AGA Abstracts 490 Postoperative Complications in a Population-Based Cohort of Crohn's Disease Laurent Peyrin Biroulet, Edward V. Loftus, William S. Harmsen, William J. Tremaine, Bruce G. Wolff, John H. Pemberton, Robert R. Cima, David W. Larson, Eric J. Dozois, Alan R. Zinsmeister, William J. Sandborn Background and Aims: We sought to describe the incidence of and factors associated with postoperative complications in Crohn's disease. Methods: Using the resources of the Rochester Epidemiology Project, we identified all patients who had undergone at least one major abdominal surgery for Crohn's disease among 310 incident cases of Crohn's disease from Olmsted County, Minnesota, diagnosed between 1970 and 2004. Medical records were reviewed for early (within 30 days of surgery) and late (≥ 30 days) complications. Factors associated with time to complication were assessed using proportional hazards regression modelling and were expressed as hazard ratios (HR) with 95% confidence intervals (CI). Results: Among 152 patients (49%) who underwent at least one major abdominal surgery until March 2009, 57 (37.5%) experienced at least one early postoperative complication (median, 1; range, 1-5). A total of 80 early complications were observed in 57 patients, with 28 infectious and 52 non-infectious events. Late complications occurring beyond 30 days after surgery were reported in 36 (23.7%) patients (median, 1; range, 1-4). A total of 55 late complications were observed in 36 patients, with 20 infectious and 35 non-infectious events. The cumulative probability of any post-operative complication was 45% (95% CI, 36.2-52.7) at 5 years and 57.6% (44.9-68.3) at 20 years. One patient died from sepsis due the occurrence of enterocutaneous fistula and bile leakage. Factors significantly associated with time to any postoperative complication were ileocolonic (HR relative to colonic, 0.45; 95% CI, 0.3-0.8) and small bowel (HR, 0.2; 95% CI, 0.1-0.4) disease at the time of diagnosis. Age, gender, smoking status, and baseline presence of intestinal complications were not associated with time to any postoperative complication. Conclusion: About one third and one fourth of Crohn's disease patients experienced at least one early or late postoperative complication, respectively. The postoperative mortality rate was 0.7%. Relative to colonic- only extent, those with ileal or ileocolonic disease were significantly less likely to experience a post-operative complication. 491 Surgery, Crohn's Disease and the Biologic Era: Has There Been an Impact? Eoin Slattery, Denise Keegan, Diarmuid P. O'Donoghue, Hugh Mulcahy Introduction: The management of Crohn's disease (CD) has changed considerably over the last 20 years. Immunomodulators and biologic therapies now play a role in treating patients with CD but little is known of their influence on surgical rates. Aim: To review the surgery rates for Crohn's in an Irish university hospital over a 20-year period and to determine if newer therapies had impacted on surgical rates Method: 722 patients attending St Vincent's University Hospital, Dublin with Crohn's disease over a 20-year period (Jan 1986 - Dec 2005). Patients were divided into 4 quartiles. Resection rates were determined in all quartiles, at both 1 and 3 years from diagnosis. Results: A downward trend was noted between the quartiles in resection surgery at 1 year (49, 39, 38 and 42 patients). A decline in surgery, 3 years from diagnosis, was noted between the first quartile (72 patients, 40%) and the second quartile (58 patients, 32%, p=0.03). No significant change in surgical rates at 3 years occurred between the other three quartiles (32%, 30% and 35% respectively, p=NS). Patients who required a resection within 3 years were diagnosed at a younger age in later years. There was a similar predominance of females requiring surgery in all groups of 60%. Patients requiring surgery were twice as likely to be ex- or current smokers in all groups. Use of infliximab, within 3 years from diagnosis, increased from 0, 0, and 16 patients (8.8%) to 40 patients (22.1%) in the last quartile. The majority of patients were treated with infliximab on an “on-demand” basis. Use of infliximab earlier within the course of disease was seen in later quartiles (i.e. within 1 year of diagnosis); 0, 0, 6 and 21 patients. Conclusion: Despite the introduction of infliximab over the past 10 years, no demonstrable difference has been seen in the rates of patients requiring resection surgery within 3 years of diagnosis. The reasons for this are unclear, but may relate to episodic treatment, rather than regular maintenance treatment. Female patients and smokers appear to be particularly at risk for resection surgery. 492 Reduced Surgical Resection Rates With Increasing Immunosuppressant use in a Population-Based Inflammatory Bowel Disease (IBD) Cohort in Cardiff (1988-2003) Arvind Ramadas, Cassandra Gwinnutt, Gareth Thomas, Geraint Williams, Antony B. Hawthorne INTRODUCTION:The benefits of immunosuppressant(IS)therapy in IBD have been demon- strated in many controlled trials, however it has been difficult to show that early and widespread use of these drugs have reduced surgical rates in routine practice. Aims and Methods: To assess changes in surgical rates in IBD in a population-based cohort of IBD patients diagnosed in Cardiff between 1988-2003. Case notes of Crohn's disease (CD), ulcerative colitis (UC) and indeterminate colitis (IC) patients from IBD incidence studies in Cardiff were reviewed retrospectively for disease characteristics and for follow-up information on the use of IS and the need for surgery for IBD. The patients were identified from the incidence studies of CD (1986-2005),UC and IC (1988-2007).We excluded UC and IC patients with isolated proctitis at diagnosis as surgery is rarely performed for isolated proctitis. The study population was divided into 2 groups (Group A= 1988-95 and Group B= 1996- 2003) based on the year of diagnosis. Results: 553 IBD patients (Group A=259 and Group B= 294) included in the final analysis. There were 309 CD, 214 UC and 30 IC patients. 5 year follow-up was available in 514 patients (93%). No significant difference in patient or disease characteristics in the 2 groups. Kaplan-Meier (KM) analysis showed a significant increase in cumulative probability of IS use in IBD over time; At 5 years this was 17% (Group A) and 45% (Group B) (p=0.0001). KM analysis also showed a significant decrease in surgical rates over time; At 5 years this was 47% in Group A and 28% in Group B (p= S-70 AGA Abstracts 0.0001). Also there was a significant reduction in resection rates in CD (p=0.0001) and UC (p=0.02) over time in the 2 groups. Cox multivariate analysis of surgical interventions in IBD showed time of diagnosis (p=0.001), early steroid use (within 3 months of diagnosis) (p=0.0001) and thiopurine use within 1st year of diagnosis (p=0.002) as independent factors predicting resection (see table). Conclusion: The decrease in surgical resections in UC and CD in this population-based cohort over the past 18 years is most likely due to the increased and earlier use of IS therapy. Cox multivariate analysis 493 An Extended Study of Appendicectomy as a Therapy for Ulcerative Proctitis Terry Bolin, Shing Wong, Roger Crouch, Jeffrey L. Engelman, Stephen M. Riordan INTRODUCTION: We have previously shown that appendicectomy can modulate the clinical course of ulcerative colitis.1 AIMS: The aims of this study were to determine: 1: the efficacy of appendicectomy in an extended cohort of patients with ulcerative proctitis undergoing appendicectomy; 2: whether clinical improvement following appendicectomy is maintained over a longer period of follow up and 3: whether appendiceal histology predicts clinical outcome. RESULTS: 50 patients with ulcerative proctitis underwent appendicectomy. The clinical activity index improved significantly from a median of 9 (range 7 - 12) to a median of 2 (range 0-12) (P<0.0005) in 40 patients (80%) with 15 (30%) having no continuing therapy. The index remained unchanged in 10 of 50 patients (20%). Initial clinical response has been maintained in all but 37 of 40 patients (93%) with the remaining 3 patients experiencing flares responsive to medical therapy that prior to appendicectomy had proven ineffective. The duration of the clinical response is now up to three years. The appendiceal histology showed ulcerative appendicitis (UA) in 25, fibrous obliteration in 10, normal in 12 and mucinous cystadenoma in 3. This histopathology was unrelated to clinical outcome. No patient has described deterioration in the index or required proctocolectomy. CONCLU- SION: Elective appendicectomy may provide an additional option for therapy of ulcerative proctitis. 1. American Journal of Gastroenterology 2009; 104:2476-2482. 494 Roux-en-Y Gastric Bypass Selectively Accelerates the Post-Prandial Rise in Circulating Taurine- And Glycine-Conjugated Bile Acids Nadia Ahmad, Lee M. Kaplan Background: The rates of obesity continue to rise and pose a serious physical, psychosocial and economic burden. Currently, the most effective therapy for severe obesity is Roux-en- Y gastric bypass (RYGB). We have recently shown that RYGB increases energy expenditure (EE), particularly diet-induced thermogenesis, in rodent models. Among the potential medi- ators of this effect, bile acids (BAs) have been shown to regulate EE via signaling through the G-protein coupled receptor TGR5 in muscle and brown adipocytes. Given these effects, we hypothesized that the increase in EE after RYGB may be mediated in part by RYGB- induced changes in circulating BA levels. Aim: To determine the effect of RYGB on circulating BAs in humans. Methods: Frequent sampling up to 3 hours after ingestion of a standard liquid meal was performed on 5 subjects before and after RYGB. All primary and secondary bile acids, their taurine and glycine conjugates, and specific sulfated moieties were measured using reversed-phase high-performance liquid chromatography / mass spectrometry. Results: One month after RYGB, there was no significant difference in the fasting and post-prandial serum levels of total BAs. However, the percentage of taurine-conjugated circulating BAs after a meal (pc) increased two-fold (by area under the curve analysis, p<0.05). There was also a substantial acceleration of the post-prandial BA excursion curve. Pre-operatively, total BA levels increased 3.7-fold within 120 minutes pc and remained elevated until at least 3 hours pc. After RYGB, total circulating BA levels peaked within the first 60-90 minutes pc and returned rapidly to baseline by 120 minutes. Upon examination of individual BAs, we found a significant and specific acceleration of the post-prandial excursion curve for the taurine and glycine conjugates of all three of the most prevalent BAs (cholic acid, chenodeoxy- cholic acid and deoxycholic acid; p<0.05 for each). Conclusion: RYGB accelerates the increase in circulating BAs in response to a meal and shifts the composition of the post-prandial circulating BA pool toward a taurine-rich profile. Given that BAs have been shown to activate thermogenesis in muscle and brown adipose tissue, this accelerated response may promote a greater thermogenic effect of food intake after RYGB and contribute to the increased EE observed after this operation. These observations suggest that manipulation of circulating concentrations of BAs could reproduce some of the metabolic effects of RYGB and therefore be a useful strategy for the development of novel therapies for obesity, diabetes and related metabolic disorders.