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Michal Mleko,1 Kazimierz Pitynski,1 Elzbieta Pluta,2 Aleksandra Czerw,3,4 Katarzyna Sygit,5 Beata Karakiewicz,6 Tomasz Banas1 1Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, Poland; 2Department of Radiotherapy, Maria Sklodowska–Curie Institute - Oncology Centre, Krakow, Poland; 3Department of Health Economics and Medical Law, Medical University of Warsaw, Warsaw, Poland; 4Department of Economic and System Analyses, National Institute of Public Health – NIH, Warsaw, Poland; 5Calisia University, Kalisz, Poland; 6Subdepartment of Social Medicine and Public Health, Department of Social Medicine, Pomeranian Medical University, Szczecin, PolandCorrespondence: Tomasz BanasDepartment of Gynecology and Oncology, Jagiellonian University Medical College, 2nd Jakubowskiego Street, Krakow, PolandTel +48 12 424 8584Fax +48 12 424 8560Email tomasz.1.banas@uj.edu.plAbstract: Systemic inflammatory reaction (SIR) is an unfavorable prognostic factor in many malignancies and has a role in all stages of the neoplastic process: initiation, promotion, and disease progression. Analysis of SIR can be performed by assessing indicators (eg, lymphocyte-to-neutrophil, platelet-to-lymphocyte, and monocyte-to-neutrophil ratios) and products of neutrophils and lymphocytes (ie, the systemic immune-inflammation index), or by examining the relationship between levels of C-reactive protein and albumin (based on the Glasgow Prognostic Score, modified Glasgow Prognostic Score, and C-reactive protein-to-albumin ratio). Risk stratification is essential in the clinical management of cancer; hence, the evaluation of these factors has potential applications in the clinical management of patients with cancer and in the development of new therapeutic targets. This review summarizes the current knowledge on SIR indicators and presents their clinical utility in malignancies of the female genital organs.Keywords: breast cancer, cervical cancer, corpus uteri cancers, C-reactive protein, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, systemic inflammatory reaction, vulvar cancer, vaginal cancer

Study Question: Can morphologic measurements (width, length and surface area) of the uterine septum predict healing-dependent abnormal anatomic results [ARs; residual septum (RS) and intrauterine adhesions in other locations (IUA-OLs)] after complete hysteroscopic metroplasty (HM)?Summary Answer: Significant predictors of ARs are the septal width and, to a lesser extent, septal surface area.What Is Known Already: Anatomic results after hysteroscopic metroplasty have very large variation. A RS >1 cm and IUA-OLs can aggravate reproductive outcomes, resulting in the need for reoperation. New criteria for diagnosing a uterine septum according to the European Society of Human Reproduction and Embryology (ESHRE) and European Society for Gynaecological Endoscopy (ESGE) have been suggested (ESHRE-ESGE criteria). Autocross-linked hyaluronic acid gel (autocross-linked polysaccharide) has an antiadhesive effect.Study Design, Size, Duration: A prospective, observational cohort study was performed with 96 women consecutively enrolled between 2007 and 2012.Participants/materials, Setting, Methods: Women who had uterine septum and previous miscarriage or infertility presented for evaluation at a university hospital, private hospital or private medical center were included. Preoperative septal width, length and surface area were determined with three-dimensional sonohysterography. Women were treated by hysteroscopy in a standardized manner with three- or four-dimensional transrectal ultrasound guidance (complete resection). Patients received either no adhesion barrier (49 patients) or adhesion barrier with autocross-linked polysaccharide (47 patients). Anatomic results were assessed with three-dimensional sonohysterography and second-look hysteroscopy. Healing-dependent ARs were reported using both American Society of Reproductive Medicine (ASRM) criterion of RS length >1 cm (ASRM>1 cm criterion) and ESHRE-ESGE criteria. Univariate and multivariate logistic regression were used to identify predictors of RS, IUA-OLs and ARs.Main Results and Role Of Chance: In patients who had no adhesion barrier, ARs were diagnosed in 11 of 49 patients (23%) using the ASRM > 1 cm criterion and in 20 of 49 patients (41%) using the ESHRE-ESGE criteria for RS [odds ratio (OR)ESHRE-ESGE:ASRM, 2.4, P = 0.05]. In the patients who had autocross-linked polysaccharide, ARsASRM > 1 cm were diagnosed in 2 of 47 patients (4%) and ARsESHRE-ESGE in 4 of 47 patients (9%). RSESHRE-ESGE was diagnosed significantly more often than RSASRM > 1 cm 19 of 96 (20%) versus 5 of 96 (5%) in all patients (ORESHRE-ESGE:ASRM > 1 cm = 4.5, P < 0.01). In patients who had no adhesion barrier, logistic regression with ASRM > 1 cm and ESHRE-ESGE criteria showed that the width and surface area were predictors of ARs. Models adjusted by patient group confirmed the significance of width as a predictor of ARsASRM > 1 cm [OR for width, 3.5 (P < 0.01); OR for group, 0.22 (P < 0.01)], width as a predictor of ARsESHRE-ESGE [OR for width, 2.2 (P < 0.01); OR for group, 0.26 (P < 0.01)] and surface area as a predictor of ARsASRM > 1 cm [OR for surface area, 1.5 (P < 0.01)]; OR for group, 0.32 (P < 0.01). In patients who had autocross-linked polysaccharide, these predictors were not significant. Receiver-operating characteristic curves showed cutoff values for ARsASRM > 1 cm (septal width, 3.42 cm; septal surface area, 4.68cm²) and ARsESHRE-ESGE (septal width, 3.42 cm; septal surface area, 3.51cm²).Limitations and Reasons For Caution: Patients were enrolled in the adhesion barrier group in a time-dependent, consecutive and non-randomized manner.Wider Implications Of the Findings: A wide septum and large surface area may be indications for adhesion barrier. The use of autocross-linked polysaccharide reduces the risk of ARs. The ESHRE-ESGE criteria may cause greater frequency of recognition of RS than the ASRM > 1 cm criterion, which could result in more frequent reoperations with use of the ESHRE-ESGE criteria, possibly without any significant effect on reproductive performance.Study Funding/competing Interest(s): This work was supported by Jagiellonian University (grant no. K/ZDS/003821). The authors have no competing interest to declare. [ABSTRACT FROM AUTHOR]

An abstract of the article "Accuracy of 2D/3D high-definition flow imaging HyFoSy and 2D/3D HyFoSy in comparison to 2D air/saline HyCoSy and laparoscopy," by I. Ludwin is presented.

Background: Epithelial ovarian cancer (EOC) is the most fatal gynaecological malignancy treated with cytoreductive surgery followed by adjuvant taxane-platinum-based chemotherapy. It has been shown that the pretreatment systemic inflammatory reaction (SIR) in women with OC can be evaluated using the neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR) and systemic inflammatory index (SII), depending on the stage of disease, and has prognostic value for overall survival. The aim of this study was to evaluate the changes in NLR, LMR, PLR and SII during chemotherapy., Methods: A total of 107 women with EOC (23 with type I and 84 with type II tumours) were included in a retrospective single-centre analysis. The Kologomorov-Smirnoff, Kruskal-Wallis or Friedman analysis of variance tests were used for data analysis, and a p value of 0.05 was considered statistically significant., Results: A significant decrease in NLR, PLR and SII but not LMR was observed during adjuvant treatment. Pretreatment NLR, PLR and SII were dependent on disease stage and tumour grade; however, this association was lost during therapy. Additionally, strong and positive mutual correlations between NLR, LMR, PLR and SII were sustained during the whole course of chemotherapy., Conclusions: During first-line adjuvant chemotherapy in women with EOC, a decrease in SIR is confirmed.

Endometrial cancer remains a common cancer affecting the female reproductive system. There is still a need for more efficient ways of determining the degree of malignancy and optimizing treatment. WNT and mTOR are components of signaling pathways within tumor cells, and dysfunction of either protein is associated with the pathogenesis of neoplasms. Therefore, the aim of our study was to assess the impact of subcellular WNT-1 and mTOR levels on the clinical course of endometrial cancer. WNT-1 and mTOR levels in the plasma membrane, nucleus, and cytoplasm were evaluated using immunohistochemical staining in a group of 64 patients with endometrial cancer of grades 1-3 and FIGO stages I-IV. We discovered that the levels of WNT-1 and mTOR expression in the cellular compartments were associated with tumor grade and staging. Membranous WNT-1 was negatively associated, whereas cytoplasmic WNT-1 and nuclear mTOR were positively associated with higher grading of endometrial cancer. Furthermore, nuclear mTOR was positively associated with FIGO stages IB-IV. To conclude, we found that the assessment of WNT-1 in the cell membrane may be useful for exclusion of grade 3 neoplasms, whereas cytoplasmic WNT-1 and nuclear mTOR may be used as indicators for confirmation of grade 3 neoplasms.

Objectives: The aim of this study was to assess the performance of the International Ovarian Tumor Analysis (IOTA) group ultrasound Simple Rules method in differentiating between benign and malignant ovarian tumors in pregnant patients., Material and Methods: A prospective observational study that involved pregnant patients referred to our center due to suspicions of ovarian masses between January 2015 and December 2017 was performed. The Simple Rules performance was evaluated against the histopathological results. Each of the 10 sonographic Simple Rules were computed by logistic regression to demonstrate their odds ratios in predicting malignancy., Results: Ultrasound were conducted in 153 subjects, and 61 of those patients underwent surgery. By assigning masses presenting inconclusive picture as probably malignant, the Simple Rules method showed sensitivity of 91.67% and specificity of 69.39%. After exclusion of masses with inconclusive findings, the method showed sensitivity of 87.5% and specificity of 94.44%. The Simple Rules risk estimation method for the 1% risk cutoff showed sensitivity of 100% and specificity of 51.02%. For the 3% cutoff, sensitivity was 91.67% and specificity was 53.06%. And for 30 % cutoff, sensitivity was 91.67% and specificity 73.47 %. The logistic regression model showed that the M-rules increased the risk of malignancy while the B-rules decreased the risk., Conclusions: Most ovarian masses in pregnant patients may be correctly categorized as benign or malignant using Simple Rules. This protocol may facilitate the management of pregnant patients presenting with adnexal masses.

Systemic inflammatory reaction (SIR) is an unfavorable prognostic factor in many malignancies and has a role in all stages of the neoplastic process: initiation, promotion, and disease progression. Analysis of SIR can be performed by assessing indicators (eg, lymphocyte-to-neutrophil, platelet-to-lymphocyte, and monocyte-to-neutrophil ratios) and products of neutrophils and lymphocytes (ie, the systemic immune-inflammation index), or by examining the relationship between levels of C-reactive protein and albumin (based on the Glasgow Prognostic Score, modified Glasgow Prognostic Score, and C-reactive protein-to-albumin ratio). Risk stratification is essential in the clinical management of cancer; hence, the evaluation of these factors has potential applications in the clinical management of patients with cancer and in the development of new therapeutic targets. This review summarizes the current knowledge on SIR indicators and presents their clinical utility in malignancies of the female genital organs., Competing Interests: The authors report no conflicts of interest in this work., (© 2021 Mleko et al.)

Background: (1) Endometrial cancer is one of the most common cancers affecting women, with a growing incidence. To better understand the different behaviors associated with endometrial cancer, it is necessary to understand the changes that occur at a molecular level. CD133 is one of the factors that regulate tumor progression, which is primarily known as the transmembrane glycoprotein associated with tumor progression or cancer stem cells. The aim of our study was to assess the impact of subcellular CD133 expression on the clinical course of endometrial cancer. (2) Methods: CD133 expression in the plasma membrane, nucleus, and cytoplasm was assessed by immunohistochemical staining in a group of 64 patients with endometrial cancer representing FIGO I-IV stages, grades 1-3 and accounting for tumor angioinvasion. (3) Results: Nuclear localization of CD133 expression was increased in FIGO IB-IV stages compared to FIGO IA. Furthermore, CD133 expression in the nucleus and plasma membrane is positively and negatively associated with a higher grade of endometrial cancer and angioinvasion, respectively. (4) Conclusions: Our findings suggest that positive nuclear CD133 expression in the tumor may be related to a less favorable prognosis of endometrial carcinoma patients and has emerged as a useful biomarker of a high-risk group.

The Polish Society of Colposcopy and Cervical Pathophysiology and the Polish Society of Gynecologists and Obstetricians provide comprehensive guidelines for colposcopy practice in secondary cervical cancer prevention in Poland. This part of the guidelines, developed by the clinical experts of the Working Group No. 1 (WG1), concerns the colposcopy protocols with the main aim of algorithmizing the procedure, together with all procedure-related processes. The detailed analysis of strong scientific evidence and an extensive literature review of current international colposcopic recommendations were carried out, with also a broad investigation of recently ongoing dynamic changes in national health systems. The attention to colposcopic limitations also occurring in Polish conditions was kept. The overriding goal was the recommended obligatory minimal colposcopy approach introduction. To enhance the standard of colposcopy, adjustment of a precolposcopic assessment, a performance technique, types of used biopsies, as well as the procedure documentation was made. Elements of the risk-based stratification for the increased risk of developing cervical cancer was also included if it was applicable for that part of the guidelines. Comprehensive colposcopy guidelines are a step towards the ongoing era of a precision medicine in cervical cancer prevention in Poland.

Objectives: Dental agenesis - a congenital lack of teeth - is one of the most frequently diagnosed developmental defects of dentition. Genetics is a crucial factor in the etiology of this disorder. Missing teeth can be caused by mutation in genes including MSX1, PAX9, AXIN2, and EDARADD. As is also true for ovarian cancer, over 20% of cases are associated with hereditary factors. Mutations in the BRCA1 and BRCA2 genes are said to be the most frequent of these. The aim of this study was to provide a systematic review of the literature on the coexistence of ovarian cancer and tooth agenesis., Material and Methods: Publications were searched for in the online databases PubMed, SCOPUS, and Wiley Online Library. Current and archival issues of the Journal of Stomatology and Dental and Medical Problems were also searched. The key words used to find relevant publications were: ovarian cancer, hypodontia, and tooth agenesis, in various combinations., Results: Three publications were qualified to this review. Two of these compared the incidence of hypodontia in women with ovarian cancer and in healthy women, and the other was aimed at locating the gene responsible for the coexistence of ovarian cancer and tooth agenesis. As shown by these studies, women with ovarian cancer are (depending on the study) 3.3 or 8.1 times more likely to have hypodontia than healthy women. However, no specific gene was found that might be responsible for the coexistence of ovarian cancer and tooth agenesis.

Introduction: DNA fragmentation factors 40 and 45 (DFF40 and DFF45) are final executors of apoptosis, and B-cell lymphoma 2 (Bcl-2) is a well-recognized apoptosis inhibitor. We aimed to evaluate DFF40, DFF45 and Bcl-2 immunoexpression in the normal human endometrium with respect to the glandular and stromal layer and in uterine myometrium., Material and Methods: DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle., Results: Compared to the myometrium and stroma, endometrial glands showed the highest DFF40 and DFF45 expression in pre- and postmenopausal specimens. DFF45, but not DFF40, glandular expression dependent on menstrual cycle phase and DFF40 and DFF45 scoring was significantly lower in postmenopausal specimens. Significantly higher Bcl-2 expression was observed in proliferative glandular endometrium compared to secretory and postmenopausal specimens. No cycle- or menopause-dependent changes were reported for stromal or myometrial DFF40, DFF45 or Bcl-2 expression. DFF40, DFF45 and Bcl-2 expression was independent of age, age at menarche and menopause, BMI, menstrual cycle and menses lengths, parity and gravidity., Conclusions: The study provides important evidence regarding menstrual cycle-dependent changes in the expression of DFF40, DFF45 and Bcl-2 in the normal human endometrium, especially in the glandular layer, and shows that their levels are stable in the normal uterine myometrium., Competing Interests: The authors declare no conflict of interest.

DNA fragmentation factor 40 (DFF40) is a key executor of apoptosis. It localizes to the nucleus together with DNA fragmentation factor 45 (DFF45), which acts as a DFF40 inhibitor and chaperone. B-cell lymphoma (Bcl-2) protein is a proven antiapoptotic factor present in the cytoplasm. In this study, we aimed to investigate DFF40, DFF45, and Bcl-2 immunoexpression in endometrial polyps (EPs) and benign endometrial hyperplasia (BEH) tissue compared with that in normal proliferative endometrium (NPE) and normal secretory endometrium (NSE) as well as normal post menopausal endometrium (NAE). This study used archived samples from 65 and 62 cases of EPs and BEH, respectively. The control group consisted of 52 NPE, 54 NSE, and 54 NAE specimens. Immunohistochemistry was used to detect DFF40, DFF45, and Bcl-2. DFF40, DFF45, and Bcl-2 were more highly expressed in the glandular layer of EPs and BEH compared with the stroma, and this was not influenced by menopausal status. Both glandular and stromal expression of DFF40, DFF45, and Bcl-2 were significantly higher in EPs compared with NPE, NSE, and NAE. Glandular BEH tissue showed significantly higher DFF40, DFF45, and Bcl-2 expression than in NPE, NSE, and NAE. No differences in the glandular expression of DFF40, DFF45, and Bcl-2 were observed between EP and BEH tissues, while Bcl-2 stromal expression in BEH was significantly lower than in EPs. Glandular, menopause-independent DFF40, DFF45, and Bcl-2 overexpression may play an important role in the pathogenesis of EPs and BEH.

Background: The expression of DNA fragmentation factor 45 (DFF45) and B-cell lymphoma 2 (BCL2) in glands of the normal human endometrium is related to phases of the menstrual cycle and decreases after menopause, whereas the expression of DNA fragmentation factor 40 (DFF40) is stable. Moreover, DF45, BCL2 and DFF40 underexpression has been reported in numerous malignancies, including uterine leiomyosarcomas. In this study, we aimed to investigate DFF45, BCL2 and DFF40 expression in endometrioid and non-endometrioid types of endometrial cancers (ECs). We also evaluated the correlations between DFF45, BCL2 and DFF40 expression levels and clinicopathological parameters and determined the value of these three proteins as prognostic markers of disease-free survival (DFS) and overall survival (OS)., Methods: Immunohistochemistry was performed to evaluate DFF45, BCL2 and DFF40 expression in 342 cases of ECs. Student's t-test, the Mann-Whitney U-test, and the chi-squared test were used for the statistical analyses as appropriate. The Cox-Mantel test, Cox's proportional hazard model, and relative risk analyses were used to evaluate associations between DFF40, DFF45, and BCL2 expression and clinicopathological characteristics., Results: DFF40 and BCL2, but not DFF45, were significantly underexpressed in non-endometrioid and high-grade endometrioid ECs compared with low- and moderate-grade endometrioid ECs. Women with DFF40- and BCL2-negative tumors had higher risks of disease recurrence, lymph node involvement, lympho-vascular space infiltration, and deep myometrial invasion compared with women with DFF40- and BCL2-positive tumors. Additionally, women with DFF40- and BCL2-negative tumors had significantly lower OS and DFS than women with DFF40- and BCL2-positive tumors. A multivariable analysis of the model, including the clinicopathological characteristics and immunohistochemical results, showed that negative BCL2 expression, lymph node involvement, and high-stage and high-grade disease were independent predictors of OS, whereas negative BCL2 expression, lymph node involvement, and high-stage disease were independent predictors of DFS., Conclusions: Compared with low- and moderate-grade endometrioid ECs, non-endometrioid and high-grade endometrioid ECs showed significant DFF40 and BCL2 underexpression. The absence of DFF40 and BCL2 expression negatively affects DFS and OS. Further prospective studies are warranted to assess the potential utility of DFF40 and BCL2 as targets in the diagnosis or treatment of ECs.

Objectives: Exosomes - microvesicles which are secreted by living cells - can be produced from different cell types and detected in various body fluids. They are the carriers of intercellular information which regulate tumor microenvironment and are considered to be involved in tumor progression and metastasis. Cancer cells can secrete more exosomes than healthy cells, and are expected to be potential tools for tumor diagnosis and treatment., Material and Methods: In this report, we present the results of microparticle analysis in peripheral and uterine blood of patients with endometrial cancer. To the best of our knowledge, this study has been the first to report microvesicle status in peripheral and uterine blood samples. The aim of the study was to determine the amount of total (TF+), endothelial (CD144+) and monocytic (CD14+) microparticles. The counting of the selected microparticles in citrate plasma was performed using flow cytometry on the BD Canto II cytometer., Results: We found that the total amount of microparticles in cancer patients was much higher than in healthy controls. Moreover, microparticle count in uterine blood was higher than in peripheral blood of patients with endometrial cancer. We also demonstrated that the amount of microparticles correlates with the histologic grade and clinical stage of the tumor., Conclusions: The most interesting finding in this work was the high level of TF, CD144 and CD14 MPs in uterine blood samples. Thus we can consider the monocyte-macrophage-derived MPs as a candidate marker of endometrial cancer and maybe very critical part of the endometrial carcinogenesis.

Retrognathia is a common feature of many fetal anomalies that may be diagnosed during ultrasound examination. The most common method used for the diagnosis of this condition is the inferior facial angle (IFA). The existing reference ranges for IFA have been established for the fetuses at 18- 28 weeks gestation and may be not applicable in the first trimester. The aim of the study was to document changes of IFA from 11+0 to 13+6 weeks gestation, to verify the reproducibility of IFA calculations obtained by the same examiner and to investigate the possible association between IFA values at the first and second trimester scans., Material and Methods: A prospective study was performed in 512 singleton pregnancies during the first trimester ultrasound exam. IFA was calculated by measuring the angle made by the cross-section of a line orthogonal to the forehead at the level of nasofrontal suture and the line from the tip of the mentum to the anterior border of the more protrusive lip. In 100 cases, stored images were used to calculate IFA twice by the same examiner. In a second trimester scan, IFA was measured again in 215 fetuses., Results: The median IFA value at the time of the first trimester (IFA-1) was 880 (IQR: 8.0) and decreased with crown-rump length (CRL) and biparietal diameter (BPD). A moderate negative correlation was shown between IFA-1 and CRL (r= 0.3; p<0.001) as well as between IFA-1 and BPD-1 (r= 0.176; p=0.010). An intraclass correlation coefficient (ICC) of 0.87 (95% CI: 0.81 – 0.91) confirmed strong intraobserver agreement between two IFA measurements. In 215 fetuses that underwent a second trimester screening, the median IFA-2 was significantly lower compared to IFA-1(215) (750; IQR: 10.0 vs.870; IQR: 8.0; p<0.001), and there was no correlation between IFA1215 and IFA-2 (r= -0.024; p=0.731)., Conclusions: In the first trimester, IFA decreases with CRL and BPD. When performed by the same operator, measurement of IFA is reproducible. There is no correlation between the IFA values in the first and second trimesters.

Objective: To externally validate the International Ovarian Tumor Analysis (IOTA) Simple Rules (SR) by examiners with different levels of sonographic experience defined by the European Federation of Societies for Ultrasound in Medicine and Biology (EFSUMB) and to assess the morphological ultrasound features of the adnexal tumors classified as inconclusive based on IOTA SR. Materials and Methods: In the two-year prospective study adnexal tumors were assessed preoperatively with transvaginal ultrasound by examiners with different levels of experience (level 1- IOTA SR1, level 2-IOTA SR2). Additionally, an expert (level 3) evaluated all tumors by subjective assessment (SA). If the rules could not be applied, the tumors were considered inconclusive. The final diagnosis was based on the histopathological result of the removed mass. The diagnostic performance measures for the assessed model were sensitivity, specificity, negative (LR-) and positive(LR+) likelihood ratios, accuracy (ACC) and diagnostic odds ratio (DOR). Results: 226 women with adnexal tumors scheduled for surgery were included in the stutdy. The prevalence of malignancy was 36.3 % in the group of all studied tumors and was 52.5 % in the inconclusive group (n = 40) (p = 0.215). Fewer tumors were classified as inconclusive by level 2 examiners compared to level 1 examiners [20 (8.8 %) vs. 40 (17.7 %); p = 0.008], resulting from the discrepancy in the evaluation of acoustic shadows and the vascularization within the tumor. For level 1 examiners a diagnostic strategy using IOTA SR1 +MA (assuming malignancy when SR inconclusive) achieved a sensitivity, specificity and DOR of 96.3 %, 81.9 %, 13.624 respectively. For level 2 examiners the diagnostic strategy for IOTA SR2 +MA achieved a sensitivity, specificity and DOR of 95.1 %, 89.6 %, 137,143, respectively. Adding SA by an expert (or level 3 examiner) when IOTA SR were not applicable improved the specificity of the test and achieved a DOR of 505.137 (SR1 +SA) and 293.627 (SR2 +SA). The SA by an expert proved to have the best diagnostic performance with a DOR of 5768.857, and a sensitivity and specificity of 97.6 % and 99.3 % respectively. Within the inconclusive group the most common tumors were unilocular-solid (n-13), solid (n-8) and multilocular-solid (n-10) ones. All multilocular tumors were classified as inconclusive because of their size (≥ 100 mm) and were found to be benign by pathology. Most of the inconclusive tumors with cystic content presented low-level (43.75 %) echogenicity, followed by ground-glass (34.37 %), mixed (12.5 %) and anechoic (9.4 %). Conclusion: The study results show excellent diagnostic performance of IOTA Simple Rules followed by subjective expert assessment in inconclusive tumors irrespective of the level of experience, while subjective assessment by an expert still has the highest diagnostic odds ratio. The number of inconclusive cases seems to depend on the level of ultrasound expertise and less experienced examiners have a tendency to overestimate blood flow and a presence of acoustic shadows within the tumors. IOTA SR were not applicable either because no benign or malignant features were found or both were identified. Within inconclusive tumors the majority of cases comprise malignant masses that are either unilocular-solid, solid tumors or small multilocular-solid ones with a diameter of less than 100 mm., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The aim of the study was to compare the natural menopause ages of healthy women with those of women with methotrexate (MTX)-treated rheumatoid arthritis (RA), and to specifically assess the effect of disease onset and activity and the use of MTX on the age of the last menstruation., Methods: We performed a retrospective review of medical records to identify the ages at which menopause occurred in women with premenopausal RA treated with MTX and in women with postmenopausal onset, irrespective of therapy. Natural menopause ages were also compared between participants with and without RA., Results: Women with premenopausal onset of RA underwent menopause at a significantly younger age than did healthy women (P < 0.001) or those with postmenopausal disease onset (P = 0.001). Menopause also occurred at younger ages in participants with postmenopausal disease onset than in healthy controls (P = 0.012). The study suggested that menopause age was positively correlated with the age at which RA was diagnosed (R = 0.51; P < 0.001) in women with premenopausal RA onset, but was independent of the participant's age at menarche, number of pregnancies, or MTX therapy. Participants with RA onset at ≤ 35 years of age had a ninefold higher risk of premature menopause (P = 0.008)., Conclusions: The age at which menopause occurs in a patient with RA depends on the patient's age at the time of disease onset and its duration, but is not influenced by MTX treatment.

Objectives: This study aimed to analyze incidence and mortality trends in breast cancer (BC), corpus uteri cancer (CUC), and ovarian cancer (OC) in Poland in the context of sociodemographic changes., Materials and Methods: Incidence and mortality data (1980-2013) were retrieved from the Polish National Cancer Registry, while socioeconomic data (1960-2013) were obtained from the World Bank. Age-standardized incidence and mortality rates were calculated by direct standardization, and join-point regression was performed to describe trends using the average annual percentage change (AAPC)., Results: A significant decrease in birth and fertility rates and a large increase in gross domestic product were observed together with a decrease in the total mortality rate among women, as well as an increase in life expectancy for women. A large, significant increase in BC incidence was observed (AAPC1980-1990 2.14, AAPC1990-1996 4.71, AAPC1996-2013 2.21), with a small but significant decrease in mortality after a slight increase (AAPC1980-1994 0.52, AAPC1994-2013 -0.66). During the period 1980-2013, a significant increase in CUC incidence (AAPC1980-1994 3.7, AAPC1994-2013 1.93) was observed, with an initial mortality-rate reduction followed by a significant increase (AAPC1980-2006 -1.12, AAPC2006-2013 3.74). After the initial increase of both OC incidence and mortality from 1994, the incidence rate decreased significantly (AAPC1980-1994 2.98, AAPC1994-2013 -0.49), as did the mortality rate (AAPC1980-1994 0.52, AAPC1994-2013 -0.66)., Conclusion: After 1994, a decrease in OC incidence was found, while the incidence of BC and CUC continued to increase. A reduction in mortality rate was observed for BC and OC predominantly at the end of the study period, while for CUC, after a long decreasing mortality trend, a significant increase was observed.

Gamma-glutamyl transferase (GGT) is a membrane enzyme present not only in the liver but also in healthy endometrial epithelium. Its overexpression has been demonstrated in numerous malignancies, where it exerts an anti-apoptotic effect and causes drug resistance in response to oxidation stress. Aim of the study was investigation of GGT expression in postmenopausal patients with endometrioid adenocarcinoma of the uterus (EAC). The material comprised 98 paraffin-embedded post-operative tumour samples of EAC from postmenopausal patients and a control group of 60 normal human postmenopausal endometrium samples. For immunohistochemical specimen staining, polyclonal IgG anti-GGT was used; for GGT expression measurement, a semi-quantitative method was applied. In EAC patients, 16 (16.33%) were diagnosed as stage IA, 46 (46.93%) as stage IB, 14 (14.29%) as stage II, and 22 (22.45%) as stage IIIA-C, according to the International Federation of Gynaecology and Obstetrics (FIGO) classification. Fifty-six (57.14%) patients were diagnosed with low- or moderate-grade (G1-2) disease, and 42 (42.86%) were diagnosed with high-grade (G3) disease. Cytoplasmic GGT staining was confirmed in all samples, while apical membrane GGT staining was observed only in G1-2 EAC specimens and the control group. In G3 EAC specimens, GGT cytoplasmic staining and high nuclear polymorphism areas were predominantly shown. Comparable high GGT median apical expression was confirmed in healthy endometrium (2.0, S.E.M. = 0.28) and in G1-2 EAC (2.0, S.E.M. = 0.27); however, in G3 tumours, GGT expression was significantly lower (0.0, S.E.M. = 0.07) than in healthy endometrium (P < 0.001 and P < 0.001, respectively). After stratification of the cancer cases according to FIGO staging, the lowest median apical GGT expression levels were in II EAC (0.0, S.E.M. = 0.64) tumours compared with IA (4.0, S.E.M. = 0.47) tumours, specimen and normal endometrium (2.0, S.E.M. = 2.8) (P < 0001). Stage IB EAC and IIIA-C EAC (1.0, S.E.M. = 0.16) cases showed only moderate median apical expression of GGT (1.0, S.E.M. = 0.24). We concluded that impaired GGT expression has the potential to become a valuable tool for stratifying EEC patients' prognosis and treatment planning.

Objective: The purpose of this research was to assess the dynamics of autonomic nervous system(ANS) and hemodynamic activity changes during uncomplicated pregnancy., Methods: We enrolled 36 pregnant women (mean age 29 ± 4.8 years) and a control group of 10 non-pregnant women (mean age 25.9 ± 0.88 years). The examination was performed in the 1st, 2nd, and 3rd trimester. Continuous registration of BP, ECG, and cardioimpedance was performed with Task Force Monitor 3040i. ANS activity was measured using the following parameters: HRV, BPV, BRS at rest, and in response to autonomic tests., Results: Compared to the 1st trimester, an increase in HR (73 vs. 92 bpm; p < 0.001) and mean BP (80 vs. 85 mmHg, p < 0.01) was observed in the 3rd trimester. In the 1st trimester, the BRS of pregnant women was insignificantly higher than in the controls (24.8 vs. 22.3 ms/mmHg); subsequently, it decreased significantly, to 13.4 ms/mmHg in the 3rd trimester (p = 0.0004). An increase in nLF (39.57 ± 13.75 vs. 58.73 ± 15.55; p = 0.001) and LF/HF ratio (1.03 ± 0.76 vs. 1.85 ± 0.8; p < 0.00002) was revealed in HRV analysis conducted in the 3rd trimester, as compared to the 1st tri- mester, along with a decrease in nHF (60.43 ± 13.71 vs. 41.26 ± 15.55; p < 0.001). An increase in LF/HF-sBPV (1.05 ± 0.48 vs. 1.58 ± 0.44; p = 0.01) was recorded in BPV analysis at rest in the 3rd trimester as compared to the respective 1st trimester value., Conclusion: Our findings suggest that pregnancy is associated with dynamic changes in autonomic balance, namely doubled dominance of the sympathetic component. Hypervolemia seems the major factor responsible for autonomic and hemodynamic changes observed during pregnancy, as it causes an increase in BP and simultaneous decrease in BRS.

Objective: To evaluate the clinical significance of the combination of cancer antigen-125 (CA-125), human epididymis protein 4 (HE4), and progesterone for the identification of ovarian masses in patients with suspected early stage ovarian cancer (OC)., Materials and Methods: This was a case-control, single-center study of 225 women with a pelvic mass of suspected ovarian origin, including 75 patients with Stage I/II OC and 150 controls. Diagnostic procedures included pelvic and rectal examinations, transvaginal ultrasound, evaluation of CA-125 and HE4 levels alone and in the Risk of Ovarian Malignancy Algorithm (ROMA), and a new algorithm combining ROMA and progesterone., Results: Median CA-125 and HE4 levels were significantly higher in patients with OC compared with women with benign ovarian tumors, irrespective of menopausal status. The highest median progesterone levels occurred in premenopausal women with benign ovarian tumors, compared with premenopausal women with OC with or without benign ovarian disease. The combination of ROMA and progesterone was significantly more accurate at detecting OC compared with ROMA or CA-125 or HE4 alone, but only in premenopausal patients., Conclusion: Different algorithms should be used for diagnosing OC, and the addition of progesterone might improve the performance of ROMA for the diagnosis of pelvic masses in premenopausal women., (Copyright © 2015. Published by Elsevier B.V.)

Background: Endometriosis is a well-known cause of infertility, and the anti-Mullerian hormone (AMH) is an accepted biomarker of ovarian reserve and response to artificial reproductive technology procedures. The present study was a prospective analysis of age-dependent AMH serum concentration in women with bilateral and unilateral ovarian endometriomas before therapy onset compared with healthy controls., Methods: This prospective cross-sectional study included 384 women aged 18-48 years. AMH serum concentration was assessed between days 3 and 6 of the menstrual cycle in 78 patients with bilateral and 157 patients with unilateral ovarian endometriomas and compared with 149 healthy controls. Ovarian endometriosis was confirmed histopathologically, and data were presented as medians with interquartile range (IQR)., Results: Stage III endometriosis was diagnosed in 53.2 %, stage IV in 18.3 %, stage V in 23.4 % and stage VI in 5.4 % of the patients. Patients with bilateral ovarian endometriomas showed the lowest median AMH levels compared with patients suffering from unilateral ovarian endometriosis (0.55; IQR: 0.59 vs. 2.00; IQR: 2.80; p < 0.001) and the control group (0.55; IQR: 0.59 vs. 2.84; IQR: 3.2; p < 0.001). Median AMH concentration values were not significantly different between patients with unilateral ovarian endometriosis and the healthy controls (2.00; IQR: 2.80 vs. 2.84; IQR: 3.2; p = 0.182). A strongly negative correlation between AMH levels and age was confirmed in healthy individuals (R = -0.834; p < 0.001) and women with unilateral ovarian endometriomas (R = -0.774; p < 0.001). Patients with bilateral ovarian endometriosis showed a significantly negative but only moderate correlation between AMH levels and age (R = -0.633; p < 0.001), which was significantly lower than in the healthy controls (R = -0.633 vs. R = -0.834; p = 0.006) but not in the patients with unilateral ovarian endometriosis (R = -0.663 vs. R-0.774; p = 0.093). Based on a multivariate regression analysis, only bilateral localization of ovarian endometrial cysts (p = 0.003) and patient age (p < 0.001), but not left/right localization of unilateral cyst or cyst volume, were negatively associated with AMH serum concentration., Conclusion: According to our data, unilateral ovarian endometriosis had a moderately negative and nonsignificant effect on AMH-based ovarian reserve evaluated prior to surgery, irrespective of age. In contrast, the ovarian reserve was significantly reduced in women with bilateral ovarian endometriomas.

Background: The aim of this study was to determine the incidence, mortality rates and trends of vulvar and vaginal cancers in Poland., Methods: Data were retrieved from the Polish National Cancer Registry. Age-standardised rates (ASRs) of cancer incidence and mortality were calculated by direct standardisation, and joinpoint regression was performed to describe the trends using the average annual percent change (AAPC)., Results: From 1999 to 2012, the number of diagnosed cases of vulvar cancer was 5,958, and the ASRs of incidence varied from 0.99 to 1.18, with a significant trend towards a decrease (AAPC -0.78; p < 0.05). The ASR of mortality varied from 0.39 to 0.62, with a slight but insignificant increase in trend (AAPC 0.72; p > 0.05). The ASR of vaginal cancer incidence varied from 0.21 to 0.31, while the ASR of mortality ranged from 0.09 to 0.22. This study also proved a significantly falling trend in vaginal cancer mortality (AAPC -4.69; p < 0.05) and a decreasing trend in vaginal cancer incidence (AAPC -1.67; p > 0.05)., Conclusion: The rarity of vulvar and vaginal cancers as well as the decline in their incidence rates should not discourage further research on the epidemiology and treatment of these conditions., (© 2015 S. Karger AG, Basel.)

Objective: To compare the diagnostic accuracy of three-dimensional sonohysterography (3D-SIS) and office hysteroscopy in uterine cavity assessment after hysteroscopic metroplasty (HM) and determine the interrater/intrarater agreement for 3D-SIS., Design: Prospective observational study., Setting: University hospital, private hospital, and clinic., Patient(s): One hundred forty-one women undergoing HM for septate uterus with a history of miscarriage and/or infertility., Intervention(s): 3D-SIS and office hysteroscopy at 6-8 weeks after HM., Main Outcome Measure(s): Shape of the uterine cavity, length of the fundal notch (≥1 or <1 cm), and the presence of intrauterine adhesions were assessed, and the interrater/intrarater agreement of 3D-SIS was evaluated in 30 randomly selected patients., Result(s): Uterine abnormalities were detected with the use of hysteroscopy in 18 (12.8%) of 141 women. 3D-SIS was highly accurate (97.2%), sensitive (97%), and specific (100%), with a positive predictive value of 100% and a negative predictive value of 85%. The diagnostic values of hysteroscopy and 3D-SIS were not significantly different (McNemar test). 3D-SIS showed substantial interrater/intrarater agreement regarding overall uterine cavity evaluation (κ = 0.79 and 0.78, respectively)., Conclusion(s): 3D-SIS demonstrated substantial interrater/intrarater agreement for the postoperative evaluation of the uterine cavity, being as diagnostically accurate as hysteroscopy. The use of second-look hysteroscopy may be limited to cases that require reoperation., (Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)