Sa2011 Adverse Metabolic Effects of Indomethacin on the Immature Human Intestine Eric Tremblay, Emanuela Ferretti, Corentin Babakissa, Nancy Perron, Ernest G. Seidman, Emile Levy, Daniel Menard, Jean-Francois Beaulieu Background: Indomethacin (INDO) is a non-steroidal anti-inflammatory drug (NSAID) used for the treatment of patent ductus arteriosus in preterm infants and as a tocolytic agent in pregnant women. The exposure of preterm infants to INDO is associated with an increased risk of developing enteropathies such as necrotizing enterocolitis. Despite increasing progress in establishing the pathways involved in NSAID-induced damage, understanding the patho- genesis of gastrointestinal injury by NSAIDs in neonates relies on a limited number of studies carried out in animal models. Aims: In the present study, we combined our method for maintaining the mid-gestation human intestine in serum-free organ culture with high- throughput genomic studies and bioinformatic pathway analysis to investigate the specific intestinal effects of INDO on the overall physiology of both the small and large intestine at mid-gestation. Methods: After determining the optimal concentration of INDO to be 1μM (.90% inhibition of intestinal prostaglandin E2 production), a dose that corresponds to the range of circulating levels in treated preterm babies, we used Illumina microarrays to establish global gene expression profiles in human intestinal explants (ileums and colons) in response to an INDO treatment of 48 h. Differentially expressed genes between control and INDO-treated explants were determined using the Mann-Whitney test (p , 0.05), and further analyzed with Ingenuity Pathway Analysis software (IPA 8.8) to identify biological functions and canonical pathways modulated by INDO. Results: The gene expression profiles identified revealed that a large proportion of statistically significant biological, physiological and metabolic functions were modulated by INDO in the immature intestine. As expected, a number of these significantly modulated functions were inflammation-related such as "Inflammatory diseases", "Inflammatory response", and "Acute phase response". Notewor- thily, we have identified a series of metabolic-related gene clusters that were found to be significantly modulated, namely "Glycolysis/gluconeogenesis", "Oxidative phosphorylation" and "Free radical scavenging/oxidoreductase activity". Further analysis by qPCR confirmed that the expression of representative genes involved in these metabolic functions, such as ALDOA, LDHA, NDUFA9, DUOX2, SOD2, and TFF1, was inhibited by INDO in both intestinal segments, indicating that this adverse metabolic effect could be a component of the pathogenesis of intestinal damage induced by INDO. Conclusion: This study identified several different metabolic pathways that are modulated by INDO in the immature human intestine and suggests a mechanistic basis for better understanding the contributing effects of INDO and other NSAIDs on neonatal intestinal pathologies. Sa2012 Risk Factors and Temporal Trends for Complicated Diverticulitis: A Population-Based Study Oforbuike Ewelukwa, Rajesh Pendlimari, Ivo C. Ditah, Alan R. Zinsmeister, Barbara Yawn, Lee J. Melton, Adil E. Bharucha BACKGROUND. In the National Inpatient Sample, hospitalization for diverticulitis (D) and the proportion of patients with D who had abscesses increased between 1991 and 2005. It has been suggested that younger patients with D have more severe disease. However, most patients with D are managed as outpatients. In the only population-based study, the incidence of D was stable between 1980-1989 and 1990-1999 but increased by 50% in 2000-2007 [Gastro 2011;140 (5)]. AIMS. To evaluate temporal trends in the incidence of complicated D and its relationship to age and gender among unselected community patients. METHODS. Medical providers in Olmsted County (OC), MN are linked by a unique indexing system, the Rochester Epidemiology Project (REP). Using data resources of the REP, we identified all OC residents diagnosed with D between 1980-2007 who consented to research. These patients were followed through their medical records to the development of at least one complication or last visit. For analysis, the initial complication in each patient was classified as: abscess only (reference group), local (obstruction, fistula, stricture or peritonitis) and systemic complications (bacteremia, septicemia). Overall survival and survival free of a complication was estimated by the Kaplan-Meier method. A proportional hazards regression model assessed the association of time to initial complication with age, gender, and calendar period. Logistic regression assessed the association of complication category with age, gender and calendar period in those with an initial complication. RESULTS. Between 1980-2007, 3229 people had D. 386 developed complicated diverticulitis; 208 (54%) of these were females. By 60 days, the cumulative incidence of an initial complication was 9.5%. The median follow-up in those without a complication was 7.6y (range 0 days - 30.7y). Altogether, 146 (38%) had local and 26 (7%) had systemic complications; abscesses (n=220 [57%]) were the most common. 84 patients had . 1 complication; 71 had just 2. The risk of developing an initial complication was not associated with age, gender or calendar period. Among patients with a complication, compared to the reference group (abscess only), (i) older patients had an increased risk of local and systemic complications (ii) men had an increased risk of developing local but not systemic complications (Table). The type of complication was not associated with calendar period. CONCLUSIONS. Approximately 10% of patients with D had a complication within 60 days. Contrary to current concepts, the risk of a complication in patients with D was not related to age or gender nor has it changed over time. Among patients with complicated D, there was an increased risk of local complications in men and local/systemic complications in older people. The medical conditions predisposing to complicated D need further study. Risk factors for type of complication in patients with complicated diverticulitis S-359 AGA Abstracts * Reference group is 1980-89 † Reference group is females Sa2013 Efficacy and Safety of Enteral Administration of Omega 3 Fatty Acids Rich Perilla Oil in Children Treated With Parenteral Nutrition and/or Elemental Diet Yuri Etani, Yukiko Nishimoto, Shinobu Ida, Hisayoshi Kawahara Background: Patients treated with parenteral nutrition (PN) and/or elemental diet (ED) are likely to result in lipid deficiency. Lipid emulsion currently available in Japan is produced from soybean oil, which is rich in ω6 fatty acids. Aim: To evaluate the efficacy of enteral administration of Perilla oil for complement of ω3 fatty acids in children with intestinal dysfunction. Patients: Three males and four females (mean age was 2 years old: range 0-6) who needed nutritional support because of chronic intestinal pseudo-obstruction (3 patients), congenital esophageal hiatus hernia, short bowel syndrome, hypoxic-ischemic encephalopa- thy and neurodegenerative disease were included. All patients had enteral nutrition of ED which contain only 0.89g of lipid / 100kcal ( ω6/ ω3 ratio = 6.7). PN was performed for 4 children. Three cases were received soybean oil based lipid emulsion infusions ( ω6/ ω3 ratio = 6.5). Methods: The dose of Perilla oil ( ω6/ ω3 ratio = 0.19) was decided to make the patient's lipid / total energy ratio over 8%, in the ω6/ ω3 ratio of around 2 to 3. Three cases received Rapeseed oil ( ω6/ ω3 ratio = 2.46) simultaneously to adjust their ω6/ ω3 ratio. These oils were given enterally using gastric or duodenal tube. The levels of linoleic acid, α-linolenic acid, arachidonic acid (AA), eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) and EPA/AA ratio were compared before and after Perilla oil administration. Results: As baseline, all 7 patients showed quite small amounts of ω3 fatty acids. After the enteral Perilla oil (2.6 ± 1.8 g/day) administration for the mean duration of 60 days (range 21-156 days), the mean levels of α-linolenic acid and EPA were increased from 11.9 to 51.4 μg/mL (p= .043) and from 7.7 to 31.1 μg/mL (p= .018), respectively. The mean EPA/ AA ratio was improved from 0.06 to 0.32 (p= .018). On the other hand, the mean levels of linoleic acid, AA and DHA did not change significantly. No patients showed adverse effects, such as diarrhea or vomiting. There was no significant change in AST, ALT, total bilirubin and total cholesterol during the observation period. Discussion: Increased ω6/ ω3 ratio may increase inflammatory mediator production. Some lipid emulsions contain ω-3 fatty acids are available in U.S. and Europe, but the ω6/ ω3 ratio is fixed. Combination of Perilla oil and rapeseed oil are able to administer enterally, and determine the ω6/ ω3 ratio depends on the patient condition. In this study these oils significantly improved the levels of α-linolenic acid, EPA and EPA/AA ratio without adverse effects in children with intestinal failure. Conclusion: The enteral administration of ω3 fatty acids rich Perilla oil showed efficacy and safety in adjustment of the ω6/ ω3 ratio in children treated with PN and/or ED. Mean levels of fatty acids before and after the administration of Perilla oil * significant difference (p , 0.05) Sa2014 Unilateral Truncal Vagotomy Reduces Stomach Weight, Oxyntic Mucosal Thickness and Neuroendocrine Cell Density but Does Not Prevent Gastric Carcinoma Development in Hypergastrinemic Female Japanese Cotton Rats Reidar Fossmark, Øystein Sørdal, Karin E. Bakkelund, Ivar S. Nordrum, Helge Waldum Background and aims: The stomach is innervated by the vagal nerve. Several studies have demonstrated that the vagal nerve has a trophic effect on the rat oxyntic mucosa and that the trophic effect of hypergastrinemia is dependent on intact vagal innervation. The effect of vagal denervation on gastric carcinogenesis has previously been examined in Mastomys natalensis and hypergastrinemic transgenic INS-GAS mice, with no effect of unilateral vagot- omy in Mastomys but an anti-carcinogenic effect in INS-GAS mice. A proportion of female Japanese cotton rats develop spontaneous hypergastrinemia and ECL cell derived gastric carcinomas. In the current study we have examined the effects of unilateral truncal anterior subdiaphragmatic vagotomy on gastric carcinogenesis. Methods: Female Japanese cotton rats were operated with unilateral truncal anterior vagotomy (n=15) or sham-operation (n=16) at age 2 months and were terminated at age 10 months. Intragastric pH and stomach weight AGA Abstracts