Evaluation of the recently established Dutch nationwide Archipelago of Ovarian Cancer Research biobank.

Fundamental and translational research in ovarian cancer aims to enhance understanding of disease mechanisms and improve treatment and survival outcomes. To support this, we established the Dutch multicenter, interdisciplinary Archipelago of Ovarian Cancer Research (AOCR) infrastructure, which includes a nationwide biobank. In this study, we share our experiences in establishing the infrastructure, offer guidance for similar initiatives, and evaluate the AOCR patient cohort.

Maximum-likelihood time-of-arrival estimation for saturated optical transient signals.

We employ right-censored Poisson point process models to develop maximum-likelihood procedures for estimating the time of arrival of transient optical signals subject to saturation distortion. The Poisson intensity is modeled as a template with an unknown scaling factor with additive background counts. Using Monte Carlo simulations, we explore the performance of different algorithms as a function of signal magnitude and saturation threshold.

Low preoperative skeletal muscle density is predictive for negative postoperative outcomes in older women with ovarian cancer.

Objective: To determine the predictive value of lumbar skeletal muscle mass and density for postoperative outcomes in older women with advanced stage ovarian cancer.

Methods: A multicenter, retrospective cohort study was performed in women ≥ 70 years old receiving surgery for primary, advanced stage ovarian cancer. Skeletal muscle mass and density were assessed in axial CT slices on level L3.

Expectation-maximization algorithm for amplitude estimation of saturated optical transient signals.

This paper addresses parameter estimation for an optical transient signal when the received data has been right-censored. We develop an expectation-maximization (EM) algorithm to estimate the amplitude of a Poisson intensity with a known shape in the presence of additive background counts, where the measurements are subject to saturation effects. We compare the results of our algorithm with those of an EM algorithm that is unaware of the censoring.

Validation and Implementation of BRCA1/2 Variant Screening in Ovarian Tumor Tissue.

BRCA1/2 variant analysis in tumor tissue could streamline the referral of patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer to genetic counselors and select patients who benefit most from targeted treatment. We investigated the sensitivity of BRCA1/2 variant analysis in formalin-fixed, paraffin-embedded tumor tissue using a combination of next-generation sequencing and copy number variant multiplex ligation-dependent probe amplification. After optimization using a training cohort of known BRCA1/2 mutation carriers, validation was performed in a prospective cohort in which screening of BRCA1/2 tumor DNA and leukocyte germline DNA was performed in parallel.

'See and treat' approach for high-grade squamous intraepithelial cervical lesions.

Purpose Of Investigation: Evaluation of the over-treatment percentage when choosing a 'see and treat' approach in patients with de- viant cervical smear test results.

Materials And Methods: The authors performed a retrospective chart review among women who were treated for cytological low-grade squamous intraepithelial lesion (LSIL) or high-grade squamous intraepithelial lesion (HSIL) from January 2009 until December 2010. All patients who were treated for deviant Pap-smears were analyzed.

Exploring Morphologic and Molecular Aspects of Endometrial Cancer Under Progesterone Treatment in the Context of Fertility Preservation.

Objective: The standard treatment of early-stage (FIGO [International Federation of Gynecology and Obstetrics] I) endometrioid endometrial cancer (EEC) is hysterectomy with bilateral salpingo-oophorectomy. An alternative approach for younger women with low-grade EEC who wish to preserve fertility may be hormonal treatment. Previous studies have suggested that progesterone may elicit its antitumor effect in EEC by interacting with the Wingless (Wnt) and/or phosphatidylinositol 3-kinase (PI3K)/Akt pathways.

Vaccination against Oncoproteins of HPV16 for Noninvasive Vulvar/Vaginal Lesions: Lesion Clearance Is Related to the Strength of the T-Cell Response.

Purpose: Therapeutic vaccination with human papillomavirus type 16 (HPV16) E6 and E7 synthetic long peptides (SLP) is effective against HPV16-induced high-grade vulvar and vaginal intraepithelial neoplasia (VIN/VaIN). However, clinical nonresponders displayed weak CD8(+) T-cell reactivity. Here, we studied if imiquimod applied at the vaccine site could improve CD8(+) T-cell reactivity, clinical efficacy, and safety of HPV16-SLP (ISA101).

The long-term immune response after HPV16 peptide vaccination in women with low-grade pre-malignant disorders of the uterine cervix: a placebo-controlled phase II study.

The capacity of a low-dose HPV16 synthetic long-peptide vaccine (HPV16-SLP) to induce an HPV16-specific T-cell response as well as to establish long-term immunologic memory in patients with low-grade abnormalities of the cervix was determined in a placebo-controlled, double-blinded phase II study. In addition, the effect of a booster vaccination after 1 year was evaluated. Patients received either the HPV16-SLP or a placebo at the start of the study.

Treatment of vulvar intraepithelial neoplasia with topical imiquimod.

Background: Alternatives to surgery are needed for the treatment of vulvar intraepithelial neoplasia. We investigated the effectiveness of imiquimod 5% cream, a topical immune-response modulator, for the treatment of this condition.

Methods: Fifty-two patients with grade 2 or 3 vulvar intraepithelial neoplasia were randomly assigned to receive either imiquimod or placebo, applied twice weekly for 16 weeks.

[Manifest carcinoma of the glandula vestibularis major (Bartholin's gland), detected one year after an inguinal lymph-node metastasis].

A 68-year-old woman had had a TNM stage-III rectal carcinoma at the age of 54 for which she had undergone a low anterior resection followed by postoperative radiotherapy and adjuvant chemotherapy with fluorouracil and levamisol. More than 10 years later she presented with a swelling in the right groin, which turned out to be a metastasis; this was a poorly differentiated carcinoma with some of the characteristics of a transitional epithelial carcinoma, for which no primary tumour was found. The lymph node was excised.

Combining HPV and MIB-1 tests reduces the number of colposcopies in women with equivocal cytology.

Background: In this study the MIB-1 immunostaining pattern as an index of cellular proliferation was analyzed in smears diagnosed as borderline dyskaryosis in order to establish whether the combination of human papillomavirus testing and MIB-1 staining could resolve equivocal cytology.

Methods: Conventional Pap smears of 108 women diagnosed as borderline dyskaryosis were stained with MIB-1 and the proliferation index was assessed. These women were evaluated by colposcopy, histological sampling, and human papillomavirus, semi-quantitative evaluated by hybrid Capture II test.

Interobserver agreement on interpreting hand drawings of colposcopy in women with borderline cytology to predict high-grade lesions.

Objective: To assess the interobserver agreement on interpreting hand drawings as a colposcopic image recording technique in women with borderline cytology and to assess the correlation between colposcopic impression and histological outcome.

Methods: We used colposcopic documentation and histology from a cohort study of women with borderline dyskaryosis. Four gynecologists and four residents scored the same 30 colposcopic documentation forms.

Can viral load, semi-quantitatively evaluated, of human papillomavirus predict cytological or histological outcome in women with atypical squamous or glandular cells of undetermined significance cytology?

Objective: 1) To assess the regression to normal cytology in women with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance (ASCUS/AGUS) and absence or clearance of human papillomavirus (HPV) infection; 2) To evaluate the association between viral load, semi-quantitatively evaluated, and cytological or histological outcome.

Material And Methods: In this cohort study HPV test and biopsy was taken in 148 women with ASCUS/AGUS cytology. After 12-18 months a HPV test and cervical smear were repeated in 121 women.

Intraoperative detection of carcinoid tumor of the ovary by gamma probe.

Purpose: To demonstrate the detection of carcinoid tumor of the ovary by gamma probe during surgery in a patient in whom the exact location of a metastatic tumor was uncertain.

Methods: Twenty-four hours after injection of 350 MBq (9.5 mCi) I-123, an anterior image of the abdomen was acquired before surgery to demonstrate MIBG accumulation.

Detection of cervical intraepithelial neoplasia in women with atypical squamous or glandular cells of undetermined significance cytology: a prospective study.

Background: (1) To assess the prevalence of histologically confirmed cervical intraepithelial neoplasia in patients with cervical smears diagnosed as atypical squamous or glandular cells of undetermined significance. (2) To evaluate the role of colposcopy and the presence of human papillomavirus in detecting underlying cervical intraepithelial neoplasia.

Materials And Methods: In this prospective cohort, 148 women with atypical squamous or glandular cells of undetermined significance were evaluated by colposcopy, histological sampling, and human papillomavirus deoxyribonucleic acid testing.

[Female circumcision; histories of 3 patients].

Three Somali women presented with problems of the infibulation they had undergone when they were girls. The first one was 22 years old and had problems with coition, the second one was 21 years old and had problems with parturition, the third one was 28 years old and had an epidermal cyst near the ventral commissure of the vulva. Infibulation is a form of female circumcision, in which the clitoris, labia minora and labia majora are removed and the ostium vaginae is reduced to less than a centimeter.

[Sickle cell anemia during pregnancy].

A 31-year-old pregnant Creole woman with sickle-cell anaemia went through a crisis of acute cholecystitis at 29 weeks' amenorrhoea. The crisis subsided after cholecystectomy, at which relative reduction of the number of sickle-cells by blood transfusions, adequate oxygenation, fluid, and antibiotic prophylaxis were provided. After 35 weeks' amenorrhoea, a healthy son was delivered by caesarean section.

Human papillomavirus infection in squamous cell carcinoma of the vulva, in various synchronous epithelial changes and in normal vulvar skin.

Objective: To investigate the prevalence of human papillomavirus (HPV) infection in various vulvar lesions.

Methods: HPV infection using consensus primer-PCR was studied in 66 patients with vulvar carcinoma and in the synchronous epithelial lesions.

Results: HPV infection was present in 13/66 carcinoma, in 1/33 VIN I, in 3/11 VIN II, in 8/16 VIN III, in 2/30 lichen sclerosus, in 1/37 squamous cell hyperplasia, and in 2/55 normal skin specimens.

p53 protein overexpression is common and independent of human papillomavirus infection in squamous cell carcinoma of the vulva.

Background: Human papillomavirus (HPV) infection and p53 abnormalities might both play a role in the carcinogenesis of subtypes of squamous cell carcinoma of the vulva. In this study, the authors investigated the prevalence of and the relationship between p53 overexpression and HPV infection in patients with vulvar carcinoma.

Methods: Immunohistochemical methods for the detection of p53 protein and consensus primer polymerase chain reaction (PCR) were used, followed by direct sequencing of the PCR product for the evaluation of HPV subtype infection.

p53 protein overexpression, a frequent observation in squamous cell carcinoma of the vulva and in various synchronous vulvar epithelia, has no value as a prognostic parameter.

In this study we have investigated the prevalence of p53 overexpression in various vulvar lesions and its significance as a prognostic parameter in patients with vulvar carcinoma. Overexpression of p53 was studied in 66 patients with squamous cell carcinoma of the vulva and in the following synchronous epithelial lesions: intraepithelial neoplasia grade I (VIN I) (n = 33), VIN II (n = 11), VIN III (n = 16), lichen sclerosus (n = 30), squamous cell hyperplasia (n = 37), normal vulvar skin of patients with vulvar carcinoma (n = 55), and in 18 samples of normal skin from healthy controls. Survival curves of the p53-positive and p53-negative patients were compared using the log-rank test.

The relevance of various vulvar epithelial changes in the early detection of squamous cell carcinoma of the vulva.

The objective of this study is to evaluate the possible relevance of vulvar epithelial changes as a risk factor for squamous cell carcinoma of the vulva. The data of 66 women surgically treated for squamous cell carcinoma of the vulva have been analyzed. More than 6500 slides from the resection specimens were revised with special emphasis on concurrent epithelial changes.

Benign and malignant pathology of the vulva.

In this review, we focus on rare benign and malignant diseases. It is shown that benign vulvar conditions require thorough examination of other parts of the body, because a relationship with systemic diseases, like cicatricial pemphigoid, pemphigus vulgaris, toxic epidermal necrolysis, infections with parasites and Behçet's syndrome, may be present. Co-operation with medical specialists is warranted.

beta-Glucuronidase deficiency as a cause of fetal hydrops.

Mucopolysaccharidosis type VII (MPS VII) was diagnosed in a case of severe fetal hydrops. beta-glucuronidase deficiency was demonstrated in the amniotic fluid, which was obtained at 25 weeks of gestation, and in the fibroblasts of the child, which were cultured after fetal death in the 26th week of gestation. In the amniotic fluid the two-dimensional electrophoresis pattern of glycosaminoglycans was in agreement with MPS VII.