973 Relationship of EMAST and Microsatellite Instability Among Patients With Rectal Cancer

following laparotomy. Subgroups were vagotomized 3-4 days prior to experiments or received pharmacological inhibition of the acetylcholine α7 subunit with the inhibitor α-bungarotoxine (1μg/kg i.p. 1h, 3h, 9h prior to ileus induction each n=6), while control animals were sham operated and remained otherwise untreated. Three hours after small bowel manipulation a 2 cm jejunal segment was harvested with the mesentery attached. Mesenteric afferent nerve discharge was recorded In Vitro generating a multi-unit signal with subsequent computerized analysis including recording of intestinal motility. Afferent nerve discharge at baseline, responses to chemical stimulation with bradykinin (0.5 μM), 5-HT (500 μM) and mechanical stimulation by continuous ramp distension to 60 mmHg were studied. Data are mean ± SEM. Results: Peak amplitudes of intestinal motor events were 0.70±0.02, 0.69±0.04, and 0.67±0.03 mmHg and afferent nerve discharge was 12±2, 11±1, 14±1 1 imp sec-1 following vagotomy, α-bungarotoxine, or sham operation, respectively with no difference between groups (all n.s.). Increase of afferent discharge to 5-HT was 6 ± 1 imp sec-1 above baseline following α-bungarotoxine which was similar compared to 8 ± 1 imp sec-1 in sham controls, while the response was reduced to 0.7±1.6 imp sec-1 in chronically vagotomized animals (p<0.05). Bradykinin was followed by 20±2, 19±1 and 22±1 imp sec-1 after vagotomy, α-bungarotoxine or sham operation respectively, while peak firing rate was 83±9, 95±12 and 80±8 imp sec-1 during intraluminal ramp distension at 60 mmHg (all n.s.). At luminal distension from 10 to 30 mmHg, afferent discharge was lower in vagotomized animals compared to sham controls (p<0.05), but unchanged after α-bungarotoxine. Conclusions: Sensitivity to 5-HT and low-threshold distension is mediated via vagal afferents during postoperative ileus, while sensitivity to high threshold distension and bradykinin is independent of intact vagal afferents. Inhibition of intestinal motility early, i.e. 3 hours after induction of postoperative ileus, does not appear to depend on vagal innervation.

with an increase in postoperative intra-abdominal infections were age and penetrating disease. CONCLUSIONS: The use of anti-TNF alpha in the perioperative period is safe and does not seem to be associated with an increase in overall or infective complications for patients with Crohn's disease undergoing surgery. 972 The Relationship Between Pre-Operative Comorbidity, the Systemic Inflammatory Response and Survival in Patients Undergoing Surgery for Colorectal Cancer Campbell S. Roxburgh, Jonathan J. Platt, Fiona Leitch, Paul G. Horgan, Donald C. McMillan Introduction: Besides tumor characteristics, colorectal cancer progression and survival is also determined by host factors, in particular a systemic inflammatory response (Glasgow Prognostic Score/GPS). The basis of this stage independent relationship with survival is unclear, however pre-op systemic inflammation may reflect comorbidity. Indeed, validated scores such as elevated Charlson comorbidity index (CCI), National Institute on Aging/ National Cancer Institute (NIA/NCI) Index and Adult Comorbidity Evaluation-27 (ACE-27) are related to poor colorectal cancer survival. This study examines the relationships between pre-op comorbidity, systemic inflammation (GPS) and survival in colorectal cancer. Methods: Patients having elective curative resection were studied (n=302,1997-2005). A pre-op Creactive protein>10mg/L and albumin<35g/dl each score 1 and the GPS is constructed (GPS 0, 1 or 2). Comorbidity data was abstracted from casenotes review. Patients were classified by 4 separate scores; the CCI, NIA/NCI index, ACE-27 and Lee Cardiac Risk Index (LCRI). Deprivation category, smoking status and body mass index (BMI) was collected. Results: Most were >65yrs (66%), Stage I/II disease (60%), a normal GPS (62%) and had a low comorbidty burden. Median follow-up was 74 months during which 135 died (85 from cancer). On multivariate analysis for cancer survival, age (HR 1.30,P=0.057), TNM stage (HR 2.73,P<0.001), LCRI (HR 1.38,P=0.014) and GPS (HR 1.85,P<0.001) were independently related. On multivariate analysis for overall survival, age (HR 1.50,P<0.001), TNM stage (HR 1.84,P<0.001), ACE-27 (HR 1.31,P=0.005) and the GPS (HR 1.61,P<0.001) were independently related. Results were similar in node negative disease (n=180). Old age was related to increasing comorbidity (ACE-27, CCI, LCRI (all P<0.005)) and elevated GPS (P<0.005). High BMI was related to higher comorbidity assessed with CCI, ACE-27 and NCI/NIA scores (all P<0.01). Smoking history and deprivation were related to increasing burden of comorbidity (all P<0.05). GPS had a weak association with comorbidity burden assessed with the ACE-27 (P=0.065), CCI (P=0.016), LCRI (P=0.095) and the NIA/NCI index (P=0.084). Discussion: Pre-op comorbidity measures, particularly Lee cardiac risk index are important indicators of cancer survival. Generalised comorbidity does not explain the relationship between the systemic inflammatory response and survival. The tumor and its response to therapy form the mainstay of current cancer reatment, however it is increasingly apparent novel “host-related” targets may be important. These include attenuation of the host inflammatory response and optimisation of host physiology.

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SSAT Abstracts

Eating Behavior in Rats Subject to Vagotomy, Sleeve Gastrectomy and Duodenal Switch Yosuke Kodama, Chun-Mei Zhao, Baard Kulseng, Duan Chen Background/aim: Obesity is a multifactorial disease and the treatments include dieting, exercises, drugs and various surgical procedures. Recently, we reported that gastric bypass surgery caused body weight loss without reducing food intake and that high-fat diet-induced obesity was associated with increased calories per meal but not per day in rats. In the present study, we examined the food intake, eating behavior and metabolic parameters in rats underwent bilateral truncal vagotomy, sleeve gastrectomy and duodenal switch procedures. Methods: Body weight (BW) was recorded weekly throughout the period of the study. The food intake, eating behavior and metabolic parameters were measured pre- and 2 or 9 weeks post-operatively by a comprehensive laboratory animal monitoring system (the so-called CLAMS). Adult rats were subjected to bilateral truncal vagotomy plus pyloroplasty to prevent gastroparesis (VTPP), pyloroplasty alone (PP) or sham operation as controls. 10 weeks after completing CLAMS measurements, sleeve gastrectomy (SG) or duodenal switch (DS)(without SG) was performed in sham- or PP-operated rats, respectively, and the same CLAMS measurements were repeated as before. Afterwards, the SG-rats were subjected to DS and the VTPPrats were subjected to both SG and DS simultaneously. Results: Survival rates were 100% for sham- (7/7), PP- (7/7) and VTPP-operations (7/7), 86% for SG (6/7), 71-83% for DS alone (5/7) or DS with SG (5/6) that was performed early, and 14% for SG+DS (1/7) that were performed at the same time. VTPP reduced BW (10%) transiently (1 week postoperatively), while PP- or sham-operation was without the effect. SG caused a reduced BW (10%) for 6 weeks, while DS alone or SG followed by DS led to a continuous BW loss from 15% at 1 week to 50% at 9 weeks postoperatively. Food intake was higher and satiety ratio was lower during nighttime than daytime in all groups of surgeries. VTPP was without any measurable effects on food intake, eating behavior and metabolic parameters. SG increased drinking activity and energy expenditure but was without the effects on food intake and eating behavior. DS regardless of accompanying with SG reduced food intake by about 60% during nighttime but not daytime, and did not affect energy expenditure. Conclusions: Weight loss after VTPP, SG or DS differed in terms of degree, duration and underlying mechanisms. DS without SG was most effective in long-term, at least partly due to the reduced food intake. In addition to food intake and eating behavior, possible involvements of absorption, gut hormones and the brain-gut axis need to be further studied.

973 Relationship of EMAST and Microsatellite Instability Among Patients With Rectal Cancer Bikash Devaraj, Sonia Ramamoorthy, Robert S. Sandler, Temitope O. Keku, Aaron Lee, Linda Luo, Kathie McGuire, Betty L. Cabrera, Katsumi Miyai, John M. Carethers Background. Elevated microsatellite instability at selected tetranucleotide repeats (EMAST) is a genetic signature identified in two-thirds of sporadic colon cancers (and other cancers) and is associated with heterogeneous expression of the DNA mismatch repair (MMR) protein hMSH3. Unlike microsatellite instability-high (MSI) in which hypermethlation of hMLH1 occurs followed by multiple susceptible gene mutations, EMAST may be associated with inflammation and relaxation of MMR function with the subsequent biological consequences not known. We evaluated EMAST and MSI in a population-based cohort of rectal cancers, as this has not been previously determined. Methods. We analyzed 147 sporadic cases of rectal cancer using 5 tetranucleotide microsatellite markers and NCI-recommended MSI (mono and dinucleotide) markers. EMAST and MSI determinations were made on analysis of DNA sequences of the PCR products, and determined positive if at least 2 loci were found to have frameshifted repeats upon comparison between normal and cancer samples from the same patient. We correlated EMAST data with race, gender, and tumor stage, and examined a subset of samples for lymphocyte infiltration. Results. Among this cohort of patients with rectal cancer (mean age 62.2 +/-10.3 years, 36% female, 24% African American), 3/147 (2%) showed MSI (3 males, 2 African American) and 49/147 (33%) demonstrated EMAST (frequency of markers positive are in Table 1). Rectal tumors from African Americans were more likely to show EMAST than Caucasians (17/36, 47% vs 30/105, 29%, P=0.04), and approached an association with advanced stage (18/29, 62% vs local disease 11/29, 38%, P=0.06). There was no association between EMAST and gender (female 19/53, 36% vs male 28/88, 32% P>0.05). In the subset of tumors analyzed for lymphocytes histologically, EMAST was more prevalent in rectal tumors that showed peri- or intra-tumoral infiltration compared to those without. Conclusions. The frequency of EMAST in rectal cancers (~33%) is less than reported for colon cancer (~66%), and MSI is rare. EMAST is associated with African American race and may be more commonly seen with metastatic disease. The etiology and consequences of EMAST is under investigation, but its association with immune cell infiltration suggests inflammation may play a role for its development. Frequency of EMAST Marker Mutations

971 Perioperative Anti-Tumor Necrosis Factor Alpha Agnents Do Not Increase the Rate of Early Postoperative Complications in Crohn's Disease Basil S. Nasir, Eric J. Dozois, Robert R. Cima, John H. Pemberton, Bruce G. Wolff, William J. Sandborn, Edward V. Loftus, David W. Larson BACKGROUND: There have been numerous studies with conflicting results regarding the use of anti-tumor necrosis factor (TNF) alpha and its relationship to postoperative outcome. The aim of our study was to examine the rate of postoperative morbidity in patients receiving anti TNF alpha in the perioperative period. METHODS: All patients undergoing surgery for Crohn's disease from 2005 till 2008 were abstracted from a prospective database. Patients who underwent surgery which included a suture or staple line at risk for leaking were selected for the study. A retrospective review of medical records was performed. The study group comprised patients treated with anti-TNF alpha within 8 weeks preoperatively or up to 30 days postoperatively. The remainder of the patients did not receive the drug in that time period. Patient characteristics, disease severity, medication use, operative intervention and 30-day complication were compared between the two groups. RESULTS: Three hundred and seventy patients were selected for analysis in this study, of which 119 received the drug within the allotted time period and 251 did not. The groups were similar in baseline characteristics, perioperative risk factors and procedures. The study group had more severe disease overall as measured by the American College of Gastroenterology (ACG) categories of disease (50% severe fulminant disease in the study group versus 18% in the unexposed group, p < 0.001). There was no significant association of anti-TNF alpha therapy and any postoperative complications (27.9% in study group versus 30.1% in unexposed group, p = 0.63) nor intra-abdominal infective complications (5.0% in study group versus 7.2% in unexposed group, p = 0.44). Univariate analysis showed that the only factors associated

SSAT Abstracts

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