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sto adenocarcinoma. The genetic differences between these histologic types warrant furtherstudy and should be applied to designing trials of novel therapies.Survival outcomes of papillary, adenocarcinoma and squamous gall bladder cancer basedon TNM stages

Comparison of overall survival among the histologic subtypes in gallbladder cancer.

Su2007

Magnetic Resonance Enterography (MRE) Remission and Radiologic HealingPredicts Clinical Remission At One Year Follow-upCary G. Sauer, Jeremy P. Middleton, Adina Alazraki, Kiery Braithwaite, Diego R. Martin,Subra Kugathasan

Background: Although mucosal healing predicts clinical remission, small bowel Crohn'sDisease (CD) is difficult to assess with endoscopy. Magnetic resonance enterography (MRE)can evaluate small bowel CD. The primary objective of this study was to determine ifMRE remission in pediatric children with CD predicts clinical remission (Physician GlobalAssessment) at one-year follow-up. Patients and Methods: An IRB-approved chart reviewour prospectively maintained Emory / Children's Healthcare of Atlanta Crohn's Disease MREDatabase from 2008-2012 was performed. All patients with CD who underwent an MREduring treatment greater than 90 days after diagnosis of CD with at least one year follow-up after the MRE were included in the study and MRE data, clinical data, and physicianglobal assessment (PGA) one year after MRE were recorded. Results: A total 62 MRE studiesfor evaluation of CD were performed at least 90 days after diagnosis with at least one-yearfollow-up after MRE. Studies were grouped into MRE remission (no active inflammation)and MRE active inflammation groups and compared. The median time disease duration was4.0 years (2.1-8.0) in the MRE remission group and 4.5 (1.9 - 8.5) years in the inflammationgroup. There was no difference between groups in gender, race, or disease duration. In theMRE remission group, 3 of 24 (12.5%) children demonstrated mild clinical disease activitywhile 21 of 24 (87.5%) children were in clinical remission one year later. In MRE studiesdemonstrating active inflammation, 12 (31.6%) children demonstrated mild clinical diseaseactivity, 4 (10.5%) children demonstratedmoderate clinical disease activity, 2 (5.3%) childrendemonstrated severe clinical disease activity, and 20 (52.6%) children demonstrated clinicalremission one year later. Conclusions: MRE remission, or lack of active disease on MREpredicted clinical remission one year later. Nearly half of all children with active inflammationon MRE during treatment continued to demonstrate clinical disease one year later regardlessof treatment changes. This study demonstrates that, similar to mucosal healing, absence ofinflammation on MRE is associated with improved outcome in children. We suggest thatMRE is an important outcome measure for children with small bowel CD beyond thereach of standard endoscopy and can be used to document objective healing and predictclinical outcome.Physician Global Assessment at One Year Follow-up

S-530AGA Abstracts

Su2008

Colon Mucosal Signal Transducer and Activator of Transcription (STAT)Protein Activation Profiles in Pediatric Inflammatory Bowel DiseaseTolulope O. Falaiye, Kay Washington, Dedrick E. Moulton, Lindsay A. Kuhnhein, PrestonD. Moore, Keith T. Wilson, Michael J. Rosen

Background & Aims: The JAK-STAT pathway is a central downstream signal transductionpathway shared by cytokines implicated in inflammatory bowel disease (IBD). Emergingtherapies target JAK-STAT signaling; yet few human studies have examined mucosal STATprotein activation, especially in children. The aim of this study was to determine whetherpediatric ulcerative colitis (UC) and sub-phenotypes of Crohn's disease (CD) exhibit differen-tial colon mucosal STAT protein phosphorylation that correlates with histologic severity.Methods: Tissue lysates were prepared from biopsies of the descending colon from pediatricsubjects. Multiplex assays for phosphorylated STAT proteins (P-STAT1, 2, 3, 5 and 6) andcytokines were performed on a Luminex platform. Tissue sections were scored using theRiley and D'Haen's indices of histologic severity for UC and CD, respectively. Results:Tissues from 34 subjects (mean age 14 [range 7-20] yrs) were examined, including 11without intestinal inflammation (Non-IBD), 5 UC, 6 colitis-only CD (CD-C), 6 ileocolonicCD (CD-IC), and 6 ileitis-only CD (CD-I). Both UC and CD-C demonstrated increasedmucosal P-STAT6 and P-STAT3 compared to Non-IBD. Median relative fluorescence intensity(RFI) for P-STAT6 was 1.0 [interquartile range 0.8-1.3] in Non-IBD, versus 2.2 [1.6-3.5]in UC (P=0.001), and 3.1 [1.1-6.8] in CD-C (P=0.05). Similarly, median RFI for P-STAT3was 1.1 [0.5-1.4] in Non-IBD, versus 3.0 [1.9-6.7] in UC (P=0.006), and 2.7 [0.9-8.8] inCD-C (P=0.02). CD-C also exhibited increased P-STAT5 (2.1 [0.8-3.7]) compared to Non-IBD (1.0 [0.7-1.2], P=0.05). There were no differences in colon mucosal P-STAT RFIsbetween either CD-IC or CD-I, and Non-IBD. Increased P-STAT6 distinguished CD-C fromCD-IC (3.1 [1.1-6.8] vs. 1.0 [0.7-1.3], P=0.05). In analyses including Non-IBD subjects andthose from each IBD phenotype, P-STAT2, 3, 5, and 6 RFIs correlated strongly with histologicseverity in UC and CD-C; however there were no correlations between P-STAT RFIs andhistologic severity in CD-IC. IL-13 signals through STAT6, and there was increased mucosalIL-13 in UC (74 [20-96] pg/mg) compared to Non-IBD (16 [10-31], P=0.05) and CD-C (8[4-16], P=0.02). Furthermore, in an analysis containing UC and Non-IBD subjects, IL-13correlated strongly with P-STAT6 (r=0.67, P=0.02). Associations were not observed betweenother cytokine-STAT signaling pairs such as IFN- γ/STAT1 or IL-6, IL-10, or IL-23/STAT3.Conclusions:We observed increased colon mucosal P-STAT6 and P-STAT3 correlating withhistologic severity in UC and CD-C, but not CD-IC, suggesting shared inflammatory signalingbetween colitis-only pediatric IBD phenotypes. While increased P-STAT6 is explained byelevated IL-13 in UC, there may be other stimuli for STAT6 activation in CD-C. Thesefindings may have implications for targeting treatments inhibiting JAK-STAT signaling.

Su2009

Medication Non-Adherence and Disease Severity in Pediatric InflammatoryBowel DiseaseGeorge M. Zacur, Shehzad A. Saeed, Katherine Loreaux, Joseph R. Rausch, Elizabeth R.Williams, Wendy Gray, Kevin A. Hommel

Background: Medical therapies for Inflammatory Bowel Disease (IBD) can be complicatedfor children and their families, and effective disease management (i.e., adherence to treatmentregimen) can often be challenging. Adherence research in pediatric IBD has been predomi-nantly descriptive, and the association between adherence and disease severity has notbeen significantly evaluated. This study examines the relationship between medication non-adherence and disease severity in pediatric patients with IBD. Methods: Participants includedpediatric patients with a confirmed diagnosis of Crohn's disease (CD), ulcerative colitis (UC),or indeterminate colitis (IC) who were prescribed aminosalicylates (ASA) and/or a thiopurineimmunomodulator (6-mercaptopurine (6MP)/Azathioprine (AZA)) and received a PhysicianGlobal Assessment (PGA) during regular clinic visits over a contiguous 2-year period.Adherence rates were calculated based on pharmacy records and a validated medicationpossession ratio formula. Non-adherence was defined as refilling ,80% of prescribedmedica-tions. Physicians provided an assessment of disease severity using the PGA as part of standardclinic procedure. The Short Pediatric Crohn's Disease Activity Index (shPCDAI) or PediatricUlcerative Colitis Activity Index (PUCAI) was calculated for each subject as an additionalmeasure of disease severity. Chi-square analysis was performed to assess the associationbetween adherence and disease severity. Results: Ninety pharmacy records were obtainedfor 70 subjects (CD=50, UC=16, IC=4). Mean age was 14 years. The overall refill frequencywas 75%, and the prevalence of non-adherence was 53%. Individual refill frequencies forASA and 6MP/AZA were 73% and 75%, respectively. The prevalence of non-adherence toASA and 6MP/AZA was 57% and 39%, respectively. Patients taking ASA who were non-adherent were more likely to have worse disease severity than adherent patients (p ,0.01).Similarly, patients who were non-adherent to 6MP/AZA were also more likely to have worsedisease (p,0.0001). Non-adherent patients on combination therapy were also found tohave worse disease severity (p,0.05). When the shPCDAI and PUCAI were used as measuresof disease severity, active disease was again related to non-adherence to both ASA (p ,0.05)and 6MP/AZA (p,0.001). Conclusions: These results suggest that disease severity is signifi-cantly related to poormedication adherence. This study should increase awareness concerningthe impact of non-adherence on disease severity and promote the development and use of