ABSTRACT
OBJECTIVE: Pelvic lymphadenectomy is considered the gold standard to diagnose and possibly treat lymphatic metastases in gynaecological cancer patients. The aim of this study is to evaluate whether all presurgical MRI detected lymph nodes were removed during the systematic pelvic lymph node dissection (PLND) in cervical cancer patients. METHODS: 21 consecutive cervical cancer patients who were scheduled to undergo a PLND were evaluated by a MRI scan prior to surgery and 6 weeks afterwards. All patients had tumour metastasis negative lymph nodes at histopathological examination. RESULTS: On average, 10 pelvic lymph nodes (range 5-17) per patient were detected by presurgical MRI. Postsurgical MRI scans showed that on average 1 (range 0-3) pelvic node per patient was not removed by surgery. In total, 14% of the presurgical MR detected nodes were not removed by surgery (31/225). Approximately half of all lymph nodes that remained after surgery were located in the obturator region. In spite of the remaining nodes, surgery and histopathological examination did detect more nodes than MRI: on average 21 lymph nodes per patient (range 9-59) were removed. Another 2 lymph nodes (range 0-6 per patient) were judged to be newly developed after surgery. CONCLUSION: Although surgery was able to remove many more lymph nodes than those detected by presurgical MRI, 14% of presurgical MRI detected lymph nodes were not removed by PLND. The value of MRI prior to surgery for the detection of pathological lymph nodes is a subject of further research.
Subject(s)
Lymph Nodes/pathology , Lymph Nodes/surgery , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Adult , Aged , Female , Humans , Lymph Node Excision , Magnetic Resonance Imaging/methods , Middle Aged , Pelvis/pathologyABSTRACT
Hypoxia-inducible factor 1alpha (HIF-1alpha) plays an essential role in the adaptive response of cells to hypoxia. The cyclin-dependent kinase inhibitor p27(Kip1) is highly expressed in the normal endometrium but is lost during endometrial carcinogenesis. However, in high-grade cancers, p27 re-expression is observed. We analysed the role of HIF-1alpha in hypoxia-induced expression of p27 in vitro and in vivo in endometrial cancer. Paraffin-embedded specimens from endometrioid endometrial carcinoma (n = 39) were stained immunohistochemically for HIF-1alpha, p27, and Ki67. HEC1B, an endometrial carcinoma cell line, was cultured under normoxic or hypoxic conditions in the presence or absence of transiently expressed short hairpin RNAs targeting HIF-1alpha. Protein expression of p27 and HIF-1alpha was assessed by western blotting. Immunohistochemical staining revealed perinecrotic HIF-1alpha expression in 67% of the cases and p27 staining centrally in the tumour islands, mostly around necrosis, in 46% of the cases. In 50% of the tumours with perinecrotic HIF-1alpha expression, p27 and HIF-1alpha perinecrotic/central co-localization was observed. In these tumour sections, hypoxia-associated p27 expression showed less proliferation around necrosis. Analysis of cultured endometrial carcinoma cells demonstrated that p27 protein expression is induced by hypoxia. This induction was abrogated by transient knockdown of HIF-1alpha using RNAi. Furthermore, hypoxia induced cell cycle arrest in HEC1B cells. We conclude that, in endometrioid endometrial carcinoma, p27 re-expression by hypoxia is HIF-1alpha-dependent and leads to cell cycle arrest. This may contribute to the survival of cancer cells in hypoxic parts of the tumour.
Subject(s)
Carcinoma, Endometrioid/metabolism , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Endometrial Neoplasms/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/physiology , Neoplasm Proteins/metabolism , Adult , Aged , Aged, 80 and over , Carcinoma, Endometrioid/pathology , Cell Cycle/physiology , Cell Hypoxia/physiology , Cell Proliferation , Endometrial Neoplasms/pathology , Female , Humans , Immunoenzyme Techniques , Ki-67 Antigen/metabolism , Middle Aged , Necrosis , Neoplasm Staging , Tumor Cells, CulturedABSTRACT
BACKGROUND: Derailments of the control mechanisms of the cell cycle can initiate carcinogenesis, and play a role in progression to cancer. AIM: To explore the expression of cell cycle proteins in normal, premalignant and malignant endometrial lesions representing the morphologically well defined stepwise model of human endometrial carcinogenesis METHODS: Observational study. Paraffin-embedded specimens from inactive endometrium (n = 16), endometrial hyperplasia (n = 23) and endometrioid endometrial carcinoma (n = 39) were stained immunohistochemically for cyclin A, cyclin B1, cyclin D1, cyclin E, cdk2, p16, p21, p27, p53 and Ki67(MIB-1)). Differences in expression between the tissues, and correlation with classical prognostic factors for the carcinomas were analysed. RESULTS: Expression of cyclin A and Ki67 gradually increased from normal through hyperplasia to carcinoma, indicating that proliferation increases over the carcinogenetic spectrum. cdk2, p16 and p21 gradually increased from normal through hyperplasia to carcinoma, indicating their potential importance in both early and late carcinogenesis. Cyclin D1, cyclin E and p53 especially increased and p27 decreased from hyperplasia to carcinoma, underlining their role in late carcinogenesis. In cancers, expression of cyclin A, p53 and Ki67 was positively correlated to grade, and cyclin A was positively correlated with cdk2, p21, Ki67, cyclin E and p53. CONCLUSION: During (endometrioid) endometrial carcinogenesis, there is increasing proliferation paralleled by progressive derailment of cyclin B1, cyclin D1, cyclin E, p16, p21, p27, p53, and cdk2, indicating the importance of these cell cycle regulators in endometrial carcinogenesis.
Subject(s)
Cell Cycle Proteins/metabolism , Cell Transformation, Neoplastic/metabolism , Endometrial Neoplasms/metabolism , Neoplasm Proteins/metabolism , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Adult , Aged , Aged, 80 and over , Cell Proliferation , Cell Transformation, Neoplastic/pathology , Disease Progression , Endometrial Neoplasms/pathology , Endometrium/metabolism , Endometrium/pathology , Female , Humans , Hyperplasia/metabolism , Hyperplasia/pathology , Middle Aged , Neoplasm Staging , Precancerous Conditions/metabolism , Precancerous Conditions/pathologyABSTRACT
In a prospective cohort study, 10 symptomatic women with recurrent vulvovaginal candidiasis were taught how to prepare vaginal smears of their own vaginal fluids on days 7, 14, 21, and 28. The 40 smears were stained with the PAS-method and examined by three different cytopathologists for presence of Candida. Thereafter, the smears were restained with Giemsa-stain to determine presence of lactobacilli, Gardnerella vaginalis ("clue cells") and neutrophils. All three cytopathologists unequivocally established Candida blastospores and (pseudo)hyphae in 27 out of the 40 PAS-stained vaginal smears, whereas in the remaining 13 smears Candida was not found. All 10 patients had Candida in their smears during the second half of their menstrual cycle.Self sampled smears prove to be reliable for establishing the presence of Candida in symptomatic patients with candidiasis. Candida is associated with a lactobacillus-predominated vaginal flora, but with the absence of Gardnerella vaginalis. Further studies may be directed towards the interaction between the various members of the vaginal flora. This study should open molecular methodology for determining the possible interactions of lactobacilli and Candida.
Subject(s)
Candida/isolation & purification , Candidiasis, Vulvovaginal/diagnosis , Candidiasis, Vulvovaginal/microbiology , Gardnerella vaginalis/isolation & purification , Lactobacillus/isolation & purification , Vaginal Smears/methods , Adult , Aged , Female , Gram-Positive Bacterial Infections/diagnosis , Gram-Positive Bacterial Infections/microbiology , Gram-Positive Bacterial Infections/pathology , Humans , Middle Aged , Predictive Value of Tests , Prospective Studies , Pruritus/etiology , Reproducibility of Results , Sensitivity and Specificity , Specimen Handling , Vagina/microbiology , Vagina/pathology , Vaginal Discharge/etiologyABSTRACT
In 2007 the Dutch DESFonds (DES Fund) starts payment to victims of exposure to diethylstilbestrol in a collective settlement. This is unique in the world because the arrangement covers the entire range of DES-related disorders and individual persons do not have to start an expensive and emotionally taxing legal procedure with uncertain outcome, which would last several years. Individuals can now be compensated based on medical evidence of DES exposure and the presence of a DES-related disorder covered by the settlement. In close collaboration with the DES Centre (an association of DES victims) a careful procedure was followed before this settlement was realised. The Dutch Expert Committee on DES-related Health Effects first reviewed the literature for evidence and established a list of disorders with a causal association with DES. For each DES-related disorder covered by the settlement, the appropriate compensation was determined by the attributive risk and the severity of the disease. The settlement is the result of close collaboration between all parties involved.
Subject(s)
Compensation and Redress , Diethylstilbestrol/adverse effects , Estrogens, Non-Steroidal/adverse effects , Neoplasms/chemically induced , Prenatal Exposure Delayed Effects , Female , Humans , Netherlands , Pregnancy , Risk FactorsABSTRACT
Depressive symptoms and urinary symptoms are both highly prevalent in pregnancy. In the general population, an association is reported between urinary symptoms and depressive symptoms. The association of depressive and urinary symptoms has not yet been assessed in pregnancy. In this study, we assessed (1) the prevalence of depressive symptoms, over-active bladder (OAB) syndrome, urge urinary incontinence (UUI) and stress urinary incontinence (SUI) during and after pregnancy using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Urogenital Distress Inventory (UDI) and (2) the association of depressive symptoms with urinary incontinence and over-active bladder syndrome during and after pregnancy, controlling for confounding socioeconomic, psychosocial, behavioural and biomedical factors in a cohort of healthy nulliparous women. Our data show a significant increase in prevalence of depressive symptoms, UUI, SUI and OAB during pregnancy and a significant reduction in prevalence of depressive symptoms, SUI and OAB after childbirth. UUI prevalence did not significantly decrease after childbirth. In univariate analysis, urinary incontinence and the OAB syndrome were significantly associated with a CES-D score indicative of a possible clinical depression at 36 weeks gestation. However, after adjusting for possible confounding factors, only the OAB syndrome remained significantly associated (OR 4.4 [1.8-10.5]). No association was found between depressive and urinary symptoms at 1 year post-partum. Only OAB was independently associated with depressive symptoms during pregnancy. Possible explanations for this association are discussed.
Subject(s)
Depression/complications , Urination Disorders/complications , Depression/epidemiology , Female , Gestational Age , Humans , Incidence , Multivariate Analysis , Netherlands/epidemiology , Pregnancy , Urination Disorders/epidemiologyABSTRACT
BACKGROUND: Cell cycle proteins and HIF-1alpha with downstream factors are often abberrantly expressed in (pre)neoplastic tissue. METHODS: Paraffin-embedded specimens of inactive endometrium with TM (n=15), ovarian inclusion cysts (n=6), cervix with TM (tubal metaplasia) (n=3), Fallopian tubes (n=7), cycling endometrium (n=9) and a ciliated cell tumor of the ovary were stained for p16 and LhS28. 39 Endometrioid endometrial carcinomas and 5 serous endometrial carcinomas were stained for p16. Additionally, inactive endometrium (n=15) was immunohistochemically stained for p21, p27, p53, cyclin A, cyclin D1, cyclin E, HIF-1alpha, CAIX, Glut-1 and MIB-1. RESULTS: A mosaic pattern of expression of p16 was seen throughout in all cases of endometrial TM (15/15), in 2/6 of the ovarian inclusion cysts with TM, in all (3/3) cervical TM and focal in 5/7 of Fallopian tube cases. Mosaic expression was also seen in a ciliated cell tumor of the ovary and in 18/39 of endometrioid endometrial carcinomas, and diffuse p16 expression was seen in 5/5 serous carcinomas. In comparison with normal endometrium, TM areas in the endometrium showed significantly increased expression of HIF-1alpha, cyclin E, p21 and cyclin A, and decreased expression of p27. Membranous expression of CAIX and Glut-1 was only seen in TM areas, pointing to functional HIF-1alpha. CONCLUSION: As p16 is consistently expressed in TM, less and only patchy expressed in the normal Fallopian tube, is paralleled by aberrant expression of cell cycle proteins, HIF-1alpha, CAIX and Glut-1 and resembles the pattern of p16 expression frequently seen in endometrial carcinomas, we propose endometrial TM to be a potential premalignant endometrial lesion.
Subject(s)
Cyclin-Dependent Kinase Inhibitor p16/analysis , Endometrium/pathology , Fallopian Tubes/pathology , Carcinoma, Endometrioid/metabolism , Carcinoma, Endometrioid/pathology , Cervix Uteri/chemistry , Cervix Uteri/pathology , Cyclin A/analysis , Cyclin D1/analysis , Cyclin E/analysis , Cyclin-Dependent Kinase Inhibitor p21/analysis , Cyclin-Dependent Kinase Inhibitor p27/analysis , Cyclin-Dependent Kinase Inhibitor p27/metabolism , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Endometrium/chemistry , Fallopian Tubes/chemistry , Female , Glucose Transporter Type 1/analysis , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/analysis , Immunohistochemistry , MetaplasiaABSTRACT
Stage IA vulvar carcinoma is not supposed to metastasize to the lymph nodes. Therefore, it is assumed that these lesions can be safely treated by less aggressive methods than macroinvasive carcinomas. However, in this case report, two patients are described who had vulvar lesions with a depth of invasion of less than 1 mm and developed lymph node metastases in the groin despite radical wide local excision of their lesions. Both the patients underwent lymphadenectomy and received postoperative radiation therapy on the groins. Neither of the two patients died of vulvar carcinoma. Thus, we conclude that vigilance for the occurrence of lymph node metastases remains necessary after radical, local excision in stage IA vulvar cancer. However, this case report also shows that adequate treatment of groin node metastases can result in a very good long-term survival.
Subject(s)
Carcinoma/pathology , Lymphatic Metastasis , Vulvar Neoplasms/pathology , Aged, 80 and over , Female , Humans , Lymph Node Excision , Middle Aged , RecurrenceABSTRACT
OBJECTIVES: The aim of this study was to evaluate whether the efficiency of the current diagnostic work up following postmenopausal bleeding could be improved by diagnostic strategies that take into account characteristics of the women in addition to the currently recommended transvaginal measurement of endometrial thickness to determine for subsequent histological assessment. DESIGN: Multicenter, prospective cohort study. SETTING: A university hospital and seven teaching hospitals in the Netherlands. SAMPLE: Consecutive women not using hormone replacement therapy, presenting with postmenopausal bleeding. METHODS: Five hundred and forty women underwent transvaginal sonography, and in case of endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling was performed. Presence of carcinoma was ruled out by the absence of abnormalities in histological specimen or by an uneventful follow up of at least 6 months. MAIN OUTCOME MEASURES: Probability of endometrial carcinoma was estimated by multivariable logistic regression models. For each diagnostic strategy, we calculated diagnostic accuracy (area under receiver operating characteristic curve [AUC]), negative predictive value (NPV) and the number of diagnostic procedures. RESULTS: A strategy with transvaginal sonography alone with a fixed threshold incorrectly classified 0.7% of the women as nonmalignant (NPV: 99.3% [98.5-100%]), with 97% sensitivity and 56% specificity. A strategy integrating characteristics of the women with transvaginal sonography could result in less false reassurances (NPV: 99.6% [99.2-100%]), with only marginal decrease in diagnostic procedures, or a minor increase in false reassurances (NPV: 99.0% [98.3-100%]), with a substantial reduction (15-20%) in the procedures. AUCs associated with these strategies could improve from 0.76 (0.73-0.79) for transvaginal sonography alone to 0.90 (0.87-0.93) for the integrated strategy. CONCLUSION: Taking into account the characteristics of the women could increase the efficiency of the diagnostic work up for postmenopausal bleeding.
Subject(s)
Endometrial Neoplasms/diagnostic imaging , Postmenopause , Uterine Hemorrhage/diagnostic imaging , Adult , Age Factors , Aged , Aged, 80 and over , Anticoagulants/therapeutic use , Body Mass Index , Cohort Studies , Endometrial Neoplasms/complications , Female , Humans , Hypertension/complications , Medical History Taking , Middle Aged , Parity , Pregnancy , Prospective Studies , Sensitivity and Specificity , Thyroid Diseases/complications , Ultrasonography , Uterine Hemorrhage/etiologyABSTRACT
We performed a prospective cohort study to characterize the feasibility of urinary stress incontinence and pelvic organ prolapse surgery in day care. Two hundred and one women were prepared for day surgery by a standardised protocol; 132 women underwent a single Tension-free Vaginal Tape/Tension-free Vaginal Tape-Obturator procedure, and 69 women had additional or only pelvic organ prolapse surgery. The main outcome measures were complications, satisfaction score and recommendation to others, recorded after 3 days and 6-10 weeks. We found that it is feasible and safe to perform pelvic organ prolapse and urinary incontinence surgery in day care. Patients' satisfaction is high in all aspects of care and the majority would recommend it to others. In multivariate logistic regression analysis, only dissatisfaction with the care provided by the staff of the surgical ward was significantly associated with a negative recommendation to others (odds ratio 7.3, 95% confidence interval 1.6-33.5).
Subject(s)
Ambulatory Surgical Procedures , Patient Satisfaction , Urinary Incontinence, Stress/surgery , Uterine Prolapse/surgery , Adult , Aged , Ambulatory Surgical Procedures/psychology , Antibiotic Prophylaxis , Attitude to Health , Catheters, Indwelling , Cohort Studies , Feasibility Studies , Female , Humans , Intraoperative Complications , Middle Aged , Postoperative Complications , Prospective Studies , Safety , Suburethral Slings , Treatment Outcome , Urinary Bladder/injuries , Urinary Catheterization/instrumentation , Urinary Incontinence, Stress/psychology , Urinary Retention/etiology , Urinary Retention/therapy , Uterine Prolapse/psychologySubject(s)
Carcinoma/epidemiology , Medical Records Systems, Computerized/statistics & numerical data , Uterine Neoplasms/epidemiology , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/therapy , Combined Modality Therapy , Dilatation and Curettage , Disease-Free Survival , Female , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , Societies, Medical , Uterine Neoplasms/diagnosis , Uterine Neoplasms/therapySubject(s)
Carcinoma/epidemiology , Fallopian Tube Neoplasms/epidemiology , Medical Records Systems, Computerized/statistics & numerical data , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/therapy , Combined Modality Therapy , Disease-Free Survival , Fallopian Tube Neoplasms/diagnosis , Fallopian Tube Neoplasms/therapy , Female , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , Societies, MedicalSubject(s)
Gestational Trophoblastic Disease/epidemiology , Medical Records Systems, Computerized/statistics & numerical data , Pregnancy Complications, Neoplastic/epidemiology , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Combined Modality Therapy , Disease-Free Survival , Female , Gestational Trophoblastic Disease/diagnosis , Gestational Trophoblastic Disease/therapy , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Pregnancy , Pregnancy Complications, Neoplastic/diagnosis , Pregnancy Complications, Neoplastic/therapy , Proportional Hazards Models , Societies, MedicalSubject(s)
Carcinoma/epidemiology , Medical Records Systems, Computerized/statistics & numerical data , Ovarian Neoplasms/epidemiology , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/therapy , Combined Modality Therapy , Disease-Free Survival , Female , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Lymphatic Metastasis , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Ovarian Neoplasms/diagnosis , Ovarian Neoplasms/therapy , Proportional Hazards Models , Societies, MedicalSubject(s)
Carcinoma/epidemiology , Medical Records Systems, Computerized/statistics & numerical data , Vaginal Neoplasms/epidemiology , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/therapy , Combined Modality Therapy , Disease-Free Survival , Female , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Societies, Medical , Vaginal Neoplasms/diagnosis , Vaginal Neoplasms/therapySubject(s)
Carcinoma , Medical Records Systems, Computerized/statistics & numerical data , Uterine Cervical Dysplasia/epidemiology , Uterine Cervical Neoplasms/epidemiology , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/epidemiology , Carcinoma/therapy , Combined Modality Therapy , Disease-Free Survival , Female , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Proportional Hazards Models , Societies, Medical , Uterine Cervical Neoplasms/diagnosis , Uterine Cervical Neoplasms/therapy , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Dysplasia/therapySubject(s)
Carcinoma/epidemiology , Medical Records Systems, Computerized/statistics & numerical data , Vulvar Neoplasms/epidemiology , Women's Health , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Carcinoma/diagnosis , Carcinoma/therapy , Combined Modality Therapy , Disease-Free Survival , Female , Global Health , Humans , International Cooperation , Kaplan-Meier Estimate , Middle Aged , Neoplasm Invasiveness , Neoplasm Staging , Societies, Medical , Vulvar Neoplasms/diagnosis , Vulvar Neoplasms/therapyABSTRACT
The objective of this study was to establish the relationship between Candida vaginalis and (pre)neoplasia and the prevalence of Candida and (pre)neoplasia related to age and ethnicity. Data were collected from 445,671 asymptomatic women invited for mass screening between 1995 and 2002 and coded according to the Dutch cervical smear coding system (KOPAC) with six grades for (pre)neoplastic changes. Prevalence and relative risks (RRs) were established for Candida and squamous abnormalities in Dutch women and four groups of immigrants. The prevalence of Candida is significantly higher in the cohort of 30-year-old women and lower in the cohorts of 45-, 50-, 55-, and 60-year-old women. The RR of having Candida was higher for Surinamese women (1.24; CI 1.08-1.42). Furthermore, the RR of having mild dysplasia was higher for Surinamese women (1.47; CI 1.14-1.89) and for women born in other countries than in The Netherlands, Turkey, and Morocco (1.36; CI 1.13-1.62). No statistically significant relationship between (pre)neoplasia and Candida was observed. C. vaginalis is more frequent among Surinamese women. Presence of Candida is not associated with an increased risk for squamous abnormalities; therefore, women carrying Candida are not at an increased risk of developing cervical cancer.