Higher EpCAM-Positive Extracellular Vesicle Concentration in Ascites Is Associated with Shorter Progression-Free Survival of Patients with Advanced High-Grade Serous Carcinoma.

Platinum-resistant high-grade serous carcinoma (HGSC) is an incurable disease, so biomarkers that could help with timely treatment adjustments and personalized approach are extensively being sought. Tumor-derived extracellular vesicles (EVs) that can be isolated from ascites and blood of HGSC patients are such promising biomarkers. Epithelial cell adhesion molecule (EpCAM) expression is upregulated in most epithelium-derived tumors; however, studies on prognostic value of EpCAM overexpression in ovarian carcinoma have shown contradictory results. The aim of our study was to evaluate the potential of total and EpCAM-positive EVs as prognostic and predictive biomarkers for advanced HGSC. Flow cytometry was used to determine the concentration of total and EpCAM-positive EVs in paired pretreatment ascites and plasma samples of 37 patients with advanced HGSC who underwent different first-line therapy. We found that higher EpCAM-positive EVs concentration in ascites is associated with shorter progression-free survival (PFS) regardless of treatment strategy. We also found a strong correlation of EpCAM-positive EVs concentration between ascites and plasma. Our findings indicate that EpCAM-positive EVs in ascites of patients with advanced HGSC have the potential to serve as prognostic biomarkers for predicting early recurrence and thereby likelihood of more aggressive tumor biology and development of chemoresistance.

Oxidative stress markers cannot be used as endometriosis biomarkers in infertile patients.

OBJECTIVES: Endometriosis is a common benign gynaecological disease that significantly compromises the quality of life of patients. To date, invasive surgery is the method of choice to visually and histologically confirm endometriosis. Thus, there is a major interest to develop noninvasive diagnostic tools. Oxidative stress is one of the proposed mechanisms of pathogenesis and may be involved in pelvic pain, dysmenorrhea, dyspareunia, and infertility in endometriosis patients. Thus, markers of oxidative stress may serve as diagnostic biomarkers for endometriosis. DESIGN: This prospective case-control study assessed erythrocyte superoxide dismutase (SOD), erythrocyte glutathione peroxidase (GPX), serum hexanoyl lysine (HEL) and peritoneal fluid HEL. PARTICIPANTS/MATERIALS, SETTING, AND METHODS: We enrolled 86 women with primary infertility; the case group included 57 women with endometriosis, and the control group included 29 women with unexplained primary infertility. All the patients underwent laparoscopy, and the diagnosis was confirmed histologically. RANDOX and RANSEL reagents were used to determine the levels of SOD and GPX, respectively, and ELISA was used to determine the levels of HEL. RESULTS: We found no statistically significant differences in the erythrocyte levels of GPX (p value 0.623) or SOD (p value 0.122) or the serum or peritoneal fluid levels of HEL (p value 0.562 and 0.329 accordingly). CONCLUSIONS: SOD, GPX, and HEL levels most likely do not differ between patients with unexplained infertility and patients with endometriosis.

AKR1B1 as a Prognostic Biomarker of High-Grade Serous Ovarian Cancer.

Although aldo-keto reductases (AKRs) have been widely studied in cancer, no study to date has examined the roles of AKR family 1 members B1 (AKR1B1) and B10 (AKR1B10) in a large group of ovarian cancer patients. AKR1B1 and AKR1B10 play a significant role in inflammation and the metabolism of different chemotherapeutics as well as cell differentiation, proliferation, and apoptosis. Due to these functions, we examined the potential of AKR1B1 and AKR1B10 as tissue biomarkers. We assessed the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 99 patients with high-grade serous ovarian cancer (HGSC) and compared these levels with clinicopathological characteristics, survival, and response to chemotherapy. A higher immunohistochemical AKR1B1 expression correlated with a better overall and disease-free survival of HGSC patients whereas AKR1B10 expression did not show any significant differences. A multivariant Cox analysis demonstrated that a high AKR1B1 expression was an important prognostic factor for both overall and disease-free survival. However, AKR1B1 and AKR1B10 were not associated with different responses to chemotherapy. Our data suggest that AKR1B1 is involved in the pathogenesis of HGSC and is a potential prognostic biomarker for this cancer.

AKR1B1 and AKR1B10 as Prognostic Biomarkers of Endometrioid Endometrial Carcinomas.

The roles of aldo-keto reductase family 1 member B1 (AKR1B1) and B10 (AKR1B10) in the pathogenesis of many cancers have been widely reported but only briefly studied in endometrial cancer. To clarify the potential of AKR1B1 and AKR1B10 as tissue biomarkers of endometrial cancer, we evaluated the immunohistochemical levels of AKR1B1 and AKR1B10 in tissue paraffin sections from 101 well-characterized patients with endometrioid endometrial cancer and 12 patients with serous endometrial cancer and compared them with the clinicopathological data. Significantly higher immunohistochemical levels of AKR1B1 and AKR1B10 were found in adjacent non-neoplastic endometrial tissue compared to endometrioid endometrial cancer. A trend for better survival was observed in patients with higher immunohistochemical AKR1B1 and AKR1B10 levels. However, no statistically significant differences in overall survival or disease-free survival were observed when AKR1B1 or AKR1B10 were examined individually in endometrioid endometrial cancer. However, analysis of AKR1B1 and AKR1B10 together revealed significantly better overall and disease-free survival in patients with both AKR1B1 and AKR1B10 staining above the median values compared to all other patients. Multivariant Cox analysis identified strong AKR1B1 and AKR1B10 staining as a statistically important survival prediction factor. Conversely, no significant differences were found in serous endometrial cancer. Our results suggest that AKR1B1 and AKR1B10 play protective roles in endometrioid endometrial cancer and show potential as prognostic biomarkers.

Preterm delivery risk in infertile women who conceived after reproductive surgery: natural conception versus IVF/ICSI.

STUDY QUESTION: Is preterm delivery an infertility treatment-related adverse outcome in infertile women who conceived after reproductive surgery? SUMMARY ANSWER: Compared with matched fertile women, preterm delivery appears to be a modest infertility treatment-related adverse outcome in infertile women who have reproductive surgery then conceived naturally or after IVF/ICSI. WHAT IS KNOWN ALREADY: Most observational studies have shown that women who receive any infertility treatment are more likely to deliver preterm than do fertile women. However, studies on the outcome of pregnancies in infertile women who conceive naturally after reproductive surgery are scarce. STUDY DESIGN, SIZE, DURATION: This was a single-centre historical two-part study: cohort and matched cohort study. Anonymized data of 761 infertile women who conceived after reproductive surgery and 758 fertile women were obtained by linking three computerized databases from 1 July 2012 to 31 December 2015. PARTICIPANTS/MATERIALS, SETTING, METHODS: In the cohort study, we evaluated the association between the mode of conception and preterm delivery <37 and <32 gestational weeks in 703 infertile women, with a singleton pregnancy who conceived after reproductive surgery, using logistic regression adjusted for relevant co-variates to calculate the adjusted odds ratio with a 95% CI. In the matched cohort study, we evaluated preterm delivery as infertility treatment-related adverse outcome using the propensity score (PS) method. The matched cohort comprised 758 infertile women and 758 fertile women with a twin or singleton pregnancy. Infertile women conceived after reproductive surgery either naturally or through IVF/ICSI. Infertile and fertile women were matched using PS matching. Infertile and fertile women were matched for pre-defined risk factors for preterm delivery. Three infertile women out of an original 761 were not included in the analysis because they lacked all required matching variables. We performed a 1:1 matching with an optimal matching algorithm with a caliper width of the linear predictor of 0.1 standard deviations. The effect of reproductive surgery on preterm delivery was evaluated in the PS-matched sample using Pearson's χ2 test and presented as the odds ratio (OR) with 95% CI. All women delivered at the Department of Perinatology, University Medical Centre Ljubljana, Slovenia. MAIN RESULTS AND THE ROLE OF CHANCE: Among 761 infertile women who conceived after reproductive surgery, 428 (56.2%) women conceived naturally and 333 (43.8%) conceived after IVF/ICSI. The incidence of twin pregnancies was significantly lower after natural conception (2.6% vs 14.1%). Among the 703 infertile women with a singleton pregnancy, 417 (59.3%) conceived naturally and 286 (40.7%) conceived after IVF/ICSI. Adjusted for maternal age and parity in infertile women with singleton pregnancies, IVF/ICSI showed a moderate association with preterm delivery <32 weeks. Compared with natural conception after reproductive surgery, the odds for preterm delivery after IVF/ICSI was 1.07 (95% CI 0.63-1.81) <37 weeks and 2.25 (95% CI 0.80-6.34) <32 weeks. Preterm delivery appears to be a modest infertility treatment-related adverse outcome. Compared with fertile women in the PS-matched sample, infertile women who conceived after reproductive surgery either naturally or after IVF/ICSI the odds of preterm delivery <37 weeks were 1.31 (95% CI 0.97-1.78) and odds of preterm delivery <32 weeks were 1.57 (95% CI 0.78-3.18). However, none of the estimations were statistically significant. LIMITATIONS, REASONS FOR CAUTION: The main limitations of the study were the retrospective design, the heterogeneity of the types of reproductive surgery performed and underlying reproductive pathologies. The low number of preterm deliveries in the present study might influence the precision of estimations. WIDER IMPLICATIONS OF THE FINDINGS: The present study aims to alter the prevailing opinion that reproductive surgery should only be considered preceding IVF to increase implantation and pregnancy rates after IVF. It implies that in selected infertile women who have had reproductive surgery, a high rate of natural conception, a low rate of multiple pregnancies, and a modest infertility treatment-related effect on preterm delivery should be the reasons to encourage natural conception after reproductive surgery. Furthermore, by allowing for natural conception, we can avoid a high-cost invasive medical procedure. STUDY FUNDING/COMPETING INTEREST(S): The study received no funding. We have no competing interest to declare. TRIAL REGISTRATION NUMBER: N/A.

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06-0.65, p = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12-0.88, p = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.

Changes in perinatal outcomes after implementation of IADPSG criteria for screening and diagnosis of gestational diabetes mellitus: A national survey.

OBJECTIVE: To compare perinatal outcomes before and after implementation of the International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria for testing of gestational diabetes mellitus (GDM). METHODS: A national, perinatal, registry-based cohort study of prospectively collected data was conducted. Patients with diabetes type 1 or 2 were excluded. Outcomes of 135 786 pregnancies before (January 1, 2004 to May 31, 2010) and 140 524 after (June 1, 2011 to December 31, 2017) the introduction of IADPSG criteria were compared using Student t test and χ2 test (P<0.05 was significant). Multivariable logistic regression was used to compare outcomes controlling for potential confounders. RESULTS: Prevalence of GDM increased from 2.6% to 9.7% (adjusted odds ratio 3.92; 95% confidence interval 3.78-4.08). Incidence of large-for-gestational age (LGA), macrosomia (birth weight >4500 g), Erb's palsy, and hypertensive disorders in pregnancy decreased despite increasing maternal age and pre-pregnancy obesity. Rates of cesarean delivery increased in both GDM and non-GDM groups, with a less pronounced increase in GDM mothers. Incidence of small-for-gestational age (SGA) increased in GDM but not in non-GDM group. CONCLUSION: Implementation of IADPSG criteria in a country with a relatively low prevalence of GDM did not result in higher rates of cesarean delivery and was associated with reductions in LGA and hypertensive disorders in pregnancy.

Potential of osteopontin in the management of epithelial ovarian cancer.

Background Osteopontin (sOPN) is a promising blood tumour marker for detecting epithelial ovarian cancer (EOC). However, other clinical uses of sOPN as a tumour marker in EOC are still lacking. Since sOPN concentrations in serum are not associated with those in ascites, we compared clinical value of sOPN concentrations in the two body fluids. Patients and methods The study included 31 women with advanced EOC and 34 women with benign gynaecological pathology. In the EOC group, serum for sOPN analysis was obtained preoperatively, after primary debulking surgery and after chemotherapy. In the control group, serum was obtained before and after surgery. Ascites and peritoneal fluid were obtained during surgery. sOPN concentrations were determined by flow cytometry bead-based assay. Results The sensitivity and specificity of sOPN in detecting EOC was 91.2% and 90.3% (cut-off = 47.4 ng/ml) in serum, and 96.8% and 100% (cut-off = 529.5 ng/ml) in ascites. Kaplan-Meier analysis showed a significant association between higher serum sOPN concentration and overall survival (p = 0.018) or progression free survival (p = 0.008). Higher ascites sOPN concentrations were associated with suboptimally debulked tumour and unresectable disease. Higher serum sOPN concentrations were associated with refractory disease or incomplete response to platinum-based chemotherapy. Conclusions The study showed that ascites sOPN level mirrors present disease and is superior to serum level for diagnostic purposes and surgical planning, although the end result of treatment is the response of the whole body in fighting the disease. The preoperative sOPN concentration in serum thus better reflects disease outcome.

Customised birthweight standard for a Slovenian population.

Objective To produce a customised birthweight standard for Slovenia. Methods This retrospective study used a cohort from the National Perinatal Information System of Slovenia (NPIS). Prospectively collected information from pregnancies delivered in all of Slovenia's 14 maternal hospitals between 1st January 2003 and 31st December 2012 was included. Coefficients were derived using a backward stepwise multiple regression technique. Results A total of 126,627 consecutive deliveries with complete data were included in the multivariable analysis. Maternal height, weight in early pregnancy and parity as well as the baby's sex were identified as physiological variables, with coefficients comparable to findings in other countries. The expected 280-day birthweight, free from pathological influences, of a standard size mother (height 163 cm, weight 64 kg) in her first pregnancy was 3451.3 g. Pathological influences on birthweight within this population included low and high maternal age, low and high body mass index (BMI), smoking, pre-existing and gestational diabetes and pre-existing and gestational hypertension. Conclusion The analysis confirmed the main physiological variables that affect birthweight in studies from other countries, and was able to quantify additional pathological factors of maternal age and gestational diabetes. Development of a country-specific customised birthweight standard will aid clinicians in Slovenia with the distinction between normal and abnormal small-for-gestational age (SGA) fetuses, thus avoiding unnecessary interventions and improving identification of at risk pregnancies, and long-term outcomes for infants.

Correlation between uterine artery Doppler and the sFlt-1/PlGF ratio in different phenotypes of placental dysfunction.

OBJECTIVE: To explore correlations between the sFlt-1/PlGF ratio and uterine arteries (UtA) Doppler indexes in placental dysfunction-related disorders (PDD). METHODS: We prospectively included women with a singleton pregnancy with preeclampsia (PE) only (n = 22), preeclampsia with fetal growth restriction (FGR) (n = 32), FGR only (n = 12), or normal pregnancy (n = 29). RESULTS: In PDDs, significantly positive correlations between the sFlt-1/PlGF ratio and the mean UtA pulsatility (mPI-UtA), as well as the resistance index (mRI-UtA) were found (p = 0.015, p = 0.019, respectively), but not in normal pregnancies. PDD with signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio and mPI-UtA, was found in 50.0%, and, by the increased sFlt-1/PlGF ratio and mRI-UtA, in 65.2%. PDD without signs of impaired placentation, evidenced by the increased sFlt-1/PlGF ratio but normal mPI-UtA, was found in 24.2%, and, by the increased sFlt-1/PlGF ratio but normal mRI-UtA, in 7.6%. A substantial proportion of women with signs of impaired placentation were diagnosed with FGR with or without PE. CONCLUSION: In PDD, the sFlt-1/PlGF ratio and UtA Doppler indexes increase proportionally. Correlations between the sFlt-1/PlGF ratio and UtA Doppler indexes might help to distinguish between PDDs with and without impaired placentation. However, further studies are needed to explore the correlations in different phenotypes of PDD.

Three-dimensional ultrasound evaluation of tongue posture and its impact on articulation disorders in preschool children with anterior open bite.

Background Tongue posture plays an important role in the etiology of anterior open bite (AOB) and articulation disorders, and is crucial for AOB treatment planning and posttreatment stability. Clinical assessment of tongue posture in children is unreliable due to anatomical limitations. The aim of the study was to present functional diagnostics using three-dimensional ultrasound (3DUS) assessment of resting tongue posture in comparison to clinical assessment, and the associations between the improper tongue posture, otorhinolaryngological characteristics, and articulation disorders in preschool children with AOB. Patients and methods A cross-sectional study included 446 children, aged 3-7 years, 236 boys and 210 girls, examined by an orthodontist to detect the prevalence of AOB. The AOB was present in 32 children. The control group consisted of 43 children randomly selected from the participants with normocclusion. An orthodontist, an ear, nose and throat (ENT) specialist and a speech therapist assessed orofacial and ENT conditions, oral habits, and articulation disorders in the AOB group and control group. Tongue posture was also assessed by an experienced radiologist, using 3DUS. The 3DUS assessment of tongue posture was compared to the clinical assessment of orthodontist and ENT specialist. Results The prevalence of AOB was 7.2%. The AOB group and the control group significantly differed regarding improper tongue posture (p < 0.001), and articulation disorders (p < 0.001). In children without articulation disorders from both groups, the improper tongue posture occured less frequently than in children with articulation disorders (p < 0.001). After age adjustment, a statistical regression model showed that the children with the improper tongue posture had higher odds ratios for the presence of AOB (OR 14.63; p < 0.001) than the others. When articulation disorders were included in the model, these odds ratios for the AOB became insignificant (p = 0.177). There was a strong association between the improper tongue posture and articulation disorders (p = 0.002). The 3DUS detected the highest number of children with improper resting tongue posture, though there was no significant difference between the 3DUS and clinical assessments done by orthodontist and ENT specialist. Conclusions The 3DUS has proved to be an objective, non-invasive, radiation free method for the assessment of tongue posture and could become an important tool in functional diagnostics and early rehabilitation in preschool children with speech irregularities and irregular tongue posture and malocclusion in order to enable optimal conditions for articulation development.

Non-ablative Er:YAG laser therapy effect on stress urinary incontinence related to quality of life and sexual function: A randomized controlled trial.

OBJECTIVE: Stress urinary incontinence (SUI) is a common complaint in women after childbirth. It affects their quality of life and sexual satisfaction and is one of the major reasons for gynaecological surgery. There is a need for effective non-invasive treatment alternatives. The aim of this study was to evaluate the efficacy and safety of non-ablative Er:YAG laser therapy in the treatment of SUI and improvement of sexual gratification in parous women. STUDY DESIGN: 114 premenopausal parous women with SUI were randomized in two groups of 57 women; a laser intervention group and sham group. Both groups were treated according to the IncontiLase® clinical treatment protocol for SUI with non-ablative thermal-only Er:YAG laser, except that there was no energy output when treating the sham group. Patients were blinded to the allocation. At baseline and 3 months after treatment patients were clinically examined, answered questionnaires for SUI severity and sexual function assessment and their pelvic floor muscle (PFM) function was assessed with perineometry. Validated International Consultation on Incontinence Questionnaire - Urinary Incontinence Short Form (ICIQ-UI SF) was used as the primary outcome measure. The Pelvic Organ Prolapse Urinary Incontinence Sexual Questionnaire short form (PISQ-12) and The Female Sexual Function Index (FSFI) were used to assess the sexual function. Patients were monitored for discomfort and side-effects during treatment and follow-up period. RESULTS: 3 months after treatment the ICIQ-UI SF (p < 0.001), PISQ-12 (p = 0.014) and FSFI (p = 0.025) scores were significantly more improved in the laser group than in the sham control group. All perineometry variables improved in the laser group after treatment; duration and maximum pressure had statistically significantly better improvement than the sham group, whereas average pressure did not. 21% of laser treated patients were dry (ICIQ-UI SF = 0) at follow up compared to only 4% of the sham control patients. No serious adverse effects were observed or reported. The treatment was well tolerated by patients. CONCLUSIONS: The non-ablative Er:YAG laser therapy improves the impact of SUI symptoms on quality of life and sexual function in premenopausal parous women significantly better than placebo. It provides a promising minimally-invasive safe treatment alternative for SUI.

Should we consider integrated approach for endometriosis-associated infertility as gold standard management? Rationale and results from a large cohort analysis.

PURPOSE: To evaluate reproductive and maternal-fetal outcomes after integrated approach for endometriosis-associated infertility (EAI). METHODS: We retrospectively analyzed reproductive and maternal-fetal outcomes of 277 women affected by EAI, subdividing patients in two groups: in the first one (surgery group), we included all women who underwent laparoscopic surgery for EAI; in the second one (integrated group), we included women who failed to conceive spontaneously after surgery within 6-12 months and underwent in vitro fertilization and embryo transfer (IVF). We evaluated delivery rate (DR), maternal and neonatal outcomes of the first pregnancies, and, finally, the type (spontaneous or IVF) of subsequent pregnancies. RESULTS: We did not find significant difference regarding DR between surgery and integrated groups. We found significantly lower birth weight (p < 0.001) and gestational age at delivery (p < 0.001) in integrated group respect to surgery group; conversely, we found higher rate of preterm birth (p < 0.001), small for gestational age (p = 0.003), and admission to the neonatal intensive care unit (p < 0.001) respect to surgery group. Finally, 92 women became pregnant for the second time: 8% were spontaneous and 20% were IVF pregnancies. CONCLUSIONS: We suggest the integrated approach as gold standard treatment for carefully selected patients (young, good ovarian reserve, partner with normal semen parameters) affected by EAI. As consequence, IVF should be reserved as the secondary treatment for women who fail to conceive spontaneously after surgery within 6-12 months, since it is able to increase DR significantly.

The Outcomes of Pregnancy and Childbirth in Adolescents in Slovenia.

INTRODUCTION: The objective of the study was to determine the course and outcomes of pregnancy and childbirth in adolescents compared to women aged 20-24 years in Slovenia. METHODS: In the retrospective study, the course of pregnancy and labour and the perinatal outcome of newborns in primiparous adolescents aged ≤19 years (study group) have been compared to the control group of primiparous women aged 20-24 years. The study group was further divided into a study subgroup of adolescents aged ≤17 years. Data were retrieved from the National Perinatal Information System in Slovenia for the period 2008-2012. Altogether, 13,663 women and their newborns were included. RESULTS: Adolescent pregnancy was associated with increased rates of unknown estimated date of delivery, preterm labour, low birth weight newborns, small for gestational age newborns and low gestational weight gain. Spontaneous labour was more common in adolescents, while emergency and elective Caesarean sections were less common than in women aged 20-24 years. In addition, pregnancy in adolescents aged ≤17 years was associated with increased rate of maternal anaemia and labour without complications. Higher rates of smoking, lower rates of parenting school attendance, lower rates of pregnancy check-ups and screening tests in pregnancy such as nuchal translucency in adolescents were found. CONCLUSIONS: The results of the study show that adolescent pregnancy is related to higher health risks for pregnant adolescents and their newborns. In addition, adolescents are subject to poorer prenatal care comparing to older women.

Cancer Stem Cell-Related Marker NANOG Expression in Ovarian Serous Tumors: A Clinicopathological Study of 159 Cases.

OBJECTIVE: The objectives of this study were to assess cancer stem cell-related marker NANOG expression in ovarian serous tumors and to evaluate its prognostic significance in relation to ovarian serous carcinoma. METHODS: NANOG protein expression was immunohistochemically evaluated in the ovarian tissue microarrays of 20 patients with benign ovarian serous tumors, 30 patients with borderline ovarian serous tumors, and 109 patients with ovarian serous carcinomas, from which 106 were of high-grade and 3 of low-grade morphology Immunohistochemical reaction was scored according to signal intensity and the percentage of positive cells in tumor samples. Pursuant to our summation of signal intensity and positive cell occurrence, we divided our samples into 4 groups: NANOG-negative, NANOG-slightly positive, NANOG-moderately positive, and NANOG-strongly positive group. Complete clinical data were obtained for the ovarian serous carcinoma group, and correlation between clinical data and NANOG expression was analyzed. RESULTS: A specific brown nuclear, or cytoplasmic reaction, was considered a positive NANOG staining. In terms of the ovarian serous carcinoma group, 69.7% were NANOG positive, 22.9% slightly positive, 22.9% moderately positive, and 23.9% strongly positive. All NANOG-positive cases were of high-grade morphology. Benign and borderline tumors and low-grade serous carcinomas were NANOG negative. There was no significant correlation between NANOG expression and clinical parameters in terms of the ovarian serous carcinoma group. CONCLUSIONS: Positive NANOG expression is significantly associated with high-grade ovarian serous carcinoma and is absent in benign, borderline, and low-grade serous lesions. In our study, there was no correlation between NANOG expression and clinical parameters, including its use in the prognosis of ovarian serous carcinoma.

Data on expression of genes involved in estrogen and progesterone action, inflammation and differentiation according to demographic, histopathological and clinical characteristics of endometrial cancer patients.

Endometrial cancer is the sixth most common cancer in women worldwide. It is associated with aberrant actions of steroid hormones, estrogens and progesterone, but also with enhanced inflammation and reduced cellular differentiation. Here, we show data on demographic and histopathological characteristics of 51 patients with endometrial cancer, together with data on correlations between the expression of 38 genes involved in estrogen and progesterone actions, inflammation and differentiation, and demographic characteristics. We also show data on changes in gene expression of these 38 genes according to histopathological and clinical characteristics of these patients. This article includes data referenced in the manuscript entitled ¼STAR and AKR1B10 are down-regulated in high-grade endometrial cancer by Sinreih et al. (in press) [1].

STAR and AKR1B10 are down-regulated in high-grade endometrial cancer.

Endometrial cancer is the most frequent gynecological malignancy in the developed world. The majority of cases are estrogen dependent, and are associated with diminished protective effects of progesterone. Endometrial cancer is also related to enhanced inflammation and decreased differentiation. In our previous studies, we examined the expression of genes involved in estrogen and progesterone actions in inflammation and tumor differentiation, in tissue samples from endometrial cancer and adjacent control endometrium. The aims of the current study were to examine correlations between gene expression and several demographic characteristics, and to evaluate changes in gene expression with regard to histopathological and clinical characteristics of 51 patients. We studied correlations and differences in expression of 38 genes involved in five pathophysiological processes: (i) estrogen-stimulated proliferation; (ii) estrogen-dependent carcinogenesis; (iii) diminished biosynthesis of progesterone: (iv) enhanced formation of progesterone metabolites; and (v) increased inflammation and decreased differentiation. Spearman correlation coefficient analysis shows that expression of PAQR7 correlates with age, expression of SRD5A1, AKR1B1 and AKR1B10 correlate with body mass, while expression of SRD5A1 and AKR1B10 correlate with body mass index. When patients with endometrial cancer were stratified based on menopausal status, histological grade, myometrial invasion, lymphovascular invasion, and FIGO stage, Mann-Whitney U tests revealed significantly decreased expression of STAR (4.4-fold; adjusted p=0.009) and AKR1B10 (9-fold; adjusted p=0.003) in high grade versus low grade tumors. Lower levels of STAR might lead to decreased de-novo steroid hormone synthesis and tumor differentiation, and lower levels of AKR1B10 to diminished elimination of toxic electrophilic carbonyl compounds in high-grade endometrial cancer. These data thus reveal the potential of STAR and AKR1B10 as prognostic biomarkers, which calls for further validation at the protein level.

Independent factors influencing large-for-gestation birth weight in singletons born after in vitro fertilization.

PURPOSE: Higher risk for birth of singletons being large for gestational age (LGA) has been revealed after in vitro fertilization (IVF) frozen-thawed embryo-transfer (FET). This phenomenon is now being investigated, since there is a speculation that these neonates could suffer from underlying epigenetic disturbances. The aim of the study was to expose independent LGA risk factors and to identify those connected to the IVF techniques. METHODS: Altogether, 4508 singleton pregnancies and births were included in the cohort case-matched study. Two hundred eleven singleton pregnancies and births after FET and 916 after fresh embryo transfer (ET) were included into two study groups. The IVF procedures were performed at the University Medical Centre Ljubljana between 2004 and 2011. For each IVF pregnancy, three matched consecutive controls after natural conception were included. Using logistic regression models, we observed LGA connection to maternal parameters (smoking, hypertension, parity, BMI, gestational diabetes, IVF conception, FET, double ET, and ICSI procedure). RESULTS: Singletons born after FET had a significantly higher risk for being LGA (p = 0.032; OR 1.697; 95 % CI 1.047-2.752). BMI 25-30 was a significant independent risk factor for LGA in the IVF groups (FET p = 0.041, OR 2.460, 95 % CI 1.030-5.857 and fresh ET p = 0.003; OR 2.188, 95 % CI 1.297-3.691). ICSI and double ET had no significant effect on LGA occurrence. CONCLUSIONS: Besides maternal BMI, FET is a significant independent LGA risk factor in IVF patients. Other observed factors (smoking, hypertension, multiparity, GDM, ICSI procedure, or number of embryos transferred) do not influence LGA risk significantly.

Impact of risk factors other than prematurity on periventricular leukomalacia. A population-based matched case control study.

OBJECTIVE: Periventricular leukomalacia (PVL) is a neonatal brain white matter injury associated with development of cerebral palsy, intellectual impairment, and visual disturbances. PVL is more common in premature neonates. Our objective was to examine the impact of several potential risk factors other than prematurity on the incidence of PVL. STUDY DESIGN: A case-control study based on the Slovenian National Perinatal Information System data for the period 2002-2011. All singleton and twin pregnancies delivered at ≥22 weeks' in Slovenia during the study period were included. Cases were pregnancies with PVL in at least one neonate. For each pregnancy in the case cohort, three pregnancies matched by gestational age and plurality were selected. Chi-square test was used to examine the associations between PVL and several potential risk factors: maternal age, pre-pregnancy body-mass-index, preexisting diabetes, gestational diabetes, pregnancy after in-vitro-fertilization, severe preeclampsia, vaginal delivery, no steroid therapy prior to delivery, small for gestational age, and fetal-inflammatory-response-syndrome. P<0.05 was considered statistically significant. RESULTS: One lakh ninety one thousand and eighty three singleton and 3377 twin pregnancies delivered at ≥22 weeks' in Slovenia during the study period. PVL was diagnosed in 86 singletons (0.045%) and 25 twins (0.74%). In all twin pregnancy cases only one twin was diagnosed with PVL. 258 singleton and 75 twin controls were matched to the 86 singleton and 25 twin cases. Of all risk factors studied, only maternal obesity and chorioamnionitis were significantly associated with PVL. CONCLUSION: Maternal obesity and chorioamnionitis increase the risk of PVL beyond that expected solely from prematurity.