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Objective Gynaecological cancer surgery is associated with high rates of venous thromboembolism (VTE) despite recommended prophylaxis. We sought to investigate the impact of extended prophylaxis with fixed dose and weight based LMWH in patients undergoing gynaecological cancer surgery. Methods VTE rates were recorded in patients who received LMWH prophylaxis (4500 IU Tinzaparin once daily) for the duration of hospital stay (2006–2012) (n = 610) and were compared with VTE rates in patients who underwent surgery after the introduction of extended prophylaxis (3500/4500 IU Tinzaparin for patients with BMI 40 kg/m2) (2012–2017) (n = 651). Peak (4 h) anti-Xa levels in a subset of patients were also evaluated. Results 73 (5.7%) cases of VTE were recorded during 1 year of follow-up. 20 cases occurred during hospital stay. There was no significant difference in the rate of VTE between the extended prophylaxis cohort and the standard prophylaxis cohort. 23/24 patients who developed VTE in the extended prophylaxis cohort received a fixed (4500 units) dose of Tinzaparin. 63% of patients who received a fixed LMWH dose had peak anti-Xa levels below the target range (0.2–0.4 IU/ml). Peak anti-Xa was lower in patients who subsequently developed VTE compared with those who received either fixed dose (P = 0.041) and weight adjusted Tinzaparin (P = 0.0006). Conclusions Extended prophylaxis with Tinzaparin does not significantly reduce VTE rates in gynaecological cancer patients post surgery. Peak anti-Xa levels may be suboptimal in many patients receiving a fixed LMWH dose. Further studies are required to determine whether weight adjusted doses of Tinzaparin may provide more effective prophylaxis following gynaecological cancer surgery.

INTRODUCTION Ovarian cancer patients are at high risk of thrombosis particularly during chemotherapy treatment however the mechanism is not understood. The aim of this study is to investigate the role of the activated protein C (aPC) pathway in the procoagulant activity observed in ovarian cancer patients undergoing neoadjuvant chemotherapy. PATIENTS AND METHODS Thrombin generation was determined before and after addition of thrombomodulin (TM) in high grade serous ovarian cancer (HGSOC) patients treated with neoadjuvant chemotherapy (n = 29) compared with HGSOC patients who were chemo naive (n = 23) and patients with benign tumours (n = 29). Plasma expression of proteins from the aPC pathway was analysed. mRNA expression was determined in endothelial (EA.hy926) and ovarian (OAW42) cell lines following addition of carboplatin and paclitaxel. RESULTS Lower levels of ETP (p

To investigate whether HE4 and CA125 could identify endometrioid adenocarcinoma patients who might most benefit from full staging surgery with lymphadenectomy.Sequential patients with a preoperative banked serum and histology of endometrioid adenocarcinoma of endometrium who had undergone surgical staging with lymph node dissection over a 5-year period between 2011 and 2016 were included from a tertiary Gynaecological Cancer Centre, Dublin, Ireland. Preoperative serum HE4 and CA125 were measured using ELISA, with the cut-offs HE4 81 pmol/L and CA125 35 U/ml. Predictive values were estimated using AUC, sensitivity, specificity and odds ratios.9.5% of the cohort had lymph node metastases. A HE4 cut-off of 81 pmol/L yielded a sensitivity of 78.6% and specificity of 53.4% for predicting lymph node metastases. Sensitivity of CA125 at 35 U/ml was 57% and specificity 91.4%. The AUC was 0.66 (0.52-0.80) for HE4 and 0.74 (0.58-0.91) for CA125. Sensitivity was 92.8% and specificity 51.1% when an elevation of either HE4 or CA125 was included, AUC was 0.72 (0.61-0.83), this combination yielded the highest NPV of 98.6%. Sensitivity was 42.9% and specificity 93.8% if both markers were elevated simultaneously, AUC was 0.68 (0.51-0.86). Preoperative clinical predictors of high-grade preoperative histology and radiology had sensitivities of 21.4% and 41.7%, respectively. Patients with a HE4 above 81 pmol/L had an odds ratio of 4.2 (1.12-15.74), p 0.05, of lymph node metastases and CA125 had an odds ratio of 14.2 (4.16-48.31), p 0.001.Serum HE4 and CA125 improved on existing methods for risk stratification of endometrioid carcinomas and warrant further investigation.

Background Gynecologic cancers are associated with high rates of venous thromboembolism (VTE), which is exacerbated by pelvic surgery and chemotherapy. Objectives The aim of this study was to develop and validate a risk score for VTE in patients with gynecologic cancer and to test the predictive ability of the score following addition of procoagulant biomarker data. Patients and methods Clinical and laboratory variables were used to develop a risk score for the prediction of VTE in patients with gynecological cancer (n = 616), which was validated in a separate cohort of patients (n = 406). Endogenous thrombin potential and D‐dimer levels were determined in a subset (n = 290) of patients and used to produce an extended score in the validation cohort. Results Multivariable regression analysis identified BMI >30, hemoglobin

INTRODUCTION CA 125, the biomarker in common clinical use for ovarian cancer, is limited by low sensitivity for early disease and high false positives. The aim of this study was to evaluate several candidate biomarkers, alone or in combination, compared with CA 125 in the prediction of malignant/borderline vs benign tumor status in premenopausal and postmenopausal women with pelvic masses. MATERIAL AND METHODS This was a retrospective observational cohort study set in St James's Hospital, a tertiary referral center for gynecological malignancy in Dublin, Ireland. Women undergoing surgery for pelvic masses between 2012 and 2018 were included. Preoperative human epididymis protein 4 (HE4), the Risk of Ovarian Malignancy Algorithm, the Risk of Malignancy Index I and II, D-dimer, and fibrinogen were assessed. Logistic regression models were fitted for each biomarker alone and in combination. Receiver operating characteristics-area under the curve (ROC-AUC) and partial AUCs in the 90%-100% specificity range were determined. RESULTS In all, 89 premenopausal and 185 postmenopausal women were included. In premenopausal women, no biomarker(s) outperformed CA 125 (AUC 0.73; 95% CI 0.63-0.84). In postmenopausal women, HE4 had a partial AUC (pAUC) of 0.71 (95% CI 0.64-0.79) compared with 0.57 (95% CI 0.51-0.69) for CA 125 (p = 0.009). HE4 + D-dimer had an improved pAUC of 0.74 (95% CI 0.68-0.81, p

To demonstrate laparoscopic ureteric reconstruction with formation of a Boari flap. We present video footage of a laparoscopic Boari flap formation in a patient with previous extensive primary debulking surgery and stenosis of a prior excision of the distal ureter with a Boari flap and stabilizing

In this video article we demonstrate the pelvic placement of an artificial mammary implant as part of total pelvic exenteration surgery. The initial steps in this procedure are inspection of the abdomen and pelvis with two port laparoscopy, and isolation of the primary tumor by circumferential

Introduction/Background Following publication of the LACC trial, laparoscopic radical hysterectomy for the treatment of cervical cancer is now debated. We aimed to measure outcomes in our own population.This review aims to compare overall survival and risk of recurrence among women who underwent open versus laparoscopic radical hysterectomy for early cervical cancer at the largest provider of gynaecological cancer care in the Republic of Ireland over 10 years. Methodology All cases of cervical cancer diagnosed from January 2005 until January 2016 were reviewed. Patient characteristics, disease stage, histology, node status, method of treatment including surgery, adjuvant radiation or chemotherapy were recorded. Intervals to death and/or recurrence were calculated. Inclusion criteria were: Stage 1A1, 1A2 or 1B1 adenocarcinoma, squamous cell or adenosquamous carcinoma of the cervix without node involvement; radical hysterectomy (open or laparoscopic). Results Of 608 new cases of cervical cancer, 476 were excluded (not treated surgically [n=392]; treated with surgery other than RH [n=18]; histology other than SCC/AC/ASC [n=14]; stage beyond IB1 [n=26]; node positive histology [n=11]; death but no recurrence [n=4]; lost to follow-up [n=11]). For the laparoscopic (n=54) and open (n=78) RH groups respectively, baseline characteristics were similar: mean age at diagnosis was 38.2 vs 43.9 years, histology was SCC in 64.8% vs 66.7%, adenocarcinoma in 7.4% vs 5.1% and adenosquamous in 29.6% vs 28.2%. Death occurred in 13.0% (n=7/54) vs 6.4% (n=5/78) [p=0.19]; recurrence was diagnosed in 13.0% (7/54) vs 9.0% (n=7/78) [P=0.46]. Conclusion Our findings showed no statistical significance between open versus laparoscopic surgery in terms of recurrence rates and overall survival. However, numerically there were more deaths within the laparoscopic group. A further sub-analysis will be conducted on tumour volume, multimodal treatment with regards to risk of recurrence. Disclosure Nothing to disclose.

e17576 Background: Cancer cachexia is associated with considerable morbidity and mortality, yet its prevalence in gynaecological malignancy is unknown. Prevalence of cachexia in de novo gynaecological cancer patients and the impact of cachexia on clinical parameters and patient-reported outcomes were investigated. Methods: A prospective, exploratory study of newly diagnosed gynaecological cancer patients was conducted at St. James’s Hospital, the largest treatment provider for gynaecological malignancy in the Republic of Ireland. Patients recently diagnosed with a gynaecological cancer were eligible. Demographics, oncological history, Clavien Dindo Classification and length of stay were collected from participants’ medical record. A questionnaire completed by participants on 3 consecutive days collected data on height, weight, weight history, recent dietary intake, nutritional impact symptoms and functional status. Cachexia was defined using the criteria established in 2011 (Fearon and Strasser et al, 2011). Participants’ staging computed tomography scans were utilised for body composition analysis. Descriptive statistics, Mann Whitney U tests and Chi-square were used to summarise and identify significant associations between variables. Logistic regression was used to model predictors of cachexia. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Core Questionnaire in conjunction with EORTC gynaecological cancer-specific modules assessed quality of life. Results: A total of 94 participants were recruited. All five gynaecological cancers were represented. Prevalence of cachexia was 21.4% and was highest in patients with cervical cancer. Any weight loss in the previous month was predictive of developing cachexia. Low albumin and anorexia were associated with cachexia, although neither reached significance. Median post-operative length of stay for cachectic patients was 5 days (range 1-57) compared to 4 days (range 0-27) for non-cachectic patients (p = 0.682). 60% of cachectic patients had some post-operative complication. Cachectic patients were more symptomatic and had lower functional status in all quality of life categories, with the exception of emotional function. Conclusions: As prevalence of cachexia in this population is at least 22%, we strongly recommend screening for cachexia at all clinical assessments. Although weight loss and body mass index can identify the majority of cachectic patients, skeletal muscle mass index should also be included where possible. Its incorporation into standard radiology assessment of cancer patients would be optimal. Further research is warranted in a larger population to fully elucidate the predictors of cachexia. Quality of life is a useful means to monitor symptoms and functional status which may contribute to or exacerbate cachexia.

Gynaecological cancers are associated with high rates of VTE varying from 6% in endometrial cancer to up to 43% in clear cell cancer of the ovary. The risk of VTE is particularly high following gynaecological cancer surgery where VTE occurs in 6–7% of patients despite LMWH prophylaxis. The presence of a gynaecological malignancy increases the rate of post-operative VTE fourfold compared with patients with benign disease. The risk of VTE persists beyond hospital stay hence guidelines recommend extended prophylaxis (28 days) with LMWH for patients undergoing pelvic abdominal surgery for cancer. Gynaecological cancer surgery has evolved with increasing use of Minimally Invasive Surgery (MIS) and improvements in post-operative care with associated shorter hospital stay. The aim of this review is to evaluate on the risk of venous thromboembolism following gynaecological cancer surgery and the role of extended thromboprophylaxis in the era of MIS. The risk of VTE following MIS for cancer is low and more data is required to justify the use of extended prophylaxis. VTE risk varies depending on tumour, patient, and treatment factors. Individual risk assessment is required to optimise prophylaxis in these patients. Barriers to the use of extended prophylaxis include concerns regarding bleeding risk and physician perception that the risk of VTE is low particularly following laparoscopy. The introduction of new oral anticoagulants may play a role in post-operative prophylaxis in the future however data is lacking in gynaecological cancer patients.

Background: Circulating tumour cells (CTCs) are silent precursors of metastatic disease that utilise various mechanisms to survive in circulation and metastasise to distal sites. Classical CTC detection relies on EpCam affinity-based technologies; however, CTCs are highly heterogeneous and often undergo EMT. Recent research highlights the ability of platelets and neutrophils to ‘cloak' CTCs and crosstalk to aid in their proliferation and survival in circulation. Aims: Assess the role of platelets and neutrophils in the characterisation of CTCs. Methods: Cell lines: Breast cancer (MCF-7) and ovarian cancer (SKOV-3, OVCAR3, OAW42) cells were exposed to healthy donor isolated platelets and neutrophils for 24h. EMT and immune evasion gene assays, flow cytometry analysis and cell proliferation assays were performed following co-culture. Cell line-blood spike-in experiments were performed for gating strategy optimisation.Patient samples: Blood specimens were prospectively collected from breast and ovarian cancer patients (central venous and peripheral blood). CTCs and immune cells were then isolated using a ClearCell FX microfluidic device. FX isolated cells were immunophenotyped by either immunofluorescence (IF) or flow cytometry. Single cells were index sorted using BD FACS Melody for subsequent scRNAseq. Results: Platelet cloaking altered EpCam, PLEK2, CCL2 and TWIST1 mRNA expression in MCF-7 cells. Platelet and neutrophil co-culture altered EpCam, PAI-1 and PD-L1 expression in ovarian cancer cell lines. Healthy neutrophils co-cultured with ovarian cancer cells increased cell viability, while induction of NETosis increased cancer cell proliferation. CTCs isolated from peripheral blood in breast and ovarian patients were EpCam/panCK+/CD45- by IF. Immunophenotyped CTCs were identified as EpCam+/E-Cadherin+/CD45-, N-Cadherin+/CD45- and as PD-L1+/EpCam+/E-Cadherin+/CD45- cells by flow cytometry. We also identified EpCam+/CD45+/CD66b+ cells in ovarian central blood. Isolated classical and non-classical CTCs were sorted based on their different immunophenotypes for downstream scRNAseq using BD Precise Whole Transcriptome Assays. Conclusion: Platelets and neutrophils alter the expression of markers used in the identification of CTCs. Neutrophils were found to increase the proliferation of cancer cells as well as increase PD-L1 expression. We identified a heterogeneous population of CTCs across different patients and found that CTCs from central venous blood have increased numbers of non-classical CTCs (CD66b+/EpCam+ cells). Molecular scRNAseq signatures of CTC subsets form the basis for identifying the most clinically relevant CTCs in circulation. Our approach may improve diagnostic accuracy, allow for immunophenotyping of cloaked CTCs, and provide prognostic information. Citation Format: Mark P. Ward, Bashir M. Mohamed, Laura Kane, Mark Bates, Janina Berghoff, Cathy L. Spillane, Tanya Kelly, John Kennedy, Feras A. Saadeh, Karsten Hokamp, Noreen Gleeson, Orla Sheils, Cara Martin, Michael Gallagher, Sean Hannify, Eric P. Dixon, Sharon A. O'Toole, John J. O'Leary. Influence of platelets and neutrophils on circulating tumour cells [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 764.

Uterine leiomyomas are the most common benign gynaecological tumours. However, 0.13 to 6% of them have malignant potential (Robboy et al. Environ Health Perspect 108(Suppl 5):779–784, 2000). Uterine smooth muscle tumours with unusual growth patterns include a spectrum of lesions such as intravenous leiomyomatosis, benign metastasizing leiomyoma and disseminated peritoneal leiomyomatosis (Vaquero et al. J Minim Invasive Gynecol 16:263–268, 2009). Benign metastasizing leiomyoma (BML) is a very rare condition with around 100 cases reported to date. BML is a cytologically bland, mitotically inactive smooth muscle tumour in extra uterine sites, occurring in conjunction with similarly appearing or previously removed uterine leiomyomas (Beck et al. Hong Kong Med J = Xianggang yi xue za zhi 18:153–155, 2012). Pulmonary metastases are the most common sites of metastases, but other sites include skin, bladder, liver, lymph nodes, oesophagus, skeletal muscles, heart, bones and central nervous system (Jo et al. Korean J Int Med 21:199–201, 2006; Arai et al. Chest 117:921–922, 2000; Kwon et al. Korean J Int Med 21:173–177, 2006; Rivera et al. J Clin Endocrinol Metab 89:3183–3188, 2004; Jautzke et al. Pathol Res Pract 192:215–223, 1996; Goyle et al. Am J Clin Oncol 26:473–476, 2003; Schneider et al. Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen 72:308–311, 2001; Andrade et al. Pathol Oncol Res: POR 4:44–47, 1998; Abramson et al. AJR Am J Roentgenol 176:1409–1413, 2001; Yoon et al. Cancer Res Treat 43:131–133, 2011; Egberts et al. Arch Gynecol Obstet 274:319–322, 2006). The condition is more common in late childbearing age, mean age of diagnosis is 43 years (Kwon et al. Korean J Int Med 21:173–177, 2006), suggesting that it is hormone related. Lung metastases in BML are usually an incidental finding during the preoperative assessment; however, on rare occasions, patients are symptomatic with cough, chest pain, haemoptysis or dyspnoea. The differential diagnosis includes pulmonary metastases from leiomyosarcoma, intravenous leiomyomatosis or metastasis from other malignancies. Lung biopsy is the only way to confirm the benign nature of these lesions. Recently, positron emission tomography (PET) scan showed promise in differentiating these benign lesions from malignant lung lesion (Sawai et al. Oncol Lett 14:3641–3646, 2017). We present three cases with pulmonary metastases from BML and discuss the pathogenesis and management of this rare condition.

Ovarian cancer is the seventh most common cancer in women and the most frequent cause of gynaecological malignancy-related mortality in women. Currently, no standardized reliable screening test exists. MicroRNA profiling has allowed the identification of signatures associated with diagnosis, prognosis and response to treatment of human tumours. The aim of this study was to determine if a microRNA signature could distinguish between malignant and benign ovarian disease. A training set of 5 serous ovarian carcinomas and 5 benign serous cystadenomas were selected for the initial experiments. The validation set included 20 serous ovarian carcinomas and 20 benign serous cystadenomas. The serum/plasma focus microRNA Exiqon panel was used for the training set. For the validation set a pick and mix Exiqon panel, which focuses on microRNAs of interest was used. A panel of 4 microRNAs (let-7i-5p, miR-122, miR-152-5p and miR-25-3p) was significantly down regulated in cancer patients. These microRNAs target WNT signalling, AKT/mTOR and TLR-4/MyD88, which have previously been found to play a role in ovarian carcinogenesis and chemoresistance. let-7i-5p, miR-122, miR-152-5p and miR-25-3p could act as diagnostic biomarkers in ovarian cancer.

Introduction Gynaecological cancer is associated with some of the highest rates of venous thromboembolism (VTE) with some subtypes of ovarian cancer associated with rates as high as 20%. VTE prophylaxis is an important part of post-operative management in gynaecological cancer patient care. Despite the evidence base and guidelines recommending extended VTE prophylaxis for patients undergoing major cancer surgery, adherence to best practice guidelines has been found to be low. Aim The aim of this study is to assess gynaecological oncologist’s awareness of the guidelines surrounding VTE prophylaxis for post-operative gynaecological cancer patients and to determine the type and duration of VTE prophylaxis implemented by gynaecological oncologists. Materials and Methods The study used the European Society Gynaecology Oncology (ESGO) membership as the population studied. ESGO is a multidisciplinary, non-profit association, founded in 1983. ESGO consisit of more than 1800 professional of different specialities dealing with gynaecological oncology. The e mail address of 650 member were avilable on the ESGO website. We send a Survey Monkey link to the questionnaire by email to a total of 650 ESGO member whose email addresses were obtained from the ESGO directory. 205 e mails returned back as the email used was invalied, only 445 e mail successfully delivered. The survey remained open for 44 days. Results were analysed on Survey Monkey. Results A 59.3% of respondents said that they decided upon appropriate VTE prophylaxis for a patient according to national/international best practice guidelines. A further 39.4% respondents said that they made their choice based upon clinical judgement. 59.8% of respondents said that they begin VTE prophylaxis pre-operatively for the high risk patients. 6.1% said that they begin prophylaxis in the operating theatre, 18.9% begin prophylaxis 6 hours post-operatively and 9.1% begin prophylaxis 12 hours post-operatively. The remaining respondents said that they begin VTE more than 24 hours post operatively 44.7% said that they prescribe VTE prophylaxis for 4 weeks. A further 15.9% said that they prescribe VTE prophylaxis for 6 weeks and 4.75% for longer than 6 weeks. Conclusions In conclusion, the adherence to current guidelines for VTE prophylaxis in the peri-operative period for gynaecological oncology patients is still poor. Awareness needs to be raised in order to decrease the morbidity/mortality of VTE in this high risk group of patients. The adoption of multidiscplinary approach to manage gynaecological cancer patients, which includes the involvment of thrombosis specialist, may reduce post operative VTE rates and improve cancer care.

Background Gynaecological cancers are associated with high rates of venous thromboembolism (VTE). Studies on ambulatory cancer patients do not support thromboprophylaxis during chemotherapy. Approximately 6–7% of gynaecological cancer patients suffer a postoperative VTE despite Low Molecular Weight Heparin prophylaxis (LMWH). Large cancer studies have shown that Calibrated Automated Thrombogram (CAT) and Microparticles (MP) assays may be useful in predicting VTE but data on gynaecological cancer patients is scarce. Objective Our objective was to identify whether the CAT assay and MP functional assays have potential as biomarkers predictive of VTE in gynaecological cancer patients. Patients and methods Gynaecological cancer patients were investigated before surgery (n = 146) and at 5, 14 and 42 days post-surgery (n = 78). Fourteen additional patients were investigated before chemotherapy and after 3 and 6 cycles of therapy. Thrombin generation was measured before and after addition of thrombomodulin. Results Patients with clear cell cancer (CCC) of the ovary and patients with endometrial cancer had higher ETP and peak thrombin compared with patients with benign disease. Patients who developed VTE (n = 8) following surgery had enhanced thrombin generation prior to surgery which persisted during the post-operative period despite LMWH prophylaxis. Both neoadjuvant and adjuvant chemotherapy showed increased thrombin generation following addition of thrombomodulin. There were no differences in MP levels during the study. Conclusions CAT assay shows potential as a promising biomarker for the prediction of VTE in gynaecological cancer patients. The identification of high risk patients combined with individualised LMWH prophylaxis might reduce VTE in this high risk group.

A 32-year-old patient with primary infertility received in vitro fertilisation (IVF) therapy. Four weeks later she developed intermittent left iliac fossa pain. Transvaginal ultrasound showed an empty uterus and an adnexal mass adjacent to the right ovary. Serum β-human chronic gonadotropin was 33 492 IU/L. At laparoscopy a mass attached to right ovary, suggestive of a right ovarian ectopic pregnancy, was excised. Histological examination confirmed an ovarian ectopic gestation, but noted enlarged chorionic villi and trophoblastic atypia, which raised the suspicion of molar pregnancy. Subsequent p57 immunohistochemistry and DNA ploidy studies excluded a mole, however. Cases of suspected molar disease in ectopic pregnancy present a diagnostic challenge for both clinicians and histopathologists, and establishing a definitive diagnosis may be difficult.

Groin node lymphadenectomy in vulva cancer carries a substantial risk of morbid sequelae. Sentinel lymph node (SLN) mapping is a valid alternative in patients with squamous cancer of diameter

A 25-year-old nulliparous woman attended an orthopaedic clinic with a 12-month history of right hip pain and was found to have a hard tender mass in her right groin. Fine-needle aspiration yielded a diagnosis of endometrial glands. The lesion was excised completely and the final diagnosis was round ligament endometriosis. The patient was pain free 3 months postsurgery.

article i nfo Article history: Introduction: Ovarian cancer is known to display a particular association with venous thromboembolism (VTE) with reports up to 42% of patients developing thromboembolic complications. Tissue Factor (TF) and its inhibitor Tissue Factor Pathway Inhibitor (TFPI) have been implicated in VTE risk in cancer. The aim of this study was to measure tumour derived TF and TFPI and to investigate their potential role in VTE in ovarian cancer patients. Methods: TF and TFPI mRNA expression was measured using TaqMan real time PCR in 99 ovarian tumour samples. Nineteen cases complicated by VTE were matched to 19 cases without VTE. TF and TFPI protein levels weremeasuredusingELISAandimmunohistochemistrywasusedtolocalizeTFexpression.TheroleofTFexpres- sion on overall survival was also determined. Results: TF mRNA and protein expression was increased in tumours from patients with clear cell carcinoma (p b 0.001). TF protein expression was also increased in endometroid carcinoma (P b 0.01) compared with benign tumours. TFPI mRNA expression was increased in clear cell carcinoma (P b 0.01). TF mRNA and antigen level was increased in malignant tumours of patients who developed VTE compared with matched malignant otumours of patients who remained thrombosis free (P b 0.01). There was no difference in TFPI expression between the two groups. Conclusion:TFexpressioninovariancancerissignificantlyhigherinpatientswhodevelopVTE.TFexpressionwas increasedinclearcellovariancancerandendometroidcancerandthismayexplainthehigherriskofVTEinthese subgroups. TF derived from these tumours may be the trigger for VTE in ovarian cancer.

Ovarian cancer has a higher incidence of venous thromboembolism (VTE) than other cancers. Clear cell cancers carry the highest risk at 11-27%. The aim of this study was to identify the predisposing factors for VTE in a population of ovarian cancer patients and to determine the influence of VTE on overall survival.VTE events were identified from hospital and general practice/community care records for all patients with ovarian cancer who were diagnosed and treated in a tertiary cancer center between 2006 and 2010.The overall incidence of VTE was 9.7% (33) in 344 patients. Sixteen (48%) had pulmonary embolism. Six (18%) presented with VTE. Five (15%) had VTE diagnosed during pre-treatment routine CT scanning. Eleven (33%) developed VTE following surgery and eleven (33%) developed VTE during chemotherapy. Risk factors associated with the occurrence of VTE were BMI≥30 (p0.01), clear cell carcinoma (p0.05), advanced stage (p0.01), high grade (p0.01) and CA125500 IU/ml (p0.001). The occurrence of VTE was associated with decreased overall survival time (p0.001).The incidence of VTE is high in ovarian cancer especially in the clear cell subtype. VTE adversely affects survival in ovarian cancer. Obesity, high grade and stage of cancer, clear cell subtype and high CA 125 level should be incorporated into protocols of VTE prophylaxis in women with ovarian cancer.

Platinum resistance is a major cause of treatment failure in ovarian cancer. We previously identified matrix metalloproteinase 9 (MMP-9) as a potential therapeutic target of chemoresistant disease. A2780cis (cisplatin-resistant) and A2780 (cisplatin-sensitive) ovarian carcinoma cell lines were used. The cytotoxic effect of MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) alone or in combination with cisplatin was determined using high content screening. Protein expression was examined using immunohistochemistry and ELISA. Co-incubation of cisplatin and an MMP-9/MMP-2 inhibitor, (2R)-2-[(4-Biphenylsulfonyl) amino]-3 phenylpropionic acid (C21H19NO4S) resulted in significantly greater cytotoxicity as compared to either treatment alone in a cisplatin resistant MMP-9 overexpressing cell line; A2780cis. In addition, pre-incubating with MMP-9i prior to cisplatin further enhances the cytotoxic effect. No significant difference was observed in MMP-9 protein in tissue but a trend towards increased MMP-9 was observed in recurrent serum. We propose that MMP-9/MMP-2i may be utilized in the treatment of recurrent/chemoresistant ovarian cancers that overexpress MMP-9 mRNA but its role in vivo remains to be evaluated.

Increased thrombin production is associated with malignancy and is a marker for venous thromboembolism (VTE). Our group has shown that thrombin generation is increased in gynaecological malignancies. Although tumour derived Tissue Factor (TF) has been implicated, the precise mechanism by which thrombin production is increased is not fully understood. Our group has shown that gynaecological cancers can alter tumour expression of cogulation proteases. These changes may be implicated in the increased thrombin generation observed. Previous studies in normal control patients by other groups have shown that multiple coagulation factors are implicated in thrombin generation and that the effects depend on assay conditions however free Tissue Factor Pathway Inhibitor (TFPI), Factors V, VIIIc and protein S, were significant determinants of thrombin generation.The aim of this study was to determine the effect of factor V factor, VIIIc, TFPI and free protein S on the thrombin generation in patients with endometrial and ovarian cancer compared with benign controls.Patients with a gynaecological malignancy (n=43) (ovarian or endometrial) were matched with patients with a benign tumour (n=43) gave full and informed consent. Venous blood samples were obtained prior to surgery and chemotherapy. Thrombin generation was was measured using a fluorogenic assay. Lag time, peak thrombin and area under the thrombin generation curve (ETP) was determined and reported for each sample. Free protein S, free TFPI and factor V were determined using ELISA. Factor VIIIc was determined using a hromogenic assay.Factor V and factor VIIIc were significantly increased in the malignant group compared with the benign group (P0.03; P0.006). Increased free TFPI levels were also observed in the malignant group but this did not reach significance (P0.06). There was no difference in free Protein S levels between the groups. Highest levels of peak thrombin generation were observed in the high grade serous and clear cell ovarian cancer patients. Changes were less marked in the endometrial patients. Free TFPI, factor V and factor VIIIc were important determinants of thrombin generation in the malignant group.Coagulation factors V and VIIIc and free TFPI are altered in patients with gynaecological malignancies and contribute to the increased thrombin generation found in these cancer patients. We have previously found increased expression of factor V in tumours from patients with ovarian cancer in addition to increased TF expression. These changes may explain the high rate of venous thromboembolism found in these patients.

A 34-year-old nulliparous woman with a long-standing history of uterine fibroids and infertility had undergone prior open myomectomy, then uterine artery embolisation in treatment of an apparent large fibroid. Imaging on referral revealed an atypical 12×11×10 cm pelvic mass with the appearance of a fibroid. At laparotomy, the lesion was encapsulated but softer than a fibroid and located deep in the paravaginal space. The histopathological outcome was an aggressive angiomyxoma.