M2057

Inflammatory-Related Gene Variants as Risk Factors for Pancreatic Cancer:Does NOS Play a Role?Kaye Reid Lombardo, Brooke L. Fridley, Julie M. Cunningham, Michael G. Sarr, GloriaM. Petersen

BACKGROUND: Recent reports continue to support a link between chronic inflammation andprogression to pancreatic cancer (PC). These cite an increased expression of proinflammatorymediators in PC but not in normal adjacent tissue, suggesting a possible mechanism ofcarcinogenesis. HYPOTHESIS: The association between inflammation and PC is facilitatedby host susceptibility, specifically by genetic polymorphisms in inflammation-related genes.METHODS: We conducted a case-control, candidate gene association study of 1,398 (1,354Caucasian) eligible patients with histologically proven primary pancreatic ductal adenocarcin-oma and 1,196 (1,189 Caucasian) healthy controls evaluated at a single institution fromOctober 1, 2000 to the present. Inflammation-related candidate genes were selected usingboth literature review and bioinformatic analysis, followed by selection of tagged singlenucleotide polymorphisms (tag SNPs). We used Illumina GoldenGate technology to genotype768 tag SNPs of 61 candidate genes. The association of each SNP, under a log-additivegenetic model, with risk for PC was evaluated using logistic regression, adjusting for knownrisk factors for PC. Statistical significance was set at <0.0001. RESULTS: Our sample wasmostly Caucasians (96.8%) and 51.3% of cases and 57.3% of controls were male. Whencomparing cases and controls, there were statistically significant differences in sex (p=0.002),race (p=0.0002), smoking status (p<0.0001), BMI (p<0.0001), and personal history of first-degree relative with PC (p =0.0053). Restricting genetic analysis to Caucasians and adjustingfor age, sex, smoking status, BMI, familial pancreatic cancer status, and diabetes diagnosedgreater than two years prior to diagnosis of PC, single SNP analysis revealed an associationbetween four SNPs in the neuronal nitric oxide synthase one gene (NOS1) and pancreaticcancer: rs547954 (p =0.00025 , OR = 1.31, (95% CI 1.13, 1.52), rs532967 (p=0.00049,OR = 1.29, (95% CI 1.12, 1.49)), rs3782203 (p=0.00055, OR = 1.27, (95% CI 1.11, 1.46)),and rs9658350(p = 0.00072, OR = 1.27, (95% CI 1.11, 1.45). In our genotyped data, thelinkage disequilibrium (LD) between these SNPs ranged from 0.72 to 0.98. These SNPshave a close physical relationship on the NOS1 gene, within 2 LD blocks (8 kb and theother 28.7 kb) in a 38 kb region of chromosome 12. CONCLUSION: Of the 61 genesevaluated, only NOS1 had a significant association with PC and may be associated with riskof PC. NOS1 is not a well studied gene in PC. These preliminary findings warrant furtherstudies to assess the impact of NOS1 on PC risk.

M2058

Prognostic Value of the Heme Oxygenase-1 Transcription Controlling GTnRepeat Promoter Polymorphism in Complete Resected Only Surgically TreatedEsophageal CancerYogesh K. Vashist, Katharina E. Effenberger, Florian Trump, Viacheslav Kalinin, BurkhardH. Brandt, Klaus Pantel, Emre F. Yekebas, Jakob R. Izbicki

Purpose: The basal transcription of heme oxygenase-1 (HO-1) regulation is dependent upona GTn repeat polymorphism (GTn) in the promoter of the heme oxygenase-1 gene (HMOX-1). Here, we evaluate the role of GTn in only surgically resected esophageal cancer (EC)patients without neoadjuvant or adjuvant treatment. Patients and Methods: Genomic DNAwas extracted from peripheral blood of 297 patients. To determine the number of theGTn repeats DNA was amplified by PCR and sequenced. The results were correlated withclinicopathological parameters, disseminated tumor cells (DTC) and clinical outcome.Results: Three genotypes (SS, SL and LL) were defined based on cut-off points for shortallele (SGTn) with GTn repeats <25 and ≥25 as long allele (LGTn). Throughout all analysesa contrary role of GTn was evident in squamous cell carcinoma (SCC) and adenocarcinoma(AC) patients. In SCC patients the SS genotype patients presented with less aggressive tumorsin terms of tumor size, presence of regional and non-regional lymph-node metastases, DTCand lower relapse rate compared to SL and LL genotype patients. In contrast, in AC patientsthe SS genotype patients displayed more aggressive tumor biology with bigger tumors, higherrate of lymph-node metastasis and DTC and tumor recurrence rate compared to LL and SLgenotype patients. The disease-free (DFS) and overall survival (OS) in SCC patients wasmarkedly reduced in LL genotypes compared to SL and SS genotypes. In parallel, in ACthe SS genotype patients displayed the worst DFS and OS. GTn was identified as anindependent prognostic factor with contrary prognostic value for tumor recurrence anddeath in SCC and AC. Conclusion: GTn is a strong prognostic marker in EC that allows tostratify patients with different histology to different risk profiles.

T1622

Early Phase Systemic Cytokine Profile of Natural Orifice TranslumenalEndoscopic Surgery (NOTES™) Cholecystectomy: Comparison WithLaparoscopic Cholecystectomy and Roux-en-Y Gastric BypassByron F. Santos, Eric S. Hungness, Edward Auyang, Daniel Enter, Edward C. Wang,Nathaniel J. Soper

Introduction: Although NOTES may offer decreased postoperative pain, wound complica-tions, and improved cosmesis compared to standard laparoscopic surgery, its immunologicimpact is unknown. NOTES requires the creation and closure of a viscotomy, potentiallycontaminating the normally sterile peritoneal cavity. We hypothesize that NOTES cholecys-tectomy is associated with increased systemic cytokine activation compared to laparoscopiccholecystectomy (LAP). Methods: Patients requiring cholecystectomy were recruited. Exclu-sion criteria were age > 65 yrs, body mass index (BMI) >40 kg/m2, choledocholithiasis,acute cholecystitis, prior pelvic or gastric surgery, endometriosis, steroid use, and immunos-uppression. NOTES patients underwent hybrid transvaginal or transgastric cholecystectomy.LAP patients underwent standard laparoscopic cholecystectomy. Laparoscopic roux-en-ygastric bypass (RYGB) patients were enrolled as a positive control group. Peripheral venousblood was collected preoperatively (Baseline) and 30 minutes postoperatively (Postop).

S-881 SSAT Abstracts

Plasma cytokine analysis was done using multiplex ELISA arrays for IL-1a, IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, IL-15, IL-17, IL-23, IFN-gamma, TNF-alpha,and TNF-beta. IL-6 and IL-10 were chosen as primary end-points based on a priori poweranalysis using preliminary data, with additional cytokines treated as secondary end-points.Cytokine levels were analyzed using a mixed-effects model. Results: 21 subjects underwentLAP (n=8), NOTES (n=5), or RYGB (n=8). Mean age ± SD (37 ± 12 v. 42 ± 11 yrs), BMI(29 ± 5 v. 30 ± 4 kg/m2), and male sex (n=2 v. n=2) were similar between LAP and NOTESgroups, respectively. Postop IL-6 was higher for NOTES versus LAP (69 ± 35 v. 22 ± 24pg/ml, p < 0.05). IL-10 was higher for RYGB versus LAP (56 ± 36 v. 14 ± 14 pg/ml, p <0.05). No significant differences were seen in levels of the secondary end-points. Conclusion:NOTES cholecystectomy is associated with increased early postoperative activation of IL-6,and possibly IL-10 compared to LAP. NOTESmay cause a greater physiologic insult comparedto laparoscopic surgery.

T1623

Microlaparoscopic Cholecystectomy: An Alternative to Single Port SurgeryKeith A. Zuccala, Denise McCormack, Pierre F. Saldinger

Introduction Recent advances in minimally invasive surgery aiming at diminishing incisionhave led to the development of single port surgery (SPS). SPS has an increased level ofcomplexity and require a higher level of surgical skills as compared to traditional laparoscopy.We have explored microlaparoscopy as a simpler alternative for routine laparoscopic cholecy-stectomy. Methods Retrospective review of consecutive elective laparoscopic cholecystectom-ies performed by a single surgeon at a teaching university hospital over a 24 months period.All surgeries were performed using a 5mm trocar for the umbilical port and 3mm trocarsfor the other ports in standard configuration. Intraoperative cholangiography was performedroutinely if technically feasible. Results 79 elective cholecystectomies were performed bymicrolaparoscopy during the 24 months period. Indications for surgery are listed in table1. 3 cases required an upgrade in trocars size for technical reasons resulting in a microlaparos-copic completion rate of 96%. Intraoperative cholangiography was completed in 70 cases(89%). There were no conversions to open surgery. There were no intra- or postoperativecomplication and all patients were discharged on the day of surgery. Conclusion Microlaparo-scopic cholecystectomy is safe and feasible. It represents a simple alternative to othertechniques that aim at minimizing incisions. Future development in visualization and instru-mentation will allow using even smaller instruments and diminishing the surgical “footprint”even further.Indication for cholecystectomy

T1624

Laparoscopic Cholecystectomy is the Preferred Approach in Cirrhosis : ANationwide, Population-Based StudyEllen J. Hagopian, Yen-Hong Kuo, Yen-Liang Kuo, John M. Davis

Background/Aim: Recent reports suggest that laparoscopic as opposed to open cholecystec-tomy may be better tolerated in cirrhotic patients. We sought to assess the impact of theselection of the surgical approach in cirrhotic patients undergoing cholecystectomy by the useof the Nationwide Inpatient Sample (NIS), the largest population-based and geographicallyrepresentative all-payer database of hospital discharges in the United States. Methods: Allpatients with cirrhosis who underwent cholecystectomy (open or laparoscopic) between2003 and 2006 were queried from the NIS. Associated complications including infection,ascites, transfusion, reoperation, and liver failure were compared amongst the groups. In-hospital mortality was determined. Results: A total of 3242 patients with liver cirrhosisunderwent cholecystectomy : 384 patients underwent open cholecystectomy (OC) whereas2858 patients underwent laparoscopic cholecystectomy (LC), which included 412 patientsconverted (LCC) from laparoscopic to open cholecystectomy. There was no difference inregard to age, sex, or race. Postoperative infection was higher in those undergoing open(OC) as opposed to those undergoing laparoscopic (LC) or laparoscopic converted to open(LCC) cholecystectomy (3.7% vs 0.7% vs 0.2%, p<0.0001). Ascites was significantly morecommon in OC as opposed to LC or LCC (18.0% vs 9.4% vs 11.4%, p<0.0001). The needfor blood transfusion was significantly higher in the OC and LCC groups as compared tothe LC group (19% vs 14% vs 6%, p<0.0001). Furthermore, reoperation occurred morefrequently following OC or LCC as opposed to LC (1.6% vs 2.4% vs 0.8%, p<0.008). Liverfailure was significantly higher after OC as compared to LC or LCC (7.0% vs 1.4% vs 1.5%,p<0.0001). In-hospital mortality was significantly higher after OC as compared to either LCor LCC (8.4% vs 1.4% vs 1.2%, p<0.0001). Conclusion: Patients with liver cirrhosis have

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