Sertoli-Leydig tumor and DICER1 gene mutation: A case series and literature review.

OBJECTIVE: Sertoli-Leydig cell tumors (SLCTs) are rare neoplasms occurring in young women with 60% associated with DICER1 mutations. This is only the second published case series of patients with SLCTs with associated DICER1 gene alterations. DICER1 syndrome is a rare inherited tumor-susceptibility syndrome affecting organs such as the ovaries. We use this case series to inform readers on this increasingly important condition in gynecology. METHODS AND RESULTS: We present three young females presenting with secondary amenorrhoea, hirsutism, acne and in one case tonic-clonic seizures. All cases had high testosterone levels and an adnexal mass on ultrasound. Following surgical removal, pathology confirmed SLCTs and genetic testing followed. All three patients had DICER1 syndrome with two patients subsequently found to be related. DISCUSSION: The prevalence of DICER1 syndrome in the population is estimated to be 1 in 10 000 with a spectrum of sex cord stromal tumors affecting young women. The associated pathological classifications and management. This paper describes the DICER1 gene and the associated tumor predisposition syndrome alongside a surveillance protocol for use in clinical practice. It promotes discussion over the importance of early clinical genetics involvement in sex-cord stromal tumors and the associated difficulties in counseling in a young patient population. Genetic testing and early detection are imperative for targeted surveillance of at-risk organs to be performed but despite this there is no international guidance. The cases highlight the psychological impact of tumors in young patients and provokes an ethical discussion over DICER1 gene's inclusion in preimplantation genetics. CONCLUSIONS: DICER1 syndrome is a rare but increasingly important condition in pediatric and adolescent gynecology with a paucity of published data and case reports. This makes international consensus on management and surveillance difficult.

FARGO-360: a multi-disciplinary survey of practice and perspectives on provision of care for patients with frailty presenting with gynecological cancers in the UK and Ireland.

OBJECTIVES: Frailty has been associated with worse cancer-related outcomes for people with gynecological cancers. However, the lack of clear guidance on how to assess and modify frailty prior to instigating active treatments has the potential to lead to large variations in practice and outcomes. This study aimed to evaluate current practice and perspectives of healthcare practitioners on the provision of care for patients with frailty and a gynecological cancer. METHODS: Data were collected via a questionnaire-based survey distributed by the Audit and Research in Gynecological Oncology (ARGO) collaborative to healthcare professionals who identified as working with patients with gynecological malignancies in the United Kingdom (UK) or Ireland. Study data were collected using REDCap software hosted at the University of Manchester. Responses were collected over a 16 week period between January and April 2021. RESULTS: A total of 206 healthcare professionals (30 anesthetists (14.6%), 30 pre-operative nurses (14.6%), 51 surgeons (24.8%), 34 cancer specialist nurses (16.5%), 21 medical/clinical oncologists (10.2%), 25 physiotherapists/occupational therapists (12.1%) and 15 dieticians (7.3%)) completed the survey. The respondents worked at 19 hospital trusts across the UK and Ireland. Frailty scoring was not routinely performed in 63% of care settings, yet the majority of practitioners reported modifying their practice when providing and deciding on care for patients with frailty. Only 16% of organizations surveyed had a dedicated pathway for assessment and management of patients with frailty. A total of 37% of respondents reported access to prehabilitation services, 79% to enhanced recovery, and 27% to community rehabilitation teams. CONCLUSION: Practitioners from all groups surveyed considered that appropriate training, dedicated pathways for optimization, frailty specific performance indicators and evidence that frailty scoring had an impact on clinical outcomes and patient experience could all help to improve care for frail patients.

The growth of 'Dry January': promoting participation and the benefits of participation.

This article explores contributors to the rapid growth of the annual UK alcohol abstinence challenge 'Dry January' and the benefits of registration. Evidence from four sources is presented: (i) registrations via the Dry January website, (ii) surveys of population-representative samples of drinkers, (iii) surveys of Dry January registrants and (iv) surveys of a control group of drinkers who wanted to change to their drinking behaviour but had not registered for Dry January. The data revealed that Dry January registrations increased 15-fold in 4 years. Participants reported that encouragement received from Dry January helped them to avoid drinking. Comparisons of Dry January registrants to the control group suggest that registering for Dry January reduced problematic drinking and enhanced the capacity to refuse alcohol. The four sources of data suggest that 'social contagion' and 'diffusion' have aided the growth of the awareness, appeal and practice of Dry January.

Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of ovarian cancer.

BACKGROUND: Ovarian cancer is the sixth most common cancer and seventh most common cause of cancer death in women world-wide. Three-quarters of women present when the disease has spread throughout the abdomen (stage III or IV) and treatment consists of a combination of debulking surgery and platinum-based chemotherapy. Although initial responses to chemotherapy are good, most women will relapse and require further chemotherapy and will eventually develop resistance to chemotherapy.PARP (poly (ADP-ribose) polymerase) inhibitors, are a novel type of medication that works by preventing cancer cells from repairing their DNA once they have been damaged by other chemotherapy agents. It is not clear how PARP inhibitors compare to conventional chemotherapy regimens for the treatment of ovarian cancer, with respect to survival, side effects and quality of life. OBJECTIVES: To determine the benefits and risks of PARP inhibitors for the treatment of epithelial ovarian cancer (EOC). SEARCH METHODS: We identified randomised controlled trials (RCTs) by searching the Cochrane Central Register of Controlled Trials (CENTRAL 2014, Issue 4), the Cochrane Gynaecological Cancer Group Trial Register, MEDLINE (1990 to May 2014), EMBASE (1990 to May 2014), ongoing trials on www.controlled-trials.com/rct, www.clinicaltrials.gov, www.cancer.gov/clinicaltrials and the National Research Register (NRR), the FDA database and pharmaceutical industry biomedical literature. SELECTION CRITERIA: Women with histologically proven EOC who were randomised to treatment groups in trials that either compared PARP inhibitors with no treatment, or PARP inhibitors versus conventional chemotherapy, or PARP inhibitors together with conventional chemotherapy versus conventional chemotherapy alone. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Two review authors independently assessed whether studies met the inclusion criteria. We contacted investigators for additional data, where possible. Outcomes included survival, quality of life and toxicity. MAIN RESULTS: We included four RCTs involving 599 women with EOC. Data for veliparib were limited and of low quality, due to small numbers (75 women total). Olaparib, on average, improved progression-free survival (PFS) when added to conventional treatment and when used as maintenance treatment in women with platinum-sensitive disease compared with placebo (hazard ratio (HR) 0.42, 95% confidence interval (CI) 0.29 to 0.60; 426 participants ; two studies), but did not improve overall survival (OS) (HR 1.05, 95% CI 0.79 to 1.39; 426 participants; two studies). We graded this evidence as moderate quality using the GRADE approach. Olaparib was associated with more severe adverse events (G3/4) during the maintenance phase compared with controls (risk ratio (RR) 1.74, 95% CI 1.22 to 2.49; 385 participants, two studies; moderate quality evidence). Quality of life data were insufficient for meta-analysis. We identified four ongoing studies. AUTHORS' CONCLUSIONS: PARP inhibitors appear to improve PFS in women with recurrent platinum-sensitive disease. Ongoing studies are likely to provide more information about whether the improvement in PFS leads to any change in OS in this subgroup of women with EOC. More research is needed to determine whether PARP inhibitors have any role to play in platinum-resistant disease.

Can we improve women's experience of operative vaginal birth?

OBJECTIVE: It is well understood that advanced skills are required for operative vaginal delivery to ensure a woman's birth experience is safe, positive and to prevent adverse long term harm. We sought to identify non-technical skills determined by women to enhance experience of operative vaginal delivery by qualitative analysis of interviews conducted during the postpartum period. DESIGN: A qualitative study using semi structured interviews took place at a University teaching hospital. Sixteen women who had an operative delivery of a term baby underwent a semi structured interview at 6-8 weeks postnatal. The women were asked to reflect on good and bad experiences of their delivery and the interview was recorded verbatim. Thematic coding of data was carried out and then analysed. Women were given the option to review the transcript for respondent validation. The anonymised transcripts were independently coded by two researchers and then compared for consistency of interpretation. The themes that emerged following the final coding were used to identify a framework of behavioural and clinical skills. RESULTS: We identified several non-technical skills that were important to women's' experience of operative delivery. Professional behaviour and relationships, decision making and communication, preconceptions and preparation for operative birth, teamwork, environment and consent were themes that emerged from women's experiences which can now provide clinicians with a comprehensive behavioural framework for operative vaginal delivery. CONCLUSION: This illustration of detailed non-technical skills that has been validated by women could be used as part of clinical training and revalidation.

Realism and construct validity of novel pelvic models of common gynecologic conditions.

OBJECTIVE: To test a novel set of pelvic trainers for realism and construct validity. METHODS: Seven models of the female pelvis were studied. Participants performed speculum and bimanual examinations, documented their findings, and recorded opinions of the models in a structured questionnaire. Results were analyzed by participant grade (inexperienced and experienced). RESULTS: Twenty-six inexperienced and 24 experienced gynecologists participated. Experienced doctors were more likely to correctly identify the uterus corresponding to 16 weeks of gestation (P<0.001), the large fibroid uterus (P=0.01), and uterine anteversion (P=0.04). Identification of the uterus containing a small fibroid, the uterus corresponding to 10 weeks of gestation, and an adnexal cyst was low overall (<35%) and not significantly different between the groups. Correct identification of cervical findings (ectropion and polyp) was high in both groups (65%-88%). Experienced doctors were more consistent-with 17 (71%) reporting the same correct finding on a repeated model, compared with 8 (31%) inexperienced doctors. Forty-nine (98%) doctors completed the structured questionnaire, 36 (73%) of whom felt the models were realistic. CONCLUSION: The models were found to be realistic and have construct validity. Senior participants were consistent at correctly identifying most abnormalities. The models may be useful for pelvic examination training; further testing is required regarding their ability to aid learning of clinical and communication skills.

The use of simulation to teach clinical skills in obstetrics.

Obstetrical practice demands sensitivity, clinical skill, and acumen. Obstetrical emergencies are rare occurrences and are most appropriately dealt with by experienced staff. Simulation provides an opportunity to gain this experience without patient risk and furthermore builds confidence and satisfaction amongst learners. There is an abundance of evidence to show the effectiveness of simulation training. Simulation has been demonstrated to reduce errors, increase knowledge, skills, communication and team working, and improve perinatal outcomes. Further research to measure the effect of training to identify what works, where and at what cost is needed. We explore the evidence for the use of simulation-based training across a broad range of obstetrical emergencies, promote collaboration amongst disciplines and discuss the formal introduction of simulation training into a curriculum. Reducing preventable harm in obstetrics is a priority for families and society at large and this article endeavors to highlight the role that simulation has to play.