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To investigate the impact of carriage of single nucleotide polymorphisms (SNPs) of the Toll-like receptor-4 (TLR4) and of autophagy-related gene 16-like-1 (ATG16L1) in preterm delivery (PTD).A prospective cohort of 145 pregnant women was studied. Women were prospectively followed-up until delivery. Genotyping for rs4986790 (Asp299Gly transition) and rs4986791 (Thr399Ile transition) of TLR4 and for rs2241880 of ATG16L1 was done by PCR-restriction fragment length polymorphism. The primary study endpoint was the impact of carriage of minor alleles of TLR4 on early PTD before gestational week 32. Associations with human chorionic gonadotrophin (hCG) were also analyzed. Peripheral blood mononuclear cells were isolated from 15 healthy women and stimulated for cytokine production.No difference in clinical characteristics was observed between women delivering full term and preterm. The frequency of early PTD was 25% among women carrying minor alleles of TLR4 and 6.8% among women carrying major alleles (P:.032). Odds ratios for PTD were 3.85 among women carrying the GG genotype of rs2241880 and major alleles of TLR4 and 0.26 among carriers of GG genotype and minor alleles of TLR4 (P:.030). The co-presence of GG genotype of rs2241880 and hCG above 70 U/L was an independent variable for PTD. Stimulated production of interleukin-6 was greater among women with GG genotypes of rs2241880.Minor alleles of SNPs of TLR4 predispose to early PTD. The GG genotype of rs2241880 of ATG16L1 is associated with PTD when hCG is supra-elevated. Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.

Background: Human Papilloma Virus has been considered as the main cause for cervical cancer. In this study we investigated epigenetic changes and especially methylation of specific sites of HPV genome. The main goal was to correlate methylation status with histological grade as well as to determine its accuracy in predicting the disease severity by establishing optimum methylation cutoffs. Methods: In total, sections from 145 cases genotyped as HPV16 were obtained from formalin-fixed, paraffin-embedded tissue of cervical biopsies, conization or hysterectomy specimens. Highly accurate pyrosequencing of bisulfite converted DNA, was used to quantify the methylation percentages of UTR promoter, enhancer and 5’ UTR, E6 CpGs 494, 502, 506 and E7 CpGs 765, 780, 790. The samples were separated in different groupings based on the histological outcome. Statistical analysis was performed by SAS 9.4 for Windows and methylation cutoffs were identified by MATLAB programming language. Results: The most important methylation sites were at the enhancer and especially UTR 7535 and 7553 sites. Specifically for CIN3+ (i.e. HSIL or SCC) discrimination, a balanced sensitivity vs. specificity (68.1%, 66.2% respectively) with positive predictive value (PPV) and negative predictive value (NPV) (66.2%, 68.2% respectively) was achieved for UTR 7535 methylation of 6.1% cutoff with overall accuracy 67.1%, while for UTR 7553 a sensitivity 60.9%, specificity 69.0%, PPV=65.6%, NPV=64.5% and overall accuracy=65.0% at threshold 10.1% was observed. Conclusion: Viral HPV16 genome was found methylated in NF-1 binding sites of UTR in cases with high grade disease. Methylation percentages of E6 and E7 CpG sites were elevated at the cancer group. © The author(s).

Problem: To study the balance of circulating heat shock protein (HSP)60 and HSP70 in pre-term delivery. Method of study: A two-stage approach was used. At first stage, we run retrospective analysis of prospective collected clinical data, and at a second stage, we studied an animal model of pre-term delivery (PTD). Blood samples were collected for prenatal screening in 3629 women. Samples from 23 women with miscarriage before gestational week 21 and 53 well-matched comparators for age, body mass index, parity, and previous miscarriage with full-term pregnancy were depicted. Women with risk factors were excluded. HSP60 and HSP70 were measured by an enzyme immunosorbent assay. PTD was induced after injection of low dose of bacterial lipopolysaccharide; mice were killed for the measurement of HSP60 and HSP70 in blood and tissues. The study endpoint was the association of the HSP60 to HSP70 ratio to miscarriage. Results: A ratio >6 could distinguish between women who will miscarry from women with term pregnancies with sensitivity 60%, specificity 81.8%, positive predictive value 81.8%, and negative predictive value 60% (OR: 6.750, P = 0.025). Mice of the LPS-group PTD had this ratio significantly increased in maternal serum, placentas, and embryos compared to the sham-operation group. Gene expression of hsp60/70 remained in tissues unaltered. Conclusion: A HSP60/HSP70 ratio equal to or more than 6 until gestational week 12 is accompanied with great likelihood for miscarriage. A similar ratio applies in an animal model of PTD induced by low-dose LPS. © 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Background/Objectives: The aim of this work was to evaluate the current vitamin D status in healthy pregnant women and their newborns living in Greece and assess possible associations between 25(OH)D and anthropometric features of their fetuses and newborns. Materials & Methods: 81 healthy women were monitored during pregnancy. Biochemical markers related to bone metabolism, 25(OH)D and PTH levels were measured in serum samples of mothernewborn pairs at 1st trimester of pregnancy and at delivery in mothers, in cord blood and at the 3rd day of life of newborns. Results: Maternal 25(OH)D levels at the 1st trimester of pregnancy (22.6±9.2ng/ml) were significantly higher than those at delivery (19.2±9.2ng/ml) (p

Purpose: To investigate DNA methylation changes in peripheral blood from patients with gestational diabetes mellitus (GDM) and preeclampsia (PE) due to poorly treated GDM. Methods: Eighteen pregnant women participated in the study: 6 with GDM, 6 with PE, and 6 healthy controls. The promoter methylation status of genes was profiled using the Human Inflammatory Response and Autoimmunity EpiTect Methyl II Signature PCR Array profiles. The results were validated with quantitative real-time polymerase chain reaction (qRT-PCR). Results: Fewer inflammation-related genes were significantly hypomethylated in PE cases compared to healthy subjects than in GDM cases. Some of the examined genes show different methylation patterns between GDM and PE. Conclusions: The epigenetic changes observed in this study indicate that GDM and PE exhibit specific DNA methylation profiles, with possible clinical applications. © 2019, Hellenic Endocrine Society.

Obesity and metabolic syndrome (MetS) during the perimenopausal period and in menopause have been linked to altered bone mass density (BMD) in various experimental studies. However, current clinical studies provide conflicting results in this field. The purpose of the present study was to evaluate this association. We conducted a prospective case control study that was based on a consecutive series of menopausal women who attended the Reproductive Endocrinology Outpatient Clinic of our hospital between January 2013 and December 2016. One hundred and forty post-menopausal women were included in the present study. After stratifying the women in two groups according to the presence of MetS we observed that bone turnover markers remained unaffected by the presence of MetS (p > 0.05). On the other hand, both the T- A nd Z-scores of women with MetS were significantly higher compared to healthly postmenopausal women [T-score: 0.4 (-0.7 to 1.3) vs.-1 (-1.62 to-0.1), p < 0.001] [Z-score: 0.55 (-0.3 to 1.7) vs.-0.4 (-1.1 to 0.4), p = 0.003]. According to the findings of our study the presence of MetS during the perimenopausal years seems to have a mild benefit on bone mass density. The pathophysiology that underlies this effect remains unclear as bone turnover markers seem to be unaffected by MetS. © 2018 2018 Walter de Gruyter GmbH, Berlin/Boston.

Background: The purpose of the present study is to present new data concerning the diagnostic efficacy of neutrophil to lymphocyte (NLR) and platelet to lymphocyte (PLR) ratios in detecting endometrial carcinoma and to summarize the existing knowledge by accumulating all the available data in the existing literature. Materials and methods: We retrospectively identified patients with evidence of endometrial pathology (vaginal bleeding or increased endometrial thickness) that undergone dilatation and curettage. For the meta-analysis we used the Medline, Scopus, Clinicaltrials.gov, EMBASE, Cochrane Central Register of Controlled Trials CENTRAL and Google Scholar databases to identify relevant articles in the field. Results: In our retrospective series we identified 106 women with endometrioid endometrial carcinoma and 72 controls. PLR and NLR values were comparable among the two groups (p >.05). Eleven studies were included in the present systematic review with a total of 4168 patients. The meta-analysis included 1013 patients. PLR values were not significantly different among the two groups. On the other hand, NLR was significantly raised among patients with endometrial carcinoma (MD 0.73, 95% CI 0.01, 1.45). Conclusion: The findings of our meta-analysis support that NLR values are significantly elevated in patients with endometrial cancer compared to controls. Moreover, there seem to be evidence to support that both PLR and NLR values increase in patients with advanced stage disease, including positive lymph nodes, lymphovascular space involvement and distant metastases. Future studies are needed in this field to reach firm conclusions and these should specifically target patients with advanced stage disease. © 2018 Elsevier Masson SAS

The purpose of our study is to evaluate the association of platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) with hormonal and metabolic parameters in patients with polycystic ovarian syndrome (PCOS) in order to assess whether these ratios may become useful tools during the evaluation of the severity of low grade inflammation. The present study is based in secondary outcomes from a prospectively collected patient database. A total of 266 women with PCOS participated in this study and blood a complete blood count examination (CBC) that was used for the calculation of PLR and NLR was available in 182 patients. Association statistics revealed that PLR had a significant correlation to 17-OH progesterone (r =-0.177, p = 0.024) and Matsuda index values (r = 0.234, p = 0.009), whereas NLR was correlated with follicle stimulating hormone (FSH) (r =-0.204, p = 0.007), free testosterone (r = 320, p < 0.001), Δ4-androstendione (r = 0.234, p = 0.003), sex hormone binding globulin (SHBG) (r =-0.350, p < 0.002) and high-density lipoprotein (HDL) (r =-0.171, p = 0.039). According to the findings of our study, both PLR and NLR seem to be correlated with some hormonal and metabolic indices. This association is clearer in the case of NLR and serum androgens as it seems to be positively affected by their levels. PLR and NLR were not affected by the presence of obesity. © 2018 Walter de Gruyter GmbH, Berlin/Boston.

The severity of polycystic ovarian syndrome (PCOS) has been clearly associated with insulin resistance, obesity and metabolic syndrome. The purpose of the present cross-sectional study is to investigate whether mild hypercholesterolemia alters the biochemical and clinical profile of PCOS patients. Our study is based on a prospectively collected population of women of reproductive age who were diagnosed with PCOS according to the definition of the Rotterdam European Society of Human Reproduction and Embryology/American Society for Reproductive Medicine (ASRM/ESHRE) criteria. For the correlation analysis we used the non-parametric Spearman's rank correlation coefficient. Partial correlation was also performed to control for potential confounders observed in the univariate analysis. Overall, 235 patients were included. Their mean age ranged between 14 and 45 years old and the body mass index (BMI) between 17 and 54. Women with mild hypercholesterolemia had a higher BMI and their fasting insulin was increased as well as indices of insulin resistance [Homeostatic model assessment (HOMA), quantitative insulin sensitivity check index (QUICKI), Matsuda index] compared to women with PCOS with normal cholesterol levels. Correlation statistics suggested that the effect of serum lipids on the hormonal profile of patients was weak. Both low-density lipoprotein (LDL) and high-density lipoprotein (HDL) exerted a significant mild negative correlation to glucose and insulin. However, after controlling the results for BMI and age (the two variables that were found significantly different in the univariate analysis) we observed that this effect was non-significant. Mild hypercholesterolemia does not affect the hormonal profile of patients with PCOS; hence, to date, there is no evidence to suggest its treatment for the correction of menstrual and hormonal abnormalities in PCOS women. © 2018 Walter de Gruyter GmbH, Berlin/Boston.

Thyroid dysfunction, predominantly hyperthyroidism, has been previously linked to impaired bone mass density (BMD) and increased risk of fractures. On the other hand, data in the field of hypothyroidism (HT) are missing. The purpose of the present study was to investigate the impact of thyroid disorders on bone density serum and urine calcium (Ca) and phosphate (P) as well as serum osteocalcin and alkaline phosphatase and urine hydroxyproline in a series of post-menopausal women. The study was conducted in the Reproductive Endocrinology Outpatient Clinic of our hospital. A consecutive series of post-menopausal women was included, after excluding patients under hormone treatment (including levothyroxine supplementation) and those who received raloxifene, tamoxifen or tibolone during the study period as well as those who received treatment during the previous 12 months were excluded from the present study. Overall, 188 women were included in the present study. Among them, 143 women had normal thyroid function, 32 women had hyperthyroidism and 13 women had HT. Correlation of thyroid function indices with osteoporosis indices revealed statistically significant correlations between thyroxine (T4) and free triiodothyronine (T3) with T-, Z-scores and BMD. Logistic regression analysis concerning the impact of HT and hyperthyroidism on T-score, Z-score and bone mass density revealed that both pathological entities negatively affect bone health (p < 0.05). The findings of our study suggest that not only hyperthyroidism, but also HT negatively affects BMD. Future studies should investigate this association and corroborate our findings. © 2018 Walter de Gruyter GmbH, Berlin/Boston.

Borderline ovarian tumours are an intermediate entity between benign and malignant epithelial ovarian neoplasms. The authors present the case of a 25-year-old patient, with a history of fertility-preserving right salpingo-oophorectomy due to an ovarian serous papillary cystadenocarcinoma six years ago. The patient recently presented with a cyst in the left ovary which raised concerns for recurrent disease. The patient underwent a left ovarian cystectomy and the histopathological examination concluded in serous borderline tumour. The patient is followed up regularly, so that a possible relapse will be diagnosed in time. In conclusion, a borderline lesion in the remaining ovary, after ovarian conservative surgery, is a challenge that could represent either a de novo emergence of borderline tumour or possibly the onset of a new ovarian cancer. The study of early molecular alterations could be a promising tool in the investigation of prognosis and management of these lesions. © 2018 S.O.G. CANADA Inc. All rights reserved.

Objective: The study aims to evaluate the predictive value of first trimester placental volume in pregnancies destined to develop fetal growth restriction (FGR) and preeclampsia (PE). Methods: Prospective observational study including placentas from 34 FGR, 12 PE, 15 GH (gestational hypertension) pregnancies, and 265 controls. Placental volume (PV) was obtained using VOCAL technique, and a z score was calculated (z-PV). The association of PV with other first trimester variables and maternal characteristics was assessed with Spearman's correlation. Results: PV increased exponentially with crown-rump length (CRL) and was unrelated to maternal factors (weight, age, parity, and smoking status) as well as first trimester uterine artery Doppler, free β-hCG, nuchal translucency, or fetal heart rate. However, PV was positively associated with maternal height, CRL, PAPP-A, and birth weight. z-PV was a strong predictor for FGR with abnormal fetal Dopplers (AUC = 0.9472, P

Ovarian cancer peritoneal carcinomatosis requires a multimodal-treatment approach. Current treatment considerations are analyzed in this update and include the management of recurrent malignant ascites and the understanding of its pathophysiology, the role of peritoneal washing cytology in detecting peritoneal metastases, capsular invasion and ovarian cancer histologic type, interpretation of pretreatment Ca-125 levels at different time points of ovarian cancer therapeutic management, characteristics of 10-year survivors of high-grade ovarian cancer, and the role of lymphadenectomy in ovarian cancer peritoneal carcinomatosis. This update also includes current considerations on the role of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in ovarian cancer peritoneal carcinomatosis as well as relevant ongoing phase III randomized controlled trial protocols. Copyright © 2018 Evgenia Halkia et al.

Objective: Artificial neural networks (ANNs) and classification and regression trees (CARTs) have been previously used for the prediction of cancer in several fields. In our study, we aim to investigate the diagnostic accuracy of three different methodologies (i.e. logistic regression, ANNs and CARTs) for the prediction of endometrial cancer in postmenopausal women with vaginal bleeding or endometrial thickness ≥5 mm, as determined by ultrasound examination. Study design: We conducted a retrospective case-control study based on data from analysis of pathology reports of curettage specimens in postmenopausal women. Methods: Classical regression analysis was performed in addition to ANN and CART analysis using the IBM SPSS and Matlab statistical packages. Results: Overall, 178 women were enrolled. Among them, 106 women were diagnosed with carcinoma, whereas the remaining 72 women had normal histology in the final specimen. ANN analysis seems to perform better with a sensitivity of 86.8%, specificity of 83.3%, and overall accuracy (OA) of 85.4%. CART analysis did not perform well with a sensitivity of 78.3%, specificity of 76.4%, and OA of 77.5%. Regression analysis had a poorer predictive accuracy with a sensitivity of 76.4%, a specificity of 66.7%, and an OA of 72.5%. Conclusion: Artificial intelligence is a powerful mathematical tool that may significantly promote public health. It may be used as a non-invasive screening tool to guide clinicians involved in primary care decision making when endometrial pathology is suspected. © 2018 The Royal Society for Public Health

Background: miRNAs have an important role as their deregulation is linked to endometrial cancer. Methods: A custom miScript® miRNA PCR Array was used to investigate for the first time the expression of eight miRNAs in forty-nine histologically confirmed Liquid Based cytology endometrial samples. The expression profile of the same miRNAs was also examined in sixty formalin-fixed tissue samples. Results: Expression of seven miRNAs was significantly higher in malignant samples with three of them (mir-182, mir-141 and mir-205) performing optimally. Conclusion: These results suggest the potential use of this non-invasive method of sampling for miRNA expression studies. Furthermore miRNA overexpression could serve as an ancillary or reflex test for optimal identification of malignant samples especially in morphologically inadequate samples. © Ivyspring International Publisher.

Background. Methylation of the human papillomavirus (HPV) DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within the L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV16 genotype. Methods. Pyrosequencing was used for DNA methylation quantification and 145 women were recruited. Results. We found that the L1 HPV16 mean methylation (±SD) significantly increased with disease severity (cervical intraepithelial neoplasia [CIN] 3, 17.9% [±7.2] vs CIN2, 11.6% [±6.5], P < .001 or vs CIN1, 9.0% [±3.5], P < .001). Mean methylation was a good predictor of CIN3+ cases; the area under the curve was higher for sites 5611 in the prediction of CIN2+ and higher for position 7145 for CIN3+. The evaluation of different methylation thresholds for the prediction of CIN3+ showed that the optimal balance of sensitivity and specificity (75.7% and 77.5%, respectively) and positive and negative predictive values (74.7% and 78.5%, respectively) was achieved for a methylation of 14.0% with overall accuracy of 76.7%. Conclusions. Elevated methylation level is associated with increased disease severity and has good ability to discriminate HPV16-positive women that have high-grade disease or worse. © The Author 2017.

Aims: Urinary incontinence in general is a major cause of quality of life impairment, morbidity and hospitalization. Its onset is strongly linked to the menopause. Our study aimed to elucidate the possible relationship between endogenous circulating estrogens and the onset and development of stress urinary incontinence (SUI). Methods: One hundred and thirty eight peri- and postmenopausal women with SUI were matched 1:1 with continent women based on age and BMI. Morning fasting blood samples were drawn from all subjects for assessment of estradiol (E2), FSH, LH, Testosterone, Δ4-Androstendione (Δ4Α), DHEAS, prolactin, SBHG as well as a biochemical profile (glucose, insulin, triglycerides, cholesterol, HDL, LDL, ApoA1, ApoB). Hormone and biochemical parameters were compared between continent and incontinent women. Results: Incontinent women had significantly lower serum estradiol levels compared to those in the control group (17.30 ± 8.16 vs. 24.22 ± 8.99, P < 0.001). Furthermore, the same association was observed for serum Δ4Α (146.07 ± 52.63 vs. 159.99 ± 42.62, P = 0.017). These associations remained significant after controlling for age, menopausal age, BMI, and number of deliveries. Conclusions: These results may indicate that within the postmenopausal range, endogenous sex hormones may be associated with the presence of SUI in women not on menopausal hormone therapy. Neurourol. Urodynam. 36:121–125, 2017. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

Background: γH2AX is a protein biomarker for double-stranded DNA breakage; its expression was studied in cervical squamous intraepithelial lesions and carcinomas. Methods: Immunostaining for phospho-γH2AX was performed in sections from histologically confirmed cervical SIL and carcinomas, as well as from normal cervices used as controls. In total, 275 cases were included in the study: 112 low grade SIL (LGSIL), 99 high grade SIL (HGSIL), 24 squamous cell carcinoma (SCC), 12 adenocarcinoma and 28 cervical specimens with no essential lesions. Correlation of histological grading, high risk vs. low risk HPV virus presence, activated vs. non-activated status (by high risk HPV mRNA expression) and γH2AX expression in both basal and surface segments of the squamous epithelium was performed. Results: Gradual increase of both basal and surface γH2AX expression was noted up from normal cervices to LGSIL harboring a low risk HPV type, to LGSIL harboring a high risk virus at a non-activated state (p

Neurofibromatosis type 1 (NF1) is an inherited neurocutaneous syndrome. NF1 patients are at increased risk for both benign and malignant tumors. The authors present the case of a female patient with a medical history of NF1, with an impressive succession of tumors, namely metastatic ovarian cancer and, 20 years later, a gastrointestinal stromal tumor (GIST) of the jejunum. The metastatic ovarian Müllerian adenosarcoma was successfully treated with total abdominal hysterectomy with bilateral salpingo-oophorectomy, radiotherapy, chemotherapy, as well as Gamma Knife radiosurgery of the metastasis in the thalamus. The jejunal GIST was surgically removed. The exploration of molecular pathways that underlie the association between NF1, GISTs, and ovarian cancer may provide valuable insight into the pathogenesis of such cases and assessment of targeted therapies.

Hyperandrogenemia is one of the major diagnostic features for the diagnosis of polycystic ovary syndrome (PCOS). The aim of this study was to estimate the prevalence and the characteristics of hyperandrogenemia in women with PCOS and to investigate the association of clinical and biochemical characteristics with body mass index (BMI) according to the presence of hyperandrogenemia. We studied 266 women diagnosed with PCOS. Hyperandrogenemia was defined by testosterone (T) and/or free testosterone (FT) and/or Δ4 androstenedione (Δ4-A) higher than 75% of the upper limits of each hormone. Patients were stratified in two groups according to a BMI threshold of 25 kg/m2. Hyperandrogenemia was present in 78.2% of the patients. Elevated levels of T were found in 58.4%, while elevated levels of FT and Δ4-A were found in 42.5% and 34.1% of patients. In normal weight women (BMI≤25 kg/m2) with hyperandrogenemia lower values of hip circumference and HOMA-IR and increased levels of T, FT, Δ4-A, 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), white blood cells (WBC) and neutrophils were observed compared to women without hyperandrogenemia. Also, in overweight women higher levels of T, FT, Δ4-A, 17-OHP, DHEAS and cortisol were measured, while lower thyroid-stimulating hormone (TSH) levels were comparable to women without hyperandrogenemia. This study showed high prevalence of hyperandrogenemia in PCOS women. Women with BMI≤25 kg/m2 have significant differences in androgens, WBC, neutrophils and HOMA-IR and women with BMI≥25 kg/m2 in androgens, TSH and cortisol according to the presence or not of hyperandrogenemia. © 2017 Walter de Gruyter GmbH, Berlin/Boston.

There is a controversy regarding ovarian metastasis in early-stage adenocarcinoma of the uterine cervix. The authors present the case of a 51-year-old woman that at the time of diagnosis was thought to suffer from a Stage II cervical carcinoma and a synchronous ovarian carcinoma, that turned out to be an ovarian metastasis from the endocervical adenocarcinoma, as attested morphologically, histochemically, and immunohistochemically. Radical hysterectomy with oophorectomy, excision of the omentum, lymph node excision, and cytological sampling of the peritoneal cavity were carried out. It is important to always bear in mind that even low-grade adenocarcinomas of the cervix can be metastatic to the ovaries. Clinicians have to be careful when managing those cases, while further investigation is needed in order to determine the exact mechanism of those metastases and the criteria needed in order to preserve the ovaries in young patients.

Introduction Differentiating between primary and secondary ovarian cancer can be a difficult task. In hereditary conditions breast malignancies and primary ovarian cancer often coexist. Presentation of case We present a 45-year-old patient with an ovarian mass two years after the diagnosis of a lobular, triple negative breast carcinoma. There was concern whether the lesion represented a metachronous ovarian cancer or a metastasis of the lobular carcinoma. The final histological examination showed a metastatic lesion, deriving from the lobular breast carcinoma, as evidenced by the immunohistochemical profile; nevertheless, there were changes in hormonal receptor expression in the metastatic lesion compared to the primary, triple negative tumor. The patient underwent genetic testing for BRCA1 and BRCA2 mutations and was negative. In the adjuvant setting the patient received 6 cycles of chemotherapy with carboplatin and paclitaxel; eighteen months later, the patient remains without disease recurrence. Discussion and conclusion This case report highlights the role of imaging, histology and predominantly immunohistochemistry as valuable tools in the assessment of ambiguous ovarian lesions after breast cancer. © 2017 The Authors

Background: Methylation of the HPV DNA has been proposed as a novel biomarker. Here, we correlated the mean methylation level of 12 CpG sites within L1 gene, to the histological grade of cervical precancer and cancer. We assessed whether HPV L1 gene methylation can predict the presence of high-grade disease at histology in women testing positive for HPV 16 genotype. Methods: Pyrosequencing was used for DNA methylation quantification and 145 women were recruited. Results: We found that the L1 HPV16 mean methylation (+/-SD) significantly increased with disease severity [CIN3=17.9%(±7.2) vs CIN2=11.6%(±6.5), p

Background: There have been various attempts to assess endometrial lesions on cytological material obtained via direct endometrial sampling. The majority of efforts focus on the description of cytological criteria that lead to classification systems resembling histological reporting formats. These systems have low reproducibility, especially in cases of atypical hyperplasia and well differentiated carcinomas. Moreover, they are not linked to the implied risk of malignancy. Methods: The material was collected from women examined at the outpatient department of four participating hospitals. We analyzed 866 consecutive, histologically confirmed cases. The sample collection was performed using the EndoGyn device, and processed via Liquid Based Cytology, namely ThinPrep technique. The diagnostic categories and criteria were established by two cytopathologists experienced in endometrial cytology; performance of the proposed reporting format was assessed on the basis of histological outcome; moreover, the implied risk of malignancy was calculated. Results: The proposed six diagnostic categories are as follows: (i) nondiagnostic or unsatisfactory; (ii) without evidence of hyperplasia or malignancy; (iii) atypical cells of endometrium of undetermined significance; (iv) atypical cells of endometrium of low probability for malignancy; (v) atypical cells of endometrium of high probability for malignancy; and (vi) malignant. The risk of malignancy was 1.42% ± 0.98%, 44.44% ± 32.46% (nine cases), 4.30% ± 4.12%, 89.80% ± 8.47%, and 97.81% ± 2.45%, respectively. Conclusion: We propose a clinically oriented classification scheme consisting of diagnostic categories with well determined criteria. Each diagnostic category is linked with an implied risk of malignancy; thus, clinicians may decide on patient management and eventually reduce unnecessary interventional diagnostic procedures. Diagn. Cytopathol. 2016;44:888–901. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Background Pre-eclampsia and eclampsia are parts of the broader spectrum of hypertensive disorders complicating pregnancy. This study aims to examine the association between serum inhibin and leptin levels and pre-eclampsia. Methods This study included 98 consecutive cases of pregnant women with pre-eclampsia, together with their 98 pregnant controls, matched for age, gestational week and time period of delivery. Maternal venous blood samples were obtained within 24 h before delivery. In addition to serum inhibin and leptin, birth order, multiple pregnancy, maternal age, maternal overweight/obesity, maternal education, maternal smoking and family history of diabetes/hypertension, were examined as risk factors. Multivariate logistic regression analysis was performed. Results At the univariate analysis, serum inhibin and leptin levels were significantly higher in cases vs. controls. Pre-eclampsia occurred more frequently in primiparous women, whereas overweight and obesity were also associated with pre-eclampsia. At the multivariate analysis, higher serum inhibin levels were associated with pre-eclampsia (multivariate OR = 1.09, 95%CI: 1.03–1.17, p = 0.004, increase per 0.1 ng/mL). On the other hand, leptin was not independently associated with the occurrence of pre-eclampsia (multivariate OR = 1.02, 95%CI: 0.95–1.09, p = 0.631, increase per 10 ng/mL). Conclusions Elevated serum inhibin levels seem to be associated with pre-eclampsia, reflecting placental dysfunction. Increased serum leptin levels may merely reflect an elevated maternal body mass index, which is a well-known risk factor for pre-eclampsia. © 2016 Elsevier B.V.

We investigated the association between the amount and duration of smoking on biochemical, clinical parameters and the ovarian morphology in women with polycystic ovary syndrome (PCOS). That was a retrospective study. These women were divided into two groups, non-smokers (217) and smokers (92). The amount of cigarettes and duration of smoking was measured in pack-years. Both groups underwent clinical evaluation, biochemical and hormone analysis, transvaginal ultrasound and oral glucose tolerance tests (OGTT). The mean value of the number of cigarettes was 14.8 (±8.8) and the median value of pack-years in the smokers group was 4.0 (1.5-7.5). Smokers group has significantly higher free testosterone (F-T), 17-hydroxyprogesterone (17-OHP), delta 4 androstenedione (Δ4-A), T4, low-density lipoprotein (LDL), and white blood cells (WBC). During correlation of all the above parameters and pack-years, there has been significant positive correlation in F-T and Δ4-A. The participants with more pack-years showed statistically higher values of F-T and Δ4-A. There was also a significant positive correlation between total cholesterol, triglycerides, WBC and pack-years of the participants. Prolactin (PRL) has been inversely associated with pack-years. We concluded that the increase of pack-years aggravated lipid profile, WBC and decreased PRL levels, in PCOS patients. © 2015 Taylor & Francis.

Purpose: Local recurrence is considered a major concern in patients diagnosed with ductal carcinoma in situ (DCIS), as its invasive occurrence is associated with high rates of distant disease and mortality. This study aims to assess the possible correlation of hormonal receptor status, Ki-67 and HER2 expression with recurrence rates in women with DCIS, taking also into account the potential prognostic effects of grade and age at diagnosis. Methods: 230 consecutive patients with DCIS were included in this study. Invasive and non-invasive recurrence events were recorded, as a total. Clinicopathological information, as well as PR positivity, ER positivity, HER2 positivity and ki-67 expression were analyzed. Multivariable Cox regression analysis was performed, examining the risk factors for recurrence. Results: Recurrence was noted in 17.8% of cases; the median follow-up was 44 months. Higher grade (adjusted HR = 1.72, 95%CI: 1.06-2.78), age at diagnosis (adjusted HR = 0.60, 95%CI: 0.43-0.83), Ki-67 expression (adjusted HR = 1.78, 95%CI: 1.11-2.88), and type of administered treatment were independently associated with increased recurrence rates. Recurrence rates were not significantly associated with ER, PR status or HER2 expression. Conclusion: In addition to high grade, administered treatment and younger age at diagnosis, high Ki-67 expression seems to be independently associated with increased likelihood of recurrence in patients with DCIS. Future studies with additional molecular markers seem necessary to further improve the identification of high-risk patients for DCIS recurrence. © 2015 Elsevier Ltd.

Purpose: The aim of this study was to estimate the prevalence, to evaluate the characteristics of the metabolic syndrome (MetS) in Greek women with polycystic ovary syndrome (PCOS) and to investigate the correlation of MetS with body mass index (BMI). Methods: In a prospective controlled study, 230 Greek female patients with PCOS and 155 age-matched healthy controls were enrolled. Diagnosis of PCOS was based on the revised criteria of Rotterdam. Both groups were examined for MetS. Diagnosis of MetS was based on the revised criteria of International Diabetes Federation (IDF). Results: The prevalence of the MetS was 12.6 %, nearly sevenfold higher than the controls. Elevated fasting plasma glucose (7.0 vs. 1.9 %) and elevated triglycerides (10.4 vs. 3.2 %) were more frequent in the PCOS cohort (p

Objective To evaluate in vitro maturation (IVM) in sub-fertile women with polycystic ovarian syndrome (PCOS) undergoing in vitro fertilisation (IVF), by comparing outcomes with a control group of non-PCOS. Study design A search strategy was developed for PubMed and studies reporting rates of the following outcomes (live birth; clinical pregnancy; implantation; cycle cancellation; oocyte maturation; oocyte fertilization; miscarriage) between patients with PCOS, PCO and controls undergoing IVM were deemed eligible. The review was conducted in accordance to the PRISMA guidelines and included studies quality was assessed through the Newcastle-Ottawa Quality scale. ORs with their corresponding 95% CIs were calculated for the main analysis and subgroup analyses were performed for PCOS cases vs. controls and PCOS vs. PCO cases. Alternative analyses were performed for live birth and clinical pregnancy, based on cycles and on women. Subgroup analyses for FSH stimulation, hCG priming and type of procedure (IVF/ICSI) were undertaken for all meta-analyses encompassing at least four study arms. Random effects models were used to calculate pooled effect estimates. Results Eleven studies were identified. A total of 268 PCOS patients (328 cycles), 100 PCO patients (110 cycles) and 440 controls (480 cycles) were included in the meta-analysis. A borderline trend towards higher birth rates among PCOS patients emerged (pooled OR = 1.74, 95% CI: 0.99-3.04) mainly reflected at the subgroup analysis vs. controls. Clinical pregnancy (pooled OR = 2.37, 95%CI: 1.53-3.68) and implantation rates (pooled OR = 1.73, 95% CI: 1.06-2.81) were higher, while cancellation rates lower (pooled OR = 0.18, 95%CI: 0.06-0.47) among PCOS vs. non-PCOS subjects; maturation and miscarriage rates did not differ between groups, while a borderline trend towards lower fertilization rates among PCOS patients was observed. Conclusion The present meta-analysis provides preliminary evidence on the effectiveness of IVM as a treatment option when offered in sub-fertile PCOS women, as the latter present at least as high outcome rates as those in non-PCOS. Copyright: © 2015 Siristatidis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Purpose To compare E-selectin, resistin and reactive oxygen species (ROS) levels in serum and follicular fluid (FF) of subfertile women undergoing Controlled Ovarian Hyperstimulation (COH) during IVF/ICSI cycles, using GnRH-agonist and -antagonist protocols. Methods In this prospective cohort study, 85 subfertile women undergoing IVF/ICSI were included. Participants underwent the GnRH-agonist and -antagonist protocols; and blood samples were collected at three time points: basic (at start of COH), on the day of hCG and at oocyte retrieval (OR); and from the FF from the first follicle aspirate. Clinical and IVF cycle characteristics, were compared between groups, together with the levels of E-selectin, resistin and ROS in serum and FF, through ELISA. Their prognostic value on pregnancy outcomes was examined. Result(s) Examining molecules levels are increasing in serum, from start of COH until OR, irrespectively of the protocol used; FF levels at OR were similar to those in serum at that day. Resistin FF levels were lower in GnRH agonists, compared with the antagonist protocol. Resistin levels at start of COH were associated with clinical pregnancy rates, and this remained significant following adjustment for age, BMI and IVF protocol used, while values of >13.5 ng/ml were associated with a six times greater odd of a pregnancy. Conclusion E-selectin, resistin and ROS levels are increasing during COH, reaching their highest values at OR, with comparable values measured in the FF at that time. Resistin values >13.5 ng/ml are linked with a 6-fold increase on the odds of a pregnancy. © Springer Science+Business Media New York 2015.

Aim: To investigate the value of the birth weight of the previous pregnancy (BW1) alone and combined with the third trimester ultrasonographically estimated fetal weight (EFW) and Doppler studies in the prediction of small (SGA) and large for gestational age (LGA) neonates in the index pregnancy (BW2). Method: Some 1298 parous women with uncomplicated singleton pregnancies who had a third trimester ultrasound scan were considered as samples in this retrospective cohort study. Maternal and pregnancy characteristics, BW1, EFW, umbilical artery, and middle cerebral artery pulsatility indices were investigated as predictors of SGA and LGA. Results: BW1, maternal weight, mode of conception, and smoking status were associated with BW2 (R2=0.39) with BW1 being the strongest predictor (R2=0.37). The addition of EFW conferred significant improvement (R2=0.63), whereas the addition of the Doppler indices did not. The sensitivity of BW1 alone in the prediction of SGA was 75% for 25% screen positive rate and increased to 92% with the addition of EFW. The equivalent figures for LGA were 68% and 93%, respectively. Conclusions: BW1 used as a continuous variable is predictive of growth deviations in the index pregnancy. Incorporating EFW enhanced the sensitivity for the detection of both conditions. © 2015 by De Gruyter.

Objective. Nowadays numerous ancillary techniques detecting HPV DNA and mRNA compete with cytology; however no perfect test exists; in this study we evaluated classification and regression trees (CARTs) for the production of triage rules and estimate the risk for cervical intraepithelial neoplasia (CIN) in cases with ASCUS+ in cytology. Study Design. We used 1625 cases. In contrast to other approaches we used missing data to increase the data volume, obtain more accurate results, and simulate real conditions in the everyday practice of gynecologic clinics and laboratories. The proposed CART was based on the cytological result, HPV DNA typing, HPV mRNA detection based on NASBA and flow cytometry, p16 immunocytochemical expression, and finally age and parous status. Results. Algorithms useful for the triage of women were produced; gynecologists could apply these in conjunction with available examination results and conclude to an estimation of the risk for a woman to harbor CIN expressed as a probability. Conclusions. The most important test was the cytological examination; however the CART handled cases with inadequate cytological outcome and increased the diagnostic accuracy by exploiting the results of ancillary techniques even if there were inadequate missing data. The CART performance was better than any other single test involved in this study. © 2015 Abraham Pouliakis et al.

Objectives To examine the distribution of cervical length (CL) in the late second and third trimesters of pregnancy and construct survival models for spontaneous delivery. Methods This cross-sectional study included 647 women with a singleton pregnancy who had routine CL measurements taken by transvaginal ultrasonography between 24 and 40 weeks' gestation. Only one measurement per patient was included in the analysis. Exploratory data analysis revealed that the distribution of CL measurements was a mixture of two Gaussian distributions, and subsequently a mixture model was applied to describe the distribution of CL. Changes in CL in relation to gestational age were examined by regression analysis and measurements were converted to Z-scores. Survival analysis was applied to the subgroups identified, to describe the probability of delivery throughout gestation. Results CL was best described by a mixture model of two subgroups with Gaussian distribution, one including women with a long cervix (73.85% of the study population, mean CL of 28.2±4.45 mm) and the other including women with a short cervix (26.15% of the study population, mean CL of 12.3±5.14 mm). CL was dependent on gestational age (GA), therefore conversion to Z-scores was employed in the analysis. Women with a short cervix had a higher probability for spontaneous delivery (hazard ratio (HR), 1.807; P

The objective of this study was to offer a brief critical summary of the literature on the role of AMH in the subfertility work up and during ART, while exploring its role in predicting ART success.

Objective: The aim of this article was to predict small for gestational age (SGA, at or less than the fifth birth weight percentile) and large for gestational age (LGA, at or greater than the 95th birth weight percentile) fetuses by using maternal and fetal parameters from the second and third trimester ultrasound examinations. Method: This article is a retrospective cohort study on 1979 singleton pregnancies that had a routine 20 to 24weeks anomaly and a 30 to 34weeks growth ultrasound scans. SGA delivered before 30 gestational weeks were excluded. Results: Second trimester estimated fetal weight (EFW2), uterine arteries pulsatility index (PI), and maternal pregnancy characteristics were predictive for SGA (SGA second trimester model: R2=0.225, area under the curve [AUC]=0.815) and LGA (LGA second trimester model: R2=0.203, AUC=0.793). Third trimester EFW (EFW3), EFW2, uterine arteries PI2, umbilical PI, and maternal pregnancy characteristics improved the prediction of SGA (SGA combined model: R2=0.423, AUC=0.896) and LGA (LGA combined model: R2=0.383, AUC=0.882). Contingent screening with risk stratification by the second trimester model performed equally well for SGA (AUC=0.882) and LGA (AUC=0.861) as the combined models. Conclusion: Second trimester model performs well in the prediction of SGA and LGA. The addition of third trimester scan offers substantial improvement. Contingency screening is feasible with similar effectiveness. © 2014 John Wiley & Sons, Ltd. What's already known about this topic? First trimester ultrasound scan in combination with maternal pregnancy characteristics and biochemical indices is predictive of small for gestational age and large for gestational age. Third trimester scan is the superior method to assess fetal growth. What does this study add? Second trimester scan has satisfactory performance in the prediction of small for gestational age and large for gestational age. Second and third trimester contingent screening for fetal growth deviations has similar performance to a routine second and third trimester screening. © 2014 John Wiley & Sons, Ltd.

'The objective of this study is to investigate the potential of classification and regression trees (CARTs) in discriminating benign from malignant endometrial nuclei and lesions. The study was performed on 222 histologically confirmed liquid based cytological smears, specifically: 117 benign cases, 62 malignant cases and 43 hyperplasias with or without atypia. About 100 nuclei were measured from each case using an image analysis system; in total, we collected 22783 nuclei. The nuclei from 50% of the cases (the training set) were used to construct a CART model that was used for knowledge extraction. The nuclei from the remaining 50% of cases (test set) were used to evaluate the stability and performance of the CART on unknown data. Based on the results of the CART for nuclei classification, we propose two classification methods to discriminate benign from malignant cases. The CART model had an overall accuracy for the classification of endometrial nuclei equal to 85%, specificity 90.68%, and sensitivity 72.05%. Both methods for case classification had similar performance: overall accuracy in the range 94-95%, specificity 95%, and sensitivity 91-94%. The results of the proposed system outperform the standard cytological diagnosis of endometrial lesions. This study highlights interesting diagnostic features of endometrial nuclear morphology and provides a new classification approach for endometrial nuclei and cases. The proposed method can be a useful tool for the everyday practice of the cytological laboratory. Diagn. Cytopathol. 2014;42:582-591. © 2013 Wiley Periodicals, Inc.

Successful embryo implantation is a complex process that involves multiple biological mechanisms and reciprocal interactions between the embryo and the proliferated endometrium. In this review, we provide an informative contribution on the pathways underlying the beneficial nature of endometrial injury toward improving implantation rates of embryos conceived and through in vitro fertilization. The evidence published to date are in favor of inducing local endometrial injury in the preceding cycle of ovarian stimulation to improve pregnancy outcomes in women with unexplained and recurrent implantation failure. Endometrial injury triggers a series of biological responses but the findings suggest that no particular pathway is solely adequate to explain the association between trauma and improved pregnancy rates rather than a cluster of events in response to trauma which benefits embryo implantation in ways both known and unknown to the scientific community. © The Author(s) 2014.

Aims: To establish reference ranges for fetal volume (FV) measured by three-dimensional ultrasound (3D-US) at 11-14 weeks of gestation and to examine the possible association of FV with maternal/pregnancy characteristics and biochemical parameters. Methods: Prospective observational study on 240 fetuses at 11-14 weeks. FV was measured by 3D-US using Virtual Organ Computer-Aided Analysis. Pearson correlation coefficient (cc) and regression analysis were used. Results: FV increased exponentially with crown rump length and was unrelated to maternal weight (cc=-0.137, P=0.071), age (cc=0.009, P=0.899), parity (0.76), smoking status (t-test, P=0.149) and mode of conception (t-test, P=0.8). Z-scores (z) of FV was not associated with z-mean uterine artery pulsatility index (cc=-0.026, P=0.733), log10 multiples of the median (MoM) free beta human chorionic gonadotrophin (cc=0.002, P=0.982), delta value (d) of nuchal translucency (cc=0.072, P=0.331) and d-fetal heart rate (cc=0.009, P=0.902), z-FV was significantly positively correlated with log10 MoM pregnancy associated plasma protein-A (PAPP-A; regression coefficient=1.420976, R2=0.0957, P