191 results found
Kasaven L, Jones BP, Ghaem-Maghami S, et al., 2022, Study protocol for a randomised controlled trial on the use of intra-operative Ultrasound Guided Laparoscopic Ovarian Cystectomy (UGLOC) as a method of fertility preservation in the management of benign ovarian cysts, BMJ Open, Vol: 12, ISSN: 2044-6055
Introduction: The lifetime risk of women undergoing surgery for the presence of benign ovarian pathology in the united kingdom (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 and completion date October 2024. The primary outcome will be the difference in anti-Mullerian hormone (pmol/L) (AMH) and antral follicle count (AFC) measured 3 and 6 months post operatively from the pre-operative baseline. Secondary outcomes include assessment of various surgical and histopathological outcomes including: duration of hospital stay (days), duration of surgery (mins), presence of intra-operative cyst rupture (yes/no), presence of ovarian tissue within the specimen (yes/no) and the grade of follicles excised with 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
Phelps DL, Borley J, Brown R, et al., 2022, The use of biomarkers to stratify surgical care in women with ovarian cancer Scientific Impact Paper No. 69[March] 2022, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, ISSN: 1470-0328
Taylor A, Sundar SS, Bowen R, et al., 2022, British Gynaecological Cancer Society Recommendations for Women With Gynecological Cancer Who Received Non-standard Care During the COVID-19 Pandemic, OBSTETRICAL & GYNECOLOGICAL SURVEY, Vol: 77, Pages: 156-157, ISSN: 0029-7828
Taylor A, Sundar SS, Bowen R, et al., 2022, British Gynaecological Cancer Society Recommendations for Women With Gynecological Cancer Who Received Non-standard Care During the COVID-19 Pandemic, Obstetrical & Gynecological Survey, Vol: 77, Pages: 156-157, ISSN: 0029-7828
Harter P, Sehouli J, Vergote I, et al., 2022, Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer (vol 385, pg 2123, 2021), NEW ENGLAND JOURNAL OF MEDICINE, Vol: 386, Pages: 704-704, ISSN: 0028-4793
Tabiri S, Kamarajah SK, Nepogodiev D, et al., 2022, Impact of Bacillus Calmette-Guerin (BCG) vaccination on postoperative mortality in patients with perioperative SARS-CoV-2 infection, BJS Open, Vol: 5, ISSN: 2474-9842
Harter P, Sehouli J, Vergote I, et al., 2021, Randomized Trial of Cytoreductive Surgery for Relapsed Ovarian Cancer, NEW ENGLAND JOURNAL OF MEDICINE, Vol: 385, Pages: 2123-2131, ISSN: 0028-4793
Manchanda R, Oxley S, Ghaem-Maghami S, et al., 2021, COVID-19 and the impact on gynecologic cancer care, INTERNATIONAL JOURNAL OF GYNECOLOGY & OBSTETRICS, Vol: 155, Pages: 94-101, ISSN: 0020-7292
Rockall A, Barwick T, Wilson W, et al., 2021, 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, Clinical Cancer Research, Vol: 27, Pages: 6457-6466, ISSN: 1078-0432
Purpose:Pre-operative nodal staging is important for planning treatment in cervical cancer (CC) and endometrial cancer (EC) 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 morphological MRI.Experimetal Design:A prospective, multicentre observational study of diagnostic accuracy for nodal metastases was undertaken in 5 gyne-oncology centres. FEC-PET/CT, FDG-PET/CT and DW-MRI were compared to nodal size and morphology on MRI. Reference standard was strictly correlated nodal histology. Eligibility included operable CC stage=>1B1 or EC (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. 267 nodal regions in 118 women 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 were 40%*, 53%, 53%, 63%* and 67% for all cases (*p=0.016); 10%, 10%, 20%, 30% and 25% in CC (n=40); 65%, 75%, 70%, 80% and 88% in EC (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 to 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.
Ahmed-Salim Y, Saso S, Meehan H, et al., 2021, A novel application of calcium electroporation to cutaneous manifestations of gynaecological cancer, European Journal of Gynecological Oncology, Vol: 42, Pages: 662-672, ISSN: 0392-2936
Introduction: Calcium electroporation (CaEP) is a new technique whereby intracellular concentrations of calcium are elevated by transient permeabilisation of the cell membrane using high-voltage electrical pulses. Tumour necrosis is induced with little damage to healthy tissue. Within gynaecological cancer, vulval cancer and vulval intraepithelial neoplasia (VIN) pose challenges for treatment, given the high recurrence rate, persistent symptoms and repeated resections required. In certain cases, CaEP may provide a suitable alternative.Methods: We present a case series of six patients with recurrent vulval squamous cell carcinoma(n=2), VIN III (n=2) and metastatic ovarian cancer (n=2), five of whom were treated with CaEP. This is the first known application of CaEP to gynaecological cancers .Results: The median follow-up time was 14 months (range 2-18 months). Within the cohort of patients, CaEP was applied a total of 10 times, achieving a complete response five times and partial response four times. Symptoms improved within six weeks for eight episodes following CaEP application. Beyond six weeks, symptoms eventually recurred in all patients and four patients required more than one CaEP procedure. CaEP was useful for palliation of distressing symptoms in one case of metastatic ovarian cancer. No intra-operative or post-operative complications have been reported to date. Conclusion: CaEP may be a promising short-term treatment in selected patients with recurrent VIN and vulval cancer, where other treatments had failed. If validated, it could provide an acceptable alternative where surgery is unacceptable. Long term follow-up is required to evaluate effects on recurrence.
Jones BP, Kasaven L, Vali S, et al., 2021, Uterine Transplantation: Review of Livebirths and Reproductive Implications, TRANSPLANTATION, Vol: 105, Pages: 1695-1707, ISSN: 0041-1337
Marcus D, King A, Yazbek J, et al., 2021, Anxiety and stress in women with suspected endometrial cancer: Survey and paired observational study, Psycho-Oncology: journal of the psychological, social and behavioral dimensions of cancer, Vol: 30, Pages: 1939-1400, ISSN: 1057-9249
ObjectiveTo determine the anxiety and stress levels of women with suspected endometrial cancer and factors affecting this.MethodsProspective 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.Results250 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.ConclusionsThese findings confirm high levels of anxiety and stress in women with suspected endometrial cancer. Adequate pre-clinic information is essential, particularly for minority groups.
COVIDSurg Collaborative Co-authors, 2021, Machine learning risk prediction of mortality for patients undergoing surgery with perioperative SARS-CoV-2: the COVIDSurg mortality score, British Journal of Surgery, Vol: 108, Pages: 1274-1292, ISSN: 0007-1323
Since the beginning of the COVID-19 pandemic tens of millions of operations have been cancelled1 as a result of excessive postoperative pulmonary complications (51.2 per cent) and mortality rates (23.8 per cent) in patients with perioperative SARS-CoV-2 infection2. There is an urgent need to restart surgery safely in order to minimize the impact of untreated non-communicable disease.As rates of SARS-CoV-2 infection in elective surgery patients range from 1–9 per cent3–8, vaccination is expected to take years to implement globally9 and preoperative screening is likely to lead to increasing numbers of SARS-CoV-2-positive patients, perioperative SARS-CoV-2 infection will remain a challenge for the foreseeable future.To inform consent and shared decision-making, a robust, globally applicable score is needed to predict individualized mortality risk for patients with perioperative SARS-CoV-2 infection. The authors aimed to develop and validate a machine learning-based risk score to predict postoperative mortality risk in patients with perioperative SARS-CoV-2 infection.
Keefe D, 2021, Fertility Treatment and Cancers-The Eternal Conundrum: A Systematic Review and Meta-analysis, OBSTETRICAL & GYNECOLOGICAL SURVEY, Vol: 76, Pages: 343-344, ISSN: 0029-7828
Marcus D, Yongue G, Shen Y, et al., 2021, Do delays to surgery influence survival in endometrial cancer?, Publisher: WILEY, Pages: 69-69, ISSN: 1470-0328
Ahmed-Salim Y, Galazis N, Bracewell-Milnes T, et al., 2021, The application of metabolomics in ovarian cancer management: a systematic review, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 754-774, ISSN: 1048-891X
Jones BP, Saso S, Yazbek J, et al., 2021, Uterine Transplantation Scientific Impact Paper No. 65 April 2021, BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY, Vol: 128, Pages: E51-E66, ISSN: 1470-0328
Allott L, Amgheib A, Barnes C, et al., 2021, Radiolabelling an F-18 biologic via facile IEDDA "click" chemistry on the GE FASTLab (TM) platform, Reaction Chemistry and Engineering, Vol: 6, Pages: 1070-1078, ISSN: 2058-9883
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 [18F]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.
Barcroft JF, Galazis N, Jones BP, et al., 2021, Fertility treatment and cancers-the eternal conundrum: a systematic review and meta-analysis., Human Reproduction, Vol: 36, Pages: 1093-1107, ISSN: 0268-1161
STUDY QUESTION: Does fertility treatment (FT) significantly increase the incidence of breast, ovarian, endometrial or cervical cancer? SUMMARY ANSWER: Overall, FT does not significantly increase the incidence of breast, ovarian or endometrial cancer and may even reduce the incidence of cervical cancer. WHAT IS KNOWN ALREADY: Infertility affects more than 14% of couples. Infertility and nulliparity are established risk factors for endometrial, ovarian and breast cancer, yet the association with FT is more contentious. STUDY DESIGN, SIZE, DURATION: A literature search was carried out using Cochrane Library, EMBASE, Medline and Google Scholar up to December 2019. Peer-reviewed studies stating cancer incidence (breast, ovarian, endometrial or cervical) in FT and no-FT groups were identified. Out of 128 studies identified, 29 retrospective studies fulfilled the criteria and were included (n = 21 070 337). PARTICIPANTS/MATERIALS, SETTING, METHODS: In the final meta-analysis, 29 studies were included: breast (n = 19), ovarian (n = 19), endometrial (n = 15) and cervical (n = 13), 17 studies involved multiple cancer types and so were included in each individual cancer meta-analysis. Primary outcome of interest was cancer incidence (breast, ovarian, endometrial and cervical) in FT and no-FT groups. Secondary outcome was cancer incidence according to specific fertility drug exposure. Odds ratio (OR) and random effects model were used to demonstrate treatment effect and calculate pooled treatment effect, respectively. A meta-regression and eight sub-group analyses were performed to assess the impact of the following variables, maternal age, infertility, study size, outliers and specific FT sub-types, on cancer incidence. MAIN RESULTS AND THE ROLE OF CHANCE: Cervical cancer incidence was significantly lower in the FT group compared with the no-FT group: OR 0.68 (95% CI 0.46-0.99). The incidences
Jones BP, Rajamanoharan A, Williams NJ, et al., 2021, Uterine Transplantation Using Living Donation: A Cross-sectional Study Assessing Perceptions, Acceptability, and Suitability, TRANSPLANTATION DIRECT, Vol: 7, ISSN: 2373-8731
Sundar S, Manchanda R, Gourley C, et al., 2021, British Gynaecological Cancer Society/British Association of Gynaecological Pathology consensus for germline and tumor testing for BRCA1/2 variants in ovarian cancer in the United Kingdom, INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, Vol: 31, Pages: 272-278, ISSN: 1048-891X
Jones BP, Rajamanoharan A, Vali S, et al., 2021, Perceptions and Motivations for Uterus Transplant in Transgender Women, JAMA NETWORK OPEN, Vol: 4, ISSN: 2574-3805
Natoli M, Gallon J, Lu H, et al., 2021, Transcriptional analysis of multiple ovarian cancer cohorts reveals prognostic and immunomodulatory consequences of ERV expression, Journal for ImmunoTherapy of Cancer, Vol: 9, ISSN: 2051-1426
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
Phelps DL, Saso S, Ghaem-Maghami S, 2020, Is ovarian cancer surgery stuck in the dark ages?: a commentary piece reviewing surgical technologies, BRITISH JOURNAL OF CANCER, Vol: 123, Pages: 1471-1473, ISSN: 0007-0920
Phelps DL, Saso S, Ghaem-Maghami S, 2020, Analysis of worldwide surgical outcomes in COVID-19-infected patients: a gynecological oncology perspective, Future Science OA, Vol: 6, Pages: 1-8, ISSN: 2056-5623
Coronavirus Disease 2019 (COVID-19) guidance limits all but the most urgent surgery in the United Kingdom. We review the literature and our experience in gynecology to assess perioperative outcomes. PubMed was searched with (surg*[Title])AND(COVID[Title]), (surg*[Title])AND(2019-nCoV[Title]), and (surg*[Title])AND(SARS-CoV-2[Title]), and 67 COVID-19-positive surgical patients across ten hospitals in four countries are included. Median mortality was 33%. Cardiac and pulmonary co-morbidities associated with higher risk of COVID-19-positive postoperative death. Mortality was high in neurosurgery (80%) and the lowest in gynecological oncology surgery (none). This analysis provides an evidence base on which to consider surgical risk assessment for different specialties. Risk of perioperative death needs to be assessed in the context of patients’ co-morbidities and surgical specialty. An individualized approach toward surgical decision making is imperative.
Tzafetas M, Mitra A, Paraskevaidi M, et al., 2020, The intelligent knife (iKnife) and its intraoperative diagnostic advantage for the treatment of cervical disease (vol 117, pg 7338, 2020), PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 18892-18892, ISSN: 0027-8424
Natoli M, Bonito N, Robinson JD, et al., 2020, Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade, Cancer Immunology Immunotherapy, Vol: 69, Pages: 1391-1401, ISSN: 0340-7004
Immune checkpoint blocking antibodies are currently being tested in ovarian cancer (OC) patients and have shown some responses in early clinical trials. However, it remains unclear how human OC cancer cells regulate lymphocyte activation in response to therapy. In this study, we have established and optimised an in vitro tumour-immune co-culture system (TICS), which is specifically designed to quantify the activation of multiple primary human lymphocyte subsets and human cancer cell killing in response to PD-1/L1 blockade. Human OC cell lines and treatment naïve patient ascites show differential effects on lymphocyte activation and respond differently to PD-1 blocking antibody nivolumab in TICS. Using paired OC cell lines established prior to and after chemotherapy relapse, our data reveal that the resistant cells express low levels of HLA and respond poorly to nivolumab, relative to the treatment naïve cells. In accordance, knockdown of IFNγ receptor expression compromises response to nivolumab in the treatment naïve OC cell line, while enhanced HLA expression induced by a DNA methyltransferase inhibitor promotes lymphocyte activation in TICS. Altogether, our results suggest a 'cross resistance' model, where the acquired chemotherapy resistance in cancer cells may confer resistance to immune checkpoint blockade therapy through down-regulation of antigen presentation machinery. As such, agents that can restore HLA expression may be a suitable combination partner for immunotherapy in chemotherapy-relapsed human ovarian cancer patients.
Natoli M, Bonito N, Robinson JD, et al., 2020, Human ovarian cancer intrinsic mechanisms regulate lymphocyte activation in response to immune checkpoint blockade (vol 45, pg 203, 2020), CANCER IMMUNOLOGY IMMUNOTHERAPY, Vol: 69, Pages: 1403-1408, ISSN: 0340-7004
Du Bois A, Sehouli J, Vergote I, et al., 2020, Randomized phase III study to evaluate the impact of secondary cytoreductive surgery in recurrent ovarian cancer: Final analysis of AGO DESKTOP III/ENGOT-ov20., Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO), Publisher: LIPPINCOTT WILLIAMS & WILKINS, ISSN: 0732-183X
Jones BP, Vali S, Saso S, et al., 2020, Endometrial autotransplantation in rabbits: Potential for fertility restoration in severe Asherman's syndrome, EUROPEAN JOURNAL OF OBSTETRICS & GYNECOLOGY AND REPRODUCTIVE BIOLOGY, Vol: 248, Pages: 14-23, ISSN: 0301-2115
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