Day :
- Endometrial cancer
Ovarian cancer
Gynecologic Surgery
Session Introduction
Sandra S Hatch
University of Texas, USA
Title: The occurrence of reactive oxygen and nitrogen species in normal endometrial tissues might explain signature hotspot mutations found in the PTEN gene in endometrial adenocarcinoma
Biography:
Dr. Hatch has been a faculty physician with UTMB for over ten years, specializing in breast and gynecological cancers. She is board certified in Radiation Oncology by the American Board of Radiology (ABR) and an active member with the American Society for Therapeutic Radiology & Oncology (ASTRO). She received her doctorate in medicine from the University of Texas Health Science Center at Houston, TX and completed her residency in radiation therapy at Baylor College of Medicine as chief resident. Before entering medical school, Dr. Hatch received her degree in engineering from Tennessee Technological University, which served as a solid foundation for the technological demands found in the field of radiotherapy.
Abstract:
Endometrial cancer is the most prevalently diagnosed gynecological cancer. The majority of type I endometrial cancer cases are reported to have a mutated PTEN tumor suppressor gene. With respect to endometrial cancer cases, the PTEN suppressor gene, codon 130, is a hotspot for mutation involving a cytosine to guanine transversion mutation. The mechanism for the C to G transversion in endometrial cancer has not been previously explained. Codon 130 contains a CpG dinucleotide, which could be methylated to 5-methylcysoine. For the first time, we have shown that methylation is present on the coding and non-coding strand at codon 130 of the PTEN gene in normal endometrial tissues. The presence of 5-methylcytosine increases oxidation of the adjacent guanine. Oxidized guanine (8-oxo-G), in the presence of peroxynitrite, can form Guanidinohydantoin (Gh) and mispair with guanine. This mechanism may explain the unusually high level of codon 130 mutations in endometrial cancer cases. 8-oxo-G and peroxynitrite can be formed in tissues from Reactive Oxygen (ROS) and Nitrogen (RNS) Species. We have used immunohistochemistry and immunofluorescence to assess the presence of such markers of damage in benign human endometrial tissues. We show that markers of ROS and RNS damage are found in benign endometrial tissues. The generation of DNA damage in histologically normal endometrial tissue is in accord with the mutagenic mechanism described above. Further study will contribute to development of methods capable of diagnosing precursors of endometrial cancer and potentially reveal new pharmacological targets
Samir A. Farghaly
Cornell University, USA
Title: Mesothelin Expression in Ovarian Cancer and its potential as Targeted Ovarian cancer Immunotherapy
Biography:
Samir A Farghaly is a Physician/Scientist and national and international expert in Obstetrics and Gynecology at Joan and Sanford I. Weill College of Medicine and the New York Presbyterian Hospital/Weill Cornell Medical Center- Cornell University, New York, USA. He received his MD from London University and PhD degree in Molecular Biology from London University. He is the Founder and Editor-in Chief of Enliven: Challenges in Cancer Detection and Therapy Journal. He is serving as a Senior Editor/Editor and member of editorial boards and editorial advisory boards of 18 international medical journals on gynecological cancers, gene expression & therapy, women’s health and gynecology. He has published 99 articles in reputed peer review journals. He has written several book chapters.
Abstract:
Ovarian cancer is the fourth most common cause of cancer death in women. Most patients are diagnosed at stage III and IV, with resultant low relative-survival rates. The current treatments with conventional cytotoxic chemotherapy and novel surgical techniques have improved the oncologic outcome of this disease. However,recurrence is common. Current evidence suggests that the immune system and its ability to recognize and eliminate microscopic disease is of significant importance in preventing recurrence. Immunotherapy for ovarian cancer is to balance the activation of the immune system against this cancer while preventing the potential for toxicity elicited by immune modulation. Mesothelin, a glycosylphosphatidylinositol (GPI) anchored cell surface protein, is a potential target for antibody-based ovarian cancer immunotherapy due to its high expression in ovarian cancer. Mesothelin plays a role in cancer ovarian progression, through three possible mechanisms. First, mesothelin may aid in the peritoneal implantation and metastasis of tumors through its interaction with mucin MUC16 (CA125). Second, mesothelin may promote cancer cell survival and proliferation via the NF-κB signaling pathway. Third, mesothelin expression promotes resistance to certain chemotherapy drugs such as TNF-α, paclitaxel, and a combination of platinum and cyclophosphamide. Human monoclonal antibodies targeting mesothelin have been isolated by phage display technology and may provide opportunities for novel ovarian cancer immunotherapy. In addition, CRS-207, is live-attenuated Listeria monocytogenes (Lm), which has been genetically modified to be safe for human use while retaining its ability to stimulate an immune response against the protein mesothelin. It is considered an active form of immunotherapy. It utilizes a live attenuated facultative intracellular bacterium, Listeria monocytogenes, as a vehicle to deliver the mesothelin antigen to kupffer cells . Once the bacteria undergo phagocytosis, both innate and adaptive immune responses occur. Ultimately, this leads to mesothelin-specific T-cell response directed toward ovarian cancer cells overexpressing mesothelin.
Biography:
Michaela Huynh is a student in the MD/PhD Combined Degree program at UTMB, Galveston. She graduated at Magna Cum Laude, Texas A&M University and Century Scholars Scholarship Program, Texas A&M University. She is involved in a number of student organizations on campus, including Students Together for Service and the Graduate Student Organization. Her research interest includes Enzymology and DNA repair mechanisms.
Abstract:
Endometrial cancer is the most prevalently diagnosed gynecological cancer. The majority of type I endometrial cancer cases are reported to have a mutated PTEN tumor suppressor gene. With respect to endometrial cancer cases, the PTEN suppressor gene, codon 130, is a hotspot for mutation involving a cytosine to guanine transversion mutation. The mechanism for the C to G transversion in endometrial cancer has not been previously explained. Codon 130 contains a CpG dinucleotide, which could be methylated to 5-methylcysoine. For the first time, we have shown that methylation is present on the coding and non-coding strand at codon 130 of the PTEN gene in normal endometrial tissues. The presence of 5-methylcytosine increases oxidation of the adjacent guanine. Oxidized guanine (8-oxo-G), in the presence of peroxynitrite, can form Guanidinohydantoin (Gh) and mispair with guanine. This mechanism may explain the unusually high level of codon 130 mutations in endometrial cancer cases. 8-oxo-G and peroxynitrite can be formed in tissues from Reactive Oxygen (ROS) and Nitrogen (RNS) Species. We have used immunohistochemistry and immunofluorescence to assess the presence of such markers of damage in benign human endometrial tissues. We show that markers of ROS and RNS damage are found in benign endometrial tissues. The generation of DNA damage in histologically normal endometrial tissue is in accord with the mutagenic mechanism described above. Further study will contribute to development of methods capable of diagnosing precursors of endometrial cancer and potentially reveal new pharmacological targets.
Alok De
Kansas City VA Medical Center, USA
Title: E. officinalis attenuates ovarian cancer through anti-angiogenic effects on tumor physiology
Biography:
Alok De has received his PhD from University of Calcutta. He is a Research Biologist at Kansas City VA Medical Center. His research focuses on to use the extract of Emblica officinalis as an alternative or adjunct therapeutic agent in helping to fight ovarian cancer . He has published more than 45 papers in reputed journals. He has been serving as reviewers of many journals and as an Editorial Board Member of Cancer Cell and Microenvironment
Abstract:
Background: Most (>70%) ovarian cancers (OC) develop resistance to platinum- and taxane-based therapy. Tumor microenvironment supports OC progression principally through parallel angiogenesis. Naturally occurring plant extracts block tumor progression through their effect on tumor microenvironment. Recently, we have found that E. officinalis extract (AE) has anti-neoplastic effect on OC cells while sparing normal cells. Hypothesis: AE alters tumor microenvironment and physiology through microRNA (miR)-regulated anti-angiogenic mechanism(s). Methods: OC cells-SKOV3 and SKOV3-derived mouse xenograft tumor were treated with AE. Effect of AE on SKOV3 cell physiology was assessed by proliferation assay, LDH assay. The expression of miRNAs, proangiogenic receptor IGF1R and angiogenic marker CD31 were determined. Expression of miR-375 in exosomes released from SKOV3 cells was studied. Results: AE attenuated cell proliferation, migration, invasiveness in SKOV3 cells in vitro. AE increased miR375 expression (>2,000-fold) in SKOV3 cells as well as in exosomes derived from SKOV3 cells (P<0.01). AE decreased the gene and protein expression of proangiogenic IGF1R, a target of miR-375 (P<0.001). Additionally, AE significantly attenuated the growth of and the expression of IGF1R, CD31 and proteins in SKOV3-derived xenograft tumor in nude mice. Conclusion: Increased exosomes and exosomal miR-375 following AE treatment may drive paracrine mechanism(s) to control tumor growth in OC by altering the tumor microenvironment leading to arrested angiogenesis.
Karl R Aigner
Medias Klinikum GmbH & Co KG, Germany
Title: Platin-refractory recurrent FIGO stage IIIc and IV ovarian cancer responds to high exposure isolated abdominal perfusion with chemofiltration
Biography:
Karl Reinhard Aigner is Medical Director of the Department of Surgical Oncology in Medias Klinikum Burghausen (Bavaria) / Germany. He had his surgical training in cardiovascular surgery at Friedrich-Alexander University in Erlangen. At Justus-Liebig University Giessen he specialized in Surgical Oncology, focusing on vascular techniques of drug delivery such as Implantofix and Jet Port catheters, and in 1981 first performed a technique of isolated perfusion of the liver with heart-lung machine in man. Furtheron he developed various techniques of segmental vascular isolation of body segments and organs, and the stopflow technique with adequately designed catheters. In 1982, together with Prof. Stephens from Sydney, he initiated the biannual International Congress of Regional Cancer Treatment (ICRCT) and from 1987 to 1991 was president of the International Society for Regional Cancer Therapy. From 1985 to 1998 he was managing editor of the International Journal Regional Cancer Treatment. He is author of numerous publications and book chapters, lectured and performed teaching operations on vascular perfusion techniques and oncological surgery in Europe the United States and Asia.
Abstract:
Introduction: Recurrent metastatic ovarian cancer treated with extended cytoreduction and combination-chemotherapy based on platinum compounds relapses within two years in almost half of the patients who responded to initial treatment. The likelihood of a second response to platinum-based chemotherapy after a recurrence is closely correlated with the recurrence-free interval. The shorter the time interval is to tumor progression, the less likely are the chances of a response to further chemotherapy. Material & Methods: The patients included in this study were mainly at FIGO stage IIIc (71%) and FIGO IV (25%). 87.5% had a four-quadrant peritoneal carcinosis and 39% (n=31) showed a histologic grade of G3 malignancy. 79% of all patients were heavily pre-treated; 6 of them had already undergone third-line and one patient fourth-line therapies. Four cycles of isolated hypoxic abdominal perfusion with Cisplatin, Adriamycin and Mitomycin were conducted at four weekly intervals. After insertion of a venous and arterial 21 Ch. stopflow-catheter via a femoral access, the vena cava was blocked beneath the right atrium, the arterial catheter was blocked above the celiac axis in the aorta. Both thighs were blocked by pneumatic cuffs. Chemotherapy in a 70 kg patient consisted of 50 mg Cisplatinum, 30 mg Adriamycin and 20 mg Mitomycin. The agents were administered as a bolus via the aorta at the level of the diaphragm followed by 15 minutes of hypoxic abdominal perfusion via an external pump and subsequent chemofiltration for 45 minutes. Adriamycin and Mitomycin were used because of their up to tenfold increased cytotoxicity under hypoxic conditions. The procedure was done under general anesthesia. Primary endpoint of the study was overall survival and secondary endpoint was control of the ascites and quality of life. Results: Clinical and histological complete remissions were 25% and 13% respectively, partial remissions 39% and 35% respectively, resulting in an overall clinical response rate of 64% and histological response rate of 48%. Complete remission of ascites within two cycles was noted in 43% and substantial reduction of ascites in 19%, totally 62%. Median progression-free survival was 8 months and median overall survival 14 months. 74%, which is three out of four patients, reported a definite decrease in abdominal symptoms and clear improvement in their pain situation. Eight patients survived between 6 and 18 years, of four patients who have currently survived between 11 and 19 years, three of them originally had G3 tumors. Toxicity & Side-effects: Chemofiltration bone-marrow toxicity ranged between WHO grade 1 and 2 and in patients with previous third- or fourth-line chemotherapy it was WHO grade 3. The predominant clinical symptom in patients with posttherapeutic tumor necrosis (15 - 20% of all patients) was fever and fatigue. Conclusion: Isolated hypoxic abdominal perfusion with subsequent chemofiltration in platin-refractory recurrent FIGO IIIc and IV ovarian cancer is a valuable option to break through chemoresistence and improve quality of life due to reduction or resolution of malignant ascites.
Ines Vasconcelos
Charité Medical University of Berlin, Germany
Title: Borderline ovarian tumors (BOTs)
Biography:
Dr. Ines Vasconcelos has completed her medical degree with honors at the University of Coimbra in Portugal and her doctoral studies with Magna Cum Laude at the Charité Medical University in Germany. She has published in several international peer-reviewed high-impact journals and serves as a member of the editorial board of the journal Advances in Modern Oncology Research (AMOR). She is currently working at the Berlin Oncological Center Kurfürstendamm
Abstract:
Borderline ovarian tumors (BOTs) were first described by Taylor in 1929 and have been a challenge for both pathologists and oncologists. BOT is a disease of younger, fertile women, generally with a benign course; however, a minority of patients progress and eventually succumb to the disease. Although the corrected survival for patients with disease confined to the ovary is 100% at 15 years, 30% of patients with serous BOT with invasive implants will develop persistent or recurrent tumor, most commonly low-grade ovarian serous carcinoma. For the group of patients with invasive implants, there is no consensus regarding standard therapy. At present, chemotherapy is offered mostly to patients with invasive implants, regardless of histological subtype. However, response to these agents remains suboptimal with recurrence estimates for patients for patients with BOT with invasive implants undergoing adjuvant treatment remaining high at 44.0%. In this presentation we will discuss the current evidence, or lack of thereof, to support the use of adjuvant treatment in patients with invasive implants in the primary treatment setting.
Marek Lankosz
AGH University of Science and Technology, Poland
Title: Evaluation of biochemical biomarkers in ovarian cancers
Biography:
Marek Lankosz is working as a Professor in the Faculty of Physics and Applied Computer Science at the AGH University of Science and Technology, Krakow, Poland. He is a Head of the Chair of Medical Physics and Biophysics. His scientific activity mainly focused on XRF microanalysis, X-ray absorption micro-spectroscopy and infra-red micro-spectroscopy. His latest research interest includes application of synchrotron radiation in biological and medical research in relation to morbidities, with focus on tumor, Parkinson disease and amyotrophic lateral sclerosis. The results of his studies were published in numerous articles
Abstract:
The ovarian surface epithelial tumors are a heterogenic group of neoplasms in which a wide spectrum of clinical behavior can be observed. The histopathological scope of these tumors ranges from benign cystic tumors to malignant high-grade carcinomas. The carcinogenesis of the above is a multistep process in which varied genetic pathways can be triggered. This raises the question of possible molecular or elemental differences between various ovarian tumors and creates a need for investigation. The main goal of this study was to investigate the role of elements and molecules in pathogenesis of ovarian cancers as well as to elucidate the metabolic activity of the cystic epithelium and the mechanism that drives the enlargement of cyst by accumulation of only liquid or semiliquid substance inside. The proposed studies would help to know if concentrations of minor- and trace elements and selected molecules in the malignant tissues could be used for differentiation of ovarian tumors. The samples designed to elemental micro-imaging were taken intra operatively from ovarian tumors of different types and degree of malignancy. Fibroma, mucinous cystadenoma, endometrial adenocarcinoma, poorly differentiated carcinoma and borderline mucinous tumors were used in investigations. Samples of tissue were cut from the material for two purposes: to conduct histopathological analysis and to map the distribution of chemical elements and molecules. X-ray fluorescence micro spectroscopy (XRF) was applied for chemical elemental analysis. The infrared micro spectroscopy was used for investigation of molecular composition of ovarian cancer tissue. It was found that K, Cl, S, Br and Fe are the most significant elements in the general discrimination between types of ovarian cancers. Significant amounts of elements such as Na, P, S, Cl, K, Ca and Fe, were present in all tumor fluids analyzed. There were also small amounts of Mg, Ni, Mn, Ni, Cu, Zn and Se. Concentrations of elements are diversified in relation to type of tumor. Changes in metal distribution in the ovarian tissues have been linked to the type of ovarian cancer. With results obtained, it was found that trace metals could be used to correctly identify cancerous tissue and effectively classify the cancer stage. The higher distribution of amide B in cystic tissue compared to neoplastic tissue was found. The concentrations of amide I, amide II and phosphodiester bonds in cancer tissue was higher.
Kennedy Gonçalves Pacheco
Vascular Surgeon and Phlebologist, Brazil
Title: The prevalence of varicocele and ovarian varicose veins in patients with cancer and/or venous thrombosis
Biography:
Kennedy Gonçalves Pacheco is a Vascular Surgeon and phlebologist specializes in treating varicose veins with Dense foam guided Eco Color Doppler at the University Pierre et Marie Curie - Paris (France). He is a member of the Brazilian Society of Angiology and Vascular Surgery, Member of the French Society of Phlebology; specializing in the treatment of Varicose Veins Pelvic by the International Ruber Hospital - Madrid – Spain.
Abstract:
Background: Infertility and hormonal alterations can be associated with Cancer and venous thrombosis. Varicocele and ovarian varicose veins are related to infertility and venous thrombosis. The objective is to investigate the association between cancer and venous thrombosis with varicose veins beside the germinating glands. Methods: 152 patients were selected from my private practice in a retrospective observational study, 98 of them having been diagnosed with venous thrombosis and 54 of them having been diagnosed with cancer. The diagnosis of ovarian varicose veins and varicocele were made through eco-color-Doppler, considering the minimum diameter of the veins (4.0; 5.0 and 6.0 mm) next to the ovaries and next to the testicles (2.0; 2.5 and 3.0 mm), with a reflux of 0.5 s. Results: Of a total of 14,800 patient, 152 with cancer and profound venous thrombosis were selected (1, 02%). Among these patients 98 were venous thrombosis cases and 54were cancer cases. When we adopted the minimum diameter in varicocele as 2.0 mm, 2.5 mm and 3.0 mm, the rate was of 96.7%, 83.6% & 55.7% respectively and in ovarian varicose veins as 4.0 mm, 5.0 mm and 6.0 mm, the rate was of 83.5%, 61.5% and 39.6%. Conclusions: Varicose veins next to the testicles and the ovaries are associated to oxidative stress, which can interfere in the hypothalamic-pituitary-gonadal axis, in the immune system and in genetics. The high prevalence of varicose veins next to the germinating glands may play a determinant role in cancer and in venous thrombosis.
Katarina Jeremić
Belgrade University School of Medicine, Serbia
Title: Fertility sparing in young patients with early stages of endometrial cancer
Biography:
Katarina Jeremić finished Medical School University of Belgrade (1996), MD (2000), PhD (2006), and academic special studies Obstetrics and Gynecology (2001), with 20 years of clinical experiences, working at Clinic for Gynecology & Obstetrics Clinical Centre of Serbia, which is the biggest one in whole region. She worked as a gynecologist for 18 years. Her present position at the Clinis is Head of gynecologic oncology department, and also she is the member of many scientific projects such as Cancer and Pregnancy. At the Medical Faculty, University Belgrade, she works as a lecturer - Associate Professor of gynecology and obstetrics. Her representative publications are about 50 publications in CC/SCI expanded and JCR indexed, and she is an active participant on more than 50 international congresses, with total number of publication about 150.
Abstract:
Endometrial cancer is the most common cancer of the female genital tract and female patient less than 40 years may account for 3-14% of all endometrial cancers. The promising fact is that in women <45 years, the tumor is mostly low grade disease localised to the endometrium, whereas survival is almost about 100%. An individualized and multidisciplinary approach to each patient, intense follow-up, respecting the current recommendations for fertility sparing. Conservative approaches of early-stage endometrial carcinoma includes hormonal therapy in selected group of young patients with endometrial carcinoma age less than 45 years and wishes fertility, showing low grade 1 endometrioid adenocarcinomas (by 2 gynoncology pathologists review) is requested limited to the endometrium with MRI excluded myomaterial invasion, without evidence of limphovascul are space involvement or extra uterine disease. Carefully and accurately pretreatment assessment of patients considering conservative therapy includes radiologic imaging, hysteroscopy preferably but also contrast-enhanced radiologic imaging -MRI imaging of the ovary (5% of patients with endometrial cancer have synchronous primaries tumors). Repeating endometrial biopsies by hysteroscopy every 6 months has been recommended, until there is a complete response or achieving pregnancy. Surgery is recommended if there is no response after 6 months of medicational treatment. Hormonal therapy that could be applied is progestins inhibits the estrogenic effect and suppresses cell proliferation (medroxy progesterone acetate, megestrl acetate), GnRh analogues, but also local gestagens (IUD), oral natural progesterons, aromatase inhibitors, even three step endoscopic (hysteroscopic ) resection - remove tumour, surrounding endometrium, myometrium. Fertility after treatment is not guaranteed, even there had been recorded reduced fertility of those treated, and there is a significant need ART (18-60%).
Shujie Yang
University of Iowa, USA
Title: Systematic dissection of the mechanisms underlying progesterone receptor downregulation in endometrial cancer
Biography:
Shujie Yang is a Research Assistant Professor of Obstetrics and Gynecology - Reproductive Science Research. Education qualification is a Post Doctorate, Obstetrics and Gynecology, University of Iowa.
Abstract:
Progesterone, acting through its receptor, PR (progesterone receptor), is the natural inhibitor of uterine endometrial carcinogenesis by inducing differentiation. PR is downregulated in more advanced cases of endometrial cancer, thereby limiting the effectiveness of hormonal therapy. Our objective was to understand and reverse the mechanisms underlying loss of PR expression in order to improve therapeutic outcomes. Using endometrial cancer cell lines and data from The Cancer Genome Atlas, our findings demonstrate that PR expression is downregulated at four distinct levels. In well-differentiated cancers, ligand-induced receptor activation and downregulation are intact. miRNAs mediate fine tuning of PR levels. As differentiation is lost, PR silencing is primarily at the epigenetic level. Initially, recruitment of the polycomb repressor complex 2 to the PR promoter suppresses transcription. Subsequently, DNA methylation prevents PR expression. Appropriate epigenetic modulators reverse these mechanisms. These data provide a rationale for combining epigenetic modulators with progestins as a therapeutic strategy for endometrial cancer. Significance: Traditional hormonal therapy for women with endometrial cancer can be molecularly enhanced by combining progestins with epigenetic modulators, thereby increasing progesterone receptor expression and significantly improving treatment efficacy
Ahmed Abdel Aziz
Michigan State University, USA
Title: A large broad ligament uterine fibroid: Successful myomectomy with robotic assisted laparoscopic myomectomy
Biography:
Ahmed Abdelaziz, is an obstetrician/gynecologist in Flint, at Michigan. Clinical interest is General Gynecology. Completed Education at Hurley Medical Center - Michigan State University.
Abstract:
Uterine leiomyomata, or myomas, are one of the most common benign tumors of the reproductive tract, affecting more than 70% of women in their lifetime. Definitive surgical treatment of myoma is hysterectomy while myomectomy is the treatment for those women who have symptomatic myomas and desire uterine or fertility preservation. Leiomyomas can arise from any tissue including the broad ligament, the incidence of broad-ligament leiomyoma is <1%. Myomectomy of large broad ligament fibroid presents certain challenges due to anatomical distortion, leading to higher incidence of ureteric injury and excessive bleeding. Still most of the myomectomies are done abdominally, this is due to the complexity and the necessity of extensive suturing for the desired multi- layered uterine closure, which is technically hard to do laparoscopically. The introduction of robotic surgery has allowed more surgeons to perform complex laparoscopic procedures
Biography:
Hani Gabra is Professor and head of Medical Oncology, Deputy Head of the Division of Cancer and Director of the Ovarian Cancer Action Research Centre at Imperial College. He is also Associate Director and Lead of the Cancer Division (Division 1) of the NIHR Clinical Research Network for North West London
Abstract:
To identify therapeutic strategies for circumventing APR in OC, we utilised isogenically matched cell lines from platinum sensitive patients who then developed APR to undertake RNA expression microarray analysis to identify genes upregulated in APR. SiRNA knockdown revealed targets whose downregulation re-sensitised cells to platinum. Preclinical development identified that AKT and DNA-PK where strong candidates for inhibition strategies. A clinical phase Ib/II trial demonstrated a 40% RECIST response rate in APR patients receiving carboplatin and paclitaxel 3 weekly, in whom a response rate of <13% would be expected. This approach opens up new possibilities for treatment of recurrent OC.
Biography:
Ahmad M. Abu-Elhasan is a Professor in the Department of Obstetrics and Gynecology, as Faculty of Medicine, Ùat Assiut University. Qualifications include M.D. In obstetric and gynecology ( infertility ) , Faculty of Medicine, Assiut university
Abstract:
Objectives: Intra-abdominal adhesion is a common morbidity after laparotomic myomectomy. We tried to determine whether post-myomectomy intra-peritoneal wash with lactated Ringer's for 48 hours may reduce the incidence or degree of adhesions. Methods: A prospective, randomized trial that included 52 eligible participants for whom abdominal myomectomies were done. Participants were randomly allocated into a treatment group (n=26), which was subjected to continuous intra-peritoneal wash for 48 hours via two intra-peritoneal drains, and a control group (n=26) with no further postoperative intervention. The incidence of de novo adhesions, its severity and extent were scored at a second look laparoscopy 8-10 weeks postoperative. Adhesions were graded using Local Adhesion Barrier Scoring System (LABS) score. Adverse effects were also assessed and reported. Results: There was no statistically significant difference as regard duration of hospital stay or the incidence of adverse events. A significantly high proportion of adhesion-free patients was found in the treatment group [11/ 23, 47.8%] compared to control group [4/21, 19%] (P<0.01). The mean number of pelvic sites covered by adhesions was significantly low in treatment group compared to control group (2.2±0.3 versus 4.6±0.8, P<0.05). The total adhesion score was significantly low in treatment group compared with controls (2.1±0.5 versus 4.8±1.4, P<0.05). Also, adhesion score was significantly low at most of the individual anatomical sites in treatment group compared with controls. Conclusion: Our results suggest that application of postoperative intraperitoneal wash with lactated Ringer's solution for 48 hours may have a reasonable safety and efficacy in minimizing postoperative pelvic de novo adhesions following abdominal myomectomy.
Biography:
Junjun Qiu has completed his PhD from Fudan University in 2014. She is now working at the Obstetrics and Gynecology Hospital of Fudan University. Her research mainly focuses on long noncoding RNA and ovarian cancer progression and was supported by funding from the National Natural Science Foundation of China (81502240) and Shanghai Science and Technology Development Funds for the Talents (15YF1401400). She has published 8 SCI papers in recent three years
Abstract:
The long non-coding RNA HOTAIR promotes the proliferation of serous ovarian cancer cells through the regulation of cell cycle arrest and apoptosis: HOX Transcript Antisense RNA (HOTAIR) is a well-known Long Non-Coding RNA (lncRNA) whose dysregulation correlates with poor prognosis and malignant progression in many forms of cancer. Here, we investigate the expression pattern, clinical significance, and biological function of HOTAIR in Serous Ovarian Cancer (SOC). Clinically, we found that HOTAIR levels were overexpressed in SOC tissues compared with normal controls and that HOTAIR overexpression was correlated with an advanced FIGO stage and a high histological grade. Multivariate analysis revealed that HOTAIR is an independent prognostic factor for predicting overall survival in SOC patients. We demonstrated that HOTAIR silencing inhibited A2780 and OVCA429 SOC cell proliferation in vitro and that the anti-proliferative effects of HOTAIR silencing also occurred in vivo. Further investigation into the mechanisms responsible for the growth inhibitory effects by HOTAIR silencing revealed that its knockdown resulted in the induction of cell cycle arrest and apoptosis through certain cell cycle-related and apoptosis-related proteins. Together, these results highlight a critical role of HOTAIR in SOC cell proliferation and contribute to a better understanding of the importance of dysregulated lncRNAs in SOC progression.
Somashekhar S P
Manipal Hospital, Bangalore, India
Title: A prospective randomised study of open versus robotic assisted para aortic lymph node dissection in high risk endometrial carcinoma – A novel technique
Biography:
Somashekhar.S.P,MS,MCh(Onco),FRCS.Edinburgh,Chairman & HOD Surgical Oncology,Manipal Health Enterprise,Graduation year 1994, MS and MCh oncosurgery 2000 year,FRCS. Edinburgh Editor in chief Indian Journal of Gynec oncology Treasurer Association of Gynecological Oncology India Consultant Surgical & Gynec. Onco & Robotic Surgeon,,Manipal Comprehensive Cancer Center,India ,Had several national and intrenstio skPublication and has authored several text Books in gynec oncology
Abstract:
Introduction: To evaluate the technical feasibility and safety of robotic assisted para aortic lymphadenectomy in comparison with open surgery in terms of adequacy of staging, blood loss, lymph node harvest, hospital stay and complications. Material & Methods: A randomized prospective study was performed which included 180 patients diagnosed with endometrial carcinoma who were divided into two groups one open and other robotic. All patients underwent type I pan hysterectomy + B/L pelvic lymphadenectomy. The high risk patients (FIGO grade 3, Tumor > 2 cm, pelvic node positive and >50% myoinvasion) were taken up for para aortic lymphadenectomy. The para-aortic node dissection was performed upto renal veins. In the Da Vinci Robotic arm, a novel single docking technique using 30 degree camera with hot shears and bipolar fenestrated grasper was used. The split and roll technique was used to perform the pre-caval and pre-aortic lymphadenectomy. Results: Out of 180 patients included in study, 113 had high risk endometrial cancer (open arm 58 and robotic arm 55). The average blood loss in open arm was 134.6 ml vs. 41.2 ml in robotic arm. In open surgery, on average 11.6 nodes were harvested when compared to 17.5 nodes in robotic arm. Duration of hospital stay for open group was 5.54 days vs. 1.94 days for robotic arm. None of the patients in either arm had any major intra-operative or post-operative complications. 23 patients in the open arm had prolonged ileus while 4 patients had ileus in robotic arm. 7 patients in open arm developed wound infection. Conclusion: This study showed results which indicate that robotic assisted para-aortic lymphadenectomy had equal oncologic outcome as compared to open technique. Minimal blood loss and less pain helped in shorter hospital stay and early return to normal activities. Robotic assisted surgery had better clinical outcome and patient satisfaction when compared to open technique.
Tevfik Guvenal
Celal Bayar University School of Medicine, Turkey
Title: Effect of surgical staging on 539 patients with borderline ovarian tumors: A Turkish Gynecologic Oncology Group study
Biography:
Tevfik Guvenal Is graduated from Cumhuriyet University School of Medicine in 1989.Istanbul Goztepe Training and Research Hospital specialist started education in 1995. did military service as an obstetrician in Eskisehir Air Hospital.Cumhuriyet University Faculty of Medicine Department of Obstetrics and Gynecology in 1999 started Department in academic life. In 2000 Hacettepe University Obstetrics and Gynecology, Gynecologic Oncology, received training in the field. In 2003 became a professor in 2009 and since 2009 Celal Bayar University Department of Obstetrics and Gynecology, Gynecologic Oncology have been working as a responsible unit. Pelvic and vaginal surgery is my area of special interest outside of Gynecologic Oncology.Board member of the Turkish Association of Gynecologic Oncology Gynecologic Oncology, Journal of Turkish and have been responsible for writing duties as chief.
Abstract:
Objective. The objectives of this study were to examine demographic and clinicopathologic characteristics and to determine the effects of primary surgery, surgical staging and the extensiveness of staging. Methods. In a retrospective Turkishmulticenter study, 539 patients, from14 institutions,with borderline ovarian tumors were investigated. Some of the demographic, clinical and surgical characteristics of the cases were evaluated. The effects of type of surgery, surgical staging; complete or incomplete staging on survival rates were calculated by using Kaplan–Meier method. Results. The median age at diagnosis was 40 years (range 15–84) and 71.1% of patients were premenopausal. The most common histologic types were serous and mucinous. Majority of the staged cases were in Stage IA (73.5%). 242 patients underwent conservative surgery. Recurrence rates were significantly higher in conservative surgery group (8.3% vs. 3%). Of all patients in this study, 294 (54.5%) have undergone surgical staging procedures. Of the patientswho underwent surgical staging, 228 (77.6%) had comprehensive staging including lymphadenectomy. Appendectomy was performed on 204 (37.8%) of the patients. The median follow-up time was 36 months (range 1–120 months). Five-year survival rate was 100% and median survival time was 120 months. Surgical staging, lymph node sampling or dissection and appendectomy didn't cause any difference on survival. Conclusion. Comprehensive surgical staging, lymph node sampling or dissection and appendectomy are not beneficial in borderline ovarian tumors surgical management
Vineet Talwar
Rajiv Gandhi Cancer Institute and Research Centre, India
Title: Efficacy and safety of adjuvant intraperitoneal chemotherapy in carcinoma ovary: A prospective observational study
Biography:
Dr. Vineet Talwar earned his DM (Medical Oncology) from Adyar Cancer Institute, Chennai. He has more than 40 publications in National and International journals and is member of the European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO), Indian Cooperative Oncology Network (ICON), Indian Society of Oncology (ISO).Dr. Talwar is a recipient of four orations from the Association Physician of India, Indian Academy of Clinical Medicine. He is also credited as a fellow of International Medical Sciences Academy (IMSA), Indian College of Physicians (FICP) and Fellow of Royal Society of Physicians (FRCP), UK.He is actively involved with the DNB Medical Oncology program which is being conducted at Rajiv Gandhi Cancer Institute and is a thesis guide as well. He actively participates in oncology updates, cancer detection camps, outreach clinics and drug trials (phase I, II, III) at the Institute.
Abstract:
Background: It has been demonstrated in few trials, that intraperitoneal and intravenous (IP/IV) chemotherapy improves survival in advanced stage ovarian cancer. But it has been associated with high treatment related toxicities leading to very low acceptance of this modality among medical oncologists. So, various modifications in treatment schedules have been tried to reduce toxicities. In this study, we decided to study the response and tolerability of IP paclitaxel on day 8 with IV paclitaxel on day 1 and IV cisplatin day 2 in carcinoma ovary, in view of paucity of data with this modification. Methods: In this prospective observational study, from March 2013 to June 2015, the efficacy and tolerability of adjuvant IP/IV chemotherapy in optimally cytoreduced stage III epithelial ovarian cancer patients were assessed. Treatment consisted of 135 mg/m2 of IV paclitaxel over a 3-hours period on day 1 followed by AUC 5 carboplatin IV on day 2 and 60 mg/m2 of IP paclitaxel on day 8 every 3 weekly for six cycles. Results: Total 40 patients were enrolled. The median age of patients was 53 yrs (32 yrs–67 yrs). Out of a total of 240 I/P cycles, 211 cycles (88%) were completed. 30 patients (76%) received all the 6 cycles by IP route. 6 out of those 30 patients had one or more adjustment including delay or dose reduction. After median follow up of 18 months, 5 patients (12.5%) had local or systemic recurrence, 2 patients (5%) had progression during treatment. Median progression free survival not reached yet. Catheter block was seen in 5 cases. Two cases had needle displacement and extravasations of drug around the port chamber. 6 patients had grade 3 abdominal pain and cramp. Grade 3/4 Leucopenia was experienced by 20 patients (50%) but Febrile Neutropenia occurred in only 4 (10%) patients. Renal complication present in 2 patients (5%) and transient transfusion reaction developed in 5 patients. Conclusions: In Indian patients, adjuvant chemotherapy with day 8 I/P paclitaxel in optimally cytoreduced epithelial ovarian cancer is associated with survival benefits comparable to western literature and better tolerated with very high treatment completion rate.
- Cervical cancer
Vaginal/Vulvar cancer
Session Introduction
Melissa Joyner
University of Texas Medical Branch, USA
Title: Locally advanced vulvar cancer outcomes following chemoradiation: A retrospective review
Biography:
Melissa Joyner is a Radiation Oncologist specializing in the treatment of gynecologic, and breast cancers. She is an Assistant Professor of Radiation Oncology at the University of Texas Medical Branch. She completed her Radiation Oncology Training at the University of Texas Health Science Center in San Antonio (UTHSCSA). She also received her Doctorate of Medicine at UTHSCSA and is Board Certified in Radiation Oncology by the American Board of Radiology (ABR).
Abstract:
Purpose & Objectives: To review results from a single institution of preoperative chemoradiation therapy in patients with locally advanced vulvar cancer who are not surgical candidate due to extent of disease. Patients were treated with intent to improve local control with organ preservation. Materials & Methods: Historical chart review of 12 patients with an average age of 52 (range 40 to 72 years old) treated between 1997-2014, all with locally-advanced clinical stage T3 or T4 squamous cell carcinomas of the vulva not amenable to surgical resection. Two of 12 patients presented with locally advanced recurrent disease and nodal relapse. All patients were treated with external beam to 4760 cGy (1.7 Gy per fraction x 28 fractions) using an accelerated fractionation schema consistent with GOG 101 protocol with a planned treatment break in conjunction with concurrent Cisplatin and 5-FU. A single patient was treated with a modified fractionation schema after 1st cycle of radiation demonstrated superior treatment response which facilitated surgical resection and was then followed with additional radiation to treat residual microscopic disease. 7 out 12 patients (58.3%) also received a boost ranging from 7.2 Gy to 17.2 Gy with a single patient receiving 12 Gy SD via vaginal cylinder. Results: Patients studied had an average of 75 months of follow-up. Sustained local control was achieved in 8/12 (66.7%). A complete clinical response (cCR) was seen in 100% of patients following treatment. Despite extensive disease at presentation, only 2/12 (16.7%) failed in the vulva after treatment. A significant number of patients remained disease free with no evidence of distant metastases or evidence of any disease with 5 of 12 alive (58%), and an additional 2 of 12 patients who expired without evidence of disease. While 2 out of 12 patients exhibited evidence of active disease, the patients are alive and are undergoing additional therapy. Only 2 of 12 patients to date have expired with evidence of disease and 1 patient expired with disease status unknown. Biopsies were done of primary and/or node in 4/12 (33%) which were negative for disease. Organ preservation was achieved in 100% of patients. Conclusions: This treatment schema provided excellent tolerance with sustained local control. All patients obtained clinical complete response and were able to avoid pelvic exenteration surgery as well as maintain preservation of their bladder and rectal function.
Aleksandar Stefanovic
Clinic for Obstetrics and Gynecology, Clinical Center of Serbia
Title: Fertility sparing surgery in early stages of cervical cancer
Biography:
Aleksandar Stefanović finished Medical School University of Belgrade (1977), MD (1995), PhD (1996), and academic special studies Obstetrics and Gynecology (1994), with 25 years of clinical experiences, working at Clinic for Gynecology & Obstetrics Clinical Centre of Serbia, which is the biggest one in whole region. He worked as a gynecologist for 18 years. His present position at the Clinis is Chairman of Clinic for Obstetrics and Gynecology, Clinical Center of Serbia-President of Expert Committee for Cervical Carcinoma Prevention and Control, also Member of Advisory Board for the implementation of Screening and Early Detection of Breast, Cervical and Colorectal Carcinoma Programme. He is the Author of National Good Practice Guidelines for Diagnosis and Treatment of Cervical Carcinoma, - Member of Multidisciplinary Team for Gynecologic Oncology, Clinic for Obstetrics and Gynecology, Clinical Center of Serbia. His representative publications is about 50 publications in CC/SCI expanded and JCR indexed, and he is an active participant on more than 50 international congresses, with total number of publication about 150.
Abstract:
The concept of fertility-preserving surgery in early cervical, radical trachelectomy with stage IA2 or IB disease. Trachelectomy is a conservative oncologic operation with aim to preserve fertility in early stages of cervical cancer female patients that have realized reproduction. Excised structures in trachelectomy are: cervix, upper 1/3 of vagina, parametria and paracolpia, with preservation of uterine corpus. After removing the vaginal fornix and cervix, uterovaginal anastomosis with non resorptive suture is performed. Indications for trachelectomy are, patients up to 45 years of age who which to conserve fertility with negative lymph nodes, no distant metastatic disease, FIGO stage cervical cancer staged IA1, IA2, IB1 (tumour size ≤ 2cm with negative lymph nodes ), with adequate cervical length, no evidence of expansion of malignat proces on the upper part of the cervical cannal, squamocellular carcinoma, rarely cervical adenocarcinoma, negative lymph nodes intraoperatively, no metastatic disease, clear resected margins. There is an ongoing debate regarding the need for uterine vessels preservation. Some authors have proved that the preservation of the uterine artery is associated with more favorable restoration of the reproductive function. Others claim that preservation of the uterine vasculature is not necessary for fertility as obstetrical outcomes are similar to those of the historical vaginal radical trachelectomy cohorts. Simple trachelectomy as alternative to radical trachelectomy in selected cases (parametrial involvement rate < 1% in patients with IB1 ≤ 2 cm, negative lymph nodes and stromal invasion ≤ 10 mm).
Karl R Aigner
Medias Klinikum GmbH & Co KG, Germany
Title: Isolated pelvic perfusion with chemofiltration for advanced stage IVa and recurrent cervical cancer
Biography:
Karl Reinhard Aigner is Medical Director of the Department of Surgical Oncology in Medias Klinikum Burghausen (Bavaria) / Germany. He had his surgical training in cardiovascular surgery at Friedrich-Alexander University in Erlangen. At Justus-Liebig University Giessen he specialized in surgical oncology, focusing on vascular techniques of drug delivery such as Implantofix and Jet Port catheters, and in 1981 first performed a technique of isolated perfusion of the liver with heart-lung machine in man. Furtheron he developed various techniques of segmental vascular isolation of body segments and organs, and the stopflow technique with adequately designed catheters. In 1982, together with Prof. Stephens from Sydney, he initiated the biannual International Congress of Regional Cancer Treatment (ICRCT) and from 1987 to 1991 was president of the International Society for Regional Cancer Therapy. From 1985 to 1998 he was managing editor of the International Journal Regional Cancer Treatment. He is author of numerous publications and book chapters, lectured and performed teaching operations on vascular perfusion techniques and oncological surgery in Europe the United States and Asia.
Abstract:
Introduction: In advanced or recurrent cervical cancer, radical resections with local irradiation may no longer be radical because of micro-invasion behind the resection margins. The more local tumor progression becomes evident, the more therapies are intensified until a point is reached where therapy-related toxicity may outweigh clinical benefit and quality of life. Material & Methods: In order to include the entire pelvis with regional lymphnodes into an isolated perfusion circuit, the femoral artery and vein were cannulated with balloon catheters under general anesthesia. Both balloons were placed above the aortic and vena cava bifurcation. Both upper thighs were blocked with pneumatic cuffs. Because of tenfold increased cytotoxicity of Adriamycin and Mitomycin, and unaffected cytotoxicity of Cisplatin under hypoxia, the 15 minutes isolation perfusion of this three drug combination was performed under hypoxic conditions followed by 30–45 minutes of chemofiltration for systemic detoxification. Results: In a patient with advanced stage IVa disease with tumor invasion of the bladder, lymphnodes and both parametria, after ineffective systemic chemotherapies, a histologically complete remission after hysterectomy was revealed after four courses of isolated pelvic perfusion. There was no significant systemic or local toxicity and the patient is in continuing complete remission after 11 years. In eight patients with advanced and pre-treated recurrent cervical cancers, after four isolated pelvic perfusions, the median progression-free survival was 202 days, the median overall survival time 245 days. Two patients actually survive recurrence-free for 20 and 36 months. Conclusion: Isolated hypoxic pelvic perfusion with chemofiltration is a valuable method for therapy of advanced or recurrent cervical cancers, refractory to conventional therapies.
Aida Moeini
University of Southern California, USA
Title: Combined vagino-abdominal approach for management of Vesicovaginal fistulas: A 10 years' experience
Biography:
Aida Moeini is Specialist in University of Southern California, USA. She is extending his valuable service as a Specialist and has been a recipient of many award and grants. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a Specialist reflect in her wide range of publications in various national and international journals.
Abstract:
Background: Vesicovaginal fistulas (VVF) are an uncommon but serious complication of gynecological surgery. Aim: The aim of this study was to report our experience with the repair of VVF using combined vaginal and extraperitoneal abdominal approaches. Materials & Methods: Between 2000 and 2012, 15 consecutive females with VVF were managed with combined vaginal and extraperitoneal abdominal procedures. After assessment by voiding cystourethrography and urethrocystoscopy, the operation was performed at the standard lithotomy position. Result: Fifteen patients were included in this study with mean age 51.8±11.9 years. The mean fistula size was 2.1±0.7 cm and all of them were located in supra-trigonal region except one case that fistula defect extend to the bladder trigon. 14 patients reported complete resolution of urinary incontinence during mean follow up of 3.5 years. Fistula was recurred in one female, 1 year after repair due to cancer recurrence and radiotherapy treatment. No intraoperative complication including massive bleeding or ureteral damage was observed. Conclusion: Our experiment with combined vaginal and extraperitoneal abdominal repair of a vesicovaginal fistula shows its feasibility and safety with good results.
Tommy Nai-Jen Chang
Chang Gung Memorial Hospital, Taiwan
Title: Pedicle perforator flaps in vulvar reconstruction – Restore the cosmesis and life quality with new generation reconstruction
Biography:
Tommy Nai-Jen Chang finished his training in the Department of Plastic and Reconstructive Surgery in Chang-Gung Memorial Hospital in Taiwan and now is now a staff and assistant professor in the department. Dr. Chang has involved in clinical practices relate to micro-vascular and micro-peripheral nerve surgeries for ten years. Dr. Chang is also experiencing in perineal reconstruction using different perforator flaps.
Abstract:
Vulvar reconstruction is challenging. Early postoperative mobilization tethers the wound, making it easily break down. Inevitable urine, stool and vaginal discharge contaminate the wound easily, resulting in infection and subsequent partial or total flap loss and may indicate further surgical debridement. Both function and aesthetic results determine satisfactory outcome. With advanced microsurgical technique, reconstructive surgeons are now able to close the wound with a perforator-based flap, and provide better restoration of its function as well as its original appearance. Different perforator flaps have been introduced in vulvar reconstruction from lower abdomen, vulvo-perineal, buttock and thigh. We recommended the use of perforator flaps from medial thigh with multiple advantages. Using perforator flaps reduces donor site morbidities by retrograde dissection of the perforator to the main pedicle without sacrificing the muscles. Harvesting the flaps from neighbor region of vulvar eliminates the requirement of microsurgical vascular anastmosis. The nature of the medial thigh provides tissue that restores similar bulk of vulvar and enhances postoperative cosmesis. Different perforators are available, including deep femoral perforator flap (also known as profunda artery perforator flap), medial ciecumflex femoral artery perforator flap, deep external pudendal artery perforator flap, and internal pudendal artery perforator flaps. In particular, the medial thigh is a region rich of perforators. Free style perforator flaps without knowing origins can also be designed safely with nice backup. Post-operative life quality was assessed using FATC-G and FATC-V questionnaires with satisfied respons. The presentation will conclude a new generation of vulvar reconstruction using the most updated technique
Yan Bin
Hubei Maternity and Child Health Hospital, China
Title: The study of the effect of tumor-infiltrating neutrophils in predicting the recurrence of cervical cancer
Biography:
Yan Bin has completed her PhD from Tongji Medical College, Huazhong University of Science and Technology (HUST) in China. Currently, she is working as a resident in the Department of Gynecologic Oncology, Hubei Maternity and Child Health Hospital in China.
Abstract:
Objective: To investigate the prognostic effect of the tumor-infiltrating neutrophils in cervical cancer, and the effect of bone marrow neutrophils on the growth and angiogenesis of U14 mice cervical cancer cell lines. Method: International Federation of Gynecology and Obstetrics (FIGO) stage I B and II A treatment-naive cervical cancer patients (N=46) were assessed for tumor-infiltrating CD66b+ neutrophils by immunohistochemistry. Results were correlated with recurrence-free survival (RFS) as end point. Bone marrow neutrophils separated form naive and tumor-bearing mouse were used to co-inoculate with the U14 mice cervical cancer cell line to observe the effect of neutrophils on the growth and angiogenesis of U14 cell line. Result: The group with a density of CD66b+ neutrophils above median in the tissue of cervical cancer was associated with shorter RFS than the group with a density of CD66b+ neutrophils below median, and the 2 groups had a statistic difference (P=0.021). The bone marrow neutrophils from the tumor-bearing mouse had the ability to promote tumor growth and angiogenesis of U14 cervical cancer cell line. Conclusion: The increasing number of the tumor-infiltrating neutrophils in cervical cancer tissues was correlated with the short recurrence free survival of the patients of cervical cancer, and the tumor environment could change the neutrophils to act in a way that favors tumor angiogenesis and tumor growth.
Yuanqing Yao
PLA General Hospital, China
Title: Robotic nerve-sparing radical hysterectomy for locally advanced cervical cancer after neo-adjuvant chemotherapy
Biography:
Yao Yuan-Qing is a professor in Department of Obstetrics and Gynecology, General Hospital of PLA, China and a professor in Nankai University, China. Professor Yao is a member of executive committee of Society of Reproductive Medicine of Chinese Medical Association. Professor Yao’s clinical expertise and research interests are minimally invasive surgery of gynecological cancer, assisted reproductive techniques and molecular mechanism of preimplantation embryo development. He performed the first case of robotic radical hysterectomy in China. Professor Yao’s research has supported by National Natural Science Foundation of China, Major State Basic Research Development Program of China
Abstract:
Objective: To evaluate the feasibility and safety of robotic nerve-sparing radical hysterectomy for Locally Advanced Cervical Cancer (LACC). Methods: In a retrospective study, data were analyzed for patients treated for cervical cancer at a center in Beijing, China, between December 2011 and September 2013. Patients were subdivided into those with early-stage disease (FIGO stage IA2–IB1) who were treated by robotic surgery (group 1), and those with LACC (stage IB2–IIB) who were treated by robotic surgery after neo-adjuvant chemotherapy (NACT). Therapeutic outcomes and complications were compared. Results: Group 1 included 32 patients and group 2 included 22 patients. Two patients in group 2 did not respond to NACT and did not undergo surgery. The operative outcomes and incidences of complications did not differ significantly between the two groups (p>0.05 for all). There were no differences in nodal yield, lengths of parametrium removed, or vaginal cuff length (p>0.05 for all). During a mean follow-up of 26 months, no patient experienced recurrence. Conclusion: Robotic nerve-sparing radical hysterectomy was found to be feasible and safe for LACC after NACT. A larger case series with longer follow-up data is needed to justify its widespread application.
Sandeep Singh
Gajra Raja Medical College, India
Title: Tele-cytology: An innovative approach for cervical cancer screening in resource-poor settings
Biography:
Dr Sandeep Singh has completed his MBBS from Gajra Raja Medical College, Gwalior affiliated to Jiwaji University, Gwalior, India from 2007-2013. He is presently associated with, Shitla sahai institute of medical science Gwalior, India. He has published 16 National and International research articles in various reputed journals and delivered paper presentations at various platforms. His core area of interest includes cervical cancer screening, generation of new screening tools and policy framing. He is actively associated with NGOs to provide health care to the underserved communities.
Abstract:
Objective: Carcinoma cervix remains a leading cause of cancer mortality among women in countries lacking any screening program. The existing screening policy and approach via conventional cytology centered mainly in Tertiary Care Center, is totally unaffordable to Indian women, especially in the remote areas. This suggests the need of depolarizing the resources via generating the near real time modalities which could be used at the door step of the needy ones. For any screening modality to be effective, it should be adequately sensitive, specific, reproducible, cheap, simple, affordable, and the most important, it should be real time to ensure wide coverage and curtail loss to follow-up. Incorporating telecytology as a screening tool could make the dream come true. Methods: Telecytology is the interpretation of cytology material at a distance using digital images. Use of mobile telecytology unit housed in a van carrying satellite equipment and the automated image capturing systems is the central theme behind this idea. The imaging equipment would be carrying out the imaging of Papanicolaou smears prepared at the screening site and sending the images to the central laboratories situated at some tertiary care level. Results: This concept could overcome the hindrance of trained cytology infrastructure in the resource poor settings and could provide an efficient and economical way of screening patients. Conclusion: There is possibility that the designed approach may not detect the entire women positive for the disease but if the desired objective was to diagnose as many cases as possible in resource poor setting, then this process offers an advantage over no screening at all.
Vincent Balaya
University Paris Descartes, France
Title: Pelvic nerve injury during radical hysterectomy for cervical cancer : Key anatomical zone
Biography:
Vincent Balaya is resident of Obstetrics/Gynecology in the departement of gynecological, oncological and breast surgery at Georges Pompidou European Hospital in Paris and researcher at the Human Anatomy departement at University Paris Descartes. Fabrice LECURU is University professor at the University Paris Descartes and head chief of departement since 2007. Its main poles of interest are the mini-invasive surgery applied to the gynecological cancers, and the surgery of the advanced cancers of the ovary. He developed these various techniques in the department of the HEGP, so offering to the women of the less noxious effective treatments for them. He also developed a very strong activity of clinical research and teaching on these themes. The department of the HEGP was certified by the AP-HP, " Expert Center " for the breast cancer treatment and the gynecological cancers
Abstract:
Objectives: By using 3D reconstruction, to provide key-points of surgical neuroanatomy of the female pelvis to improve nerve-sparing radical hysterectomy. Method: Computer-assisted anatomical dissection of three human female pelvis fetus of 12,15 and 24 weeks of gestation, a classic dissection of a 88-years-old woman and a review of the surgical literature up to 2014 on Medline. Results: The Superior Hypogastric Plexus (SHP) divides underneath the promontory into two Hypogastric Nerves (HN). HN descend along the lateral side of the rectum, then run postero-medially to the ureter and in the lateral part of the uterosacral ligament until the superior angle of the Inferior Hypogastric Plexus (IHP). Pelvic Splanchnic Nerves (PSN) emerge from ventral rami of S2, S3 and S4 and run on the postero lateral side of the rectum until the posterior edge of the IHP. IHP extend from the anterolateral face of the rectum and passes lateral to the cervix and the vaginal fornix. Efferences of the IHP are constituted by vesical, vagino-rectal and inferior rectal plexus. Discussion: Preservation of SHP necessitates an approach on the right side of the aorta and a blunt dissection of the promontory before lomboaortic lymphadenectomy. To preserve HN only the medial fibrous part of the uterosacral ligament should be resected. The middle rectal artery, the deep uterine vein and the ureter should be identified to preserve PSN and IHP during resection of paracervix. Vesical branches can be preserved by blunt dissection of the posterior layer of the vesico-uterine ligament after identifying the inferior vesical vein.
- Gynecologic Oncology
Gynecologic Oncology treatment
Breast cancer
Session Introduction
Ingegerd Hellstrom
University of Washington, USA
Title: Detection of the HE4 protein in urine as a biomarker for ovarian neoplasms
Biography:
Dr. Hellstrom’s main area of interest is in ovarian cancer. Her most recent research activity is in the area of tumor diagnostics, they have identified two new biomarkers for the diagnosis of ovarian carcinoma by assaying serum and other body fluids. She is currently conducting a pilot study to provoke an immune response to ovarian cancer cells by “silencing†TGF-beta, a gene which can normally suppress the immune system
Abstract:
We have measured HE4 levels in urines and sera from normal donors, patients with ovarian neoplasms of low malignant potential (LMP) and ovarian cancer patients and correlated levels with clinical factors in ovarian cancer patients. Archived samples from controls, patients with LMP tumors and ovarian cancer were tested using commercial assays, as were serially collected serum and urine samples from women treated for stage III/IV serous ovarian cancer. Stage I/II and Stage III/IV serous ovarian cancer patients had HE4-positive urines similar to serum samples when tested at the same level of specificity (95%), while urine HE4 was more sensitive from patients with LMP tumors where 28% were HE4-positive versus 4% of sera (P=0.002). Mean levels of serum CA125 and HE4 decreased comparably in patients during initial treatment regardless of their primary platinum response, but mean urine HE4 levels decreased only 7% in primary platinum resistant patients while decreasing 68% in those who were sensitive. By 7 months after diagnosis, urine HE4 levels were higher in primary platinum resistant patients compared to those who proved to be sensitive (p=0.051) and persisted 12 months after diagnosis (p=0.014). HE4 values in urine also became positive in advance of clinical recurrence in several women while serum HE4 and serum CA-125 remained normal. We conclude that measuring HE4 in urine complements serum assays for the detection of ovarian cancer and propose that a “blinded†prospective study is performed on a much larger patient material and including women at increased risk for ovarian carcinoma
Liane Deligdisch
Mount Sinai Medical Center, USA
Title: Early Ovarian Carcinoma: Clinical-Pathological Correlations and Molecular Studies.
Biography:
Liane Deligdisch, MD is Professor of Pathology and Obstetrics-Gynecology and Reproductive Science, The Mount Sinai Medical Center and School of Medicine, New York, NY, USA. Nathan G. Kase, MD is Professor in Obstetrics-Gynecology and Reproductive Sciences, Professor of Endocrinology and Dean Emeritus, The Mount Sinai School of Medicine, New York, NY, USA. Carmel J. Cohen, MD is Professor of Obstetrics, Gynecology and Reproductive Science and Professor of Gynecologic Oncology, Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York, NY, USA. Research interest includes Anal Intraepithelial Lesions,Cervical Cancer,Cervical Intraepithelial Neoplasia,Cervicitis,Endometrial Cancer,Endometrial,Hyperplasia,Endometrial Intraepithelial Neoplasia,Endometriosis.
Abstract:
Ovarian carcinoma (OC) is the most lethal gynecological tumor, most cases being diagnosed in late stages due to paucity of symptoms and absence of specific tumor markers in early stages of the disease. Preinvasive (dysplastic) lesions have been described in the ovaries by histologic, morphometric and immunohistologic methods, and in the fallopian tubes. Five year survival of OC is 30-35% in all stages and 80-90% in the rarely diagnosed stage I when the tumor is confined to the ovary(ies). Review of 99 cases of Stage I OC revealed a shift in the histologic distribution of early OC which are mostly non-Serous OC (NSOC) vs. the predominance of Serous OC (SOC) in all stages. The predominant early OC are endometrioid, mucinous and clear cell carcinomas. The rare Stage I SOC are detected randomly, most due to intense follow-up of high-risk patients (BRCA1/2 positivity, personal or family breast cancer). The clinical background of the patients is different in the NSOC patients who are younger, often hyperestrogenic and infertile, with coexisting endometriosis, endometrial polyps/hyperplasia/neoplasia, symptomatic lesions leading to an earlier diagnosis than the mostly asymptomatic SOC. Stage I OC is a heterogeneous group of tumors requiring different therapeutic approaches. Our recent molecular studies including markers, some of which targeting stem cells (HLA, Notch 3, Betacatenin, GLI-2, Cyclin E) offer an insight into early carcinogenesis of OC and may have an impact on therapeutic choices of this elusive and often deadly neoplasm.
Gwyn Richardson
University of Texas Medical Branch, USA
Title: Bilateral salpingectomy: An opportunity for cancer prevention
Biography:
Gwyn Richardson is an Assistant Professor of Gynecologic Oncology at the University of Texas Medical Branch in Galveston TX. She is also the Associate Clerkship Director for the Obstetrics and Gynecology 3rd year Medical School Clerkship. She holds the Francis Eastland Conally Professorship in Gynecologic Oncology
Abstract:
Objective: Among cancer patients, thromboembolic events are a common and potentially fatal complication. This study was designed to determine the incidence of thromboembolic events in relation to the diagnosis, treatment and progression of disease in cervical cancer patients. Study Design: We reviewed records for cervical cancer patients treated at a single institution from 1995-2008. Data collected included demographic characteristics, stage, histologic type, treatment received, time to recurrence, salvage therapy, thromboembolic event and its temporal relationship to cancer diagnosis, and survival. Results: Seven hundred sixty-six patients were diagnosed with invasive cervical cancer during study period. Records were available on 747 patients for mean follow up of 33 months. The incidence of thromboembolic events in cervical cancer patients was 9.0%. Incidence of thromboembolic events was higher in patients with advanced stage. There was no statistically significant difference when accounted by race, smoking history or tumor histology. As expected in patient with advanced stage, treatment modality was related to increased incidence of thromboembolic events. Survival analysis data showed that patients with thromboembolic events had a significantly poorer survival than patients without thromboembolic events. Conclusions: Thromboembolic events at the time of cervical cancer diagnosis are associated with advanced disease and poor prognosis. Following therapy, thromboembolic events may be the first sign of recurrence and confers a grim prognosis.
Magdalena Klink
Polish Academy of Sciences, Poland
Title: Anti-ovarian cancer cells activity of nitric oxide donors
Biography:
Magdalena Klink has completed her PhD in 1994 and habilitation in 2005, at the University of Lodz. Since 2004 she has been working at the Institute of Medical Biology, Polish Academy of Sciences in Lodz, now an associate professor. She was the manager of several research projects funded by national organizations and the contractor of project from the European Regional Development Fund (POIG). She is supervisor in two finished doctoral. She is the author of 48 scientific publications and editor of a monograph. For several years, she serves as editor of the Mediators of Inflammation. In WSZKiPZ lectures in biology with genetics
Abstract:
Despite a significant improvement in the conventional anti-ovarian cancer therapies, tumor cell resistance to various cytostatic drugs remains a relevant problem. The Nitric Oxide (NO) donors - synthetic compounds that release NO, in vivo and/or in vitro, have been considered as a potential anti-cancer agent. The effect of NO donors on the biological activity of ovarian cancer cells in the presence or absence of cisplatin was determined. Two members of NONOates family with different half-live time were used. Various ovarian cancer cell lines as well as cancer cells isolated from ascites of patients with advanced stage of diseases were used in these studies. We found that NO donors inhibited the ovarian cancer cells growth mainly by induction their apoptosis. Moreover, NO donors decreased the activity of signaling proteins (STAT3 and AKT) involved in uncontrolled proliferation of ovarian cancer cells. We also found that NO donors have low ability to inhibit the production and secretion of pro-metastatic factors. Our study showed that NO donors significantly enhanced the susceptibility of ovarian cancer cells to cytotoxicity of cisplatin. We demonstrated that NO donors increased the number of late apoptotic ecrotic ovarian cancer cells treated with cisplatin. We also found that none of NO donors or their combination with cisplatin affects the expression of genes (ABCB1, BIRC5 and PTEN) involved in the drug resistance. The obtained results show that NO donors have a high potential of being a supporting compounds in the ovarian cancer therapies
Biography:
Adrian Senderowicz has served as Senior Vice President and Chief Medical Officer since September 2015. Dr. Senderowicz was most recently Chief Medical Officer and Senior Vice President, Clinical Development and Regulatory Affairs at Ignyta, Inc. Previously, he was Vice President, Global Regulatory Oncology at Sanofi, Chief Medical Officer at Tokai Pharmaceuticals, and Senior Medical Director, Oncology Clinical Development at AstraZeneca. Before his tenure at AstraZeneca, Dr. Senderowicz held a variety of leadership positions at the U.S. Food and Drug Administration Division of Oncology Drug Products in the Center for Drug Evaluation and Research and a variety of clinical and research positions with the National Cancer Institute/National Institutes of Health (NCI), including Investigator and Chief, Molecular Therapeutics Unit. He currently serves as a director of Puma Biotechnology, Inc., a publicly traded biopharmaceutical company. He completed his Internal Medicine residency training at the Icahn School of Medicine at Mount Sinai, and a Clinical Oncology Fellowship at the NCI. Dr. Senderowicz holds an M.D. degree from the School of Medicine at the Universidad de Buenos Aires in Argentina.
Abstract:
Background: Cerulean Pharma, Inc. is developing CRLX101, an investigational NDC with a camptothecin payload. CRLX101 has been investigated in more than 350 patients to date. Regimens administered have included monotherapy and combination therapy with bevacizumab in patients with renal cell carcinoma (Keefe, ASCO 2015, abstract #4543) and platinum-refractory ovarian cancer (Krasner, ASCO 2014, abstract #5581). Based on preclinical and early clinical data suggesting synergy between taxanes and topoisomerase 1 inhibitors, we started a Phase 1b trial for this combination in patients with platinum-resistant ovarian cancer. Methods: Cohorts of 3 patients were accrued in this trial. Two dose levels were planned as dose level 1: CRLX101 12 mg/m2 (every other week) in combination with paclitaxel 80 mg/m2 (weekly, 3 weeks on/1 week off); and dose level 2: CRLX101 15 mg/m2 (every other week) in combination with the same regimen of paclitaxel 80 mg/m2. The primary objective was to determine the maximum tolerated dose (MTD) administered in combination with weekly paclitaxel. Secondary objectives included pharmacokinetics, overall safety, tolerability, and initial signs of clinical activity of CRLX101 with weekly paclitaxel. Results: As of March 11, 2016, a total of 9 patients have been enrolled and treated at dose levels one (n=3) and two (n=6) and all 9 patients are evaluable for safety and response. Median age is 61 years (range, 49–73); median number of previous regimens was 3 (range, 1–4); GOG score performance status was 0 (6 patients) or 1 (3 patients). No dose-limiting toxicities have been reported at either dose level, thus the RP2D for this schedule is CRLX101 15 mg/m2 (every other week) and paclitaxel 80 mg/m2 (3 weeks on/1 week off). Adverse events (AEs) suspected to be related to study treatment were fatigue (6 patients, 67%), neutrophil count decreased (4 patients, 44%), nausea (4 patients, 44%), vomiting, alopecia, headache, infusion-related reaction, and urinary tract infection (all seen in 2 patients, 22%), as well as dizziness, sinusitis, ALT increased, AST increased, constipation, cystitis noninfective, dyspnea, anemia, and peripheral sensory neuropathy (all seen in 1patient, 11%). The only grade ≥3 treatment-related AE was neutropenia, which occurred in 2 patients (one grade 3 and one grade 4). Partial response and stable disease rates were 56% (5/9), and 11% (1/9), respectively. Moreover, CA125 responses (≥50% decline from baseline) were demonstrated in 33% of patients (3/9). As of March 11, 2016, 2 patients (at 15 mg/m2) are still receiving therapy. Conclusions: CRLX101 given every other week in combination with weekly paclitaxel (3 weeks on/1 week off) has demonstrated early signs of antitumor activity and has been generally welltolerated to date in patients with platinum-resistant ovarian cancer.
Klesia Pirola Madeira
Federal University of Espirito Santo, Brazil
Title: Breast cancer: Estrogen receptor SNPs as risk markers and hormone receptors expression as therapeutic drivers
Biography:
Klesia Pirola Madeira obtained her Doctoral degree in Biotechnology from the Federal University of Espirito Santo (UFES) in 2013. She is currently a Professor in the Department of Pharmacy and Nutrition at UFES. Her research focuses on using in vitro systems to identify novel compounds that effectively target the PI3K. Her findings will be important in designing more efficacious therapeutics against various cancers that rely on this pathway for their survival.
Abstract:
Breast cancer (BC) is the second leading cause of cancer-related death in US women. The ability to effectively treat patients can be complicated by risk factors including single nucleotide polymorphisms (SNPs) in the estrogen receptor gene (ESR1) and misdiagnosis of hormone receptors expression levels. Recently, single nucleotide polymorphisms in PvuII and XbaI have been discovered in the ESR1 gene. To study the significance of these changes, we analyzed the allelic frequenices of these SNPs in samples isolated from patients with BC. We found higher P and X alleles frequencies in Erα-positive BC. Furthermore, the pp and xx genotypes were found exclusively in patients with HT-TMX responsive BC. Analysis of the expression levels of the ER status in 61 BC cases using SP1 and 1D5 monoclonal antibodies revealed a high concoradance rate (96.7%) betwen both antibodies based on immunohistochemical analysis applying the Allred score. Similar analysis of the PgR status in 53 BC cases revealed that the monoclonal antibodies PgR636 and SP42 were suitable for diagnositic purposes while monoclonal the antibody ab62621 should be excluded due a lack of specifity. Taken together, we have revealed that the P allele is a novel biomaker for BC, confirmed that both the pp and xx genotypes enhance responsiveness to chemotherapy, and identified monoclonal antibodies that improve the accuracy of detecting ER and PgR status in BC patients.
Jan Blaakaer
Aarhus University Hopital, Denmark
Title: Is it possible to define an optimal time for chemotherapy after surgery for ovarian cancer?
Biography:
Professor, M.D., DMSc., Department of Gynaecology, Aarhus University Hospital. I graduated, as a medical doctor from Odense University in 1982 and became a specialist in gynecology and obstetrics in 1991. I became a Doctor of Medical Science (DMSc) in 1998 with a thesis submitted to Copenhagen University on ovarian cancer. All in all, I am the author of 135 peer-reviewed publications dealing with topics in gynecology and obstetrics. Moreover, I have written more than 80 publications in textbooks, booklets and newspapers. For a period of five years, I was a member of the European Board and College of Obstetrics and Gynecology (EBCOG), 1996-2000. I was Vice-president as well as President of the Danish Society of Obstetrics and Gynecology (DSOG), and for several years a member of the executive committee of the Nordic Society of Obstetrics and Gynecology (NFOG). At the moment I am member of the executive board of the Nordic Society of Gynecological Oncology (NSGO). My research is primarily concentrated on ovarian cancer and HPV related cancers, especially cervical and vulvar cancer. At the moment I am supervisor for 18 Ph.D. students and four research years students.
Abstract:
Objective: To investigate the actual time from primary surgery for ovarian cancer (OC) to initiation of chemotherapy (TI) amongst Danish women in 2005-2006, and to compare the survival for groups with early initiation (≤ median TI) and late initiation of adjuvant chemotherapy (>median TI). Methods: All Danish women who underwent surgery for OC in the period between 1 January 2005 to 31 December 2006 recorded in the Danish Gynaecological Cancer Database (DGCD) were included. The five-year survival was estimated overall and by TI exposure. The Cox proportional hazard regression analysis was used to compute the adjusted hazard ratio (HR). Results: The median TI was 32 days (25-75% quartile: 24 days; 41 days). The strongest prognostic factors for death were residual tumour and the International Federation of Obstetrics and Gynecology (FIGO) stage. The unadjusted HR for death in patients with TI > 32 days compared with TI ≤ 32 days was 0.85 (95% CI: 0.70; 1.04), p-value 0.12. When adjusted for residual tumour and FIGO-stage the HR was 1.13 (95% CI: 0.92; 1.39), p-value 0.26. The overall five-year survival was 42.8%, (95% CI: 38.9%; 46.5%). Conclusions: This nationwide population-based cohort study revealed a non-significant increased risk of death for patients with TI>32 days compared with the reference TI≤32 days. The strongest prognostic factors were residual tumour after surgery and FIGO-stage. The overall five-year survival was 42.8% (95% CI: 38.9%; 46.5%).
Liselotte Mettler
University Hospitals Schleswig-Holstein Campus Kiel ,Germany
Title: Surgical and medical therapy of endometriosis with hormonal and non-hormonal targets
Biography:
Liselotte Mettler was Deputy Director of the Department of Obstetrics and Gynecology, University Hospitals Schleswig-Holstein and from 2002-2008 also Head of the Gynecological Endocrinology and Reproductive Medicine Division at the same department. She is executive Director of the International Academy of Human Reproduction (IAHR) and believes in the goals and activities of this Scientific and Clinical Academy. She is president of the 16th World Congress of Human Reproduction in March 2015 in Berlin, Germany,Her research interast are in Reproductive Medicine, Gynecologic Endoscopic Surgery, Endometriosis, Ocarian tumours, hysterectomies
Abstract:
Study question: To evaluate 3 therapy strategies - Hormone therapy, surgery, and combined treatment for genital endometriosis in a university based teaching hospital. Summary answer: In the quest to find the most effective treatment of genital endometriosis, this clinical randomized study shows the lowest incidence of recurrence with combined surgical and medical treatment and improved pregnancy rate in any medically treated patients with or without surgery with the highest cure rate in the combined treatment group. What is already known? Endometriosis is a systemic disease, which needs various treatments as up to date no single treatment is successful in every patient. Study design, size and duration: Four hundred fifty patients with genital endometriosis, stages I-III, aged 18 to 44 years, before first laparoscopy: Patients were randomly assigned to 1 of 3 treatment groups, hormone therapy, surgery, or combined treatment. Patients were reevaluated at second-look laparoscopy, at 2 to 2 months after 3-month hormone therapy in groups 1 and 3 and at 5 to 6 months in group 2 (surgical treatment alone). Outcome data were focused on the endometriosis stage, recurrence of symptoms, and pregnancy rate. Main results and role of chance: All treatment options, independent of the initial Endoscopic Endometriosis Classification stage, achieved an overall cure rate of R50%. A cure rate of 60% was achieved with the combined treatment, 55% with exclusively hormone therapy, and 50% with exclusively surgical treatment. Recurrence of symptoms was lowest in patients who received combined treatment. Significant benefit was achieved for dysmenorrhea and dyspareunia. An overall pregnancy rate of 55% to 65% was achieved, with no significant difference between the therapeutic options. Limitations and reasons for caution: Although a good number of patients were included into this RCT, no clear picture of an optimal therapy could be obtained. In this still complex and poorly understood disease therefore all know therapy concepts should be used for the treatment of patients. Wider implications of the findings: After an initial diagnostic laparoscopy, be careful with repetitive laparoscopic surgeries.
Ines Vasconcelos
Charité Medical University of Berlin, Germany
Title: Is there a role for chemotherapy in the treatment of invasive borderline ovarian tumors?
Biography:
Dr. Ines Vasconcelos has completed her medical degree with honors at the University of Coimbra in Portugal and her doctoral studies with Magna Cum Laude at the Charité Medical University in Germany. She has published in several international peer-reviewed high-impact journals and serves as a member of the editorial board of the journal Advances in Modern Oncology Research (AMOR). She is currently working at the Berlin Oncological Center Kurfürstendamm
Abstract:
Borderline ovarian tumors (BOTs) were first described by Taylor in 1929 and have been a challenge for both pathologists and oncologists. BOT is a disease of younger, fertile women, generally with a benign course; however, a minority of patients progress and eventually succumb to the disease. Although the corrected survival for patients with disease confined to the ovary is 100% at 15 years, 30% of patients with serous BOT with invasive implants will develop persistent or recurrent tumor, most commonly low-grade ovarian serous carcinoma. For the group of patients with invasive implants, there is no consensus regarding standard therapy. At present, chemotherapy is offered mostly to patients with invasive implants, regardless of histological subtype. However, response to these agents remains suboptimal with recurrence estimates for patients for patients with BOT with invasive implants undergoing adjuvant treatment remaining high at 44.0%. In this presentation we will discuss the current evidence, or lack of thereof, to support the use of adjuvant treatment in patients with invasive implants in the primary treatment setting.
Morva Tahmasbi Rad
Goethe University, Germany
Title: Learning curve for laparoscopic staging of early and locally advanced cervical and endometrial cancer
Biography:
Morva Tahmasbi Rad is Specialist in Obstetrics and Gynecology at Goethe University, Germany. She is extending his valuable service as a Specialist and has been a recipient of many award and grants. Her research experience includes various programs, contributions and participation in different countries for diverse fields of study. Her research interests as a Specialist reflect in her wide range of publications in various national and international journals.
Abstract:
Background: Laparoscopic staging is rapidly evolving as an important surgical approach in the field of gynecology oncology. However, the specific learning curve associated with this approach remains poorly investigated. This study aimed to evaluate the learning curve for laparoscopic staging of uterine cancers. Methods: A series of 28 consecutive laparoscopic hysterectomies with or without pelvic and/or para-aortic lymph node sampling for the treatment of early and locally advanced endometrial or cervical cancer were performed between July 2008 and January 2011. The analyses of the learning curves of the institution were performed for 20 patients who had undergone pelvic lymphadenectomy and/ or para-aortal lymph node sampling. The learning curve period has also been compared with the last 26 patients who received laparotomy staging (“open†group) due to the same diagnosis and by the same surgical team. To assess the short and long-term outcomes, we used validated questionnaires to record the clinical and follow-up results, any complaints or subjective reports from the patients, and details of their quality of life. All data were collected prospectively in a database and reviewed retrospectively. The learning was evaluated using the cumulative sum (CUSUM) method. Results: The CUSUM learning curve consisted of two distinct phases: phase 1 (the initial 9 cases) and phase 2 (the subsequent cases) which presented the mastery phase, with the operative time of 397.7±63.5 versus 300.6±19.4 min (p>0.0001). The significance of the difference between the two phases and “open†group changed in terms of number of lymph nodes retrieved, intra-operative blood loss and hospital stay. The conversion rate of phase 1 was higher than phase 2 [2 (22.2%) and 1 (9%), respectively]. Conclusion: This series confirms previous study findings concerning the feasibility and the safety of laparoscopic staging and provides information for surgeons in single centers considering adopting an endoscopic strategy to monitor the different aspects of outcomes during the implementation process for internal benchmarking. The operative outcome of laparoscopic staging intervention improves with experience. The data reported in this article suggest that after a learning curve of 9 patients, a relevant improvement at least regarding the duration of the operation can be achieved for experienced surgeons who start performing laparoscopic staging of uterine cancers. However, due to the limited number of patients as well as number of para-aortic lymph node sampling procedures, further studies are required for firm conclusions to be drawn.
Hossam El Sokkary
Alexandria university, Egypt
Title: Role of pelvic lymphadenectomy in stage 1A endometrial carcinoma diagnosed preoperatively by pelvic ultrasonography and CT scan
Biography:
Hossam Hassan Aly Hassan El Sokkary is Lecturer of Obstetrics and Gynecology, Alexandria University, Alexandria, Egypt. He was Obstetrics and Gynaecology Residents at El Shatby Alexandria University Hospital, Alexandria, Egypt from 20 October 1996 to 19 October 1999. He was Assistant Lecturer from 4 January 2004 to 22 September 2008
Abstract:
Introduction: Endometrial cancer is the commonest gynecological cancer mostly affecting women in the postmenopausal age group. There is a debate regarding the need of pelvic lymphadenectomy in managing stage 1A diagnosed preoperatively, we try to evaluate this need. Objective: To evaluate the role of pelvic lymphadenectomy in stage 1A endometrial carcinoma diagnosed preoperatively by pelvic ultrasonography and CT scan as microscopic invasion of pelvic lymph nodes will not be seen by this imaging technique. Methods: 60 cases of endometrial carcinoma diagnosed by fractional curettage and proved to be stage 1A preoperatively by clinical examination, vaginal US and CT scan (negative myometrial invasion, ascites, LN spread and local spread) underwent total abdominal hysterectomy with salpingo-oopherectomy, peritoneal wash for cytology, omentectomy and pelvic lymphadenectomy (external iliac and obturator groups) after written informed consent. Histopathology of the uterus, tubes, ovaries, omentum and cytology of peritoneal wash were done for surgical staging, in addition histopathology of pelvic LN was done. Results: Histopathology of the cases revealed the following: 52 cases were endometrioid adenocarcinoma distributed as follows: 10 patients were grade 1, 35 patients were grade 2 and 7 patients were grade 3. Eight cases were serous papillary adenocarcinoma, 3 of them were grade 1 and 5 cases were grade 2. As regards myometrial invasion 9 cases of endometrioid carcinoma show invasion, 1 of grade 1, 3 of grade 2 and 5 of grade 3 in comparison to 4 cases of papillary serous adenocarcinoma 1 of grade 1 and 3 of grade 2, so 13 cases have been proved by histopathology to have myometrial invasion. As regards histopathology of pelvic LN 12 cases out of 60 have been proved to have metastatic lesion. Conclusion: There is no need for lymphadenectomy in stage 1A diagnosed preoperatively using CT scan and vaginal US, preventing high risk surgical intervention in this early stage
Xueqing Wang
Beijing Jishuitan Hospital, China
Title: Cell-cycle synchronization reverses Taxol resistance of human ovarian cancer cell lines
Biography:
Xueqing Wang worked in the Department of Obstetrics and Gynecology of Beijing Jishuitan Hospital as a Doctor and graduated from Peking Union Medical College Hospital with Doctoral degree in 2008. She has published many papers in reputed journals.
Abstract:
Taxol inhibits cell replication by disrupting normal mitotic spindle formation and arresting cell growth in the M phase of the cell cycle. Passage through mitosis is an absolute requirement for Taxol-induced death. The replication time of some ovarian cancer cells is approximately 27 h and resistant cell lines even more longer. Results from our laboratory indicates that most cells were in G0/G1 or S stage during the whole cells cycle and the resistant cell lines have a significantly higher proportion of cells existing in the G0-G1 stage of the cell cycle compared to the sensitive cell lines. Thus, a disparity exists between the longer doubling time of cancer cells (27 h) and the shorter window of Taxol action (3 h-9 h), as such most cells do not occupy the M stage during the short window of Taxol action. We speculated that formation of drug resistance toward Taxol in ovarian cancer could be partly attributed to the longer doubling time of these cells. We used cell-cycle synchronization to test the above assumption. Cell-cycle synchronization resulted in an increase in the number of cells passing through the M stage at a given time and reduced the toxicity of Taxol toward cells in the non-proliferative phase, improving its effectiveness and decreasing the chance of drug-resistant formation.
Bishoy Y A El-Aarag
Menofia University, Egypt
Title: Novel phthalimide analogs as anti-angiogenic and anti-cancer agents
Biography:
Bishoy El-Aarag has awarded PhD degree in the field of medical Biochemistry (Cancer Science and Therapy) through a scientific channel between Egypt (Menoufia University) and Japan (Okayama University). He works as a lecturer of Biochemistry at Faculty of Science, Menoufia University, Egypt
Abstract:
Phthalimide moiety is one of thalidomide metabolites and might be the effective part of thalidomide toward many diseases. The mode of action of thalidomide in cancer therapy mainly depends on its immunomodulatory and anti-angiogenic activity, therefore, the current study focused on the efficacy of the newly synthesized phthalimide derivatives as immunostimulatory/immunosuppressive agents against immune cells, and their growth inhibitory effect against various cancer cell lines, as well as their anti-angiogenic activity. A facile synthetic approach of novel phthalimide dithiocarbamate and dithioate analogs 4a-k, 5a-e and 5g-k was achieved by the reaction of N-chloromethyl or N-bromoethylphthalimide with carbon disulfide (CS2) and different amines. Phthalimide derivatives 5e and 5i exhibited the highest cytotoxic activities against MCF-7 and Hep-G2 cells. Both derivatives 5e and 5i inhibited nitric oxide (NO), tumor necrosis factor-α (TNF-α), vessel endothelial growth factor (VEGF) and its receptor (VEGFR). Derivative 5e showed immunosuppressive activity through its inhibition of immune cell functions and proliferation. Taken together, our study improved that some of the newly synthesized phthalimide derivatives may act as anti-angiogenic and anti-cancer agents
Kannan Vaidyanathan
Pushpagiri Institute of Medical Science & Research Center, India
Title: Mutation pattern in BRCA1/2 genes in Indian hereditary breast/ovarian cancers
Biography:
Kannan Vaidyanathan, MBBS, MD (Biochemistry) did Post-doctoral fellowship from Indian Institute of Science, Bangalore, India. He is Professor & Head, Department of Biochemistry and Deputy Medical Superintendent, Pushpagiri Medical College Hospital, Tiruvalla, Kerala. He has 75 publications, 25 indexed in PubMed, 3 textbooks and 2 textbook chapters. His textbook on Biochemistry sells ~25000 copies worldwide every year and has been translated to other languages, including Slovakian and Spanish. Awards won by him include APFCB (Asia Pacific Federation of Clinical Biochemists) Silver Jubilee scholarship (2007) and KP Sinha – PS Krishnan award for best original research article in Indian Journal of Clinical Biochemistry (2011).
Abstract:
Hereditary breast/ovarian cancers are responsible for 5-10% of breast cancers and 7-10% of ovarian cancers. Breast cancer is one of the most common cancers in Indian women. Women carrying BRCA1 or BRCA2 mutations have a lifetime risk of between 60% and 85% for development of breast cancer, and 26% and 54% for development of ovarian cancer for BRCA1, and between 10% and 23% for BRCA2. In this study, 61 breast and/or ovarian cancer patients with a positive family history of breast and/or ovarian cancer were screened for BRCA1/2 mutations. For mutation screening, conformation sensitive gel electrophoresis was used, followed by DNA sequencing, were heteroduplexes were detected. In the BRCA1 gene, 15 mutations were identified; (mutation frequency, 24.6%) and in the BRCA2 gene, two mutations were detected (mutation frequency, 3.28%). Of the BRCA1 mutations identified, 3 were novel mutations and 3 more were previously reported mutations. The mutation, 185delAG was found in 10 patients at a very high frequency of 16.4%. This mutation is detected in high proportion in Ashkenazi Jewish population (18% in breast/ovarian cancers and 1% in general population). A large number of polymorphisms were also detected in BRCA2 gene, which were normal population variants. The mutation spectrum of BRCA1/2 in other Indian studies also indicate a higher incidence of 185delAG mutation, and the important studies shall be reviewed. Haplotype analysis was carried out, and it was found to be different from Ashkenazi Jewish population. The possibility of founder mutation status need to be considered for BRCA1 185delAG mutation.
Somashekhar S P
Manipal Hospital, India
Title: Hyperthermic Intraperitoneal Chemotherapy in Ovarian Carcinoma
Biography:
Somashekhar.S.P,MS,MCh(Onco),FRCS.Edinburgh,Chairman & HOD Surgical Oncology,Manipal Health Enterprise,Graduation year 1994, MS and MCh oncosurgery 2000 year,FRCS. Edinburgh Editor in chief Indian Journal of Gynec oncology Treasurer Association of Gynecological Oncology India Consultant Surgical & Gynec. Onco & Robotic Surgeon,,Manipal Comprehensive Cancer Center,India ,Had several national and intrenstio skPublication and has authored several text Books in gynec oncology
Abstract:
Background: Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS+ HIPEC) has been proposed as treatment for recurrent epithelial ovarian carcinoma. We evaluated the outcomes of CRS+HIPEC in recurrent epithelial ovarian cancers, in Indian patients. Methods: In this prospective non-randomized study between February 2013 & January 2015, 26 patients with advanced recurrent EOC, with no extra-abdominal disease treated with secondary CRS+HIPEC in a tertiary care cancer institution, Southern India, were analyzed. Belmonte® hyperthermia (HIPEC) pump with cisplatin 100 mg/m2, 41.5-43â°C for 90 minutes, in platinum sensitive cases & doxorubicin 15 mgs/m2+cisplatin 75 mgs/m2 in platinum resistant cases was used. Results: Among twenty six patients 18 were upfront & 8 were post chemotherapy. Median peritoneal carcinomatosis Index was 9.5 (Range 3-19). The extent of cytoreduction associated with longer hospital stay (p<0.001), delayed gastrointestinal recovery (p=0.039), infections (p=0.036), and ARDS (p=0.041). Completeness of cytoreduction score CC0 achieved in 24 and CC1 in 2 patients. Bowel resection required in 34.6%. Diaphragm stripping was required in 30.7% with resection in 7.6%. Median hospital stay was 12 days (range: 10-42 days). No 30 days mortality. Bowel fistula happened in 7.6% cases requiring re-exploration, temporary stomas, and wound related complications in 26%. At median follow-up of eighteen months, 11.5% recurrences (both platinum resistant cases recurred in peritoneal cavity and one patient also in liver parenchyma) and one platinum sensitive patient recurred isolated in peritoneal cavity. One death observed at 5th month of follow up due to pulmonary embolism. Conclusions: In our Indian study, secondary CRS+HIPEC is shown to be very promising in recurrent epithelial ovarian cancers patients with no extra-abdominal disease & good performance status and can be done with acceptable morbidity, using dedicated HIPEC machine resulting in good peritoneal control of disease & DFS.
Hazan Ozyurt
Dr. Lutfi Kirdar Kartal Research and Educational Hospital, Turkey
Title: The effect of escitalopram on anastrozole plasma concentrations in breast cancer patients
Biography:
Hazan Ozyurt is specialist in Radiation Oncology and has a PhD degree in Pharmacology and Clinical Pharmacology. She has published papers about normal tissue effects of radiation, the clinical outcomes of rectal and cervical cancer after chemoradiotherapy in respect to genetic characteristics of tumors and GABAergic and nitrergic systems of brain
Abstract:
Introduction: Anastrozole, an aromatase inhibitor, catalyses the conversion of androstenedione to estrodiol in peripheral tissues in postmenopausal women through inhibition of the cytochromal P450 enzyme. Genetic variability of the metabolizing enzymes, CYP3A and UGT1A, along with BMI may affect the pharmacokinetics and pharmacodynamics of anastrozole. Although depressive mood disorder is commonly observed in breast cancer patients and escitalopram, selective serotonin transport inhibitor, is one of the used agent in the treatment, pharmacokinetic interaction through the CY3A4 that metabolizes both anastrozole and escitalopram has not been investigated before. Aim: In this study we aimed to provide data showing the effects of escitalopram on anastrozole levels in breast cancer patients that may results in toxicity or in inefficacy. Methods: Escitalopram prescribed19 female breast cancer patients on the treatment of anastrazole more than one month were included in the study. Plasma anastrozole and serum estradiol concentrations were measured before and one month after escitalopram use. Because there were inter individual variations between the last anastrozole dose and blood sampling, maximum plasma concentrations (Cmax) were back extrapolated by using the following pharmacokinetic formula LogC= LogCmax-k. t1/2. Results: The mean Cmax of anastrozole was 27±2.9 ng/mL in 19 patients. There was no significant difference in Cmaxanastrozole level in respect to previous treatments, BMI (29.9 ≤ vs 29.9>) and other drugs used currently. 12 of 19 patients completed one month escitalopram treatment and the mean Cmax of anastrazole increased from 25.2±3.1 ng/mL to 37.3±3.4 ng/mL after escitalopram (p<0.05). The median estradiol level of 19 patients were <10 pg/mLand no significant change was occurred after escitalopram administration. While the Cmaxof anastrozole increased significantly (p<0.01). After escitalopram in obese patients (BMI > 29.9), no significant change was observed in non-obese patients (BMI ≤ 29.9). Conclusion: Escitalopram increases anastrozole level and this effect is more prominent in obese than non-obese patients. Pharmacokinetic interaction through CYP 3A4 may be the responsible from these findings. The effect of BMI on this interaction may be explained by the redistribution of both drugs from adipose tissue.
Sandeep Singh
Gajra Raja Medical College, India
Title: Laser induced breakdown spectroscopy (LIBS) in cervical cancer screening: A proposed tool
Biography:
Dr Sandeep Singh has completed his MBBS from Gajra Raja Medical College, Gwalior affiliated to Jiwaji University, Gwalior, India from 2007-2013. He is presently associated with, Shitla sahai institute of medical science Gwalior, India. He has published 16 National and International research articles in various reputed journals and delivered paper presentations at various platforms. His core area of interest includes cervical cancer screening, generation of new screening tools and policy framing. He is actively associated with NGOs to provide health care to the underserved communities.
Abstract:
Objective: Cervical cancer, one of the few highly preventable cancers through successful screening, is the most common cause of death from cancer in women in the developing world. This brief hypothesis postulates a screening tool aimed to have a real time screening of cervical cancer using LIBS modality. Methods: Laser Induced Breakdown Spectroscopy (LIBS) is a spectrochemical method for determining the elemental composition of various samples present in any phase, by simultaneously vaporizing and exciting the sample and thus it improves the spectrochemical techniques by eliminating the requirement of sample pre-treatment. LIBS system focuses a high peak power laser pulse onto a targeted material to produce a laser spark or microplasma. Elemental line spectra is created, collected and analyzed by a fiber spectrophotometer since nano- to micro-grams of material are ablated in femto- to nano-seconds (depending on the laser pulse duration), the whole process can be considered as minimally destructive and real time. Results: The postulated hypothesis is aimed to use laser induced breakdown spectroscopy (LIBS) in the screening of cervical cancer as trace mineral elements act as biological signature in tissues like bones, teeth, hair, blood, etc., from the living phase and store information regarding habitat, nutrition, and other environmental conditions. Previous researches have shown significant differences in concentrations of trace elements between normal and cancerous tissue cells. Conclusion: The technique is exemplified by suggested use of LIBS in studying biological samples such as tissues, gall stones, biological aerosols and in vivo cancer detection.
- Gynecologic Surgery
Session Introduction
Yeh Chen Lee
Peter MacCallum Cancer Centre, Australia
Title: Quality of Risk-reducing Salpingo-oophorectomy in Australasian Women at High Risk of Pelvic Serous Cancer
Biography:
Dr Yeh Chen Lee is a medical oncologist and currently pursueing a clinical fellowship at the Peter MacCallum Cancer Centre under the supervision of Prof Kelly-Anne Phillips. Her subspecialty interest lies in gynaecological and breast cancer, in particular cancer prevention for women at high risk of developing breast and ovarian cancer.
Abstract:
The quality of risk-reducing salpingo-oophorectomy (RRSO) performed in Australasian women was previously reported to be suboptimal. Here we describe the quality of contemporary RRSO in women enrolled in the Kathleen Cuningham Consortium for Research into Familial Breast Cancer (kConFab) and determine if it has improved. Eligible women had high risk of pelvic serous cancer (PSC) and had RRSO between 2008 and 2014. RRSO surgical and pathology reports were reviewed; “adequate†surgery and pathology were defined as complete removal of all ovarian and extra-uterine fallopian tube tissue and paraffin embedding of all removed ovarian and tubal tissue respectively. Associations between clinical factors and “adequate†pathology were assessed using logistic regression. The data were compared with published historical data from the same cohort using Chi-square test. Of 164 eligible women followed for a median of 40 months, 80 and 48 were BRCA1 and BRCA2 mutation carriers respectively. Most RRSOs were performed laparoscopically (74%) by gynaecologic oncologists (58%). 158/159 (99%) had “adequate†surgery and 108/164 (66%) had “adequate†pathology. Independent predictors of “adequate†pathology included surgery by a gynaecologic oncologist rather than a general gynaecologist (p=<0.001), more recent year of surgery (p=0.038), and clinical notes that indicated high risk (p=0.018). Both surgery and pathology were significantly more likely to be “adequate†(p=<0.001) in this contemporary sample. Hence, the quality of RRSO performed in Australasian women has improved dramatically over time. Surgery by a gynaecologic oncologist who informs the pathologist that the woman is at high risk for PSC is associated with optimal RRSO
- Cervical Cancer
Session Introduction
Elisabeth Wikström Shemer
International Agency for Research on Cancer , Sweden
Title: Evaluation of a portable field colposcope in a non cytology based cervical cancer screening program in rural India
Biography:
Dr.Elisabeth Wikström Shemer is a Senior Consultant of Obstetrics and Gynecology and affiliated with Department of Clinical Sciences, Karolinska Institute, Stockholm, Sweden. Dr. Wikström Shemers' research focus on cervical cancer, colposcopy and improving screening methods to the underserved as well as intrahepatic cholestasis pf pregnancy. She has also invented a small. portable, battery-driven colposcope, the Gynocular to improve access to colposcopy. Dr. Wikström Shemer has been awarded the SKAPA prize for the invention of the Gynocular, Stockholm Stads innovations stipendium 2010, the Red Dot award 2013, as well as Vinnova 2009 and 2014 for developing digital health and the 33-list 2015 award. She is and MD, Ph.D in Obstetrics and Gynecology from the Karolinska Institute, Stockholm Sweden and serves as Gynius' Medical Director
Abstract:
Objectives: After the introduction of non cytological tests like visual inspection after acetic acid (VIA) or Human Papillomavirus (HPV) test, there is a paradigm shift in screening for cervical cancer. Though ‘screen and treat’ strategy is being recommended in low resource settings, the low positive predictive values of both the tests will lead to lot of overtreatment. GynocularTM is a battery-operated, portable device with three-step magnification and green-filter. Present study was conducted in a community setting to evaluate GynocularTM in detection of cervical neoplasias. Methodology: Women between 30-60 years were screened using VIA and HPV test. Women positive on either test had evaluation by GynocularTM using IFCPC 2011 colposcopy classification and swede score. Punch biopsy was obtained from any lesion detected by GynocularTM. HPV positive women also had random punch biopsy from the cervix. The sensitivity, specificity and agreement between histology and gynocular diagnosis were estimated. Results: Total 6884 women were screened from April, 2014 to March, 2015. Total 684 women were examined by GynocularTM. A total of 28 cases of CIN2+ were detected. The sensitivity and specificity of Gynocular (IFCPC Grade-2 threshold) to detect CIN 2+ were 92.9% and 96.1% respectively. The exact agreement between Gynocular examination and histology to classify the cervical lesions was 55.5% with kappa value of 0.29 (95% C.I. 0.22–0.36) indicated ‘fair’ agreement. Conclusion: There is a great need for an inexpensive colposcope to be used for programs in LMICs. The agreement of GynocularTM with histology was same as that of colposcopy reported in our earlier study conducted in the same setting. The logistic advantage of the device and ability to capture images using mobile phone are beneficial to use Gynocular TM for cervical cancer screening program.
- Gynecologic Oncology Diagnosis
- Gynecologic Oncology Cause