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.

Mortality risk among workers with exposure to dioxins.

BACKGROUND: In several studies, dioxin exposure has been associated with increased risk from several causes of death. AIMS: To compare the mortality experience of workers exposed to dioxins during trichlorophenol (TCP) and pentachlorophenol (PCP) production to that of the general population and to examine mortality risk by estimated exposure levels. METHODS: A retrospective cohort study which followed up workers' vital status from 1940 to 2011, with serum surveys to support estimation of historical dioxin exposure levels. RESULTS: Among the 2192 study subjects, there were nine deaths in TCP workers from acute non-lymphatic leukaemia [standardized mortality ratio (SMR) = 2.88, 95% confidence interval (CI) 1.32-5.47], four mesothelioma deaths (SMR = 5.12, 95% CI 1.39-13.10) and four soft tissue sarcoma (STS) deaths (SMR = 3.08, 95% CI 0.84-7.87). In PCP workers, there were eight deaths from non-Hodgkin's lymphoma (SMR = 1.92, 95% CI 0.83-3.79), 150 from ischaemic heart disease (SMR = 1.20, 95% CI 1.01-7.89) and five from stomach ulcers (SMR = 3.38, 95% CI 1.10-7.89). There were no trends of increased mortality with increased dioxin exposure except for STS and 2,3,7,8-tetrachlorodibenzo-p-dioxin levels. This finding for STS should be interpreted with caution due to the small number of deaths and the uncertainty in diagnosis and nosology. CONCLUSIONS: While some causes of death were greater than expected, this study provides little evidence of increased risk when dioxin exposures are considered.

"Intrinsic" elimination rate and dietary intake estimates for selected indicator PCBs: toxicokinetic modeling using serial sampling data in US subjects, 2005-2010.

Changes in measured concentrations of persistent compounds such as polychlorinated biphenyls (PCBs) in an individual over time reflect not only intrinsic elimination rates but also any ongoing intake of the compounds and changes in the volume of distribution. Thus, "apparent" elimination rates calculated from data on changes in serum lipid-adjusted concentration may over- or under-estimate the "intrinsic" elimination rates for such compounds. Serum PCB concentrations were measured in 43 individuals approximately 5years apart. Changes in measured concentrations and body weights were used to estimate mass-based apparent elimination rates. The changes in estimated body mass of PCBs 105, 118, 138, 153, and 180 were input into a simple first-order model employing previously estimated intrinsic elimination rates to estimate congener-specific average dietary intake rates over the period between samples. Calculated median dietary intakes were compared to previous estimates. Intrinsic elimination rates were adjusted for two congeners. The analyses support central tendencies of intrinsic elimination rates of approximately 5years for PCBs 105 and 118, 11years for PCB 138, 14.4years for PCB 153, and 20years or more for PCB 180. Estimated dietary intakes for this population and time period depend on the assumed intrinsic elimination rates and range from 0.1ngkg(-1)d(-1) for PCB 105 to approximately 1-2ngkg(-1)d(-1) for PCB 180. Estimated body burdens of PCB 180 changed very little over the five-year period, suggesting near steady-state exposure levels. As a result, estimates for both elimination half-life and ongoing intake rates for this congener are highly uncertain.

Slips, trips and falls at a chemical manufacturing company.

BACKGROUND: Slips, trips and falls (STF) are a major cause of workplace injury. AIMS: To examine risk factors for STF at a large US chemical manufacturing company. METHODS: We conducted a case-control study of occupational STF. Cases were identified from company injury records between 1 April 2009 and 1 May 2011. Four controls per case were randomly selected from all active company workers employed during the same time. Data were collected through a questionnaire and from company medical examinations. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (95% CI) for personal, environmental and health-related risk factors for STF. RESULTS: There were 74 cases and 309 controls. The response rate was 65% for the cases and 68% for the controls. Most STF were unrelated to production activities. When examining all factors in a logistic regression model, increased OR were observed for increased body mass index (OR = 1.44, 95% CI: 1.03-2.02), having arthritis (OR = 2.11, 95% CI: 1.01-4.37), lack of exercise (OR = 2.25, 95% CI: 1.01-5.05), carrying materials (OR = 3.01, 95% CI: 1.41-6.43) and being female (OR = 2.46, 95% CI: 1.17-5.19). Reduced risk of STF was observed for never having smoked (OR = 0.48, 95% CI: 0.24-0.95), long service (OR = 0.53, 95% CI: 0.34-0.81) and persons working over 8h a day (OR = 0.42, 95% CI: 0.20-0.88). CONCLUSIONS: Risk factors for STF in a large US chemical company are similar to those reported from other workplaces, but we found that staying fit and healthy is important for reducing risk.

The healthy worker effect in US chemical industry workers.

BACKGROUND: Occupational studies typically observe a 20% deficit in overall mortality, broadly characterized as the healthy worker effect (HWE). Components of the HWE may be addressed by various analytical approaches. AIMS: To explore the HWE in a modern industrial cohort. METHODS: Standardized mortality ratios (SMRs) were calculated for 114,683 US chemical industry employees, who worked at least 3 days between 1960 and 2005. RESULTS: SMRs were 79 (95% confidence interval 78-80) for all causes, 81 (95% confidence interval 79-82) for heart disease, 70 (95% confidence interval 67-73) for non-malignant respiratory disease, 83 (95% confidence interval 81-85) for smoking-related cancers (buccal, cervix, oesophagus, stomach, pancreas, lung, larynx, bladder and kidney) combined and 97 (95% confidence interval 95-100) for other cancers. CONCLUSIONS: The low SMRs observed in this study are likely due to differential smoking between the cohort and the background population. Future considerations to control for the HWE should take this into account.

Correlates of serum dioxin to self-reported exposure factors.

The aim of the current analysis was to examine the determinates of lipid-adjusted body levels of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) from occupational histories, age, body mass index, and self-reported information from a questionnaire. We collected serum from 346 workers at a New Zealand chemical plant that manufactured and formulated the herbicide, 2,4,5-trichlorophenoxyacetic acid (2,4,5-T). Age, body mass index, and employment history were significant determinates of TCDD. The self-reported data on occupation, residence, and general diet were not predictive of serum levels and we observed no evidence of increased TCDD levels from living close to the site. For participants with putative occupational exposure, employment history and personal factors were important to understand the range of TCDD serum levels. For employees without direct occupational exposure, and resulting lower dioxin levels, we recommend further efforts to develop and validate questionnaires to better evaluate environmental sources of dioxins.

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.

Lymphohaematopoietic cancer risk among chemical workers exposed to benzene.

AIMS: To determine cause specific mortality in a cohort of 2266 chemical workers exposed to benzene in various manufacturing processes after 1935. METHODS: The cohort has accumulated over 80 000 person-years of observation; about 70% of the workers were followed for more than 30 years since first exposure. RESULTS: Mortality from non-malignant diseases of the blood was increased (SMR 2.17, 95% CI 0.87 to 4.48), and correlated with duration of benzene exposure, although risk had decreased from the previous investigation of this cohort. The risk for leukaemia was slightly above background (SMR 1.14, obs 12, 95% CI 0.59 to 1.99) but has also decreased since the earlier study of this cohort. SMRs for acute non-lymphocytic leukaemia (ANLL), chronic lymphatic leukaemia, and non-Hodgkin's lymphoma were 1.11, 0.42, and 1.06 respectively. There was evidence of a weak trend of increasing SMRs for leukaemia and possibly ANLL with increasing low-level cumulative exposure but not with other measures. CONCLUSION: Leukaemia and ANLL results were consistent with the mildly increased risk estimates from lower exposure subgroups of the Pliofilm cohort.

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.

Cancer risk for chemical workers exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin.

AIMS: To describe the long term mortality experience of a cohort of 2187 male chemical production workers previously exposed to substantial levels of dioxin. METHODS: Vital status for a previously identified cohort was determined for an additional 10 years, to 1995. Dioxin exposures took place before 1983 and were sufficient to result in chloracne in 245 individuals. Mortality rates were compared with national figures and with a large pool of co-workers in unrelated production jobs. RESULTS: All cancers combined (standardised mortality ratio (SMR) = 1.0, 95% CI 0.8 to 1.1) and lung cancer (SMR = 0.8, 95% CI 0.6 to 1.1) were at or below expected levels. Rates for soft tissue sarcoma (SMR = 2.4, 95% CI 0.3 to 8.6) and non-Hodgkin's lymphoma (SMR = 1.4, 95% CI 0.6 to 2.7) were greater than expected overall, but below expectation in the update period. No trend of increasing risk with increasing exposure was observed for these cancers. Workers who developed chloracne had very low all-cancer rates (SMR = 0.5, 95% CI 0.3 to 1.0), and lung cancer rates (SMR = 0.3, 95% CI 0.0 to 1.1). CONCLUSIONS: We found no coherent evidence of increased cancer risk from dioxin exposure in this cohort. Our study highlights the wide range of cancer rates and the lack of consistency across dioxin studies.

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.

A longitudinal study of respiratory health of toluene diisocyanate production workers.

A longitudinal comparison of 305 toluene diisocyanate (TDI) and 581 hydrocarbons workers employed at a Texas chemical manufacturing facility from 1971 through 1997 tested whether workplace exposure to TDI was associated with changes in any of the respiratory measures collected by the company's health surveillance program. Mean TDI exposures measured 96.9 ppb-months, or 2.3 ppb per job. At the end of the study, there were no differences in self-reported symptoms between the groups. Longitudinal analyses of symptoms and pulmonary function showed no correlation with TDI exposure, yielding an average annual decrease in forced expiratory volume at 1 second of 30 mL per year. We concluded that exposure to TDI at workplace concentrations was not associated with respiratory illnesses in this cohort, and consistent with other recent research, it seemed not to accelerate the normal age-related decline in pulmonary function.

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.