Objective To evaluate the performance of diagnostic prediction models for ovarian malignancy in all patients with an ovarian mass managed surgically or conservatively. Design Multicentre cohort study. Setting 36 oncology referral centres (tertiary centres with a specific gynaecological oncology unit) or other types of centre. Participants Consecutive adult patients presenting with an adnexal mass between January 2012 and March 2015 and managed by surgery or follow-up. Main outcome measures Overall and centre specific discrimination, calibration, and clinical utility of six prediction models for ovarian malignancy (risk of malignancy index (RMI), logistic regression model 2 (LR2), simple rules, simple rules risk model (SRRisk), assessment of different neoplasias in the adnexa (ADNEX) with or without CA125). ADNEX allows the risk of malignancy to be subdivided into risks of a borderline, stage I primary, stage II-IV primary, or secondary metastatic malignancy. The outcome was based on histology if patients underwent surgery, or on results of clinical and ultrasound follow-up at 12 (±2) months. Multiple imputation was used when outcome based on follow-up was uncertain. Results The primary analysis included 17 centres that met strict quality criteria for surgical and follow-up data (5717 of all 8519 patients). 812 patients (14%) had a mass that was already in follow-up at study recruitment, therefore 4905 patients were included in the statistical analysis. The outcome was benign in 3441 (70%) patients and malignant in 978 (20%). Uncertain outcomes (486, 10%) were most often explained by limited follow-up information. The overall area under the receiver operating characteristic curve was highest for ADNEX with CA125 (0.94, 95% confidence interval 0.92 to 0.96), ADNEX without CA125 (0.94, 0.91 to 0.95) and SRRisk (0.94, 0.91 to 0.95), and lowest for RMI (0.89, 0.85 to 0.92). Calibration varied among centres for all models, however the ADNEX models and SRRisk were the best calibrated. Calibration of the estimated risks for the tumour subtypes was good for ADNEX irrespective of whether or not CA125 was included as a predictor. Overall clinical utility (net benefit) was highest for the ADNEX models and SRRisk, and lowest for RMI. For patients who received at least one follow-up scan (n=1958), overall area under the receiver operating characteristic curve ranged from 0.76 (95% confidence interval 0.66 to 0.84) for RMI to 0.89 (0.81 to 0.94) for ADNEX with CA125. Conclusions Our study found the ADNEX models and SRRisk are the best models to distinguish between benign and malignant masses in all patients presenting with an adnexal mass, including those managed conservatively. Trial registration ClinicalTrials.gov NCT01698632.

Uterine fibroids (UFs) are the most common benign tumors of the female genital tract. Their prevalence usually is estimated at 30–40%, but may reach up to 70–80% in predisposed groups of women. UFs may cause various clinical issues which might constitute the major reason of the overall deterioration of the quality of life. The mechanisms leading to UFs formation and growth still remain poorly understood. The transformation of smooth muscle cells of the uterus into abnormal, immortal cells, capable of clonal division, is thought to be a starting point of all pathways leading to UF formation. Micro-ribonucleic acids (miRNAs) are non-coding single-stranded RNAs about 22 nucleotides in length, that regulate gene expression. One of recent advances in this field is the comprehension of the role of miRNAs in tumorigenesis. Alterations in the levels of miRNAs are related to the formation and growth of several tumors which show a distinct miRNA signature. The aim of this review is to summarize the current data about the role of miRNAs in the pathophysiology of UFs. We also discuss future directions in the miRNA research area with an emphasis on novel diagnostic opportunities or patient-tailored therapies. In our opinion data concerning the regulation of miRNA and its gene targets in the UFs are still insufficient in comparison with gynecological malignancies. The potential translational use of miRNA and derived technologies in the clinical care is at the early phase and needs far more evidence. However, it is one of the main areas of interest for the future as the use of miRNAs in the diagnostics and treatment of UFs is a new and exciting opportunity.

Background: To evaluate the accuracy of subjective assessment (SA), the International Ovarian Tumor Analysis (IOTA) group Simple Rules Risk (SRR) and the Assessment of Different NEoplasias in the adneXa (ADNEX) model for the preoperative differentiation of adnexal masses in pregnant women. Methods: The study population comprised 36 pregnant women (median age: 28.5 years old, range: 20–42 years old) with a mean gestation age of 13.5 (range: 8–31) weeks at diagnosis. Tumors were prospectively classified by local sonographers as probably benign or probably malignant using SA. Final tumor histological diagnosis was used as the reference standard in all cases. Logistic regression SRR and ADNEX models were used to obtain a risk score for every case. Serum CA125 and human epidydimis protein 4 (HE4) concentrations were also retrieved and the Risk of Ovarian Malignancy Algorithm (ROMA) value was calculated. The calculated predictive values included positive and negative likelihood ratios of ultrasound and biochemical tests. Results: Final histology confirmed 27 benign and 9 malignant (including 2 borderline) masses. The highest sensitivity (89%) and specificity (70%) were found for the subjective tumor assessment. Although no malignancy was classified as benign using the SRR criteria (sensitivity = 100%), the specificity of this scoring system was only 37%. At the cut-off risk level of >20%, the ADNEX model had a sensitivity of 78% and a specificity of 70%. Serum levels of CA125, HE4 and the ROMA risk model correctly identified adnexal malignant tumors with a sensitivity of 67%, 25% and 25%, respectively. Corresponding specificities were 72%, 100% and 100%, respectively. The highest positive and negative likelihood ratios were found for SA (LR+ = 3.0 and LR− = 0.16, respectively). Overall diagnostic accuracy of all predictive methods used in this study were similar (range: 70–75%) except for SRR (53%). Conclusion: Subjective assessment remains the best predictive method in complex adnexal masses found at prenatal ultrasound in pregnant women. For less experienced sonographers, both the SRR and ADNEX scoring systems may be also used for the characterization of such tumors, while serum tumor markers CA125 and HE4, along with the ROMA algorithm appear to be less accurate.

BACKGROUND: Borderline ovarian tumors (BOTs) and early clinical stage malignant adnexal masses can make sonographic diagnosis challenging, while the clinical utility of tumor markers, e.g., CA125 and HE4, or the ROMA algorithm, remains controversial in such cases. OBJECTIVE: To compare the IOTA group Simple Rules Risk (SRR), the ADNEX model and the subjective assessment (SA) with serum CA125, HE4 and the ROMA algorithm in the preoperative discrimination between benign tumors, BOTs and stage I malignant ovarian lesions (MOLs). METHODS: A multicenter retrospective study was conducted with lesions classified prospectively using subjective assessment and tumor markers with the ROMA. The SRR assessment and ADNEX risk estimation were applied retrospectively. The sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR−) were calculated for all tests. RESULTS: In total, 108 patients (the median age: 48 yrs, 44 postmenopausal) with 62 (79.6%) benign masses, 26 (24.1%) BOTs and 20 (18.5%) stage I MOLs were included. When comparing benign masses with combined BOTs and stage I MOLs, SA correctly identified 76% of benign masses, 69% of BOTs and 80% of stage I MOLs. Significant differences were found for the presence and size of the largest solid component (p = 0.0006), the number of papillary projections (p = 0.01), papillation contour (p = 0.008) and IOTA color score (p = 0.0009). The SRR and ADNEX models were characterized by the highest sensitivity (80% and 70%, respectively), whereas the highest specificity was found for SA (94%). The corresponding likelihood ratios were as follows: LR+ = 3.59 and LR− = 0.43 for the ADNEX; LR+ = 6.40 and LR− = 0.63 for SA and LR+ = 1.85 with LR− = 0.35 for the SRR. The sensitivity and specificity of the ROMA test were 50% and 85%, respectively, with LR+ = 3.44 and LR− = 0.58. Of all the tests, the ADNEX model had the highest diagnostic accuracy of 76%. CONCLUSIONS: This study demonstrates the limited value of diagnostics based on CA125 and HE4 serum tumor markers and the ROMA algorithm as independent modalities for the detection of BOTs and early stage adnexal malignant tumors in women. SA and IOTA methods based on ultrasound examination may present superior value over tumor marker assessment.

Objectives: Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS. To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times. Material and methods: Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry. Results: Patients median age was 54 yrs (range: 29–72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12–23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS. Conclusions: Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents. Objectives: Tumor endothelial marker 7 (TEM7) and nestin have been proposed to be new candidates for neoangiogenesis assessment. Nestin is also cancer stem cells marker in various malignant tumors. AIMS. To investigate the expression of TEM7, nestin and nestin-related microvessel density (MVD) in high-grade serous ovarian cancer samples and to study their correlation with overall survival (OS) and disease-free survival (DFS) times. Material and methods: Tumor samples obtained from 70 women with FIGO IIIc/IV ovarian serous cancer were studied with immunohistochemistry. Results: Patients median age was 54 yrs (range: 29–72 years), 86% died of the disease with median OS = 28.5 months and median DFS = 10 months (3 years DFS = 19%; 5 years. DFS = 13.8%). High nestin expression was found in 16 (23%) patients with 3 years and 5 years OS of 14% and 0%. In low-nestin expression group OS and DFS were 42% and 25%, respectively. Median nestin-MVD (16, range:12–23) was not correlated with cancer cells nestin expression and with both DFS and OS. High TEM7 expression was found in 29 women (41%) of whom 21 (72%) died of the disease. A 5-year OS in these women was 27% as compared to 8% in low TEM7 expression group, but TEM7 presence had no association with nestin, nestin-MVD and both OS and DFS. Conclusions: Nestin as a marker of cancer stem cells may assist in the prediction of OS and DFS in women with high grade serous ovarian cancer. Nestin may also be considered a novel therapeutic target for antiangiogenic agents.

Preconception lifestyle modifications and reduction of several known risk factors may have an influence on future pregnancy outcomes. The aim of the study was to analyze health behaviors and personal values as well as to assess the relationship between these factors in women without children, in pregnant women and in women who had already delivered babies. The questionnaire survey included the Health Behavior Inventory (HBI), the Personal Value List (PVL) and sociodemographic data and was conducted in 538 women. These women were divided into three groups: women who had recently delivered (n = 235), pregnant women (n = 121) and childless women (n = 182). Pregnant women demonstrated a significantly higher level of declared health behaviors, and also, they rated higher on the subscales values “positive mental attitude” and “health practices”, in comparison to women who had recently delivered and to childless women. In all tested groups, the highest rated personal value was “a successful family life”, while the most appreciated symbol of happiness was “love and friendship”. Our results suggest that the system of values and the perception of happiness symbols may influence women’s health behaviors. Positioning “health” in the hierarchy of personal values as the most important one may facilitate the introduction of healthy behaviors. This, in turn, could reduce several adverse pregnancy outcomes that are potentially modifiable with changing preconception health attitudes. Our results also identify several unanswered questions and highlight areas where new research is needed.