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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.

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 (

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.

We aimed to evaluate the effectiveness of lifestyle interventions in improving the quality of life (QoL) of endometrial and ovarian cancer survivors.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.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.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.

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.

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.

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.

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.

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.