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.

Introduction: Endometrial carcinoma is diagnosed by histopathological assessment of the sampled endometrium. After establishing the diagnosis the patient needs to be further evaluated in order to establish an optimal treatment. The most important factors that determine the treatment plan include: age, reproduction status, the depth of myometrial invasion, cervical invasion, histopahological type of tumor, histological and nuclear grade. Surgery is the most common treatment. The choice of optimal surgical procedure may include various imaging methods. Aim of the study: Testing the usefulness of applying the ultrasound diagnostics in preoperative evaluation of patients diagnosed with endometrial carcinoma. Method: The prospective study included 61 patients diagnosed with endometrial carcinoma. The ultrasound was used to estimate the presence and depth of invasion of the uterine muscle and cervical inclusion. The obtained parameters were compared to histopathological findings from surgically removed uterus. Results: The sensitivity of the ultrasound method in the estimation of myometrial invasion in the tested sample was 77.59%, specificity was 100.00%, predictive value of the positive test was 79.03%. The sensitivity of the ultrasound method in the estimation of cervical invasion in the tested sample was only 11.11%, specificity was 90.91%, predictive value of the positive test was 33.33%, predictive value of the negative test was 71.43%, whereas total accuracy of the method was 67.74%. Conclusion: Ultrasound diagnostics can be used in the assessment of the depth myometrial invasion but not in the assessment of cervical inclusion.

The incidence of preinvasive changes in the cervix is constantly rising. It is particularly alarming that there is a larger number of younger patients in whom some stage of these changes has been diagnosed or who had already received some type of treatment before. Technological development and improvement of various forms of treatment have lead to changes in the surgical approach to intraepithelial lesions of the cervix. The techniques that have been developed for this purpose, besides the cold-knife conization, include loop excision, radio wave conization, laser conization and, recently, the conization by Harmonic scalpel. The question that inevitably arises is: Has the technological development led to more conservative approaches and improvement in the results of surgical treatment? This paper will try to partly answer this question and initiate some new questions and dilemmas. A comparative review of all of the abovementioned surgical techniques and their detailed analysis is expected to provide at least some answers to the controversial opinions for and against the new surgical procedures. The results of surgical treatments and their complications were analyzed with particular emphasis on the influence that these methods have on fertility. The conclusion is that there is no ideal surgical procedure which could replace and neglect the experience of a colposcopist. New surgical techniques have brought more surgical comfort and faster recovery but have not demonstrated significant change in the final results of treatment and recurrence.

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.

Background. Epithelial ovarian cancer (EOC) accounts for 25% of all malignancies in the female genital tract and it is the most common cause of death among women who develop gynecologic malignancies. According to recent reports at least 20% of EOC are diagnosed at stage I of the disease. Because women tend to give birth to their first child at an older age, and due to the usage of more sensitive diagnostic procedures, the diagnosis of EOC during reproductive age has become more frequent. Therefore, the demand for fertility-sparing surgery in early-stage of EOC is increased. Case report. We presented the case of accomplished reproduction at 41 after the conservative treatment of mucinous ovarian cancer. In the absence of a complete surgical staging, her decision was to spare her fertility capacities opposed to the treatment recommendations of the oncological council. The bottom-line of this report was to give its contribution to the ongoing controversies in the decision to recommend the conservative surgical treatment of the EOC and also to reveal the need of reconsideration of the necessity of a complete surgical staging in patients with stage I of mucinous ovarian cancer. Conclusion. The profile of EOC cases in which a conservative surgical approach is the appropriate one has not yet been defined. Correct surgical staging is still an indispensable guideline for that kind of clinical decision. In the case of stage I of mucinous ovarian cancer with the low tumor grade, the necessity of a complete surgical staging should be reconsidered.

Introduction: Endometrial cancer is the second most common gynecological tumor. There is still no recommended screening method for endometrial cancer. The application of transvaginal sonography, hysteroscopy and Pap test may prove useful in screening for this disease. Atypical glandular cells represent an important finding in Pap tests and they are related to histopathological verification of the endometrium. The aim of the study was to determine the usefulness of the Pap test in assessing the cervical infiltration, as well as to determine the significance of hormonal status and histopathological type of tumor in a pathological Pap test in patients with endometrial cancer. Methods: The study was retrospective. The analysis included the data obtained from 62 operated patients diagnosed with enometrial cancer, medical history (menopausal status), histopathological findings after surgery (type and stage of the disease) and a preoperative Pap smear. The chi squared and Fisher’s test were used. Results: The difference in the prevalence of pathological Pap test in premenopausal and postmenopausal group of patients was not statistically significant. The difference in the prevalence of pathological Pap test in the group of endometrioid and non-endometrioid tumours of the uterine corpus had statistical significance. The difference in the prevalence of pathological Pap test compared to the present stage (I and II) was not statistically significant. Conclusion: Pap smear does not correlate with menopausal status in women with endometrial carcinoma. Abnormal Pap test is more commonly found in cases of non-endometroid tumours. Pap smears cannot be used to assess cervical involvement.

Background/Aim. A repeated or habitual miscarriage (PSP) is defined as three or more consecutive losses of pregnancy. In the first three months of pregnancy, habitual miscarriages occur in about 1% of pregnant women, out of which 50% are of an unknown etiology. It is believed that among them, the greatest number is the consequence of an inadequate alloimmune response of a women to the pregnancy. The endocrine and immune systems are in a close interaction during the implantation and maintaining of pregnancy. This communication is the most obvious on endometrium of pregnancy decidua. The aim of the study was to identify the number and the subpopulation distribution of the decidual NK cells in the decidua by using an immunohistochemical method. Methods. The research included a group of 30 women who had had two spontaneous miscarriages consecutively in the first three months of their pregnancy, while the curettage after the third spontaneous abortion was histopathologically and immunohistochemically analyzed. The control group consisted of 20 women without a problematic reproductive anamnesis, who had had their pregnancy terminated for social reasons. The criteria for the eliminating from the research were the diagnosed uterus anomalies, positive screening on thrombophilia, as well as women suffering from diabetes melitus and the ones with the thyroid gland function disorder. Results. The number and the phenotype structure of the uterus NK cells were significantly different between the decidua of a normal pregnancy and that in PSP. In the decidua in PSP, there were much more NK cells with the phenotype of the peripheral circulation CD57 and CD56dim, while in the decidua of the control group the dominant cells were the typical uNK cell subpopulation CD56bright. Conclusion. The above mentioned results show that the disregulation of the immunocompetent cells of the decidua, by creating an inadequate cytokine milieu, is one of the mechanism of rejecting the semiallogeneic blastocyst.

INTRODUCTION:Absent or reversed end-diastolic blood flow in the umbilical artery is usually associated with poor perinatal outcome and high perinatal mortality rate.CASE REPORT:We present the case of a pregnant woman with absent end-diastolic blood flow in the umbilical artery in the 27th week of pregnancy with initial restriction of fetal growth. Allthough it was more and more obvious that the fetal growth was hindered, the Doppler, cardiotocographic and biophysical parameters did not get any worse as the pregnancy developed. The full fetal maturation was reached after the intense monitoring of the fetal condition and the pregnancy was terminated in the 37th week by elective Cesarean section.CONCLUSION:The basic purpose of prenatal fetal monitoring in the situation of hindered fetal growth with chronic hypoxia is to predict the phase of decompensation and to terminate pregnancy before it is developed. The major problem is in great individual variations at the moment of development of decompensation phase, so the major obstetric aim in the monitoring of the fetus hindered in growth is to determine the optimal time and way of delivery.

Sazetak Ucestalost izvodenja carskog reza je u znatnom porastu poslednjih pedeset godina. Sa povecanjem ucestalosti izvodenja carskog reza, povecava se i broj trudnoca koje se odvijaju nakon prethodnog carskog reza. Cilj je bio da se utvrdi uticaj prethodnog carskog reza na nastanak placentnih komplikacija: piacente previje, ablacije placente i srastanja posteljice, kao i odnos broja prethodnih carskih rezova i pojave ovih komplikacija. Istrazivanje je sprovedeno na Ginekolosko-akuserskoj klinici u Nisu u toku desetogodisnjeg perioda ad 1996. do 2005. godine, koji obuhvata 32358 porodaja, 1 280 porodaja nakon prethodnog carskog reza, 131 slucaj pIacente previje i 118 slucajeva ablacije placente. Eksperimentalnu grupu predstavljaju slucajevi piacente previje/ablacije posteljice u trudnoci nakon prethodnog carskog reza, a kontrolnu grupu cine ovi slucajevi bez prethodnog carskog reza. Incidencija pIacente previje bez prethodnog carskog reza iznosi 0,33%, a nakon jednog carskog reza 1,86% (p<O,OO 1), 5,49% nakon dva prethodna carska reza, a 14,28% nakon tri carska reza. Ablacija posteljice javila se u 0,33% trudnoca bez prethodnog carskog reza, 1,02% trudnoca nakon jednog carskog reza (p<O,OO 1) i u 2,02% nakon dva carska reza. Razlika u ucestalosti intrapartalnih histerektornija nakon prethodnog carskog reza (0,86%) u odnosu na one bez njega (0,006%) visoko je statisticki znacajna (p<O,OO 1). Prethodni carski rez predstavlja znacajan faktor rizika za pojavu placentnih komplikacija. Kljucne reci: Ponovljeni carski rez; Placenta previja; Abrupcija pIacente; Placenta akreta; Histerektomija; Komplikacije u trudnoci

INTRODUCTION:The incidence of cesarean section has been rising in the past 50 years. With the increased number of cesarean sections, the number of pregnancies with the previous cesarean section rises as well. The aim of this study was to establish the influence of the previous cesarean section on the development of placental complications: placenta previa, placental abruption and placenta accreta, as well as to determine the influence of the number of previous cesarean sections on the complication development.MATERIAL AND METHODS:The research was conducted at the Clinic of Gynecology and Obstetrics in Nis covering 10-year-period (from 1995 to 2005) with 32358 deliveries, 1280 deliveries after a previous cesarean section, 131 cases of placenta previa and 118 cases of placental abruption. The experimental groups was presented by the cases of placenta previa or placental abruption with prior cesarean section in obstetrics history, opposite to the control group having the same conditions but without a cesarean section in medical history.RESULTS:The incidence of placenta previa in the control group was 0.33%, opposite to the 1.86% incidence after one cesarean section (p<0.001), 5.49% after two cesarean sections and as high as 14.28% after three cesarean sections in obstetric history. Placental abruption was recorded as placental complication in 0.33% pregnancies in the control group, while its incidence was 1.02% after one cesarean section (p<0.001) and 2.02% in the group with two previous cesarean sections. The difference in the incidence of intrapartal hysterectomy between the group with prior cesarean section (0.86%) and without it (0.006%) shows a high statistical significance (p<0.001).CONCLUSION:The previous cesarean section is an important risk factor for the development of placental complications.

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.

Pri donosenju odluke o lecenju bolesnice sa karcinomom endometrijuma znacajno je: 1) da li je bolest u odmaklom stadijumu ili je prisutan recidiv tumora, 2) da li je prethodno sprovedena terapija i ako jeste, koji vid terapije (zracenje ili hemioterapija), 3) da li je tumor merljiv ili nemerljiv i 4) o kom se histoloskom tipu tumora radi. Kod pojave recidiva znacajno je da li se on javio u prethodno zracenom polju ili van njega. Treba imati u vidu da je prezivljavanje bolesnica sa odmaklim i recidivirajucim karcinomom endometrijuma oko jedne godine i da su dosadasnji protokoli pokazali manje ili vise izrazenu toksicnost. S tog aspekta, vazno je i da primenjena terapija ne izazove znacajno oboljenje i narusavanje kvaliteta zivota bolesnice. Terapija uznapredovalog, metastatskog i recidivirajuceg karcinoma endometrijuma zahteva individualni pristup u zavisnosti od zivotne dobi i opsteg stanja bolesnice, mesta recidiva i prethodno sprovedene terapije. Pored hemioterapije, terapijske mogucnosti koje su na raspolaganju za sada su palijativna hirurgija i radioterapija, kao i hormonska terapija. .

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.

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.

Pregnancy after the 40th week of gestation is often a great dilemma for obstetrician in diagnostic, therapeutic and in psychological terms as well. The aim of this study was to confirm the phenomenon of placental insufficiency in pregnancy after the 40th gestation week, the modality of delivery and perinatal outcome.The study comprised 3405 deliveries in a period of one year, 391 of which were terminated after the end of the 40th gestation week, including healthy pregnant women with singleton pregnancies. Control group included healthy pregnant women delivered between the 37th and 40th gestation week.The incidence of deliveries after the 40th week of gestation is 11.48%. Non-stress test was reactive in 99.65% of women in the study group. At the same time, CST (constriction– stress test) was assessed as negative in 78.67% of cases. The pathological CST was found in only 1.33% of cases. Doppler ultrasound measurements showed the increased resistance in umbilical artery flow in 3% of cases. Vacuum extraction was used for 16.62%of deliveries in the study group, and 8.73% of deliveries in the control group (χ2=23.24;p<0.001). In the study group, Caesarean section was performed in 14.58% of cases, and in control group in 9.07% (χ2=11.09; p<0.001).Placental insufficiency induced by duration of pregnancy is a rear phenomenon in uncompromised pregnancy. There was no significant difference in the morbidity and mortality rates between the study and control group.

Constant rise of incidence of intraepithelial uterine cervix lesions in young patients implies a larger number of therapeutic surgical procedures. The paper aims to assess the risk of such surgical procedures on later pregnancy and delivery. The paper is a retrospective study performed at the Clinic of Gynecology and Obstetrics in Nis. The study enrolled 30 pregnant women in the experimental group with conization of the uterine cervix in their history, and 90 pregnant women without history data on previously performed conizations. The investigation demonstrated a significantly higher percentage of deliveries before 37 week of gestation in our experimental group – 20% vs 5.5% in the control group. Deliveries in experimental group more commonly started with preterm rupture of membranes (pPROM) – in 13.3% while the corresponding percentage in control group was only 2.22%. Related to operative completion of delivery with cesarean section, there were no significant differences between the groups (6.6% vs 3.3% in experimental and control group, respectively). There was a statistically significant difference in cervix injury during labour in experimental (10%) compared to control group (1.1%). Uterine cervix conization represents a risk for preterm labour in late pregnancy. In these women, delivery more commonly starts with preterm rupture of membranes and uterine cervix injuries are more common. Therefore, conization should be utilized only if strictly indicated in young patients, and those with conization should be closely monitored.

Important parameters of natural development have been shown and analyzed in this work about the community of Nis in the period of 1978 to 1999. It has been noticed that the birthrate has been below 16 live born on 1000 inhabitants (16 promille) since 1980 which does not enable stable rate of reproduction. During 1999. the birthrate was 9.3 promille. The mortality rate grew progressively from 1978 (7.2) and it was 11.4 in 1999 which is a consequence of the presence of the 65 year or older age group. The negative natural birthrate appeared at first in 1997 and it was 2.2 in 1999. A depopulation and aging of the population is present in the community of Nis.

In the period from 1997 to 2001 at the Clinic for Gynecology and Obstetrics of the Clinic Center, Nis, there were 140 treated patients suffering from the cervix uteri carcinoma in I-B and II-A stadiums according to the FIGO classification. In 16 (11,42%) patients there was modified radical hysterectomy (class 11) done while in 124 (88,57%) the Wertheim-Meigs hysterectomy (class III) done. Inter operative complications (lesions) were recorded in 8 (5,69%) patients, namely, urinary tract lesions in 4 (2,85%) while blood vessel ones in 3 (2,13%) patients. The obturator nerve is cut in 1 (0,71%) patient. Immediate postoperative complications were recorded in 56 (39,96%) patients. Most often they are infection-induced. Urinary infections were noticed in 25 (17,85%) patients, febrility in 22 (15,71%) and infections of the operative wound in 3 (2,14%) patients. Later complications of the operative cervix treatment were noticed in 37 (26,42%) patients. Their emergence depends on the fact whether the patient was radiated before or before and after the operation. Most often later complications emerge in the patients that undenvent, after the operation, brachytherapy and transcutaneous radiotherapy (27 or 19,28%); the least frequent were in only 3 (2,14%) of the operated patients. The most frequent later complications are those of the urinary tract (fistulas, cystitis) in 11 (7,83%) patients as well as changes upon the last part of the gastrointestinal tract, namely, hemorrhage colitis in 9 (9,28%), late ileus in 3 (2,14%) and rectovaginal fistula in 3 (2,14%) patients. Hydronephrosis was recorded in 7 (5,00%) patients. There were no lethal cases. All the patients are still living.

The use and efficiency of the post coital contraception as an urgent procedure in preventing the generation of undesired pregnancy - as a consequence of unprotected coitus during the fertile days of the menstrual cycle - are analyzed as well as the presence of side effects of this type of contraception, its importance and perspective