Dinoprostone vaginal insert versus intravenous oxytocin to reduce postpartum blood loss following vaginal or cesarean delivery.

OBJECTIVE: To compare the impact of a dinoprostone vaginal insert and intravenous oxytocin in reducing blood loss of women undergoing vaginal or cesarean delivery. METHODS: This study was conducted among term singleton pregnancies delivered vaginally or by elective cesarean section. In the vaginally delivered cases, active management of the third stage of labor was conducted. During cesarean delivery, 20 IU of intravenous oxytocin was administered. Women, who either delivered via the vaginal or abdominal route, were then randomly allocated to receive 10 mg vaginal dinoprostone insert for 12 hours (group I, n: 100) or intravenous oxytocin (group II, n: 100), respectively. RESULTS: Mean blood loss and need for additional uterotonics and postpartum hemoglobin and hematocrit levels at 24 and 36 hours after delivery did not differ between the two groups. Women allocated to the dinoprostone vaginal insert arm experienced more nausea and vomiting. CONCLUSION: Dinoprostone vaginal insert was as effective as intravenous oxytocin in the prevention of postpartum blood loss.

Is placebo as effective as estrogen regimens on vasomotor symptoms in women with surgical menopause?

OBJECTIVE: To evaluate the short-term effects of two hormone therapy (HT) regimens and placebo on the Greene Climacteric Scale (GCS) of women with surgical menopause following six months of treatment. METHODS: This 6-month, prospective, randomized, parallel-group, masked evaluator study compared the efficacy of once daily administration of 0.625 mg conjugated equine estrogen (group I), 3.9 mg transdermal 17beta-estradiol patch applied every week (group II) and placebo (group III). Mean GCS before and after six months of treatment in each group was compared. RESULTS: In groups I and II, vasomotor symptoms (p < 0.005, p < 0.05), somatic symptoms (p < 0.05, p < 0.05) and total score (p < 0.005, p < 0.01) significantly reduced from baseline values respectively, while the other subscores revealed no statistically important differences following six months of HT. In group III, vasomotor (p < 0.05), subscore and total score (p < 0.05) decreased significantly while other subscore reductions were not significant. CONCLUSIONS: Estrogen regimens and placebo seem to be effective in alleviating vasomotor symptoms. Additional larger prospective randomized studies need to be conducted in an aim to look at not only short-term but also long-term effects on climacteric symptoms, in comparison to both placebo arms and different dose and mode of HT use.

Digital and transvaginal ultrasound cervical assessment for prediction of successful labor induction.

OBJECTIVE: To compare the values of preinduction transvaginal cervical length measurements and Bishop score to predict successful labor induction. METHODS: A prospective, observational trial of nulliparous women undergoing labor induction. Inclusion criteria were gestational age between 36 and 42 weeks, singleton cephalic presentation of the fetus, and intact membranes. Preinduction cervical ripening was performed using 25 microg intravaginal misoprostol (PGE1), repeated every 4 h, up to a maximum of 3 doses. Induction was subsequently continued by oxytocin and amniotomy. RESULTS: A total of 43 women met the inclusion criteria. Mean preinduction cervical length for women with successful or failed labor induction was 26 mm (95% Confidence interval [CI], 27-32) and 34 mm (95% CI, 33-38), respectively (P=0.002). Mean Bishop scores for successful and failed induction groups were 5.4 (95% CI, 5.2-6.2) and 3.1 (95% CI, 2.8-3.5), respectively (P=0.003). CONCLUSION: Digital examination and transvaginal ultrasound of the cervix predict successful labor induction with reasonable accuracy.

Cervicovaginal fetal fibronectin (FFN) for prediction of preterm delivery in symptomatic cases: a prospective study.

OBJECTIVE: To assess the clinical value of cervicovaginal fetal fibronectin (FFN) in the prediction of preterm delivery (PTD) in women with signs and symptoms of preterm labor (PTL). METHOD: This investigation prospectively studied a cohort of a women with symptoms of PTL, between 24 and 37 weeks' gestation with < 3 cm of cervical dilatation and intact membranes. Cases were evaluated in terms of maternal demographic characteristics like age, body mass index, number of parities, previous PTL history, Bishop scores at admission, gestational age at delivery, mode of delivery, use of tocolytic or steroids, presence of histologic chorioamnionitis, neonatal outcomes and delivery before 34 weeks' gestation as well as within seven days of admission. RESULTS: A total number of 68 cases were included in the study. There were no statistically significant differences between positive and negative FFN groups in terms of maternal characteristics, mode of delivery and adverse neonatal outcomes. However, FFN + cases had higher Bishop scores on admission (3.4 +/- 1.2 vs 2.5 +/- 0.3, p = 0.03) and lower gestational age at delivery (33.4 +/- 3.1 weeks vs 36.8 +/- 2.1 weeks, p = 0.002). Likelihood ratio (LR) for positive results was 1.83 (95% CI: 1.61-2.26) for predicting birth before 34 weeks' gestation, with a corresponding negative LR of 0.62 (95% CI: 0.3-1.2). LR for positive results was 4.34 (95% CI: 3.65-5.12) for predicting birth within seven days of testing, with a corresponding negative LR of 0.3 (95% CI: 0.2-0.5). CONCLUSION: Based on the results of cervicovaginal FFN, positive tests represent an increased likelihood of PTD among women with symptoms of threatened preterm labor.

A prospective randomized trial of labor induction with vaginal controlled-release dinoprostone inserts with or without oxytocin and misoprostol+oxytocin.

OBJECTIVE: This study was designed in an aim to compare the efficacies of three labor induction methods, dinoprostone (PGE2) vaginal insert with or without concomittant oxytocin and misoprostol (PGE1) combined with oxytocin infusion. METHODS: This was a prospective observational trial of nulliparous women undergoing labor induction from December 2006 to January 2007. Inclusion criteria were: gestational age between 36 to 42 weeks, singleton cephalic presentation of the fetus, intact membrane and unfavorable cervical Bishop score < 6, and absence of spontaneous uterine contractions. Participants were then randomly assigned to preinduction cervical ripening with a dinoprostone vaginal insert (10 mg) administered into the posterior fornix for a total of 12 hours without oxytocin (group I); with oxytocin (group II), and with misoprostol (50 microg) intravaginally in the posterior fornix with repeat dosing at 6-hour intervals with a maximum dose of four with oxytocin (group III). RESULTS: A total number of 106 women met the inclusion criteria without distribution for 19 cases in group I, 44 and 43 cases in groups II and III, respectively. There were no statistically significant differences in terms of the demographic characteristics, indication of labor induction, interval from-induction-to-delivery, cardiotocographic abnormalities and neonatal outcomes and mode of deliveries among the three groups (p > 0.05). CONCLUSIONS: Three methods of labor induction were equally efficient in achieving succesful delivery without any maternal and fetal adverse outcomes.

Effect of cigarette smoke and alpha-tocopherol (vitamin E) on fertilization, cleavage, and embryo development rates in mice: an experimental in vitro fertilization mice model study.

OBJECTIVE: The objective was to elucidate the effects of cigarette smoke per se or vitamin E on mice exposed to cigarette smoke, with regard to fertility and cleavage rates, and embryo development in an experimental in vitro fertilization (IVF) mice model. STUDY DESIGN: Female and male mice, weighing 18-25 g and aged 14-16 weeks, were separated and divided into cigarette smoke-exposed (SE) and non-smoke-exposed (NSE) groups. A specially designed cage with a cigarette smoking machine was constructed. The SE (20 cigarettes/day) group was put in the cage for 10 weeks. SE and NSE female and male mice were given 50mg/kg of vitamin E intraperitoneally for 10 weeks and were cross-mated thereafter so as to produce seven different subgroups of mice population as follows: group I-NSE male and female mice (control); group II-SE female mice and NSE male mice; group III-NSE female with SE male mice; group IV-SE male and SE female mice; group V-SE female mice treated with vitamin E and SE only male mice; group VI-SE only female and male mice treated with vitamin E; and finally group VII-vitamin E-treated SE male and female mice. Following superovulation with FSH, follicles of female mice were obtained via laparotomy under high-dose ether. Male mice testicles were retrieved via the same surgical procedure. Both gametes were obtained and used for IVF. Fertilization, cleavage rates, and day 3 embryo grading were assessed in four groups. RESULTS: With regard to fertilization rate, group II (36%) significantly differed from group I (85%, p=0.002), group III (68.7%, p=0.04), but not from group IV (20.6%, p=0.34). Taking embryo development rate into consideration, group II (32%) had a lower percentage of embryo development compared with group I (75%, p<0.01) and group III (62.5%, p<0.001), but not group IV (17.2%, p=0.42). Percentages of embryo cleavage, embryo development, and day 3 grade I embryos did differ among four of the groups (p>0.05). CONCLUSIONS: Fertilization and cleavage rates were mainly affected in the SE female mice population. The impact of vitamin E on fertilization, cleavage, and embryo development rates was not relevant among SE male and SE female mice.

Gynecologic problems among elderly women in comparison with women aged between 45-64 years.

BACKGROUND: As women age, they face a variety of co-morbid medical problems as well as gynecologic problems that may differ from those of younger women. Clinicians should know how to screen and manage those problems among elderly women. OBJECTIVE: With this background, the study was designed to assess the gynecologic problems on admission among elderly women and women aged between 45-64 years. METHODS: A retrospective analysis of symptom distribution of 200 women aged over 65 years and 200 women aged between 45-64 years from January 1999 to December 2003 was performed in an university clinic. PARTICIPANTS: Geriatric women and women aged between 45-64 years with gynecologic complaints on admission to outpatient clinics between January 1999 and December 2003. Analyses of demographic data and data related to symptom distribution, using appropriate parametric and non-paramertic statistical tests, were performed. RESULTS: Geriatric women had a higher number of pregnancies (p < 0.01) but lower percentage of hormone replacement therapy use (p < 0.1) compared to women aged 45-64 years. No significant difference was observed in terms of the age at menopause. Vaginal fullness was felt most commonly by elderly women (p < 0.01) in contrast to menopausal vasomotor symptoms which were relevant in the younger age group (p < 0.01). As a clinical diagnosis, pelvic relaxation with uterine prolapse and genital malignancies were the common two diagnoses among geriatric women (p < 0.05). Postmenopausal vaginal bleeeding was observed more often among geriatric women compared to women aged 45-64 years (19.5% vs 12%, p = 0.03). Endometrial and ovarian cancer distribution did not differ among the two groups when the initial complaint was postmenopausal bleeding. CONCLUSION: Type and management of gynecologic problems in women aged over 65 can be challenging and differ from those for younger women. Thus, caring for these women in their reproductive years as well as in later life should be an aim for all obstetrician-gynecologists.

Effect of smoking on semen parameters of men attending an infertility clinic.

OBJECTIVE: To assess the effects of smoking on total sperm count, progressive sperm motility and sperm morphology among couples attending an infertility clinic. METHODS: A total of 223 sperm samples (126 smokers and 97 nonsmokers) from men attending an infertility clinic for routine infertility workup were compared on the basis of standard semen analysis. RESULTS: Cigarette smoking is negatively correlated with progressive motile sperm count (r = -0.1464, p = 0.042), but not with sperm concentration (p = 0.961), total motile sperm count (p = 0.890) and sperm morphology (p = 0.838). Furthermore, packages/ year (cumulative dose of cigarettes) did not correlate with any of the sperm parameters including sperm density (p = 0.976), total (p = 0.559) and progressive (p = 0.406) motile sperm count and sperm morphology (p = 0.449). CONCLUSIONS: Although the effect of smoking on male infertility remains inconclusive, smoking had an adverse effect on the progressive sperm motility, irrespective of total amount of cigarettes smoked per day.

Possible factors affecting the age at menopause among women in the central anatolian region of Turkey.

OBJECTIVE: We aimed to investigate the age at menopause and possible related factors in a Turkish population. STUDY DESIGN: In a three-year period, a retrospective analysis of 541 spontaneous menopause cases were evaluated. All postmenopausal women with spontaneous cessation of menses for > or = 12 months and serum FSH levels > 40 IU/l were included in the study. Sociodemographic status, reproductive and medical history, menopausal symptoms, and previous contraceptive and hormonal therapy use were assessed based on an interview using a standardized information system. Age at menarche, parity, menopausal age of mother and sister, history of lactation, physical activity, cigarette smoking, oral contraceptive use and body mass index (BMI) were assessed. RESULTS: Menopausal age of the enrolled cases was positively correlated with mothers and sisters' ages at menopause. Postmenopausal smokers had an earlier age at menopause compared to non-smokers. CONCLUSION: Cigarette smoking results in earlier menopause in the Turkish population. Menopausal ages of mothers and sisters clearly correlated with the age at menopause.

A ten-year gestational diabetes mellitus cohort at a university clinic of the mid-Anatolian region of Turkey.

OBJECTIVE: The study attempts to analyze a 10-year retrospective cohort of gestational diabetes mellitus (GDM) cases, elucidating the maternal complications and perinatal morbidity and mortality. STUDY DESIGN: The study participants were 110 diabetic singleton pregnancies receiving obstetric care at the Department of Obstetrics and Gynecology, Osmangazi University School of Medicine in Eskisehir, Turkey from January 1995 to December 2004. In 70 of the GDM cases, mean age, diagnostic criteria used to define GDM, gestational age at delivery, presence of additional risk factors, method of clinical management, mode of delivery, fetal birthweights and newborn characteristics were assessed. RESULTS: The prevalence of GDM in the past ten-year period was 3.1% (110/3548). Mean age of enrolled GDM cases was 32.6 +/- 5.3 years. With regard to diagnostic criteria of GDM, 24 (37.1%) cases were diagnosed based on a 100 g, three-hour oral glucose tolerance test (OGTT), while 18 (25.7%) cases were referred to our unit without any information on the specific criteria of GDM diagnoses. In less than a third of the cases (25.7%), a one-hour 50 g glucose challenge test (GCT) resulted > or =185 mg/dl completing the diagnoses. More than half of the cases (57.1%) revealed controlled glucose homeostasis on diet, while 30 (42.9%) pregnant women needed insulin therapy to control blood glucose levels to within normal physiologic limits. Fetal macrosomia was present in 18 (25.7%) pregnancies. Meanwhile, most of the fetuses (62.9%) were within the normal growth percentiles throughout the pregnancy. There was no difference detected in body mass index (BMI) of women undergoing cesarean section and spontaneous vaginal births (25.1 +/- 1.2 vs 26.2 +/- 2.3 kg/m2, respectively, p = 0.45). Vacuum extraction and forceps applications were indicated in 10% of all GDM groups. Fetuses born to women having cesarean section were heavier at birth compared to those of women having vaginal births (3940 +/- 320 g vs 430 +/- 117 g, p = 0.08) Most frequent neonatal morbidity was hyperbilirubinemia in 25 (35.7%) newborns. Interestingly, of those women with GDM, only ten (14.3%) cases consented to follow-up evaluation of glucose intolerance between six and eight weeks postpartum. CONCLUSIONS: Proposed risks from abnormal glucose intolerance in pregnancy are multiple. Early diagnosis, patient education, proper follow-up and postpartum testing in women with GDM will certainly decrease poor perinatal outcomes, enabling also a secondary prevention of type 2 diabetes in the long term.

Preterm premature rupture of membranes and neonatal outcome prior to 34 weeks of gestation.

OBJECTIVES: To investigate the impact of preterm premature rupture of membranes on neonatal outcome. METHODS: A retrospective study was conducted among singleton pregnancies with or without intact amniochorional membranes. The impact of maternal age, gestational age at birth, 1- and 5-min Apgar scores, birthweight, presence of meconium, use of tocolytics, corticosteroids and antibiotics, mode of delivery, umbilical artery pH, histologic presence of chorioamnionitis, and state of the membranes were analyzed in relation to neonatal outcome. Neonatal outcomes were categorized into: none, presence of respiratory distress syndrome, early neonatal sepsis, neonatal death, and days at neonatal intensive care unit. RESULTS: A total of 180 preterm deliveries with ruptured (n=80) and intact membranes (n=100) constituted the study group (group 1) and the control group (group 2), respectively. Compared with group 2, there were more cases in group 1 of maternal antibiotic use (P<0.001), short-term tocolysis (P=0.03), and histologic chorioamnionitis (P<0.001). Multiple logistic regression analysis showed that gestational age at delivery (P=0.009), 1-min Apgar score (P=0.013), and umbilical artery pH (P=0.05) were the independent factors affecting neonatal outcome. CONCLUSIONS: Neonatal outcome was mainly affected by prematurity rather than by preterm premature rupture of membranes.

A hospital-based multicentric study results on gestational trophoblastic disease management status in a developing country.

OBJECTIVE: To determine the clinical management of gestational trophoblastic disease in Turkey. MATERIAL AND METHODS: An inquiry form was sent to 55 health centers including university hospitals, maternity hospitals with residency programs and maternity hospitals without residency programs in 1997. The inquiry consisted of questions about the type of classification systems in use, distribution of cases according to those classifications, use of prophylactic chemotherapy and its indications, and drug preference for single-agent or combined chemotherapies. RESULTS: The overall response rate to the conducted inquiry was 47.1%. A clinical classification system was identified in 60% of the hospitals in Turkey. Generally, methotrexate was the most used single-agent chemotherapy. With regard to first-line combined chemotherapy, MAC (methotrexate, antinomycin-D, cyclophosphamide) was the preferred combination. EMA-CO (etoposide, methotrexate, actinomycin-D, cyclophosphamide, vincristine) was the most common used second-line chemotherapeutic regimen. CONCLUSION: Due to insufficient data acquisition from all the medical centers and a lack of national population-based studies, it is difficult to draw a conclusion with respect to the interpretation of the data about the management protocols of gestational trophoblastic disease.

Hydatidiform mole at extreme ages of reproductive life in a developing country from 1932 to 2000.

PURPOSE OF INVESTIGATION: To determine the rates of hydatidiform mole (HM) cases at extreme reproductive life in a developing country. METHODS: A descriptive study was performed to assess the number of pregnancies and deliveries in Turkey, from 1932 to 2000, based on nationally or internationally published data from different university and state maternity hospitals. RESULTS: A spectrum of prevalence rates in different hospitals were depicted. Almost all of represented data were hospital-based. Percentages of all HM cases < 19 years old and > 40 years old compared to the total number of HMs in each study were not mentioned. In addition, the number of HM compared to total number of deliveries and pregnancies in those age groups were not provided in those studies. CONCLUSION: There appears to be a need for further descriptive studies on a national basis, in regard to assess total number of HM cases per total pregnancies and deliveries for those age groups.

Preoperative serum vascular endothelial growth factor (VEGF) in ovarian masses.

PURPOSE OF THE INVESTIGATION: To determine the diagnostic value of serum vascular endothelial growth factor (VEGF) in the preoperative assessment of the nature of ovarian masses. MATERIALS AND METHODS: A prospective cohort study was conducted from August 2001 to September 2002 on 40 premenopausal and 23 postmenopausal patients with ovarian masses. During preoperative workup, patient age, serum Ca-125 levels, serum VEGF levels, and tumor volume based on ultrasonographic examination were determined. Laparoscopic (n=23) or laparotomic (n=39) approaches were undertaken to obtain the final pathologic result. According to the final ovarian pathology, follicular cysts, corpus luteum cysts and endometriomas were grouped as non-neoplastic ovarian masses (n=40, group I). Serous or mucinous cyctadenomas, dermoid tumors and fibromas were allocated into the neoplastic benign ovarian mass group (n=10, group II). Primary malignant ovarian neoplasms were categorized into the neoplastic-malign group (n=12, group III). RESULTS: Mean ages of cases among groups I, II and III were 39.0 +/- 2.0, 42.2 +/- 5.2 and 56.9 +/- 4.2, respectively. As age of the cases enrolled in this sudy increased, the more likely was the occurrence of neoplastic malign ovarian pathologies (p < 0.001). Among postmenopausal cases diagnosed with an ovarian mass, serum Ca-125 levels were 113.5 +/- 20 IU/ml compared to those in premenopausal cases (85.8 +/- 16.0, p = 0.05). The values for serum VEGF values among pre- and postmenopausal ovarian masses were 46.2 +/- 6.7 pg/ml and 68.2 +/- 7.9, respectively (p = 0.04). In group I, serum VEGF levels of endometriomas (56.5 +/- 1.5 pg/ml) were higher compared to those of follicular or corpus luteum cysts (30.6 +/- 2.8, p = 0.05). In contrast, tumor size appeared to be larger in non-endometriotic. non-neoplastic cysts (10.1 +/- 2.0 cm), compared to endometriomas (6.4 +/- 0.6 cm, p < 0.01). Serum VEGF levels of group III were higher than other groups (p < 0.001). With respect to the discriminating benign or malign nature of the mass, with a specific cut-off value of serum VEGF level of 68.7 pg/ml, the sensitivity, specificity, positive and negative likelihood ratios were 92.3%, 88.0%, 3.3 and 0.1, respectively. For serum Ca-125 levels, the sensitivity, specificity, positive and negative likelihood ratio with a statistically relevant cut-off value of 102 IU/ml were, 76.9%, 76.0%, 3.21 and 0.3, respectively. Area under curve (AUC) for serum VEGF and Ca-125 values were 0.938 (95% CI: 0.81-0.96) and 0.769 (95% CI: 0.64-0.86), respectively (p = 0.02). Among the postmenopausal group, AUC for serum VEGF and Ca-125 was detected as 0.902 (95% CI: 0.70-0.98) and 0.873 (95% CI: 0.66-0.91) (p = 0.14). CONCLUSION: Serum VEGF has the potential to be considered as a tumor marker with a good diagnostic relevance in differentiating the nature of ovarian masses.

Microvessel density (MVD) as a prognosticator in endometrial carcinoma.

PURPOSE: To assess microvessel density (MVD) as a marker for angiogenesis in endometrial carcinoma (EC) and normal endometrium at the proliferative and secretory phase, and to determine its prognostic value on survival among cases with EC. METHODS: Forty-three endometrial carcinoma cases were surgically staged and recruited for this case-control study. Tissue specimens from hysterectomies due to benign conditions (uterine descensus, myoma uteri, chronic pelvic pain, adenomyosis), that belonged to proliferative (n = 10) and secretory (n = 10) endometrium (n = 10), were studied as the control group (n = 20). MVD was assessed in hot areas where a high density of microvessels were detected within tumoral tissue and normal endometrium at proliferative and secretory phases. Among EC, various prognosticators such as tumor stage, histological and nuclear grade, tumor size, lympho-vascular space involvement (LVSI), cervical involvement, myometrial invasion, adnexal and lymph node involvement, peritoneal cytology and MVD were analysed in regard to survival. RESULTS: The mean age of cases with EC was 58.3 +/- 1.4. MVD was apparently high in EC cases (p < 0.05). Among control cases, endometrium from proliferative and secretory phases of the menstrual cycle was not statistically different (48.5 +/- 3.6 vs 47.4 +/- 3.8, respectively). MVD was correlated with high surgical stage (p < 0.001), cervical involvement (p = 0.01), adnexal involvement (p = 0.04), lympho-vascular space involvement (p = 0.02), pelvic and para-aortic lymph node metastasis (p < 0.001) and positive peritoneal cytology (p < 0.001). On univariate analysis, with a MVD cut-off value of 81/0.739 mm2, surgical stage (p < 0.001), LVSI (p < 0.001), retroperitoneal lymph node involvement (p < 0.001), adnexal metastasis (p < 0.001), peritoneal cytology (p = 0.005) and MVD count (p < 0.001) appeared to be independent factors for survival. On multivariate analysis, only pelvic lymph node involvement (p = 0.03) and MVD (p = 0.02) were found to be independent prognosticators on survival. CONCLUSIONS: Angiogenesis is apparent in both initial and further evolution of a tumoral process. MVD appears to have a substantial prognostic value on survival in EC cases.

Bcl-2 expression in preinvasive and invasive cervical lesions.

PURPOSE: To determine the correlation between bcl-2 expression and clinicopathological findings in cervical intraepithelial neoplasias (CIN I, II, III) and invasive cervical lesions, and its effect on overall survival rate. METHODS: Fifty specimens derived from 22 preinvasive and invasive cervical cancer cases up to surgical stage IIb (21 squamous cervical carcinoma and 7 adenocarcinoma cases) were preserved in paraffin blocks from primary surgery and constituted the study group. Tissues were processed and stained by immunohistochemical methods to assess the degree of bcl-2 expression. RESULTS: Positive bcl-2 expression was detected in 54% (13/21) of invasive lesions, while negative in 46% of cases. In CIN's, overall bcl-2 positivity was detected in 68% of cases. Bcl-2 expression was highly relevant between low grade (CIN I) and high grade (CIN II-III) lesions (p < 0.05). As regards degree of tissue staining for bcl-2 in CIN III cases, a statistically relevant difference was detected in comparison with low-grade preinvasive lesions (p < 0.05). In invasive cervical cancer cases, patients with bcl-2 positivity had a longer survival rate. By using the Cox regression model, univariate analysis did not show any specific prognostic factor to be important for survival rate, whereas, on multivariate analysis, histopathologic subtypes (p = 0.0390) and stage of tumor (p = 0.0451) had a statistically significant impact on overall survival rate. CONCLUSIONS: Bcl-2 expression, especially in preinvasive lesions, may play a role in the apoptotic process and be regarded as a marker for disease progression. In invasive cervical carcinomas, bcl-2 expression has not been shown to be effective in overall survival rates.

Prognostic value of matrix metalloproteinase-9 (gelatinase-B) expression in epithelial ovarian tumors.

PURPOSE OF INVESTIGATION: To determine the expression of matrix metalloproteinase-9 (MMP-9) expression in malignant and borderline ovarian tumors and its correlation to prognosis. METHODS: Forty-five patients with primary epithelial ovarian tumors were enrolled in this retrospective study from 1988 to 2002. Only malignant (n = 30) and borderline (n = 15) ovarian tumors constituted the study group. All cases were surgically staged according to FIGO criteria. Patient characteristics and clinico-pathological findings were obtained from hospital records. Paraffin-embedded tissue blocks were treated with MMP-9 immunohistochemical stain. The percentage of the total number of tumors staining positively was categorised and awarded a score of 0 to 4: < 5% as 0, < or = 6-25% as 1, 26-50% as 2, 51-75% as 3 and 76-100% as 4. The intensity of immunostaining was scored on a 3-point scale: 1, weak; 2, moderate and 3, intense. A weighed score for each tumor specimen was produced by multiplying the percentage score with the intensity score and was defined as the 'epithelial MMP-9 score'. Stromal staining was also assessed as weak, moderate and intense. Cases with final epithelial MMP-9 scores < or = 6 and > 6 were then recategorised into two groups, accordingly. Based on degree of stromal staining, cases were recategorised into two final groups as mildly stained and intense or moderately stained. Tumor stages were regrouped as early (Stage I-II) and late (Stage III-IV), respectively. RESULTS: Mean ages of cases with malignant and borderline ovarian tumors were 57.2 +/- 3.1 and 49.7 +/- 2.1 years, respectively. Epithelial MMP-9 scores were higher in malignant tumors compared to borderline tumors (p = 0.014). However, with regard to stromal MMP-9 staining, no significant difference was observed among malignant and borderline tumors (p = 0.113). Among malignant ovarian tumors, epithelial MMP-9 scores did not differ between early versus late-staged and well versus poorly differentiated tumors. Median survival time of cases with epithelial MMP-9 scores < or = 6 and > 6 were 24 months and 32 months, respectively (log-rank: 0.93, p = 0.335). Cases with weak stromal MMP-9 staining had a longer median survival (48 months) compared to cases with moderate or intense stromal MMP-9 staining (24 months, log-rank: 4.46, p = 0.03). CONCLUSION: Epithelial MMP-9 expression generally appears in the malignant form of ovarian tumors compared to borderline tumors. MMP-9 expression in the stroma but not in the epithelium contributes to poor survival in ovarian cancers.

Microvessel density as a prognostic factor in preinvasive and invasive cervical lesions.

OBJECTIVE: To assess angiogenesis in preinvasive and invasive cervical lesions and its prognostic value in squamous cell carcinoma (SCC). METHODS: Twenty-seven cervical intraepithelial lesions (CIN I, II and III), 27 Stage Ib-IIa SCC and 12 normal cervical epithelium were included in the study. Clinico-pathological prognostic factors were re-evaluated from the patients' files and previous tissue sections. Microvessel density (MVD), a marker for angiogenesis, was assessed from new tissue blocks by an immunohistochemical staining method. Statistical tests included Kruskall-Wallis analysis, the Mann-Whitney U-test, Fisher's exact t-test to analyse the categorical data and Cox regression and Kaplan-Meier survival analyses to define the effect of prognosticators on survival. RESULTS: CIN II and III lesions had significantly higher MVD counts than normal epithelium and CIN I lesions, both of which had similar MVD count. Compared to preinvasive lesions invasive SCC had significantly higher MVD counts. Among SCC cases, only pelvic lymph node involvement appeared to be independent risk factor on unvariate analysis. However, MVD, as a cut-off value of 21 determined by ROC analysis, was found to be an independent prognosticator in early stage SCC cases by multivariate analysis. CONCLUSION: Despite the small number of enrolled cases, the results of this study suggest that angiogenesis involved in the development and progression of cervical neoplasms and MVD might be used as a prognostic factor.

Impact of piroxicam beta-cyclodextrin on the efficacy of the intrauterine device in a rat model.

OBJECTIVE: To elucidate the effect of piroxicam beta-cyclodextrin (PbetaCD), a non-steroidal anti-inflammatory drug (NSAID), on the efficacy of the intrauterine device (IUD) in a rat model. METHODS: Forty nulliparous female Wistar rats were allocated to one of four groups, comprising each 10 of these animals. Group I: neither IUD nor medication; group II: IUD, but no medication; group III: IUD and PbetaCD; and group IV: PbetaCD only. In groups II and III, a string of 3/0 silk suture of 2 cm long was transcervically placed in one of the horns of the bicornuate uterus of the rat. Rats in group III were treated during the 18 days following IUD placement with 3 mg/kg/day PbetaCD administered via a feeding tube; group IV received PbetaCD for the same length of time, but had no IUD inserted. The rats were then mated. Thereafter, vaginal smears were taken and assessed daily, in the early morning, for the presence of spermatozoa. The day when spermatozoa were detected was considered to be the first day of gestation. On gestational day 19, both uterine horns of all rats were evaluated for the presence and number of embryos. RESULTS: In group II, mean embryo counts in the horn with or without IUD were 1.0 +/- 0.2 and 4.5 +/- 0.3, respectively (p < 0.01). The comparison of group II with group I showed that the presence of an IUD in one horn did not affect the mean embryo counts in the contralateral horn (4.5 +/- 0.3 versus 5.1 +/- 0.9, p > 0.05). In groups II and III, mean numbers of embryos in the horn with IUD were 1.0 +/- 0.2 and 2.7 +/- 0.4, respectively (p < 0.01). No difference in the mean embryo counts was observed between group I (5.1 +/- 0.9) and IV (4.8 +/- 0.9; p > 0.05). CONCLUSIONS: The IUD had a contraceptive effect in the rat model. The IUD in one horn did not affect the number of embryos in the contralateral horn. In this model, IUDs appear to exert a local effect, i.e. counteracted by PbetaCD. This drug had no adverse effect on the fertility of rats without IUD in situ.