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 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.

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.

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.

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.

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.

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.

Lymph node detection by MRI before and after a systematic pelvic lymphadenectomy.

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.

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.

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).

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.

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).

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.

Hypoxia-inducible factor 1 alpha is essential for hypoxic p27 induction in endometrioid endometrial carcinoma.

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.

Symptomatic candidiasis: Using self sampled vaginal smears to establish the presence of Candida, lactobacilli, and Gardnerella vaginalis.

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.

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.

[Settlement effected for damages for victims of diethylstilbestrol (DES)].

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.

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.

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.

Progressive derailment of cell cycle regulators in endometrial carcinogenesis.

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)).

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.

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.

p16 is consistently expressed in endometrial tubal metaplasia.

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.