Papanicolaou's nebular cells are related to HPV infection and HSIL.

Metaplastic cells with nebular cytoplasmic changes in the cervical smear are classified in the Dutch coding system for cervical screening as KOPAC O8 cells. Since these nebulated cells are already documented by Papanicolaou, we refer to these cells as Papanicolaou's nebular cells. We examined the simultaneous presence of these characteristic metaplastic cells and high-grade squamous intraepithelial lesion (HSIL) in a population-based data base from January 1991 and December 1996. The odds ratio (OR) of nebular cells concurring with HSIL increases with age. For the age cohort 30 years, the OR was 7.8 with a 95% confidence interval (CI) of 4.4-13.9. For the age cohort 60 years, the OR was 35.3 with a 95% CI of 7.8-159.2. Aiming to determine the nature of these nebular metaplastic cells, we performed Chlamydia and HPV PCR on 587 and 1,483 smears, respectively. With an OR of 0.9 [0.3-2.4] it is unlikely that Chlamydia plays a role in the appearance of these nebular cells in the smear. This study shows that with an OR of 5.9 [1.7-21.3] HPV is not only related to large koilocytosis but also to a nebular change of small metaplastic cells. This study reports that nebular changes of small metaplastic cells are related to cervical cancer and to HPV infection.

Longitudinal 3.0T MRI analysis of changes in lymph node volume and apparent diffusion coefficient in an experimental animal model of metastatic and hyperplastic lymph nodes.

PURPOSE: To perform a longitudinal analysis of changes in lymph node volume and apparent diffusion coefficient (ADC) in healthy, metastatic, and hyperplastic lymph nodes. MATERIALS AND METHODS: Three groups of four female Copenhagen rats were studied. Metastasis was induced by injecting cells with a high metastatic potential in their left hind footpad. Reactive nodes were induced by injecting Complete Freund Adjuvant (CFA). Imaging was performed at baseline and at 2, 5, 8, 11, and 14 days after tumor cell injection. Finally, lymph nodes were examined histopathologically. RESULTS: The model was highly efficient in inducing lymphadenopathy: subcutaneous cell or CFA inoculation resulted in ipsilateral metastatic or reactive popliteal lymph nodes in all rats. Metastatic nodal volumes increased exponentially from 5-7 mm(3) at baseline to 25 mm(3) at day 14, while the control node remained 5 mm(3). The hyperplastic nodes showed a rapid volume increase reaching a plateau at day 6. The ADC of metastatic nodes significantly decreased (range 13%-32%), but this decrease was also seen in reactive nodes. CONCLUSION: Metastatic and hyperplastic lymph nodes differed in terms of enlargement patterns and ADC changes. Enlarged reactive or malignant nodes could not be differentiated based on their ADC values.

The role of hypoxia inducible factor-1alpha in gynecological cancer.

Understanding the mechanisms of carcinogenesis and progression of gynecological tumors is important as these insights might lead to improved diagnostic tools for the pathologist, improved prediction of prognosis, response to therapy, and eventually better biology-based disease management, thereby improving prognosis and quality of life for the individual patient. Hypoxia is an important event in carcinogenesis because it renders a more aggressive phenotype with increased invasiveness and proliferation, formation of metastases and poorer survival. Although selecting patients with hypoxic tumors may therefore be clinically important, there is no consensus as to the method best suited for routine assessment of hypoxia. One of the potential tumor hypoxia markers is hypoxia inducible factor 1 (HIF-1). HIF-1 is the key cellular survival protein under hypoxia, and is associated with tumor progression and metastasis in various solid tumors. In this review, we show that in gynecological cancers, HIF-1A is emerging as an important factor in carcinogenesis, and that overexpression of HIF-1A and its target genes CA9 and SLC2A1 seems associated with shorter progression free- and overall survival. Since hypoxia and HIF-1A expression are associated with treatment failure, targeting HIF-1A could be an attractive therapeutic strategy with the potential for disrupting multiple pathways crucial for tumor growth. Currently, HIF-1A inhibitors are being studied in clinical trials in recurrent ovarian- and cervical cancer, and trials in other gynecological cancers are expected.

Trends in inflammatory status of the vaginal flora as established in the Dutch national screening program for cervical cancer over the last decade.

OBJECTIVE: To describe recent trends in the prevalence of cytologic patterns of the vaginal flora (koilocytosis, Trichomonas, dys-bacteriosis, Candida, Gardnerella, Actinomyces, Chlamydia trachomatis) over the last decade. STUDY DESIGN: From 1996 to 2005 > 500,000 cervical smears were screened in the context of the Dutch national screening program on a 5-year basis. Data from the first screening period were compared with those of the second screening period. RESULTS: Prevalences differed from 34.8 for dysbacteriosis to 0.2 for C trachomatis. Bacterial imbalance (dysbacteriosis, unequivocal Gardnerella and Trichomonas) showed a decline in all age groups. Cases of human papillomavirus (HPV)-related koilocytosis have dramatically increased among young women (30 and 35 years). CONCLUSION: Bacterial imbalance of the vaginal flora has significantly decreased during the past decade in all age cohorts. Campaigns on consciousness of vaginal hygiene might have contributed to this amazing effect. We ought to be concerned about the increase in HPV-related koilocytosis.

Detection of lymph node metastases by gadolinium-enhanced magnetic resonance imaging: systematic review and meta-analysis.

BACKGROUND: Gadolinium-based contrast agents are used with magnetic resonance imaging (MRI) to highlight tumor vascularity in organs. They are also widely used for primary tumor visualization. We conducted a systematic review and meta-analysis of the existing evidence of the accuracy of gadolinium-enhanced MRI for staging lymph node metastases. METHODS: We systematically searched the MEDLINE, Cochrane, CANCERLIT, and EMBASE databases for studies published in English or German from January 1, 1988, to January 1, 2008, that assessed the diagnostic accuracy of gadolinium-enhanced MRI in the evaluation of lymphatic metastases compared with histopathologic examination as the reference test. Based on a priori-defined clinical considerations, we studied three subgroups of studies: those that used a single malignancy criterion and those that used multiple malignancy criteria with or without contrast highlighting. Summaries of MRI sensitivity and specificity for detecting lymph node metastases were calculated using a bivariate regression model. All statistical tests were two-sided. RESULTS: The literature search yielded 43 full-text papers that were considered for inclusion in the meta-analysis. We performed quantitative pooled analyses on the 32 studies that provided data on patient-level diagnosis. The weighted estimates of sensitivity and specificity for all studies combined were 0.72 (95% confidence interval [CI] = 0.66 to 0.79) and 0.87 (95% CI = 0.82 to 0.91). Estimates of sensitivity and specificity were essentially unchanged for studies that used a single malignancy criterion (0.71 [95% CI = 0.61 to 0.79] and 0.88 [95% CI = 0.80 to 0.93], respectively; n = 11 studies) or multiple malignancy criteria without contrast enhancement (0.70 [95% CI = 0.58 to 0.79] and 0.86 [95% CI = 0.68 to 0.94], respectively; n = 6 studies). The sensitivity increased to 0.84 (95% CI = 0.70 to 0.92), with a specificity of 0.82 (95% CI = 0.72 to 0.89) for the nine studies that incorporated contrast enhancement in their multiple malignancy criteria. Six studies did not define the malignancy criteria they used. CONCLUSIONS: The overall accuracy of gadolinium-enhanced magnetic resonance imaging for the detection of nodal metastases is moderate. Incorporating contrast enhancement in the malignancy criteria substantially improves the accuracy of this diagnostic test.

Inflammatory events as detected in cervical smears and squamous intraepithelial lesions.

The Dutch cytological coding system, KOPAC, enables to code for eight inflammatory events, that is koilocytosis (related to human papillomavirus (HPV)), Trichomonas, dysbacteriosis [related to bacterial vaginosis (BV)], Candida, Gardnerella, Actinomyces, Chlamydia, and non-specific inflammation (leucocytosis). This study presents an analysis of 1,008,879 smears. Of each smear, the age of the woman and the reason for smear taking (screening or indication) was available. The cytoscores (per mille) for these codes were calculated. For the screening smears, the cytoscores were for koilocytosis (HPV) 2.6, for Trichomonas vaginalis 1.9, for dysbacteriosis 31.4, for Candida albicans 9.8, for Gardnerella vaginalis 0.7, for Actinomyces 6.9, for Chlamydia 0.8, and for non-specific inflammatory changes 66.4. For the calculation of the Odds Ratio (OR), normal smears were used as a reference. The cytoscores for Chlamydia and Gardnerella covaried with high grade SIL (HSIL), with an OR of 7 and 12, respectively. In addition, the OR for Trichomonas vaginalis, for dysbacteriosis, and for leucocytosis proved to be significantly high in the indication smears. This study provides an oversight of HSIL and the full range of cervical infections as detected by cytology, proving that this infectious byproduct of screening can be very valuable.

The impact of hospital type on the efficacy of chemotherapy treatment in ovarian cancer patients.

OBJECTIVE: The hospital type affects the surgical outcomes of ovarian cancer patients. In the present study, we wanted to investigate the effect of hospital type on chemotherapy efficacy. METHODS: Data were collected from 1077 ovarian cancer patients treated from 1996 to 2003 in a random sample of 18 Dutch hospitals. Hospitals were categorized by the number of medical oncologists working in a hospital and additionally by chemotherapy volume (< or =100, 101-200, or >200 patients yearly) and ovarian cancer patient-volume (< or =6, 7-12, >12 yearly). The outcomes were the proportions of patients achieving complete remission, recurrence rates, and disease-free and overall survival. Data were analyzed using multivariable logistic regression (complete remission and recurrence) and Cox regression (survival). RESULTS: Data of 761 of the 777 patients who received chemotherapy could be analyzed. Hospital type did not affect the complete remission rates, recurrence rates, or the disease-free survival. Overall survival was better in hospitals with 2 or more medical oncologists and in hospitals with a high ovarian cancer patient-volume (hazard ratios both 0.8 (95% confidence interval=0.7-1.0)). CONCLUSIONS: Thus, hospital type did not influence the outcomes of first-line chemotherapy in ovarian cancer patients. However, overall survival was better in hospitals with 2 or more medical oncologists and in hospitals with a high ovarian cancer patient-volume, suggesting differences in second-line chemotherapy.

Gardnerella infection as distinguished from cervical dysbacteriosis: the advantageous spin-off of cervical screening.

OBJECTIVE: To evaluate cytologic diagnoses of dysbacteriosis and Gardnerella infection and to obtain insight into the diagnostic problems of Gardnerella. STUDY DESIGN: One hundred randomly selected samples of each of 3 diagnostic series were rescreened by 2 pathologists, resulting in 2 rescreening diagnoses and a consensus diagnosis. A smear was considered unequivocal when the original O code and the O code of the consensus diagnoses were equal and discordant when the flora diagnoses of the 2 pathologists differed. RESULTS: Discordance was highest in the dysbacteriotic series (20%) and lowest in the healthy group (4%). Unequivocal diagnoses were established in 65% of the dysbacteriotic smears, 80% of the Gardnerella smears and 93% of the healthy smears. Misclassification of Gardnerella occurred in the presence of clusters of bacteria mixed with spermatozoa. CONCLUSION: Blue mountain cells in Gardnerella infection can be identified unequivocally in cervical smears. Because of the clinical importance of treating Gardnerella, such advantageous spin-offs of cervical screening should be exploited.

Specialized and high-volume care leads to better outcomes of ovarian cancer treatment in the Netherlands.

OBJECTIVE: We investigated the influence of hospital and gynecologist level of specialization and volume on surgical results and on survival of ovarian cancer patients. METHODS: Data were collected from 1077 ovarian cancer patients treated from 1996 to 2003 in a random sample of 18 Dutch hospitals. Hospitals and gynecologists were classified according to specialization (general, semi-specialized or specialized) and by volume (12 cases/year). Outcomes were percentage of adequately staged and optimally debulked patients and length of overall survival. Data were analyzed using multivariable logistic regression (surgical results) and Cox regression (survival). RESULTS: The level of specialization and the volume of hospitals and of gynecologists were strongly related to the proportion of adequately staged patients (adjusted odds ratio (OR) specialized hospitals 3.9 (95% confidence interval (CI) 2.0-7.6); specialized gynecologists 9.5 (95% CI 4.7-19)). Patients with stage III disease had a higher chance of optimal debulking when treated in specialized hospitals (adjusted OR 1.7 (95% CI 1.1-2.7)) or by high volume gynecologists (adjusted OR 2.8 (95% CI 1.4-5.7)). Overall survival was best in patients treated in specialized hospitals and by high-volume gynecologists. CONCLUSION: The specialization level of hospitals and the surgical volume of gynecologists positively influence outcomes of surgery and survival. Concentration of ovarian cancer care thus seems warranted.

Is centralization of ovarian cancer care warranted? A cost-effectiveness analysis.

OBJECTIVE: To evaluate the cost-effectiveness of tertiary referral care for ovarian cancer patients in the Netherlands. METHODS: We collected clinical and registry data on 1077 newly diagnosed ovarian cancer patients treated from 1996-2003 in a random sample of Dutch hospitals. Decision modelling was used to compare the cost-effectiveness of treatment in general hospitals, semi-specialized hospitals, and tertiary care centers. The actual direct medical costs of ovarian cancer treatment were evaluated. Long-term outcomes in terms of costs, quality-adjusted life-years (QALYs), and incremental costs per QALY gained were estimated. To assess uncertainty, multivariable sensitivity analyses and scenario analyses were performed. RESULTS: Treatment of ovarian cancer patients in semi-specialized hospitals costs on average euro882 more than in general hospitals (95% confidence interval -720 to 2462) and yields 0.12 additional QALYs (95% CI 0.02 to 0.22), resulting in an incremental cost-effectiveness ratio (ICER) of euro7135. Patients treated in tertiary care centers incurred again higher costs (euro10,591, 95% CI 8757 to 12,480) and also higher QALYs (0.10, 95% CI 0 to 0.21), resulting in an ICER of euro102,642 compared to semi-specialized hospitals. If the optimal debulking rate in tertiary care centers would increase to 70%, costs could drop below euro30,000 per QALY. CONCLUSION: Current treatment of ovarian cancer patients in semi-specialized hospital settings is a cost-effective strategy, while treatment in tertiary care centers becomes only cost-effective when better surgical results would be achieved.

Cytologically diagnosed Gardnerella vaginalis infection and cervical (pre)neoplasia as established in population-based cervical screening.

OBJECTIVE: Cervical inflammation has been proposed as a cofactor in the development of cervical cancer. The purpose of this study was to document the prevalence of cervical (pre)neoplastic changes in asymptomatic women with a cytologically diagnosed Gardnerella vaginalis infection. STUDY DESIGN: Data were collected from 800,498 Dutch asymptomatic women, participating in the Dutch national screening program. Prevalences of (pre)neoplasia were calculated for G vaginalis smears using a healthy flora as reference. RESULTS: The prevalence of G vaginalis infection was 0.6 per thousand. The odds ratio for (pre)neoplasia was significantly higher in smears with G vaginalis infection compared with smears of women with a healthy vaginal flora (odds ratio, 10.3; 95% confidence interval, 6.6-16.1). CONCLUSION: Cytologically diagnosed G vaginalis smears show a strong covariation with the presence of cervical (pre)neoplasia. Future research should therefore focus on the exact causal relation between cytologic G vaginalis infection and the presence of (pre)neoplastic changes of the cervix.

Gardnerella vaginalis and Lactobacillus sp in liquid-based cervical samples in healthy and disturbed vaginal flora using cultivation-independent methods.

Our objective was to determine the morphotype of the adherent bacteria in liquid-based cytology (LBC) in smears with healthy and disturbed vaginal flora. And to use PCR technology on the same fixed cell sample to establish DNA patterns of the 16S RNA genes of the bacteria in the sample. Thirty samples were randomly selected from a large group of cervical cell samples suspended in a commercial coagulant fixative "(BoonFix)." PCR was used to amplify DNA of five bacterial species: Lactobacillus acidophilus, Lactobacillus crispatus, Lactobacillus jensenii, Gardnerella vaginalis, and Mycoplasma hominis. The LBC slides were then analyzed by light microscopy to estimate bacterial adhesion. DNA of lactobacilli was detected in all cell samples. Seventeen smears showed colonization with Gardnerella vaginalis (range 2.6 x 10(2)-3.0 x 10(5) bacteria/mul BoonFix sample). Two cases were identified as dysbacteriotic with high DNA values for Gardnerella vaginalis and low values for Lactobacillus crispatus. The sample with the highest concentration for Gardnerella vaginalis showed an unequivocal Gardnerella infection. This study indicates that the adherence pattern of a disturbed flora in liquid-based cervical samples can be identified unequivocally, and that these samples are suitable for quantitative PCR analysis. This cultivation independent method reveals a strong inverse relationship between Gardnerella vaginalis and Lactobacillus crispatus in dysbacteriosis and unequivocal Gardnerella infection.

Specialized care and survival of ovarian cancer patients in The Netherlands: nationwide cohort study.

BACKGROUND: There is much debate on the necessity of regionalization of ovarian cancer care. We investigated the association between hospital type and survival of patients with ovarian cancer in The Netherlands. METHODS: A retrospective, population-based cohort study was performed on all Dutch patients diagnosed with ovarian cancer from January 1, 1996, through December 31, 2003. We used data from the Netherlands Cancer Registry that were linked to mortality data from the Statistics Netherlands database to obtain the date and cause of death. Five-year relative survival ratios, defined as the ratio of the observed survival in the patient population to the expected survival of women in the general population with the same age, were determined for the total population and for groups stratified by tumor stage and/or hospital type. The association between hospital type and disease-specific survival was analyzed by use of multivariable Cox regression analyses. RESULTS: We analyzed data from 8621 women with epithelial ovarian cancer, of whom 3482 (40%) were treated in general hospitals, 3510 (41%) were treated in semispecialized hospitals, and 1557 (18%) were treated in specialized hospitals. Five-year relative overall survival ratios of patients treated in general, semispecialized, and specialized hospitals were 38.0% (95% confidence interval [CI] = 36.0% to 39.9%), 39.4% (95% CI = 37.5% to 41.4%), and 40.3% (95% CI = 37.4% to 43.1%), respectively; median survival of patients aged 50-75 years was 36 months (interquartile range [IQR] = 13 to >54 months), 37 months (IQR = 14 to >54 months), and 38 months (IQR = 15 to >55 months), respectively. Age and cancer stage were associated with the relationship between hospital type and ovarian cancer-specific survival but histologic tumor type, grade, year of diagnosis, and socioeconomic status were not. Among patients with early-stage ovarian cancer, treatment in semispecialized and specialized hospitals was associated with lower risks of ovarian cancer-specific mortality than treatment in general hospitals. Among patients with stage I-IIA disease who were aged 50-75 years, risk of ovarian cancer-specific mortality was 30% and 42% lower after treatment in semispecialized and specialized hospitals, respectively, than in general hospitals (for semispecialized hospitals, hazard ratio [HR] = 0.70, 95% CI = 0.53 to 0.93; for specialized hospitals, HR = 0.58, 95% CI = 0.38 to 0.87). Among patients with advanced ovarian cancer, hospital type was not associated with survival. CONCLUSION: Hospital type was statistically significantly associated with survival among Dutch ovarian cancer patients with early-stage ovarian cancer: Patients who were treated in specialized and semispecialized hospitals survived longer than patients treated in general hospitals.

Candida and dysbacteriosis: a cytologic, population-based study of 100,605 asymptomatic women concerning cervical carcinogenesis.

BACKGROUND: The objective of this study was to investigate whether the presence of vaginal Candida or dysbacteriosis predisposes women to an increased susceptibility for (pre)neoplasia over time. METHODS: A retrospective, longitudinal, cohort study was performed and was conducted in a population of 100,605 women, each of whom had 2 smears taken over a period of 12 years as part of the Dutch Cervical Screening Program. From these women, a cohort of 1439 women with Candida and a cohort of 5302 women with dysbacteriosis were selected as 2 separate study groups. The control cohort consisted of women who had completely normal cervical smears (n = 87,903 women). These groups were followed retrospectively over time. The odds ratios (OR) for squamous abnormalities in the follow-up smear for the women in these 3 cohorts were established. RESULTS: The dysbacteriotic cohort was significantly more likely to have low-grade squamous intraepithelial lesions (LSIL) and high-grade squamous intraepithelial lesions (HSIL+) in their follow-up smear (OR, 1.85; 95% confidence interval [95% CI], 1.28-2.67 and OR, 2.00; 95% CI, 1.31-3.05, respectively) compared with women in the control group. In contrast, the Candida cohort had no significantly increased or decreased risk of developing SIL. The equivocal diagnosis 'atypical squamous cells of undetermined significance' was rendered significantly more often in the follow-up smear of both study cohorts (Candida cohort: OR, 1.42; 95% CI, 1.03-1.95; dysbacteriotic cohort: OR, 1.44; 95% CI, 1.22-1.71). CONCLUSIONS: The results from this study indicated that the presence of Candida vaginalis was not associated with an increased risk for SIL over time. In contrast, women with dysbacteriosis had a significantly increased risk of developing (pre)neoplastic changes. These findings should be taken into account in further research concerning predisposing factors for cervical carcinogenesis.

Pregnancy-related pelvic girdle pain in the Netherlands.

OBJECTIVE: In this longitudinal cohort study, we assessed the prevalence, associated delivery-related and psychosocial factors and consequences of self-reported pelvic girdle pain during and after pregnancy in the Netherlands. METHODS: A total of 412 women, expecting their first child, answered questionnaires regarding back and pelvic girdle pain, habits, and biomedical, sociodemographic and psychosocial factors, at 12 and 36 weeks gestation, and 3 and 12 months after delivery. In addition, birth records were obtained. Possible associations were studied using non-parametric tests. RESULTS: The prevalence of self-reported pelvic girdle pain was at its peak in late pregnancy (7.3%). One out of 7 women suffering from pelvic girdle pain at 36 weeks gestation, and almost half of the women suffering from pelvic girdle pain 3 months after delivery, continued to report symptoms 1 year after delivery. Women reporting pelvic girdle pain are less mobile than women without pain or women with back pain only, and more frequently have to use a wheelchair or crutches. No association was found between obstetric factors and pelvic girdle pain. Women with pelvic girdle pain report more co-morbidity and depressive symptoms. RECOMMENDATIONS: Normal obstetric procedures can be followed in women reporting pregnancy-related pelvic girdle pain. Prognosis is generally good, however, women reporting pelvic girdle pain 3 months after delivery need extra consideration. Attention needs to be given to psychosocial factors, in particular depressive symptoms.

The invasive front in endometrial carcinoma: higher proliferation and associated derailment of cell cycle regulators.

The aim of the study was to explore whether expression of proliferation and hypoxia-related proteins differs in the central parts and the invasive front in endometrial carcinomas. Proliferation-associated proteins Ki67 and cyclin A; cell cycle regulators p16, p21, p53, cyclin D1, cyclin E, and cdk2; and hypoxia-inducible factor 1alpha and its downstream factors glucose transporter 1, carbonic anhydrase IX, and vascular endothelial growth factor were immunohistochemically stained in paraffin-embedded specimens from endometrioid (n = 33), mucinous (n = 1), and serous (n = 5) endometrial carcinomas. The percentages of positive cells at the invasive front and central tumor parts were scored and compared. Ki67 (P < .001), cyclin E (P = .018), p16 (P = .003), and cdk2 (.001) were expressed higher at the invasive front than centrally (Wilcoxon signed ranks test). Higher expression of these antigens at the invasive front was seen in 31 of 38 cases for Ki67, in 16 of 39 cases for cyclin E, in 15 of 39 cases for cdk2, and in 11 of 39 cases for p16. The other cell cycle proteins and the hypoxia-related factors did not show significant differences in expression between the central parts and the invasive front. Endometrial carcinomas clearly show an invasive front that is characterized by higher proliferation and progressive derailment of the cell cycle regulators cyclin E, p16, and cdk2, but not by an increased hypoxic response.

Hypoxia and angiogenesis in endometrioid endometrial carcinogenesis.

BACKGROUND: Hypoxia-inducible factor 1alpha (HIF-1alpha) plays an essential role in the adaptive response of cells to hypoxia, triggering biologic events associated with aggressive tumor behavior. METHODS: Expression of HIF-1alpha and proteins in the HIF-1alpha pathway (Glut-1, CAIX, VEGF) in paraffin-embedded specimens of normal (n=17), premalignant (n=17) and endometrioid endometrial carcinoma (n=39) was explored by immunohistochemistry, in relation to microvessel density (MVD). RESULTS: HIF-1alpha overexpression was absent in inactive endometrium but present in hyperplasia (61%) and carcinoma (87%), with increasing expression in a perinecrotic fashion pointing to underlying hypoxia. No membranous expression of Glut-1 and CAIX was noticed in inactive endometrium, in contrast with expression in hyperplasia (Glut-1 0%, CAIX 61%, only focal and diffuse) and carcinoma (Glut-1 94.6%, CAIX 92%, both mostly perinecrotically). Diffuse HIF-1alpha was accompanied by activation of downstream targets. VEGF was significantly higher expressed in hyperplasias and carcinomas compared to inactive endometrium. MVD was higher in hyperplasias and carcinomas than in normal endometrium (p<0.001). CONCLUSION: HIF-1alpha and its downstream genes are increasingly expressed from normal through premalignant to endometrioid adenocarcinoma of the endometrium, paralleled by activation of its downstream genes and increased angiogenesis. This underlines the potential importance of hypoxia and its key regulator HIF-1alpha in endometrial carcinogenesis.

Association between urogenital symptoms and depression in community-dwelling women aged 20 to 70 years.

OBJECTIVES: To determine the association between urogenital symptoms and the occurrence of depressive symptoms. METHODS: A random sample of 3200 community-dwelling women, aged 20 to 70 years, was invited to answer a questionnaire. A total of 2042 questionnaires (63.8%) were returned. Urogenital symptoms were assessed with the Urogenital Distress Inventory and depressive symptoms with the Center for Epidemiological Studies Depression scale. A cutoff value of 16 or more on the Center for Epidemiological Studies Depression scale was considered as possible clinical depression. Univariate and multivariate logistic regression statistics were used. RESULTS: The prevalence of depressive symptoms (Center for Epidemiological Studies Depression scale score of 16 or more) was significantly greater in women with urinary incontinence than in those without (odds ratio 1.9, 95% confidence interval 1.6 to 2.3). However, this statistically significant association existed for all urogenital symptoms when assessed individually. After multivariate adjustment, the statistical significant association with depressive symptoms was lost for most urogenital symptoms. Only nocturia remained significantly associated with depression throughout all analyses (odds ratio 1.4, 95% confidence interval 1.1 to 1.8 for the symptom itself; and odds ratio 2.0, 95% confidence interval 1.3 to 3.2, when considering only bothersome nocturia symptoms). CONCLUSIONS: After adjusting for the influence of coexisting urogenital symptoms, no association between urinary incontinence and depression could be demonstrated. Only nocturia remained significantly associated with depressive symptoms.

The effect of vaginal and cesarean delivery on lower urinary tract symptoms: what makes the difference?

A prospective cohort study was undertaken to evaluate the effect of pregnancy and childbirth in nulliparous pregnant women. The focus of this paper is on the difference in the prevalences and risk factors for lower urinary tract symptoms (LUTS) between woman who delivered vaginally or by cesarean and secondly the effect of LUTS on the quality of life between these two groups was analyzed. Included were 344 nulliparous pregnant women who completed four questionnaires with the Urogenital Distress Inventory and the Incontinence Impact Questionnaire (IIQ). Two groups were formed: vaginal delivery group (VD), which included spontaneous vaginal delivery and an instrumental vaginal delivery and cesarean delivery group (CD). No statistical significant differences were found in the prevalences of LUTS during pregnancy between the two groups. Three months after childbirth, urgency and urge urinary incontinence (UUI) are less prevalent in the CD group, but no statistical difference was found 1 year postpartum. Stress incontinence was significantly more prevalent in the VD group at 3 and 12 months postpartum. The presence of stress urinary incontinence (SUI) in early pregnancy is predictive for SUI both in the VD as in CD group. A woman who underwent a CD and had SUI in early pregnancy had an 18 times higher risk of having SUI in year postpartum. Women were more embarrassed by urinary frequency after a VD. After a CD, 9% experienced urge urinary incontinence. Urge incontinence affected the emotional functioning more after a cesarean, but the domain scores on the IIQ were low, indicating a minor restriction in lifestyle. In conclusion, after childbirth, SUI was significantly more prevalent in the group who delivered vaginally. Besides a vaginal delivery, we found both in the VD and in the CD group that the presence of SUI in early pregnancy increased the risk for SUI 1 year after childbirth. Further research is necessary to evaluate the effect of SUI in early pregnancy on SUI later in life. Women were more embarrassed by urinary frequency after a vaginal delivery. UUI after a CD compared to a vaginal birth limited the women more emotionally; no difference was found for the effect of SUI on the quality of life between the two groups.

The prevalence of voiding difficulty after TVT, its impact on quality of life, and related risk factors.

OBJECTIVE: To determine the prevalence of voiding difficulty (VD), quality of life, and related risk factors after tension-free vaginal tape (TVT). DESIGN: Prospective cohort study in 703 women with a TVT procedure for stress urinary incontinence. MAIN OUTCOME MEASURES: VD stated by women, Urogenital Distress Inventory (UDI-6) question 5 (difficulty in emptying the bladder), maximum flow rate, postvoid residual urine, necessity of postoperative catheterization, tape division, and impact on quality of life (Incontinence Impact Questionnaire, IIQ-7). RESULTS: Postoperative catheterization (>24 h) was necessary in 11% and tape division in 1.3% of patients. There were 26% of women who stated VD and 25% reported moderate to great impairment on the UDI-6 after 36 months. While the negative impact on the outcome of TVT in women with abnormal voiding compared to women without is higher, the impact decreased significantly after TVT, implying a considerable improvement in quality of life. Pre-operative existing voiding difficulty and concomitant prolapse surgery were independent risk factors. CONCLUSIONS: Symptoms of VD occurred after TVT and caused lesser improvement in quality of life.