P202

P202

ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS 313 P199. PANCREATIC REGENERATION PROTEIN (REG) MODULATES GLUCOSE TOLE...

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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS

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P199. PANCREATIC REGENERATION PROTEIN (REG) MODULATES GLUCOSE TOLERENCE TESTING. J. Pierre, C. M. Mueller, D. Viterbo, E. Bernstein, Y. Lin, M. H. Bluth, M. E. Zenilman; Suny Downstate Medical Center, Brooklyn, NY

Conclusion: These results clearly demonstrate that the renal dysfunction does not suppress the hepatic regeneration capacity following partial hepatectomy. The function of the liver on day 7 after PHx also was not different. These results provide a possibility that the hepatectomy can be aggressively indicated even for the patient with a chronic renal failure.

Background: Pancreatic Reg protein has been shown to play a role in rejuvenating damaged pancreas. We have shown that Reg protein decreases with age and that antibody neutralization of Reg in young rats worsens glucose tolerance. The ability of Reg protein to serve as a therapeutic intervention for diabetes has not been determined. We investigated the effect of Reg protein administration on glucose animal model of aging and diabetes. Methods: Wistar rats underwent intraperitoneal glucose tolerance tests (GTT) by injecting 1 gram glucose/kg body weight and measuring serum levels at 15 minutes pre-, immediately post- and at 15, 30, 45, 60, 90, and 120 minutes post-injection. Baseline controls consisted of 2 month old (Young) and 11 month old (Middle-aged) rats (10/group). Old rats (20 months, n⫽20) were randomly divided into two groups and injected IP with either recombinant rat Reg protein (1 mg/kg/day, n⫽10) or vehicle (n⫽10) for a period of 14 days at which time GTT curves were again determined. Pre- and Post-treatment GTT curves were compared at each timepoint and statistically analyzed using the Wilcoxin Signed Ranks test with significance set at P⬍0.05. Results: Worsening GTT was noted with aging. Old rats had worse GTT when compared with Young and Middle aged controls (p⬍0.05). Administration of Reg protein resulted in improved glucose tolerance in Old rats who had markedly elevated baseline GTT levels (p⬍0.05). In contrast, Reg treatment in Old rats with normal baseline GTTs showed no effect (p⫽ .078). Conclusions: Reg protein improved glucose tolerance in aged rats who exhibited abnormal GTT. As Reg levels decrease in aging and is associated with diabetes, replacement therapy can reverse the process.

P201. EVIDENCE FOR RETINOBLASTOMA PROTEIN INVOLVEMENT IN RESECTION-INDUCED ENTEROCYTE PROLIFERATION. J. A. Taylor, J. Guo, B. W. Warner; Division of Pediatric General and Thoracic Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

P200. IS THERE ANY EFFECT OF RENAL FAILURE ON THE HEPATIC REGENERATION CAPACITY FOLLOWING PARTIAL HEPATECTOMY IN RATS. T. Kawai, Y. Yokoyama, M. Nagino, Y. Nimura; Nagoya University Graduate School of Medicine, Nagoya, Japan Aims: Several factors are known to inhibit hepatic regeneration capacity following partial hepatectomy (PHx). The effects of renal dysfunction on the regeneration capacity have not been fully elucidated before, although many renal failure patients are subjected to hepatectomy due to hepatobiliary diseases. In this study, we sought to determine the effects of renal dysfunction on the hepatic regeneration capacity using rat chronic renal failure model. Materials and Methods: After establishing renal failure (CRF group) by semi-total renal resection, the rats were subjected to 70% partial hepatectomy (PHx). Rats without renal failure were used as control (Sham group). The hepatic regeneration rate was measured on day 1, 2, and 7 after PHx. The blood and liver samples were obtained for the further studies. Clearance of intravenously injected indocyanine green into the bile was measured by cannulating the bile duct and collecting the bile flow for 30 min. The expression of hepatic regenerationassociated genes in the liver were determined by real-time RT-PCR. Results: The hepatic regeneration rate was not significantly different between Sham and CRF group on day 1, 2, and 7 after PHx (Fig. 1). The change of plasma ALT, AST, and total bilirubin levels over the time course did not show any difference between Sham and CRF group. Mitotic index evaluated by histologic examination on day 2 after PHx also did not show any difference between these two groups. Indocyanine green clearance rate was almost identical between Sham and CRF group on day 7 following PHx (Fig. 2). Although the baseline expression of the hepatic regeneration associated genes, such as IL-6, TNF-␣, HGF, c-fos, c-jun, and c-myc, in the liver of CRF group were lower than that of Sham, the rate of upregulation of these genes were not significantly different between these two groups.

Introduction: Massive small bowel resection (SBR) results in an adaptive intestinal response manifested as taller villi, deeper crypts, and increased rates of enterocyte proliferation. Retinoblastoma (Rb) proteins are well-established to modulate cell cycle progression and recently have been found to be important in the regulation of normal enterocyte homeostasis. The present study was designed to test the hypothesis that Rb proteins are involved in resection-induced enterocyte proliferation. Methods: C57/Bl6 male mice were randomly subjected to 50% SBR or sham resection and harvested on post-operative day 1, 3, 7, and 28. Enterocytes were isolated and Western blot was performed for total Rb (active form) and site-specific phosphorylated Rb (inactivated form). Immunohistochemistry was then performed for site-specific phosphorylated Rb on the remnant murine small intestine during adaptation. Results: In unoperated mice, Rb phosphorylation at S807/811 and T826 was only present in crypts, while phosphorylation at S780 could be seen in both crypts and villi. Crypt-specific Rb phosphorylation at S807/811 and T826 was significantly increased in enterocytes of mice subjected to SBR compared to sham. Expression of cyclin D1 and Rb pathway-targeted gene cdc2 was also significantly increased after SBR. However, these expression patterns were not detected until after adaptation was wellestablished (post-operative day 28). Conclusions: These results show for the first time that Rb is phosphorylated at specific sites in different regions of the small intestine, and that Rb phosphorylation in the crypt proliferative zone is increased after SBR. While the functional significance of these Rb phosphorylation patterns is currently unknown, a significant role for Rb protein activity during the maintenance phase of intestinal adaptation is suggested. P202. LONG TERM OUTCOMES COLLIS GASTROPLASTY WITH FUNDOPLICATION FOR THE SHORT ESOPHAGUS. S. K. Mittal, A. M. Bachelani, L. Esberg, A. M. Lundeen, C. J. Filipi; Creighton University, Omaha, NE Background: Collis gastroplasty with fundoplication is an accepted treatment for the short esophagus. Efficacy and need for this procedure has been questioned. Few studies have reported long term follow-up for patients undergoing a Collis gastroplasty. Methods: Operative data for all patients undergoing anti-reflux surgery at Creighton University was prospectively entered into a data base. A retrospective review was completed to identify patients who underwent an esophageal lengthening procedure. Data regarding pre-operative risk factors and operative procedures was

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ASSOCIATION FOR ACADEMIC SURGERY AND SOCIETY OF UNIVERSITY SURGEONS—ABSTRACTS

collected. Patients were contacted by phone and administered a questionnaire regarding their symptom control, medication usage and satisfaction after surgery. Symptoms were scored on a scale of 0-3. and satisfaction on a scale of 1-10. Patients were also asked if they would recommend the procedure to a friend. Results: Seventy patients (F⫽ 41) aged 33-81 years underwent laparoscopic (n ⫽33) or transthoracic (n⫽37) Collis gastroplasty with fundoplication between Jan’96 to May’2005. Fifty three were primary and 17 re-operative procedures. There was one in-hospital death due to a pulmonary embolism and sepsis 42 days after a trans-thoracic procedure. Three patients have died during follow-up from unrelated causes while 8 patients could not be contacted. For the remaining 58 patients mean follow-up was 42.8 months (range 3-111). Fifty patients were more than 1 year postoperative, 33 more than 3 years and 14 more than 5 years. Mean dysphagia, heartburn and chest pain scores are 0.46, 0.41 and 0.17 respectively with the majority of patients (71%, 78% and 83% respectively) reporting no symptoms in these categories. Seven (12%) report significant gas-bloat. Overall, 81% (47 out of 58) patients were satisfied with their outcome (satisfaction grade 8 or higher). Only 8 patients (13.7%) were dissatisfied with the results (grade ⬍⫽ 5), and the remaining patients experienced no significant improvement. Eighty-five percent (49/58) said they would recommend the procedure to a friend. There was no statistically significant difference between sub-groups trans-thoracic vs. laparoscopic or primary vs. re-do procedure as related to symptom outcome. Conclusions: Collis gastroplasty with fundoplication results in excellent long-term patient satisfaction and symptom control. P203. DETERMINATION OF A NON-INVASIVE MODEL FOR PREDICTING OBESITY IN RATS BY DISCRIMINANT FUNCTION ANALYSIS. B. M. Smith, J. A. Ways, S. J. Deraedt, K. M. Langenderfer, A. L. Nestor, S. J. Lee, M. Welch, S. A. Khuder, G. T. Cicila, D. C. Allison; University of Toledo College of Medicine, Toledo, OH The rat is an important model for the study of complex genetic traits such as obesity. Such studies are dependent on accurately measuring the phenotype for breeding populations. Previously, both the Lee Index (body weight 1/3 / naso-anal length) and the Body Mass Index (body weight / naso-anal length 2 ) have been utilized in studies to identify obese rats. The present study examined the accuracy of these indices by testing a heterogeneous population of rats. Further, using discriminant function analysis, we formulated a new, more accurate model for identifying obesity in the rat. Methods: Rats of various strains [DA, Copenhagen (COP), Buffalo (BUF), DA.COP(chr 16), COP.DA(chr 3), F 1 (DAxBUF), and F 2 (DA x BUF)] were measured for body weight, naso-anal length, sternum-to-pubic symphysis length, greatest circumference, and skin fold thickness at the biceps brachii, triceps brachii, and the abdomen. Rats were dissected at 15 weeks of age, and the weights of the subcutaneous, visceral, and retroperitoneal fat pads were measured. A stepwise discriminant analysis of these variables was performed on a training set (n⫽144) to identify significant predictors of obesity. The validity of the discriminant function in predicting obesity was then tested on a second group of rats (n⫽105) from the various strains. Results: Stepwise discriminant function analysis identified four significant variables: body weight (BW), naso-anal length (NA), skin fold thickness at the triceps (SFT), and sternum-to-pubic symphysis length (SP) (p⬍ 0.0001 for each variable). The discriminant function, BW / (NA⫹SP⫹SFT) 5 , correctly categorized 92 of 105 rats (88%) in the second group. In contrast, the Lee Index and the Body Mass Index each categorized only 40 of 144 rats (28%) correctly. Conclusions: The rat is an important model organism for studying phenotypes with complex inheritance, such as obesity. Although the Lee and Body Mass Indices are used in many genetic

and observational studies, we did not find these indices to accurately predict obesity in our rat strains. We developed a new non-invasive index by discriminant function analysis that is significantly more accurate in identifying obese rats. This index will be useful for selective breeding and genome scans to identify the genes controlling obesity.

GASTROINTESTINAL VI: CLINICAL P204. FACTORS AFFECTING LENGTH OF STAY FOLLOWING COLONIC RESECTIONS. T. M. Schmelzer, G. Mostafa, S. Camp, A. E. Lincourt, W. W. Hope, W. L. Newcomb, K. W. Kercher, T. S. Kuwada, B. Heniford; Carolinas Medical Center, Charlotte, NC Introduction: Length of stay (LOS) is an important measure of outcome after major surgery. The goal of this study was to identify the factors that affect LOS after colonic resection. Successful identification of these factors can influence patient expectations and the cost effective management of post-operative surgical patients. Methods: A retrospective analysis was performed of adult patients who underwent colonic resection over an 8 year period at a tertiary institution. Data collected included demographics, preoperative comorbidities and medications, operative findings, and post-operative morbidity and mortality. The overall outcome for this study was the postoperative hospital LOS. Statistical analysis involved descriptive statistics as well as both simple and multiple linear regression to identify variables associated with the overall LOS. A p-value of ⬍0.05 was used for all significance determinations. Results: A total of 899 patients were identified and included in the study. 187 resections were done as urgent operations and 712 were elective. Two hundred and forty five cases were performed laparoscopically. Complications were reported in 205 cases (22.8%) and there were 32 deaths (3.6%). The mean LOS was 10.6 days. Simple linear regression demonstrated 38 variables that were significantly associated with prolonged LOS. After multiple regression analysis this was reduced to nineteen. There were no demographic criteria that were predictive. Coumadin was the only preoperative medication associated with a prolonged LOS. The comorbidities that were significant predictors of prolonged LOS were alcoholism, end-stage renal disease, and illicit drug abuse. Analgesia used, ASA score, total colectomy, and open resections were the operative variables that adversely affected LOS. Post-operative complications accounted for the majority of the significant predictors of prolonged LOS and included CVA, cardiac failure, DVT, hypoxia, intra-abdominal abscess, renal failure, respiratory failure, urinary tract infection, wound dehiscence, and death. The only category of variables that affected LOS after colon surgery was post-operative complications (p⫽ 0.0180). Conclusions: Length of stay after colonic resection can be predicted with definable variables. No specific diagnosis is predictive for increased LOS. The incidence of post-operative medical complications is the most significant marker of a prolonged LOS. The only comorbidities that are predictive of prolonged LOS are alcoholism, illicit drug use,and end-stage renal disease. A laparoscopic approach in colonic resections reduces the post operative LOS. P205. WITHDRAWN P206. A REVIEW OF 3237 CONSECUTIVE CASES OF CLOSTRIDIUM DIFFICILE COLITIS: RISK FACTORS FOR SURGICAL MORTALITY. J. F. Hall, D. Berger; Massachusetts General Hospital, Boston, MA Introduction: C. difficile is a spore forming gram-positive bacteria that produces a broad spectrum of clinical presentations