Does preoperative locally applied estrogen treatment facilitate prolapse-associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse? A randomised controlled double-masked, placebo-controlled, multicentre study.

OBJECTIVE: To evaluate whether locally applied vaginal estrogen affects prolapse-associated complaints compared with placebo treatment in postmenopausal women prior to surgical prolapse repair. DESIGN: Randomised, double-masked, placebo-controlled, multicentre study. SETTING: Urogynaecology unit at the Medical University of Vienna and University Hospital of Tulln. POPULATION: Postmenopausal women with symptomatic pelvic organ prolapse and planned surgical prolapse repair. METHODS: Women were randomly assigned local estrogen cream or placebo cream 6 weeks preoperatively. MAIN OUTCOME MEASURES: The primary outcome was differences in subjective prolapse-associated complaints after 6 weeks of treatment prior to surgery, assessed with the comprehensive German pelvic floor questionnaire. Secondary outcomes included differences in other pelvic floor-associated complaints (bladder, bowel or sexual function). RESULTS: Out of 120 women randomised, 103 (86%) remained for the final analysis. After 6 weeks of treatment the prolapse domain score did not differ between the estrogen and the placebo groups (4.4 ± 0.19 versus 4.6 ± 0.19; mean difference, -0.21; 95% CI -0.74 to 0.33; P = 0.445). Multivariate analysis, including only women receiving the intervention, showed that none of the confounding factors modified the response to estradiol. CONCLUSIONS: These results demonstrate that preoperative locally applied estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with symptomatic pelvic organ prolapse. TWEETABLE ABSTRACT: Preoperative local estrogen does not ameliorate prolapse-associated symptoms in postmenopausal women with pelvic organ prolapse.

Expression of matrix metalloproteinases in patients with uterine smooth muscle tumors: an immunohistochemical analysis of MMP-1 and MMP-2 protein expression in leiomyoma, uterine smooth muscle tumor of uncertain malignant potential, and leiomyosarcoma.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis. We compared the expression of MMP-1 and MMP-2 protein in patients with leiomyoma, uterine smooth muscle tumor of uncertain malignant potential (STUMP), and leiomyosarcoma (LMS). METHODS: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue in 26 patients with leiomyoma, in 24 patients with STUMP, and in 21 patients with LMS. RESULTS: MMP-1 was expressed in 92% of leiomyomas, in 83% of STUMP, and in 86% of LMS, whereas MMP-2 was expressed in 12% of leiomyomas, in 17% of STUMP, and in 48% of LMS. A statistically significant difference regarding the frequency of MMP-2 expression was observed between LMS and STUMP (P =.025) as well as between LMS and leiomyoma (P =.006), but not between STUMP and leiomyoma (P >.05). Likewise, the staining intensity did significantly differ between LMS and leiomyoma (P =.025), but no statistical significant difference was observed between LMS and STUMP (P >.05) and between STUMP and leiomyoma (P >.05). CONCLUSION: The stronger MMP-2 expression in patients with LMS compared with STUMP and leiomyoma indicates that this protein might be a marker for tumor invasion or metastasis in patients with uterine LMS. Furthermore, MMP-2 seems to be a useful immunohistochemical parameter to distinguish cases of smooth muscle tumors in which histologic features are ambiguous or borderline. Further studies including larger numbers of patients are necessary to establish MMP-2 as a routine marker for tumor invasion and progression.

MMP-1 and MMP-2 expression in uterine leiomyosarcoma and correlation with different clinicopathologic parameters.

OBJECTIVE: Matrix metalloproteinases (MMPs) have been suggested to play an important role in tumor invasion and metastasis because they degrade a wide range of components of the extracellular matrix. In the present study, we analyzed the expression of MMP-1 and MMP-2 proteins in patients with uterine leiomyosarcoma. METHODS: MMP-1 and MMP-2 expression was investigated by immunohistochemistry from paraffin-embedded tissue sections in 21 patients with uterine leiomyosarcoma (LMS). The immunohistochemical findings were correlated with different clinicopathologic characteristics of the patients. RESULTS: MMP-1 was expressed in 86% and MMP-2 was expressed in 48% of uterine LMS. There was a statistically significant positive correlation between vascular space involvement and MMP-2 expression (P =.05) and between age and MMP-2 expression, with patients over 50 years old having significantly more frequent MMP-2-positive tumors than patients younger than 50 years (P =.006). The relationship between MMP-2 expression and tumor stage and recurrence disease did not reach statistical significance. A trend towards prolonged disease-free survival was observed in women with MMP-2-negative LMS compared with patients with MMP-2-positive LMS (P =.09). Furthermore, a univariate analysis revealed that early tumor stage (P =.0001), age at diagnosis less than 50 years (P =.02), and the absence of vascular space involvement (P =.04) were associated with longer overall survival. CONCLUSION: The statistically significant positive correlation between MMP-2 expression and vascular space involvement as well as the prolonged disease-free survival rate in patients with MMP-2 negative uterine LMS suggest that MMP-2 plays an important role in tumor invasion and metastasis. Further clinical studies with larger numbers of cases need to be performed to verify these findings.

The effect of epidural analgesia on the occurrence of obstetric lacerations and on the neonatal outcome during spontaneous vaginal delivery.

The aim of this study was to determine if epidural analgesia is associated with increased risk of obstetric lacerations during spontaneous vaginal delivery. Furthermore we assessed the effect of epidural analgesia on maternal and neonatal parameters. This multicenter study consisted of an analysis of data from the delivery databases of the University Hospital of Vienna and the Semmelweis Women's Hospital Vienna. This study was restricted to a sample that included all women with uncomplicated pregnancy, a gestational age >37(th) weeks and a pregnancy with cephalic presentation. Epidural analgesia was set during the first stage of labour. Techniques and management styles of epidural analgesia were the same in both hospitals. No statistically significant association was found between epidural analgesia and the occurrence of perineal tears (p=0.83), vaginal (p=0.37) or labial trauma (p=0.11). Furthermore the results demonstrated a statistically significant higher rate of primiparous women using epidural analgesia (p=0.001). A statistically significant prolonged second stage of labour was observed in women undergoing epidural analgesia (p=0.0001). Episiotomy was statistically significant more frequent in women requiring epidural analgesia (p=0.0001). Women who were treated with epidural analgesia were more likely to have labour augmented with oxytocin (p=0.001). No statistically significant differences in neonatal outcomes determined by APGAR score (p=0.84) and cord pH (p=0.23) were observed between the two groups. Women undergoing epidural analgesia demonstrated a prolonged second stage of labour, a higher rate of episiotomy and an increased use of oxytocin to augment labour. Some of these adverse effects might be caused by the higher rate of primiparous women using epidural analgesia. However, epidural analgesia showed no evidence of a detrimental effect on the integrity of the birth-canal in spontaneous vaginal delivery. In our opinion it is a save and effective method of pain relief during labour.

Prognostic parameters in carcinosarcomas of the uterus: a clinico-pathologic study.

BACKGROUND: Carcinosarcomas of the uterus are highly aggressive malignant neoplasms with early lymphatic and hematogenous spread. The most important prognostic factor in carcinosarcoma is the extent of the tumor at the time of diagnosis. The prognostic impact of other factors such as myometrial invasion, menopausal age, age, parity and adjuvant therapy is still being discussed controversially. MATERIALS AND METHODS: Nineteen patients with histologically proven carcinosarcoma were included in the analysis. The patients were staged according to a modification of the International Federation of Gynecology and Obstetrics (FIGO) staging system for endometrial cancer. For each patient, the histological material was reviewed by an experienced pathologist. Carcinosarcoma was defined histologically as any tumor of uterine origin composed of carcinomatous and sarcomatous components. RESULTS: The median follow-up time was 91 months (25% quartile, 47 months; 75% quartile, 145 months). The median overall survival of the 19 patients was 59 months, resulting in a 5-year overall survival rate of 43%. Three out of the nineteen (16%) patients demonstrated progressive disease while 6 out of 10 (32%) patients developed recurrent disease with a median disease free survival of 16 months (range 8-54). Eleven out of nineteen (58%) patients died of the disease. A univariate model revealed that early tumor stage (stage 1) (p<0.023), low myometrial invasion (p<0.017) and late onset of the menopause (p<0.050) were significantly associated with a lengthened overall survival in patients with carcinosarcoma. Age (p=0.34), parity (p=0.16) and adjuvant radiotherapy (p=0.45) did not influence overall survival of patients with carcinosarcoma. CONCLUSION: Early tumor stage, low myometrial invasion and late onset of the menopause are associated with a lengthened overall survival in patients with carcinosarcoma.

Perineal lacerations during spontaneous vaginal delivery.

BACKGROUND: The aim of the study was to assess the frequency of perineal lacerations during normal spontaneous vaginal delivery and to evaluate potential risk factors. METHODS: The study is based on an analysis of data from the obstetric database of the University Hospital of Vienna and the Semmelweis Women's Hospital Vienna, from February 1999 through to July 1999. Women with vaginal deliveries, uncomplicated pregnancies, uncomplicated first and second stage of labor, gestational age > 37 weeks and pregnancies with cephalic presentation were included. RESULTS: Of 1009 women, 36.2% had perineal lacerations (18.1% had first-degree, 15.2% second-degree, and 2.9% third-degree perineal tears). Univariate logistic regression models showed that only low parity (p = 0.004), the absence of episiotomy (p = 0.0001), and a large head diameter of the infant (p = 0.005) increased the risk for perineal laceration. After adjustment in multivariate analysis, low parity (p = 0.0001), the absence of episiotomy (p = 0.0001) and a large head diameter (p = 0.0004) remained independent risk factors for perineal laceration. Additionally, advanced age of the mother was associated with an increased risk of perineal laceration (p = 0.03). When analyzing the probability for third-degree perineal tears, a strong association with primiparity (p = 0.01), the use of episiotomy (p = 0.0001), a prolonged second stage of labor (p = 0.0001), a large head diameter of the infant (p = 0.01) and the use of oxytocin (p = 0.008) was found. CONCLUSIONS: Primiparous women who are being delivered of a large child are at a greater risk for severe perineal lacerations. In the study population episiotomy did not appear to protect against severe perineal lacerations.

Risk factors for third-degree perineal tears in vaginal delivery, with an analysis of episiotomy types.

OBJECTIVE: To determine the risk factors for third-degree perineal tears during vaginal delivery and to investigate the relation between different types of episiotomy and the occurrence of such tears. STUDY DESIGN: This retrospective multicenter study consisted of an analysis of data from the delivery databases of the University Hospital of Vienna and Semmelweis Frauenklinic Wien between February and July 1999. The study was restricted to a sample that included all women with uncomplicated pregnancy as well as uncomplicated first and second stages of labor, gestational age > 37 weeks and a pregnancy with cephalic presentation. Women with multiple gestations, noncephalic presentation, cesarean deliveries, shoulder dystocia and gestational age < or = 37 weeks were excluded from the study. RESULTS: Among the 1,118 births, 37 women (3.3%) experienced third-degree perineal tears. The use of episiotomy per se and the type of episiotomy (midline) as well as forceps delivery, primiparity, large infant head diameter, prolonged second stage of labor and use of oxytocin were identified as risk factors for third-degree perineal tears during vaginal delivery. When analyzing different types of episiotomy, there was approximately a sixfold-higher risk of third-degree perineal tears in women undergoing midline episiotomy as compared to mediolateral episiotomy. A stepwise logistic regression analysis revealed that episiotomy, prolonged second stage of labor and large infant head diameter remained independent risk factors for third-degree perineal tears. CONCLUSION: We found several risk factors for third-degree perineal tears. The use of midline episiotomy was associated especially with an increased risk of severe anal sphincter tears. To prevent women from long-term sequelae due to third-degree perineal tears, avoidable risk factors should be minimized whenever possible.

Prognostic parameters in endometrial stromal sarcoma: a clinicopathologic study in 31 patients.

OBJECTIVE: The aim of this study was to evaluate the behavior of endometrial stromal sarcomas (ESS) in relation to their clinical and pathologic features and to identify possible prognostic factors. METHODS: Thirty-one patients with histologically proven ESS were included in the analysis. Endometrial stromal sarcoma is characterized by proliferations composed of cells with endometrial stromal cell differentiation. A breakpoint of 10 mitoses per 10 high-power fields was used in the statistical analysis to distinguish between low-grade and high-grade endometrial stromal sarcoma and to evaluate the prognostic value of mitotic count in patients with ESS. RESULTS: The median follow-up time was 72 months (range 34-110). The median overall survival of the 31 patients was 127 months, resulting in a 5-year overall survival rate of 62%. Adjuvant therapy was administered to 25 patients; among those, 20 patients received postoperative radiotherapy and 5 patients received chemotherapy. Ten of the irradiated patients and 3 patients undergoing chemotherapy developed disease recurrence. Concerning the response rate to adjuvant chemotherapy, 1 patient showed a complete response, 1 patient a partial response, 1 patient stable disease, and 2 patients progressive disease. Altogether, 14 patients developed recurrent disease with a median disease-free survival of 11 months (range 5-60). Twelve patients died of the disease. A univariate model revealed that early tumor stage (P < 0.0007), low myometrial invasion (P < 0.008), and low mitotic count (P < 0.005) were associated with a lengthened overall survival in patients with endometrial stromal sarcoma. Age and adjuvant therapy did not influence overall survival of patients with ESS. CONCLUSION: Early tumor stage, low myometrial invasion, and low mitotic count are associated with a lengthened overall survival in patients with ESS.

Paclitaxel-carboplatin chemotherapy does not cause encephalopathy in patients with ovarian cancer: a prospective EEG mapping study in 28 patients.

BACKGROUND: The objective of this study was to evaluate possible effects of a paclitaxel containing chemotherapy, on the central nervous system (CNS) in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. Patients were tested with resting EEG (R-EEG) before and after chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. A decrease of beta power and an increase of delta and theta power as well as a deceleration of the total centroid frequency clearly demonstrated a reduced vigilance in patients with ovarian cancer compared to healthy controls. On the other hand, the observed increase of beta power, a decrease of delta and theta power, and an acceleration of the total centroid from pre- to post-treatment demonstrated an improvement of vigilance in patients with ovarian cancer after treatment with paclitaxel/carboplatin. CONCLUSIONS: The results of this study suggest that chemotherapy consisting of paclitaxel and carboplatin does not cause adverse effects on the central nervous system. Improved vigilance was measured in patients with ovarian cancer after chemotherapy.

Serum levels of angiogenin (ANG) in invasive cervical cancer and in cervical intraepithelial neoplasia (CIN).

BACKGROUND: The propensity of malignant tumors to increase in size, to invade locally and to metastasize is dependent on angiogenesis, which is induced by a variety of proteins including the family of fibroblast growth factors, vascular endothelial growth factor and angiogenin (ANG). The aim of the present study was to measure the serum levels of ANG in patients with CIN and invasive cervical cancer and to evaluate a possible correlation between ANG and various clinicopathologic parameters. MATERIALS AND METHODS: Blood was collected from 62 patients with invasive cervical cancer and 47 patients with CIN. Serum samples of 30 age-matched healthy women acting as a control group were obtained. Determination of serum levels of ANG was performed using a quantitative human ANG immunoassay. RESULTS: The overall median ANG serum level was 272.0 pg/ml (range 101.6-869.2). The median serum levels of ANG were 248.9 (range 101.6-307.2) for healthy female controls, 246.8 (range 169.7-468.1) for patients with CIN and 308.1 pg/ml (range 180.1-869.2) for patients with invasive cervical cancer. Serum levels of ANG were significantly elevated in patients with invasive cervical cancer compared with patients with CIN (p < 0.05) as well as healthy female controls (p < 0.05). No difference was found between ANG serum levels in women with CIN, and healthy controls (p < 0.05). No correlations were found between serum levels of ANG and clinico-pathologic parameters (p > 0.05). CONCLUSIONS: Our data indicate the important role of ANG in tumor angiogenesis in invasive cervical cancer as ANG serum levels were significantly elevated in these patients. However, elevated ANG serum levels seem to occur only after the transformation from pre-invasive to invasive lesions.

Interleukin-8 serum level shift in patients with ovarian carcinoma undergoing paclitaxel-containing chemotherapy.

BACKGROUND: Paclitaxel has been described to induce interleukin-8 (IL-8) transcription and secretion in human ovarian carcinoma cells. The objective of this study was to investigate possible clinical implications of the effect of paclitaxel on IL-8 serum levels in patients suffering from ovarian carcinoma. METHODS: Thirty-one patients with ovarian carcinoma who were treated with combination chemotherapy consisting of paclitaxel and carboplatin entered the study. IL-8 serum levels and CA 125 serum levels were detected three times for each patient directly before chemotherapy, after three cycles of chemotherapy, and after six cycles of chemotherapy. In addition, serum samples from 59 healthy, age-matched women were obtained. A quantitative human IL-8 immunoassay was used to determine the IL-8 serum levels. RESULTS: Seventy-eight percent of patients responded to chemotherapy, with 61% achieving a complete response and 16% achieving a partial response. The median IL-8 serum level before chemotherapy was 75 pg/mL (range, 2.7-903.3 pg/mL), the level during chemotherapy was 23.75 pg/mL (range, 0.5-248.2 pg/mL), and the level after chemotherapy was 17.65 pg/mL (range, 0.6-377.0 pg/mL). The median IL-8 serum level in controls was 15.6 pg/mL (range, 1.4-106.3 pg/mL). The authors found a statistically significant decrease in both IL-8 serum levels (P < 0.05 and P < 0.05) and CA 125 serum levels (P < 0.05 and P < 0.05) from the first to the second measurement and from the first to the third measurement, respectively. They found no correlation between the shifts of IL-8 serum levels and CA 125 serum levels during chemotherapy. CONCLUSIONS: The authors found a significant decrease in IL-8 serum levels in patients undergoing a paclitaxel-containing chemotherapy regimen, indicating that IL-8 possibly acts as a useful monitoring marker in patients with ovarian carcinoma.

Fibrosarcoma of the uterus: a case report.

BACKGROUND: This case report presents the management of a patient with fibrosarcoma of the uterus. Until recently, no cases of fibrosarcomas of the uterus have been reported in the literature. CASE REPORT: A 40-year-old woman presented with complaints of slight vaginal bleeding, watery, white discharge and abdominal pain of 3 weeks' duration. The patient underwent total abdominal hysterectomy. Intraoperative findings included an enlarged irregular-shaped uterus with lots of leiomyoma nodules. The largest leiomyoma nodule was about 8 cm in size and contained an area classified as a fibrosarcoma, presenting cellular immature-appearing fibroblasts growing in a fascicular arrangement. Because of the limited extension of the fibrosarcoma, no adjuvant therapy was performed. After surgical therapy the patient was followed without any evidence of disease for five years. CONCLUSION: Fibrosarcoma is a poorly-circumscribed infiltrative spindle soft tissue sarcoma, which is characterized by local growth and has a propensity for local recurrence. Metastases can occur, mostly to lung and bone. The treatment of choice is wide surgical excision usually followed by radiation therapy due to the high local recurrence rate.

Paclitaxel does not cause central nervous adverse effects: a prospective vigilance-controlled EEG mapping study in ovarian cancer patients.

BACKGROUND: The objective of this study was to evaluate potential adverse effects of paclitaxel-containing chemotherapy on the central nervous system in women with ovarian cancer. METHODS: Twenty-eight women with histologically confirmed epithelial ovarian carcinoma and treated with combination chemotherapy consisting of paclitaxel and carboplatin were entered into the study. Patients were tested with vigilance-controlled EEG before and after chemotherapy. Additionally, a battery of neuropsychologic tests before, after 3 cycles and at the end of the chemotherapy were performed. RESULTS: Twenty of the 28 patients responded to chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. A reduced vigilance in patients with ovarian cancer prior to chemotherapy compared to healthy controls was observed (clearly demonstrated by an attenuated total power, a decrease in fast alpha and slow beta activity, an increase in delta and theta activity as well as a deceleration of the centroid of the total power spectrum). On the other hand, an improved vigilance in patients with ovarian cancer treated with paclitaxel/carboplatin was observed (demonstrated by an increase in total power and an increase in beta power, being more pronounced in the right than in the left hemisphere, between pre- and post-treatment). The results of EEG mapping concurred with those of psychometric tests. The test results did not deteriorate during chemotherapy. A statistically significant improvement in the alphabetical crossout test from the first to the third measurement was observed, indicating an improvement in short-term attention, concentration and the constancy of work during chemotherapy. CONCLUSIONS: Combination chemotherapy consisting of paclitaxel and carboplatin does not cause encephalopathy, but a trend towards an improved vigilance and an improvement of short-term attention and concentration was observed in patients with ovarian cancer after chemotherapy.

Paclitaxel/carboplatin as first-line chemotherapy in advanced ovarian cancer: efficacy and adverse effects with special consideration of peripheral neurotoxicity.

BACKGROUND: The aim of this study was to investigate the response and survival probability of patients with advanced ovarian cancer treated with a combination of paclitaxel and carboplatin as first-line chemotherapy. Additionally we investigated the extent of adverse effects due to chemotherapy with special consideration for peripheral neurotoxicity. MATERIALS AND METHODS: Thirty-seven women with epithelial ovarian cancer, treated with a combination chemotherapy consisting of paclitaxel and carboplatin, were included in the analysis. A total of 234 courses of paclitaxel/carboplatin were applied. Paclitaxel was administered at a dose of 175 mg/m2, infused over 3 hours, every 21 days. Carboplatin was administered at an area under the concentration-time curve (AUC) of 6. RESULTS: Thirty of the 37 patients responded to the chemotherapy, demonstrating an overall response of 81%. Seven patients died of the disease (19%). The mean overall survival was 20 months (25% quartile: 19, median and 75% quartile not reached). Thirteen patients (34%) developed peripheral neurotoxicity. In 10 cases (76%) neurotoxicity occurred after the fifth and sixth chemotherapy cycle. In all cases of severe neurotoxicity pathologic sensory nerve conduction-measurements were observed. In one patient a weakness of the left leg was observed. Apart from alopecia, other adverse effects were rare. CONCLUSION: This study confirmed the therapeutic benefit of the combination of paclitaxel and carboplatin as first-line chemotherapy in patients with ovarian cancer. Neurologic toxicity, increasing with every cycle of the chemotherapy, was a clinically significant adverse effect in our study. However, peripheral neuropathy mainly affected sensory fibers, without involving motor nerves.

A paclitaxel-containing chemotherapy does not cause central nervous adverse effects: a prospective study in patients with ovarian cancer.

BACKGROUND: The objective of this study was to evaluate the possible effects of a paclitaxel containing chemotherapy on different neuropsychological parameters in women with ovarian cancer. MATERIALS AND METHODS: Twenty-eight women with histologically documented epithelial ovarian carcinoma and treated with a combination chemotherapy consisting of paclitaxel and carboplatin entered the study. The patients were tested with a battery of different neuropsychological tests before, after 3 cycles and at the end of the chemotherapy. RESULTS: Twenty of the 28 patients responded to the chemotherapy (71%). Eleven patients (39%) developed peripheral neurotoxicity. The median values of 6 tests performed before the first chemotherapy cycle scored out of the normal range. These patients with deviant test results at the beginning of the paclitaxel/carboplatin infusions did not deteriorate during chemotherapy. We found a statistically significant improvement of the alphabetical cross out test from the first to the third measurement (mean increase = 4.07; 95% confidence interval = [0.99; 7.15]) (p < 0.05), indicating an improvement of the short-term attention, the concentration and the constancy of working during chemotherapy. The other tests failed to show statistically significant changes during chemotherapy (p > 0.05). CONCLUSION: According to our results, a chemotherapy consisting of paclitaxel/carboplatin caused no signs of acute central nervous toxicity or neuropsychological deterioration.