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Marcin Piechocki,1 Wojciech Kozio&lstrok;ek,1 Damian Sroka,1 Anna Matrejek,1 Paulina Mizio&lstrok;ek,1 Nazarii Saiuk,1 Monika Sledzik,1 Adriana Jaworska,1 Krzysztof Bereza,2 Elzbieta Pluta,3 Tomasz Banas1 1Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, Poland; 2Department of Mother and Child Health;Faculty of Health Sciences;Institute of Nursing and Midwifery;Jagiellonian University Medical College, Krakow, Poland; 3Department of Radiotherapy, Maria Sklodowska–Curie Institute - Oncology Centre, Krakow, PolandCorrespondence: Tomasz BanasDepartment of Gynecology and Oncology, Jagiellonian University Medical College, 2nd Jakubowskiego Str, Krakow, Poland, Tel +48 12 424 8584, Fax +48 12 424 8560, Email tomasz.1.banas@uj.edu.plBackground: This study aimed to analyze and determine the incidence and mortality trends in gynecological and breast cancers (BCs) in Poland. The gynecological cancers assessed were cervical cancer (CC), corpus uteri cancer (CUC), ovarian cancer (OC), vaginal cancer (VAC), and vulvar cancer (VUC).Patients and Methods: Data concerning the incidence and mortality for the period of 1980– 2018 were obtained from the Polish National Cancer Registry (PNCR). Joinpoint regression analysis was performed to identify trends, which were described using the annual percentage change (APC) and the average annual percent change (AAPC).Results: Statistically significant increases were observed in BC incidence (AAPC: 2.3; CI: 1.8 to 2.9; p< 0.05), CUC incidence (AAPC: 2.3; CI: 1.9 to 2.7; p< 0.05), CUC mortality (AAPC: 0.4; CI: 0.1 to 0.7; p< 0.05) and VUC mortality (AAPC: 1.16, CI: 0.1 to 2.2; p< 0.05). VAC mortality decreased (AAPC: − 3.5, CI: − 5.0 to – 2.0; p< 0.05), as did CC incidence and mortality (AAPC: − 2.1, CI: − 2.3 to − 1.8; p< 0.05, AAPC: − 2.0, CI: − 2.2 to – 1.8; p< 0.05, respectively). Between 1980 and 1993, OC incidence initially increased and then stabilized (AAPC: 0.9; CI: 0.7 to 1.1; p< 0.05). After 2007, OC mortality decreased (AAPC: 0.0; CI: − 0.2 to 0.2; p=0.8). Trends in VUC and VAC incidence and BC mortality were not statistically significant.Conclusion: The results of this study showed a significant increase in OC, CUC, and BC incidence, and a decrease in the incidence of CC and VAC. The VUC trends were stable. Mortality trends for BC initially fluctuated and, since 2010, has begun to increase. Throughout the observed period, mortality due to VUC and CUC increased, whereas decreased among patients with CC. OC mortality was stable, but not significant. Furthermore, the study showed a correlation between age group and rate of incidence and mortality of each assessed cancer.Keywords: gynecological cancers, breast cancer, incidence, mortality, average annual percentage change

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-in&fllig;ammation 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

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.

Background: In Poland, breast cancer (BC) is the most frequently diagnosed cancer in women and the second most common cause of death after lung cancer. This disease has important economic implications for patients, public payers, and the whole Polish economy. This study aimed to estimate the total National Health Fund (NHF) expenditures on the diagnosis and treatment of patients with breast cancer. In addition, the costs of productivity losses were also calculated., Methods: Cost estimation was prepared using a top-down approach. Direct cost calculations were based on data reported by NHF for patients with the diagnosis of breast cancer. Medical care costs included the following components: screening program, oncological package, surgical treatment, hospitalization, drug program, chemotherapy, radiotherapy, and outpatient care. Indirect costs in the form of absenteeism costs were calculated based on data from Statistics Poland (gross domestic product, number of employees) and the Social Insurance Institution database (the number of sick leave days)., Results: Total expenditures for BC including direct costs and indirect costs amounted to EUR 305,371, EUR 332,998, and EUR 344,649, respectively in 2017, 2018, and 2019. Total healthcare costs in 2019 were EUR 4114 lower than in 2018, which resulted from the reduction in expenditure on the drug program (decrease of EUR 13,527), despite the observed increase in all remaining resources. From direct costs, the highest expense was spent on the drug program (nearly 50% of total direct costs), but this expense dropped significantly in 2019. For the remaining parameters, the costs increased year by year, of which the most expensive were surgical treatment (15%), radiotherapy (12%), and the screening program (10%). BC generated over EUR 120 thousand of social costs in 2019 and compared to 2017, there was an increase in productivity loss by 26%., Conclusions: Our results from 2017-2019 demonstrated that total expenditure for BC in Poland increased from year to year. Breast cancer generated almost EUR 345 thousand expenses in 2019, which translates into a significant burden on the public payer's budget and the society in Poland.

Background: Liver resections have become the first-line treatment for primary malignant tumors and, therefore, are considered a core aspect of surgical training. This study aims to evaluate the learning curve for the safety of open hemihepatectomy procedures for patients suffering from hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICC)., Methods: This single tertiary center retrospective analysis includes 81 consecutive cases of right or left hemihepatectmy. A cumulative sum (CUSUM) control chart was used to investigate the learning curve., Results: The CUSUM curve for operative time and blood loss level peaked at the 29th and 30th case, respectively. The CUSUM curve for minor adverse effects (mAEs) and severe adverse effects (sAEs) showed a downward slope after the 27th and 36th procedures; the curve, however, remained within the acceptable range throughout the entire study., Conclusion: When performing open hemihepatectomies in patients with HCC and ICC, the stabilization of the operative time and intraoperative blood loss level are gained earlier than sAEs risk reduction.

Background: Inpatient falls are common hospital adverse events. We aimed to determine inpatient fall rates in an urban public hospital and analyzed their characteristics across clinical departments., Methods: The study was conducted in a 350-bed urban, multi-specialty public hospital in the 2013-2019 period. Patient data were retrieved from the hospital's standardized falls reporting system. Descriptive statistics and statistical tests: chi2 and ANOVA tests with multiple comparison tests (post-hoc analysis) were used. For fall incidence estimation a joint-point regression was applied. p -value of 0.05 was considered as statistically significant for all the calculations., Results: The highest prevalence of falls was reported in the rehabilitation and internal medicine wards (1.915% and 1.181%, respectively), the lowest in the orthopedic (0.145%) and rheumatology wards (0.213%) ( p < 0.001). The vast majority of falls took place in the late evening and during the night (56.711%) and were classified as bed falls (55.858%). The crude incidence rate (cIR) of falls was 6.484 per one thousand hospitalizations. In the 2013-2017 period, an increase in total cIR was observed, reaching the peak value in 2016; it was followed by a slight decline from 2017 to 2019, however, differences in changes were observed between the wards., Conclusion: Fall rates and trends as well as circumstances of inpatient falls varied significantly among clinical departments, probably due to differences in patient characteristics., Competing Interests: The authors declare no conflicts of interest.

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.)

Introduction and Objective: Lymph node involvement is a strong predictor of disease recurrence and patient survival in vulvar cancer. The aim of the study was to evaluate the feasibility of sentinel lymph node (SLN) screening, the incidence of skip metastases, and lymph node lymphangiogenesis., Material and Methods: Fifty-five patients participated in this prospective, single centre study. A double SLN screening method was employed using radiocolloid (technetium-99 sulfur colloid) and 1.0% Isosulfan Blue. Immunohistochemistry, using a mouse monoclonal antibody against D2-40, was used to evaluate lymphatic vessel density (LVD). All calculations were performed using STATISTICA software v. 10 (StatSoft, USA, 2011); p < 0.05 was considered significant., Results: Using both methods of SLN detection, 100% accuracy was achieved, and skip metastases were diagnosed in only one woman (1.82%). Peri-tumour median LVD was significantly increased compared with matched intra-tumour samples (p < 0.001), while median LVD was significantly lower in negative, compared with positive SLN, regardless of whether matched non-SLN were negative (p < 0.001) or positive (p = 0.005). Metastatic SLN exhibited significantly higher median LVD compared with matched negative non-SLN (p = 0.015), while no significant difference in median LVD was detected between positive SLN and matched positive non-SLN. However, negative SLN had a significantly higher median LVD compared with matched negative non-SLN (p = 0.012)., Conclusions: SLN detection is a safe and feasible procedure in vulvar cancer. In patients without nodular involvement, SLN, compared with non-SLN, exhibited significantly higher median LVD, which may be an indication of its preparation to host metastases, and thus requires further investigation.

Introduction: Ability to work is most often defined as a relationship between a person's resources and requirements specific to a particular type of work. It is the result of interaction between job requirements in terms of physical and mental strain, capabilities and skills of the employee, as well as his/her health condition and own evaluation of functioning in a given organizational and social situation., Objective: The primary objective of the study was to evaluate the current value of the Work Ability Index (WAI) in a sample of employees in Poland., Material and Methods: The study sample was selected purposefully from 422,000 employees covered by the largest occupational health provider in Poland. The standard WAI questionnaire provided by CAWI (Computer-Assisted Web Interview) methodology was voluntary and completed anonymously by 688 employees within 12 months (0.16% response rate). The results were statistically analyzed using the Pearson's chi-squared test and correlation coefficient, independent-sample T test and one-way analysis of variance (p<0.05)., Results: It was found that the average value of WAI was 37.5 ± 7.7, and 37% of the participants represented low to moderate ability to work. The results showed no significant correlation between the WAI value and its 7 compounds and demographic variables. Nonetheless, a dependency between WAI level and industrial branch was observed., Conclusions: Subjects with moderate and low WAI (1/3 of the study population) had particular indications to implement prophylactic actions, especially for the health care employees and civil servants, whose ability to work may be subject to accelerated deterioration.

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.

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: 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: Expression of SOX-2 and Oct4 as markers for the identification of cancer stem cells (CSCs) has been revealed in several malignancies. In this study, the co-expression of SOX-2 and Oct4 and their correlation with clinicopathological features of endometrial adenocarcinomas (EACs) was investigated., Methods: SOX-2 and Oct4 expression was assessed by immunohistochemistry in 27 (39.13%) stage IA and in 42 (60.87%) stage IB International Federation of Gynaecology and Obstetrics (FIGO) EACs and related to the clinicopathological features of patients., Results: The expression of SOX-2 was confirmed in 62/69 tumour specimens compared to Oct4 expression in 46/69 specimens (P = 0.015) and no difference in median staining intensity between SOX-2 and Oct-4 was observed. The highest median SOX-2 expression was found in high-grade (G3) EAC samples compared to moderate-grade (G2) EAC specimens (P = 0.020) and low-grade (G1) specimens (P = 0.008), while no differences in median Oct4 expression in EAC samples according to grading were present. In G3 specimens, significantly higher median SOX-2 expression was noted compared to Oct4 (P = 0.002). SOX-2 and Oct4 co-expression was observed only in G1 EAC (R: 0.51; P = 0.031). Age of EAC diagnosis was positively correlated with SOX-2 expression (b = 0.193; R(2) = 10.83%; P = 0.003) but not to age of menarche, menopause, parity or body mass index., Conclusions: There is no need to use SOX-2 expression as a poor outcome predictor in stage I EAC, and SOX-2 expression should be analysed in more advanced stages.

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.)

Study Objective: To predict the 1-step complete resection rate after transrectal ultrasound-guided hysteroscopic myomectomy and to determine the usefulness of intraoperative transrectal ultrasonography (TRUS) in monitoring hysteroscopic electroresection of submucosal myomas., Design: Prospective cohort study (Canadian Task Force classification II-1)., Setting: University hospital., Patients: One hundred twenty women with symptomatic (abnormal uterine bleeding or reproductive disorder), single, submucosal myomas underwent hysteroscopic electroresection. Groups 1 and 2 were monitored, respectively, with or without TRUS. Anatomical inclusion criteria were myoma ≤5 cm and myometrial free margin ≥3 mm above the myoma., Interventions: Myomas were evaluated preoperatively via sonohysterograpy and were graded according to the guidelines outlined by the European Society of Hysteroscopy (ESH), including size and myometrial free margin, and according to the STEPW (size, topography, extension, penetration, and lateral wall) classification. On the basis of sonographic findings, patients with myomas >3 cm received gonadotropin-releasing hormone therapy for 1 to 3 months. Hysteroscopic myomectomy was performed with or without TRUS guidance. At 4 to 8 weeks after the initial procedure, postoperative transvaginal ultrasonography, sonohysterography, or second-look hysteroscopy was performed., Measurements and Main Results: In the TRUS group, a significantly higher percentage of 1-step complete resections was observed than in the group without TRUS (91% vs 73%) (p = .02). This was associated with a statistically significant difference in the subgroups of myomas that were deeply penetrating into the myometrium (89% vs 55%) (p < .01). One-way logistic analysis of data for all treated patients indicated the use of TRUS, as well as the ESH and STEPW classifications, as significant factors influencing the 1-step complete resection. At multivariable logistic regression analysis, use of TRUS (odds ratio [OR], 2.74; p < .001), myomas graded 0 or 1 according to ESH (OR, 3.55; p < .001), and size <3 cm (OR, 2.35; p < .05) were significantly associated with 1-step complete resection (area under the curve, 0.80; p < .001). In the TRUS group there were two significant predictors: size <3 cm (OR = 5.21; p < .05) and myometrial free margin <5 mm (OR, 0.18; p < .05)., Conclusion: Intraoperative use of TRUS during hysteroscopic myomectomy increases the chance of complete 1-step removal of submucosal myomas that deeply penetrate the myometrium., (Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.)

Study Objective: To estimate the diagnostic accuracy and to compare the diagnostic value of 3-dimensional sonohysterography (3D-SIS), 3-dimensional transvaginal ultrasonography (3D-TVS), 2-dimensional sonohysterography (2D-SIS), and 2-dimensional transvaginal ultrasonography (2D-TVS) (initial and expert diagnosis) in the differential diagnosis of septate, bicornuate, and arcuate uteri., Design: Prospective clinical study (Canadian Task Force II-2)., Setting: University hospital and private hospital and clinic., Patients: A total of 117 women with a history of recurrent abortions or infertility and a 2D-TVS initial diagnosis of a septate, bicornuate, or arcuate uterus., Interventions: Expert 2D-TVS, 3D-TVS, 2D-SIS, and 3D-SIS performed by experienced examiners and hysteroscopy with laparoscopy to establish the final diagnosis., Measurements and Main Results: Hysteroscopy performed in conjunction with laparoscopy (HL) detected 23 arcuate, 60 septate, 22 bicornuate, and 12 normal uteri. 3D-SIS showed perfect diagnostic accuracy (100.0%) in general detection of uterine abnormalities, compared with initial 2D-TVS (77.8%), expert 2D-TVS (90.6%), 2D-SIS (94.0%), and 3D-TVS (97.4%). In the overall diagnosis of uterine anomalies, all of the diagnostic methods had statistically significantly better diagnostic value than initial 2D-TVS (p < .001), whereas 3D-SIS was the only method that was better than expert 2D-TVS (p < .001)., Conclusions: Although 3D-SIS was identical to HL, with the highest accuracy, there was no significant difference in diagnostic value between 3D-TVS with 2D-SIS and 3D-SIS or between expert 2D-TVS and 3D-TVS with 2D-SIS. The high diagnostic value of these ultrasonographic tools questions the need for endoscopy in the differential diagnosis of the most common congenital uterine anomalies., (Copyright © 2013 AAGL. Published by Elsevier Inc. All rights reserved.)

Postprandial hypotension is the independent risk factor of general mortality, coronary disorders and stroke. It is reviewed risk factors, pathogenesis, symptoms, treatment and prognosis of this disease.

Background: Human endometrium undergoes cyclic structural and functional modifications, and if no conception occurs menstruation is observed as the result of endometrial cell apoptosis via DFF40/DFF45 complex activation. In postmenopausal endometrium, the proliferative potential of endometrial cells is decreased, while their susceptibility to apoptosis increases., Methods: The study group comprised 104 nonpregnant adult women (78 of reproductive age and 36 after menopause) with no neoplasm or hormonal treatment during the past 6 months. Immunohistochemistry and Western blot methods were used for DFF45 identification and semiquantitative assessment of its amount., Results: Significantly more DFF45-positive cells were detected in the endometrial glands compared to stroma, and this pattern was constant throughout the whole menstrual cycle and also present in postmenopausal endometrial species. The lowest mean relative amount of DFF45 was detected in postmenopausal endometrial samples. In women of reproductive age, the highest mean relative amount of DFF45 was identified in an early secretory phase of the menstrual cycle, the lowest median value of the relative amount of DFF45 was observed in the late proliferative phase, and the difference was significant., Conclusion: The DFF45 level in human endometrium corresponds to the respective phase of the menstrual cycle and decreases significantly after menopause., (Copyright © 2012 S. Karger AG, Basel.)