Search

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., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Semiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients' survival analysis., Methods: Training (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic., Results: Although the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis., Conclusions: The Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival., Trial Registration: ClinicalTrials.gov NCT03543215, https://clinicaltrials.gov/ , date of registration: 30th June 2017., (© 2024. The Author(s).)

Tertiary lymphoid structure (TLS) is associated with prognosis in copy-number-driven tumors, including high-grade serous ovarian cancer (HGSOC), although the function of TLS and its interaction with copy-number alterations in HGSOC are not fully understood. In the current study, we confirm that TLS-high HGSOC patients show significantly better progression-free survival (PFS). We show that the presence of TLS in HGSOC tumors is associated with B cell maturation and cytotoxic tumor-specific T cell activation and proliferation. In addition, the copy-number loss of IL15 and CXCL10 may limit TLS formation in HGSOC; a list of genes that may dysregulate TLS function is also proposed. Last, a radiomics-based signature is developed to predict the presence of TLS, which independently predicts PFS in both HGSOC patients and immune checkpoint inhibitor (ICI)-treated non-small cell lung cancer (NSCLC) patients. Overall, we reveal that TLS coordinates intratumoral B cell and T cell response to HGSOC tumor, while the cancer genome evolves to counteract TLS formation and function., Competing Interests: Declaration of interests D.J.P. has received lecture fees from ViiV Healthcare, Bayer Healthcare, BMS, Roche, EISAI, and Falk Foundation; travel expenses from BMS and Bayer Healthcare; consulting fees from Mina Therapeutics, EISAI, Roche, Avamune, Exact Sciences, Mursla, DaVolterra, and Astra Zeneca; and research funding (to institution) from MSD and BMS., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Determination of survival time in women with endometrial cancer using clinical features remains imprecise. Features from MRI may improve the survival estimation allowing improved treatment planning., Purpose: To identify clinical features and imaging signatures on T2-weighted MRI that can be used in an integrated model to estimate survival time for endometrial cancer subjects., Study Type: Retrospective., Population: Four hundred thirteen patients with endometrial cancer as training (N = 330, 66.41 ± 11.42 years) and validation (N = 83, 67.60 ± 11.89 years) data and an independent set of 82 subjects as testing data (63.26 ± 12.38 years)., Field Strength/sequence: 1.5-T and 3-T scanners with sagittal T2-weighted spin echo sequence., Assessment: Tumor regions were manually segmented on T2-weighted images. Features were extracted from segmented masks, and clinical variables including age, cancer histologic grade and risk score were included in a Cox proportional hazards (CPH) model. A group least absolute shrinkage and selection operator method was implemented to determine the model from the training and validation datasets., Statistical Tests: A likelihood-ratio test and decision curve analysis were applied to compare the models. Concordance index (CI) and area under the receiver operating characteristic curves (AUCs) were calculated to assess the model., Results: Three radiomic features (two image intensity and volume features) and two clinical variables (age and cancer grade) were selected as predictors in the integrated model. The CI was 0.797 for the clinical model (includes clinical variables only) and 0.818 for the integrated model using training and validation datasets, the associated mean AUC value was 0.805 and 0.853. Using the testing dataset, the CI was 0.792 and 0.882, significantly different and the mean AUC was 0.624 and 0.727 for the clinical model and integrated model, respectively., Data Conclusion: The proposed CPH model with radiomic signatures may serve as a tool to improve estimated survival time in women with endometrial cancer., Evidence Level: 4 TECHNICAL EFFICACY: Stage 2., (© 2022 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.)

Purpose: To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images., Methods: A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models., Results: Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively., Conclusion: It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.

With increased use of mass spectrometry imaging (MSI) in support of pharmaceutical research and development, there are opportunities to develop analytical pipelines that incorporate exploratory high-performance analysis with higher capacity and faster targeted MSI. Therefore, to enable faster MSI data acquisition we present analyte-targeted desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) utilizing a triple-quadrupole (TQ) mass analyzer. The evaluated platform configuration provided superior sensitivity compared to a conventional time-of-flight (TOF) mass analyzer and thus holds the potential to generate data applicable to pharmaceutical research and development. The platform was successfully operated with sampling rates up to 10 scans/s, comparing positively to the 1 scan/s commonly used on comparable DESI-TOF setups. The higher scan rate enabled investigation of the desorption/ionization processes of endogenous lipid species such as phosphatidylcholines and a co-administered cassette of four orally dosed drugs-erlotininb, moxifloxacin, olanzapine, and terfenadine. This was used to enable understanding of the impact of the desorption/ionization processes in order to optimize the operational parameters, resulting in improved compound coverage for olanzapine and the main olanzapine metabolite, hydroxy-olanzapine, in brain tissue sections compared to DESI-TOF analysis or matrix-assisted laser desorption/ionization (MALDI) platforms. The approach allowed reducing the amount of recorded information, thus reducing the size of datasets from up to 150 GB per experiment down to several hundred MB. The improved performance was demonstrated in case studies investigating the suitability of this approach for mapping drug distribution, spatially resolved profiling of drug-induced nephrotoxicity, and molecular-histological tissue classification of ovarian tumors specimens.

Background: This study aimed to assess the impact of multiple COVID-19 waves on UK gynaecological-oncology services., Methods: An online survey was distributed to all UK-British-Gynaecological-Cancer-Society members during three COVID-19 waves from 2020 to2022., Results: In total, 51 hospitals (including 32 cancer centres) responded to Survey 1, 42 hospitals (29 centres) to Survey 2, and 39 hospitals (30 centres) to Survey 3. During the first wave, urgent referrals reportedly fell by a median of 50% (IQR = 25-70%). In total, 49% hospitals reported reduced staffing, and the greatest was noted for trainee doctors, by a median of 40%. Theatre capacity was reduced by a median of 40%. A median of 30% of planned operations was postponed. Multidisciplinary meetings were completely virtual in 39% and mixed in 65% of the total. A median of 75% of outpatient consultations were remote. By the second wave, fewer hospitals reported staffing reductions, and there was a return to pre-pandemic urgent referrals and multidisciplinary workloads. Theatre capacity was reduced by a median of 10%, with 5% of operations postponed. The third wave demonstrated worsening staff reductions similar to Wave 1, primarily from sickness. Pre-pandemic levels of urgent referrals/workload continued, with little reduction in surgical capacity., Conclusion: COVID-19 led to a significant disruption of gynaecological-cancer care across the UK, including reduced staffing, urgent referrals, theatre capacity, and working practice changes. Whilst disruption eased and referrals/workloads returned to normal, significant staff shortages remained in 2022, highlighting persistent capacity constraints.

Introduction: Delays in the diagnosis and treatment of endometrial cancer negatively impact patient survival. The aim of this study was to establish whether rapid evaporative ionisation mass spectrometry using the iKnife can accurately distinguish between normal and malignant endometrial biopsy tissue samples in real time, enabling point-of-care (POC) diagnoses. Methods: Pipelle biopsy samples were obtained from consecutive women needing biopsies for clinical reasons. A Waters G2-XS Xevo Q-Tof mass spectrometer was used in conjunction with a modified handheld diathermy (collectively called the 'iKnife'). Each tissue sample was processed with diathermy, and the resultant surgical aerosol containing ionic lipid species was then analysed, producing spectra. Principal component analyses and linear discriminant analyses were performed to determine variance in spectral signatures. Leave-one-patient-out cross-validation was used to test the diagnostic accuracy. Results: One hundred and fifty patients provided Pipelle biopsy samples (85 normal, 59 malignant, 4 hyperplasia and 2 insufficient), yielding 453 spectra. The iKnife differentiated between normal and malignant endometrial tissues on the basis of differential phospholipid spectra. Cross-validation revealed a diagnostic accuracy of 89% with sensitivity, specificity, positive predictive value and negative predictive value of 85%, 93%, 94% and 85%, respectively. Conclusions: This study is the first to use the iKnife to identify cancer in endometrial Pipelle biopsy samples. These results are highly encouraging and suggest that the iKnife could be used in the clinic to provide a POC diagnosis.

Background: There is increasing recognition that prehabilitation is important as a means of preparing patients physically and psychologically for cancer treatment. However, little is understood about the role and optimal nature of prehabilitation for gynaecological cancer patients, who usually face extensive and life-changing surgery in addition to other treatments that impact significantly on physiological and psychosexual wellbeing., Review Question: This scoping review was conducted to collate the research evidence on multimodal prehabilitation in gynaecological cancers and the related barriers and facilitators to engagement and delivery that should be considered when designing a prehabilitation intervention for this group of women., Methods: Seven medical databases and four grey literature repositories were searched from database inception to September 2021. All articles, reporting on multimodal prehabilitation in gynaecological cancers were included in the final review, whether qualitative, quantitative or mixed-methods. Qualitative studies on unimodal interventions were also included, as these were thought to be more likely to include information about barriers and facilitators which could also be relevant to multimodal interventions. A realist framework of context, mechanism and outcome was used to assist interpretation of findings., Results: In total, 24 studies were included in the final review. The studies included the following tumour groups: ovarian only (n = 12), endometrial only (n = 1), mixed ovarian, endometrial, vulvar (n = 5) and non-specific gynaecological tumours (n = 6). There was considerable variation across studies in terms of screening for prehabilitation, delivery of prehabilitation and outcome measures. Key mechanisms and contexts influencing engagement with prehabilitation can be summarised as: (1) The role of healthcare professionals and organisations (2) Patients' perceptions of acceptability (3) Factors influencing patient motivation (4) Prehabilitation as a priority (5) Access to prehabilitation., Implications for Practice: A standardised and well evidenced prehabilitation programme for women with gynaecological cancer does not yet exist. Healthcare organisations and researchers should take into account the enablers and barriers to effective engagement by healthcare professionals and by patients, when designing and evaluating prehabilitation for gynaecological cancer patients., (© 2022. The Author(s).)

Introduction: The lifetime risk of women undergoing surgery for the presence of benign ovarian pathology in the UK is 5%-10%. Despite minimally invasive surgical techniques, evidence suggests a number of healthy ovarian follicles and tissues are resected intraoperatively, resulting in subsequent decline of ovarian reserve. As such, there is an increasing demand for the implementation of fertility preservation surgery (FPS). This study will evaluate the effect on ovarian reserve following two different surgical interventions for the management of benign ovarian cysts., Methods and Analysis: We will conduct a two-armed randomised controlled trial comparing laparoscopic ovarian cystectomy, considered gold standard treatment as per the Royal College of Obstetricians and Gynaecologists (RCOG) Green Top guidelines for the management of benign ovarian cysts, with ultrasound-guided laparoscopic ovarian cystectomy (UGLOC), a novel method of FPS. The study commencement date was October 2021, with a completion date aimed for October 2024. The primary outcome will be the difference in anti-Müllerian hormone (AMH) (pmol/L) and antral follicle count (AFC) measured 3 and 6 months postoperatively from the preoperative baseline. Secondary outcomes include assessment of various surgical and histopathological findings, including duration of hospital stay (days), duration of surgery (minutes), presence of intraoperative cyst rupture (yes/no), presence of ovarian tissue within the resected specimen (yes/no) and the grade of follicles excised within the specimen (grade 0-4). We aim to randomise 94 patients over 3 years to achieve power of 80% at an alpha level of 0.05., Ethics and Dissemination: Findings will be published in peer-reviewed journals and presented at national and international conferences and scientific meetings. The Chelsea NHS Research and Ethics Committee have awarded ethical approval of the study (21/LO/036)., Trial Registration Number: NCT05032846., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

During the COVID-19 pandemic, pressures on clinical services required adaptation to how care was prioritised and delivered for women with gynecological cancer. This document discusses potential 'salvage' measures when treatment has deviated from the usual standard of care. The British Gynaecological Cancer Society convened a multidisciplinary working group to develop recommendations for the onward management and follow-up of women with gynecological cancer who have been impacted by a change in treatment during the pandemic. These recommendations are presented for each tumor type and for healthcare systems, and the impact on gynecological services are discussed. It will be important that patient concerns about the impact of COVID-19 on their cancer pathway are acknowledged and addressed for their ongoing care., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Treatment for patients with recurrent ovarian cancer has been mainly based on systemic therapy. The role of secondary cytoreductive surgery is unclear., Methods: We randomly assigned patients with recurrent ovarian cancer who had a first relapse after a platinum-free interval (an interval during which no platinum-based chemotherapy was used) of 6 months or more to undergo secondary cytoreductive surgery and then receive platinum-based chemotherapy or to receive platinum-based chemotherapy alone. Patients were eligible if they presented with a positive Arbeitsgemeinschaft Gynäkologische Onkologie (AGO) score, defined as an Eastern Cooperative Oncology Group performance-status score of 0 (on a 5-point scale, with higher scores indicating greater disability), ascites of less than 500 ml, and complete resection at initial surgery. A positive AGO score is used to identify patients in whom a complete resection might be achieved. The primary end point was overall survival. We also assessed quality of life and prognostic factors for survival., Results: A total of 407 patients underwent randomization: 206 were assigned to cytoreductive surgery and chemotherapy, and 201 to chemotherapy alone. A complete resection was achieved in 75.5% of the patients in the surgery group who underwent the procedure. The median overall survival was 53.7 months in the surgery group and 46.0 months in the no-surgery group (hazard ratio for death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.02). Patients with a complete resection had the most favorable outcome, with a median overall survival of 61.9 months. A benefit from surgery was seen in all analyses in subgroups according to prognostic factors. Quality-of-life measures through 1 year of follow-up did not differ between the two groups, and we observed no perioperative mortality within 30 days after surgery., Conclusions: In women with recurrent ovarian cancer, cytoreductive surgery followed by chemotherapy resulted in longer overall survival than chemotherapy alone. (Funded by the AGO Study Group and others; DESKTOP III ClinicalTrials.gov number, NCT01166737.)., (Copyright © 2021 Massachusetts Medical Society.)

Purpose: Preoperative nodal staging is important for planning treatment in cervical cancer and endometrial cancer, but remains challenging. We compare nodal staging accuracy of 18 F-ethyl-choline-(FEC)-PET/CT, 18 F-fluoro-deoxy-glucose-(FDG)-PET/CT, and diffusion-weighted-MRI (DW-MRI) with conventional morphologic MRI., Experimental Design: A prospective, multicenter observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centers. FEC-PET/CT, FDG-PET/CT, and DW-MRI were compared with nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable cervical cancer stage ≥ 1B1 or endometrial cancer (grade 3 any stage with myometrial invasion or grade 1-2 stage ≥ II)., Results: Among 162 consenting participants, 136 underwent study DW-MRI and FDG-PET/CT and 60 underwent FEC-PET/CT. In 118 patients, 267 nodal regions were strictly correlated at histology (nodal positivity rate, 25%). Sensitivity per patient ( n = 118) for nodal size, morphology, DW-MRI, FDG- and FEC-PET/CT was 40%*, 53%, 53%, 63%*, and 67% for all cases (*, P = 0.016); 10%, 10%, 20%, 30%, and 25% in cervical cancer ( n = 40); 65%, 75%, 70%, 80% and 88% in endometrial cancer ( n = 78). FDG-PET/CT outperformed nodal size ( P = 0.006) and size ratio ( P = 0.04) for per-region sensitivity. False positive rates were all <10%., Conclusions: All imaging techniques had low sensitivity for detection of nodal metastases and cannot replace surgical nodal staging. The performance of FEC-PET/CT was not statistically different from other techniques that are more widely available. FDG-PET/CT had higher sensitivity than size in detecting nodal metastases. False positive rates were low across all methods. The low false positive rate demonstrated by FDG-PET/CT may be helpful in arbitration of challenging surgical planning decisions., (©2021 The Authors; Published by the American Association for Cancer Research.)

The COVID-19 pandemic resulted in significant reconfiguration of gynecologic cancer services and care pathways across the globe, with a transformation of working practices. Services had to adapt to protect their vulnerable patients from infection, whilst providing care despite reduced resources/capacity and staffing. The international gynecologic cancer community introduced modified clinical care guidelines. Remote working, reduced hospital visiting, routine COVID-testing, and use of COVID-free surgical areas/hubs enabled the ongoing and safe delivery of complex cancer care, with priority levels for cancer treatments established to guide decision-making by multidisciplinary tumor boards. Some 2.3 million cancer surgeries were delayed or cancelled during the first peak, with many patients reporting significant anxiety/concern for cancer progression and COVID infection. Although COVID trials were prioritized, recruitment to other cancer trials/research activity was significantly reduced. The impact of resultant protocol deviations on outcomes remains to be established. During the recovery healthcare services must maintain capacity and flexibility to manage future surges of infection, address the large backlog of patients with altered or delayed treatments, along with salvaging screening and prevention services. Training needs/mental well-being of trainees need addressing and staff burnout prevented. Future research needs to fully evaluate the impact of COVID-19 on long-term patient outcomes., (International Journal of Gynecology & Obstetrics© 2021 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Uterine transplantation (UTx) is a fertility restoring treatment for women with absolute uterine factor infertility. At a time when there is no question of the procedure's feasibility, and as the number of livebirths begins to increase exponentially, various important reproductive, fetal, and maternal medicine implications have emerged. Detailed outcomes from 17 livebirths following UTx are now available, which are reviewed herein, along with contextualized extrapolation from pregnancy outcomes in other solid organ transplants. Differences in recipient demographics and reproductive aspirations between UTx and other transplant recipients make extrapolating management strategies and outcomes in other solid organ transplants inappropriate. Whereas preterm delivery remains prominent, small for gestational age or hypertensive disorders do not appear to be as prevalent following UTx when compared to other solid organ transplants. Given the primary objective of undertaking UTx is to achieve a livebirth, publication of reproductive outcomes is essential at this early stage, to reflect on and optimize the management of future cases., Competing Interests: The authors declare no funding or conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the anxiety and stress levels of women with suspected endometrial cancer and factors affecting this., Methods: Prospective survey and paired observational study of consecutive women with suspected endometrial cancer in a rapid access gynaecology clinic. Structured questionnaire including a GAD-7 anxiety test and a modified stress thermometer were used. Patients ranked their perception of a cancer diagnosis on 0-5 Likert scale (0 = confident not cancer and 5 = cancer). Patients requiring an endometrial tissue biopsy were asked to rank their pain on a visual analogue scale (VAS), this was paired with the survey results., Results: 250 patients completed the study and 23 of which underwent an endometrial tissue biopsy. The median age was 50-59 years old and 59% of women spoke English as their first language. 32% of patients had significant levels of anxiety with GAD-7 score ≥10. The median stress score was three out of five on Likert scale. GAD-7 anxiety scores were higher in women who perceived that they received insufficient information prior to clinic (sufficient information 5 vs. insufficient information 9.5, P = 0.00036) or had a disability (disability 9 vs. no disability 5.5, P = 0.00374). The median VAS score from the biopsies was seven out of 10 (range 1-10). Patients with higher anxiety levels (GAD-7 scores) were more likely to believe they had cancer P <0.00001., Conclusions: These findings confirm high levels of anxiety and stress in women with suspected endometrial cancer. Adequate pre-clinic information is essential, particularly for minority groups., (© 2021 The Authors. Psycho-Oncology published by John Wiley & Sons Ltd.)

The use of biologics in positron emission tomography (PET) imaging is an important area of radiopharmaceutical development and new automated methods are required to facilitate their production. We report an automated radiosynthesis method to produce a radiolabelled biologic via facile inverse electron demand Diels-Alder (IEDDA) "click" chemistry on a single GE FASTLab™ cassette. We exemplified the method by producing a fluorine-18 radiolabelled interleukin-2 (IL2) radioconjugate from a trans -cyclooctene (TCO) modified IL2 precursor. The radioconjugate was produced using a fully automated radiosynthesis on a single FASTLab™ cassette in a decay-corrected radiochemical yield (RCY, d.c.) of 19.8 ± 2.6% in 110 min (from start of synthesis); the molar activity was 132.3 ± 14.6 GBq μmol -1 . The in vitro uptake of [ 18 F]TTCO-IL2 correlated with the differential receptor expression (CD25, CD122, CD132) in PC3, NK-92 and activated human PBMCs. The automated method may be adapted for the radiosynthesis of any TCO-modified protein via IEDDA chemistry., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

A uterine transplantation is a nonvital, quality-of-life-enhancing solid organ transplant. Given improvements in donor risk profile and the anticipated shortage of suitable deceased donors, nondirected donation could facilitate sustainability as uterine transplantation moves from research into the clinical realm. The aim of this article is to determine perceptions and identify motivations of potential nondirected living uterus donors and assess acceptability and suitability., Methods: A cross-sectional survey using an electronic questionnaire among women who have inquired about donating their uterus for uterine transplantation., Results: The majority of respondents "strongly agreed" or "agreed" that the most prevalent motivations to donate their uterus include helping someone carry and give birth to their own baby (n = 150; 99%), helping others (n = 147; 97%), and because they no longer need their womb (n = 147; 97%). After considering risks of uterus donation, the majority were still keen to donate their uterus (n = 144; 95%), but following a process of exclusion using donor selection criteria, less than a third (n = 42; 29%) were found to be suitable to proceed., Conclusions: This study demonstrates novel insight into the motivations of women who wish to donate their uterus and displays high levels of acceptability after consideration of the risks involved. Despite the physical risk and transient impact upon ability to undertake activities of daily living, women who donate their uterus expect to gain psychological and emotional benefits from enabling another woman to gestate and give birth to their own future children. However, currently used selection criteria reduce the number of potential donors significantly., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 The Author(s). Transplantation Direct. Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: Competing interests: SS has received honoraria from Astra Zeneca outside the submitted work. CF has received honoraria from Ethicon, Tesaro, MSD/Astra Zeneca, Clovis, Roche, GSK. RM reports grants from Barts Charity, grants from The Eve Appeal, personal fees from Astra Zeneca, MSD, outside the submitted work. RB reports personal fees from GSK, personal fees from AstraZeneca, personal fees from Clovis, from Tesaro, outside the submitted work. RE reports personal fees from Astra Zeneca, personal fees from Clovis Pharma, personal fees from GSK, outside the submitted work., (© IGCS and ESGO 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Importance: Uterus transplant has been demonstrated to be a viable fertility-restoring treatment for women categorized as female at birth with absolute uterine factor infertility. Recent advancements, as well as considerations of fairness and equality in reproductive care, have now led to the possibility of uterus transplant being undertaken in transgender women., Objective: To investigate the reproductive aspirations of transgender women and their perceptions of uterus transplant., Design, Setting, and Participants: This cross-sectional survey study used a 27-item electronic questionnaire to investigate the reproductive aspirations of 182 transgender women older than 16 years, including their perceptions of and motivations for uterus transplant, between May 1 and November 1, 2019., Main Outcomes and Measures: Perceptions of and motivations for uterus transplant, including perceived significance of the ability to gestate, menstruate, and have a physiologically functioning vagina., Results: A total of 182 transgender women completed the questionnaire; most women (109 [60%]) were aged 20 to 29 years. Most did not have children prior to transitioning (167 [92%]) and expressed a desire to have children in the future (171 [94%]). In addition, most respondents agreed or strongly agreed that the ability to gestate and give birth to children (171 [94%]) and menstruate (161 [88%]) would enhance perceptions of their femininity. Similarly, high proportions strongly agreed or agreed that having a transplanted, functioning vagina would improve their sexual experience (163 [90%]), improve their quality of life (163 [90%]), and help them to feel like more of a woman (168 [92%]). Nearly all respondents (180 [99%]) believed that uterus transplant would lead to greater happiness in transgender women. More than three-quarters of the respondents (140 [77%]) strongly agreed or agreed that they would be more inclined to cryopreserve sperm if uterus transplant became a realistic option., Conclusions and Relevance: This study provides insights into the reproductive aspirations of transgender women and reports on their multifaceted motivation to undergo uterus transplant. The survey responses suggest that transgender women would choose to have female physiologic experiences, such as menstruation and gestation, as well as potentially having a physiologically functioning transplanted vagina. If proven feasible and safe in this setting, uterus transplant may facilitate the achievement of reproductive aspirations, improve quality of life, and further alleviate dysphoric symptoms in transgender women.

Background: Endogenous retroviruses (ERVs) play a role in a variety of biological processes, including embryogenesis and cancer. DNA methyltransferase inhibitors (DNMTi)-induced ERV expression triggers interferon responses in ovarian cancer cells via the viral sensing machinery. Baseline expression of ERVs also occurs in cancer cells, though this process is poorly understood and previously unexplored in epithelial ovarian cancer (EOC). Here, the prognostic and immunomodulatory consequences of baseline ERV expression was assessed in EOC., Methods: ERV expression was assessed using EOC transcriptional data from The Cancer Genome Atlas (TCGA) and from an independent cohort (Hammersmith Hospital, HH), as well as from untreated or DNMTi-treated EOC cell lines. Least absolute shrinkage and selection operator (LASSO) logistic regression defined an ERV expression score to predict patient prognosis. Immunohistochemistry (IHC) was conducted on the HH cohort. Combination of DNMTi treatment with γδ T cells was tested in vitro , using EOC cell lines and patient-derived tumor cells., Results: ERV expression was found to define clinically relevant subsets of EOC patients. An ERV prognostic score was successfully generated in TCGA and validated in the independent cohort. In EOC patients from this cohort, a high ERV score was associated with better survival (log-rank p=0.0009) and correlated with infiltration of CD8+PD1+T cells (r=0.46, p=0.0001). In the TCGA dataset, a higher ERV score was found in BRCA1/2 mutant tumors, compared to wild type (p=0.015), while a lower ERV score was found in CCNE1 amplified tumors, compared to wild type (p=0.019). In vitro , baseline ERV expression dictates the level of ERV induction in response to DNMTi. Manipulation of an ERV expression threshold by DNMTi resulted in improved EOC cell killing by cytotoxic immune cells., Conclusions: These findings uncover the potential for baseline ERV expression to robustly inform EOC patient prognosis, influence tumor immune infiltration and affect antitumor immunity., Competing Interests: Competing interests: DP received lecture fees from ViiV Healthcare, Bayer Healthcare and travel expenses from BMS and Bayer Healthcare; consulting fees for Mina Therapeutics, EISAI, Roche, Astra Zeneca; received research funding (to institution) from MSD and BMS., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Ovarian cancer surgery endeavours to remove all visible tumour deposits, and surgical technologies could potentially facilitate this aim. However, there appear to be barriers around the adoption of new technologies, and we hope this article provokes discussion within the specialty to encourage a forward-thinking approach to new-age surgical gynaecological oncology.

The original version of this article unfortunately contained a mistake. Complete figure captions are missing.

Objective: The aim of this study was to demonstrate the use of intraoperative ultrasound-guided ovarian wedge resection in the treatment of recurrent serous borderline ovarian tumors (sBOTs) that are too small to be visualized laparoscopically., Methods: This was a prospective analysis of all women with recurrent sBOTs that were not visible laparoscopically, who underwent intraoperative ultrasound-guided ovarian wedge resection between January 2015 and December 2016 at the West London Gynaecological Cancer Centre, Imperial College NHS Trust, London, United Kingdom., Results: We evaluated 7 patients, with a median age of 35 years (range, 28-39 years). Six women were nulliparous, whereas 1 woman had a single child. Previous surgical intervention left 5 women with a single ovary, whereas the remaining 2 had previous ovarian-sparing surgery. The median size of recurrence was 18 mm (range, 12-37 mm). All women underwent uncomplicated intraoperative guided ovarian wedge resections. Histological assessment confirmed sBOT in all 7 cases. Six of the women remain disease-free. One woman recurred postoperatively with her third recurrence, who previously had bilateral disease and noninvasive implants with microinvasive disease and micropapillary pattern. No cases progressed to invasive disease. The median follow-up time was 12 months (range, 1-20 months). One pregnancy has been achieved postoperatively but resulted in miscarriage., Conclusions: Continuous intraoperative ultrasound can be used to facilitate complete tumor excision in recurrent sBOT while minimizing the removal of ovarian tissue in women with recurrent sBOT. It is essential that surgical techniques evolve simultaneously with diagnostic imaging modalities to enable surgeons to treat such pathology.

Adoptive T cell immunotherapy is a promising treatment strategy for epithelial ovarian cancer (EOC). However, programmed death ligand-1 (PD-L1), highly expressed on EOC cells, interacts with programmed death-1 (PD-1), expressed on T cells, causing immunosuppression. This study aims to block PD-1/PD-L1 interactions by delivering PD-L1 siRNA, using various folic acid (FA)-functionalized polyethylenimine (PEI) polymers, to SKOV-3-Luc EOC cells, and investigate the sensitization of the EOC cells to T cell killing. To enhance siRNA uptake into EOC cells, which over express folate receptors, PEI is modified with FA or PEG-FA so that siRNA is complexed into nanoparticles with folate molecules on the surface. PEI modification with a single functional group lowers the polymer cytotoxicity compared to unmodified PEI. FA-conjugated polymers increase siRNA uptake into SKOV-3-luc cells and decrease unspecific uptake into monocytes. All polymers result in 40% to 50% PD-L1 protein knockdown. Importantly, SKOV-3-Luc cells treated with either PEI-FA or PEI- polyethylene glycol (PEG)-FA/PD-L1 siRNA complexes are up to twofold more sensitive to T cell killing compared to scrambled siRNA treated controls. These findings are the first to demonstrate that PD-L1 knockdown in EOC cells, via siRNA/FA-targeted delivery, are able to sensitize cancer cells to T cell killing., (© 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Objective: The aim of this study was to assess the effect of the excision margin after cone for stage Ia1 cervical cancer on long-term outcomes., Study Design: Retrospective observational study. Patients were divided into 3 groups. Group A underwent immediate reflex hysterectomy; group B had cervical intraepithelial neoplasia (CIN) at the margins but were followed up; group C had clear margins., Results: We identified 111 women: 19 (17.1%) in group A; 29 (26.1%) in group B; and 63 (56.8%) in group C. Women in group A were older (median, 40 years vs 35 years; P = .0001) with higher rate of endocervical margin involvement (89.5 vs 48.1%, P = .007) than in group B. The women had been followed for a total of 960 woman-years with median follow-up of 398 weeks (quartiles: 258,612). Women with clear margins in the initial excision were more likely to remain free of disease than those with involved (P < .0001). Further surgery was required due to abnormal cytology in 9 (31.0%) women from group B and 7 (11.1%) from group C (P = .04). The cumulative rate of recurrent CIN2+ was 6.4% in group B and 2.7% in group C (P = .17). In group B, recurrences were more common in positive endocervical rather than ectocervical margins (66.6% vs 33.4%, P < .05); all had high-grade CIN at the margins., Conclusion: The risk of posttreatment CIN2+ is substantially reduced when complete excision is achieved at first treatment. Conservative management is contraindicated in women with microinvasion at the margin. When CIN involves the margin, there is a greater risk of residual disease and of further treatment., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Serous borderline tumors (SBOTs) are a challenging group of ovarian tumors positioned between benign and malignant disease. We have profiled the DNA methylomes of 12 low-grade serous carcinomas (LGSCs), 19 SBOTs, and 16 benign serous tumors (BSTs) across 27,578 CpG sites to further characterize the epigenomic relationship between these subtypes of ovarian tumors. Unsupervised hierarchical clustering of DNA methylation levels showed that LGSCs differ distinctly from BSTs, but not from SBOTs. Gene ontology analysis of genes showing differential methylation at linked CpG sites between LGSCs and BSTs revealed significant enrichment of gene groups associated with cell adhesion, cell-cell signaling, and the extracellular region, consistent with a more invasive phenotype of LGSCs compared with BSTs. Consensus clustering highlighted differences between SBOT methylomes and returned subgroups with malignant- or benign-like methylation profiles. Furthermore, a two-loci DNA methylation signature can distinguish between these SBOT subgroups with benign- and malignant-like methylation characteristics. Our findings indicate striking similarities between SBOT and LGSC methylomes, supporting a common origin and the view that LGSC may arise from SBOT. A subgroup of SBOTs can be classified into tumors with a benign- or a malignant-like methylation profile that may help in identifying tumors more likely to progress into LGSCs., (Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Objective: A cross-sectional, observational study to evaluate physical and psychological symptoms experienced by patients following completion of treatment for ovarian cancer and compared to symptoms documented in their hospital notes., Methods: Women attending follow-up clinic at Hammersmith Hospital having undergone treatment for primary or relapsed ovarian cancer were asked to complete two validated questionnaires (EORTC QLQ-C30 and QLQ-OV28) and a "wellbeing thermometer". Results were assessed and stratified by patient age, tumour stage, relapse status, type of chemotherapy received and treatment-free interval. Symptoms reported in questionnaires were compared to those documented in patients' hospital notes., Results: Of 116 women approached, 100 (86%) participated in this study and had received chemotherapy for ovarian cancer between 2003 and 2010. The most frequently described and severe symptoms reported in the questionnaires were emotional symptoms, negative feelings about treatment or prognosis, fatigue and pain. Dyspareunia, cognitive impairment and peripheral neuropathy were also frequently described. Symptom severity was independent of variables such as disease stage, type of chemotherapy received and relapse status. The "wellbeing thermometer" scores closely correlated with pain, fatigue, weakness, gastrointestinal symptoms and attitude to disease or treatment (p<0.001). There was a marked discordance between questionnaire-reported symptoms and those recorded in hospital notes., Conclusions: The majority of women surveyed experienced persistent psychological and physical symptoms following ovarian cancer treatment; in particular: psychological concerns, sexual inactivity and fatigue, all potentially reversible with appropriate interventions. Our results highlight the extent of symptoms described by ovarian cancer survivors and the need for them to be adequately acknowledged and addressed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

The idea of using organ transplantation to solve quality-of-life issues was first introduced a century ago, with cornea transplants and thrusted before the world again in 1998, following a controversial hand transplant. Uterus transplantation (UTn) has been proposed as another quality-of-life transplant for the cure of permanent uterine factor infertility. In order to proceed in humans, a greater appreciation of the immunological mechanisms that underlie UTn is desirable. Allogeneic UTn (animal model) was first described by 2 studies in 1969. The first and only human UTn, performed in 2000, was an early attempt with limited use of animal model experiments prior to moving onto the human setting. Since then, work using rat, mouse, ovine, goat, and nonhuman primate models has demonstrated that the uterus is a very different but manageable organ immunologically compared to other transplanted organs. Therefore, specifically exploring immunological issues relating to UTn is a valuable and necessary part of the inevitable scientific process leading to successful human UTn.

Background: Over 60,000 women are treated for cervical intraepithelial neoplasia (CIN) each year in England, most by excision. Management of women who have incomplete excision is controversial and the subject of much debate. Consequently, the completeness of excision is often ignored in the planning of subsequent treatment. We aimed to assess the effect of completeness of excision on the risk of post-treatment disease., Methods: We undertook a meta-analysis of studies published between Jan 1, 1960, and Jan 31, 2007, that studied the risk of post-treatment disease (ie, CIN of any grade or invasive cancer) in relation to completeness of excision. Studies were included if they described treatment of CIN by excision; numbers of women with involved margins; prevalence of and numbers of women with post-treatment disease in relation to margin status. Criteria for post-treatment disease had to be stated as a defined abnormal cytology or histology. Studies were excluded if they described treatment of cervical glandular intraepithelial disease (CGIN); if all or nearly all women had reflex hysterectomy done soon after initial treatment; if women were immunosuppressed (eg, if they were HIV-positive); or if no control group with disease-free margins was used. The endpoint of our analysis was the relative risk (RR) of post-treatment disease in those whose treatment histology suggested that excision was complete compared with those in whom excision was incomplete or uncertain. RR meta-analysis was done by use of a random effects model., Findings: The initial Medline search identified 1756 publications, from which 125 publications were short-listed. Of these, 65 and one unpublished study met our inclusion criteria; therefore, 66 studies were included in this meta-analysis. These studies described findings in 35,109 women of whom 8091 (23%) had at least one margin of the excision biopsy involved with disease. After incomplete excision, RR of post-treatment disease of any grade was 5.47 (95% CI 4.37-6.83) and RR of high-grade disease (ie, CIN 2 or 3, or high-grade squamous intraepithelial lesion) was 6.09 (3.87-9.60) compared with the reference group who had complete excision. High-grade post-treatment disease occurred in 597 of 3335 (18%) women who had incomplete excision versus 318 of 12 493 (3%) women who had complete excision., Interpretation: Incomplete excision of CIN exposes women to a substantial risk of high-grade post-treatment disease. Some of these women would be safer with a second treatment, especially if deep margins are involved, but most will need close follow-up for at least 10 years. Every effort should be made to avoid incomplete excision. Adding extensive ablation in the treatment crater to compensate for inadequate excision should be avoided because this might delay detection of inadequately treated invasive disease and because the effectiveness of additional ablation to destroy any residual CIN cannot be assessed. Furthermore, extensive ablation does not decrease any risk of preterm delivery in subsequent pregnancies.