Hematological and biochemical markers in determining the diagnosis and stage prediction of endometrial cancer.

OBJECTIVES: To establish whether there is a statistically significant difference in hematological and biochemical parameters between the patients with premalignant changes of the uterine mucosa and those with malignant changes. The aim is to establish whether hematological and biochemical parameters may be useful in predicting the stages of endometrial malignancy and in differentiating premalignant and malignant endometrial changes. MATERIAL AND METHODS: A retrospective study included 100 patients (70 with endometrial carcinoma diagnosis and 30 with atypical hyperplasia). We compared hematological and biochemical parameters in both groups. RESULTS: CRP, granulocytes, platelets, neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) are statistically significantly higher in patients with malignant changes. Lymphocyte count is statistically significantly lower in patients with malignant changes. Platelet count is statistically significantly lower in patients with stages I and II in comparison to patients with higher disease stage. NLR and PLR have good discriminatory power for carcinoma presence. Patients with advanced changes have statistically significantly higher CRP values, higher granulocyte and platelet count, as well as higher values of NLR and PLR, and statistically significantly lower values of lymphocytes and MPV in comparison to benign changes. CONCLUSIONS: There is a possibility of using hematological and biochemical parameters in the assessment of endometrial changes as well as in the prediction of stages, in confirmed malignant changes of the endometrium.

Predictors of poor neonatal outcomes in fetuses diagnosed with congenital urinary tract anomalie.

OBJECTIVES: Urinary tract anomalies account for approximately one-quarter of all antenatally detected anomalies. The aim of this study was to identify factors associated with severe adverse neonatal outcomes of a prenatally diagnosed urinary tract anomaly. MATERIAL AND METHODS: A retrospective-prospective study included 101 pregnant women with prenatally diagnosed fetal urinary tract anomalies presented to the Council for Fetal Anomalies. Prenatal diagnoses were compared with autopsy findings in cases of terminated pregnancy or with clinical and operative findings of the infants. RESULTS: The mortality rate in the group of patients with fetal obstructive uropathy (60 patients) was 10% and in the group of patients with fetal multicystic dysplastic kidney (38 patients) 15.7%. Surgery was performed on 53.4% of the children, whereas more than half of the operations involved resolving associated urinary tract anomalies. Postoperative renal function deterioration occurred in 19% of the children. CONCLUSIONS: The prognosis of renal function in obstructive uropathies is excellent if oligoamnios does not develop prenatally and in case of timely provided surgical care is provided postnatally. The finding of the bilateral multicystic dysplastic kidney is associated with poor prognosis. The prognosis in fetal unilateral multicystic dysplastic kidney depends primarily on the condition of the contralateral kidney and the existence of associated anomalies.

Knowledge about Cervical Cancer and Awareness of Human Papillomavirus (HPV) and HPV Vaccine among Female Students from Serbia.

Background and objectives: Persistent infection with carcinogenic human papillomavirus (HPV) is the leading cause of cervical cancer. The study explored students' knowledge about cervical cancer and awareness of human papillomavirus and the HPV vaccine. Materials and Methods: A questionnaire-based survey was carried out among 1616 first-year female college students at the University of Nis. It examined socio-demographic characteristics, measured the score of knowledge about cervical cancer, assessed awareness regarding HPV and the HPV vaccine and inquired about the source of information about cervical cancer and HPV. Results: The average cervical cancer knowledge score was 16.35 ± 7.92 (min 0, max 30), with medical professional education, parents' education level, place of residence and relationship status having significant effects on the score. The awareness about HPV and the HPV vaccine was low, with only 14.2% of students having heard about both HPV and its vaccine. The most commonly reported sources of information were the media, while the most competent one was organized health education. Conclusions: Health promotion campaigns and educational programs are necessary in order to reduce cervical cancer burden and should be directed particularly towards those who have demonstrated low cervical cancer knowledge and low awareness regarding HPV and its vaccine.

T lymphocytes in the third trimester decidua in preeclampsia.

OBJECTIVE: The aim of study was to conduct immunohistochemical quantification of CD3+ and CD8+ decidual lymphocytes in preeclampsia. METHODS: A study group included 30 cases of preeclampsia and a control group included 20 healthy pregnant women, all delivered by Cesarean section. Samples of placental bed were analyzed after immunohistochemical staining of CD45+, CD3+ and CD8+ cells. RESULTS: The group with preeclampsia included a significantly higher number of CD3+ (p < 0.01) and CD8+ (p < 0.05) T lymphocytes. CONCLUSION: It is certain that thebalance dysregulation of T cell of the immune milieu of deciduais of importance in etiopathogenesis and manifestations of preeclampsia.

Diagnostic performance of human epididymis protein 4 compared to a combination of biophysical and biochemical markers to differentiate ovarian endometriosis from epithelial ovarian cancer in premenopausal women.

AIM: This study is a comparison of human epididymis protein 4 (HE4) with cancer antigen 125 (CA125), using the Risk of Ovarian Malignancy Algorithm (ROMA), Copenhagen Index (CPH-I), Risk of Malignancy Index (RMI) and Morphology Index (MI) to differentiate ovarian endometriosis from epithelial ovarian cancer (EOC) in premenopausal women. METHODS: The study was performed at the University Clinic of Obstetrics and Gynecology in Skopje. One hundred and sixty-four premenopausal patients were divided into three study groups, including ovarian endometriosis (37), other benign pelvic masses (57) and EOCs (11), and a control group (59). After ultrasonography, all subjects underwent blood sampling. Surgery and histological verification was performed. Pelvic masses were classified based on histological findings. Mann-Whitney, receiver operating characteristic-area under the curve (AUC), sensitivity, specificity and Kruskal-Wallis tests were used for statistical analysis. The level of significance α was set at 5%. RESULTS: For each of the tested markers, sensitivity, specificity and accuracy to distinguish ovarian endometriosis from EOC were as follows: HE4 (81.82%, 100%, 95.83%); CA125 (81.82%, 48.65%, 56.25%); ROMA (90.91%, 83.78%, 85.42%); CPH-I (81.82%, 97.30%, 93.75%); RMI (90.91%, 35.14%, 47.92%); and MI (100%, 75.68%, 81.25%), respectively. The AUC for ovarian endometriosis compared to EOC for tested markers was as follows: HE4 (AUC = 0.934), CA125 (AUC = 0.821), ROMA (AUC = 0.929), CPH-I (AUC = 0.924) and RMI (AUC = 0.880), respectively. CONCLUSION: HE4 and CPH-I perform best to discriminate ovarian endometriosis from EOC in premenopausal women. MI has maximal sensitivity to detect EOC.

Flexible GnRH antagonist protocol vs. long GnRH agonist protocol in patients with polycystic ovary syndrome treated for IVF: comparison of clinical outcome and embryo quality.

OBJECTIVES: Polycystic ovary syndrome (PCOS) is a common endocrine disorder, primarily affecting women of the reproductive age. The aim of the study was to assess the clinical efficacy and embryo quality in flexible gonadotropin-releasing hormone (GnRH) antagonist protocol in comparison to the long GnRH agonist protocol in PCOS women undergoing in vitro fertilization (IVF). MATERIAL AND METHODS: This prospective, randomized study was conducted at the Department of Gynecology and Obstetrics, Clinical Center Nis, Serbia, between 2013 and 2014. The treatment included either a flexible GnRH antagonist protocol (n = 45, antagonist group) or a long GnRH agonist protocol (n = 45, agonist group). RESULTS: The length of the stimulation, total amount of gonadotropins used, as well as the average number of the aspirated and mature oocytes were higher in the agonists group. The endometrial thickness was also greater in the agonists group. A higher number of Class I and Class IV embryos were obtained after the agonist treatment and higher number of Class II and Class III embryos were obtained after the antagonist treatment. Pregnancy, implantation, and miscarriage rates were comparable between the groups. CONCLUSIONS: The GnRH antagonist protocol in PCOS patients has a pregnancy rate comparable to that of the GnRH agonist protocol. Since this protocol has a lower rate of complications and is more convenient for patients, we believe that the GnRH antagonist protocol should be used as the first-line treatment for PCOS patients in an IVF program.

Metastatic malignant melanoma of the uterus diagnosed by colposcopy.

Introduction: Primary and metastatic malignant melanomas represent a rare diagnosis with a small number of described cases. The aggressive nature of the tumor, non-specific symptoms, difficult diagnosis, and no official protocol about the treatment result in poor disease prognosis. Case Outline: The authors presented a 41-year-old multigravida patient. She had an operation of malignant melanoma in the occipital area of the head. She went to her gynecologist because of increased pale pink vaginal secretion. Gynecological examination didn't show any significant abnormalities apart from a slightly enlarged uterus. Papanicolaou test and vaginal secretion examination were normal. Colposcopically, a significant dark brown hyperpigmented area around 1 cm in size was observed on the posterior lip of the cervix, near the orifice and cervical canal, suspicious of melanoma, which was proven on targeted biopsy of the hyperpigmented change on the cervix, and by magnetic resonance imaging of the lesser pelvis. Classic hysterectomy with adnexectomy and regional pelvic lymphadenectomy were performed. Conclusion: This case report pointed out the significance of applying colposcopy in diagnosing suspected metastatic melanoma of the uterine cervix, along with other diagnostic methods and anamnestic data.

In vitro fertilization outcome in women with endometriosis & previous ovarian surgery.

BACKGROUND & OBJECTIVES: Women with endometriosis often need in vitro fertilization (IVF) to concieve. There are conflicting data on the results of IVF in patients with endometriosis. This study was undertaken to elucidate the influence of endometriosis on IVF outcome to give the best counselling for infertile patient with this problem. METHODS: The outcome measures in 78 patients with surgically confirmed endometriosis were compared with 157 patients with tubal factor infertility, all of whom have undergone IVF. The groups were matched for age and follicle stimulating hormone (FSH) levels. Outcome measures included number of follicles, number of oocytes, peak oestradiol (E2) concentrations and mean number of ampoules of gonadotropins. Cumulative pregnancy, miscarriage and live birth rates were calculated in both the groups. RESULTS: Higher cancelation rates, higher total gonadotropin requirements, lower peak E2 levels and lower oocyte yield were found in women with endometriosis and previous surgery compared with those with tubal factor infertility. However, no differences were found in fertilization, implantation, pregnancy, miscarriage, multiple births and delivery rates between the endometriosis and tubal factor infertility groups. INTERPRETATION & CONCLUSIONS: The present findings showed that women with endometriosis and previous surgery responded less well to gonadotropins during ovarian stimulation and hence the cost of treatment to achieve pregnancy was higher in this group compared with those with tubal factor infertility. However, the outcome of IVF treatment in patients with endometriosis was as good as in women with tubal factor infertility.

[Persistent human papillomavirus infection in the etiology of cervical carcinoma: the role of immunological, genetic, viral and cellular factors].

The aim of this paper was to present the role of human papillomavirus (HPV) in cervical carcinogenesis from several aspects. By explaining the HPV virus lifecycle and structure, its effect on cervical cell cycle and subversion of immune response can be better understood. Early E region of the viral genome encodes proteins that are directly involved in carcinogenesis. The E6 protein binds to p53 protein (product of tumor-suppressor gene) blocking and degrading it, which in turn prevents cell cycle arrest and apoptosis induction. E6 is also capable of telomerase activation, which leads to cell immortalization; it also reacts with host proto-oncogene c-jun, responsible for transcription, shortens G1 phase and speeds up the transition from G1 to S phase of the cells infected by HPV. E7 forms bonds with retinoblastoma protein (product of tumor-suppressor gene) and inactivates it. It can inactivate cyclin inhibitors p21, p27, and abrogate the mitotic spindle checkpoint with the loss of protective effect of pRB and p53. The immune system cannot initiate early immunological reaction since the virus is non-lytic, while the concentration of viral proteins--antigens is low and has a basal intracellular position. Presentation through Langerhans cells (LC) is weak, because the number of these cells is low due to the effect of HPV. E7 HPV reduces the expression of E-cadherin, which is responsible for LC adhesion to HPV-transformed keratinocytes. Based on these considerations, it may be concluded that the process of cervical carcinogenesis includes viral, genetic, cellular, molecular-biological, endocrine, exocrine and immunological factors.

[Influence of air pollution on birth weight].

INTRODUCTION: Epidemiological studies point out that exposure to air pollution during pregnancy is a risk for low birth weight. OBJECTIVE: The aim of this study was to evaluate the effects of outdoor and indoor air pollution on the occurrence of low birth weight. METHODS: The measurement of outdoor air pollutants, sulphur dioxide and black smoke was carried out daily at the Institute for Public Healthcare of Nis at two measuring locations, in Nis and Niska Banja during 2003. Subjects were 367 pregnant women, nonsmokers and who were not profesionally exposed to air pollution. Data on exposure to source of indoor air pollution (passive smoking and mode of heating) was determined on the basis of a questionnaire. Data on the characterisitics of newborns were taken from the register of Obstetrics and Gyanecology Clinic of Nis. RESULTS: We determined that exposure of pregnant women to outdoor air pollution and wood heating systems had influence on the occurence of low birth weight. Exposure to passive smoking had no influence on neonatal low birth weight. CONCLUSION: Exposure of pregnant women to outdoor and indoor air pollutants can have negative influence on the occurrence of low birth weight.

[Influence of air pollution on pregnant women's health and pregnancy outcomes].

UNLABELLED: Outdoor and indoor air pollution pollutants can be a potential cause to a lot of negative effects on the health of pregnant women and outcome of pregnancy. The objective of this paper was to estimate the influence of outdoor and indoor air pollution on the health of pregnant women and outcome of pregnancy. MATERIAL AND METHODS: The study subjects were the pregnant women, non-smokers, who were not professionally exposed to air pollution. They were divided into the exposed group (n = 189) and control group (n = 178) during the exposure to outdoor air pollution. The data on exposure to sources of indoor air pollution (smoke produced by burning fossil fuels and passive smoking) during pregnancy were obtained from the questionnaire. Data on health condition and outcome of pregnancy were obtained from medical records of tested pregnant women. RESULTS: The research results have shown that the frequency of anemia (OR = 6.76; 95% CI = 1.28-7.72), upper respiratory symptoms (OR = 9.53; 95% CI = 1.32-3.8) and bleeding (OR = 20.5; 95% CI = 2.03-6.97) was significantly higher in pregnant women exposed to outdoor air pollution as compared with the control group. The occurrence of upper respiratory symptoms (OR = 40.42; 95% CI = 2.96-8.91) and bleeding (OR = 53.21; 95% CI = 4.3-15.73) was significantly higher in pregnant women who had been exposed to fossil fuel smoke. Exposure to passive smoking had significant influence on the development of upper respiratory symptoms (OR = 34.58; 95% CI = 3.05-11.66).

[The role of human papillomavirus typization and cytology in early detection of relapse of cervical intraepithelial neoplasia].

BACKGROUND/AIM: Female patients who underwent ceratin treatment forms of cervical intraepithelial neoplasia (CIN) are at five times greater risk for disease relapse in comparison to the rest of female population. The aim of the study was to investigate validity of human papillomavirus (HPV) typization and cytology in detection of relapse. METHODS; The prospective clinical investigation included 35 patients with relapse and 30 ones without it after adequate treatment of cervical intraepithelial neoplasia. HPV typization using PCR methods and cytological test (conventional Pap smear) were performed in all the patients. Validation of tests applied was performed by determining their sensitivity, specificity, and positive and negative predictive value. RESULTS: More severe degrees of CIN relapse occur significantly more often in patients which remain HPV positive despite of the treatment. The patients which remain positive on HPV type 18 or, on both HPV types 18 and 16, have more often CIN relapses of more severe degree in relation to those just positive on HPV type 16. HPV typization has higher predictive value for diagnosis of the rezidual disease in older patients. Sensitivity of HPV typization for diagnosis all CIN relapse degrees is 68.57%, for more severe degrees (HSIL and MIC) 90.47%, specificity is 93.33%, while positive and negative predictive values are 90.47% and 93.53%, respectively. Sensitivity of cytology for diagnosis of more severe CIN relapses is 80.95%. HPV typization used along with cytology ofters the highest sensitivity (95.23%). CONCLUSION: Both tests, HPV typization and Pap smear, offer satisfactory sensitivity and high specificity in detection of relapse, parcticularly those with more severe degree. The highest sensitivity in detection of CIN relapse is obtained by using both tests.

[Postpartum intra-abdominal haemorrhage--case report].

INTRODUCTION: The most frequent cause of gynaecological haemoperitoneum is ruptured ectopic pregnancy. Haemoperitoneum after a normal vaginal delivery is rare and it is associated with high maternal mortality. CASE REPORT: A 22-year-old primipara had a normal vaginal delivery. She experienced acute abdominal pain and hypovolemic shock ten hours after the delivery and was referred to our hospital twenty one hours after the delivery. An urgent ultrasound profile was done, which revealed free fluid in pelvis and in the whole abdomen. An immediate laparotomy was done and 2 litres of blood were found within the peritoneal cavity. The uterine wall was intact. We found a haematoma on the anterior wall of rectum and livid colours of broad ligament. The peritoneal cavity was cleaned and revised. Any injury of the spleen or liver was excluded. DISCUSSION AND CONCLUSION: Haematoperitoneum after a normal vaginal delivery is rare but life threatening to mothers. It is important to recognize this condition to avoid delay in diagnosis and treatment because of high maternal mortality. Our patient was bleeding from superficial rectal vessels. Only a few cases with undefined aetiologies have been reported in literature.

[The role of colposcopy and typization of human papillomavirus in further diagnostic proceedings in patients with ASC-US cytological finding of the uterine cervix].

BACKGROUND/AIM: Bethesda system of classification of cytological findings was introduced in 2001 two subcategories in the category of atypical squamous cells (ASC) findings: ASC of undetermined significance (ASC-US) and ASC which cannot exlude high-grade intraepithelial lesions (ASC-H). The aim of our study was to assess a possible association of these two subcategories with pathologic biopsy finding and to find out the best further diagnostic proceedings. METHODS: At the Clinic of Gynecology and Obstetrics, Nis 130 patients with ASC findings were analyzed. Colposcopy was performed in all study participants. Patients with pathological colposcopic findings underwent cervical biopsy. In 10 patients with pathologic histologic and 15 with benign findings human papilloma virus (HPV) typization was done using the Hybrid Capture method. RESULTS: Patients with ASC-H finding had significantly more pathologic biopsies compared with patients with ASC-US finding (57.84: 20.72). CONCLUSION: Colposcopy was exhibited somewhat higher sensitivity compared to HPV typization (94.7 : 90), but lower sensitivity (79.27 : 86.6). The usage of HPV typization in the triage of patients with ASC cytologic smear induces statistically significant reduction of unnecessary percentage of cervical biopsies.

[Acute abdomen in a patient with Mayer-Rokitansky-Kuster-Hauser syndrome].

BACKGROUND: Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome is a malformation of female genital tract (incidence 1 in 4000 female newborn children). It appears as a result of a disorder in the development of Millerian cannals. Etiology is unknown. Syndrome MRKH is the most frequent cause of primary amenorrhoea (90%). Patients with MRKH have a normal female phenotype, with normal pubic hairness and thelarche, and female karyotype (46XX) followed by primary amenorrhoea. Hormonal status corresponds to healthy women, where the appearance of ovarian tumors and tumors on rudiment parts of uterus is possible. CASE REPORT: We presented a case of acute abdomen in a patient with previously not diagnosed MRKH. The diagnosis was done during the operation. Small pelvis and an abdominal part were filled with torquated tumor lump, where ovaries, oviducts, uterus or something resembling rudiment of uterus were not recognized through careful examination. Furthemore, the patient had a short, dead-end vagina. Tumorectomy was done and hystopathological finding showed the presence of vascular leiomyoma. CONCLUSION: The diagnosis of complex syndromes, such as MRKH, can, despite modern diagnostics, be absent for non-medical and psycho-social reasons. We can expect ovarian and uterine pathology on hypoplastic structures in these patients, as well as in healthy women. Vascular leiomyoma in the patients with MRKH was not found in the available literature.

[Assessment of endometrial receptivity by color Doppler and ultrasound imaging].

INTRODUCTION: Color Doppler sonography is a new method used to investigate changes during the menstrual cycle in infertile women. The objective of this study was to investigate the correlation of uterine and endomterial-subendomterial blood flow in infertile women using ultrasound and color Doppler sonography. MATERIAL AND METHODS: A prospective clinical study included 65 infertile women divided into three groups. Transvaginal ultrasound examination was performed on days XI, XIV and XX All results were statistically analyzed. We investigated the correlation between cycles, pregnancy outcome and distribution of endomterial-subendomterial blood flow, as well as uterine arterial blood flow. RESULTS AND CONCLUSION: Endomterial-subendometerial blood flow distribution pattern assessed by transvaginal color Doppler, as well as good flow in uterine vessels, are necessery for good pregnancy rates. Thin endomterium, undetectable subendomterial blood flow and higher uterine arterial resistance, were associated with low pregnancy rate and poor outcome.

[Prognostic and therapeutic implication of residual tumorous tissue in cervix conizate].

BACKGROUND/AIM: Conization is an excisive technique used for both diagnostic and therapeutic purposes. If conizate margines do not show any pathologic changes (negative findings) it is also the only therapeutic measure which should be applied. In case of conizate margins affected by the disease (positive findings), it is necessary not only to assess various parameters but also to decide on a further therapeutic approach. The aim of this study was to determine the incidence of positive findings and its impact on a further optimal therapeutic approach choice. METHODS: The data for analyses were retrospectively acquired through an insight into the medical records of the female patients who had undergone conization in the Institute for Gynecology and Obstetrics, Clinical Center of Serbia, within a period from 1995 to 2000. Histopathologic analyses of the bioptic and cervical conizate and reconizate samples were performed in the same institute. The acquired data were analyzed and statistically processed. RESULTS: Within the above mentioned period, a total of 823 conizations were done. In 76 patients, positive findings were determined. The acquired data analysis revealed positive findings decrease during this period, yet with no statistical significance. Higher statistically significant incidence of positive findings, however, was revealed in the patients over 40 years of age. Also, a statistically significantly higher incidence of positive findings was revealed in the apex as compared with other localizations. During the period observed, there was the raise of the number of patients only followed up after the conization without reconization. Also evident was decreasing in the number of histerectomies followed by increasing in the number of reconizations, as the method for reintervention. The most common cause of histerectomy was the apex positive findings with no statistical significance, while of reconization it was positive finding on lateral conizate margins with statistical significance. The association of the apical conizate positive finding with that in the curettements in all the cases was in correlation with positive findings at reintervention. CONCLUSION: According to the results obtained by analyzing and statistical processing of the acquired data, it could be concluded that reconization does represent a more suitable reintervention in patients with positive conizate findings as compared to histerectomy.