Tu1936

Understanding the Psychosocial Barriers Facing Pediatric Patients WithInflammatory Bowel Diseases: A Pilot StudyMadhulika Eluri, Maureen Kelly, Sandra C. Kim

Background: Perceived stigmatization has been associated with poor disease outcomesin adolescents with chronic illnesses. Studies have shown that children diagnosed withinflammatory bowel diseases (IBD) are at greater risk for low self-esteem, poor social function-ing and depression. Stressors associated with transitioning from pediatric to adult care couldexacerbate these issues. While stigmatization has been studied in adult patients with IBD,little is known about the effects of perceived stigma on adolescent IBD patients or its effecton transitioning. Aims: To explore social determinants of IBD-related stigma, we (a) designeda cross-sectional quantitative questionnaire measuring perceived stigma, health status, qualityof life, and transition readiness, and (b) analyzed domains of IBD-related stigma to predicttransition readiness.Methods:We developed an adolescent-specific IBD questionnaire mod-eled on the Perceived Stigma Scale for IBS (PSS-IBS), which assessed three domains of stigma:disclosure, attitude, and feelings of rejection/shame. The questionnaire was administered topts 15-23 yrs old with established IBD. Descriptive statistics were obtained on all studyparticipants. Logistic regression analyses were used to compare subjects who had healthcareprovider (HCP)-initiated interventions regarding care transition with those who had not,against IBD-related social stigma domains. Results: We enrolled 41 IBD pts (mean:17±2yrs; 54%F, 46%M). Demographic data were as follows:Race/ethnicity (71% Caucasian, 22%African American, 7% Other);Education (63% in high school, 29% in college, 2% in middleschool, 5% pursuing GED);Insurance status (71% private, 24% Medicaid/Healthchoice, 5%unsure).12% of pts reported excellent health status, 49% very good, 29% good, 7.5%fair, and 2.5% poor. Logistic regression analyses showed that pts who had not discussedtransitioning with their HCP had greater attitude-related stigma regarding their IBD. Subjectswho felt that their condition limited their social activities/hobbies were 2.9 times less likelyto have discussed transition with the HCP (p ≤0.02). These pts also reported receivinginadequate disease self-management information. Only 45% of those who had not discussedtransition, vs 87% of those who had, felt they had enough information to address theirmedical needs independently. Discussion: Our findings indicate the importance of thepediatric healthcare team in effectively addressing potential psychosocial barriers to healthand developing more effective patient education strategies as a means of improving adoles-cent-adult care transitioning. More specific measures of barriers, such as socioeconomicstatus, could also be clinically useful in enhancing how we transition adolescent patientsto adult care successfully, leading to improved medical outcomes and quality of life forthese patients.

Tu1937

Colorectal Cancer Cell Liver Metastasis Is Promoted by C-MET Activation andUpregulation of CD44 ExpressionVictoria A. Elliott, Piotr Rychahou, Yekaterina Zaytseva, B. Mark Evers

Colorectal cancer (CRC) is the second leading cause of cancer-related deaths in the UnitedStates. Metastatic or recurrent disease is the most common cause of death in these patients.Despite extensive research into the biology of cancer progression, the molecular mechanismsinvolved in CRC metastasis are not well characterized. A thorough understanding of thegenetic and epigenetic mechanisms that program metastasis establishment and secondarytumor formation is important for the development and of novel anticancer therapies. There-fore, the purpose of our study was to identify the genes that promote CRC liver metastasis.METHODS. To determine genes that regulate CRC liver metastasis and correlate with themetastatic potential of human CRC cells, we performed intrasplenic injection of metastaticHT29 cells and derived three human CRC cell lines (HT29LM1, HT29LM2, HT29LM3)after three rounds of in vivo selection of liver metastases (LM) in immunodeficient mice.For in vitro evaluation, we also used the parental human CRC cell line KM12C and itshighly metastatic derivative KM12L4A cell line established after four rounds of in vivoselection. HT29LM0, KM12C CRC cell lines and clones with different metastatic potentialwere evaluated by Western blot analysis. RESULTS. Approximately 40-50% of mice afterintrasplenic injections of HT29 cells develop extensive colon cancer liver metastases; incontrast, all mice injected with HT29LM3 developed extensive colorectal cancer liver metasta-ses. Western blot analysis of PI3K/Akt, Ras/ERK, β-catenin, E-cadherin pathways showeduniform expression and activation in in vitro cultures of the parental HT29 cell line and its

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highly metastatic clones. We found that expression of CD44, a transmembrane glycoproteininvolved in cell-cell and cell-matrix interactions, was gradually increased in all metastaticclones of HT29 cell lines, with maximum expression in the highly-metastatic HT29LM3 cellline. The KM14L4A cell line also exhibited higher CD44 expression compared to parentalKM12C cell line. We also demonstrated strong and gradual activation of c-Met at theTyr1234/1235 phosphorylation sites in all metastatic clones of HT29 cell line with maximumactivation in the HT29LM3 cell line. CONCLUSIONS. Taken together, our findings indicatethat CD44 overexpression and c-Met activation are simultaneously increased in metastaticCRC cells and correlate with the CRC liver metastasis phenotype. These observations suggestthat collaboration between the CD44 and the c-Met signaling pathways may play a criticalrole in CRC metastasis and could be used as a potential therapeutic target for treatment ofCRC metastases.

Tu1938

Improved Work Productivity in Caregivers of Pediatric Patients With Crohn'sDisease Treated With AdalimumabWallace Crandall, Frank Ruemmele, Gigi Veereman, Johanna C. Escher, Andreas Lazar,Mei Yang, Martha Skup, Jingdong Chao, Parvez Mulani, Roopal Thakkar, Jeffrey S.Hyams

Background: Adalimumab (ADA) can induce response and remission in children withmoderate/severe Crohn's disease (CD). Aim: We sought to assess the effect of ADA on abilityto work and perform regular activities in the caregivers of pediatric patients with CD.Methods: IMAgINE 1 was a 52-week, randomized study assessing efficacy and safety ofADA in children with moderate to severe CD failing prior therapy, including infliximab.After a 4 week open-label induction, 188 patients aged 6-17 years were randomized 1:1 tostandard dose (20 mg, bodyweight [BW] ,40 kg, or 40 mg, BW ≥40 kg; N=93) or lowdose (10 mg, BW ,40 kg, or 20 mg, BW ≥40 kg; N=95) double-blind ADA every otherweek. Patients experiencing flare/nonresponse could switch to blinded weekly dosing andto standard dose open label therapy after Week 12. Caregivers completed the 4-domainWork Productivity and Activity Impairment questionnaire for CD (WPAI-CD) at each visitto assess the effect of the patients' CD on work productivity and daily activity (0% = noimpairment; 100% = severe impairment). A 7% absolute change in WPAI-CD domain hasbeen described as the minimum clinically important difference (MCID). Paired t-tests assessedwithin-group changes from baseline for each domain at each timepoint (by group; by groupand prior anti-TNF use; by group and Week 4 response). Between-group differences inchange from baseline were assessed using ANCOVA, with group as factor and adjusting foranti-TNF exposure, Week 4 response (defined as a Pediatric Crohn's Disease Activity Indexscore decrease ≥15 points from baseline at Week 4), and baseline WPAI-CD domain. Last-observation-carried-forward was used for patients who discontinued or dose escalated.Results: At baseline, caregivers of patients in the standard dose group were more impairedin each domain: presenteeism (40.9% vs. 28.7%, P=.01), work impairment (47.0% vs.36.7%, P=.05), absenteeism (15.4% vs. 10.3%, P=.19), and activity impairment (44.8% vs.34.7%, P=.02). Caregivers of patients in both dose groups demonstrated improvements inpresenteeism, work impairment, and activity impairment at all time points compared withbaseline (figure). Improvements were generally larger in anti-TNF Naïve patients and earlyresponders. Following randomizing at Week 4, the standard dose group demonstratedslightly more change from baseline compared with low dose, but differences were notstatistically significant. Conclusion: ADA treatment was associated with improved workproductivity and activity impairment in caregivers of pediatric patients with CD.

Tu1939

Clinical Value of Finding Bile in the Stomach During Upper Endoscopy inPediatric PatientsHazim Zaghloul, Janet Poulik, Laura Gonzalez-Krellwitz, Shailender Madani, SuhasiniMacha, Namir Al-Ansari, Najeeb Zoubi, Maridine Co, Marwan Zidan, Mohammad El-Baba

Bile reflux into the stomach has been suggested as a cause of gastric mucosal lesions inadult patients after gastric or biliary surgery. Bile reflux gastropathy has also been observedin patients who have not had surgery. The endoscopic and histological significance of findingbile in the stomach in children during endoscopy is not adequately studied. The primaryobjective of the study is to evaluate the endoscopic and histological changes of gastric mucosain children who were found to have bile in their stomach during endoscopy (group A) andcompare it with the findings in a control group (group B). Methods: This is a prospectivestudy in which pediatric patients (,18 years) undergoing elective endoscopy were enrolledbetween the period of February 2012 and July 2012 at Children's Hospital of Michiganafter giving informed consent. In group A, presence of bile in stomach was described bythe endoscopist as: bile staining of the mucosa, bile lakes, or both. Biopsies were reviewedby an experienced pathologist at our hospital who was blinded to presence of bile. Thepathologist evaluated the biopsies for presence of reactive mucosal changes including: pit

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