Risk Factors for Ovarian Cancer : An Umbrella Review of the Literature

Simple Summary Ovarian cancer is the most lethal cancer of the female genital tract despite major advances in both surgical and oncological treatments. This is in part due to difficulties in identifying those most at risk of developing ovarian cancer, and that there are currently no effective screening strategies. Whilst 20% of cases have a genetic component, the majority have no obvious cause. Many risk factors have been associated with ovarian cancer, although the strength of this evidence remains unclear. This umbrella review attempts to review the validity of associations between non-genetic risk factors and the risk of developing or dying from ovarian cancer. There were six associations that were supported by strong evidence. Greater height, BMI and use of HRT increased the risk, whilst the use of oral contraceptive pill reduced that risk. This review will enable further research into these areas and may promote identification of individuals at high risk. Several non-genetic factors have been associated with ovarian cancer incidence or mortality. To evaluate the strength and validity of the evidence we conducted an umbrella review of the literature that included systematic reviews/meta-analyses that evaluated the link between non-genetic risk factors and ovarian cancer incidence and mortality. We searched PubMed, EMBASE, Cochrane Database of Systematic Reviews and performed a manual screening of references. Evidence was graded into strong, highly suggestive, suggestive or weak based on statistical significance of the random effects summary estimate and the largest study in a meta-analysis, the number of cases, between-study heterogeneity, 95% prediction intervals, small study effects, and presence of excess significance bias. We identified 212 meta-analyses, investigating 55 non-genetic risk factors for ovarian cancer. Risk factors were grouped in eight broad categories: anthropometric indices, dietary intake, physical activity, pre-existing medical conditions, past drug history, biochemical markers, past gynaecological history and smoking. Of the 174 meta-analyses of cohort studies assessing 44 factors, six associations were graded with strong evidence. Greater height (RR per 10 cm 1.16, 95% confidence interval (CI) 1.11-1.20), body mass index (BMI) (RR >= 30 kg/m(2) versus normal 1.27, 95% CI 1.17-1.38) and three exposures of varying preparations and usage related to hormone replacement therapy (HRT) use increased the risk of developing ovarian cancer. Use of oral contraceptive pill reduced the risk (RR 0.74, 95% CI 0.69-0.80). Refining the significance of genuine risk factors for the development of ovarian cancer may potentially increase awareness in women at risk, aid prevention and early detection.Peer reviewe

Detecting Endometrial Cancer by Blood Spectroscopy: A Diagnostic Cross-Sectional Study

Endometrial cancer is the sixth most common cancer in women, with a rising incidence worldwide. Current approaches for the diagnosis and screening of endometrial cancer are invasive, expensive or of moderate diagnostic accuracy, limiting their clinical utility. There is a need for cost-effective and minimally invasive approaches to facilitate the early detection and timely management of endometrial cancer. We analysed blood plasma samples in a cross-sectional diagnostic accuracy study of women with endometrial cancer (n = 342), its precursor lesion atypical hyperplasia (n = 68) and healthy controls (n = 242, total n = 652) using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy and machine learning algorithms. We show that blood-based infrared spectroscopy has the potential to detect endometrial cancer with 87% sensitivity and 78% specificity. Its accuracy is highest for Type I endometrial cancer, the most common subtype, and for atypical hyperplasia, with sensitivities of 91% and 100%, and specificities of 81% and 88%, respectively. Our large-cohort study shows that a simple blood test could enable the early detection of endometrial cancer of all stages in symptomatic women and provide the basis of a screening tool in high-risk groups. Such a test has the potential not only to differentially diagnose endometrial cancer but also to detect its precursor lesion atypical hyperplasia—the early recognition of which may allow fertility sparing management and cancer prevention

The association between obesity and weight loss after bariatric surgery on the vaginal microbiota

Background: Obesity and vaginal microbiome (VMB) dysbiosis are each risk factors for adverse reproductive and oncological health outcomes in women. Here, we investigated the relationship between obesity, vaginal bacterial composition, local inflammation and bariatric surgery. Methods: Vaginal bacterial composition assessed by high-throughput sequencing of bacterial 16S rRNA genes and local cytokine levels measured using a multiplexed Magnetic Luminex Screening Assay were compared between 67 obese and 42 non-obese women. We further assessed temporal changes in the microbiota and cytokines in a subset of 27 women who underwent bariatric surgery. Results: The bacterial component of the vaginal microbiota in obese women was characterised by a lower prevalence of a Lactobacillus-dominant VMB and higher prevalence of a high diversity (Lactobacillus spp., and Gardnerella- spp. depleted) VMB, compared with non-obese subjects (

Provision of obstetrics and gynaecology services during the COVID-19 pandemic:a survey of junior doctors in the UK National Health Service

Objective: The COVID-19 pandemic is disrupting health services worldwide. We aimed to evaluate the provision of obstetrics and gynaecology services in the UK during the acute-phase of the COVID-19 pandemic. Design: Interview-based national survey. Setting: Women’s healthcare units in the National Health Service. Population: Junior doctors in obstetrics and gynaecology. Methods: Participants were interviewed by members of the UKARCOG trainees’ collaborative between 28th March and 7th of April 2020. We used a quantitative analysis for closed-ended questions and a thematic framework analysis for open comments. Results: We received responses from 148/155 units (95%), majority of the participants were in years 3-7 of training (121/148, 82%). Most completed specific training drills for managing obstetric and gynaecological emergencies in women with COVID-19 (89/148, 60.1%) and two-persons donning and doffing of Personal Protective Equipment (PPE) (96/148, 64.9%). The majority of surveyed units implemented COVID-19 specific protocols (130/148, 87.8%), offered adequate PPE (135/148, 91.2%) and operated dedicated COVID-19 emergency theatres (105/148, 70.8%). Most units reduced face-to-face antenatal clinics (117/148, 79.1%), and suspended elective gynaecology services (131/148, 88.5%). The two-week referral pathway for oncology gynaecology was not affected in half of the units (76/148, 51.4%), while half reported a planned reduction in oncology operating (82/148, 55.4%). Conclusion: The provision of obstetrics and gynaecology services in the UK during the acute phase of the COVID-19 pandemic seems to be in line with current guidelines, but strategic planning is needed to restore routine gynaecology services and ensure safe access to maternity care on the longterm

Understanding the role of obesity and complex metabolic dysregulation in the development of endometrial cancer

A rapidly increasing major public health problem is the continuum of obesity, metabolic disorders and development of cancer. Obesity is associated with an up to 5-fold increase in endometrial cancer. I hypothesised that complex metabolic dysregulation, including insulin resistance and increased local inflammation may contribute to the multi-factorial aetiology of endometrial cancer. This thesis examined the strength and validity of evidence for associations between risk factors and endometrial cancer with an umbrella review of the literature. Key components of the insulin signalling (IGF-R/mTOR/Akt) pathway in benign and endometrial cancer tissues were investigated, assessing whether protein expression correlated with obesity and insulin resistance status. Phospholipid expression according to metabolic status was investigated using mass spectrometry imaging, and vaginal microbiota composition and local cytokine expression is described in obese women, with assessment of temporal changes after partial correction of metabolic dysregulation by bariatric surgery. Body mass index and waist-to-hip ratio were risk factors strongly associated with increased endometrial cancer risk. Proteomic analysis found upregulation of proteins involved in insulin and oncogenic signalling pathways in obese and insulin resistant women with normal endometrial tissue, suggesting an ‘at-risk’ metabolic profile for endometrial carcinogenesis. Lipidomic analysis of endometrial tissue found increased expression of distinct phosphatidylinositol and phosphatidylethanolamine lipid species among cancer tissues, and benign endometrium had higher relative abundance of phosphatidylglycerol species. These findings have added to our understanding of upregulated lipid-associated metabolic pathways in endometrial cancer. Characterisation of the vaginal microbiota in obesity found increased bacterial species diversity, which transitioned towards dominance of reproductive health-promoting low-diversity bacteria after surgically-induced weight loss. The multi-factorial aetiology of endometrial cancer is complex and the signalling pathways that are activated leading to endometrial cancer development need further investigation. Understanding the impact on these pathways by metabolic changes brought about by obesity and insulin resistance may lead to identifying biomarkers with preventative and treatment potential.Open Acces

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Assessment of accuracy of medical certificates of stillbirth issued in 2018 in UK Obstetric units

Spectroscopy of blood samples for the diagnosis of endometrial cancer and classification of its different subtypes

5596 Background: Symptoms of endometrial cancer often appear in early stages, thus a diagnosis, based on microscopic histological examination of endometrial tissue, can be given relatively on time. However, this procedure interferes subjective interpretation allowing human error, while screening of the asymptomatic population is not widely performed because of the high cost of the available tests (e.g. transvaginal ultrasound) and the relative invasiveness [biopsy or dilation and curettage (D+C)]. Consequently, there is a widespread need to develop inexpensive, non-invasive techniques that would accurately diagnose endometrial cancer, as well as classify the different subtypes. Spectrochemical methods generate a signature fingerprint of biological material in the form of spectra. Unlike immunological methods, which detect only one molecule at a time, the spectra obtained from a clinical sample represent all the molecular constituents within that sample, including proteins, lipids and carbohydrates; this provides a holistic picture of the sample. Previous studies have confirmed spectroscopy’s ability to diagnose gynecologic cancers in blood. Methods: Attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy was used to analyse blood plasma and serum from 71 women with endometrial cancer and 18 age-matched healthy controls; classification algorithms were then applied to extract the underlying biological information. Results: Principal component analysis followed by support vector machine (PCA-SVM) diagnosed endometrial cancer with 100% accuracy in plasma and 95% in serum. Discrimination between the different subtypes [endometrioid adenocarcinoma (n = 43) vs carcinosarcoma (n = 14)] was achieved with 98.33% accuracy in both plasma and serum. The spectral regions responsible for discrimination were attributed to protein and lipid alterations. Conclusions: Our preliminary results suggest an accurate and objective diagnostic tool for endometrial cancer with blood testing, allowing therefore thoughts for a potential screening test in high risk populations. Future work will include higher number of normal cases and different subtypes and grades

Worth the paper it's written on- A cross-sectional study of Medical Certificate of Stillbirth accuracy in the UK

BackgroundThe Medical Certificate of Stillbirth (MCS) records data about a baby’s death after 24 weeks of gestation but before birth. Major errors that could alter interpretation of the MCS were widespread in two UK-based regional studies.MethodsA multicentre evaluation was conducted, examining MCS issued 1 January 2018 to 31 December 2018 in 76 UK obstetric units. A systematic case-note review of stillbirths was conducted by Obstetric and Gynaecology trainees, generating individual ‘ideal MCSs’ and comparing these to the actual MCS issued. Anonymized central data analysis described rates and types of error, agreement and factors associated with major errors.ResultsThere were 1120 MCSs suitable for assessment, with 126 additional submitted data sets unsuitable for accuracy analysis (total 1246 cases). Gestational age demonstrated ‘substantial’ agreement [K = 0.73 (95% CI 0.70–0.76)]. Primary cause of death (COD) showed ‘fair’ agreement [K = 0.26 (95% CI 0.24–0.29)]. Major errors [696/1120; 62.1% (95% CI 59.3–64.9%)] included certificates issued for fetal demise at <24 weeks’ gestation [23/696; 3.3% (95% CI 2.2–4.9%)] or neonatal death [2/696; 0.3% (95% CI 0.1–1.1%)] or incorrect primary COD [667/696; 95.8% (95% CI 94.1–97.1%)]. Of 540/1246 [43.3% (95% CI 40.6–46.1%)] ‘unexplained’ stillbirths, only 119/540 [22.0% (95% CI 18.8–25.7%)] remained unexplained; the majority were redesignated as either fetal growth restriction [FGR: 195/540; 36.1% (95% CI 32.2–40.3%)] or placental insufficiency [184/540; 34.1% (95% CI 30.2–38.2)]. Overall, FGR [306/1246; 24.6% (95% CI 22.3–27.0%)] was the leading primary COD after review, yet only 53/306 [17.3% (95% CI 13.5–22.1%)] FGR cases were originally attributed correctly.ConclusionThis study demonstrates widespread major errors in MCS completion across the UK. MCS should only be completed following structured case-note review, with particular attention on the fetal growth trajectory