Bromodomain inhibitor i-BET858 triggers a unique transcriptional response coupled to enhanced DNA damage, cell cycle arrest and apoptosis in high-grade ovarian carcinoma cells.

BACKGROUND: Ovarian cancer has a specific unmet clinical need, with a persistently poor 5-year survival rate observed in women with advanced stage disease warranting continued efforts to develop new treatment options. The amplification of BRD4 in a significant subset of high-grade serous ovarian carcinomas (HGSC) has led to the development of BET inhibitors (BETi) as promising antitumour agents that have subsequently been evaluated in phase I/II clinical trials. Here, we describe the molecular effects and ex vivo preclinical activities of i-BET858, a bivalent pan-BET inhibitor with proven in vivo BRD inhibitory activity. RESULTS: i-BET858 demonstrates enhanced cytotoxic activity compared with earlier generation BETis both in cell lines and primary cells derived from clinical samples of HGSC. At molecular level, i-BET858 triggered a bipartite transcriptional response, comprised of a 'core' network of genes commonly associated with BET inhibition in solid tumours, together with a unique i-BET858 gene signature. Mechanistically, i-BET858 elicited enhanced DNA damage, cell cycle arrest and apoptotic cell death compared to its predecessor i-BET151. CONCLUSIONS: Overall, our ex vivo and in vitro studies indicate that i-BET858 represents an optimal candidate to pursue further clinical validation for the treatment of HGSC.

In silico enhancer mining reveals SNS-032 and EHMT2 inhibitors as therapeutic candidates in high-grade serous ovarian cancer.

BACKGROUND: Epigenomic dysregulation has been linked to solid tumour malignancies, including ovarian cancers. Profiling of re-programmed enhancer locations associated with disease has the potential to improve stratification and thus therapeutic choices. Ovarian cancers are subdivided into histological subtypes that have significant molecular and clinical differences, with high-grade serous carcinoma representing the most common and aggressive subtype. METHODS: We interrogated the enhancer landscape(s) of normal ovary and subtype-specific ovarian cancer states using publicly available data. With an initial focus on H3K27ac histone mark, we developed a computational pipeline to predict drug compound activity based on epigenomic stratification. Lastly, we substantiated our predictions in vitro using patient-derived clinical samples and cell lines. RESULTS: Using our in silico approach, we highlighted recurrent and privative enhancer landscapes and identified the differential enrichment of a total of 164 transcription factors involved in 201 protein complexes across the subtypes. We pinpointed SNS-032 and EHMT2 inhibitors BIX-01294 and UNC0646 as therapeutic candidates in high-grade serous carcinoma, as well as probed the efficacy of specific inhibitors in vitro. CONCLUSION: Here, we report the first attempt to exploit ovarian cancer epigenomic landscapes for drug discovery. This computational pipeline holds enormous potential for translating epigenomic profiling into therapeutic leads.

Pelvic Exenteration for the Treatment of Locally Advanced Vulvar Cancer in South West Wales.

The treatment of locally advanced vulvar carcinoma (LAVC) represents a major challenge. We investigated the role of pelvic exenteration as a treatment of LAVC. Women who underwent pelvic exenteration for primary and recurrent LAVC in our centre between 2001 and 2019 were included. Among the 19 women included during the study period, 14 women (73.7%) had primary LAVC while 5 women (26.3%) had recurrent disease. Surgical resection margins were microscopically clear (R0) in 94.7% of patients-14/14 undergoing primary treatment and 4/5 undergoing treatment for recurrent disease. Complete closure of the wound was achieved in 100% of women, with no wound left to heal by secondary intention. Tumour size was a predictor of requiring myocutaneous flap reconstruction, with all tumours less than 40 mm undergoing primary closure, while almost all tumours 40 mm diameter or greater (14/15 women) required flap reconstruction (p = 0.001). The 30-day major morbidity rate was 42% and there was no perioperative death. The mean overall survival was 144.8 months (2-206 months), with 1-, 2- and 5-year survival rates of 89.5%, 75.1% and 66.7%, respectively. In our centre, a primary surgical approach to the management of LAVC has resulted in good survival outcomes with acceptable morbidity rates.

The predictive role of thrombocytosis in benign, borderline and malignant ovarian tumors.

Ovarian cancer is a lethal gynecological malignancy. Although CA-125 is commonly measured in women with adnexal mass, it is estimated that it only has a positive predictive value (PPV) of 69% and a negative predictive value (NPV) of 88% for the detection of ovarian cancer. The aim of this study was to investigate the diagnostic significance and predictive impact of thrombocytosis in women with suspected or confirmed ovarian cancer. This was a retrospective study of women who had surgery for adnexal mass over a 48-month period between September 2014 and September 2018 at Swansea Gynecological Oncology Center in Wales, UK. A total of 294 women who underwent surgery for high-risk pelvic mass or biopsy-confirmed ovarian cancer were identified. 206 women (70%) had final histology confirming ovarian cancer, 54 women (18%) had benign tumors while 34 women (12%) had borderline tumors. 90/206 women (43.7%) with ovarian cancer had thrombocytosis prior to primary surgery or neoadjuvant chemotherapy compared to 8/54 (14.8%) for benign tumors and 4/34 (11.8%) for borderline tumors. Thrombocytosis was observed in 23.2%, 40%, 45.1%, and 65.1% of Stages I, II, III, and IV ovarian cancer, respectively. Thrombocytosis was a stronger predictor of ovarian malignancy in younger women of less than 60 years (p = .041). Overall, the positive likelihood ratio of platelet count in the detection of ovarian cancer was 2.61 while the negative likelihood ratio was 0.72, with a diagnostic odds ratio of 3.625. Thrombocytosis was strongly associated with advanced stage ovarian cancer (Stage III/IV) (p = .002). Interestingly, 4/8 (50%) women with thrombocytosis in the benign ovarian tumor group were diagnosed with ovarian fibroma/fibrothecoma, which often mimics advanced ovarian cancer at presentation. Predictive markers for borderline tumors continue to remain a challenge. We believe that there is a role for platelet count in primary care algorithm for women with suspected ovarian cancer. We suspect that platelets play a role in the metastasis of ovarian cancer.

Primary Mucinous Carcinoma of the Fallopian Tube: Case Report and Review of Literature.

Primary mucinous carcinoma of the fallopian tube is extremely rare. We report the detailed characterization of a mucinous carcinoma arising in the fimbrial end of the fallopian tube in a 74-yr-old woman. The patient presented with recurrent urinary tract infection and urinary tract obstruction secondary to a large right ovarian mass. She had an appendicectomy as an 11 yr old. Serum CA-125 was raised at 239 U/mL. Computed tomographic scans showed bilateral, cystic ovarian tumors but no other intra-abdominal abnormality. The patient underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omental biopsy. Microscopy showed mucinous carcinoma arising from the left tubal fimbriae, in association with mucinous metaplasia over the uninvolved fimbrial folds. There was no mucinous metaplasia in the contralateral fallopian tube, endometrial lining, cervix, or on the uterine serosal surface. A mucinous borderline tumor of gastrointestinal subtype was identified in the left ovary. The right ovary contained a benign mucinous cystadenoma of mixed gastrointestinal and endocervical-like/Müllerian subtype. The fallopian tube tumor expressed CK7, claudin 18, and MUC6, but not CK20, CDX2, CEA, pyloric gland mucin (recognized by HIK1083), ER, or vimentin. The immunolabelling pattern for p53 was wild-type, and p16 expression was nonblock. The metaplastic mucinous tubal epithelium also marked for CK7, CK20, CDX2, and CEA but had mutation-type p53 labelling (p53 null), a low Ki-67 index, and was immunopositive for HIK1083, MUC6, and claudin 18. This is the first detailed characterization of a primary mucinous fallopian tube carcinoma and the adjacent metaplastic mucinous epithelium, and confirms it to be of gastric type.

Exercise Programme in Endometrial Cancer; Protocol of the Feasibility and Acceptability Survivorship Trial (EPEC-FAST).

INTRODUCTION: Obesity has been associated with impaired quality of life and poorer outcomes in endometrial cancer survivors. Lifestyle interventions promoting exercise and weight reduction have been proposed for survivorship care. However, studies evaluating exercise programmes for endometrial cancer survivors are lacking. PURPOSE: The objective of this study is to evaluate the feasibility of an individualised exercise intervention for endometrial cancer survivors to improve quality of life. METHODS AND ANALYSIS: This is a feasibility study in which women will undergo a 10-week exercise programme with a personal trainer. The study population comprises women with confirmed diagnosis of endometrial cancer, who have completed surgical treatment with curative intent, and are aged 18 years or older. The study will take place at the Royal Cornwall Hospital Trust, UK. Feasibility will be evaluated in terms of recruitment, adherence and compliance to the programme. Secondary outcomes are quality of life, psychological distress, fatigue, pain and complication rates. In addition, the acceptability of the programme will be assessed. ETHICS AND DISSEMINATION: Ethical approval was obtained through the Exeter NRES Committee. The study results will be used to optimise the intervention content, and may serve as the foundation for a larger definitive trial. Results will be disseminated through peer-review journals, congresses, relevant clinical groups and presented on the Trust's website. TRIAL REGISTRATION NUMBER: NCT02367950; pre-results.

The effect of lifestyle interventions on the quality of life of gynaecological cancer survivors: A systematic review and meta-analysis.

OBJECTIVE: We aimed to evaluate the effectiveness of lifestyle interventions in improving the quality of life (QoL) of endometrial and ovarian cancer survivors. METHODS: The review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and the Cochrane Handbook for Systematic Reviews of Interventions. We performed a search of MEDLINE (1946-2015), EMBASE (1980-2015), CINAHL (1981-2015), PsycINFO (1806-2015) and the Cochrane Trial Register to identify studies evaluating the effect of lifestyle interventions on the QoL of endometrial and ovarian cancer survivors. RESULTS: Eight studies fulfilled the inclusion criteria and comprised a total of 413 patients. Three studies were randomised controlled trials (RCTs), which showed that lifestyle interventions may improve physical functioning and significantly reduce fatigue in endometrial cancer survivors. In addition, lifestyle interventions in endometrial cancer survivors resulted in significant weight loss and improved physical activity levels, but did not show improvements in global QoL in the meta-analysis (P=0.75, P=0.49). Non-randomised trials in ovarian cancer survivors support the feasibility of lifestyle interventions and suggest they may result in QoL improvements. CONCLUSIONS: Lifestyle interventions have the potential to improve the QoL of endometrial cancer and ovarian cancer survivors, and may significantly reduce fatigue. However, the current evidence is limited and there is a need for future studies to further evaluate lifestyle interventions and their effect on QoL outcomes.

The impact of BMI on surgical complications and outcomes in endometrial cancer surgery--an institutional study and systematic review of the literature.

OBJECTIVES: We aimed to evaluate the association between body mass index (BMI), perioperative complications and outcomes in endometrial cancer (EC) patients at our institution. In addition, we performed a systematic review to compare our results to the literature. METHODS: This was a retrospective study of surgically managed EC patients between January 2006 and January 2015. Patient characteristics, surgical complications and intra- and postoperative outcomes were evaluated across BMI groups; BMI <30kg/m(2), BMI ≥30kg/m(2) and BMI ≥40kg/m(2). The systematic review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: In total, we identified 627 women of which 514 were included; 249 women had a BMI of <30kg/m(2), 195 women had a BMI of 30-39.9kg/m(2), and 70 women were morbidly obese (BMI ≥40kg/m(2)). Obese women (BMI ≥30kg/m(2)) had significantly more postoperative surgical complications, including wound complications and antibiotics use, which was confirmed by the systematic review. The increase in complications mainly occurred in open surgery and morbidly obese patients were at highest risk. Obesity did not impact other outcomes including 30-day mortality. CONCLUSION: Obesity is associated with an increased risk of surgical morbidity in EC patients, and is most profound in open surgery and among the morbidly obese. Laparoscopic surgery may well prevent the majority of postoperative complications in this group of patients, and should therefore be the favoured approach.

Body mass index, physical activity and quality of life of ovarian cancer survivors: time to get moving?

OBJECTIVE: To evaluate the association between body mass index (BMI), physical activity (PA) and the quality of life (QoL) of ovarian cancer survivors. METHODS: We performed a two-centre cross-sectional study of women who had been treated for ovarian cancer between January 2007 and December 2014 at the Royal Cornwall Hospital Trust and the Plymouth Hospitals NHS Trust. QoL was assessed using the EORTC QLQ-C30 and QLQ-OV28 questionnaires, and PA using the Godin Leisure Time Exercise questionnaire. RESULTS: In total, 293 ovarian cancer survivors were invited to participate, of which 209 women (71.3%) responded. Thirty-five percent of women were overweight and 18% were obese, whilst only 21% met recommendations for PA. Obesity was associated with significantly poorer global QoL, physical, cognitive and social functioning, a poorer body image and more symptomatology. Sedentary behaviour was associated with poorer QoL scores including global QoL, physical, role, social and sexual functioning. After adjustment, BMI and PA both remained independently associated with QoL scores. CONCLUSION: Obesity and inactivity are associated with poorer QoL among ovarian cancer survivors. Future interventions promoting PA and weight loss should be evaluated as possible means to improve the QoL of this population.

Quality of life in ovarian cancer survivors: the influence of obesity.

OBJECTIVE: In this study, we evaluated the effect of body mass index (BMI) on the quality of life of ovarian cancer survivors. METHODS: Women diagnosed with ovarian cancer at the Royal Cornwall Hospital Trust between January 2008 and May 2013 were identified. Ovarian cancer survivors were invited to participate by completing the European Organization for Research and Treatment of Cancer QLQ-C30 (quality of life) questionnaire. Univariate and multiple regression analyses were used to determine associations between BMI and quality-of-life outcomes. RESULTS: A total of 176 ovarian cancer survivors were invited to participate, of which 133 were eligible for this study. In total, 81 ovarian cancer survivors (60.4%) completed the questionnaire, of which 26 responders (32.1%) were overweight (BMI, 25-29.9 kg/m²) and 27 (33.3%) were obese (BMI, ≥30 kg/m²). Increasing BMI was significantly associated with poorer quality-of-life outcomes in terms of physical functioning and emotional functioning, and this effect persisted for physical functioning after multiple regression analysis. CONCLUSIONS: Increasing BMI is associated with poorer quality-of-life outcomes in terms of physical and emotional functioning in ovarian cancer survivors. Further research is needed to evaluate the association between BMI and quality of life from diagnosis to survivorship to develop novel interventions.

Nurse-Led Telephone Follow-up: Improving Options for Women With Endometrial Cancer.

BACKGROUND: Nurse-led follow-up (NLFU) has been identified as a suitable means of follow-up care in cancer patients, and its acceptability has already been demonstrated in other areas of cancer care. OBJECTIVES: The objectives of this study were to evaluate the effect of NLFU on quality of life and patient satisfaction compared with conventional follow-up (CFU) in women treated for endometrial cancer and to evaluate the feasibility of NLFU, in terms of patient acceptance and referral to consultant clinic. METHODS: Participants included women diagnosed with endometrial cancer between 2008 and 2013. At time of study, 118 women were receiving NLFU, and 178 women were receiving CFU. Quality of life and patient satisfaction were evaluated through the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire and the In-patient Satisfaction With Care Measure questionnaires. Feasibility of NLFU was retrospectively assessed through patient's records. RESULTS: Seventy-eight women in NLFU and 112 women in CFU completed the questionnaires. Quality-of-life outcomes and satisfaction levels did not differ between both forms of follow-up. Almost all women in NLFU (98%) found NLFU an acceptable alternative to CFU. CONCLUSION: Women receiving NLFU reported similar quality of life and satisfaction with care as did women in CFU, making it a promising alternative for follow-up care of women with endometrial cancer. IMPLICATIONS FOR PRACTICE: Options are improved for women with endometrial cancer by offering alternative follow-up strategies within the national healthcare.

The impact of BMI on quality of life in obese endometrial cancer survivors: does size matter?

BACKGROUND: Survivorship and quality of life issues are becoming increasingly relevant in endometrial cancer as a result of the marked increase in incidence of the disease combined with excellent and improving long term survival. OBJECTIVE: The purpose of this study was to evaluate the effect of obesity on quality of life (QoL) in endometrial cancer survivors. METHODS: Participants were endometrioid endometrial cancer survivors diagnosed between 2008 and 2013. Quality of life was measured through the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire (QLQ-C30, version 3.0). Associations between BMI and quality of life were determined by means of multivariate analyses. RESULTS: 322 women diagnosed with endometrioid endometrial cancer were invited to participate. Excluded were 15 women with unknown BMI, 40 with non-endometrioid histology and 10 with concurrent cancer. The QLQ-C30 questionnaire was completed by 158 (61.5%) women, of which 63 women (40%) were obese (BMI ≥ 30-39.9), and 30 women (19%) were morbidly obese (BMI ≥ 40). Morbidly obese women reported worse physical, role and social functioning and more somatic complaints. CONCLUSION: Morbid obesity is associated with poorer quality of life in endometrial cancer survivors. Life style interventions such as exercise programs and diet interventions could be viable means to improve the quality of life of obese endometrial cancer survivors. Future research should focus on means to improve quality of life in obese endometrial cancer survivors.

Adjuvant radiotherapy and/or chemotherapy after surgery for uterine carcinosarcoma.

BACKGROUND: Uterine carcinosarcomas are uncommon with about 35% not confined to the uterus at diagnosis. The survival of women with advanced uterine carcinosarcoma is poor with a pattern of failure indicating greater likelihood of upper abdominal and distant metastatic recurrence. OBJECTIVES: To evaluate the effectiveness and safety of adjuvant radiotherapy and/or systemic chemotherapy in the management of uterine carcinosarcoma. SEARCH METHODS: We searched the Cochrane Gynaecological Cancer Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), 2012, Issue 10, MEDLINE and EMBASE up to November 2012. We also searched registers of clinical trials, abstracts of scientific meetings, reference lists of included studies and contacted experts in the field. SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing adjuvant radiotherapy and/or chemotherapy in women with uterine carcinosarcoma. DATA COLLECTION AND ANALYSIS: Two review authors independently abstracted data and assessed risk of bias. Hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) and risk ratios (RRs) comparing adverse events in women who received radiotherapy and/or chemotherapy were pooled in random-effects meta-analyses. MAIN RESULTS: Three trials met the inclusion criteria and these randomised 579 women, of whom all were assessed at the end of the trials. Two trials assessing 373 participants with stage III to IV persistent or recurrent disease, found that women who received combination therapy had a significantly lower risk of death and disease progression than women who received single agent ifosfamide, after adjustment for performance status (HR = 0.75, 95% confidence interval (CI): 0.60 to 0.94 and HR = 0.72, 95% CI: 0.58 to 0.90 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of nausea and vomiting, where significantly more women experienced these ailments in the combination therapy group than the Ifosamide group (RR = 3.53, 95% CI: 1.33 to 9.37).In one trial there was no statistically significant difference in the risk of death and disease progression in women who received whole body irradiation and chemotherapy, after adjustment for age and FIGO stage (HR = 0.71, 95% CI: 0.48 to 1.05 and HR = 0.79, 95% CI: 0.53 to 1.18 for OS and PFS respectively). There was no statistically significant difference in all reported adverse events, with the exception of haematological and neuropathy morbidities, where significantly less women experienced these morbidities in the whole body irradiation group than the chemotherapy group (RR= 0.02, 95% CI: 0.00 to 0.16) for haematological morbidity and all nine women in the trial experiencing neuropathy morbidity were in the chemotherapy group). AUTHORS' CONCLUSIONS: In advanced stage metastatic uterine carcinosarcoma as well as recurrent disease adjuvant combination, chemotherapy with ifosfamide should be considered. Combination chemotherapy with ifosfamide and paclitaxel is associated with lower risk of death compared with ifosfamide alone. In addition, radiotherapy to the abdomen is not associated with improved survival.

Chronic granulomatous inflammation of the vulva: an unusual presentation with diagnostic and therapeutic difficulties.

Inflammation of the vulva can present as a manifestation of a localized problem or as part of a systemic disorder. Granulomatous vulvitis is a rare inflammatory condition that has histologic similarities to Crohn disease. Clinically, it presents with painless, chronic relapsing erythema, and edema, typically affecting the genital area. We report a case of extensive granulomatous vulvitis in a patient with no gastrointestinal evidence of Crohn disease. We describe difficulties with diagnosis and limitations in the treatment of isolated vulval granulomatous disease and aim to promote earlier recognition of the disease.

Cytological follow-up of women older than 50 years with high-grade cervical smear treated by large loop excision.

OBJECTIVE: To evaluate cytological surveillance for women older than 50 years, to detect recurrent or residual disease after treatment of cervical intraepithelial neoplasia by loop excision. MATERIALS AND METHODS: Women undergoing a large loop excision for high-grade squamous intraepithelial lesion or glandular cytological abnormalities during a period of 4 years (2000-2003) were identified from the colposcopy database. Women younger than 50 years or with a history of previous loop excision were excluded. Clinical data, histology, and follow-up cytology results for up to 2 years after treatment were collected. RESULTS: Eighty-nine patients were identified. Age of the women ranged from 51 to 66 years, with a median of 51.5 years. Thirty-two (36%) had severe dyskaryosis, 53 (60%) had moderate dyskaryosis, and 4 (4%) had glandular abnormalities on cervical cytology before the loop biopsy. Cervical intraepithelial neoplasia (CIN) 2,3 and glandular abnormalities, CIN 1, and no abnormalities were found in 50 (56%), 18 (20%), and 19 (22%) loop specimens, respectively. Invasive disease was found in 2 (2%) cases. They were excluded from further analysis. The lesion was completely excised in 58 (65%) and incompletely excised in 23 (26%) patients. It was not possible to comment on the margin status in 8 (9%) cases. These were excluded from further analysis. Of the 23 women who had margins involved, 8 (35%) had ectocervical, 12 (52%) had endocervical, and 3 (13%) had both margins involved. All women had follow-up cervical smears at the cytology clinic. At 6-month follow-up, 3 patients had persistent CIN and 4 had borderline changes on cervical smears. At 2 years follow-up, 3 patients had high-grade squamous intraepithelial lesion abnormalities, 2 of whom had clear margins at their loop biopsy earlier.Twenty percent of the women with positive endocervical margins on loop excision needed further treatment for residual or persistent disease on follow-up. Overall, 4 (5%) of the 79 patients who had a loop biopsy went on to have cytological abnormalities suggestive of persistent/residual disease needing further treatment. CONCLUSION: Cytological surveillance for post-loop biopsy follow-up seems to be a good option for detecting residual disease in this high-risk group of patients.

Recurrent smear abnormalities where repeat loop treatment is not possible: is hysterectomy the answer?

OBJECTIVE: The objective of this study was to determine the outcome of women who underwent hysterectomy for recurrent cytological abnormalities where repeat loop treatment was considered not to be technically possible because of insufficient remaining cervical tissue. METHODS: Women undergoing a hysterectomy for the above indication at the Northern Gynaecological Cancer Centre over a period of 10 years (1992-2001) were identified from a prospectively collected database. Case notes were then reviewed and women undergoing hysterectomy for other indications were excluded. Relevant demographic and clinical data were then extracted. RESULTS: 33 patients meeting the above criteria were identified. The overall hysterectomy rate for this indication was 0.73%. 20 out of the 33 women had significant pathology on the hysterectomy specimen. 95% of these had high-grade disease with one having a Stage 1A1 squamous carcinoma. None of the patients required more radical treatment than a simple hysterectomy. There were no major complications following the hysterectomy. Positive endocervical margins on the previous loop specimen (P = 0.05) was an important correlating factor predicting the presence of CIN on the hysterectomy specimen. One out of the thirty hysterectomies (3.3%) performed using the vaginal route had incomplete excision compared to one of three (33%) using the abdominal route. Hysterectomy was successful in treating 85.2% of the women; only 4 women subsequently developed vaginal intraepithelial neoplasia. CONCLUSION: Simple hysterectomy appears to be a suitable diagnostic and treatment option for women with recurrent high-grade cytological abnormalities where further loop treatment is technically not possible. Incomplete excision at the endocervical margin on the previous loop specimen was the main factor associated with the presence of cervical intraepithelial neoplasia at hysterectomy.

Current knowledge of risks and benefits of prophylactic oophorectomy at hysterectomy for benign disease in United Kingdom and Republic of Ireland.

OBJECTIVE: To estimate current practice of prophylactic oophorectomy at hysterectomy for benign disease and also define the role of the variables considered prior to making the decision of prophylactic oophorectomy among consultant obstetricians and gynaecologists in UK and Republic of Ireland. DESIGN: A postal questionnaire was sent to all 1536 practising consultant gynaecologists in UK and Republic of Ireland. METHODS AND MAIN OUTCOMES MEASURED: Of the 809 replies received, 21% of the respondents routinely performed prophylactic oophorectomy. There was a wide regional variation; 40% consultants in Wales considered prophylactic oophorectomy compared to 16% in the Northern and Yorkshire regions. Consultants with a special interest with a more surgical bias were more likely to consider performing prophylactic oophorectomy. The majority of respondents estimated that prophylactic oophorectomy would reduce risk of ovarian cancer by up to 5%, and that following hysterectomy and ovarian conservation there was an increased risk of premature menopause. CONCLUSION: There is a large variation and uncertainty in the practice of prophylactic oophorectomy in UK and Ireland.

Current practice of hysterectomy and oophorectomy in the United Kingdom and Republic of Ireland.

The purpose of this study was to estimate current surgical practice of hysterectomy and prophylactic oophorectomy of UK and Irish consultant gynaecologists. Individual and regional variation in surgical practice and factors influencing surgical practice were assessed. A postal questionnaire was sent to all 1536 consultants in obstetrics and gynaecology currently practising in the United Kingdom and Ireland, with a 52.7% response rate. Approximately 60% of hysterectomies were abdominal, 37% vaginal and 4% laparoscopic-assisted, with junior consultants performing a greater proportion of hysterectomies vaginally. There was a wide variation in method of hysterectomy, both individually and regionally. Only 21% of consultants would routinely consider performing prophylactic oophorectomy and of these the majority would perform this procedure in women aged between 46 and 50 years old. This large variation in surgical practice indicates a need to form a consensus on optimal surgical techniques and to ensure adequate surgical training for all gynaecologists.