prediction of the clinical phenotype and surgery in patients with Crohn's colitis. Aim: To further evaluated and validate the histomorphometric features of early colonic biopsies from patients with Crohn's colitis and their relationship to evolving clinical phenotypes. Methods: Colonic biopsies from 100 CD patients classified according to the Montreal classification with at least 5 years post biopsy follow up were analyzed. The results were used to predict post biopsy clinical phenotypes and outcomes. Data analysis was performed using multivariate regression models, discriminant score (DS) computations and Neural Network (NNET). Results: Multivariate analysis differentiated between B1 and B2 phenotypes (sensitivity-81%, specificity-74%, accuracy on cross validation-75%). ROC analysis of the discriminant score (DS) yielded an area under the curve (AUC) of 0.74 (CI 0.6-0.84). A NNET model also differentiated between B1and B2 phenotypes (sensitivity- 87%, specificity-67% on the testing population). Differentiation between B1 and B3 phenotypes, had a sensitivity of 69% and a specificity of 76% with an accuracy of 70.5% on cross validation. ROC analysis of the DS

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AGA Abstracts

AGA Abstracts

serum and urine metabolites related to dietary intake were identified to be associated with those patients who subsequently relapse. Interestingly, metabolites predicting relapse involved both short and long term dietary intake, host metabolism and gut bacterial function.

to represent similar entities that can be managed and followed-up in a similar fashion. However, further studies such as BRAF testing, with increased case numbers will help in drawing more definitive conclusions.

AGA Abstracts

Su1306 Protease Activity Analysis and Pathologic Examination on the Same Endoscopic Biopsy Specimen in Inflammatory Bowel Disease William W. Bivin, Kofi Clarke, Crystal Falco, Sydney D. Finkelstein, Jan F. Silverman Background: Inflammatory bowel disease (IBD) is characterized by an inflammatory cell infiltrate associated with changes in mucosal architecture, which consists of an increased turnover of extracellular matrix components. Matrix metalloproteinases (MMP) are the most important group of proteolytic enzymes responsible for extracellular matrix breakdown in IBD. Protease activity (PA) levels may help differentiate Crohn's disease (CD)-related colitis from ulcerative colitis (UC). MMPs have been shown to correlate with IBD severity, and overactivity may contribute to the risk of developing dysplasia. A significant number of molecular biomarker assays compete with histopathology for the same tissue, and we developed a technique to assay MMP activity levels and perform histopathology on the exact same mucosal biopsy while preserving histologic integrity. Design: Following patient consent, 15 endoscopic mucosal biopsies (6CD, 9UC) sampled in vivo from IBD colon and terminal ileum were immediately placed in 1 mL of isotonic saline and incubated at room temperature for 2 hours. Following incubation, the biopsies were transferred to formalin and processed by standard methods for histopathologic evaluation. The saline was retained and 25 μL was assayed against a panel of fluorogenic reagents for the detection of PA for 3 MMP markers involved in inflammation. The fluorescent signal was recorded every 2 minutes for 120 minutes, and average fluorescent signal output was calculated for each data point. The percent increase in fluorescent signal was calculated using background adjusted averages of protease detection reagent with and without incubated solution [(Bx Signal 120m)-(Neg Control Signal 120m)]/(Neg Control Signal 120m). Based on previous validation studies, an increase in signal >20% over background signal was considered a significant increase in PA. Results: Preliminary results show that the mean percent increase in PA level is significantly higher in CD compared to UC for all 3 proteases tested. The mean percent signal increase in CD vs. UC samples were 272.5% vs. 88%, 29% vs. 3.3%, and 123.7% vs. 25.1%, respectively. Histopathology using routinely processed FFPE tissue following saline incubation was satisfactory for pathologic interpretation. Conclusions: The extracellular PA level can be measured in the exact same IBD mucosal biopsies sampled for pathologic evaluation while maintaining histologic integrity and can provide useful complementary information for the histologic differentiation of CD-related colitis and UC. Su1307 The Value of Cross-Sectional Imaging to Detect Crohn's Disease Recurrence After Ileo-Colonic Anastomosis Juan P. Trivella, Andres Yarur, James Wong, Daniel A. Sussman Background: Ileocolonoscopy represents the gold standard in the evaluation of post-operative recurrence of Crohn's disease (CD) at the site of ileocolonic anastomosis (ICA). Magnetic resonance enterography (MRE) and computed tomography (CT) scans are increasingly used techniques for bowel imaging. The aim of this study was to compare colonoscopy with these imaging techniques for determining recurrence in CD patients that had undergone ileal resection (IR) with ICA. Methods: This is a cross-sectional study including patients seen at the University of Miami Hospital and Jackson Memorial Hospital (Florida, USA). We included patients with CD and a history of IR with ICA who underwent colonoscopy for the evaluation of the neo-terminal ileum mucosa proximal to the ICA and either MRE or CT within 30 days pre- or post-index ileocolonoscopy. Data collected for each patient included demographics, symptoms and IBD medications on the index date. Imaging findings at the neo-terminal ileum and anastomosis were assessed by five radiologic parameters including mucosal enhancement, wall thickening, presence of vascular engorgement, lymphadenopathy and luminal stenosis. The comparator was the degree of inflammation at the level of the ICA on ileocolonoscopy graded using the Rutgeerts score (RS) (i0-i4). Results: 30 patients met the inclusion criteria. The baseline characteristics are shown in Table 1. An ICA graded with a RS ≥2 was associated with mucosal enhancement in the area of the anastomosis on crosssectional imaging (OR: 6.0 [95%CI: 1.0-35.9], p=0.03), but not with wall thickening (OR: 1.56 [95%CI: 0.3-7.8], p=0.6), presence of lymphadenopathy (OR: 4.3 [95%CI: 0.8-22.4], p=0.03) or radiologic evidence of stenosis (OR: 3.0 [95%CI: 0.6-14.8], p=0.17). No association was noted between the presence of symptoms and a RS ≥2 (OR: 0.5 [95%CI: 0.1-2.5], p=0.4). The accuracy of the discriminatory capacity of mucosal enhancement on imaging for patients with a RS≥2 was fair, with an area under the ROC = 0.74 (p=0.024) (Figure 1). For wall thickening, the area under the curve was 0.63 (p=0.21). Conclusions: Our data suggest that in CD patients with IR and ICA, cross-sectional imaging can be helpful to assess for recurrence of disease Table 1: Baseline characteristics of the study population

AGA Abstracts

Figure 1: Discriminating capacity of mucosal enhancement in imaging for a Rutgeerts score ≥2 Su1308 Accuracy of IGRA and ASCA in Differentiating Intestinal Tuberculosis From Crohn's Disease: A Meta-Analysis of Diagnostic Studies Kelvin K. Tsoi, Hoyee W. Hirai, Sunny H. Wong, Francis K. L. Chan, Justin C. Wu, Joseph J. Y. Sung, Siew C. Ng Background: Crohn's disease (CD) and intestinal tuberculosis (ITB) are chronic granulomatous disorders with very similar pathologic and endoscopic findings. With the emergence of CD globally and in areas of high TB endemicity, distinguishing CD from ITB is a clinical challenge. A number of studies have evaluated the diagnostic yield of two blood tests, including (1) Interferon-gamma releasing assay (IGRA), and (2) anti-Saccharomyces cerevisiae antibody (ASCA), in differential diagnosis of ITB from CD, but these studies have produced conflicting results. Aim: A meta-analysis of the published literature was carried out to assess the clinical usefulness of IGRA and ASCA in the diagnosis of ITB and CD. Methods: Literature search without language restriction was conducted on September 2013 across different electronic databases, including AMED, EBM, MEDLINE and EMBASE and Google Scholar. Manual searches for the abstracts published in major the academic conferences were performed. Studies evaluating the performance of IGRA or ASCA in distinguishing ITB from CD were eligible. The main outcomes were the sensitivity and specificity with the corresponding 95% confidence interval (95% C.I.) of IGRA for the diagnosis of ITB and ASCA for the diagnosis of CD. A random-effects model was used to combine the estimates from the studies with significant heterogeneity; otherwise, a fixed-effects model was applied. A pooled summary receiver operating characteristics (SROC) curve was constructed to graphically present the combined results. The area under the curve (AUC) was used to measure the accuracy of diagnostic test. A subgroup analysis was performed based on the brands of IGRA (QuantiFERON vs. T-Spot). Results: A total of 16 studies with overall sample size 1,356 were included in this meta-analysis. Mean age of patients was 36.3 years and 44.6% were male. Nine of them evaluated the performance of IGRA and 7 studies evaluated the performance of

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