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.

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.

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.

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.