T2095 Assessment of “Gene-Environment” Interaction in Cases of Familial and Sporadic Pancreatic Cancer

T2095 Assessment of “Gene-Environment” Interaction in Cases of Familial and Sporadic Pancreatic Cancer

or antibiotic treated groups. Conclusions: In a pilot study of a murine model designed to simulate NOTES gastric spillage, pre-op gastric antibiotic l...

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or antibiotic treated groups. Conclusions: In a pilot study of a murine model designed to simulate NOTES gastric spillage, pre-op gastric antibiotic lavage decreased the adhesion and infection rate when compared to saline only lavage.

(frozen or preserved) using a combination of flexible and rigid instruments. Pouch creation was achieved by needle knife dissection of a retrogastric window using a flexible gastroscope introduced transvaginally. Articulated linear staplers were placed through a transumbilical port to transect the stomach. Measurements of the bilary and alimenary limbs were accomplished with flexible and rigid graspers. A 21 mm anvil was introduced through a needleknife incision into the small intestine and connected to the flexible shaft of a flexible transesophageal stapler to form a gastrojejunostomy. A linear stapler was used for the jejunojejunal anastomosis. Results: It was feasible to perform bypass surgery in all cadavers. Dissection and pouch creation was easier than expected using flexible instruments to form the pouch. Ordinary rigid instruments (graspers and staplers) were too short for some transvaginal or transrectal manipulations. Anvil manipulation and docking was difficult using flexible instruments. Combinations of flexible and rigid visualization and manipulation were especially helpful for pouch creation and stapler manipulation. Transabdominal port access number was reduced from 5-7 to 1-3 with 1-2 translumenal access ports. Conclusions: Roux-enY bypass surgery ís technically feasible in human cadavers using a NOTES hybrid approach. Port numbers can be reduced. A combination of flexible with rigid endoscopic techniques devices offers specific advantages for components of this type of surgery. Changes in instrument design are required to improve complex hybrid endosurgical procedures.

T1921 Roux-en-Y Gastric Bypass Improves Obesity-Related Steatosis and Is Associated with Reduction in Serum Adiponectin Drew A. Rideout, Yanhua Peng, Steven S. Rakita, William R. Gower, Min You, Michel M. Murr Background: Non-Alcoholic Fatty Liver Disease (NAFLD) is a manifestation of obesity and leads to cirrhosis. Adiponectin, an adipocyte hormone, has direct effects on inflammation and lipid metabolism. We tested the hypothesis that Roux-en-Y gastric bypass (RYGB) improves liver steatosis in a rat model of obesity and induces changes in serum adiponectin. Methods: Five-week-old Sprague-Dawley male rats were randomized to regular chow or high fat diet (HFD) for 14 weeks to induce obesity prior to undergoing RYGB (n=4) or sham (n=3). Subsequently, rats were sacrificed at 9 weeks post-operatively. Body weight (weekly) and serum adiponectin were measured. Liver sections were stained with H&E and Oil Red. All tests were repeated in triplicate; gels were quantified using densitometry; data are mean±SD; t-test, p<0.05 was significant. Results: HFD induces obesity and increases body weight in rats (452±24gm vs. 406±22gm; p<0.01 vs. regular chow). RYGB induces progressive and significant weight loss in obese rats (364±45gm vs. 496±32gm; p<0.01 vs. sham). Prior to RYGB, rats fed HFD had an increased serum adiponectin compared to regular chow (16,185±2,459 vs. 7,309±434; p<0.01 vs. regular chow); RYGB reduced serum adiponectin in obese rats compared to obese sham controls (914±564 vs. 3,441±933; p<0.05 vs. sham); similarly; serum adiponectin was reduced after RYGB as compared to levels from the same obese rats pre-operatively (5,099±878 vs. 6,916±415; p<0.01). HFD increased the number and size of fat droplets in the liver compared to regular chow. RYGB decreased liver weight by 30% and significantly reduced the number and size of fat droplets in the liver compared to obese sham rats. More importantly, the degree of steatosis improved in rats after RYGB as compared to the same rats pre-operatively. Conclusion: HFD induces obesity and steatosis in obese rats. Surgically-induced weight loss in a rat model of RYGB exhibits an anti-lipogenic profile by improving liver steatosis. The novel observation that RYGB reduces serum adiponectin warrants further investigation into the complex signaling between peripheral adipose tissue and the liver in obese rats with NAFLD.

T2097 A Novel System for Classifying Paraesophageal Hernias Tommy H. Lee, Carlos Godinez, Stephen M. Kavic, Ivan M. George, George T. Fantry, Adrian E. Park Introduction: The current system for classifying paraesophageal hernias is based on the herniated contents and the location of the gastroesophageal (GE) junction in relation to the diaphragmatic hiatus. While this system represents a basic anatomic description of the hernia, there is little clinical relevance to aid in pre-operative or intra-operative management. New imaging technology permits the study of these hernias in 3-dimensions, providing an understanding of their anatomy at a greater level of detail and relevance to the clinician. Methods: 24 patients who underwent laparoscopic paraesophageal hernia repair were reviewed. Pre-operative CT scans were reconstructed using a unique protocol with semiautomatic segmentation. Reconstructions permitted analysis of the geometry of hiatal defects and herniated contents. Patients were categorized by hiatal shape, angulation of herniated contents, and the location of the herniated stomach. These groupings were then compared to patient outcomes, specifically, need for Collis gastroplasty, need for buttress of hiatus repair, gastrostomy, and intra-operative complications. Results: Analysis revealed four distinct defect morphologies. The geometry of the herniated contents was described according to the amount of stomach situated in the chest, and by the angle formed by three anatomic structures: the GE junction, the base of the diaphragmatic crura, and the antrum (the “PEH angle”). Symmetric defects less often required gastric fixation, but were more likely to need a Collis gastroplasty. The mean PEH angle was 87°. Patients requiring an esophageal lengthening had a mean angle of 82°, compared to 100° in those who did not. Stomach location also influenced operative events, as evidenced by a 57% incidence of intra-operative complications such as enterotomies and liver injuries in patients with a stomach equally above and below the diaphragm, compared to 15% in those with the stomach mostly above, and 0% in those with the stomach mostly below (p = .106, Fisher Exact Test). Conclusion: Paraesophageal hernias remain a significant management challenge. Patients and surgeons alike stand to benefit from highly detailed pre-operative information on hernia anatomy and visceral relationships. Combining advances in imaging and computing power, we propose a novel classification system based on advanced reconstruction techniques, which allows us to view these challenging surgical problems in ways not previously possible with fluoroscopy or even CT alone. Key anatomic features and relationships identified by these means can aid in pre-operative decision making and patient counseling, and predict operative difficulty.

T2095

SSAT Abstracts

Assessment of “Gene-Environment” Interaction in Cases of Familial and Sporadic Pancreatic Cancer Theresa P. Yeo, Ralph H. Hruban, Alison P. Klein, Kieran Brune, Charles J. Yeo Introduction: Pancreatic cancer (PC) is the fourth leading cause of cancer death in the United States. This study characterizes one of the largest national registries of familial PC (FPC) and sporadic PC (SPC), focusing on demographics, clinical factors, self-reported environmental and occupational lifetime exposures and survival status. Background: Reported risk factors for PC include: advancing age, a family history of PC, high-risk inherited syndromes, cigarette smoking, exposure to occupational and environmental carcinogens, African-American race, high fat/high cholesterol diet, obesity, chronic pancreatitis, and diabetes mellitus. Methods: This retrospective cross-sectional, case-only analysis includes cases of FPC (n = 569) and SPC (n = 689) from the Johns Hopkins National Familial Pancreas Tumor Registry (NFPTR) enrolled between 1994 and 2005. Results: Significant findings include: 1) Mild, multiplicative interaction between family history of PC and exposure to asbestos, environmental radon, and environmental tobacco smoke (ETS) (Odds Ratios > 1.0). 2) Non-smoker ETS exposed cases were diagnosed at a significantly younger mean age (64.0 years) than non-smoker non-ETS exposed cases (66.5 years) (p < 0.0004). 3) FPC smokers with ETS exposure were diagnosed at a significantly (p = 0.05) younger mean age (63.7 years) compared to FPC non-smokers without ETS exposure (66.6.years). 4) Mean age at diagnosis for Ashkenazi Jewish SPC subjects was significantly younger (by 2.1 years) than Ashkenazi Jewish FPC cases (p = 0.05). 5) Ashkenazi Jewish FPC subjects who smoked were diagnosed 5.9 years earlier than Ashkenazi Jewish FPC non-smokers (p = 0.05). 6) Median survival for unresected FPC cases was significantly shorter (168 days) compared to unresected SPC cases (200 days) (p = 0.04),survival significantly improved to 713 days for FPC cases and 727 days for SPC cases after surgical resection. Conclusions: These are the first data to show that occupational and environmental exposures may act synergistically with inherited or acquired genetic polymorphisms, resulting in earlier occurrence of PC. Exposure to cigarette smoking and ETS is associated with a younger mean age of diagnosis in FPC and SPC cases and those with an Ashkenazi Jewish heritage, compared to non-exposed cases. These results imply that unaffected individuals from families with a history of PC who smoke, have had early life ETS exposure, or have certain occupational and environmental exposures may benefit from screening and early identification of pre-malignant lesions.

W1635 Management of Preoperatively Suspected Choledocholithiasis: A Decision Analysis Bilal Kharbutli, Vic Velanovich BACKGROUND: The management of symptomatic or incidentally-discovered common bile duct (CBD) stones is still controversial. Of patients undergoing elective cholecystectomy for symptomatic cholelithiasis, 5-15% will also harbor CBD stones, and those with symptoms suggestive of choledocholithiasis will have an even with higher incidence. Options for treatment include preoperative ERCP with sphincterotomy (ERCP/ES) followed by laparoscopic cholecystectomy, laparoscopic cholecystectomy with intraoperative cholangiogram (LC/IOC), followed by either laparoscopic common bile duct exploration (LCBDE) or placement of a common bile duct double lumen catheter with postoperative management. The purpose of this analysis was to determine the optimal management of such patients. METHODS: A Decision Analysis was performed to analyze the management of patients with suspected common bile duct stones. The basic choice was between preoperative ERCP/ES followed by LC, LC/IOC followed by LCBDE or Common Duct Double Lumen Catheter (Fitzgibbons tube) placement with either expectant management or postoperative ERCP/LS. Data on morbidity and mortality was obtained from the literature. Sensitivity analysis was done varying the incidence of positive CBD stones on IOC with associated morbidity and mortality. RESULTS: One stage management of symptomatic CBD stones with LC/LCBDE is associated with less morbidity and mortality (7% and 0.19%) than two stage management utilizing preoperative ERCP/ES (13.5% and 0.5%). Sensitivity analysis shows that there is an increase in morbidity and mortality for LC/LCBDE as the incidence of positive IOC increases but are still less than two stage management even with a 100% positive IOC (9.4%, 0.5%). If a double lumen catheter is to be used for positive IOC, the morbidity would be higher than the two stage management only if the positive IOC incidence is more than 65% but still with no mortality. CONCLUSION: LCBDE has a lower morbidity and mortality rates compared to preoperative ERCP/ES in the management of patients with suspected CBD stones even if the chance of CBD stones reaches 100%. Using a Common Duct Double Lumen catheter may be considered if LCBDE is not feasible and the chance of CBD stone is less than 65%.

T2096 Natural Orifice Translumenal Endoscopic Surgery for Roux-en-Y Gastric Bypass: An Experimental Surgical Study in a Human Cadaver Model Monika E. Hagen, Francois Pugin, Oliver J. Wagner, Paul Swain, Nicolas C. Buchs, Margherita Cadeddu, Priya A. Jamidar, Jean Fasel, Philippe Morel Background: Advantages of a NOTES or NOTES hybrid approach to Roux-en-Y gastric bypass (RYGB) might include: easier access to the peritoneal cavity, subtantial reduction in number of ports and port related complications, improved cosmesis and others. NOTES was initially concieved as a procedure for relatively minor intraperitoneal operations. The most common NOTES procedure currently is cholecystectomy which is of moderate complexity. RYGB is a complex surgical procedure of advanced level. The technical feasibility of a NOTES-RYGB and limitations of available flexible and rigid instrumentation for such a procedure is unknown. Methods: NOTES hybrid RYGB was performed in 4 human cadavers

SSAT Abstracts

A-896