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Uterine transposition
Abstracts / Gynecologic Oncology 145 (2017) 2–220
Analysis and nSolver Advanced Analysis. Next-generation sequencing (NGS) was performed on plasma cfDNA and tumor DNA from 14 patients. Mutations were compared using standard statistical tests. Results: The top 3 pathways affected by NACT were immune signaling (P = 1.30− 09), cell proliferation (P = 5.03− 08), and cellto-cell signaling (P = 7.49− 06). The top 5 upregulated genes were NR4A3, NR4A1, DUSP5, FOS, and FOSL1. NGS cfDNA analysis detected more mutations in cancer-related genes than in tumor DNA. The cfDNA pre-NACT contained 19 mutated genes with 57 specific mutations; the tumor DNA contained 6 mutated genes with 38 specific mutations. Findings were similar when comparing postNACT mutations. cfDNA demonstrated more genetic diversity after NACT. Of the 57 mutations in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 mutations in the tumor DNA remained unchanged. Conclusion: Analysis of matched tumors showed significant alterations in cell cycle, DNA damage, chromatin modification, Wnt, TGFB, and JAK-STAT signaling. These changes likely reflect tumor dysregulation caused by NACT. Furthermore, plasma cfDNA detects more mutations than DNA extracted from solid tumor and may better capture clonal evolution.
doi:10.1016/j.ygyno.2017.03.046
20 - Scientific Plenary Pretty fly for GPI: Altered carbohydrate metabolism in ovarian cancer R.A. Previsa, T.J. Mossa, B. Zanda, J.M. Hansena, R.L. Dooda, G.N. Armaiz-Penab, Y.A. Lyonsa, R.L. Colemana, A.K. Sooda. aThe University of Texas MD Anderson Cancer Center, Houston, TX, USA, bPonce Research Institute, Ponce, Puerto Rico
13
Fig. 1. Overall survival.
doi:10.1016/j.ygyno.2017.03.047
Scientific Plenary V: The Farr Nezhat Surgical Innovation Session Tuesday, March 14, 2017 Moderators: Paola A. Gehrig, MD, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Farr R. Nezhat, MD, FACOG, FACS, Weill Cornell Medical College, New York, NY, USA William Edward Winter III, MD, Legacy Medical Group - Gynecologic Oncology, Lake Oswego, OR, USA 21 - Scientific Plenary
Objective: To identify the biological consequences of glucose-6phosphate isomerase (GPI) dysregulation within the carbohydrate metabolism pathway in ovarian cancer. Method: We profiled 101 high-grade serous ovarian cancer (HGSOC) samples and 15 normal ovarian tissues samples; 172 significantly altered metabolites were identified. We classified these metabolites into altered pathways and carried out full-scale gene expression systems-based analyses. We further examined GPI levels in a separate cohort of 75 epithelial ovarian cancer patients and evaluated the effect of upregulation in this pathway on survival and in vivo models. Results: We carried out genomic analyses coupled with synthetic lethality screens (in 3 chemo-resistant cell lines) followed by integrated analyses of these datasets. The most enriched pathway identified was carbohydrate metabolism, specifically within the glycolytic and pentose phosphate pathway. Our analyses revealed the GPI is the key driver of these changes. The impact of GPI knockdown using siRNA was evaluated in a murine orthotopic model of ovarian cancer (SKOV3ip1). There was significantly decreased tumor growth (P = 0.0007) and metastases (P b 0.0001) in the siGPI group. We measured GPI in 75 epithelial ovarian cancer patients. Within this cohort, the median age was 58 years, with the majority having advanced-stage disease (93.3%) and high-grade serous histopathology (56%). GPI levels were measured using qRT-PCR from these patients’ tumors and normalized to normal fallopian tube (average 50, range 0.005–575.6) and ovarian scrapings (mean 2.2, range 0.0002–25). Significantly worse overall survival was noted in patients with elevated GPI levels (P = 0.02). (See Fig. 1.) Conclusion: We developed a novel systems-based approach using altered metabolites and genes to predict a malignant phenotype specific to HGSOC patients. Altered metabolism coupled with genomic analyses identified GPI as a key driver of altered ovarian cancer metabolism that will uncover novel biomarkers and therapeutic approaches.
Uterine transposition R. Ribeiroa, F.K. Tsumanumab, G.G. Brandalizeb, R.E. Fariab, L. Telesb, J.C. Rebolhoa. aHospital Erasto Gaertner, Curitiba, Brazil, bHospital Onix, Curitiba, Brazil The Surgical Film presents the case of a 26 yo patient with rectal cancer. In the first part of the video, the technique for dissecting the uterus and placing it at the level of the umbilicus is presented. In the second part, the uterus is repositioned after chemorradiation of the pelvis. The follow-up is also presented.
doi:10.1016/j.ygyno.2017.03.048
22 - Scientific Plenary Incidence of surgical site infection after implementation of a reduction bundle in gynecologic cancer patients undergoing colon surgery at a comprehensive cancer center M.B. Schiavonea, L.A. Moukarzelb, K. Leonga, Q. Zhoua, A. Iasonosa, K. Long Rochea, M.M. Leitaoa, D.S. Chia, N.R. Abu-Rustuma, O. Zivanovica. a Memorial Sloan Kettering Cancer Center, New York, NY, USA, bJohns Hopkins School of Medicine, Baltimore, MD, USA Objective: Surgical site infections (SSIs) are substantial causes of morbidity, prolonged hospitalization, cost, and death in patients undergoing colorectal procedures. The aim of our study was to investigate the incidence of SSI before and after the implementation
Analysis and nSolver Advanced Analysis. Next-generation sequencing (NGS) was performed on plasma cfDNA and tumor DNA from 14 patients. Mutations were compared using standard statistical tests. Results: The top 3 pathways affected by NACT were immune signaling (P = 1.30− 09), cell proliferation (P = 5.03− 08), and cellto-cell signaling (P = 7.49− 06). The top 5 upregulated genes were NR4A3, NR4A1, DUSP5, FOS, and FOSL1. NGS cfDNA analysis detected more mutations in cancer-related genes than in tumor DNA. The cfDNA pre-NACT contained 19 mutated genes with 57 specific mutations; the tumor DNA contained 6 mutated genes with 38 specific mutations. Findings were similar when comparing postNACT mutations. cfDNA demonstrated more genetic diversity after NACT. Of the 57 mutations in the plasma pre-NACT, only 6 persisted, whereas 33 of 38 mutations in the tumor DNA remained unchanged. Conclusion: Analysis of matched tumors showed significant alterations in cell cycle, DNA damage, chromatin modification, Wnt, TGFB, and JAK-STAT signaling. These changes likely reflect tumor dysregulation caused by NACT. Furthermore, plasma cfDNA detects more mutations than DNA extracted from solid tumor and may better capture clonal evolution.
doi:10.1016/j.ygyno.2017.03.046
20 - Scientific Plenary Pretty fly for GPI: Altered carbohydrate metabolism in ovarian cancer R.A. Previsa, T.J. Mossa, B. Zanda, J.M. Hansena, R.L. Dooda, G.N. Armaiz-Penab, Y.A. Lyonsa, R.L. Colemana, A.K. Sooda. aThe University of Texas MD Anderson Cancer Center, Houston, TX, USA, bPonce Research Institute, Ponce, Puerto Rico
13
Fig. 1. Overall survival.
doi:10.1016/j.ygyno.2017.03.047
Scientific Plenary V: The Farr Nezhat Surgical Innovation Session Tuesday, March 14, 2017 Moderators: Paola A. Gehrig, MD, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA Farr R. Nezhat, MD, FACOG, FACS, Weill Cornell Medical College, New York, NY, USA William Edward Winter III, MD, Legacy Medical Group - Gynecologic Oncology, Lake Oswego, OR, USA 21 - Scientific Plenary
Objective: To identify the biological consequences of glucose-6phosphate isomerase (GPI) dysregulation within the carbohydrate metabolism pathway in ovarian cancer. Method: We profiled 101 high-grade serous ovarian cancer (HGSOC) samples and 15 normal ovarian tissues samples; 172 significantly altered metabolites were identified. We classified these metabolites into altered pathways and carried out full-scale gene expression systems-based analyses. We further examined GPI levels in a separate cohort of 75 epithelial ovarian cancer patients and evaluated the effect of upregulation in this pathway on survival and in vivo models. Results: We carried out genomic analyses coupled with synthetic lethality screens (in 3 chemo-resistant cell lines) followed by integrated analyses of these datasets. The most enriched pathway identified was carbohydrate metabolism, specifically within the glycolytic and pentose phosphate pathway. Our analyses revealed the GPI is the key driver of these changes. The impact of GPI knockdown using siRNA was evaluated in a murine orthotopic model of ovarian cancer (SKOV3ip1). There was significantly decreased tumor growth (P = 0.0007) and metastases (P b 0.0001) in the siGPI group. We measured GPI in 75 epithelial ovarian cancer patients. Within this cohort, the median age was 58 years, with the majority having advanced-stage disease (93.3%) and high-grade serous histopathology (56%). GPI levels were measured using qRT-PCR from these patients’ tumors and normalized to normal fallopian tube (average 50, range 0.005–575.6) and ovarian scrapings (mean 2.2, range 0.0002–25). Significantly worse overall survival was noted in patients with elevated GPI levels (P = 0.02). (See Fig. 1.) Conclusion: We developed a novel systems-based approach using altered metabolites and genes to predict a malignant phenotype specific to HGSOC patients. Altered metabolism coupled with genomic analyses identified GPI as a key driver of altered ovarian cancer metabolism that will uncover novel biomarkers and therapeutic approaches.
Uterine transposition R. Ribeiroa, F.K. Tsumanumab, G.G. Brandalizeb, R.E. Fariab, L. Telesb, J.C. Rebolhoa. aHospital Erasto Gaertner, Curitiba, Brazil, bHospital Onix, Curitiba, Brazil The Surgical Film presents the case of a 26 yo patient with rectal cancer. In the first part of the video, the technique for dissecting the uterus and placing it at the level of the umbilicus is presented. In the second part, the uterus is repositioned after chemorradiation of the pelvis. The follow-up is also presented.
doi:10.1016/j.ygyno.2017.03.048
22 - Scientific Plenary Incidence of surgical site infection after implementation of a reduction bundle in gynecologic cancer patients undergoing colon surgery at a comprehensive cancer center M.B. Schiavonea, L.A. Moukarzelb, K. Leonga, Q. Zhoua, A. Iasonosa, K. Long Rochea, M.M. Leitaoa, D.S. Chia, N.R. Abu-Rustuma, O. Zivanovica. a Memorial Sloan Kettering Cancer Center, New York, NY, USA, bJohns Hopkins School of Medicine, Baltimore, MD, USA Objective: Surgical site infections (SSIs) are substantial causes of morbidity, prolonged hospitalization, cost, and death in patients undergoing colorectal procedures. The aim of our study was to investigate the incidence of SSI before and after the implementation