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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.

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.

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.

Objectives DNA fragmentation factors 40 and 45 (DFF40 and DFF45) are responsible for final DNA-laddering during apoptosis, whereas Bcl-2 (B-cell lymphoma 2) is an apoptosis inhibitor. Our aim was to investigate the expression of DFF40, DFF45, and Bcl-2 in uterine leiomyosarcomas (uLMS), leiomyomas (uLM), and the normal myometrium. Furthermore, the correlation between DFF40, DFF45, and Bcl-2 expression and clinicopathological parameters in leiomyosarcomas was assessed. Their prognostic value in disease-free survival (DFS) and overall survival (OS) was also calculated. Materials and methods This study included 53 cases of uLMS from patients matched for age and menopausal status with 53 cases of uLM and 53 controls of normal myometrium (uM). Case samples of uterine myometrium from leiomyosarcomas (uLMS-M) and leiomyomas (uLM-M) were also studied. Immunohistochemical scoring was undertaken for DFF40, DFF45, and Bcl-2. Results DFF40, DFF45, and Bcl-2 were significantly underexpressed in uLMS compared with uLMS-M and uM. In uLMS samples, no correlation between the analyzed proteins was observed. Negative DFF40 and Bcl-2, but not DFF45, staining was a predictor of poorer DFS and OS in women with uLMS. uLM showed DFF40 and Bcl-2 overexpression compared with uM and uLM-M, with a significant positive correlation between DFF40 and DFF45. No differences in DFF40, DFF45, and Bcl-2 expression were observed between the uLMS-M, uLM-M, and uM samples, with a significant positive correlation between DFF40 and DFF45 expression. Conclusion DFF40, DFF45, and Bcl-2 are significantly underexpressed in uLMS, but only a lack of DFF40 and Bcl-2 negatively influences DFS and OS. Disruption of DFF40 and DFF45 expression was observed in uLMS, but not in uLM or control and case myometrium; this may play a role in tumor pathogenesis.

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.

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.

DNA fragmentation factors 40 and 45 (DFF40 and DFF45) and B-cell lymphoma 2 (Bcl-2) expression were evaluated in the normal human endometrium and myometrium. DFF40, DFF45, and Bcl-2 expression was assessed via immunohistochemistry in the proliferative, secretory, and atrophic endometrium and myometrium collected postmenopausally and premenopausally during the proliferative and secretory phases of the menstrual cycle. The endometrium showed significantly higher DFF40 and DFF45 expression than that in the uterine myometrium; compared to the stroma, endometrial glands showed the highest expression in pre- and postmenopausal specimens. Glandular expression of DFF45 was dependent on the menstrual cycle, reaching its highest level in the secretory endometrium. The glandular expression of DFF40 and DFF45 was significantly lower in postmenopausal specimens than that in premenopausal tissue. No cycle-dependent changes were reported for stromal or myometrial DFF40 or DFF45 expression. Compared to the endometrial stroma and myometrium, Bcl-2 showed the highest expression in the glandular proliferative endometrium and the lowest expression in the stromal secretory endometrium and myometrium during the secretory phase of the cycle. DFF45 and Bcl-2 showed menstrual cycle-dependent expression, which was limited to the glandular layer of the endometrium.

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.

Tomasz Banas,1 Grzegorz Juszczyk,2 Kazimierz Pitynski,1 Dorota Nieweglowska,1 Artur Ludwin,1 Aleksandra Czerw2 1Department of Gynecology and Oncology, Jagiellonian University Medical College, Krakow, 2Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland 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. Keywords: average annual percentage change, breast cancer, corpus uteri cancer, epidemiology, incidence, mortality, ovarian cancer

AIM To evaluate the diagnostic accuracy of sonohysterography (SHG), hysterosalpingography (HSG) and diagnostic hysteroscopy (DH) in uterine anomaly detection and to assess the role of these various modalities in the differential diagnosis of arcuate, septate and bicornuate uteri. METHODS Eighty-three women, with a history of recurrent spontaneous abortions or infertility and initial diagnosis of uterine anomaly were included in the study. Diagnostic work-up comprised of SHG, HSG and DH. To assess the accuracy of these methods all the patients underwent hysterolaparoscopy to establish the final diagnosis. The correlation between the results of each method was evaluated and diagnostic accuracy of each method was assessed in the whole group of women as well as in subgroups of arcuate, septate and bicornuate uteri using receiver operator curve (ROC) method by estimating the area under the curve (AUC). RESULTS In the overall diagnosis of uterine anomalies, SHG with accuracy of 95.2% and correlation index of 0.873 (P < 0.001) proved to be a significantly better tool compared to DH (SHG(AUC) = 0.924 versus DH(AUC) = 0.761 P = 0.008), while no significant differences were observed between SHG versus HSG and DH versus HSG. SHG showed significantly higher accuracy (100.0%) compared to DH (80.7%) and HSG (80.7%) in differentiation of a septate (SHG(AUC) = 1.000 versus DH(AUC) = 0.816 P < 0.001 and SHG(AUC) = 1.000 versus HSG(ACC) = 0.818; P < 0.001) and bicornuate uterus (SGH(AUC) = 1.000 versus DH(ACC) = 0.707; P < 0.001 and SHG(ACC) = 1.000 versus HSG(AUC) = 0.790; P = 0.002). CONCLUSION SHG is a noninvasive, cost-effective method available in an outpatient setting that is highly accurate in identifying uterine anomalies, in particular septate and bicornuate uterus.

Objective: Endometriosis, defined as a spread of endometrium outside the uterus cavity, affects up to 30% women of reproductive age, with the ovaries being its most common localization. In the ectopic lesions, endometrial cells show abnormal proliferation and impaired apoptosis. The DNA destruction during apoptosis is a direct result of activation of the DFF40/DFF45 complex. DFF40 (DNA fragmentation factor of 40 kDa) is responsible for direct DNA fragmentation while DFF45 (DNA fragmentation factor of 45 kDa) acts not only as a DFF40 inhibitor, but also as its chaperone. Therefore, the presence of DFF45 is required for proper DFF40 synthesis. The aim of this study was to determine the DFF45 level in human ovarian endometriosis. Study design: The endometriosis samples were collected from 43 affected women, while the 81 normal endometrial specimens were obtained from the control group. Western blot and immunohistochemistry tests were used to determine the DFF45 level in examined tissues. Results: The expression of DFF45 in normal human endometrium and ovarian endometriosis was confirmed using both the Western blot and the immunohistochemistry tests. In normal eutopic proliferatory endometrium, a lower DFF45 expression was observed compared with secretory endometrium, while no cyclic changes in DFF45 expression were observed in the ovarian endometriomas. In the normal eutopic endometrium, stronger DFF45 staining was noted in the endometrial glands in comparison to the stroma, irrespective of menstrual cycle phase. However, in the ovarian endometriosis no difference between the glandular layer and stroma in DFF45 immunoreactivity was appreciated. The lowest level of DFF45 was observed in ovarian endometriosis when compared with both normal eutopic proliferatory and secretory endometria using the Western blot and immunohistochemistry analysis. Conclusions: A decreased level of DFF45 observed in ovarian endometriosis may be a part of an apoptosis-resistant mechanism enhancing the disease progression.

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

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.

Laparoscopic myomectomy (LM) is a recently developed surgical technique, and every obstetrician should be aware of its possible complications, which can occur not only during labor but also during pregnancy. We report a case of a primigravid woman who was hospitalized at 35 weeks' gestation because of irregular abdominal pain. She conceived spontaneously 3 years after LM. After a 20-h stay on the obstetrician ward due to increased abdominal tenderness and vaginal bleeding, the patient was qualified for an emergency cesarean section without any symptoms of fetal distress in cardiotocography. During cesarean section a newborn with 9 Apgar points was delivered and a rupture of the uterine wall was seen. Dehiscence of the pregnant uterus following LM is an incidental case, and can therefore be misdiagnosed. Close attention should be paid to every pregnancy in previously operated uteri as the dehiscence of the pregnant uterus can occur without symptoms of fetal distress.

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.

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.

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.Prospective cohort study (Canadian Task Force classification II-1).University hospital.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.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 myomas3 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.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 size3 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: size3 cm (OR = 5.21; p.05) and myometrial free margin5 mm (OR, 0.18; p.05).Intraoperative use of TRUS during hysteroscopic myomectomy increases the chance of complete 1-step removal of submucosal myomas that deeply penetrate the myometrium.

There is considerable controversy regarding the possible over-treatment of patients with mild Cervical Intraepithelial Neoplasia (CIN), with lesions being often excised or ablated. Thus, identifying the markers of potentially malignant lesions would be of a great prognostic value. In the current study, we hypothesized that using colposcopic, cytological and histological findings together with assessing the expression of molecular growth factors can predict CIN outcome. The study group consisted of 285 women between 19 and 81 years of age (median age, 37,8 years). The follow up were 60 months and considered 138 women: 50 women with Subclinical Papillomavirus Infection (SPI), 50 women with CIN1 and 38 women with CIN2. All patients underwent cytology, colposcopy, and sampling for subsequent testing for HPV. In cases in which colposcopy suggested the presence of suspicious lesions, biopsy specimens were taken. HPV DNA was genotyped for HPV types 16, 18, 31, 33, and 45 by multiplex PCR. Transcripts of HR HPV types 16, 18, 31, 33, and 45 were detected by the NucliSens EasyQ HPV assay. The VEGF expression was analyzed with immunohistochemistry, RNA extraction, cDNA synthesis and RT-PCR analysis and Western blot. We found that so called lymphangiogenetic switch (over expression of VEGF C and VEGFR-2) appears already in CIN 2, which is a rare observation, Persistent HPV HR infection is not only a trigger but also a maintenance factor in the cervical carcinogenesis. CIN2/3 and cervical cancer is in high percentage associated with the presence of HR DNA HPV as well as E6/E7 DNA mRNA. In CIN2/3 and cervical cancer VEGF and its receptor expression correlate with the stage of cervical carcinogenesis. Progression of cervical intraepithelial neoplasia occurs when co expression of all: HR DNA HPV, E6/E7 HR HPV mRNA and VEGF is present.

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 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.

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.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.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.The DFF45 level in human endometrium corresponds to the respective phase of the menstrual cycle and decreases significantly after menopause.

Background The coexistence of endometrial and immune cells during decidualization is preserved by the ability of endometrial cells to regulate the cytotoxic immune activity and their capability to be resistant to immune-mediated apoptosis. These phenomena enable the survival of endometrial ectopic cells. RCAS1 is responsible for regulation of cytotoxic activity. Metallothionein expression seems to protect endometrial cells against apoptosis. The aim of the present study was to evaluate RCAS1 and metallothionein expression in human ovarian and scar endometriomas in relation to the presence of immune cells and their activity. Methods Metallothionein, RCAS1, CD25, CD69, CD56, CD16, CD68 antigen expression was assessed by immunohistochemistry in ovarian and scar endometriomas tissue samples which were obtained from 33 patients. The secretory endometrium was used as a control group (15 patients). Results The lowest metallothionein expression was revealed in ovarian endometriomas in comparison to scar endometriomas and to the control group. RCAS1 expression was at the highest level in the secretory endometrium and it was at comparable levels in ovarian and scar endometriomas. Similarly, the number of CD56-positive cells was lower in scar and ovarian endometriomas than in the secretory endometrium. The highest number of macrophages was found in ovarian endometriomas. RCAS1-positive macrophages were observed only in ovarian endometriomas. CD25 and CD69 antigen expression was higher in scar and ovarian endometriomas than in the control group. Conclusion The expression of RCAS1 and metallothionein by endometrial cells may favor the persistence of these cells in ectopic localization both in scar following cesarean section and in ovarian endometriosis.

Introduction: The participation of immune tolerance during pregnancy was suggested to be an important factor predisposing to the implantation of decidual cells after cesarean section in Pfannenstiel scar. Delivery at term is related to the termination of immune tolerance to fetal antigens that is maintained throughout pregnancy. Substantial proportion of cesarean section deliveries is performed before the onset of true term labor. The aim of this study was to analyze the clinical symptoms of spontaneous beginning of labor in pregnant women in whom cesarean sections were performed and in whom Pfannenstiel scar endometriomas were observed during follow-up. Materials and Methods: We have retrospectively analyzed 81 patients following the surgical removal of scar endometrioma after cesarean section. Obstetrical histories of cesarean sections in the number of 5,370 preceding the occurrence of the scar endometrioma were analyzed. These data were collected in six different Gynecological and Obstetrical wards in Malopolska Province in Poland. Analysis of data was started by the retrospective evaluation of regular uterine contractions, uterine cervix ripening before cesarean section and the indications for surgery. Results: In 67 women from the group of 81 patients cesarean sections were performed with unripe uterine cervix and without the presence of regular uterine contractions. Elective indications for cesarean sections were predominant in this group of women. The relative risk of scar endometriomas occurrence following cesarean sections performed before onset of labor in comparison to cesarean sections following spontaneous onset of labor was statistically significantly higher [RR = 2.16, 95% CI = 1.21–3.83; OR = 2.18, 95% CI = 1.22–3.89]. Conclusions: Cesarean section performed before spontaneous onset of labor may increase substantially the risk of occurrence of scar endometriomas.

Hemocidins are a novel class of antibacterial peptides generated proteolytically from hemoglobin. These peptides play a particularly important role in maintaining vaginal homeostasis during menstrual bleeding. To investigate the hemoglobin fragmentation process during the last stages of pregnancy, we examined uterine secretion (lochia) samples from a group of 22 healthy women who underwent cesarean delivery at term. Patients were divided into three groups: (I) the elective cesarean deliveries without symptoms of spontaneous labor, (2) the nonelective cesarean deliveries with spontaneous beginning of labor, and (3) the nonelective cesarean deliveries during advanced labor. The samples were subjected to chromatographic estimation of free hemoglobin and peptides. In three representative patients the identification of all lochial peptides was performed. All samples contained a significant amount of free hemoglobin and its level increased with labor progression. The presence of peptide fractions was also detected in most lochia samples. They were confirmed to be human hemoglobin fragments, almost identical to the recently described bactericidal hemocidins from menstrual discharge. The level of peptides also increased during labor. The subgroup with advanced labor demonstrated the highest amount of hemocidins. The presented results prove that proteolysis of free hemoglobin in the female upper reproductive tract begins together with the clinical symptoms of normal labor. We speculate that cesarean delivery affects molecular mechanisms involved in antibacterial hemocidins generation and, in effect, might be responsible for the increased risk of gynecologic infections in cesarean deliveries.

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.Prospective observational study.University hospital, private hospital, and clinic.One hundred forty-one women undergoing HM for septate uterus with a history of miscarriage and/or infertility.3D-SIS and office hysteroscopy at 6-8 weeks after HM.Shape of the uterine cavity, length of the fundal notch (≥1 or1 cm), and the presence of intrauterine adhesions were assessed, and the interrater/intrarater agreement of 3D-SIS was evaluated in 30 randomly selected patients.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).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.

Objectives: To evaluate the diagnostic accuracy of 3D-SIS, 3D-TVS, 2D-TVS (initial TVS diagnosis and an expert TVS) and 2D-SIS in the differential diagnosis of septate, bicornuate and arcuate uteri. Methods: 117 women with recurrent abortion or infertility and 2D-TVS initial diagnosis of septate, bicornuate or arcuate uterus were included in the study. Diagnostics work-up comprised of initial 2D-TVS diagnosis, followed by 2D-TVS performed by an experienced examiners, 3D-TVS, 2D-SIS and 3D-SIS. In order to assess the accuracy of these methods all the patients underwent hysterolaparoscopy (HL) to establish the final diagnosis. The correlation between the results of each method was evaluated and diagnostic accuracy of each method was assessed in the whole group of women as well as in the subgroups of arcuate, septate and bicornuate uteri using receiver operator curves (ROC) method by estimating the area under the curve (AUC). Results: The 3D-SIS was found to be the best diagnostic method with an exact agreement with HL-obtained diagnosis. Other tools had a lower positive correlation (gamma index 3D-TVS: 0.93; 2D-SIS: 0.89, 2D-TVS by expert user: 0.77; and initial 2D-TVS: 0.48; all statistically significant, P < 0.001). All techniques, except initial 2DTVS diagnosis, were found to have the highest (100%) accuracy, sensitivity and specificity in detection of bicornuate uterus cases. Both 2D-SIS and 3D-SIS were found to be better tools in detection of septate uterus (ACC 100%). They were followed by 3D-USG (ACC 97.5%). In diagnosis of arcuate uterus, after 3D-SIS,the 3D-TVS was found to have the highest accuracy (96.2%). Conclusions: 3D-SIS is the most accurate differentiation method of septate, bicornuate and arcuate uterus. It should be used in cases of ambiguous 3D-TVS results. 2D-SIS is comparable to 3D-SIS in differentiation of septate uterus with bicornuate uterus and it may be used in order to verify 2D-TVS results that depend on the investigator’s experience, especially when the access to 3D-imaging technology is restricted.