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Retinoids Display Minimal Impact on Glycolysis in Human Neuroblastoma Patient Derived Xenografts
Vol. 225, No. 4S2, October 2017
Scientific Poster Presentations: 2017 Clinical Congress
e139
neonates (69.2%) treated with ECMO/HD survived to discharge, and six appeared neurologically normal or mildly delayed. Four survivors later received liver transplantation. Higher initial and peak ammonia levels were associated with increased mortality (p<0.001).
INTRODUCTION: Although rare, the incidence of venous thromboembolism (VTE) in pediatric surgical patients is increasing. Evidence-based guidelines for VTE screening and prevention in adult patients are plentiful, but none currently exist for nonorthopedic/ trauma pediatric surgical patients.
CONCLUSIONS: ECMO/HD is an effective adjunct to rapidly clear severe hyperammonemia in newborns, reducing long-term neurodevelopmental morbidity. Higher ammonia levels are associated with greater odds of mortality.
METHODS: The National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2012 to 2015) was queried for patients who underwent general surgery procedures and were diagnosed with VTE postoperatively. Patient and operative variables were assessed to identify those associated with VTE.
Retinoids Display Minimal Impact on Glycolysis in Human Neuroblastoma Patient Derived Xenografts Jamie Aye, MD, Laura L Stafman, MD, Evan F Garner, MD, Jerry Stewart, Karina J Yoon, PhD, Stuart L Cramer, MD, Elizabeth A Beierle, MD, FACS Children’s of Alabama/University of Alabama, Birmingham, AL
RESULTS: From 2012 to 2015, 238 of 218,432 patients (0.11%) were identified as having VTE after surgical procedures. Of the patients diagnosed with VTE, 28.6 % had undergone adbominopelvic general surgery procedures. In this subset of patients, the odds of experiencing VTE were increased on multivariate regression for patients older than 15 years and those with pre-existing renal failure or a diagnosis of septic shock, patient with American Society of Anesthesia Classification > 2, and for anesthetic times longer than 2 hours. There was no increased risk of VTE based on malignancy, chemotherapy, inflammatory bowel disease, or laparoscopic surgical approach. While female sex was associated with increased risk for all surgical patients, the difference was not significant in general surgery procedures of the abdomen and pelvis.
INTRODUCTION: The Warburg effect describes energy production by cancer cells as an increased utilization of glycolysis despite the ample presence of oxygen. Inhibitors of glycolysis have been studied as potential anticancer agents. Thirteen-cis-retinoic acid (RA) is a differentiating agent currently used as maintenance therapy for high-risk neuroblastoma. Researchers have demonstrated retinoids may modify the glycolytic tendencies of some cancer cells. To date, no study has examined the role of retinoids on the Warburg effect in neuroblastoma. We sought to determine if retinoids alter the glycolytic pathway as part of their cellular effect in neuroblastoma. METHODS: We utilized 2 neuroblastoma human patient derived xenografts (PDXs), COA3 and COA6. Cells were treated with RA or UAB30, a novel synthetic retinoid known to affect neuroblastoma cell proliferation. Glucose uptake was measured by flow cytometry analysis of 2-NBDG, a fluorescent glucose analog, and reported as median fluorescent intensity. Extracellular lactate was measured by spectrometry using an L-lactate assay kit (Cayman). Results were compared with student’s t-test and p0.05 was considered significant. RESULTS: Glucose uptake in COA3 and COA6 cells was not altered after treatment with RA or UAB30 compared to untreated control cells. Extracellular lactate production tended to increase after treatment with RA or UAB30; however, these increases were not statistically significant. CONCLUSIONS: These findings suggest retinoids have minimal impact on glycolysis in human neuroblastoma PDXs. The mechanisms responsible for these observations require further delineation as they have significant implications for the treatment of neuroblastoma. Risk Factors for Venous Thromboembolic Events in Pediatric Surgical Patients: Defining When Prophylaxis Is Indicated Sarah B Cairo, MD, MPH, Hibbut-Ur-Rauf Naseem, MD, David H Rothstein, MD, FACS Women and Children’s Hospital of Buffalo, State University of New York, University at Buffalo, Buffalo, NY
CONCLUSIONS: In pediatric patients undergoing general surgery procedures, a model specifically incorporating the risk factors from this study will help identify patients at increased risk of VTE. Additional studies are needed to verify the application of these factors in a risk assessment model including comparison prophylaxis methods.
Short-Term Outcomes in Children Undergoing Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis Katerina Dukleska, MD, Erin A Teeple, MD, Allison A Aka, MD, Charles D Vinocur, MD, Loren Berman, MD Thomas Jefferson University Hospitals, Philadelphia, PA; Nemours-Alfred I duPont Hospital for Children, Wilmington DE INTRODUCTION: Restorative proctocolectomy with ileal pouchanal anastomosis (RP-IPAA) is the standard of care for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Outcomes are well described in adults including predictors of readmissions and reoperations; however, there is a paucity of data in children. Using the National Surgical Quality Improvement Program-Pediatric, we sought to describe patient outcomes and to identify factors associated with reoperation and readmission. METHODS: Using the 2012 to 2015 Participant Use Files, children aged 6-18 years who underwent RP-IPAA were identified. Only those diagnosed with UC or FAP were included. Indications for RP-IPAA were identified along with rates of complications including infection, reoperation, and readmission. Associations
Scientific Poster Presentations: 2017 Clinical Congress
e139
neonates (69.2%) treated with ECMO/HD survived to discharge, and six appeared neurologically normal or mildly delayed. Four survivors later received liver transplantation. Higher initial and peak ammonia levels were associated with increased mortality (p<0.001).
INTRODUCTION: Although rare, the incidence of venous thromboembolism (VTE) in pediatric surgical patients is increasing. Evidence-based guidelines for VTE screening and prevention in adult patients are plentiful, but none currently exist for nonorthopedic/ trauma pediatric surgical patients.
CONCLUSIONS: ECMO/HD is an effective adjunct to rapidly clear severe hyperammonemia in newborns, reducing long-term neurodevelopmental morbidity. Higher ammonia levels are associated with greater odds of mortality.
METHODS: The National Surgical Quality Improvement Program-Pediatric (NSQIP-P) database (2012 to 2015) was queried for patients who underwent general surgery procedures and were diagnosed with VTE postoperatively. Patient and operative variables were assessed to identify those associated with VTE.
Retinoids Display Minimal Impact on Glycolysis in Human Neuroblastoma Patient Derived Xenografts Jamie Aye, MD, Laura L Stafman, MD, Evan F Garner, MD, Jerry Stewart, Karina J Yoon, PhD, Stuart L Cramer, MD, Elizabeth A Beierle, MD, FACS Children’s of Alabama/University of Alabama, Birmingham, AL
RESULTS: From 2012 to 2015, 238 of 218,432 patients (0.11%) were identified as having VTE after surgical procedures. Of the patients diagnosed with VTE, 28.6 % had undergone adbominopelvic general surgery procedures. In this subset of patients, the odds of experiencing VTE were increased on multivariate regression for patients older than 15 years and those with pre-existing renal failure or a diagnosis of septic shock, patient with American Society of Anesthesia Classification > 2, and for anesthetic times longer than 2 hours. There was no increased risk of VTE based on malignancy, chemotherapy, inflammatory bowel disease, or laparoscopic surgical approach. While female sex was associated with increased risk for all surgical patients, the difference was not significant in general surgery procedures of the abdomen and pelvis.
INTRODUCTION: The Warburg effect describes energy production by cancer cells as an increased utilization of glycolysis despite the ample presence of oxygen. Inhibitors of glycolysis have been studied as potential anticancer agents. Thirteen-cis-retinoic acid (RA) is a differentiating agent currently used as maintenance therapy for high-risk neuroblastoma. Researchers have demonstrated retinoids may modify the glycolytic tendencies of some cancer cells. To date, no study has examined the role of retinoids on the Warburg effect in neuroblastoma. We sought to determine if retinoids alter the glycolytic pathway as part of their cellular effect in neuroblastoma. METHODS: We utilized 2 neuroblastoma human patient derived xenografts (PDXs), COA3 and COA6. Cells were treated with RA or UAB30, a novel synthetic retinoid known to affect neuroblastoma cell proliferation. Glucose uptake was measured by flow cytometry analysis of 2-NBDG, a fluorescent glucose analog, and reported as median fluorescent intensity. Extracellular lactate was measured by spectrometry using an L-lactate assay kit (Cayman). Results were compared with student’s t-test and p0.05 was considered significant. RESULTS: Glucose uptake in COA3 and COA6 cells was not altered after treatment with RA or UAB30 compared to untreated control cells. Extracellular lactate production tended to increase after treatment with RA or UAB30; however, these increases were not statistically significant. CONCLUSIONS: These findings suggest retinoids have minimal impact on glycolysis in human neuroblastoma PDXs. The mechanisms responsible for these observations require further delineation as they have significant implications for the treatment of neuroblastoma. Risk Factors for Venous Thromboembolic Events in Pediatric Surgical Patients: Defining When Prophylaxis Is Indicated Sarah B Cairo, MD, MPH, Hibbut-Ur-Rauf Naseem, MD, David H Rothstein, MD, FACS Women and Children’s Hospital of Buffalo, State University of New York, University at Buffalo, Buffalo, NY
CONCLUSIONS: In pediatric patients undergoing general surgery procedures, a model specifically incorporating the risk factors from this study will help identify patients at increased risk of VTE. Additional studies are needed to verify the application of these factors in a risk assessment model including comparison prophylaxis methods.
Short-Term Outcomes in Children Undergoing Restorative Proctocolectomy with Ileal Pouch-Anal Anastomosis Katerina Dukleska, MD, Erin A Teeple, MD, Allison A Aka, MD, Charles D Vinocur, MD, Loren Berman, MD Thomas Jefferson University Hospitals, Philadelphia, PA; Nemours-Alfred I duPont Hospital for Children, Wilmington DE INTRODUCTION: Restorative proctocolectomy with ileal pouchanal anastomosis (RP-IPAA) is the standard of care for ulcerative colitis (UC) and familial adenomatous polyposis (FAP). Outcomes are well described in adults including predictors of readmissions and reoperations; however, there is a paucity of data in children. Using the National Surgical Quality Improvement Program-Pediatric, we sought to describe patient outcomes and to identify factors associated with reoperation and readmission. METHODS: Using the 2012 to 2015 Participant Use Files, children aged 6-18 years who underwent RP-IPAA were identified. Only those diagnosed with UC or FAP were included. Indications for RP-IPAA were identified along with rates of complications including infection, reoperation, and readmission. Associations