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Su1855 Morbidity and Morality Rates After Bariatric Surgery in a Regionalized Surgical Care Program: the Ontario Experience
undergoing AGB, PWL strongly predicted 12-month EWL (b=1.55, p=0.02, r2=0.053). Incidence of any complication or readmission was not significantly different between patients with positive and negative PWL for each surgery type. However, using a multivariate logistic regression model controlling for preoperative age>50, BMI>50, white race, private insurance, and male sex, we found that low PWL increased chance of any complication after surgery, among all surgery types (OR=1.35, p=0.05). CONCLUSION: Preoperative weight loss can significantly reduce the chance of developing complications after bariatric surgery, as well as improve percent excess weight loss 12-months postoperatively for gastric band patients.
Su1921 Metformin Alters Cellular Metabolism of Colon Cancer Cells Co-Cultured With Adipocytes Jennifer W. Harris, Yekaterina Zaytseva, B. Mark Evers, Tianyan Gao Currently two thirds of the nation's population is considered overweight or obese by measurement of body mass index. Colon and rectal cancers are intimately linked to the development and maintenance of obesity. Obesity is strongly associated with changes in the physiological function of adipose tissue, leading to insulin resistance, chronic inflammation, and altered secretion of adipokines, and carcinogenesis. Metformin, an oral hypoglycemic agent and an activator of AMP activated protein kinase (AMPK), has recently been tested for its anticancer effect. The goal of this study is to determine if using metformin in adipogenic environments alters cellular metabolism that leads to tumor inhibition. METHODS. (i) Pre-adipocytes, 3T3L1 cells, were differentiated using dexamethasone, 3-Isobutyl-1-methyl-2,6(1H,3H)purinedione (IBMX), and insulin and were grown in a transwell co-culture system with human colon cancer lines including SW480, HT29, and HCT116. Cell lysates were prepared from co-cultured cancer cells and analyzed using Western blot analysis. (ii) Primary adipocytes were isolated from either epididymal fat of C57/BL6 mice or human mesenteric fat of patients with colon cancer. Conditioned media was collected from cultured adipocytes and incubated with SW480, HT29 or HCT116 cells. Cell lysates were prepared from cancer cells and analyzed by Western blot. (iii) SW480, HT29, HCT116 cells were treated with different concentrations (0 mM, 0.25 mM, 0.50 mM, 1.0 mM, 5.0mM) of metformin for 12 hours. The rates of glucose consumption and lactate production were measured using cell medium. Cell lysates were prepared and analyzed by Western blot. RESULTS. We found that co-culturing colon cancer cells with differentiated 3T3L1 cells or primary adipocytes from mouse and human altered the activation status of signaling molecules, including mammalian target of rapamycin (mTOR), AMPK, and extracellular signal related kinases (ERK). In addition, metformin treatment resulted in a decrease in cell proliferation and an increase in AMPK activity in colon cancer cells. Significantly, the rates of glucose consumption and lactate production were decreased in a dose-dependent manner in metformin-treated cells. CONCLUSIONS. Cancer cells grown in adipogenic environments have increased potential for increased growth, metastasis, and invasion. Treating cells with agents that downregulate pathways common to adipogenesis and oncogenesis may provide therapeutic avenues to decrease cancer development.
Su1855 Morbidity and Morality Rates After Bariatric Surgery in a Regionalized Surgical Care Program: the Ontario Experience Aristithes Doumouras, Fady Saleh, Mehran Anvari, Dennis Hong Introduction: As part of the diabetes and obesity prevention strategy in Ontario, the Ministry of Health formed the Ontario Bariatric Network (OBN) in 2009. The OBN introduced the first Bariatric Centres of Excellence program for bariatric surgery in Canada, consisting of 7 hospitals within 4 centers. Since its inception, there has been no systematic, populationbased outcomes reported. Our objective was to evaluate the mortality and major morbidity of bariatric surgery in Ontario during the initial years of the implementation of a regionalized surgical care program. Methods: Provincial population-based cohort study that included all patients aged >18 years who received a Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or laparoscopic adjustable gastric band (LAGB) procedure in the province of Ontario from March 2008 until 2011.for the purposes of weight loss who met National Institute of Health criteria for weight loss surgery. Data was derived from the Canadian Institute for Health Information Discharge Abstract Database and Hospital Morbidity Database. Our patient population was defined using descriptive statistics and compared across procedures using the Pearson's Chi2 test for categorical data and the Kruskal-Wallis test for continuous data. Complication and mortality rates and their confidence intervals were defined by the exact binomial distribution and univariate comparisons of complications and mortality rates between the three bariatric procedures were performed using the Fisher's exact test. . Results: Over the program's initial 4 years, 5,618 procedures (90.5% RYGB, 7.5% SG and 2.0% LAGB) were performed. Mean age was 44.4 +10.3. 81.8% were female. 28.4% of our patient had type 2 diabetes. The overall serious complication rate was 5.3% (95% CI: 4.7 - 5.9). Complications were most common after RYGB (5.5%; 95% CI: 4.9 - 6.1) followed by SG (4.3%; 95% CI: 2.6 - 6.7) and LAGB (0.9%; 95% CI: 0.02 - 4.9) procedures (p<0.05). Reoperative rate was 0.71% on initial admission. The mortality rate for all procedures was 0.12% (95% CI: 0.05-0.26), greatest in patients who underwent SG at 0.24% (95% CI: 0.01-1.31), followed by RYGB at 0.12 (95% CI: 0.04-0.26), and LAGB at 0%, but these differences were not statistically significant (p=0.503). Conclusions: Major morbidity and mortality in patients undergoing bariatric surgery since the inception of the Ontario Bariatric Network centre of excellence model is relatively low. The rates are comparable to other major population-based reports on bariatric surgery.
Su1922
Introduction: MMP3, a member of the matrix metalloproteinase (MMPs) family, plays a role in the breakdown of extracellular matrix (ECM) and connective tissue remodeling and is thought to facilitate solid tumor progression and metastasis. MMP3 biosynthesis is regulated by epidermal growth factor, TNF- α, and IL1; the active form of MMP3 stimulates the epithelial-mesenchymal transition (EMT) during tumor development. Together with its activator, matriptase, MMP3 may promote tumor angiogenesis and growth via regulation of VEGF bioavailability. MMP3 over expression has been demonstrated in many malignancies including breast, lung, and ovarian cancer. Plasma MM3 levels in colorectal cancer (CRC) patients (pts) have not been well studied. This study's purpose was to compare plasma MM3 levels in pts with CRC and benign colonic pathology (BCP). Method: Preoperative (PreOp) plasma samples were obtained from CRC and BCP pts undergoing elective resection. Clinical, demographic and final pathological data were prospectively collected. Plasma MMP3 levels were determined via ELISA in duplicate and are reported as median + 95%CI (ng/ml). Expression levels were determined in the tumors and paired normal tissues of a subpopulation of study patients by QRT-PCR. The candidacy of MMP3 as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and by the area under the ROC curve (AUC) results. The Mann-Whitney test was used for statistical analysis, (significance p<0.05). Results: The study population consisted of 182 CRC (62% colon, 28% rectal) and 82 BCP pts (adenoma 26%, diverticulitis 67%, other 7%). CRC pts were older (mean age 67 vs.58, p<0.001) but the male/female ratios were similar. The median PreOp plasma MMP3 level was higher in the cancer pts (14.6, CI: 13.7, 15.8) than the BCP group (9.3, CI: 8.5, 10.5, p<0.001).The CRC stage distribution was: Stage-1, 24%; Stage2, 37%, Stage-3, 29%, Stage- 4, 10%. Plasma MMP3 levels were significantly higher in the Stage 3 and 4 pts than in the stage 1 group ( p=0.01).The AUC value for the ROC curve (which assesses the diagnostic potential of plasma MMP3 levels) was 0.759(sensitivity 75%, specificity 67%). MMP3exprersion was elevated in all CRC tumors tested vs. paired normal tissues (n=28). Conclusion: The median plasma MMP3 level in the setting of CRC was 55% higher than noted in the BCP group (p<0.001). Plasma MMP3 levels were higher in stage 3 and 4 versus the stage 1 pts.AUC levels suggest MMP3 may have value as a prognostic marker for CRC. The source of the additional MMP3 is likely the tumor and stroma. In addition, inflammatory cells in the peritumor environment, via cytokine elaboration, may enhance MMP3 expression in tumor and stromal cells and, thus, contribute to the higher plasma MMP3 levels. Further study with larger populations of control and CRC pts is warranted.
Su1920 Colorectal Cancer Is Associated With Elevated Plasma Levels of Chitinase 3Like-1 H m C. Shantha Kumara, Hiromichi Miyagaki, Jeanine Arkenbosch, Xiaohong Yan, Sonali A. Herath, Sahani De Silva, Linda Njoh, Vesna Cekic, Richard L. Whelan Introduction: Chitinase 3-Like1 (CHI3L1) is a secreted heparin binding glycoprotein expressed in many cell types including immune cells, endothelium and cancer cells. CHI3L1 enhances macrophage chemotaxis into cancers and macrophage production of IL8 and MCP1 in the tumor microenvironment which promotes tumor angeogenesis and progression. CHI3L1 also regulates cellular and tissue responses via IL-13 receptor alpha 2 and promotes in vitro cancer cell proliferation, human endothelial cell migration and tubule formation. CHI3L1 expression has been noted in gliblastoma, colon, breast, and hepatocellular carcinomas and increased blood levels of CHI3L1 have been noted in patients with breast, lung, ovarian and prostate cancers. Blood levels in the setting of colorectal cancer (CRC) have not been well studied. This study's purpose was to compare preoperative (PreOp) plasma CHI3L1 levels in CRC and benign colonic pathology (BCP) patients. Method: Preoperative (PreOp) plasma samples were obtained from consenting CRC and BCP patients undergoing elective resection. Demographic, clinical, operative and pathologic data were collected. CHI3L1 levels in preop plasma samples were determined via ELISA in duplicate and reported as median + 95%CI (ng/ml). The expression of CHI3L1in self paired CRC specimens with normal tissue of a subpopulation of study patients was assessed by QRT-PCR. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to assess plasma CHI3L1 as a diagnostic tool for CRC. The Mann-Whitney test was used for statistical analysis (significance p<0.05). Results: A total of 188 CRC (79% colon, 21% rectal) and 78 BCP patients (adenoma 27%, diverticulitis 65%, other 8%) were studied. The male/ female ratio's were similar but the CRC patients were older (p<0.001). The CRC stage distribution was: Stage 1, 24%; Stage 2, 37%; Stage 3, 30%; and Stage 4, 9%. The median plasma CHI3L1 levels were significantly higher in the CRC (87.7, CI: 80.5, 106.8) vs. the BCP patients (36.2, CI: 30.3, 43.5; P=< 0.001). Plasma CHI3L1 levels were significantly higher in stage 4 patients vs. stage 1(p= 0.02). The AUC value for ROC curve was 0.806(sensitivity 55%, specificity 96%). All CRC samples (n=28) tested shows elevated expression of CHI3L1vs. paired normal tissue. Conclusion: The CRC median CHI3L1level was 2.4 (142.3%) times higher than the BCP result and 52% higher in stage 4 vs. stage 1 patients. ROC curve analysis suggests a PreOp plasma CHI3L1 level has potential as a marker for early CRC detection. Higher levels of CHI3L1 in plasma of CRC may be from tumor, stromal or inflammatory cells associated with the cancer. CHI3L1 supports neoangeogenesis and tumor growth at tumor site. Further study with larger populations of control and CRC patients is warranted.
S-1053
SSAT Abstracts
SSAT Abstracts
Plasma Levels of Matrix Metalloproteinase 3 (MMP3) Is Significantly Increased in Patients With Colorectal Cancer H m C. Shantha Kumara, Xiaohong Yan, Hiromichi Miyagaki, Jeanine Arkenbosch, Sahani De Silva, Linda Njoh, Vesna Cekic, Richard L. Whelan
Su1921 Metformin Alters Cellular Metabolism of Colon Cancer Cells Co-Cultured With Adipocytes Jennifer W. Harris, Yekaterina Zaytseva, B. Mark Evers, Tianyan Gao Currently two thirds of the nation's population is considered overweight or obese by measurement of body mass index. Colon and rectal cancers are intimately linked to the development and maintenance of obesity. Obesity is strongly associated with changes in the physiological function of adipose tissue, leading to insulin resistance, chronic inflammation, and altered secretion of adipokines, and carcinogenesis. Metformin, an oral hypoglycemic agent and an activator of AMP activated protein kinase (AMPK), has recently been tested for its anticancer effect. The goal of this study is to determine if using metformin in adipogenic environments alters cellular metabolism that leads to tumor inhibition. METHODS. (i) Pre-adipocytes, 3T3L1 cells, were differentiated using dexamethasone, 3-Isobutyl-1-methyl-2,6(1H,3H)purinedione (IBMX), and insulin and were grown in a transwell co-culture system with human colon cancer lines including SW480, HT29, and HCT116. Cell lysates were prepared from co-cultured cancer cells and analyzed using Western blot analysis. (ii) Primary adipocytes were isolated from either epididymal fat of C57/BL6 mice or human mesenteric fat of patients with colon cancer. Conditioned media was collected from cultured adipocytes and incubated with SW480, HT29 or HCT116 cells. Cell lysates were prepared from cancer cells and analyzed by Western blot. (iii) SW480, HT29, HCT116 cells were treated with different concentrations (0 mM, 0.25 mM, 0.50 mM, 1.0 mM, 5.0mM) of metformin for 12 hours. The rates of glucose consumption and lactate production were measured using cell medium. Cell lysates were prepared and analyzed by Western blot. RESULTS. We found that co-culturing colon cancer cells with differentiated 3T3L1 cells or primary adipocytes from mouse and human altered the activation status of signaling molecules, including mammalian target of rapamycin (mTOR), AMPK, and extracellular signal related kinases (ERK). In addition, metformin treatment resulted in a decrease in cell proliferation and an increase in AMPK activity in colon cancer cells. Significantly, the rates of glucose consumption and lactate production were decreased in a dose-dependent manner in metformin-treated cells. CONCLUSIONS. Cancer cells grown in adipogenic environments have increased potential for increased growth, metastasis, and invasion. Treating cells with agents that downregulate pathways common to adipogenesis and oncogenesis may provide therapeutic avenues to decrease cancer development.
Su1855 Morbidity and Morality Rates After Bariatric Surgery in a Regionalized Surgical Care Program: the Ontario Experience Aristithes Doumouras, Fady Saleh, Mehran Anvari, Dennis Hong Introduction: As part of the diabetes and obesity prevention strategy in Ontario, the Ministry of Health formed the Ontario Bariatric Network (OBN) in 2009. The OBN introduced the first Bariatric Centres of Excellence program for bariatric surgery in Canada, consisting of 7 hospitals within 4 centers. Since its inception, there has been no systematic, populationbased outcomes reported. Our objective was to evaluate the mortality and major morbidity of bariatric surgery in Ontario during the initial years of the implementation of a regionalized surgical care program. Methods: Provincial population-based cohort study that included all patients aged >18 years who received a Roux-en-Y gastric bypass (RYGB), sleeve gastrectomy (SG) or laparoscopic adjustable gastric band (LAGB) procedure in the province of Ontario from March 2008 until 2011.for the purposes of weight loss who met National Institute of Health criteria for weight loss surgery. Data was derived from the Canadian Institute for Health Information Discharge Abstract Database and Hospital Morbidity Database. Our patient population was defined using descriptive statistics and compared across procedures using the Pearson's Chi2 test for categorical data and the Kruskal-Wallis test for continuous data. Complication and mortality rates and their confidence intervals were defined by the exact binomial distribution and univariate comparisons of complications and mortality rates between the three bariatric procedures were performed using the Fisher's exact test. . Results: Over the program's initial 4 years, 5,618 procedures (90.5% RYGB, 7.5% SG and 2.0% LAGB) were performed. Mean age was 44.4 +10.3. 81.8% were female. 28.4% of our patient had type 2 diabetes. The overall serious complication rate was 5.3% (95% CI: 4.7 - 5.9). Complications were most common after RYGB (5.5%; 95% CI: 4.9 - 6.1) followed by SG (4.3%; 95% CI: 2.6 - 6.7) and LAGB (0.9%; 95% CI: 0.02 - 4.9) procedures (p<0.05). Reoperative rate was 0.71% on initial admission. The mortality rate for all procedures was 0.12% (95% CI: 0.05-0.26), greatest in patients who underwent SG at 0.24% (95% CI: 0.01-1.31), followed by RYGB at 0.12 (95% CI: 0.04-0.26), and LAGB at 0%, but these differences were not statistically significant (p=0.503). Conclusions: Major morbidity and mortality in patients undergoing bariatric surgery since the inception of the Ontario Bariatric Network centre of excellence model is relatively low. The rates are comparable to other major population-based reports on bariatric surgery.
Su1922
Introduction: MMP3, a member of the matrix metalloproteinase (MMPs) family, plays a role in the breakdown of extracellular matrix (ECM) and connective tissue remodeling and is thought to facilitate solid tumor progression and metastasis. MMP3 biosynthesis is regulated by epidermal growth factor, TNF- α, and IL1; the active form of MMP3 stimulates the epithelial-mesenchymal transition (EMT) during tumor development. Together with its activator, matriptase, MMP3 may promote tumor angiogenesis and growth via regulation of VEGF bioavailability. MMP3 over expression has been demonstrated in many malignancies including breast, lung, and ovarian cancer. Plasma MM3 levels in colorectal cancer (CRC) patients (pts) have not been well studied. This study's purpose was to compare plasma MM3 levels in pts with CRC and benign colonic pathology (BCP). Method: Preoperative (PreOp) plasma samples were obtained from CRC and BCP pts undergoing elective resection. Clinical, demographic and final pathological data were prospectively collected. Plasma MMP3 levels were determined via ELISA in duplicate and are reported as median + 95%CI (ng/ml). Expression levels were determined in the tumors and paired normal tissues of a subpopulation of study patients by QRT-PCR. The candidacy of MMP3 as a diagnostic marker for CRC was validated by the receiver operating characteristic (ROC) curve and by the area under the ROC curve (AUC) results. The Mann-Whitney test was used for statistical analysis, (significance p<0.05). Results: The study population consisted of 182 CRC (62% colon, 28% rectal) and 82 BCP pts (adenoma 26%, diverticulitis 67%, other 7%). CRC pts were older (mean age 67 vs.58, p<0.001) but the male/female ratios were similar. The median PreOp plasma MMP3 level was higher in the cancer pts (14.6, CI: 13.7, 15.8) than the BCP group (9.3, CI: 8.5, 10.5, p<0.001).The CRC stage distribution was: Stage-1, 24%; Stage2, 37%, Stage-3, 29%, Stage- 4, 10%. Plasma MMP3 levels were significantly higher in the Stage 3 and 4 pts than in the stage 1 group ( p=0.01).The AUC value for the ROC curve (which assesses the diagnostic potential of plasma MMP3 levels) was 0.759(sensitivity 75%, specificity 67%). MMP3exprersion was elevated in all CRC tumors tested vs. paired normal tissues (n=28). Conclusion: The median plasma MMP3 level in the setting of CRC was 55% higher than noted in the BCP group (p<0.001). Plasma MMP3 levels were higher in stage 3 and 4 versus the stage 1 pts.AUC levels suggest MMP3 may have value as a prognostic marker for CRC. The source of the additional MMP3 is likely the tumor and stroma. In addition, inflammatory cells in the peritumor environment, via cytokine elaboration, may enhance MMP3 expression in tumor and stromal cells and, thus, contribute to the higher plasma MMP3 levels. Further study with larger populations of control and CRC pts is warranted.
Su1920 Colorectal Cancer Is Associated With Elevated Plasma Levels of Chitinase 3Like-1 H m C. Shantha Kumara, Hiromichi Miyagaki, Jeanine Arkenbosch, Xiaohong Yan, Sonali A. Herath, Sahani De Silva, Linda Njoh, Vesna Cekic, Richard L. Whelan Introduction: Chitinase 3-Like1 (CHI3L1) is a secreted heparin binding glycoprotein expressed in many cell types including immune cells, endothelium and cancer cells. CHI3L1 enhances macrophage chemotaxis into cancers and macrophage production of IL8 and MCP1 in the tumor microenvironment which promotes tumor angeogenesis and progression. CHI3L1 also regulates cellular and tissue responses via IL-13 receptor alpha 2 and promotes in vitro cancer cell proliferation, human endothelial cell migration and tubule formation. CHI3L1 expression has been noted in gliblastoma, colon, breast, and hepatocellular carcinomas and increased blood levels of CHI3L1 have been noted in patients with breast, lung, ovarian and prostate cancers. Blood levels in the setting of colorectal cancer (CRC) have not been well studied. This study's purpose was to compare preoperative (PreOp) plasma CHI3L1 levels in CRC and benign colonic pathology (BCP) patients. Method: Preoperative (PreOp) plasma samples were obtained from consenting CRC and BCP patients undergoing elective resection. Demographic, clinical, operative and pathologic data were collected. CHI3L1 levels in preop plasma samples were determined via ELISA in duplicate and reported as median + 95%CI (ng/ml). The expression of CHI3L1in self paired CRC specimens with normal tissue of a subpopulation of study patients was assessed by QRT-PCR. The receiver operating characteristic (ROC) curve and area under the ROC curve (AUC) were used to assess plasma CHI3L1 as a diagnostic tool for CRC. The Mann-Whitney test was used for statistical analysis (significance p<0.05). Results: A total of 188 CRC (79% colon, 21% rectal) and 78 BCP patients (adenoma 27%, diverticulitis 65%, other 8%) were studied. The male/ female ratio's were similar but the CRC patients were older (p<0.001). The CRC stage distribution was: Stage 1, 24%; Stage 2, 37%; Stage 3, 30%; and Stage 4, 9%. The median plasma CHI3L1 levels were significantly higher in the CRC (87.7, CI: 80.5, 106.8) vs. the BCP patients (36.2, CI: 30.3, 43.5; P=< 0.001). Plasma CHI3L1 levels were significantly higher in stage 4 patients vs. stage 1(p= 0.02). The AUC value for ROC curve was 0.806(sensitivity 55%, specificity 96%). All CRC samples (n=28) tested shows elevated expression of CHI3L1vs. paired normal tissue. Conclusion: The CRC median CHI3L1level was 2.4 (142.3%) times higher than the BCP result and 52% higher in stage 4 vs. stage 1 patients. ROC curve analysis suggests a PreOp plasma CHI3L1 level has potential as a marker for early CRC detection. Higher levels of CHI3L1 in plasma of CRC may be from tumor, stromal or inflammatory cells associated with the cancer. CHI3L1 supports neoangeogenesis and tumor growth at tumor site. Further study with larger populations of control and CRC patients is warranted.
S-1053
SSAT Abstracts
SSAT Abstracts
Plasma Levels of Matrix Metalloproteinase 3 (MMP3) Is Significantly Increased in Patients With Colorectal Cancer H m C. Shantha Kumara, Xiaohong Yan, Hiromichi Miyagaki, Jeanine Arkenbosch, Sahani De Silva, Linda Njoh, Vesna Cekic, Richard L. Whelan