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Ovarian cancer is one of the most common gynecological cancers diagnosed in pregnancy. Its management is often very problematic due to the proximity of the adnexa to the developing fetus and chemotherapy-related toxicity risk. Tumor markers and imagining studies play important roles in diagnosis, help differentiate benign masses from malignancy and allow to plan the treatment. Due to the physiological changes that occur in pregnancy, levels of tumor markers can be altered and reduce their diagnostic value. We review current recommendations for the management and treatment of ovarian cancer in pregnant patients considering gestational age at diagnosis, tumor histology, stage of the disease, risk of obstetrical complications, and patient's preferences., Competing Interests: The authors report no conflicts of interest for this work., (© 2021 Michalczyk and Cymbaluk-Płoska.)

Chemo- and radio-therapy can often affect reproductive organs impairing hormonal regulation, fertility, and sexual function. As cancer treatments become more effective and many patients have long term survival, concerns related to patient's quality of life and reproductive health become relevant. It is especially important for girls and young females facing cancer therapy who have not yet started family planning. Chemotherapy protocols using alkylating agents and abdominal radiotherapy, which are frequently used in the treatment of childhood and adolescent cancer, can cause gonadal injury. The most common clinical manifests are ovarian hormone insufficiency, premature ovarian insufficiency, early menopause and infertility. In this review we assess current literature and summarize current recommendations on the reproductive function of girls and young females undergoing cancer treatment and their follow-up. Fertility preservation methods are discussed, including psychological and ethical considerations and barriers. Improvement of reproductive health and quality of life of adolescents and young adults (AYA) undergoing cancer treatment is an important issue. Further research should be continued to develop efficient and accessible methods for fertility preservation in young patients. An expert panel including oncologists, radiation oncologists, endocrinologists and gynecologists should always consider fertility preservation in pediatric, adolescent and AYA cancer patients, minding patients' medical condition, cancer staging and potential risk of treatment-related gonadotoxicity.

(1) Background: The prevalence of complementary and alternative methods (CAM) use among oncological patients has been rising constantly over the last few decades and a variety of both pharmacological and non-pharmacological methods have been developed. Many advertisements promise to relieve side effects of chemotherapy or even to cure the disease, thus encouraging patients to use CAM; (2) Methods: The objective of the study was to determine which patients' characteristics are associated with the use of complementary medicine during cancer treatment, their pattern of use, and if it has any association with its safety profile. This survey-based prospective multicenter study of 316 patients examined the use of complementary medicine among patients undergoing chemotherapy treatment in cancer centers in Poland between 2017 and 2019; (3) Results: The Chi2 analysis showed that patients' opinion regarding the safety of unconventional methods is related to the use of CAM ( p = 0.00147). Moreover, patients' thinking that alternative medicine can replace traditional therapy was correlated with his/her education ( p = 0.01198). Moreover, we performed univariate and multivariate analysis to determine factors associated with CAM use including sociodemographic and clinical characteristics. Finally, we conducted survival analysis of patients undergoing chemotherapy treatment with 42 months of follow-up time of our prospective study. Using Kaplan-Meier curves and log-rank analysis, we found no statistical difference in overall survival between the groups that used and did not use any form of CAM ( p = 0.211); (4) Conclusions: CAM use is common among patients undergoing chemotherapy treatment and should be considered by medical teams as some agents may interact with chemotherapy drugs and affect their efficacy or cause adverse effects.

Prematurity has been one of the greatest challenges faced by perinatal medicine for many years. The recommended therapy for women with threatened preterm labor at 24 to 34 weeks' gestation is a single course of glucocorticoids. The greatest benefits have been proven when labor occurs at least 24 hours, but no later than 7 days after steroid administration. Applied treatment is not without influence on neonates' development., Aim: The aim of this study is to analyze the time between the administration of a course of glucocorticoids to patients with threatened preterm labor between 24 and 34 weeks of gestation and labor., Materials and Methods: 459 deliveries by patients between 24 and 34 weeks' gestation who had received betamethasone (two 12 mg doses) or dexamethasone (four 6 mg doses) were analyzed. Their indications for glucocorticoid therapy were divided into four categories: the signs of threatened preterm labor, premature rupture of membranes, iatrogenic prematurity and cervical incompetence. The neonates (n=530) were divided into two main groups: group 1 of those born within the first 7 days (n1=127) and group 2 of those born more than 7 days (n2=403) after the glucocorticoids therapy. Statistical analysis was performed using the Statistica 13.3 software with calculations performed using the Mann- Whitney U and χ2 tests, assuming the level of statistical significance of <0.05 (p<0.05)., Results: The neonates born within the first 7 days after the glucocorticoid therapy accounted for 23.96% (127 children). The average time of delay between the course of glucocorticoids and labor was 33 days, with the longest interval being 116 days. The most common indications for glucocorticoids were iatrogenic causes in group 1 (35.40%) and the signs of threatened preterm labor (67.63%) in group 2., Conclusions: The percentage of births at the recommended time after steroidotherapy (not later than 7 days) was lower than expected. The prenatal steroid therapy qualification methods, should be reanalyzed, especially when signs of preterm labor are observed., (© 2020 MEDPRESS.)

Zinc (Zn) and copper (Cu) are essential microelements, which take part in cellular metabolism, feature in enzymatic systems, and regulate enzyme activity. Homeostasis of these micronutrients is tightly regulated by multiple compensatory mechanisms that balance their concentrations including transporters, importers, and metallothioneins. An altered intake of only one of these trace elements may cause an imbalance in their levels and result in their competition for absorption. Relatively low levels of zinc and increased levels of copper may result in an increased level of oxidative stress and impair the antioxidant properties of multiple enzymes. Altered levels of trace elements were discovered in various pathologies including immunological, degenerative, and inflammatory diseases. Moreover, due to the role of Zn and Cu in oxidative stress and chronic inflammation, they were found to influence cancerogenesis. We review the roles of zinc and copper and their mechanisms in tumor growth, metastasis potential, microenvironment remodeling, and drug resistance. We highlight their role as potential biomarkers for cancer diagnosis, treatment, and prognosis, concentrating on their impact on gynecological malignancies.

(1) Background: Disorders of sexual life negatively impact self-esteem and social relationships. This problem affects patients after gynecological surgery. Providing access to specialist sexologist care constitutes an important aspect of support for this patient group. (2) Objective: The aim of the study was to assess the sexual life of women depending on the time since surgery, extent of gynecological surgery and postoperative chemotherapy and/or radiotherapy. (3) Methods: The study included 136 patients from gynecological outpatient clinics in Szczecin, Poland. The women answered questions from a special three-part questionnaire. Participation was anonymous and voluntary. The data obtained in the survey were subject to statistical analysis. (4) Results: Among patients with a sparing of the cervix, most have never or almost never experienced discomfort or pain during intercourse, and believe that the quality of their sex life has not deteriorated after surgery. It was found that cervical removal, despite the existence of other conditions, increases the chance of pain during sexual activity 11 times. We found that the removal of adnexa did not increase the risk of changing sexual activity. In patients who had not undergone postoperative chemo- and/or radiotherapy, sexual activity did not change after surgery, and they never or almost never experienced discomfort or pain during intercourse. On the other hand, it was shown, despite the smaller study group, that patients treated with postoperative chemo- and/or radiotherapy did not initiate sexual intercourse. (5) Conclusion: The more extended the gynecological surgery of the uterus, the greater the limitation of sexual life.

Psoriatic arthritis (PsA) is a chronic, progressive, inflammatory arthropathy associated with psoriasis as well as a complex pathogenesis. Genetic and environmental factors trigger the development of the immune-mediated auto-inflammatory response in different sites: skin, bone marrow, entheses and synovial tissues. Studies of the last two decades have changed the view of PsA from a mild, non-progressive arthritis to an inflammatory systemic disease with serious health consequences, not only associated with joint dysfunction, but also with an increased risk of cardiovascular disease and socioeconomic consequences with significantly reduced quality of life. The joint damage starts early in the course of the disease, thus early recognition and treatment with modern biological treatments, which may modify the natural history and slow down progression of this debilitating disease, is essential for the patient long-term outcome., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Termedia.)

Background: Herlyn-Werner-Wunderlich Syndrome is a rare malformation syndrome characterized by uterus didelphys with obstructed hemivagina and ipsilateral renal agenesis. Symptoms appear most often after menarche and are secondary to hematocolpos. We compare clinical symptoms, diagnosis and treatment of two patients, a 13-year-old and a 17-year-old., Case Report: Despite the non-uniform clinical symptoms, it should be noted that in both patients, the 13-year-old and the 17-year-old, hematocolpos, which was probably the cause of lower abdominal pain, was diagnosed with ultrasound. The diagnosis was complemented by laparoscopy, which determined the diagnosis of malformation of uterus didelphys with obstructed hemivagina. The patients had a history of kidney agenesis, which, after gynecological diagnosis, turned out to be ipsilateral. In the 13-year-old, agenesis was diagnosed by uroscintigraphy, while in the 17-year-old it was diagnosed by urography. Incision and drainage of the residual vagina was performed in the course of therapeutic management. In both cases, the clinical situation required a repeated widening of the orifice., Conclusions: Lower abdominal pain accompanying hematocolpos suggested Herlyn-Werner-Wunderlich Syndrome (HWWS) as the cause of symptoms. 3D transvaginal ultrasound enabled the determination of a congenital uterine defect with high probability, although inconclusive cases required confirmation by laparoscopy. Incision of the blocked vagina and drainage of hematocolpos were the key components of treatment. The treatment of HWWS is a multi-step process.

The activity of an allosteric agonist of muscarinic M 1 receptor, VU0357017, and a positive allosteric modulator (PAM) of M 5 receptor, VU0238429, were investigated alone or in combination with the mGlu 2 receptor PAM, LY487379 using the following behavioural tests: prepulse inhibition (PPI), novel object recognition (NOR), and spatial delayed alternation (SDA). VU0357017 (10 and 20 mg/kg) and VU0238429 (5 and 10 mg/kg) reversed deficits in PPI while VU0238429 (2.5 and 5 mg/kg) was effective in SDA. The simultaneous administration of subeffective doses of M 1 or M 5 activators (5, 1, or 0.25 mg/kg) with LY487379 (0.5 mg/kg) induced the same effect as that observed for the active dose of each compound. Selective M 1 or M 5 receptor blockers antagonized the effect exerted by these combinations, and pharmacokinetic studies confirmed independent transport through the blood-brain barrier. The expression of both receptors (M 1 and M 5 ) was established in brain structures involved in cognition (neocortex, hippocampus, and entorhinal cortex) in both the rat and the mouse brains by immunofluorescence staining. Specifically, double neuronal staining of mGlu 2 -M 1 and mGlu 2 -M 5 receptors was observed in many areas of the rat brain, while the number of double-stained mGlu 2 -M 1 receptors was moderate in the mouse brain with no mGlu 2 -M 5 colocalization. Finally, the combined administration of subeffective doses of the compounds did not alter prolactin levels or motor coordination, in contrast to the compounds given alone at the highest dose or in combination with standard neuroleptics., Competing Interests: Declaration of competing interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Galectin 3 is a modulator of several basic biological functions. It may be involved in the development of obesity and type 2 diabetes-risk factors of endometrial cancer. The study involved 144 patients, after abrasion due to postmenopausal bleeding. Galectin 3 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays. Median serum galectin 3 concentrations revealed significant differences between FIGO III and IV vs. FIGO I and II patients. Statistically higher concentrations were reported for patients with lymph node metastases compared to patients without it ( p = 0.001) as well as in patients with lymphovascular space invasion compared to patients without LVSI ( p = 0.02). No statistically significant differences were observed for median of galectin 3 levels depending on the surgical procedure (laparoscopy vs. laparotomy, p = 0.0608). Patients with galectin 3 levels exceeding the median value were characterized by overall survival being shorter by 11.9 months. High levels of galectin 3 were correlated with shorter disease-free survival, the difference is up to 14.8 months. Galectin 3 can be an independent prognostic factor in patients with endometrial cancer. Among the recognized prognostic factors and the concentrations of the galectin 3 marker at the adopted time points, the univariate analysis showed a significant effect of staging, grading, and cutoff galectin 3 on the OS. For multivariate analysis, the galectin 3 cutoff point had the greatest significant impact on OS.

Endometrial cancer is one of the most common cancers of the reproductive organ in women. The incidence of it increases from year to year. In our study we assessed role of FGF21 and FGF23 in the diagnostics of patients with endometrial cancer. The study involved 182 patients, who were undergoing abrasion due to perimenopausal bleeding. FGF21, FGF23, and leptin concentration were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation). The median of FGF21 protein (181.8 pg/mL) as well as leptin (16.9 ng/mL) in patients with endometrial cancer was statistically significant higher compared to median of those proteins among patients from control group (152.1 pg/mL and 14.1 ng/mL, respectively). However, no significant differences were found in these groups at median FGF23 concentrations. For FGF21 and leptin, the AUC values were 0.81/0.79, while FGF23, the AUC values was 0.66 for all study patients. Leptin and FGF21 concentrations were statistically significantly higher in patients with poorly differentiated G3 tumors compared to patients with moderately differentiated G2 tumors and with moderately differentiated G2 with highly differentiated G1 respectively: p = 0.02/ p = 0.03 and p = 0.02/ p = 0.005. FGF21 appears to be useful as a diagnostic as well as prognostic factor in patients with endometrioid endometrial carcinoma.

Psoriasis is a common, chronic, inflammatory, immune-mediated skin disease affecting about 2% of the world's population. According to current knowledge, psoriasis is a complex disease that involves various genes and environmental factors, such as stress, injuries, infections and certain medications. The chronic inflammation of psoriasis lesions develops upon epidermal infiltration, activation, and expansion of type 1 and type 17 Th cells. Despite the enormous progress in understanding the mechanisms that cause psoriasis, the target cells and antigens that drive pathogenic T cell responses in psoriatic lesions are still unproven and the autoimmune basis of psoriasis still remains hypothetical. However, since the identification of the Th17 cell subset, the IL-23/Th17 immune axis has been considered a key driver of psoriatic inflammation, which has led to the development of biologic agents that target crucial elements of this pathway. Here we present the current understanding of various aspects in psoriasis pathogenesis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2020 Termedia Sp. z o. o.)

Despite on-going medical advances, ovarian cancer survival rates have stagnated. In order to improve IP delivery of platinum-based antineoplastics, we aimed to develop a sustained drug delivery system for carboplatin (CPt). Toward this aim, we pursued a double emulsion process for obtaining CPt-loaded microcapsules composed of poly(ethylene terephthalate-ethylene dilinoleate) (PET-DLA) copolymer. We were able to obtain PET-DLA microspheres in the targeted size range of 10-25 µm (median: 18.5 µm), to reduce intraperitoneal clearance by phagocytosis and lymphoid transit. Empty microspheres showed the lack of toxicity in vitro. The double emulsion process yielded 2.5% w/w CPt loading and obtained microcapsules exhibited sustained (>20 day) zero-order release. The encapsulated CPt was confirmed to be bioavailable, as the microcapsules demonstrated efficacy against human ovarian adenocarcinoma (SK-OV-3) cells in vitro. Following intraperitoneal injection in mice, we did not observe adhesions, only mild, clinically-insignificant, local inflammatory response. Tissue platinum levels, monitored over 14 days using atomic absorption spectroscopy, revealed low burst and reduced systemic uptake (plasma, kidney), as compared to neat carboplatin injection. Overall, the results demonstrate the potential of the developed microencapsulation system for long-term intraperitoneal sustained release of carboplatin for the treatment of ovarian cancer.

Background Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) are used as markers of preeclampsia. The aim of this paper was to assess the correlations between the sFlt-1/PlGF ratio values within the <38, 38-85 and >85 brackets and perinatal outcomes in pregnancies that require determination of these markers. Methods A total of 927 pregnant patients between 18 and 41 weeks' gestation suspected of or confirmed with any form of placental insufficiency (preeclampsia, intrauterine growth restriction [IUGR], gestational hypertension, HELLP syndrome, placental abruption) were included in the study. In each of the patients, the sFlt-1/PlGF ratio was calculated. Patients were divided into three groups according to the sFlt-1/PlGF ratio brackets of <38, 38-85 and >85. Results Significantly worse perinatal outcomes were found in the sFlt-1/PlGF >85 group, primarily with lower cord blood pH, neonatal birth weight and shorter duration of gestation. Statistically significant correlations between the values of these markers and the abovementioned perinatal effects were found. Conclusion An sFlt-1/PlGF ratio value of >85 suggests that either preeclampsia or one of the other placental insufficiency forms may occur, which is associated with lower cord blood pH, newborn weight and earlier delivery. Determining the disordered angiogenesis markers and calculating the sFlt-1/PlGF ratio in pregnancies complicated by placental insufficiency may lead to better diagnosis, therapeutic decisions and better perinatal outcomes.

Negative and cognitive symptoms of schizophrenia contribute to an impaired social and professional life for schizophrenic patients, and in most cases, these symptoms are treatment resistant. Therefore, identification of new treatment strategies is sorely needed. Metabotropic glutamate receptors (mGlu) and muscarinic (M) receptors for acetylcholine have been considered promising targets for novel antipsychotics. Among them, mGlu 2 and M 4 subtypes seem to be of particular importance. In the present study, the effect of mutual activation of mGlu 2 and M 4 receptors was assessed in MK-801-based animal models of negative and cognitive symptoms of schizophrenia, that is, social interaction and novel object recognition tests. Low sub-effective doses of LY487379 (0.5 mg/kg), a positive allosteric activator of the mGlu 2 receptor, and VU152100 (0.25-0.5 mg/kg), a positive allosteric modulator of the M 4 receptor, were simultaneously administered in the aforementioned tests. Combined administration of these compounds prevented MK-801-induced disturbances in social interactions and object recognition when acutely administered 30 min before MK-801. Prolonged (7 days) administration of these compounds resulted in the loss of effectiveness in preventing MK-801-induced disruptions in the novel object recognition test but not in the social interaction test. In the next set of experiments, MK-801 (0.3 mg/kg) was administered for seven consecutive days, and the activity of the compounds was investigated on day eight, during which time MK-801 was not administered. In this model, based on prolonged MK-801 administration, the effectiveness of the compounds to treat MK-801-induced disruptions was evident at low doses which were ineffective in preventing the behavioural disturbances induced by an acute MK-801 injection. Combined administration of the compounds did not exert better efficacy than each compound given alone. Pharmacokinetic analysis confirmed a lack of possible drug-drug interactions after combined administration of LY487379 and VU152100. Our data show that modulation of M 4 and mGlu 2 receptors may potentially be beneficial in the treatment of negative and cognitive symptoms of schizophrenia.

Background: Since more than two decades Risk-reducing salpingo-oophorectomy (RRSO) is recommended and widely accepted by BRCA1/2 carriers as a method reducing ovarian cancer risk and improving survival rate. After RRSO, there remains a risk of breast cancer and peritoneal cancer. The characteristics of these neoplasms are not well known. In this study, we determined the selected parameters such as age at cancer diagnosis, time from RRSO to the diagnosis of cancer, and significance of BRCA1 mutation type in patients diagnosed with breast or peritoneal cancer during postoperative follow-up., Methods: The material comprised of 195 BRCA1 carriers who performed RRSO between years 1999-2012. In this period, 16 patients developed cancer (6-primary breast cancer, 3-contralateral breast cancer, 5-relapse of breast cancer, 2-peritoneal cancer). They were subject of the further analysis., Results: During the follow-up period mean age of patients after RRSO at the time of cancer diagnosis was 53.19. The mean age of patients diagnosed with primary breast cancer was 50, contralateral breast cancer - 58.67, recurrence of breast cancer - 51 and peritoneal cancer 60. The mean time periods from RRSO to the diagnosis of primary, contralateral, recurrence breast cancer were 53, 58.67 and 25,4 months respectively and of peritoneal cancer 46 months. BRCA1 c.5266dupC mutation carriers demonstrated significantly shorter time of cancer development compared to patients carrying c.181T > G and c.4035delA mutations. Peritoneal cancer was only observed in two c.181T > G BRCA1 mutation carriers., Conclusions: The mean age of cancer diagnosis and the mean time periods from RRSO to the diagnosis of cancer are similar to those observed by other researchers. The carriers of c.181T > G and c.5266dupC BRCA1 mutation should be the subject further studies in context of breast and peritoneal cancer risk or time of cancer development after RRSO, respectively., Competing Interests: All participants gave informed written consent prior blood donating. The study was approved by Ethics Committee of the Pomeranian Medical University in Szczecin, Poland (decision No. BN-001/174/05).Not applicable.The authors declare that they have no competing interests.Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Recent preclinical studies point to muscarinic and GABA B receptors as novel therapeutic targets for the treatment of schizophrenia. This study was aimed to assess the role of muscarinic and GABA B receptor interactions in animal models of schizophrenia, using positive allosteric modulators (PAMs) of GABA B receptor (GS39783), muscarinic M 4 (VU0152100) and M 5 (VU0238429) receptor, and partial allosteric agonist of M 1 receptor (VU0357017). DOI-induced head twitches, social interaction and novel object recognition tests were used as the models of schizophrenia. Analyses of DOI-induced increases in sEPSCs (spontaneous excitatory postsynaptic currents) were performed as complementary experiments to the DOI-induced head twitch studies. Haloperidol-induced catalepsy and the rotarod test were used to examine the adverse effects of the drugs. All three activators of muscarinic receptors were active in DOI-induced head twitches. When administered together with GS39783 in subeffective doses, only the co-administration of VU0152100 and GS39783 was effective. The combination also reduced the frequency but not the amplitude of DOI-induced sEPSCs. Neither VU0357017 nor VU0238429 were active in social interaction test when given alone, and also the combination of VU0152100 and GS39783 failed to reverse MK-801-induced deficits observed in this test. All muscarinic activators when administered alone or in combination with GS39783 reversed the MK-801-induced disruption of memory in the novel object recognition test, and their actions were blocked by specific antagonists. None of the tested compounds or their combinations influenced the motor coordination of the animals. The compounds had no effect on haloperidol-induced catalepsy and did not induce catalepsy when administered alone. Pharmacokinetic analysis confirmed lack of possible drug-drug interactions after combined administration of GS39783 with VU0357017 or VU0152100; however, when the drug was co-administered with VU0238429 its ability to pass the blood-brain barrier slightly decreased, suggesting potential drug-drug interactions. Our data show that modulation of cholinergic and GABAergic systems can potentially be beneficial in the treatment of the positive and cognitive symptoms of schizophrenia without inducing the adverse effects typical for presently used antipsychotics., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Endometrial cancer is one of the most common tumor of the woman genital organs., Objective: The goal of this study was to determine the lipocalin-2 levels in patients with endometrial cancer compared to those with normal endometrium or mild endometrial pathologies., Methods: Study included 123 patients with BMI > 21 kg/m2 who were admitted due to abnormal bleeding, in which 52 patients with endometrial cancer. The NGAL, CA125, HE4 serum levels were determined for all patients., Results: Significantly lower median NGAL serum levels were found in a group of patients with normal endometrium compared to the endometrial cancer group, p= 0.006. NGAL protein area under ROC curves value as a diagnostic test, differentiating between endometrial cancer and other benign changes endometrium is AUC - 0.81 (p< 0.00001). The NGAL protein had a high sensitivity in all patients included in the analysis: 84% vs. 82% in pre-menopausal patients, and 81% in postmenopausal women with a specificity of 78%, 80% and 87%, respectively. The independent variable for FIGO and model logistic regression proves that NGAL is statistically significant (p= 0.000602), the odds ratio is 3.66. The model for grading shows, that NGAL increase by one ng/ml increases risk chances by 2.32 times in diagnosis with less cancer differentiation., Conclusions: Our preliminary studies demonstrate that lipocalin-2 may be of value in the diagnostics of uterine body cancers.

Introduction: Higher cortisol levels are associated with cardiovascular morbidity and mortality in the elderly, partially resulting from biologic effects of glucocorticoids (GCs) on endothelial cells observed in an experimental setting. These features are replicated in patients with endogenous GC excess (Cushing's syndrome) or with exogenous hypercortisolism due to excessive pharmacological application of GCs. Both groups present also an increased cardiovascular disease event rate. GCs may also adversely influence recovery after myocardial infarction. Recently it was proposed that microRNAs (miRNAs) - small noncoding RNAs functioning as antisense regulators of gene expression by targeting mRNA - may have a central role in regulating endothelial function through multiple mechanisms. Thus, the purpose of this study was to evaluate the effects of chronic GC excess on the expression of selected endothelium-controlling miRNAs expressed in nucleated cells circulating in peripheral blood (PBNCs) of patients with endogenous hypercortisolism either due to corticotrophin-independent or corticotrophin-dependent Cushing's syndrome (CS)., Material and Methods: Peripheral blood nuclear cells were collected from 35 healthy subjects and 31 patients with endogenous hypercortisolism as a source of miRNAs. A self-validated individual quantitative RT-PCR study was then performed to evaluate the expression levels of selected miRNAs in PBNCs. Additionally, endothelin-1 (ET-1) expression in peripheral blood was assessed with respect to endothelial dysfunction using Western blotting., Results: The ET-1 expression levels in CS were higher than in controls, confirming endothelial dysfunction in the CS group. Furthermore, miRNA analysis revealed a significantly decreased intracellular expression of selected endothelium-related miRNAs in patients with endogenous hypercortisolism, including miRNA-17-5p, miRNA-126-3p, and miRNA-126-5p, compared to controls. In contrast, two other angiogenic miRNAs, miRNA-150-5p and miRNA-223-3p, were significantly upregulated compared to controls., Conclusions: Cardiovascular events related to hypercortisolism remain a challenging problem in medical practice. This study has demonstrated that the chronic excess of GCs in endogenous CS might induce significant dysregulation of selected miRNAs involved in the control of endothelium biology. However, the lack of knowledge about specific miRNA expression postpones the full understanding of the biological roles of such miRNAs in hypercortisolism. Moreover, dysregulated miRNAs seem to be promising targets for further research, especially to search for potential therapies for several GC-induced cardiovascular complications.

Ovarian cancer is characterised by the greatest mortality among all tumors of the reproductive tract. This study included 246 patients which consisted of 136 women with ovarian cancer without genetic mutation and 110 women with benign ovarian cysts. We created two mathematical logic models containing positive and negative risk factors of ovarian cancer such as: age at last menstruation cycle, patient age, OC, HRT, smoking, education status, and alcohol consumption. The calculated cut-off point for the first model was 0.5117. Classification determined on the basis of that cut-off point yielded 87.19% of correctly classified cases, of which 91.38% are "case" and 81.61% - "noncase". For the second model the designated cut-off point was set at 0.5149 and the percentage of correctly classified patients was 88.12%, with 92.24% correctly rated as cancer patients and 82.56% of the cases rightly recognised as having no ovarian cancer. Logit is a simple mathematical model that can be a useful tool for identification of patients with increased risk of ovarian cancer., Competing Interests: Competing interests The authors declare that there is no conflict of interest regarding the publication of this article.

The α V  β 3 integrin plays an important role in many physiological functions and pathological disorders. α V  β 3 is minimally expressed in normal quiescent endothelial cells, but significantly upregulated during neovascularization. In this study, we evaluated a 64 Cu-labeled dimeric cRGD tracer targeted at α V  β 3 integrin and report its applicability to assess peripheral angiogenesis in diabetes mellitus (DM). We established a murine model of type-1 DM characterized by elevated glucose, glycated serum protein (GSP), and glycated hemoglobin A1c (HbA1c). We demonstrated that our imaging probe is specific to α V  β 3 integrin under both normo- and hyperglycemic conditions. We found that the analysis of in vivo PET-CT images correlated well with gamma well counting (GWC). Both GWC and PET-CT imaging demonstrated increased uptake of 64 Cu-NOTA-PEG4-cRGD 2 in the ischemic hindlimb in contrast to non-ischemic control. GWC of the distal ischemic tissue from DM mice showed significantly lower probe accumulation than in non-DM mice. The immunofluorescence staining of the ischemic tissues showed a 3-fold reduction in CD31 and 4-fold reduction in the α V  β 3 expression in DM vs. non-DM animals. In conclusion, we successfully demonstrated that diabetes-associated reductions in peripheral angiogenesis can be non-invasively detected with PET-CT imaging using targeted dimeric-cRGD probe.

Background: This study assessed the prognostic value of HE4 marker measurements at various stages of first-line chemotherapy for ovarian cancer., Methods: The study consisted of 90 ovarian cancer patients, including 48 women undergoing primary surgical treatment and 42 patients qualified for neoadjuvant chemotherapy. Each patient underwent HE4 and CA 125 level measurements at the time of diagnosis and subsequently as follows: after surgical treatment, after the third course of adjuvant chemotherapy, before interval cytoreductive surgery and after chemotherapy. The HE4 value was assessed based on the PSF, OS, DFS, surgical outcome, two-year survival and platinum sensitivity., Results: Preoperative HE4 levels were a predictor of platinum sensitivity (AUC- 0.644; p = 0.035) and DFS (AUC = 0.637; p = 0.0492). A univariate logistic regression analysis showed that serum HE4 significantly correlated with PFS (baseline results over median HR = 2.96, p = 0.0009; baseline over 75 percentile HR = 2.44, p = 0.0062; normalization after treatment HR = 0.46, p = 0.0125; 50% reduction before IDS HR = 0.64, p = 0.0017). In the multivariate analysis, normalization after treatment and 50% reduction before IDS significantly influenced the PFS (HR = 0.29, p = 0.00008; HR = 0.23, p = 0.0024). The HE4 levels also correlated with the OS as follows: values below the median (HR = 1.88, p = 0.0087), normalization after chemotherapy (HR = 0.08, p = 0.0003), and 50% reduction before IDS (HR = 0.39, p = 0.0496)., Conclusions: The significant effect of the normalization of the HE4 marker after therapy and 50% reduction of HE4 levels before interval cytoreductive surgery on PFS and OS confirmed that HE4 might be an independent prognostic factor of treatment response. HE4 measurements performed during first-line treatment of ovarian cancer may have prognostic significance.

Introduction: Adipose tissue is considered an endocrine organ and produces a number of biologically active substances., Aims: To consider the role that four adipokines - leptin, omentin-1, vaspin, and galectin-3 - play in the diagnosis of endometrium cancer and to investigate the association between serum concentrations of adipose tissue metabolism products and the diagnostics and prognosis in endometrial cancer., Patients and Methods: The study included 168 patients with body mass index (BMI) >20 kg/m 2 admitted due to post-menopausal bleeding., Results: A receiver operating characteristic curves test was performed to determine the diagnostic values of the proteins tested. For leptin and galectin-3 the area under the curve (AUC) values were 0.79/0.68, while for vaspin and omentin-1 the AUC values were 0.82/0.86 for all study patients. The final model identified the following independent risk factors: glucose concentration, BMI, waist circumference, leptin, and vaspin concentrations. Diagnostic values of leptin and galectin-3 with regard to differentiation between high (Fédération Internationale de Gynécologie Obstétrique [FIGO] III and IV) and low (FIGO I and II) stages of clinical tumor advancement and prediction of tumor grading (G1 vs G3) based on the AUC curve were 0.82/0.70 and 0.80/0.74. The AUC values for vaspin and omentin-1 with respect to differentiation between histopathological advancement and grading were 0.86/0.81 and 0.83/0.77, respectively. Significantly lower values of mean omentin-1 and vaspin concentrations were also demonstrated in cases of lymphatic vessel invasion, lymph node metastases, or deep endometrial infiltration ( p =0.002, p =0.01, p =0.003, respectively)., Conclusion: It appears that elevated concentrations of leptin, vaspin, and omentin-1 may indicate the presence of endometrial cancer. Furthermore, leptin serum level and vaspin appear to be useful tools in the assessment of clinical staging of endometrial cancer., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Background: MMP and TIMP play an important role in the degradation of extracellular matrix components which are essential for tumor growth, invasion and metastasis. Aim of this research was to assess MMP3 and TIMP3 as prognostic factors among patients with ovarian cancer., Results: It was found that high levels of output MMP3 correlated with shortened overall survival time of patients by 9.7 months. In addition, it has been shown that high concentrations of output MMP3 were significantly associated with a shorter disease free time in median concentrations implemented p = 0.0059. Statistically significant dependence has been shown between an average concentration of TIMP3 protein to the overall survival of patients. The higher output concentration of TIMP3, the longer patients' survival by 8.9 month. In addition, it was found that high TIMP3 concentrations output were associated with a significantly longer disease free duration at a median concentrations p = 0.007., Conclusion: Preliminary research shows that output levels of MMP3 and TIMP3 proteins correlate with overall survival of patients. In some cases also time free of illness.

Obesity is a well-known factor that leads to many diseases including endometrial cancer. The adipose tissue is a heterogeneous organ of internal secretion. Visfatin is a newly discovered protein produced by fat tissues. The purpose of this work was to evaluate serum level concentrations of visfatin in patients with endometrial cancer based on clinical progression and histopathological tumor differentiation. The diagnostic capabilities of visfatin protein in high differentiation (FIGO III and IV) from a lower (FIGO I and II) clinical stage and prognostic degree of cell differentiation (G1 versus G2, G2 versus G3) on the basis of the analysis of the area under the ROC curve are as follows: 0.87, 0.81, and 0.86. Significantly higher concentrations of visfatin have been observed in patients with invasion of the blood vessels ( p = 0.02) and lymph node metastases ( p = 0.01) in reference to the depth of infiltration of the endometrium ( p = 0.004), as well as the size of the tumor ( p = 0.003). Visfatin serum concentrations did not differ due to the invasion of the lymphatic vessels only. Visfatin seems to be a good marker of endometrial cancer progress. High visfatin serum level predicts poor prognosis in endometrial cancer patients.

Purpose: To determine whether thrombospondin-1 might be used as a prognostic factor in ovarian cancer patients., Method: Ninety-six female subjects hospitalized in years 2011-2014 was included in the study. Transvaginal ultrasound examination was performed in all patients. In 39 cases of suspected ovarian cancer, CT scans were also performed. Each patient had been subjected to collection of a 5-mL blood sample before the laparoscopic procedure. Thrombospondin-1 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex) at the Laboratory of the Department of General Pathology., Results: Statistical analysis performed using the Kaplan-Meier survival curves and log-rank test revealed no statistically significant correlations between the median, 75th percentile and 95th percentile thrombospondin-1 levels with progression-free survival of patients (p= 0.47). In the univariate OS model, median thrombospondin-1 level was a significant variable. Correlation was demonstrated between baseline thrombospondin-1 levels and overall survival of patients (p= 0.04, HR = 0.99). The higher the baseline TSP1 level, the longer the overall survival of patients., Conclusion: In our study, we were the first to demonstrate correlation between the levels of thrombospondin-1 and overall survival of patients. Therefore, it appears that thrombospondin-1 may be used as a prognostic factor in ovarian cancer patients.

Introduction: Endometrial cancer is the one of the most common cancers of the genital organ. HE4 and MMP2 are both proteins whose serum levels increase in endometrial cancer., Aim: To explore the diagnostic potential of the serum levels of HE4 and MMP2 in patients with endometrial cancer and benign endometrial diseases. To assess the relationship between the serum levels of HE4 and MMP2 and the typical prognostic factors in patients with endometrial cancer., Materials and Methods: Included in the study was a group of 112 patients presenting with bleeding abnormalities at the Pomeranian Medical University in years 2012-2016. Serum HE4 concentrations were measured using the Elecsys Electrochemiluminescence Immunoassay (ECLIA). MMP2 concentrations were quantified in the serum using multiplex immunoassays., Results: We observed statistically significant differences in mean serum levels of HE4 and MMP2 between the group of endometrial cancer patients and the group of patients with no changes in the endometrium ( P =0.002/0.003). The diagnostic potential of HE4 and MMP2 in differentiation of high (International Federation of Gynecology and Obstetrics [FIGO] III and IV) vs low (FIGO I and II) clinical stage of tumor and prediction of cellular differentiation grade (G1 vs G3) on the basis of the analysis of the area under the curve is, respectively, 0.86 and 0.82 for HE4 and 0.82 and 0.74 for MMP2. The HE4 marker was significantly more specific than MMP2 in every study group and amounted to 93% vs 86% in all patients included in the analysis, 94% vs 84% in pre-menopausal patients and 84% vs 79% in post-menopausal patients., Conclusion: HE4 and MMP2 are characterized by high specificity and may be useful as biomarkers in the diagnostics of endometrial cancer. When determined preoperatively, HE4 is correlated with the prognostic factors of endometrial cancer and may be helpful in the planning of individual treatment of endometrial cancer patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Cyclic peptides containing the Arg-Gly-Asp (RGD) sequence have been shown to specifically bind the angiogenesis biomarker α V β 3 integrin. We report the synthesis, chemical characterization, and biological evaluation of two novel dimeric cyclic RGD-based molecular probes for the targeted imaging of α V β 3 activity (a radiolabeled version, 64 Cu-NOTA-PEG 4 -cRGD 2 , for PET imaging, and a fluorescent version, FITC-PEG 4 -cRGD 2 , for in vitro work). We investigated the performance of this probe at the receptor, cell, organ, and whole-body levels, including its use to detect diabetes associated impairment of ischemia-induced myocardial angiogenesis. Both versions of the probe were found to be stable, demonstrated fast receptor association constants, and showed high specificity for α V β 3 in HUVECs (K d  ~ 35 nM). Dynamic PET-CT imaging indicated rapid blood clearance via kidney filtration, and accumulation within α V β 3 -positive infarcted myocardium. 64 Cu-NOTA-PEG 4 -cRGD 2 demonstrated a favorable biodistribution, slow washout, and excellent performance with respect to the quality of the PET-CT images obtained. Importantly, the ratio of probe uptake in infarcted heart tissue compared to normal tissue was significantly higher in non-diabetic rats than in diabetic ones. Overall, our probes are promising agents for non-invasive quantitative imaging of α V β 3 expression, both in vitro and in vivo.

Objective . We assess the behavior of serum concentrations of HE4 marker in female carriers of BRCA1 and assess the diagnostic usefulness of HE4 in ovarian and endometrial cancer. Methods . A total of 619 women with BRCA1 gene mutation, ovarian, endometrial, metastatic, other gynecological cancers, or benign gynecological diseases were included. Intergroup comparative analyses were carried out, the BRCA1 gene carriers subgroup was subjected to detailed analysis, and ROC curves were determined for the assessment of diagnostic usefulness of HE4 in ovarian and endometrial cancer. Results . Statistically lower serum HE4 and CA 125 levels were observed in BRCA1 gene mutation premenopausal carriers. Occult ovarian/fallopian tube cancer was found 3.6%. Each of those patients was characterized by slightly elevated levels of either CA 125 (63.9 and 39.4 U/mL) or HE4 (79 pmol/L). The ROC-AUC curves were 0.892 and 0.894 for diagnostic usefulness of ovarian cancer and 0.865 for differentiation of endometrial cancer from endometrial polyps. Conclusions . Patients with BRCA1 gene mutations have relatively low serum HE4 levels. Even the slightest elevation in HE4 or CA 125 levels in female BRCA1 carriers undergoing prophylactic surgery should significantly increase oncological alertness. The HE4 marker is valuable in ovarian and uterine cancer diagnosis., Competing Interests: The authors declare that they have no competing interests.

Aim of the Study: An ERAS protocol provides the latest perioperative care principles, whose primary aim is to reduce complication rates, and therefore mortality. The aim of this study is to establish the progress of the ERAS pathway implementation in our gynaecology department., Material and Methods: This was a retrospective analysis of two sets of 100 consecutive medical records: patients treated before (PRE-ERAS) and after (ERAS) introduction of the ERAS protocol. All patients were comparable and all underwent major gynaecological surgery. Patients as well as medical and nursing staff were informed about the proposed preparation, surgical management and postoperative routine., Results and Conclusions: Patients were given supper and drank water during the night. Laparoscopic surgery was used in 44% and spinal anaesthesia was given for open surgery in 43 study patients. Use of drains was reduced only by 23%, bowel preparation by 15%. Intravenous fluid administration was reduced by 22%. Use of postoperative morphine was minimised to 12 patients. Postoperative nausea was managed with the regular use of anti-emetics. Anti-coagulation was given to 80% of the study group. Difficulties in the introduction of the ERAS protocol were due to refusal by some patients to mobilise and eat early postoperatively. Patients in the ERAS programme group were discharged earlier.Further information about the ERAS protocol in the media would facilitate patients' education among conservative society. In order to introduce new and innovative treatment methods, one has to take into account the cultural and ideological factors, especially when patient involvement is essential., Competing Interests: The authors declare no conflict of interest.

The objectives of the study were to assess the relationship between the serum levels of MMP-9 and NGAL and the clinical staging and histopathological grade of the tumor. Lipocalin-2/NGAL and MMP-9 concentrations were quantified in serum by multiplex fluorescent bead-based immunoassays (Luminex Corporation, Austin, TX, USA). The AUC values for NGAL and MMP-9 were 0.9 and 0.78, respectively. The diagnostic potential of NGAL and MMP-9 in differentiating high-stage (FIGO III and IV) and low-stage (FIGO I and II) cancer and predicting the cell differentiation grade (G1 versus G3) on the basis of the analyses of AUC values was determined to be 0.91 and 0.79 for NGAL and 0.82 and 0.84 for MMP-9, respectively. Multifactorial logistic regression analysis in the final method revealed that NGAL and MMP-9 variables were independent of the endometrial cancer risk. OR values for NGAL and MMP-9 were 1.23 (95% CI 1.421-3.27; p = 0.034) and 1.09 (95% CI: 1.38-4.12; p = 0.026), respectively. The NGAL/MMP-9 complex may be useful in the assessment of tumor stage before surgical treatment.

Detectability of early stages of ectopic pregnancies has increased due to improvements in ultrasonographic and biochemical techniques. Since the patients' future procreative plans must be taken into consideration when commencing treatment, the goal of this work was to compare the effects of treatment methods and their impact on fertility. The study included 91 patients treated surgically for ectopic pregnancy. The choice of treatment depended on patients' general condition, ultrasonographic evaluation and serum level of beta-hCG. A combination of laparoscopic and conservative systemic treatment was applied in 70% of cases. More rapid beta-hCG reduction was noted when laparoscopy and intra-oviductal injection of hyperosmolar glucose or methotrexate (MTX) were combined with intramuscular administration of MTX at a dose of 50 mg/m2. Follow-up examination of 66 patients revealed that the greatest number of spontaneous pregnancies (48%) resulted after this combination therapy. We conclude that this combination treatment is safe and provides satisfactory results in terms of future fertility., Competing Interests: Conflict of interest statement: Authors state no conflict of interest.

New poly(ester-amide) copolymers modified with polyethers were developed for carboplatin encapsulation. These new copolymers contain hydrophobic blocks made of tyrosine derivative and dimer fatty acid, and poly(ethylene glycol) (PEG) as hydrophilic blocks. Short-term hydrolytic degradation revealed high water absorption, slight increase of pH of simulated body fluid and change of sample shape, which indicated the erosive mechanism of polymers degradation. Poly(ester-amide)-PEG copolymers were used for microspheres preparation and carboplatin encapsulation. A double emulsification process was used to produce microspheres with an average diameter of 20-30 μm. It was found that the amount of drug released was controlled by the molecular mass of PEG used for microspheres preparation. Mathematical models were used to elucidate the release mechanism of the carboplatin from the microspheres. The results demonstrate that poly(ester-amide)-PEG copolymers may be used for targeted carboplatin encapsulation and release.

The present study aimed to investigate the usefulness of the Risk of Ovarian Malignancy Algorithm (ROMA) in the preoperative stratification of patients with ovarian tumors using a novel combination of laboratory tests. The study group (n=619) consisted of 354 premenopausal and 265 postmenopausal patients. The levels of carbohydrate antigen 125 (CA125) and human epididymis protein 4 (HE4) were determined, and ROMA calculations were performed for each pre- and postmenopausal patient. HE4 levels were determined using an electrochemiluminescence immunoassay, while CA125 levels were determined by a chemiluminescence microparticle immunoassay. A contingency table was applied to calculate the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV). Receiver operating characteristic curves were also constructed, and areas under the curves (AUCs) were compared between the marker determinations and ROMA algorithms. In terms of distinguishing between ovarian cancer and benign disease, the sensitivity of ROMA was 88.3%, specificity was 88.2%, PPV was 75.3% and NPV was 94.9% among all patients. The respective parameters were 71.1, 90.1, 48.2 and 91.1% in premenopausal patients and 93.6, 82.9, 86.6 and 91.6% in postmenopausal patients. The AUC value for the ROMA algorithm was 0.926 for the ovarian cancer vs. benign groups in all patients, 0.813 in premenopausal patients and 0.939 in postmenopausal patients. The respective AUC values were 0.911, 0.879 and 0.934 for CA125; and 0.879, 0.783 and 0.889 for HE4. In this combination, the ROMA algorithm is characterized by an extremely high sensitivity of prediction of ovarian cancer in women with pelvic masses, and may constitute a precise tool with which to support the qualification of patients to appropriate surgical procedures. The ROMA may be useful in diagnosing ovarian endometrial changes in young patients.

After several years of research, HE4 was found to be characterized by slightly worse sensitivity but significantly higher specificity as compared with CA125. Further studies led to the diagnostic potential of both markers (CA125 and HE4) being combined in a single risk of malignancy algorithm (ROMA) algorithm. The objective of this study was to assess the diagnostic capabilities of the ROMA algorithm using age ranges instead of dichotomization of patients according to the pre- and postmenopausal status. A total of 413 female patients were included in the study, including 162 premenopausal and 251 postmenopausal women. Calculation of the final ROMA values was achieved by means of stepwise reduction of coefficients in the proposed formula of: %ROMA = exp(PI)/[1-exp(PI)]*100) and PI = A + W(HE4)(*)ln(HE4) + W(CA125)(*)ln (CA125) and the arrangement of values with consideration to the age group, HE4 level, differentiation of modification, and directional coefficients as well as determination of individual deviations affecting the widening of the median. The cutoff value of modified algorithm ROMA P for the entire study population was calculated from receiver operating characteristic (ROC) curve and DeLong method at the levels of 23.5 %. Marked higher sensitivity and negative predictive value (NPV) values are observed for the standard ROMA algorithm while higher specificity and positive predictive value (PPV) values are observed for the modified algorithm ROMA P. The proposed age-related modification of algorithm calculation does not require the patients being dichotomized according to their pre- or postmenopausal status, and satisfactory diagnostic values may be obtained using a single cutoff point for the entire population.

Background: There are no effective methods of diagnosis of early-stage ovarian cancer. Conservative care over patients at high risk of ovarian and breast cancers is ineffective. Prophylactic surgery is considered the best prophylaxis among BRCA1/BRCA2 carriers., Methods: One hundred ninety-five patients, carriers of one of three most common mutations of the BRCA1 gene (Am J Hum Genet: 66: (6)1963-1968, 2000) in the Polish population (5382insC, 4153delA and C61G), who undergone prophylactic salpingo-oophorectomy. The study group consisted of consecutive mutation carriers living in Poland, in the West Pomeranian province. Histopathological examination of the surgical material failed to reveal presence of malignancy., Results: During follow-up we diagnosed two peritoneal cancers and 14 breast cancers. Diagnosis of breast cancer before prophylactic surgery increased the risk of peritoneal cancer almost three times. Time from diagnosis of breast cancer to prophylactic surgery increased the risk of peritoneal cancer after prophylactic surgery. This was strongly expressed (HR = 5.0; p = 0.030) in cases of over five-year-long delay in prophylactic surgery. Diagnosis of breast cancer before prophylactic surgery correlated with the risk of death (p = 0.00010). Presence of 5382insC mutation decreased and C61G mutation increased the risk of peritoneal cancer (p = 0.049 vs. p = 0.013)., Conclusions: Occurrence of primary peritoneal cancer after prophylactic surgery is similar to that reported in international literature. Primary breast cancer occurred less often than in international literature. We suspect that the risk of development of breast cancer among BRCA1 carriers undergoing prophylactic surgery can differ in a population. The next goal should be to study the molecular basis for the risk of development of malignancies in any population. Carriers of BRCA1 gene diagnosed with breast cancer should undergo prophylactic surgery within five years from the diagnosis of breast cancer.

Background: The aim of our study was to evaluate the behaviour of the human epididymis protein 4 (HE4) in the peritoneal fluid encountered in various female genital diseases., Methods: We enrolled 139 patients, 40 with ovarian cancer (group I), 82 with benign diseases (group II), and 17 with other malignant neoplasms (group III). The HE4 tumor marker concentrations were determined in serum, in the peritoneal effusion and ovarian cyst/ tumor fluids, CA125 in the serum only. We compared the groups, examined correlations and determined corresponding ROC curves. We evaluated the relationship between the HE4 marker concentration in the peritoneal effusion in the group I, depending on the selected prognostic parameters., Results: The HE4 median value between the study groups did not differ statistically significantly and were as follows: in group I 3322 pmol/L, in the group II 2150 pmol/L and in the group III 627 pmol/L (p = 0.206376 for the groups I and II, p = 0.05929 for the groups I and III and p = 0.0797 for the groups II and III. In group I there were no differences found in the HE4 concentrations in the peritoneal fluid, depending on the stage, grade, the presence of neoplastic cells and the peritoneal dissemination., Conclusions: The HE4 marker concentrations in the peritoneal fluid are highly irrespective of the pathology observed in the female sexual organ. Therefore, it seems that its determinations in the peritoneal fluid are completely useless in terms of diagnostics. More research is needed on the role of the HE4 marker, especially the place of its formation and possible use in the targeted therapy.

Aim: Evaluation of patient age and time of the prophylactic surgery as well as incidence of genital cancers and precancerous states observed in histopathology of the postoperative material from BRCA1 gene mutation carriers previously treated for breast cancer., Material and Methods: 206 carriers of one of the three most common BRCA1 gene mutations (5382insC, C61G and 4153delA) in the Polish population, who were offered the option of prophylactic salpingo-oophorectomy The study group comprised 85 patients with the diagnosis of breast cancer before gynecological preventive surgery The study group was further divided into two subgroups for more detailed assessment of the tested variables. The first subgroup included 67 patients with breast cancer (unilateral or bilateral synchronous). The second subgroup included 18 patients with bilateral metachronous (the second diagnosis of breast cancer was at least 12 months after the first breast cancer diagnosis). The control group consisted of 121 patients with no cancerous lesions before preventive gynecologic surgery The patients undergoing prophylactic treatment had no prior symptoms in female sexual organ and no changes in the diagnostic tests., Results: The patients with a history of breast cancer underwent genetic testing and preventive surgery of the genital tract at a significantly later age than controls (respectively p = 0.0003, p = 0.0006). The patients with bilateral metachronous breast cancer underwent preventive surgery significantly earlier (p = 0.03). There was a trend indicating a 2.5 times higher risk of developing ovarian cancer among BRCA1 mutation carriers who had already been diagnosed and treated for breast cancer when compared to women without breast cancer diagnosis. The incidence of other genital cancers and precancerous states in BRCA1 gene mutation carriers with history of breast cancer was not statistically significant as compared to controls. Data on the clinical stage, morphological grade, histological type, age and type of pathology and the type of BRCA1 gene mutation did not show a statistically significant difference between the groups., Conclusions: Each patient diagnosed with breast cancer should be strongly recommended a genetic test to reduce adverse consequences resulting from postponing the test and, if applicable, the preventive operation until later in life. Preventive surgery should be considered especially in BRCA1 gene mutation carriers previously treated for breast cancer because of the increased risk of ovarian cancer

Objectives: The aim of this work was to compare concentrations of adiponectin in the serum of obese women with endometrial cancer, endometrial hyperplasia with atypia, and normal endometrium., Methods: We enrolled 105 obese women treated at the Department of Gynecological Surgery and Oncology of Adults and Adolescents. The patients were allocated to groups depending on the histological diagnosis (R - endometrial cancer, P - polyps, K - normal endometrium). We subdivided group R depending on the stage and grade of cancer., Results: Significantly lower concentrations of adiponectin were found in patients with endometrial cancer (mean 15.28 microg/ml) as compared with polyps (29.94 microg/ml, p < 0.001) or normal endometrium (22.7 microg/ml, p < 0.05). Stage of cancer had no significant effect on the adiponectin level. When cancer grade was compared, lower levels of adiponectin were observed in patients with G3 (12.86 microg/ml) than G1 (19.04 microg/ml, p < 0.05)., Conclusion: Reduced levels of adiponectin may represent an independent risk factor for endometrial cancer.