Myometrium Invasion, Tumour Size and Lymphovascular Invasion as a Prognostic Factor in Dissemination of Pelvic Lymphatics at Endometrial Carcinoma.

OBJECTIVE: The aim of this work is to show the importance of the depth of myometrium invasion, tumour size and lymphovascular invasion as prognostic factors in dissemination of lymphatic nodes at endometrial carcinoma (CE). MATERIALS AND METHODS: In the period from 2010 to 2015 at the University Clinic for Gynecology and Obstetrics in Banja Luka, 221 endometrial cancer surgeries were done (laparatomy 184-83%, laparascopy 37-16,74%). Patients who had uterus bleeding in peri/postmenopause or those whose endometrium thickness was bigger than 5 mm which was established by ultrasound, or those who had in their cavum uteri pathological (PH) diagnosis, underwent fractional curettage (FC) or hysteroscopy in order to obtain pathohistological endometrium diagnosis. Substances which were removed by fractional curettage, biopsy or by surgery were sent to patohystological analysis. We analysed the following factors: age (5 groups), histological grade (G) of tumour, depth of myometrial invasion (DIM), whether it is more or less than 50%, the size of the tumour (if it is bigger or smaller than 2 cm), positive or negative lymphovascular invasion (LVI), positive or negative pelvic lymph nodes (PLN). RESULTS: Within histological type the endometrioid type CE 166 (75,11%) was most dominant. Adenocarcinoma of endometrium was present 25 (11,31%), serous CE 11 (4,97%) and clear cell KE 2 (0,90%). Dominant population with CE was over 60 years old 127 (57,46) of female patients. At G3 where DIM was <50% positive PLN were present 2 (3.92%), whereas if DIM was>50%, 6 (26,73%) patients with positive PLN were registred. Tumour size < 2 cm was found with 57 (25,79%) female patients with positive PLN 8 (14,03%), while 164 (74,20%) patients had tumours > 2 cm who had 21 (12,80) PLN metastases. At G1 when tumour was <2 cm, positive PLN had 3 patients (5,88), while when tumour was >2 cm, positive PLN were found at 6 patients (9,69%). At G3 whose size was <2 cm, positive PLN were found at 2 patients (16,66%), but when tumour was >2 cm, PLN metastases were more frequent, 6 (25,00%). Negative LVI was found with 168 patients (76,01%) whose PLN were positive 16 (9,52%), while positive LIV was with 53 patients (23,99%) of whom 14 had PLN metastases (26,41%). At G1 two patients had positive PLN (2,32%) with negative LVI, while with positive LVI, positive PLN were found at 3 patients (11,11%). At G3 having negative LVI positive PLN were found with 6 patients (24,00%), while if LIV was positive, the number of positive PLN were 6 (54,54%). CONCLUSIONS: With low risk for lymphatic spread (DIM less than 50%, tumour size smaller than 2 cm and lack of LVI at G1 CE) we also encounter low metastasis rate of PLN. Diagnoses of this kind have an aim to lower the number of pelvic lymphadenectomies. With patients who have a high risk of lymphatic spread (myometrium invasion >50%, tumour size > 2cm, LVI present at G2 and G3) metastasis rate of PLN is high, therefore it is necessary to perform pelvic and paraaortic lymphadenectomy which lowers the mortality rate for more than 50% and at the same time patients get an absolute chance of 5-year survival period.

Correlation of Oxidative Stress Markers with Ultrasound and Cardiotocography Parameters with Hypertension Induced Pregnancy.

INTRODUCTION: Pregnancy induced hypertension (PIH), especially preeclampsia, is a state of extremely increased oxidative stress (OS), due to decrease of antioxidant capacity in comparison to normotensive pregnant women. The consequences of increased state of oxidative stress with hypertension disorder in pregnancy are disorder of placental blood flow, intrauterine hypoxia of the fetus and disturbance in transfer of O2 manifested as pathological ultrasound (US) parameters (amount of amniotic fluid and biophysical profile of fetus) and cardiotocography parameters (CTG). AIM: The aim of this research is to analyze correlation of TBARS oxidative stress markers with ultrasound parameters of pregnancy course and cardiotocography parameters in pregnant women with PIH. PATIENTS AND METHODS: Research has been performed at the Clinic of Gynecology and Obstetrics, University Clinical Centre of the Republic of Srpska. It covered 200 pregnant women, 100 of them with PIH and 100 healthy pregnant women, at gestational age from 28 to 40 weeks. All pregnant women were analyzed for US parameters of pregnancy course and CTG records as well as oxidative stress biomarker, values of Thiobarbituric Acid (TBARS). RESULTS: Pregnant women with PIH had high statistical significant (pre)pathological CTG records and US- biophysical profile, less amount of amniotic fluid and delivered in lower gestation compared to healthy pregnant women. TBARS high values are statistical high significant frequent with pregnant women with PIH, who had pathological and pre-pathological biophysical profile and CTG records, as well as with US less amount of amniotic fluid (p<0.01). The highest TBARS values were presented with PIH pregnant women and US of less amount of amniotic fluid 42.3 µmol. CONCLUSION: There is statistical strong connection between TBARS values, being used as oxidative stress markers, and diagnostic methods used in PIH diagnostics, ultrasound (amount of amniotic fluid, fetus biophysical profile) and cardiotocography recording. TBARS could also be significant in clinical application for assessment of pregnant women with PIH in order to make decisions on pregnancy termination period.

Correlation between cervical infection and preterm labor.

Aim To investigate a correlation between cervical canal infection and imminent preterm labor and to identify most frequent pathogens. Methods A prospective study was conducted in obstetrics/gynecology departments of Health Center and the University Clinical Center Tuzla, and General Hospital Tesanj (Bosnia and Herzegovina, B&H) between October 2013 and May 2014. An examined group included 50 healthy pregnant women with singleton pregnancy of the gestation age between the 28th and 37th week, with cervical changes that are related to imminent preterm labor. Changes were detected by ultrasound biometry of cervix and modified Bishop score. A control group included 30 healthy pregnant women with singleton pregnancy of the gestation age between the 28th and 37th week of pregnancy without signs of imminent preterm labor. Cervical mucus was microbiologically analyzed for identification of pathogens. Results The infection in cervical canal was proven in 35 (70%) examinees and four (13%) patients from the control group (p=0.015). In seven (20%) cases each Ureaplasma and Mycoplasma were detected followed by E. coli in five (14%) cases (p=0.001). Conclusion Cervical canal infection is associated with changes on cervix and premature rupture of fetal membranes, i.e. preterm labor and imminent preterm labor. Screening for infection before pregnancy should be the main task of family doctors as well as gynecologists.

Oxidative Stress Marker and Pregnancy Induced Hypertension.

BACKGROUND: Pregnancy induced hypertension (PIH) is a state of extremely increased oxidative stress. Hence, research and test of role and significance of oxidative stress in hypertensive disturbance in pregnancy is very important. AIM: Aims of this research were to determine a level of thiobarbituric acid reactive substance (TBARS) as oxidative stress marker in blood of pregnant woman with pregnancy induced hypertension and to analyze correlation of TBARS values with blood pressure values in pregnancy induced hypertensive pregnant women. PATIENTS AND METHODS: Research has been performed at the Clinic of Gynecology and Obstetrics, University Clinical Centre in the Republic of Srpska. It covered 100 pregnant women with hypertension and 100 healthy pregnant women of gestation period from 28 to 40 weeks. Level of TBARS is determined as an equivalent of malondialdehyde standard, in accordance with recommendations by producer (Oxi Select TBARS Analisa Kit). RESULTS: Pregnancy induced hypertension is a state of extremely increased oxidative stress. All pregnant women experiencing hypertension had increased TBARS values in medium value interval over 20 µmol, 66%, whereas in group of healthy pregnant women, only 1% experienced increased TBARS value. Pregnant women with difficult preeclampsia (32%) had high TBARS values, over 40 µmol, and with mild PIH, only 4.9% pregnant women. CONCLUSION: Pregnant women with pregnancy induced hypertension have extremely increased degree of oxidative stress and lipid peroxidation. TBARS values are in positive correlation with blood pressure values, respectively the highest TBARS value were present in pregnant women with the highest blood pressure values.

Hemodynamics of arterial and venous circulation in the intrauterine fetal evaluation.

INTRODUCTION: The purpose of each antenatal control focuses on the detection and prevention of hypoxic-ischemic injury and fetal death (1)) using modern biophysical tests and Doppler parameters. GOAL: This study examines the correlation of changes in arterial compared to venous hemodynamics of the fetus and is determined by the most sensitive and most specific Doppler parameter in the assessment of intrauterine fetal status. MATERIAL AND METHODS: The study was conducted as prospective and included 119 pregnant women. All subjects underwent NST (nonstres test), and Doppler measurements of blood flow in the umbilical artery (Aum), fetal aorta (Ao) and the central cerebral artery (MCA). In case of borderline and pathological arterial flow was measured through the ductus venozus (DV) and umbilical vein (VU). At birth to the child was determined umbilical artery blood pH and Apgar score (AS) in the first minute. Based on the clinical condition of the newborn and outcome was calculated perinatal morbidity and mortality. RESULTS: In all cases with a pathological arterial flow, which is verified during measurement also the pathological venous flow and confirmed fetal acidemia at birth and low Apgar scores? In this group, the two neonates died in the first week. CONCLUSION: There is a justification for the analysis of venous flow in the event borderline and pathologic findings in fetal arterial system. It has been proven that the cerebroumbilical (C/U) index is most effective parameter in predicting changes in the venous system and this the most sensitive Doppler parameter in predicting fetal acidosis and the most specific Doppler flow through the central cerebral artery.

The evaluation of impact of BPH surgical treatment with the open prostatectomy and transurethral resection of the prostate methods on the quality of life.

INTRODUCTION/OBJECTIVE: Benign prostatic hyperplasia is one of the most common diseases in older men. The objective of this study was to evaluate the impact of the surgical treatment of the benign prostatic hyperplasia (BPH) with the methods of open prostatectomy (OP) and transurethral resection of the prostate (TURP) on the quality of life. METHODS: The research material was based on 80 patients, out of whom 40 patients were treated with the method of open prostatectomy (Group A), and the other 40 patients with the method of transurethral resection of prostate gland (Group B) due to benign prostatic hyperplasia. All patients were under the age of 80 years old (approximate age in Group A 70.23 with variation interval of 21 years old, and in Group B 69.37 with variation interval of 22 years old), with the International Prostate Symptom Score (IPSS) value >19 points, postvoid residual urine higher than 150 ml, the weight of benign prostatic gland hyperplasia tissue over 30 grams for method of prostate transurethral resection, and over 80 grams for the method of open prostatectomy. The quantification of the quality of life, as a consequence of urinary symptoms, was done by the Quality of Life Index (QLI) which is question No 8 in IPSS. All patients were determined the value of this score before the operation, and then in postoperative period in time intervals of 4.8 and 12 weeks. RESULTS: The QLI arithmetic mean, before the operation, was 5.55 points in Group A, and 5.45 points in Group B. During postoperative checkups in time intervals of 4.8 and 12 weeks, the arithmetic means in Group A were 0.975, 0.450 and 0.100 points, and in Group B 1.850, 1.700 and 1.575 points. By analyzing the obtained results, there was a highly statistically significant difference between preoperative test results and the results during all the postoperative checkups in both groups, A and B. By testing the difference of the QLI arithmetic mean between the patients in both groups, preoperatively there was no statistically significant difference, but during all postoperative checkups, there was a highly statistically significant difference between the test values. CONCLUSION: The surgical treatment of BPH leads to significant improvement of the quality of life, as a consequence of urinary symptoms. The improvement of the quality of life was more evident in patients whose BPH was treated with the OP method.

Importance of the cytoplasmic super-oxide dismutase in the normal tissue of the endometrium and the endometrium carcinoma.

OBJECTIVES: The objective of the study is comparing pathohistological picture and test results of the activity of the enzymes of the anti-oxidative protection -cytoplasmic super-oxide dismutase (CuZnSOD) from the blood and endometrium in the promotion of the progression or regression of the hyperplasia and endometrium carcinoma. MATERIALS AND METHODS: The study has been carried out on 70 patients. We have analysed:The age patients, the supersonic test - transvaginal probe, pathohistological diagnosis (PHD) analysis of the curet of the patient-we have gathered the tissue of the normal and the pathologicaly changed endometrium from the exploratory curretage, determining the CuZnSOD in the blood and in the tissue of the normal and pathological endometrium of the uterus. The Group A has been made out of 30 of them who did not have the irregular bleeding from the uterus, and 40 of them represented the Group B with the irregular bleeding, who also had PHD confirmed hyperplasia or malign changes of the endometrium. We have tested if there has been the pathalogical changes in the small pelvis (the ovary tumor, myoma etc.) in both groups. RESULTS: Dominant age in the Group B is 41 - 50 (55%), in Group A, age difference is not that apparent (p > 0.05). The results of the arithmetic mean of the CuZnSOD in the blood (19.90%) and (29.05%) in the endometrium which is lower than the Group A (blood-29.95%, endometrium-32.56%). Lower values CuZnSOD in the blood (18.9%) and endometrium (30.09%) we have in the experimental group patients who have had bleeding as well as those beside bleeding had some other gynecological - patological proces (myoma, cyst on the ovary etc.) CONCLUSIONS: According to the facts we can see the significance of the activity of the enzymes of the anti-oxidative system in the diagnostic of the hyperplasia and endometrium carcinoma as well as the possibility of their application in the clinical practice.

[Treatment of cervical cancer in the Republic of Srpska].

INTRODUCTION: Since 1897, when the first radical hysterectomy with lymphadenectomy was done by Wertheim in Vienna, this operation has had the central role in the surgical treatment of invasive cervical tumors. MATERIAL AND METHODS: In the period from 1997 to 2010, 177 patients diagnosed with invasive cervical cancer according to the International Federation of Gynecology and Obstetrics (FIGO) stage IB1 - II were operated at the Department of Obstetrics and Gynecology in Banja Luka. All patients underwent radical hysterectomy by Wertheim - Meigs. The aim of this study is to present the technique of this operation, as well as its effectiveness in the treatment of cervical cancer. RESULTS: The distribution of the patients having invasive cervical cancer according to the International Federation of Gynecology and Obstetrics classification was as follows: I B1 - 35.67%, I B2 - 23.17%, II A - 15.48%, II B - 25.68% on average is 21.3 removed lymph glands. The rate of intraoperative and postoperative complications was 8 (4.51%) and 17 (9.60%), respectively. Of the 26 patients who were operated in the period from 2005 - 2010, 13 had stage II B according to the International Federation of Gynecology and Obstetrics; there were 6 lethal outcomes (23.08) and the five-year survival rate was 76.92%. DISCUSSION AND CONCLUSION: By applying the proper surgical technique and early prevention of immediate complications, we achieved satisfactory results in operative morbity and mortality, intraoperative and postoperative complications of the lesion for radical surgery by the Wertheim-Meigs-in the treatment of cancer of the uterus in the I B - II B stage according to the International Federation of Gynecology and Obstetrics classification.

Surgery of condyloma acuminatum permagnum and permagnum recurrence after two years.

The authors in their paper show the case with the female patient D.S. 51 years old, which was surgically treated for genital condyloma in 1981, 1986, 1999, 2006 and 2008. Under registration number 3119/2006 was received at Gynecology and Obstetrics Clinic in Banja Luka with the diagnosis of condyloma acuminatum permagnum. Patient suffered from a huge tumorous, cauliflower formation, which was located on the mons pubis, and down to the anus, laterally to the right of the gluteal region to the left thigh. Patient was operated-Vulvectomia simplex cum extirpatio tumoris reg glutealis l dex. We obtained pathohistological findings (no. 4876 / 06) which read: condyloma acuminatum permagnum. After two years patient was rehospitalized at Gynecology and Obstetrics Clinic in Banja Luka, (registration number 1311/08) with almost identical findings in the same region under the diagnosis of condyloma acuminatum permagnum recidivans, St. post. vulvectomiam simplex et extitpationem tumoris glutealis reg l dex. All preoperative findings - laboratory analysis, X-ray of the lung and heart and ultrasound of the small pelvis were within the reference values. In this paper we describe the location of the tumor and how it is resolved - Extirpatio tumoris reg glutealis l. dex. et perianalis.Pathohistological findings confirmed previous diagnosis. In this paper we highlight our experiences regarding the operations of an unusually large tumors of genital condyloma and recurrent genital condyloma that were almost of the same size. Our experience could be useful to work on the education about sexually transmitted diseases, in order to improve the prevention of the viral diseases (vaccination), the treatment of these illnesses and to disseminate the warning that the regular check-ups with gynecologist are necessary.

The activity of mitochondrial superoxide dismutase in normal and pathological endometrium and correlation with the hormonal status of women.

GOAL: The goal of the study is to demonstrate the activity of superoxide dismutase mitochondria (MnSOD-e) in normal and pathologic endometrium and correlation of hormonal status of these cases with the MnSOD-e activity. MATERIALS AND METHODS: We analyzed 70 female patients, of which 30 of them had bleeding from the uterus (Group A) and 40 women had bleeding from the uterus, as well as a confirmed histopathological diagnosis of endometrial hyperplasia or endometrium carcinoma (Group B). In the follow-up we analyzed: age (respondents divided into five categories), parity (without pregnancy and multiple pregnancies), ultrasound (to determine whether there are pathological changes in the small pelvis), hormonal status of women (we took the blood of subjects to determine follicle stimulating hormone-FSH, luteinizing hormone-LH, progesterone-Pr, estradiol-Es), histopathological analysis (the material was collected by exploratory curettage of normal and pathologically altered endometrium), determining the activity of antioxidant enzymes in the blood and endometrium (we determined the activity of MnSOD-e, whose activity was determined in normal and pathological endometrium). RESULTS: Within age groups dominated patients from 41-50 years, as well as multiple pregnancies. In the experimental group the mean results had lower values of the MnSOD enzyme in blood (0.93) and endometrium (1.94) as compared to the control group in blood (1.27), and endometrium (2.79). The MnSOD-e levels in the follicular phase was approximately at the same level in the experimental and control group, while the values in the luteal phase and stage of menopause was greater in control compared to the experimental group. MnSOD-e levels in endometrium in the follicular phase and stage of menopause were lower in experimental than in the control group, whereas in the luteal phase in the experimental group the value was higher than in the control group. CONCLUSIONS: On the basis of the results, which show a decrease in MnSOD activity both in the blood and endometrium of patients with hyperplasia and endometrium carcinoma we can see the importance of detecting activity of these enzymes in the diagnosis of the mentioned histological lesions, and therefore also possibilities of their application in clinical practice.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium.

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasia or adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Superoxide dismutase and lipid hydroperoxides in blood and endometrial tissue of patients with benign, hyperplastic and malignant endometrium

Epidemiological and experimental data point to involvement of oxygen derived radicals in the pathogenesis of gynecological disorders, as well as in cancer development. The objective of the present study was to examine changes in activities and levels of copper/zinc superoxide dismutase (CuZnSOD) and lipid hydroperoxides (LOOH) in blood and endometrial tissue of patients diagnosed with uterine myoma, endometrial polypus, hyperplasia simplex, hyperplasia complex and adenocarcinoma endometrii. The results of our study have shown decreased SOD activities and unchanged SOD protein level in blood of all examined patients in comparison to healthy subjects. Decrease of both SOD activity and level was found in endometrium of patients with hyperplasia simplex, hyperplasia complex and adenocarcinoma in comparison to women with polypus or myoma. LOOH level was elevated in both tissues of patients with hyperplasiaor adenocarcinoma in comparison to healthy subjects or patients with benign diagnosis. Our findings suggest that the decrease in SOD activity and level, as well as the increase in LOOH level, in patients with gynecological disorders, render these patients more susceptible to oxidative damage caused by reactive oxygen species (ROS). An imbalance in ROS formation and SOD level may be important in the pathogenesis and/or perpetuation of tissue damage in gynecological patients. Since evidence suggests that SOD may be a therapy target for cancer treatment, our findings provide a basis for further research and options for clinical applications.

Resultados epidemiológicos e experimentais apontam para o envolvimento dos radicais derivados do oxigênio na patogênese das moléstias ginecológicas, assim como no desenvolvimento do câncer. O objetivo do presente estudo foi o de examinar as alterações nas atividades e níveis de Cu/Zn superóxido dismutase (CuZnSOD) e hidroperóxidos lipídicos (LOOH)no sangue e tecido endometrial de pacientes diagnosticados com mioma uterino, pólipo endometrial, hiperplasia simplex, hiperplasia complex e adenocarcinoma do endométrio. Os resultados de nosso estudo mostraram atividades de SOD diminuídas e nível de SOD proteína inalterado no sangue de todos os pacientes examinados em comparação a indivíduos saudáveis. Diminuição de ambos, atividade de SOD e nível protéico, foram encontrados no endométrio de pacientes com hiperplasia simplex, hiperplasia complex e adenocarcinoma em comparação às mulheres com pólipos e/ou mioma. O nível de LOOH estava elevado em ambos os tecidos de pacientes com hyperplasia e adenocarcinoma em comparação a indivíduos saudáveis ou pacientes com diagnóstico benigno. Nossos resultados sugerem que um decréscimo na atividade e nível protéico de SOD, assim como um incremento no nível de LOOH, em pacientes com desordens ginecológicas, tornam esses pacientes mais susceptíveis ao dano oxidativo causado pelas espécies reativas de oxigênio (ROS). Um desequilíbrio na formação de ROS e no nível de SOD pode ser importante na patogênese e/ou perpetuação do dano tecidual em pacientes ginecológicos. Desde que existe evidência de que SOD pode ser um alvo para terapia de câncer, nossos resultados fornecem uma base para futura pesquisa e opções para aplicações clínicas.