Recent Submissions

  • The emergence of DNAM-1 as the facilitator of NK cell-mediated killing in ovarian cancer

    Pounds, Rachel; Croft, Wayne; Pearce, Hayden; Hossain, Tasnia; Singh, Kavita; Balega, Janos; Jeevan, David N; Sundar, Sudha; Kehoe, Sean; Yap, Jason; et al. (Frontiers Media, 2025-01-06)
    Introduction: Ovarian cancer (OC) is the sixth most common malignancy in women and the poor 5-year survival emphasises the need for novel therapies. NK cells play an important role in the control of malignant disease but the nature of tumour-infiltrating and peripheral NK cells in OC remains unclear. Methods: Using flow cytometric analysis, we studied the phenotype and function of NK cells in blood, primary tumour and metastatic tissue in 80 women with OC. The cell type contexture of metastatic OC tissue was explored utilising scRNAseq analysis, with a focus on portraying an immunogenic tumour microenvironment and determining the characteristics of a dysfunctional NK cell population. Results: The proportion of peripheral NK cells was markedly elevated with a highly activated profile and increased cytotoxicity. In contrast, NK cell numbers in primary tumour and metastasis were substantially reduced, with downregulation of activatory receptors together with elevated PD-1 expression. scRNA-Seq identified 5 NK cell subpopulations along with increased exhausted and immature NK cells within tumour tissue compared to normal tissue. These features were attenuated following chemotherapy where higher levels of activated and cytotoxic NK cells associated with improved disease-free survival. Correlation of NK cell phenotype with clinical outcomes revealed high levels of DNAM-1 expression on tissue-localised and peripheral NK cells to be associated with reduced survival. Expression of PVR, the DNAM-1 ligand, was significantly increased on tumours and DNAM-1 mediated NK cell lysis of primary tumour tissue was observed in vitro. Discussion: These findings reveal profound modulation of the tumour tissue and systemic profile of NK cells which likely contributes to the high rates of local progression and metastasis seen with OC. Immunotherapeutic approaches that overcome local immune suppression and enhance DNAM-1-targeted lysis of OC offer the potential to improve disease control.
  • Vulval flap reconstruction in women with benign, preneoplastic and malignant vulval conditions : a prospective study

    Kwong, Fong Lien; Pounds, Rachel; Farah, Yasmin; Yap, Jason; Kwong, Fong Lien; Pounds, Rachel; Farah, Yasmin; Yap, Jason; Pan Birmingham Gynaecological Cancer Centre; Medical and Dental; et al. (Wiley, 2025-03-31)
    Objectives: To (i) evaluate the surgical morbidity, (ii) identify correlates of these and, (iii) explore whether flap reconstruction following vulvectomy improves patient symptoms and quality of life. Design: Single arm prospective study. Setting: Single tertiary vulval centre, UK. Population: Consecutive cases of women undergoing radical vulvectomy and flap reconstructions for benign and (pre)invasive vulval conditions. Methods: Prospective data collection from April 2020-February 2024. All women were given two validated questionnaires preoperatively and at 3-, 6- and 12-months to evaluate their satisfaction with the aesthetic, genitourinary and psychosexual outcomes. Main outcome measures: Early and late complications within 30 days. Patient reported outcome measures preoperatively and post-reconstruction. Results: 136 flaps in 69 women were analysed. 92.6% (126/136) and 83.1% (113/136) flaps developed none-to-mild complications at 7 days, and between days 8 to 30, respectively. Five necrotic flaps in two patients were surgically debrided. All flaps had healed/healing at 30 days. We did not identify any correlates of complications. At 12 months, women reported an improvement in genital symptoms (p < 0.001). 80.4% (37/46) reported no urinary incontinence vs. 48.1% (26/54) preoperatively, p = 0.0038. 24.4% (11/45) were sexually active vs. 9.3% (5/54) preoperatively, p = 0.0410. More women felt attractive (p = 0.0498), were satisfied with their body (p = 0.0407) and comfortable in intimate situations (p = 0.0273). 88.9% (40/45) stated that reconstruction helped with acceptance of their cancer diagnosis and surgery. Conclusions: Locoregional flap reconstruction has low surgical morbidity, leads to a significant improvement in genitourinary and psychosexual functions. In women with cancer, reconstruction supports women to cope with their diagnosis.
  • Promoting equitable genetic testing in ovarian cancer : the demonstration of improvement for molecular ovarian cancer testing (DEMO) project

    Leung, Elaine Yl; Funingana, Ionut Gabriel; Bird, Lisa; Alcaraz, Marie-Lyne; Evans, Anuji; Considine, Anna; Freeman, Susan; Jimenez-Linan, Mercedes; Spencer, Catherine; Phanasan, Kiran; et al. (BMJ Publishing Group, 2025-02-25)
    Parallel genetic testing (testing for both tumour and germline gene changes) after the diagnosis of ovarian cancer should be considered the standard of care and is crucial to support treatment decisions. The demonstration of improvement for molecular ovarian cancer testing (DEMO) project aimed to develop patient-focused tools to promote equitable genetic care in diverse communities with high proportions of patients with limited English proficiency and biopsy guidelines to address the variations in specimen quality in different geographical regions in the UK. Our three work packages (WP) aimed to promote awareness by addressing the information gaps in different community groups (WP1), develop infrastructure to evaluate the different tissue collection pathways in different regions (WP2) and support continuing professional development (CPD) to encourage best practices with the involvement of patients (WP3). Our output included a multimedia multilanguage information package with paired National Health Service-branded written materials to support genetic testing after ovarian cancer diagnosis (https://ovarian.org.uk/demo-uk/), a scalable database to enable a multisite audit of parallel genetic testing pathways and a collection of CPD events that had patient involvement as an essential component. In addition, we have collaborated with patient and community groups to contribute to a national consensus guidance on genetic testing in ovarian cancer. Our co-production work has been recognised by local and regional awards as an exemplar for patient and public involvement (PPI). This has supported the start of a legacy co-production group in gynaeoncology (https://www.dhlnetwork.com/gohildas) to address the critical unmet need for sustainable and equity-oriented PPI to advocate for underserved communities. The DEMO project has contributed to raising awareness of the importance of equitable genetic care in ovarian cancer. We will continue to build on this groundwork to support future quality improvement projects and research, with the ultimate goal of improving the outcomes of patients with ovarian cancer.
  • Key clinical findings from the IMPROVE-UK quality improvement projects : an overview

    Phillips, Andrew James; Bowen, Rebecca; Wells, Mary; McNeish, Iain; Sundar, Sudha; Sundar, Sudha; Gynaecological Oncology; Medical and Dental; University Hospitals of Derby and Burton NHS Foundation Trust; Royal United Hospital Bath NHS Trust; Imperial College Healthcare NHS Trust; Sandwell and West Birmingham NHS Trust; et al. (BMJ Publishing Group, 2025-02-25)
    Introduction: Survival from ovarian cancer in the UK is poor compared with international comparators. The Ovarian Cancer Audit Feasibility Pilot demonstrated variation in 1-year and 5-year survival across the UK as well as significant variation in treatment rates. In 2020, IMPROVE-UK was established as the first major programme to address inequalities in ovarian cancer management and survival across the UK, to develop a legacy of best practice sharing across the country and to establish and evaluate quality improvement projects that could drive care at scale. Methods: Following a competitive process, seven quality improvement projects were funded to address inequalities in care and identify strategies to improve and equalise survival rates for all women with ovarian cancer in the UK, to address health inequalities from geography, age or ethnicity. Results: Projects addressed the secondary care diagnostic pathway, genomic testing, prehabilitation and improving treatment-related decision-making, particularly decisions for surgery. All seven projects at least partial achieved their aims with numerous areas across all projects identified where processes could be refined and incorporated into standard care to improve outcomes of women diagnosed with ovarian cancer. Dissemination of information regarding best practice has been undertaken. Conclusion: IMPROVE-UK was the first programme of its kind addressing significant inequalities of care in women with ovarian cancer. We demonstrate systematic quality improvement projects in ovarian cancer targeting various aspects of the treatment journey. Scaling up the results of the improve UK pilots is likely to improve survival in the UK and potentially internationally.
  • Quality of life from cytoreductive surgery in advanced ovarian cancer: Investigating the association between disease burden and surgical complexity in the international, prospective, SOCQER-2 cohort study.

    Sundar, Sudha; Cummins, Carole; Kumar, Satyam; Long, Joanna; Arora, Vivek; Balega, Janos; Broadhead, Tim; Duncan, Tim; Edmondson, Richard; Fotopoulou, Christina; et al. (Wiley, 2022-01-10)
    Objective: To investigate quality of life (QoL) and association with surgical complexity and disease burden after surgical resection for advanced ovarian cancer in centres with variation in surgical approach. Design: Prospective multicentre observational study. Setting: Gynaecological cancer surgery centres in the UK, Kolkata, India, and Melbourne, Australia. Sample: Patients undergoing surgical resection (with low, intermediate or high surgical complexity score, SCS) for late-stage ovarian cancer. Main outcome measures: Primary: change in global score on the European Organisation for Research and Treatment of Cancer (EORTC) core quality-of-life questionnaire (QLQ-C30). Secondary: EORTC ovarian cancer module (OV28), progression-free survival. Results: Patients' preoperative disease burden and SCS varied between centres, confirming differences in surgical ethos. QoL response rates were 90% up to 18 months. Mean change from the pre-surgical baseline in the EORTC QLQ-C30 was 3.4 (SD 1.8, n = 88) in the low, 4.0 (SD 2.1, n = 55) in the intermediate and 4.3 (SD 2.1, n = 52) in the high-SCS group after 6 weeks (p = 0.048), and 4.3 (SD 2.1, n = 51), 5.1 (SD 2.2, n = 41) and 5.1 (SD 2.2, n = 35), respectively, after 12 months (p = 0.133). In a repeated-measures model, there were no clinically or statistically meaningful differences in EORTC QLQ-C30 global scores between the three SCS groups (p = 0.840), but there was a small statistically significant improvement in all groups over time (p < 0.001). The high-SCS group experienced small to moderate decreases in physical (p = 0.004), role (p = 0.016) and emotional (p = 0.001) function at 6 weeks post-surgery, which resolved by 6-12 months. Conclusions: The global QoL of patients undergoing low-, intermediate- and high-SCS surgery improved at 12 months after surgery and was no worse in patients undergoing extensive surgery. Tweetable abstract: Compared with surgery of lower complexity, extensive surgery does not result in poorer quality of life in patients with advanced ovarian cancer.
  • Re-intervention and patient satisfaction rates following office radiofrequency endometrial ablation: a comparative retrospective study of 408 cases.

    Ghoubara, Ahmed; Gunasekera, Seuvandhi; Rao, Lavanya; Ewies, Ayman; Gunasekera, Seuvandhi; Rao, Lavanya; Ewies, Ayman; Sandwell and West Birmingham NHS Trust; Medical and Dental; Sandwell and West Birmingham NHS Trust; University of Birmingham; Aswan University Hospital (Taylor and Francis Group, 2021-10-23)
    This retrospective study assessed the efficacy and long-term satisfaction of radiofrequency endometrial ablation outside the context of clinical trials in 408 women, and compared the outcome between office-setting (211, 52%) and day-case procedures under general anaesthetics (197, 48%). The Kaplan Meir time-to-event analysis showed that the cumulative number of women undergoing surgical re-intervention was 32 with a probability of 9.4% (95% CI: 6.3 - 12.5%) at 2-years, and 45 with a probability of 14.5% (95% CI: 10.3 - 18.2%) at 5-years. There was no statistically significant difference in the re-intervention rate between office and day-case groups (HR = 0.7, 95% CI: 0.68 - 3.1, p = .3). The satisfaction rate, measured by Visual Analogue Scale, was not statistically different (p = .5) between office (109; 80.7%) and day-case (96; 82.8%) groups. This study showed lower surgical re-intervention rate than previously reported in observational studies, and high rates of long-term women satisfaction. The outcomes were similar in office and day-case settings.Impact statementWhat is already known on this subject? Previous studies have shown the safety and effectiveness of radiofrequency endometrial ablation for treating heavy periods. However, studies investigating it, outside clinical trials, either included a small sample size, a short-term follow-up, poor reporting so that it is impossible to judge whether some women underwent re-intervention in another centre, failed to discriminate in analysis between second-generation techniques, or assessed only short-term satisfaction.What do the results of this study add? This is the largest series reported from a single centre and the first study reporting long-term satisfaction in women, outside clinical trials. Surgical re-intervention was used as the primary outcome measure which is an objective measure rather than the change in the monthly flow which is rather subjective. More importantly, the study records the similarity, in the outcome and women's satisfaction rate, between office and day-case procedures under general anaesthetics.What are the implications of these findings for clinical practice and/or further research? Endometrial ablation service is widely implemented in office-setting in the UK. We hope the result of this study encourages implementation on a larger scale in office across centres in the world with its multiple advantages both to women and service alike.
  • The evolving role of one-step nucleic acid amplification (OSNA) for the intra-operative detection of lymph node metastases: A diagnostic accuracy meta-analysis

    Tranoulis, Anastasios; Georgiou, Dimitra; Yap, Jason; Attard-Montalto, Stephen; Twigg, Jeremy; Elattar, Ahmed; singh, Kavita; Balega, Janos; Kehoe, Sean; Tranoulis, A,; et al. (Elsevier, 2021-06)
    Background: One Step Nucleic Acid Amplification (OSNA) assay has recently emerged as a rapid molecular diagnostic tool for the detection of lymph node (LN) metastases. It is a molecular technique that analyses the entire LN tissue using a reverse-transcriptase loop-mediated isothermal amplification reaction to detect tumour specific cytoceratin 19 mRNA. Aim: To ascertain the diagnostic accuracy of OSNA assay in detecting LN metastases amongst different types of malignancy. Design: We systematically searched MEDLINE, SCOPUS, ClinicalTrials.gov, and Cochrane Database, from inception up to August 2020. Quality assessment was performed using the Modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We calculated pooled diagnostic indices using the random-effects model. Meta-regression and sub-group analyses were performed to address heterogeneity. Results: 31 studies were included in this meta-analysis, including four different types of cancer. The risk of bias and the overall quality of included studies was moderate to high. There was no evidence of publication bias. The pooled diagnostic odds ratio (DOR) for detecting LN metastases in gynaecological, head & neck/thyroid, gastrointestinal and lung cancer were 100.38, 76.17, 275.14, and 305.84, respectively. Conclusions: Our findings suggest that OSNA assay had a high diagnostic accuracy in detecting metastatic LNs in different types of malignancy. This evidence is constrained by the limited studies available for few tumour types and the rather high heterogeneity for few outcomes.
  • The Major Constituent of Green Tea, Epigallocatechin-3-Gallate (EGCG), Inhibits the Growth of HPV18-Infected Keratinocytes by Stimulating Proteasomal Turnover of the E6 and E7 Oncoproteins.

    Yap, Jason K W; Kehoe, Sean T; Woodman, Ciaran B J; Dawson, Christopher W; Yap, Jason K W; Kehoe, Sean T; Sandwell and West Birmingham NHS Trust; Medical and Dental; University of Birmingham; Sandwell West Birmingham NHS Trust; University of Warwick (MDPI, 2021-04-11)
    Epigallocatechin-3-gallate (EGCG), the primary bioactive polyphenol in green tea, has been shown to inhibit the growth of human papilloma virus (HPV)-transformed keratinocytes. Here, we set out to examine the consequences of EGCG treatment on the growth of HPV18-immortalised foreskin keratinocytes (HFK-HPV18) and an authentic HPV18-positive vulvar intraepithelial neoplasia (VIN) clone, focusing on its ability to influence cell proliferation and differentiation and to impact on viral oncogene expression and virus replication. EGCG treatment was associated with degradation of the E6 and E7 oncoproteins and an upregulation of their associated tumour suppressor genes; consequently, keratinocyte proliferation was inhibited in both monolayer and organotypic raft culture. While EGCG exerted a profound effect on cell proliferation, it had little impact on keratinocyte differentiation. Expression of the late viral protein E4 was suppressed in the presence of EGCG, suggesting that EGCG was able to block productive viral replication in differentiating keratinocytes. Although EGCG did not alter the levels of E6 and E7 mRNA, it enhanced the turnover of the E6 and E7 proteins. The addition of MG132, a proteasome inhibitor, to EGCG-treated keratinocytes led to the accumulation of the E6/E7 proteins, showing that EGCG acts as an anti-viral, targeting the E6 and E7 proteins for proteasome-mediated degradation.
  • The chromatin landscape of high-grade serous ovarian cancer metastasis identifies regulatory drivers in post-chemotherapy residual tumour cells

    Croft, W; Pounds, Rachel; Jeevan, D; Singh, K; Balega, J; Sundar, Sudha; Williams, A; Ganesan, R; Kehoe, S; Ott, S; et al. (Nature Research, 2024-09-28)
    Disease recurrence following chemotherapy is a major clinical challenge in ovarian cancer (OC), but little is known regarding how the tumour epigenome regulates transcriptional programs underpinning chemoresistance. We determine the single cell chromatin accessibility landscape of omental OC metastasis from treatment-naïve and neoadjuvant chemotherapy-treated patients and define the chromatin accessibility profiles of epithelial, fibroblast, myeloid and lymphoid cells. Epithelial tumour cells display open chromatin regions enriched with motifs for the oncogenic transcription factors MEIS and PBX. Post chemotherapy microenvironments show profound tumour heterogeneity and selection for cells with accessible chromatin enriched for TP53, TP63, TWIST1 and resistance-pathway-activating transcription factor binding motifs. An OC chemoresistant tumour subpopulation known to be present prior to treatment, and characterised by stress-associated gene expression, is enriched post chemotherapy. Nuclear receptors RORa, NR2F6 and HNF4G are uncovered as candidate transcriptional drivers of these cells whilst closure of binding sites for E2F2 and E2F4 indicate post-treated tumour having low proliferative capacity. Delineation of the gene regulatory landscape of ovarian cancer cells surviving chemotherapy treatment therefore reveals potential core transcriptional regulators of chemoresistance, suggesting novel therapeutic targets for improving clinical outcome.
  • Friend or foe? The prognostic role of endometriosis in women with clear cell ovarian carcinoma. A UK population-based cohort study.

    Tranoulis, Anastasios; Buruiana, Felicia Elena; Gupta, Bindiya; Kwong, Audrey; Lakhiani, Aarti; Yap, Jason; Balega, Janos; Singh, Kavita; Tranoulis, Anastasios; Buruiana, Felicia Helena.; et al. (Springer, 2021-09-01)
    Purpose: The prognostic role of endometriosis amongst women with ovarian clear cell carcinoma (OCCC) remains debatable. The aim of this study was to ascertain the effect of endometriosis on the prognosis of OCCC. Methods: A retrospective review of the medical records of 94 women diagnosed and treated for OCCC at a tertiary gynaecological cancer centre in the UK, spanning the period 2010-2019. Women were divided into two groups according to the presence of endometriosis. Clinico-pathological characteristics, progression-free survival (PFS) and overall survival (OS) were collated between the two groups. Results: Forty-six cases of endometriosis-free OCCC (Ef-OCCC) were collated with 48 cases of endometriosis-related OCCC (Er-OCCC). There was no significant difference between the two groups regarding age (p-value = 0.2), FIGO stage (p-value = 0.8), residual disease (RD) (p-value = 0.07), adjuvant chemotherapy agent (p-value = 0.4) or chemo-resistance (p-value = 0.9). The presence of endometriosis did not significantly affect either OS or PFS. The median OS in the Ef-OCCC and Er-OCCC was 55.00 (95% CI 32.00-189.00) and 71.00 (95% CI 47.00-97.00; log rank = 1.35, p-value = 0.2) months. The median PFS in the Ef-OCCC and Er-OCCC group was 39.00 (95% CI 19.00-143.00) and 39.00 (95% CI 19.00-62.00; log rank = 0.7, p-value = 0.4) months. Survival differences between the two groups were not significant after stratification analysis for independent prognosticators. Conclusion: Endometriosis was not independently associated with the prognosis of OCCC either in crude analysis or after stratification for stage and RD. Further larger, well-designed prospective studies are warranted to draw firmer conclusions on the intrinsic link between endometriosis and OCCC.
  • British Gynaecological Cancer Society (BGCS) ovarian, tubal and primary peritoneal cancer guidelines : recommendations for practice update 2024

    Moss, Esther; Taylor, Alexandra; Andreou, Adrian; Ang, Christine; Arora, Rupali; Attygalle, Ayoma; Banerjee, Susana; Bowen, Rebecca; Buckley, Lynn; Burbos, Nikos; et al. (Elsevier, 2024-06-21)
    No abstract available.
  • Diagnostic Accuracy of FEC-PET/CT, FDG-PET/CT, and Diffusion-Weighted MRI in Detection of Nodal Metastases in Surgically Treated Endometrial and Cervical Carcinoma.

    Rockall, Andrea G; Barwick, Tara D; Wilson, William; Singh, Naveena; Bharwani, Nishat; Sohaib, Aslam; Nobbenhuis, Marielle; Warbey, Victoria; Miquel, Marc; Koh, Dow-Mu; et al. (American Association for Cancer Research, 2021-09-15)
    Preoperative nodal staging is important for planning treatment in cervical cancer and endometrial cancer, but remains challenging. We compare nodal staging accuracy of 18F-ethyl-choline-(FEC)-PET/CT, 18F-fluoro-deoxy-glucose-(FDG)-PET/CT, and diffusion-weighted-MRI (DW-MRI) with conventional morphologic MRI.
  • British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for genetic testing in epithelial ovarian cancer in the United Kingdom

    Leung, Elaine Yl; Nicum, Shibani; Morrison, Jo; Brenton, James D; Funingana, Ionut-Gabriel; Morgan, Robert D; Ghaem-Maghami, Sadaf; Miles, Tracie; Manchanda, Ranjit; Bowen, Rebecca; et al. (BMJ Publishing Group, 2024-09-02)
    Standard of care genetic testing has undergone significant changes in recent years. The British Gynecological Cancer Society and the British Association of Gynecological Pathologists (BGCS/BAGP) has re-assembled a multidisciplinary expert consensus group to update the previous guidance with the latest standard of care for germline and tumor testing in patients with ovarian cancer. For the first time, the BGCS/BAGP guideline group has incorporated a patient advisor at the initial consensus group meeting. We have used patient focused groups to inform discussions related to reflex tumor testing - a key change in this updated guidance. This report summarizes recommendations from our consensus group deliberations and audit standards to support continual quality improvement in routine clinical settings.
  • Venous thromboembolism during neoadjuvant chemotherapy for ovarian cancer

    Oxley, Samuel; Ahmed, Sarah; Baxter, Kathryn; Blake, Dominic; Braden, Victoria; Brincat, Mark R; Bryan, Stacey; Dilley, James; Dobbs, Stephen; Durden, Andrew; et al. (BMJ Publishing Group, 2024-08-24)
    Objective: To determine the incidence of venous thromboembolism in patients with advanced epithelial ovarian cancer undergoing neoadjuvant chemotherapy in UK gynecological cancer centers. Secondary outcomes included incidence and timing of venous thromboembolism since cancer presentation, impact on cancer treatment, and mortality. Methods: All UK gynecological cancer centers were invited to participate in this multi-center retrospective audit through the British Gynecological Cancer Society. Data were captured on all patients undergoing neoadjuvant chemotherapy for International Federation of Gynecology and Obstetrics (FIGO) stage III/IV epithelial ovarian cancer within a 12-month period during 2021-2022. Patients on anticoagulation prior to cancer presentation were excluded. Patients who were diagnosed with venous thromboembolism between cancer presentation and commencing neoadjuvant chemotherapy were also excluded from our analysis of venous thromboembolism rates from neoadjuvant chemotherapy. Results: Fourteen UK gynecological cancer centers returned data on 660 eligible patients. The median age was 67 years (range 34-96). In total, 131/660 (19.8%) patients were diagnosed with venous thromboembolism from cancer presentation until discharge following cytoreductive surgery. Between commencing neoadjuvant chemotherapy and post-operative discharge, 65/594 (10.9%) patients developed venous thromboembolism (median 11.3%, IQR 5.9-11.3); 55/594 (9.3%) during neoadjuvant chemotherapy, 10/594 (1.7%) during post-operative admission. There was no significant difference across centers (p=0.47). Of these 65 patients, 44 (68%) were diagnosed with pulmonary embolism and 30 (46%) with deep-vein thrombosis (nine had both), including in major abdominal/pelvic vessels, with 36 (55%) presenting symptomatically and 29 (45%) diagnosed incidentally on imaging. Venous thromboembolism resulted in mortality (n=3/65, 5%), and delays/changes/cancelation of treatment (n=18/65, 28%). Conclusion: Across a large, representative sample of UK gynecological cancer centers, one in five patients undergoing neoadjuvant chemotherapy were diagnosed with a potentially preventable venous thromboembolism, including one in nine diagnosed after commencing chemotherapy. This led to adverse clinical consequences for one third, including delay to oncological treatment and mortality. This high venous thromboembolism rate justifies the consideration of thromboprophylaxis in this patient group.
  • Correspondence on 'Staging by imaging in gynecologic cancer and the role of ultrasound : an update of European joint consensus statements' by Fischerova et al

    Kwong, Audrey; Nevin, James; Yap, Jason; Kwong, Audrey; Nevin, James; Yap, Jason; Pan Birmingham Gynaecological Cancer Centre; Medical and Dental; Sandwell and West Birmingham NHS Trust; University of Birmingham (BMJ Publishing Group, 2024-08-07)
    No abstract available
  • British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumor testing for 1/2 variants in ovarian cancer in the United Kingdom.

    Sundar, Sudha; Manchanda, Ranjit; Gourley, Charlie; George, Angela; Wallace, Andrew; Balega, Janos; Williams, Sarah; Wallis, Yvonne; Edmondson, Richard; Nicum, Shibani; et al. (BMJ Publishing Group, 2021-01-19)
    The British Gynecological Cancer Society and the British Association of Gynecological Pathologists established a multidisciplinary consensus group comprising experts in surgical gynecological oncology, medical oncology, genetics, and laboratory science, and clinical nurse specialists to identify the optimal pathways to BRCA germline and tumor testing in patients with ovarian cancer in routine clinical practice. In particular, the group explored models of consent, quality standards identified at pathology laboratories, and experience and data from pioneering cancer centers. The group liaised with representatives from ovarian cancer charities to also identify patient perspectives that would be important to implementation. Recommendations from these consensus group deliberations are presented in this manuscript.
  • British Gynaecological Cancer Society (BGCS) uterine cancer guidelines: Recommendations for practice.

    Morrison, Jo; Balega, Janos; Buckley, Lynn; Clamp, Andrew; Crosbie, Emma; Drew, Yvette; Durrant, Lisa; Forrest, Jenny; Fotopoulou, Christina; Gajjar, Ketan; et al. (Elsevier, 2021-11-25)
    The remit of this guideline is to collate and propose evidence-based guidelines for the diagnosis and management of uterine cancer. This document covers all uterine cancers of any histological type.
  • Investigating age and ethnicity as novel high-risk phenotypes in mucinous ovarian cancer : retrospective study in a multi-ethnic population

    Olaoye, Tejumola; -, Ayushi; Boyle, William; Williams, Anthony; Ganesan, Raji; Subba, Kamana; Goyal, Akanksha; Leung, Elaine; Chowdhary, Rahul; Pascoe, Jennifer; et al. (BMJ Publishing Group, 2024-06-11)
    Objectives: Primary mucinous ovarian carcinoma represents 3% of ovarian cancers and is typically diagnosed early, yielding favorable outcomes. This study aims to identify risk factors, focussing on the impact of age and ethnicity on survival from primary mucinous ovarian cancer. Methods: A retrospective observational study of patients treated at Sandwell and West Birmingham Hospitals NHS Trust and University Hospital Coventry and Warwickshire. Patients included were women aged ≥16 years, with primary mucinous ovarian cancer confirmed by specialist gynecological histopathologist and tumor immunohistochemistry, including cytokeratin-7, cytokeratin-20, and CDX2. Statistical analyses were performed using R integrated development environment, with survival assessed by Cox proportional hazards models and Kaplan-Meier plots. Results: A total of 163 patients were analyzed; median age at diagnosis was 58 years (range 16-92), 145 (89%) were International Federation of Gynecology and Obstetrics stage I and 43 (26%) patients had infiltrative invasion. Women aged ≤45 years were more likely to have infiltrative invasion (RR=1.38, 95% CI 0.78 to 2.46), with increased risk of death associated with infiltrative invasion (HR=2.29, 95% CI 1.37 to 5.83). Compared with White counterparts, South Asian women were more likely to undergo fertility-sparing surgery (RR=3.52, 95% CI 1.48 to 8.32), and have infiltrative invasion (RR=1.25, 95% CI 0.60 to 2.58). South Asian women undergoing fertility-sparing surgery had worse prognosis than those undergoing traditional staging surgery (HR=2.20, 95% CI 0.39 to 13.14). In FIGO stage I disease, 59% South Asian and 37% White women received adjuvant chemotherapy (p=0.06). South Asian women exhibited a worse overall prognosis than White women (HR=2.07, 95% CI 0.86 to 4.36), particularly pronounced in those aged ≤45 years (HR=8.75, 95% CI 1.22 to 76.38). Conclusion: This study identified young age as a risk factor for diagnosis of infiltrative invasion. Fertility-sparing surgery in South Asian women is a risk factor for poorer prognosis. South Asian women exhibit poorer overall survival than their White counterparts.
  • Aberrant activation of the Hedgehog signalling pathway in squamous cell carcinoma of the vulva as a potential target for cancer therapy.

    Yap, Jason; Uddin, Khalil; Pounds, Rachel; O'Neill, Danielle; Kehoe, Sean; Ganesan, Raji; Dawson, Christopher W; Yap, Jason; Pounds, Rachel; Pan Birmingham Gynaecological Cancer Centre; et al. (Nature Research, 2021-09-03)
    In a previous study, we showed that the Hedgehog (Hh) signalling pathway is aberrantly activated in vulval squamous cell carcinoma (VSCC). In this study, we further validated our findings on a prospective cohort of primary VSCC cases, where immunohistochemical staining confirmed that key Hh pathway components were overexpressed in VSCC compared to normal vulval epithelium. We also undertook a series of in vitro studies to determine the extent of Hh pathway activation in VSCC-derived cell lines, and examine the consequences of pathway inhibition on the growth of these cells. We found that of six cell lines tested, four displayed elevated baseline Hh pathway activity that was dependent on SHH ligand, or in one case, a PTCH1 gene mutation. Hh signalling appeared necessary to sustain cell growth, as SHH ligand depletion with Robotikinin or SMO inhibition, either with chemical inhibitors (Itraconazole or LDE-225) or SMO-specific siRNA, attenuated GLI1 activity and cell proliferation in both monolayer and organotypic raft culture. Furthermore, treatment of Hh-dependent cell lines with SMO inhibitors sensitised cells to Cisplatin. Findings from our study offer us the opportunity to explore further the development of targeted chemotherapy for women with VSCC driven by aberrant Hh activation.
  • Office hysteroscopic morcellation service: Evaluation of women experience and factors affecting satisfaction.

    Pervaiz, Zahra; Korrapati, Sivanandana; Ghoubara, Ahmed; Ewies, Ayman A. A.; Pervaiz, Z; Korrapati, S; Ghoubara, A; Ewies, A; Sandwell and West Birmingham NHS Trust; Medical and Dental; et al. (Elsevier, 2021-07-28)
    Objectives: To evaluate the hysteroscopic morcellation service in office-setting in everyday practice outside the context of clinical trials. The primary objectives were to assess level of acceptability and factors affecting women satisfaction. The secondary objectives included assessment of complete resection rate, complications rate, pain score during the procedure and on discharge, and the correlation between the lesion size as subjectively estimated by the hysteroscopists versus the volume of morcellated tissues as semi-quantitively measured by the laboratory. Method: The clinical data was compiled for 287 consecutive women undergoing hysteroscopic morcellation in office-setting from 1 January 2017 to 31 March 2021 in a teaching hospital in the UK. A questionnaire, formulated on the Visual Analogue Scale (VAS), was completed immediately after the procedure by the last 110 women undergoing the procedure. Results: The mean age of the cohort (n = 278) was 54.5 years (SD ± 12.5). Only 7 (2.4%) women required two-stage procedure because of size (fibroid ≥ 4 cm), vascularity or multiplicity of lesions. No complications were encountered. The majority of women completing the questionnaire (n = 110) found office procedure acceptable (105, 95.5%, VAS ≥ 7), were willing to have it again if indicated (102, 92.7%, VAS ≥ 7), would recommend it to family and friends (105, 95.5%, VAS ≥ 7) and confirmed receiving adequate preoperative information by doctors and nurses (107, 97.3%, VAS ≥ 7). The level of preoperative explanation and information-giving showed significant (p < 0.01) positive correlation with the level of acceptability and recommendation to others and significant (p = .007) negative correlation with the pain experienced on discharge. The median (IQR) estimated size at hysteroscopy was 2 cm (1-6 cm) for polyps and 2.5 cm (1-4 cm) for fibroid. The median (IQR) volume of the morcellated specimens as estimated by laboratory was 2000 mm3 (1100-3800 mm3). The estimated size at hysteroscopy was positively correlated with the specimen's volume (Spearman's rho (r) = 0.31, 95% = CI, 0.14-0.45, p < 0.01). Conclusion: Office hysteroscopic morcellation is associated with high satisfaction rate and low pain score on discharge. Good preoperative explanation and information-giving was the crucial factor that increased women satisfaction. Subjective estimation of lesion size by hysteroscopists may be an accurate and simple method of measurement.

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