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Capsule Endoscopy Evaluation in Patients With Chronic DiarrheaStefania Maiero, Mara Fornasarig, Maria Tabuso, Enrico Orzes, Renato Cannizzaro

Background and aim : Video Capsule Endoscopy (VCE) is a tool to investigate small bowelpathology. Common indications for VCE are: obscure gastrointestinal bleeding (OGIB),unexplained iron deficiency anemia, small bowel tumors, Crohn's disease and Celiac disease.The role of VCE in the evaluation of chronic diarrhea has not been yet clearly defined. Theaim of this study was to evaluate the diagnostic yield of VCE for chronic diarrhea. Materialand methods : 787 patients who underwent VCE between October 2003 and September2012 in our Institution after previous negative diagnostic work-up were retrospectivelyreviewed for indications and findings. We included in our study patients with chronicdiarrhea and excluded patients with a confirmed diagnosis of Crohn's disease, celiac diseaseand IBS. Results : Out of 787 patients diarrhea was the primary indication in 32 (4%)patients of which 16 F and 16 M (mean age 47). All patients had non-diagnostic colonoscopy,gastroscopy, blood and stool tests. The VCE revealed abnormalities to explain chronicdiarrhea in 17 patients out of 32. In three patients we found alterations suggestive of celiacdisease; in two patients we found ulcerations suggestive of Crohn's disease; in two patientswe found aspecific ileitis; in one patient we found chemiotherapic related ileitis; in twopatients we diagnosed accelerated transit; in seven patients we found submucosal masses.VCE facilitated diagnosis in 53% of patients with previous negative diagnostic work-up.Conclusions : The results of our study suggest that VCE is a valid diagnostic tool forchronic diarrhea. Further studies are warrented to evaluate the higher dignostic role andcost effectivness of VCE in chronic diarrhea.

Su1129

Patients Perception of Colonoscopy: Astonishing Reasons for Colon CapsuleEndoscopy PreferenceMarek Benes, Pavel Drastich, Julius Spicak

Introduction: Colonoscopy is considered to be the gold standard for colon evaluation andscreening for colorectal cancer (CRCA). Classical colonoscopy (CC) is an invasive methodwith an unfavourable reputation amongst patients which may be a reason for noncompliancewith CRCA screening programs. Colon capsule endoscopy (CCE) is an innovative non-invasive technique which has gained patients interest in CRCA screening despite the fact ofbeing very costly. Aim and methods: The aim of this prospective, multicentric study wasto assess reasons for preference for CCE over CC. The data from all consecutive patientsscheduled to undergo CCE were obtained using a questionnaire. Results: From December2010 to October 2012 one hundred patients (68 men, 32 women, average age 52 years)were included in the study. Seventy eight (78%) patients had university education and 20patients (20%) were high school graduates. Seventy nine (79%) were senior managers withat least 10 or more employees. Sixty five (65%) had their salary at least four times thenation's avarage income. The main reasons of CCE preference were concerns about a patient̀sprivacy and embarrassment (38 patients, 30 males, 8 females), concerns of pain (35 patients,18 males, 17 females) , fear of a loss of discernment (20 patients, 15 males, 5 females).Forty six (46%) patients had undergone CC in the past. In this subgroup, privacy issue wasmain reason for 33 (71%) patients and pain for 13 (28%) patients. Forty two patients (42%)would never undergo a screening CC even though 19 (45%) of them had a positive familyhistory. Conclusions: The main reason for CCE preference over CC was mental discomfortand fear of embarrassment during CC, rather than concerns of pain. The results imply aneed of improvement of our CC management.

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Severe Polypharmacy and Major Medication Interactions Are Associated WithIncreasing Age and Comorbidity Among Inflammatory Bowel Disease PatientsAlyssa M. Parian, Christina Y. Ha

Background: Comorbidities are associated with increased rates of hospitalizations, surgicalcomplications, and mortality among older inflammatory bowel disease (IBD) patients. How-ever, polypharmacy and medication interactions may contribute to the increased morbidity.The aim of this study was to assess the prevalence of polypharmacy and medication interac-tions within a cohort of older IBD patients. Methods: A cross-sectional study of 128 IBDpatients aged 65 years and older was performed at a tertiary IBD referral center during theperiod of January 2010 to November 2012. Patients were surveyed regarding IBD activityand treatment regimen, comorbid conditions (scored using the Charlson comorbidity index),and polypharmacy including prescription and over-the-counter medications. Medicationinteractions were identified and classified using a publicly available drug interaction tool.Primary outcomes of interest included the severity of polypharmacy and medication interac-tions relative to IBD activity. Results: Older IBD patients were taking an average of 9.5 (95%CI 8.6-10.3) routine medications. Crohn's disease (CD) patients were taking an average of10.3 (95% CI 9.1-11.5) medications compared to 8.7 (95% CI 7.7-9.7) medications amongulcerative colitis (UC) patients, p=0.04. Approximately half (n=57, 44.5%) of studied patientshad severe polypharmacy (.10 routine medications). Severe polypharmacy was associatedwith comorbidity index scores (p,0.0001) and steroid use (p=0.01), not disease activity

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or type (Table 1). Although the majority (n=84, 65.6%) of older IBD patients were routinelytaking 5 or more prescription medications, this was higher among older men (74.6%) thanwomen (55.7%, p=0.03). Overall, 79.7% (95% CI 71.9-85.8) of patients had at least onemedication interaction with the majority involving IBD therapies (63.3%, 95% CI 54.7-71.1). One-third (32.0%, 95% CI 24.6-40.6) of the IBD therapy-related interactions wereclassified as severe. These IBD-medication interactions were highest among the patients overthe age of 70, p=0.01 (Figure). Conclusion: Older age and comorbidity increases the riskfor severe polypharmacy and major medication interactions. Physicians caring for older IBDpatients should check for inappropriate medication use and interactions prior to prescribingany IBD therapy to prevent potential adverse effects.

Su1131

Incidence Rate of Lymphoma by the Cumulative Duration of Exposure toThiopurines: A Nationwide Retrospective Cohort From the Veterans' AffairsHealthcare SystemAli Abbas, Yordanka N. Koleva, Nabeel Khan

Background: Thiopurine treatment is associated with increased risk of lymphoma. It isunknown if this risk is related the duration of exposure to thiopurines. The aim of thisstudy is to identify incidence rate of lymphoma by the cumulative duration of thiopurinesexposure. Methods: Ulcerative colitis (UC) patients followed-up in the Veterans Affairs (VA)healthcare system between October, 1st, 2001 and October, 1st, 2011 were identified usingICD9 codes. We used retrospective cohort study design. Patients were followed from theindex date of UC diagnosis in the VA system to the date of lymphoma diagnosis or October,1st, 2011. Cumulative duration of thiopurines exposure during the follow-up was calculatedusing pharmacy records. Lymphoma cases were firstly identified by ICD9 codes then bymanual chart review to confirm the diagnoses and the dates. Person-year contribution wascalculated for the included patients and the incidence rate of lymphoma was calculated fornon-thiopurines users and by each year of cumulative thiopurine use. Univariate hazardratios (HR) were calculated comparing the incidence rate of lymphoma by year of thiopurinesuse against the incidence rate among unexposed group. Results: We included 36,891 patientsin the analysis, median follow-up of 6.7 years. Total person-year of follow-up analyzed was

199,204. Majority were Caucasians (75%), males (93%) with median age at inclusion of 60years. Among the included patients, 4,734 used thiopurines with median duration of oneyear. Numbers of lymphoma cases identified were 119 and 18 among non-users and whileusing thiopurines respectively. The incidence rate of lymphoma among those who neverused thiopurines was 0.6 compared to 0.9, 1.6, 1.6, 5, 8.9 per 1000 person-year for the1st, 2nd, 3th, 4th and .4 years of thiopurine use respectively (Figure). The incidence ratesof the fourth and more than four years were significantly different from the incidence rateof non-users, yielding HR of lymphoma of 8 and 14 for the fourth year and more than fouryear of thiopurines use respectively (p,0.001). Conclusion: In this nationwide cohort ofUC patients, the incidence rate of lymphoma significantly increased after the third year ofcumulative exposure to thiopurines.

Incidence rate of lymphoma by the cumulative duration of exposure to thiopurines

Su1132

Toxicity and Mortality Related to the Use of Ciclosporin in Steroid RefractoryUlcerative Colitis: A Multicentric Nationwide Study (ENEIDA)Ingrid Ordás, Eugeni Domenech, Valle García-Sánchez, Mireia Peñalva, Alex Cañas, OlgaMerino, Fernando Fernández-Bañares, Fernando Gomollon, Isabel Vera, Ana Gutiérrez,Esther Garcia-Planella, Javier P. Gisbert, Mariam Aguas, Elena Gento, Fernando Muñoz,Maddi Aguirresarobe, Carmen Muñoz, Luis Fernandez, Pere Vilar, Xavier Calvet, ManuelBarreiro-de Acosta, Carlos E. Jiménez, Miguel A. Montoro, Joaquin Hinojosa, CristinaSaro, Alberto Mir, Luisa De-Castro, Mariana F. Garcia-Sepulcre, Fernando Bermejo, MariaEsteve

Introduction: A recent randomized controlled trial comparing ciclosporin (CyA) with inflixi-mab (IFX) in the setting of steroid refractory ulcerative colitis (SR-UC) has shown similarefficacy and safety for both treatments. However, the safety profile of CyA remains to be aconcern in some countries. Aims: 1) To evaluate the toxicity and mortality related to theuse of CyA in patients with severe SR-UC flares in clinical practice 2) To compare CyAadverse events (AEs) with other treatment regimens (IFX and surgery) with the same indica-tion. Patients and Methods: Multicenter, community-based cohort study. Patients wereidentified using a prospectively maintained database (ENEIDA registry). Data collectedincluded: age, sex, disease extent, treatment (CyA, IFX, surgery and/or combination ofthese), dose, treatment duration, AEs, concomitant use of immunomodulators, prophylactictreatment in case of triple immunosuppression, clinical remission, colectomy rate at 1 and5 years and mortality rate related to the steroid-refractory flare. To avoid an inclusion bias,all participating centers reviewed the cases of death diagnosed with UC and its causes since1990. Results: From 5783 UC patients, 473 (8.2%) met the inclusion criteria (SR-UC). Allcases received treatment with corticosteroids. Treatment regimens for induction of remissionwere the following: CyA (n=210; 47.1%), IFX (n=44; 9.5%), CyA-IFX (n=24; 5.2%), IFX-CyA (n=3; 0.6%), Colectomy (n=92; 19.8%), CyA-Colectomy (n=59; 12,7%), IFX-Colectomy(n=10; 2.2%), CyA-IFX-Colectomy (n=12; 2.6%), IFX-CyA-Colectomy (n=2; 0.4%). Globalremission rate was 73.6%. The mortality rate associated to CyA and the global mortalityrate was 2.5% and 10% respectively (52% related to colectomy), varying from 0 to 13.5%according to different centers. There was no difference between CyA and IFX-relatedmortality(n=5, 2.5% vs. n=1, 2.3%; p=1, respectively), neither between CyA-colectomy and IFX-colectomy (n=6, 10% vs. n=0, 0%; p=0.27). Patients treated with CyA presented less AEs[n=18, 9.5% (infections 3.7%)] than IFX treated patients [n=12, 27.3%; p=0.002 (infections11.4%)]. From patients treated with colectomy (without having received medical rescuetherapy; either CyA or IFX), 34.8% presented AEs (n=23), infections being the more frequent(n=7; 10.6%). Conclusions: we provide safety results of the largest series of patients treatedwith CyA for severe SR-UC. The lower rate of AEs associated with CyA compared to IFXand a similar mortality rate between both treatment strategies give support to the use ofCyA as a first-line rescue therapy in cases of SR-UC. Colectomy in cases of severe SR-UCshould be performed in experienced centers due to the elevated mortality rate associatedwith the procedure.

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Influence of Biologic Agents on Short-Term Postoperative Complications inPatients With Crohn's Disease: A Prospective, Single-Surgeon Cohort StudyCheryl C. Lau, Marla Dubinsky, Gil Y. Melmed, Eric A. Vasiliauskas, Dermot P.McGovern, Dror Berel, Zuri A. Murrell, Andrew Ippoliti, David Q. Shih, Manreet Kaur,Stephan R. Targan, Phillip Fleshner

Aim: Biologic therapy is an essential component in the management of patients with Crohn'sdisease (CD). Current evidence on the influence of biologic therapy on postoperative out-comes is conflicting. Method: A prospectively maintained CD registry of patients operated

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on by a single surgeon was reviewed. The cohort was divided into 2 groups based onexposure to biologics before surgery: Group A had been treated with biologics and GroupB was not treated with biologics. Patient demographics, disease severity and cumulativerates of postoperative outcomes within 30 days of surgery were reviewed. These variableswere also compared in 3 subgroups of Group A: infliximab alone group, infliximab incombination with other biologics group, and other biologics excluding infliximab group.Associations between Groups A and B and postoperative outcomes were analyzed usingFisher's exact and t-test. Associations between each of the biologics subgroups (in comparisonto Group B) and covariates were analyzed using multinomial logistic regression model,and ANOVA model, followed by pairwise post-hoc analysis, with adjustment for multiplecomparisons. Results: The study cohort comprised 458 consecutive patients (median age33; 55% males). Group A included 213 (47%) patients and Group B included 245 (53%)patients. In Group A, 126 (59%) had been on infliximab alone, 51 (24%) had been oninfliximab and other biologics, and 36 (17%) had been treated with adalimumab and/orcertolizumab without infliximab. Patient demographics and disease severity in the two groupswere similar, except Group A had a higher incidence of preoperative immunomodulatoruse (98% vs 88%, p=0.0002), and lower rates of internal penetrating disease behavior (37%vs 51%; p=0.005) and preoperative enteric perforation (23% vs 36%; p=0.002). Surgery inGroup A was not associated with significantly higher risk of overall postoperative morbidityand infectious complications. However, compared to Group B, subgroup analyses demon-strated an increased risk of postoperative intraabdominal infections in the infliximab-alonegroup (10% vs 4%, OR 3.5, p=0.047). Rates of readmission (14% vs 7%, p=0.06) and ileus(14% vs 7%, p=0.06) after surgery were also higher in the infliximab-alone group althoughthese did not reach statistical significance. Onmultivariate analysis, postoperative hospitaliza-tion stay and time to tolerance of diet was higher in the infliximab alone group. Conclusion:Preoperative biologic therapy was not associated with an overall increased risk of postopera-tive complications in our CD cohort. However, subgroup analysis showed increased risksof postoperative intraabdominal infections, time to tolerance of diet and postoperativehospitalization stay in the infliximab-alone treated group.

Su1134

Prediction of Dose of Tacrolimus Required for Remission Induction ofUlcerative Colitis PatientsSakiko Hiraoka, Jun Kato, Toshihiro Inokuchi, Asuka Nakarai, Tomoko Hirakawa,Mitsuhiro Akita, Keita Harada, Hiroyuki Okada, Kazuhide Yamamoto

Background and Aims: Calcineurin inhibitors such as cyclosporine A and tacrolimus havebeen shown to be effective for treatment of steroid-dependent or steroid-refractory ulcerativecolitis (UC) patients with moderate to severe activity. Tacrolimus is usually taken orallywith efficacy, and therefore, it can be prescribed for outpatients. However, large varietyin dose required for reaching sufficient trough levels among individuals has made theadministration for outpatients difficult. This study aimed to identify factors that regulatedthe dose of tacrolimus required for achieving sufficient trough levels for remission inductionof UC patients. Methods: Data on all patients with moderate to severe UC who had beentreated with tacrolimus at our hospitals from September 2006 to October 2012, wereanalyzed. No patients had renal function disorders, and patients who were readministeredtacrolimus were excluded. The initial oral dose of tacrolimus was 0.05-0.15 mg/kg/day.Trough concentrations were measured and doses were adjusted with the aim of achievingwhole blood trough concentrations of 10-15 ng/ml. Medical charts provided clinical informa-tion including demographic data, such as age, gender, and duration of the disease, severityof disease, and extent of disease. In addition, we examined medications (5-aminosalicylates,corticoisteroids, immunomodulator use), bowel movements (frequency/day), diet (fastingor not), and laboratory data (WBC, CRP) at starting tacrolimus. Tacrolimus dose was analyzedwith correction by body weight. Results: We administered tacrolimus to 47 UC patients(24 (51%) male, median (range) age of 37(12-70) years) during the study period. Of the47 patients, 41 (87%) achieved a clinical remission or response with the tacrolimus therapy.Median daily dose of tacrolimus required for sufficient trough levels was 0.19 (0.07-0.42)mg/kg. Because the dose required for each patient showed bimodal distribution, patientswere divided into two groups by the required dose ( , 0.2mg/kg or ≥ 0.2mg/kg). Age,gender, and CRP (. 1.5 mg/dL) differed significantly between the two groups. Multivariateanalysis revealed that male (OR = 7.10; 95% CI, 1.35-50.0) and CRP . 1.5 mg/dL (OR =7.24; 95% CI, 1.39-53.2) were independent factors for the required dose ≥ 0.2mg/kg. Theremission rate and adverse events did not differ significantly between the two groups.Conclusions: The required dose of tacrolimus for remission induction of UC showed bimodaldistribution and predictive factors for requirement of high dose were identified. For furthergeneralization of tacrolimus, the additional analysis including genetic polymorphisms onthe pharmacokinetics is required.

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