VHL: Trends and Insight into a Multi-Modality, Interdisciplinary Approach for Management of Central Nervous System Hemangioblastoma.

Von Hippel-Lindau (VHL) is a multi-system disease which results in significant morbidity from central nervous system (CNS) involvement as well as ocular, renal and neuro-endocrine effects. Haemangioblastomas of the CNS present a number of challenges. The natural history of these lesions is varied, as is the size and location within the CNS. Whilst surgery is considered the mainstay of treatment and best chance at curing these lesions, this is also often associated with significant risks due to the anatomical location of these lesions, most commonly the posterior fossa and spinal cord.We review the literature and describe our experience across two separate European VHL referral centres. Alternative treatment options and combined modalities are increasingly being used in the context of managing CNS haemangioblastomas. We analyse the increasing use of stereotactic radiosurgery and the evolution of medical treatments as potential future adjuncts to surgery. The availability of multiple modalities in our armamentarium is essential in tailoring a personalised treatment approach to these patients. Owing to the multi-systemic nature of the disease, in our experience, managing the care of patients with VHL is best delivered using an interdisciplinary approach utilising multiple specialties and adopting an individually tailored holistic approach.

The subsurface lesion in erosive tooth wear.

OBJECTIVES: This study compared the surface change on natural and polished enamel exposed to a joint mechanical and chemical wear regimen. METHODS: Human enamel samples were randomly assigned to natural (n = 30) or polished (n = 30) groups, subjected to erosion (n = 10, 0.3% citric acid, 5 min), abrasion (n = 10, 30 s), or a combination (n = 10). Wear in the form of step height was measured with a non-contact profilometer, and surface changes were inspected with SEM on selected sections. Data was normalised and underwent repeated measures MANOVA, accounting for substrate and erosive challenge as independent variables, with Bonferroni correction for significant post hoc interactions. RESULTS: After four cycles, polished samples had mean step heights of 3.08 (0.40) µm after erosion and 4.08 (0.37) µm after erosion/abrasion. For natural samples, these measurements were 1.52 (0.22) µm and 3.62 (0.39) µm, respectively. Natural surfaces displayed less wear than polished surfaces under erosion-only conditions (p<0.0001), but the difference disappeared with added abrasion. SEM revealed a shallow subsurface layer for polished surfaces and natural ones undergoing only erosion. However, natural surfaces exposed to both erosion and abrasion showed deeper subsurface changes up to 50 µm. CONCLUSION: Natural enamel, when exposed to erosion alone, showed less wear and minimal subsurface alterations. But with added abrasion, natural enamel surfaces saw increased wear and notable subsurface changes compared to polished ones. CLINICAL SIGNIFICANCE: The pronounced subsurface lesions observed on eroded/abraded natural enamel surfaces highlight how combined wear challenges may accelerate tooth tissue loss.

CTC-5: A novel digital pathology approach to characterise circulating tumour cell biodiversity.

Metastatic progression and tumor evolution complicates the clinical management of cancer patients. Circulating tumor cell (CTC) characterization is a growing discipline that aims to elucidate tumor metastasis and evolution processes. CTCs offer the clinical potential to monitor cancer patients for therapy response, disease relapse, and screen 'at risk' groups for the onset of malignancy. However, such clinical utility is currently limited to breast, prostate, and colorectal cancer patients. Further understanding of the basic CTC biology of other malignancies is required to progress them towards clinical utility. Unfortunately, such basic clinical research is often limited by restrictive characterization methods and high-cost barrier to entry for CTC isolation and imaging infrastructure. As experimental clinical results on applications of CTC are accumulating, it is becoming clear that a two-tier system of CTC isolation and characterization is required. The first tier is to facilitate basic research into CTC characterization. This basic research then informs a second tier specialised in clinical prognostic and diagnostic testing. This study presented in this manuscript describes the development and application of a low-cost, CTC isolation and characterization pipeline; CTC-5. This approach uses an established 'isolation by size' approach (ScreenCell Cyto) and combines histochemical morphology stains and multiparametric immunofluorescence on the same isolated CTCs. This enables capture and characterization of CTCs independent of biomarker-based pre-selection and accommodates both single CTCs and clusters of CTCs. Additionally, the developed open-source software is provided to facilitate the synchronization of microscopy data from multiple sources (https://github.com/CTC5/). This enables high parameter histochemical and immunofluorescent analysis of CTCs with existing microscopy infrastructure without investment in CTC specific imaging hardware. Our approach confirmed by the number of successful tests represents a potential major advance towards highly accessible low-cost technology aiming at the basic research tier of CTC isolation and characterization. The biomarker independent approach facilitates closing the gap between malignancies with poorly, and well-defined CTC phenotypes. As is currently the case for some of the most commonly occurring breast, prostate and colorectal cancers, such advances will ultimately benefit the patient, as early detection of relapse or onset of malignancy strongly correlates with their prognosis.

The early wear susceptibility of cementum, enamel and dentine in vitro.

OBJECTIVES: To assess the differential early wear susceptibility of cementum, enamel and dentine at a micron level. METHODS: Whole human molar buccal surfaces incorporating natural enamel and cementum (n = 20) confirmed by imaging (digital microscopy: Keyence, VHX-7000 Milton Keynes, UK), were mounted, scanned (profilometry: XYRIS 4000, Taicaan, Southampton, UK), and allocated to receive erosion (citric acid, pH 2.7, 30 min (n = 10)) or erosion/abrasion challenges (3 cycles of (citric acid, pH 2.7, 10 min, 60 300 g linear abrasion strokes), n=10). Samples were polished and the experiment repeated on polished enamel, and polished coronal and radicular dentine within the same tooth. Profilometric wear data were obtained using superimposition: GeoMagic (3Dsystems, Darmstadt, Germany) and subtraction: MountainsMap (DigitalSurf, Besancon, France). Data were normal. A general linear model was used to assess differences between groups and substrates. RESULTS: The mean step height (SD) for natural enamel was 8.82 µm (2.53) for erosion and 11.48 µm (2.95) for erosion/abrasion. For natural cementum, the mean step height was 6.00 µm (2.29) for erosion and 4.67 µm (1.58) for erosion/abrasion. Dentine step heights ranged from 7.20 µm (1.53) for erosion and 9.79 µm (1.01) for erosion/abrasion with no statistical differences in dentine wear. Natural cementum surfaces had the lowest wear (p<0.001). Dentine had significantly less wear than natural enamel (p<0.02). CONCLUSIONS: Cementum surfaces demonstrated the most wear resistance, followed by dentine under erosion dominant conditions in this in vitro study. Further in-vivo investigations are needed to confirm the intraoral stability of cementum. CLINICAL SIGNIFICANCE: Cementum may be the least susceptible of dental substrates to wear and dentine does not wear at a faster rate than enamel under erosive conditions. This adds to our knowledge on the development of non-carious cervical lesions and questions whether wear rates will accelerate once dentine is exposed.

The interplay of saliva, erosion and attrition on enamel and dentine.

Purpose: This investigation aimed to compare the protective role of saliva against erosion and attrition challenges. Method: Polished enamel and dentine samples (n = 160) were prepared and randomly assigned to either the saliva or saliva-free group (n = 40 enamel and n = 40 dentine/group). Within each subgroup, they were allocated to four subgroups: negative control (deionized water exposure 10 min), erosion (0.3% citric acid 10 min), attrition (120 S of 300 g force), or combined erosion/attrition (0.3% citric acid 10 min then 120 S of 300 g force). Experimental cycles were repeated three times. Data analysis was performed using SPSS. Results: The mean and standard deviation (SD) of step heights produced by the attrition and erosion/attrition groups in enamel in the saliva-free group were 5.6 µm (2.4) and 13.4 µm (2.8), respectively, while they were 2.4 µm (3.8) and 12.9 µm (3.5) in the saliva group, with no significant difference between the saliva and saliva-free groups. For dentine, the corresponding step heights were 25.2 µm (5.5) and 35.9 µm (7.9) for the saliva-free group, but 21.8 µm (5.3) and 27.3 µm (6.4) for the saliva group (p < 0.001). Conclusion: There was a trend that saliva decreased wear, but this was only statistically significant for erosion/attrition dentine wear.

A Systematic Review of the Factors Associated with Post-Traumatic Growth in Parents Following Admission of Their Child to the Intensive Care Unit.

This systematic review aims to identify the demographic, clinical and psychological factors associated with post-traumatic growth (PTG) in parents following their child's admission to the intensive care unit (ICU). Papers published up to September 2021 were identified following a search of electronic databases (PubMed, Medline, Web of Science, PsycINFO, CINAHL, PTSDpubs and EMBASE). Studies were included if they involved a sample of parents whose children were previously admitted to ICU and reported correlational data. 1777 papers were reviewed. Fourteen studies were eligible for inclusion; four were deemed to be of good methodological quality, two were poor, and the remaining eight studies were fair. Factors associated with PTG were identified. Mothers, and parents of older children, experienced greater PTG. Parents who perceived their child's illness as more severe had greater PTG. Strong associations were uncovered between PTG and post-traumatic stress, psychological well-being and coping. PTG is commonly experienced by this population. Psychological factors are more commonly associated with PTG in comparison with demographic and clinical factors, suggesting that parents' subjective ICU experience may be greater associated with PTG than the objective reality.

Extended thromboprophylaxis post gynaecological cancer surgery; the effect of weight adjusted and fixed dose LMWH (Tinzaparin).

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 < 40kg/m2 and 75 IU/kg for 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.

A multiplanet system of super-Earths orbiting the brightest red dwarf star GJ 887.

The closet exoplanets to the Sun provide opportunities for detailed characterization of planets outside the Solar System. We report the discovery, using radial velocity measurements, of a compact multiplanet system of super-Earth exoplanets orbiting the nearby red dwarf star GJ 887. The two planets have orbital periods of 9.3 and 21.8 days. Assuming an Earth-like albedo, the equilibrium temperature of the 21.8-day planet is ~350 kelvin. The planets are interior to, but close to the inner edge of, the liquid-water habitable zone. We also detect an unconfirmed signal with a period of ~50 days, which could correspond to a third super-Earth in a more temperate orbit. Our observations show that GJ 887 has photometric variability below 500 parts per million, which is unusually quiet for a red dwarf.

Doctor-Patient Communication in an Outpatient Setting

Aim To evaluate doctor patient communication within gynaecological oncology services in Ireland. Methods An anonymous and confidential 20 question survey was designed by the patient advocacy group ISGOPPI and distributed in three gynaecological oncology outpatient clinics in tertiary referral centres. Results A total of 84 patients completed the survey in the 3 Dublin hospitals. Doctors surveyed ranged from senior house officer to consultant level. Overall women were very satisfied with the communication they had received from their doctor. 85% felt that they the doctor listened to them and took their opinion into account. 84% of patients felt that the doctor's body language was appropriate throughout the consultation. One of the main issues for women surveyed was waiting times. 33% of women waited over an hour to see their doctor and over 30% of women did not receive contact details of the clinical nurse specialist. Conclusion Overall our study shows that patients in gynae-oncology clinics are satisfied with the communication from their doctors. The main issues for patients were waiting times and contact details for follow up questions.

Tooth wear and aging.

BACKGROUND: In an ageing population, tooth wear is likely to increase. It is increasing in prevalence in the younger population and a greater number of patients are retaining their teeth into old age. METHODS: This paper is a narrative review of the clinical presentation, the epidemiology and the restorative intervention for erosive tooth wear. The dilemmas in managing this common condition with the aging dentition in mind are described. The paper discusses evidence-based prevention methods and highlights how preventive intervention may be preferable over extensive restorative care and high maintenance needs. Patient wishes, expectations and commitment to treatment and maintenance require consideration during clinical decision making. CONCLUSION: Successful management of erosive tooth wear in an ageing population depends on effective diagnosis, preventive intervention and holistic advice regarding restorative intervention.

A systematic review and meta-analysis revealing realistic outcomes following paediatric torsion of testes.

INTRODUCTION: Reported testicular loss rates following paediatric testicular torsion often reflect the surgical decision-making process, rather than long-term survival of the testes. OBJECTIVES: We aim to perform systematic analysis and meta-analysis to investigate testicular salvage rates and to assess predictors of long-term viability. STUDY DESIGN: Systematic review according to PRISMA guidelines was performed to investigate immediate and long-term (>12 months) testicular loss rates following torsion in the paediatric population. Literature search and study inclusion were performed by two investigators. A study quality score was derived and attributed to each study. Predictors of testicular loss were described. Proportions meta-analysis was performed with random effects modelling, and testing for heterogeneity. RESULTS: Twelve studies were includedm, 6 reporting early orchidectomy rates, and 6 reporting long-term outcomes. Study quality was generally low. DISCUSSION: The mean early testicular loss rate was 39%, whereas meta-analysis revealed late loss to approach 50%. Predictors of outcomes include prehospital symptom duration, location of presentation, transfer to a tertiary centre, social affluence and use of ultrasound prior to diagnosis or transfer. CONCLUSIONS: This study has shown a considerable late testicular loss rate, which must be relayed to families even after testicular salvage. Delay in time to presentation is consistently found to predict poor outcomes.

Randomised Controlled Clinical Trial Investigating The Impact of Implementation Planning on Behaviour Related to The Diet.

There is a perceived gap between dietary advice given by health practitioners and adherence to the advice by patients. We investigated whether a behaviour change technique (implementation-planning) was more effective than standard-of-care diet advice at reducing dietary acid intake using quantitative erosive tooth wear progression as an objective clinical outcome. This study was a randomised controlled, double-blind, single-centre clinical trial in the UK. Participants (n = 60) with high dietary acid intake (≥2 daily), were recruited and randomly assigned (1:1) to receive either implementation-planning or standard-of-care diet advice in a single clinical session. Questionnaires and impressions were taken at baseline and 6 months later. Dental casts were scanned using laser profilometry and superimposed using surface-matching software. Data were analysed per protocol and intention-to-treat using independent t-tests and Mann-Whitney tests. The intervention group reduced their dietary acid intake between meals to 1 intake per day compared to 2 intakes per day for the controls and demonstrated reduced dental hard tissue volume loss (-0.00 mm3 (SD = 0.01)) compared to controls (-0.07 mm3 (SD 0.17)), p = 0.049. This paper supports the use of implementation planning in clinical practice and presents a non-invasive method of intervention assessment in behaviour change. Larger trials are needed to confirm the generalisability of results.

Tooth wear risk assessment and care-planning in general dental practice.

Objective To assess charting, risk assessment and treatment-planning of tooth wear between recently qualified and experienced dentists in general dental practice.Design Service evaluation.Setting Multi-setting evaluation of three mixed NHS/Private general dental practices in North-East London.Methods The clinical notes of new patient examinations on dentate adults presenting from the 1 October 2016 to 31 December 2016 were audited collecting data on tooth wear charting, risk assessment and treatment planning. Data were analysed using descriptives, chi square and logistic regressions in SPSS. Significance was inferred at p <0.05.Results Foundation dentists and experienced dentists performed 85 and 200 new patient examinations, respectively, during the evaluation period. Tooth wear was charted for 48% of those attending foundation dentists and 5% of those attending experienced dentists. Diet was assessed in 50.6% of patients examined by foundation dentists and 1.0% of patients examined by experienced dentists. Foundation dentists were more likely to chart tooth wear, risk assess and preventively manage tooth wear compared to experienced dentists (p <0.001).Conclusion This service evaluation highlights that improvements are required in recording, risk assessing and preventive treatment planning of erosive tooth wear. Experienced dentists were less likely to risk assess tooth wear and less likely to provide preventive treatment. Experienced GDPs may benefit from re-training in this area.

The role of the diet in tooth wear.

An acidic diet has been associated with erosive tooth wear. However, some people who consume dietary acids develop erosive tooth wear and some do not. This review paper provides an overview of the risk factors of dietary acid consumption which increase the likelihood of developing severe erosive tooth wear. Increased frequency of dietary acid consumption, particularly between meals appears to be the predominant risk factor. However, habitually drinking acidic drinks by sipping them slowly or swishing, rinsing or holding acidic drinks in the mouth before swallowing will also increase risk of progression. Consuming fruit over long time periods at a single sitting and dietary acids being served at increased temperatures have also been implicated. Additions of fruit or fruit flavourings to drinks and regular consumption of vinegars, pickles, acidic medications or acidic sugar-free sweets are potential hidden risk factors that should be discussed with patients at risk of erosive tooth wear progression. Behaviour change is difficult to achieve but specific, targeted behavioural interventions and offering alternatives may increase success.

Shorter anogenital and anoscrotal distances correlate with the severity of hypospadias: A prospective study.

INTRODUCTION: Anogenital distance (AGD) is a recognised marker of in utero androgen action. OBJECTIVE: This study aimed to evaluate the relationship between severity of hypospadias and AGD. STUDY DESIGN: Boys undergoing hypospadias repair in a single tertiary centre between May 2012 and February 16 were included in the study. Anogenital distance was measured from the centre of the anus to the base of the penis, and anoscrotal distance (ASD) from the centre of the anus to the junction between the smooth perineal skin and scrotal skin. Trained paediatric urologists made all measurements using digital callipers. RESULTS: Fifty-nine boys with hypospadias and 31 age-matched controls undergoing circumcision (median age 1.37 years, range 1.01-1.96) had AGD and ASD measured under anaesthetic. The patients were divided into two groups, according to hypospadias severity: group 1 - distal penile/subcoronal/glandular (n = 40); and group 2 - perineal/penoscrotal/midshaft (n = 19). The median AGD for controls was 74.0 mm (range 53.2-87.8) and for hypospadias it was 72.3 mm (range 50.7-90.0) (P = 0.816). The median ASD for controls was 42.3 mm (range 31.0-56.1) and for hypospadias it was 39.4 mm (range 20.7-77.0) (P = 0.224). Considering severity of hypospadias, the median AGD for group 1 and group 2 was 73.7 mm (range 50.7-90.0) and 63.3 mm (range 53.6-77.0), respectively (P < 0.001). The median ASD was also higher in group 1, at 41.3 mm (range 20.7-65.0), compared to 35.2 mm (range 23.5-77.0) in group 2 (P = 0.119) (Summary Fig.). DISCUSSION: This study showed that more severe forms of hypospadias are associated with shorter AGD and ASD. These findings agree with two previous studies that identified reduced AGD in boys with hypospadias. However, these studies did not investigate an association with severity of hypospadias. As hypospadias is multifactorial, only a small proportion of cases are thought to be associated with impaired in utero androgen exposure. The shorter AGD in boys with severe hypospadias compared with mild hypospadias would indicate that AGD is a marker of the severity of androgen production. This may also suggest that less severe forms of hypospadias have a different aetiology involving a later stage of development, and that they are not the result of reduced androgen exposure in the male programming window between the 8-14 weeks gestation. CONCLUSION: This study identified that boys with more severe hypospadias are more likely to have a shorter AGD and ASD than boys with mild hypospadias. This may indicate that there is a more profound impairment of in utero androgen action in severe hypospadias.

OC-12 - Peri operative venous thromboembolism prophylaxis in gynaecological cancer patients. A survey of current practice.

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.

PO-14 - Tumour expression of coagulation proteases of the aPC pathway - a role in the pathogenesis of gynaecological cancers?

INTRODUCTION: The close relationship between coagulation, thrombosis and cancer has long been established. Gynaecological cancers, in particular ovarian cancers, carry a high risk of thrombosis but coagulation activation is also thought to play a role in tumorigenesis and metastasis. In experimental animal models of metastasis, mice with a genetic procoagulant phenotype are prone to develop metastasis and anticoagulant therapy dramatically reduces pulmonary metastasis in these models. The aPC pathway is a key natural anticoagulant pathway, in addition to its role in venous thrombosis, dysregulation of this pathway is also thought to play a role in the pathogenesis of some cancers. No data exists in ovarian and endometrial cancers. AIM: The aim of this study is to determine the expression of key proteins of the activated protein C pathway in endometrial and ovarian malignant tumours compared to benign tumours and to assess their role in patient survival. MATERIALS AND METHODS: RNA was extracted from 78 (54 malignant and 24 benign) fresh frozen ovarian and endometrial tumours samples. Tumour biopsies were mRNA expression of endothelial protein C receptor (EPCR), protein S (PS), protein C (PC), thrombomodulin (TM), Factor V (FV) and VIII (FVIII) and PAR-1 and PAR-2 was measured using TaqMan Low Density Arrays. mRNA fold change relative to benign expression was determined using the 2 -delta delta Ct method with 18s as internal standard. All patients gave full and informed consent and the study had the approval of the hospital ethics committee. Total cell protein was extracted from ovarian tumour tissue. Enzyme-linked immunosorbent assay (ELISA) was used to measure protein plasma expression RESULTS: EPCR (P<0.001), protein S (P<0.0001) and Factor VIII (P<0.003) mRNA expression was significantly downregulated in malignant tumours compared with benign. Factor V and PAR-2 were significantly upregulated (P<0.001; P<0.004). Protein C was not consistently expressed. Reduced EPCR and TM protein expression was also observed in malignant tumours with increased plasma levels of Factor V. Reduced protein S and increased FV were associated with decreased survival. Plasma levels of Factor V were related to grade in the endometrial cancer group. PAR-2 mRNA expression was increased in ovarian tumours (P<0.001) however PAR-1 expression remained unchanged. CONCLUSIONS: Our results show reduced expression of key proteins associated with activation of protein C combined with increased expression in FV in gynaecological malignancies. These changes may contribute to local thrombin production and tumour progression and metastasis. Further work is required to determine the precise mechanisms involved.