1
management of these patients. Method: Subjects were asked to endoscopically measure a ring of known diameter in a standardized plastic model of the esophagus and gastric pouch using 4 commonly used endoscopic measuring techniques and a double channel endoscope. Subjects used visual estimation (VE), instrument reference (IR) to a biopsy forceps, an 18 mm esophageal dilating balloon (DB) as reference, and a 30 mm endoscopic ruler (ER) made from an ERCP guide wire tip. The 5 models (33, 27, 24, 18 and 13 mm) were presented in random order. Data was collected and maintained in a database. Results: Ten(9 surgeons, 1 gastroentrologist) subjects participated. Endoscopic experience was >1000 scopes for 4 subjects; 250-500 for 3; <100 for 3. The VE was the least accurate with an average diversion (AD) from the actual diameter of 6.25 ± 4.95 mm (24.20 %); followed by IR, 3.89 ± 3.05 mm (14.80 %); then the ER, 2.4 ± 1.9 mm (9.20 %).The DB was the most accurate with AD of 1.46 ± 0.9 mm (7.20 %). Of the 200 total measurements, only 8 (4%) were accurate, 142 (71%) underestimated the size, and 50 (25%) overestimated. Underestimation was noted in 82.5% (33/40) of VE and IR measurents; ER had only 60% (24/40) underestimation; DB underestimated only 40% (16/40) of the time .Overestimation was highest using DB 55% (22/40), followed by ER method 45% (14/40), then IR 15% (6/ 40); and lowest in VE 12.5% (5/40). Measurements of the largest model diameter (33 mm) were underestimated 98% of the time. In the smallest diameter model (13 mm), 16% of the measurements were underestimated; 2% were accurate; and 82% were overestimated. Conclusion: Endoscopic measurement of lumen diameter is very inaccurate. Underestimation is the most likely error in measurement. The larger the diameter the more likely it will be underestimated; and the smaller the diameter the more likely it will be overestimated. Endoscopists should avoid visual estimation and use a standard reference tool (dilating balloon) to measure anastomotic diameter. This will allow more effective intervention for clinical problems related to anastomotic size. T1606 Trends and Outcomes of Hospitalizations for Peptic Ulcer Disease in the United States, 1993-2006 Y. Richard Wang, Joel Richter, Daniel T. Dempsey Objectives Despite progress in diagnosis and treatment, peptic ulcer disease (PUD) remains a common reason for hospitalization. The purpose of this study was to quantify the time trends of hospitalizations for PUD in the United States (U.S.) since 1993. Data and Methods The Healthcare Cost and Utilization Project Nationwide Inpatient Sample is a 20% stratified sample of all hospitalizations in the U.S. It was used to study hospitalizations with PUD as the principal diagnosis during 1993-2006, including details on ulcer site, complications, procedures, and mortality. Statistical methods included the chi-square test and multivariate logistic regression. Results The national estimate of hospitalizations for PUD decreased significantly from 222,601 in 1993 to 156,108 in 2006 (-29.9%), with a larger reduction in duodenal ulcers (95,552 in 1993 vs. 60,029 in 2006, -37.2%) than gastric ulcers (106,987 in 1993 vs. 86,064 in 2006, -19.6%). The inpatient mortality rate of PUD decreased from 3.8% to 2.7% during 1993-2006 (p<0.001). Hemorrhage remained the most common complication (71.6% in 1993; 73.3% in 2006) but perforation had the highest mortality (15.1% in 1993; 10.6% in 2006). In comparison to 1993, patients hospitalized for PUD in 2006 had more use of endoscopy to control bleeding (22.2% vs. 12.9%, p<0.001), similar use of oversewing of ulcer (7.4% vs. 7.6%), less use of gastrectomy (2.1% vs. 4.4%, p<0.001), and less use of vagotomy (1.7% vs. 5.7%, p<0.001). In multivariate logistic regressions, the determinants of mortality were similar in 1993 and 2006. Neither weekend admission nor low hospital PUD volume was associated with a higher mortality rate. Conclusions Hospitalizations for PUD have decreased in the U.S. from 1993 to 2006, suggesting a decrease in the prevalence and/or severity of ulcer complications over this recent time period. Over this time span, there has been a significant decrease in PUD mortality, a significant increase in the use of therapeutic endoscopy for bleeding ulcer, and a significant decrease in the use of definitive surgery (vagotomy and/or resection) for ulcer complications. Further research is necessary to determine if these trends are causally related. T1607 Reduced Surgical Revisions Associated with Placement of Subpectoral Gastric Electrical Stimulator: Six Year Experience At a Single Institution Jessica M. Gutierrez, Kiley Black, John I. Allen, Eric M. Johnson Background: Gastric electrical stimulation (GES) has become an alternative for patients with gastroparesis that do not respond to medical treatment. Traditionally the GES leads have been placed in the stomach and the neurostimulator placed in a subcutaneous pocket in the abdominal wall. Our experience shows reduced incidence of surgical revision if the neurostimulator is placed in a subpectoral pocket. Methods: Retrospective chart review from 2001-2007 of 64 patients that had GES placement, 25 patients in the abdominal wall, 38 subpectoral and one infraclavicular. Data collected included need for surgical revision. The implantation procedure was done by open and laparoscopic technique depending on patient and surgeon preference. In both cases the pylorus was identified and the leads were placed into the muscularis of the stomach at 9.5 and 10.5cm from the pylorus. An upper endoscopy was preformed to ensure that the leads did not transgress the mucosa. The leads were anchored into the stomach, then tunneled either to a pocket in the abdominal wall or subpectoral pocket previously created. Results: Fourteen surgical revisions of the gastric stimulator were performed in 11 patients ( eight abdominal and one infraclavicular): two due to lead fracture, eight due to abdominal pain, one due to migration of a lead into the stomach, one due to migration of the stimulator toward the J-tube, one patient that the GES pushed up against the rib cage causing pain and one placed subclavicular with pain at the site. No revisions were performed in the subpectoral group. The estimation of risk adjusted by sex, age and diabetes showed that abdominal pacer had a greater risk of revisions compared to subpectoral placement with hazard ratio of 7.1 CI 95%:0.86-59.5, p=0.06. Conclusions: This is the first report of placing the GES in the subpectoral position. We believe that 80% (12/14) of our revisions could likely have been prevented with subpectoral placement. Patients with abdominal placement of the device were more likely to have discomfort leading them to manipulate or attempt to shift the device resulting in lead failure and connection break. Abdominal placement was also found to have more pain at the site A-921 SSAT Abstracts requiring device revision. Subpectoral placement in our experience may limit the amount of revisions and pain associated with the device. Longer term follow up is needed in this group of patients. T1608 Incidence and Risk Factors for the Development of Anemia Following Roux- en-Y Gastric Bypass Surgery for Morbid Obesity I. Michael Leitman, Matthew Seigerman, Amanda J. Lefkowitz, Omar H. Llaguna, Dimitrios V. Avgerinos, Jerome D. Taylor Background: Iron deficiency anemia is a common finding in patients who undergo Roux- en-Y gastric bypass (RYGBP) for morbid obesity. This is the result of altered absorption but may also be compounded by occult losses. The present study evaluates risk factors for the development of anemia Methods: A retrospective analysis of patients undergoing Roux-en- Y gastric bypass (RGB) from January 2003 to November 2007 was performed. All patients had a preoperative body mass index (BMI) > 40 kg/m2. A total of 200 patients were evaluated. All patients were given daily ferrous sulfate tablets supplements two weeks following opera- tion. Hematological and metabolic indices were routinely evaluated following surgery. Patients were followed for a minimum of 80 weeks. Chi Square analysis was utilized to determine statistical significance for categorical data. Results: There were 38 males and 162 females with an average age of 40.8. 21 patients (11 percent) developed post-operative anemia and 179 patients did not. Anemia was due to iron deficiency in all cases. The groups had similar demographics, surgical procedure and co-morbidities. Menstruating females (p <.02) and those with peptic ulcer disease (p <.01) were risk factors for the development of post-operative anemia. Conclusions: Iron deficiency anemia is a frequent problems following bariatric surgery. RGB surgery compounds occult blood loss. Increased ferrous sulfate supple- mentation may be necessary to prevent iron depletion in populations at increased risk for the development of anemia. T1843 Effective Combination of mTOR-Inhibitor Rapamycin with 5-FU / Oxaliplatin in Advanced Colorectal Cancer Monitored By TIMP-1 (Tissue Inhibitor of Metalloproteinases 1) Stephan A. Vorburger, Markus Wagner, Alexander L. Laemmle, Markus Trochsler, Daniel Candinas Anti-tumor activity of mTOR-inhibitor rapamycin has been shown in various tumors. Based on observations on a transplanted patient, recieving rapamycin, we wanted to evaluate the potential of rapamycin for the treatment of colorectal peritoneal carcinomatosis alone or in combination with surgery. We established syngenic, orthotopic animal models with CT26 peritoneal tumors in Balb/C mice and orthotopic xenograft models with SW620 in nude mice. Rapamycin was administered intraperitoneally or per gavage, alone or combined with 5-FU and oxaliplatin. Tumor growth was analyzed and expression of tissue inhibitor of matrix-metalloproteinases 1 (TIMP-1) in the tumor and serum was determined by ELISA. Rapamycin downregulated TIMP-1 in-vitro. In-Vivo, rapamycin markedly suppressed growth of established syngenic and xenografted peritoneal tumors (P<0.01). This anti-tumor effect was comparable after intraperitoneal or oral administration. Tumor suppression was further increased when rapamycin was combined with 5-FU and/or oxaliplatin. TIMP-1 serum levels correlated well (Correlation Coefficient = 0.75; P<0.01) with rapamycin activity. Hence, rapamycin suppressed advanced stage colorectal cancer growth even when applied orally. The combination of rapamycin with current chemotherapy regimens significantly increased anti-tumor efficacy without apparent toxicity. Because the treatment effect can be monitored by serum TIMP-1, clinical trials should now be considered. T1844 Genomic Instability in Cultured Human Colon Epithelial Cells Following Exposure to Environmental Stress Kewal K. Maudar, Gorantla Raghuram, Arpit Bhargava, Pradyumna K. Mishra Introduction: Cellular response to xenobiotics and environmental mutagens is a complex phenomenon and involves participation of diverse classes of genes that orchestrate DNA repair, cell cycle control, signal transduction, apoptosis and oncogenesis. Although it is difficult to ascertain the specific biological endpoints from diverse sources of genomic instability, such elucidations are highly relevant to risk assessments based upon the toxic levels of environmental agents. Isocyanates are the group of ubiquitous chemicals with a wide range of industrial activities. Yet, the patho-physiological implications resulting from their occupational and large scale accidental exposures are hitherto unknown. Objective: To appraise the genomic instability caused by isocyanates on human colon epithelial cells. Materials & Methods: We performed our varied experiments on the cultured human colon epithelial-FHC cell line using N-succinimidyl N-methyl carbamate, a surrogate chemical to methyl isocyanate. Evaluation of DNA damage kinetics was done through Qualitative and quantitative assessment of extent of phosphorylation states of γH2AX, ATM, ATR and p53. Quantification of secreted nucleosomes pre and post treatment and annexin-V FITC/PI assay, active caspase 3 assay, TUNEL, apoptotic DNA laddering, were done to infer the apoptotic index and the apoptotic DNA fragmentation respectively. Cytometric bead array provided the means of assaying secreted inflammatory cytokines in culture supernatant previous to and following exposure. Abnormalities at chromosomal and microsatellite level of the genome following exposure were measured through cytogenetic analysis and inter simple sequence repeat PCR respectively. Results: All the DNA damage responsive parameters displayed an increasing trend along with significant higher apoptotic index and elevated inflammatory cytokine levels in isocyanate treated cells in contrast to their control counterparts. Interest- ingly, cytogenetic analyses revealed varied chromosomal anomalies and also the analyses through inter simple sequence repeat PCR presented a greater instability at the microsatellite level thus giving the credence as the endpoints of genomic instability. Conclusion: Together these results imply that the isocyanates are potent enough to cause genomic instability under SSAT Abstracts

T1608 Incidence and Risk Factors for the Development of Anemia Following Roux-en-Y Gastric Bypass Surgery for Morbid Obesity

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management of these patients. Method: Subjects were asked to endoscopically measure aring of known diameter in a standardized plastic model of the esophagus and gastric pouchusing 4 commonly used endoscopic measuring techniques and a double channel endoscope.Subjects used visual estimation (VE), instrument reference (IR) to a biopsy forceps, an 18mm esophageal dilating balloon (DB) as reference, and a 30 mm endoscopic ruler (ER)made from an ERCP guide wire tip. The 5 models (33, 27, 24, 18 and 13 mm) werepresented in random order. Data was collected and maintained in a database. Results: Ten(9surgeons, 1 gastroentrologist) subjects participated. Endoscopic experience was >1000 scopesfor 4 subjects; 250-500 for 3; <100 for 3. The VE was the least accurate with an averagediversion (AD) from the actual diameter of 6.25 ± 4.95 mm (24.20 %); followed by IR,3.89 ± 3.05 mm (14.80 %); then the ER, 2.4 ± 1.9 mm (9.20 %).The DB was the mostaccurate with AD of 1.46 ± 0.9 mm (7.20 %). Of the 200 total measurements, only 8(4%) were accurate, 142 (71%) underestimated the size, and 50 (25%) overestimated.Underestimation was noted in 82.5% (33/40) of VE and IR measurents; ER had only 60%(24/40) underestimation; DB underestimated only 40% (16/40) of the time .Overestimationwas highest using DB 55% (22/40), followed by ER method 45% (14/40), then IR 15% (6/40); and lowest in VE 12.5% (5/40). Measurements of the largest model diameter (33 mm)were underestimated 98% of the time. In the smallest diameter model (13 mm), 16% ofthe measurements were underestimated; 2% were accurate; and 82% were overestimated.Conclusion: Endoscopic measurement of lumen diameter is very inaccurate. Underestimationis the most likely error in measurement. The larger the diameter the more likely it will beunderestimated; and the smaller the diameter the more likely it will be overestimated.Endoscopists should avoid visual estimation and use a standard reference tool (dilatingballoon) to measure anastomotic diameter. This will allow more effective intervention forclinical problems related to anastomotic size.

T1606

Trends and Outcomes of Hospitalizations for Peptic Ulcer Disease in theUnited States, 1993-2006Y. Richard Wang, Joel Richter, Daniel T. Dempsey

Objectives Despite progress in diagnosis and treatment, peptic ulcer disease (PUD) remainsa common reason for hospitalization. The purpose of this study was to quantify the timetrends of hospitalizations for PUD in the United States (U.S.) since 1993. Data and MethodsThe Healthcare Cost and Utilization Project Nationwide Inpatient Sample is a 20% stratifiedsample of all hospitalizations in the U.S. It was used to study hospitalizations with PUD asthe principal diagnosis during 1993-2006, including details on ulcer site, complications,procedures, and mortality. Statistical methods included the chi-square test and multivariatelogistic regression. Results The national estimate of hospitalizations for PUD decreasedsignificantly from 222,601 in 1993 to 156,108 in 2006 (-29.9%), with a larger reductionin duodenal ulcers (95,552 in 1993 vs. 60,029 in 2006, -37.2%) than gastric ulcers (106,987in 1993 vs. 86,064 in 2006, -19.6%). The inpatient mortality rate of PUD decreased from3.8% to 2.7% during 1993-2006 (p<0.001). Hemorrhage remained the most commoncomplication (71.6% in 1993; 73.3% in 2006) but perforation had the highest mortality(15.1% in 1993; 10.6% in 2006). In comparison to 1993, patients hospitalized for PUD in2006 had more use of endoscopy to control bleeding (22.2% vs. 12.9%, p<0.001), similaruse of oversewing of ulcer (7.4% vs. 7.6%), less use of gastrectomy (2.1% vs. 4.4%, p<0.001),and less use of vagotomy (1.7% vs. 5.7%, p<0.001). In multivariate logistic regressions, thedeterminants of mortality were similar in 1993 and 2006. Neither weekend admissionnor low hospital PUD volume was associated with a higher mortality rate. ConclusionsHospitalizations for PUD have decreased in the U.S. from 1993 to 2006, suggesting a decreasein the prevalence and/or severity of ulcer complications over this recent time period. Overthis time span, there has been a significant decrease in PUD mortality, a significant increasein the use of therapeutic endoscopy for bleeding ulcer, and a significant decrease in the useof definitive surgery (vagotomy and/or resection) for ulcer complications. Further researchis necessary to determine if these trends are causally related.

T1607

Reduced Surgical Revisions Associated with Placement of Subpectoral GastricElectrical Stimulator: Six Year Experience At a Single InstitutionJessica M. Gutierrez, Kiley Black, John I. Allen, Eric M. Johnson

Background: Gastric electrical stimulation (GES) has become an alternative for patients withgastroparesis that do not respond to medical treatment. Traditionally the GES leads havebeen placed in the stomach and the neurostimulator placed in a subcutaneous pocket inthe abdominal wall. Our experience shows reduced incidence of surgical revision if theneurostimulator is placed in a subpectoral pocket. Methods: Retrospective chart review from2001-2007 of 64 patients that had GES placement, 25 patients in the abdominal wall, 38subpectoral and one infraclavicular. Data collected included need for surgical revision. Theimplantation procedure was done by open and laparoscopic technique depending on patientand surgeon preference. In both cases the pylorus was identified and the leads were placedinto the muscularis of the stomach at 9.5 and 10.5cm from the pylorus. An upper endoscopywas preformed to ensure that the leads did not transgress the mucosa. The leads wereanchored into the stomach, then tunneled either to a pocket in the abdominal wall orsubpectoral pocket previously created. Results: Fourteen surgical revisions of the gastricstimulator were performed in 11 patients ( eight abdominal and one infraclavicular): twodue to lead fracture, eight due to abdominal pain, one due to migration of a lead into thestomach, one due to migration of the stimulator toward the J-tube, one patient that the GESpushed up against the rib cage causing pain and one placed subclavicular with pain at thesite. No revisions were performed in the subpectoral group. The estimation of risk adjustedby sex, age and diabetes showed that abdominal pacer had a greater risk of revisionscompared to subpectoral placement with hazard ratio of 7.1 CI 95%:0.86-59.5, p=0.06.Conclusions: This is the first report of placing the GES in the subpectoral position. Webelieve that 80% (12/14) of our revisions could likely have been prevented with subpectoralplacement. Patients with abdominal placement of the device were more likely to havediscomfort leading them to manipulate or attempt to shift the device resulting in lead failureand connection break. Abdominal placement was also found to have more pain at the site

A-921 SSAT Abstracts

requiring device revision. Subpectoral placement in our experience may limit the amountof revisions and pain associated with the device. Longer term follow up is needed in thisgroup of patients.

T1608

Incidence and Risk Factors for the Development of Anemia Following Roux-en-Y Gastric Bypass Surgery for Morbid ObesityI. Michael Leitman, Matthew Seigerman, Amanda J. Lefkowitz, Omar H. Llaguna,Dimitrios V. Avgerinos, Jerome D. Taylor

Background: Iron deficiency anemia is a common finding in patients who undergo Roux-en-Y gastric bypass (RYGBP) for morbid obesity. This is the result of altered absorption butmay also be compounded by occult losses. The present study evaluates risk factors for thedevelopment of anemia Methods: A retrospective analysis of patients undergoing Roux-en-Y gastric bypass (RGB) from January 2003 to November 2007 was performed. All patientshad a preoperative body mass index (BMI) > 40 kg/m2. A total of 200 patients were evaluated.All patients were given daily ferrous sulfate tablets supplements two weeks following opera-tion. Hematological and metabolic indices were routinely evaluated following surgery.Patients were followed for a minimum of 80 weeks. Chi Square analysis was utilized todetermine statistical significance for categorical data. Results: There were 38 males and 162females with an average age of 40.8. 21 patients (11 percent) developed post-operativeanemia and 179 patients did not. Anemia was due to iron deficiency in all cases. The groupshad similar demographics, surgical procedure and co-morbidities. Menstruating females (p<.02) and those with peptic ulcer disease (p <.01) were risk factors for the development ofpost-operative anemia. Conclusions: Iron deficiency anemia is a frequent problems followingbariatric surgery. RGB surgery compounds occult blood loss. Increased ferrous sulfate supple-mentation may be necessary to prevent iron depletion in populations at increased risk forthe development of anemia.

T1843

Effective Combination of mTOR-Inhibitor Rapamycin with 5-FU / Oxaliplatinin Advanced Colorectal Cancer Monitored By TIMP-1 (Tissue Inhibitor ofMetalloproteinases 1)Stephan A. Vorburger, Markus Wagner, Alexander L. Laemmle, Markus Trochsler, DanielCandinas

Anti-tumor activity of mTOR-inhibitor rapamycin has been shown in various tumors. Basedon observations on a transplanted patient, recieving rapamycin, we wanted to evaluate thepotential of rapamycin for the treatment of colorectal peritoneal carcinomatosis alone or incombination with surgery. We established syngenic, orthotopic animal models with CT26peritoneal tumors in Balb/C mice and orthotopic xenograft models with SW620 in nudemice. Rapamycin was administered intraperitoneally or per gavage, alone or combined with5-FU and oxaliplatin. Tumor growth was analyzed and expression of tissue inhibitor ofmatrix-metalloproteinases 1 (TIMP-1) in the tumor and serum was determined by ELISA.Rapamycin downregulated TIMP-1 in-vitro. In-Vivo, rapamycin markedly suppressed growthof established syngenic and xenografted peritoneal tumors (P<0.01). This anti-tumor effectwas comparable after intraperitoneal or oral administration. Tumor suppression was furtherincreased when rapamycin was combined with 5-FU and/or oxaliplatin. TIMP-1 serum levelscorrelated well (Correlation Coefficient = 0.75; P<0.01) with rapamycin activity. Hence,rapamycin suppressed advanced stage colorectal cancer growth even when applied orally.The combination of rapamycin with current chemotherapy regimens significantly increasedanti-tumor efficacy without apparent toxicity. Because the treatment effect can be monitoredby serum TIMP-1, clinical trials should now be considered.

T1844

Genomic Instability in Cultured Human Colon Epithelial Cells FollowingExposure to Environmental StressKewal K. Maudar, Gorantla Raghuram, Arpit Bhargava, Pradyumna K. Mishra

Introduction: Cellular response to xenobiotics and environmental mutagens is a complexphenomenon and involves participation of diverse classes of genes that orchestrate DNArepair, cell cycle control, signal transduction, apoptosis and oncogenesis. Although it isdifficult to ascertain the specific biological endpoints from diverse sources of genomicinstability, such elucidations are highly relevant to risk assessments based upon the toxiclevels of environmental agents. Isocyanates are the group of ubiquitous chemicals with awide range of industrial activities. Yet, the patho-physiological implications resulting fromtheir occupational and large scale accidental exposures are hitherto unknown. Objective:To appraise the genomic instability caused by isocyanates on human colon epithelial cells.Materials & Methods: We performed our varied experiments on the cultured human colonepithelial-FHC cell line using N-succinimidyl N-methyl carbamate, a surrogate chemical tomethyl isocyanate. Evaluation of DNA damage kinetics was done through Qualitative andquantitative assessment of extent of phosphorylation states of γH2AX, ATM, ATR and p53.Quantification of secreted nucleosomes pre and post treatment and annexin-V FITC/PI assay,active caspase 3 assay, TUNEL, apoptotic DNA laddering, were done to infer the apoptoticindex and the apoptotic DNA fragmentation respectively. Cytometric bead array providedthe means of assaying secreted inflammatory cytokines in culture supernatant previous toand following exposure. Abnormalities at chromosomal and microsatellite level of the genomefollowing exposure were measured through cytogenetic analysis and inter simple sequencerepeat PCR respectively. Results: All the DNA damage responsive parameters displayed anincreasing trend along with significant higher apoptotic index and elevated inflammatorycytokine levels in isocyanate treated cells in contrast to their control counterparts. Interest-ingly, cytogenetic analyses revealed varied chromosomal anomalies and also the analysesthrough inter simple sequence repeat PCR presented a greater instability at the microsatellitelevel thus giving the credence as the endpoints of genomic instability. Conclusion: Togetherthese results imply that the isocyanates are potent enough to cause genomic instability under

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