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M van Beurden

Publications and source records attributed to M van Beurden.

14 recordsLinked to original sources
PubMed2006

The role of gene expression profiling in the clinical management of ovarian cancer.

Several studies have addressed the clinical value of gene expression profiling in the field of ovarian cancer. This paper reviews the current status of knowledge that can be derived from such studies. Gene expression profiles can be used to reveal sets of genes that can distinguish normal ovarian tissue from invasive ovarian carcinomas. Independent validation of these sets may result in the identification of (a set of) markers valuable for the detection in an early stage. Microarray analysis has shown that different histological subtypes of ovarian cancer might be partly reflected by a different aetiology through the deregulation and activation of different pathways. In addition, this heterogeneity could therefore also lead to different tumour behaviours. Worldwide, the combination of paclitaxel and platinum chemotherapy has been incorporated in the standard protocol for the management of patients with advanced stage ovarian cancer, although the outcome in individual patients is uncertain. Gene expression profiling was found to be a prognostic tool with respect to chemosensitivity and had a predictive performance of 78-86%. With increasing numbers of data from published reports, access to these data for the reproducibility of its results and pooling becomes more and more important and will possibly lead to more individualisation of therapy.

Female↗
PubMed2006

In the absence of (early) invasive carcinoma, vulvar intraepithelial neoplasia associated with lichen sclerosus is mainly of undifferentiated type: new insights in histology and aetiology.

BACKGROUND: Differentiated vulvar intraepithelial neoplasia (VIN) is presumed to be the precursor of invasive squamous cell carcinoma (SCC) of the vulva. It is commonly assumed that differentiated VIN is related to lichen sclerosus (LS). However, evidence for this is limited to a small number of studies describing epithelial alterations adjacent to vulvar SCC. AIM: To study the histology and human papillomavirus (HPV) status in patients with a history of both LS and VIN without coexistent SCC. METHODS: Original biopsy specimens and surgical specimens of patients retrieved from the pathology files were revised for the presence of LS, VIN and (early) invasive SCC, specifically focused on the two different types of VIN: differentiated and undifferentiated. Thereafter, VIN lesions were tested for the presence of HPV DNA. RESULTS: Twenty-seven patients fulfilled the criteria for LS and VIN without SCC. In all 27 patients, LS was found to be related to undifferentiated VIN. Grading yielded the following results: VIN 1 (n=10), VIN 2 (n=11) and VIN 3 (n=6). Additionally, VIN lesions from 26 patients could be tested for the presence of HPV DNA. HPV DNA, predominantly type 16, was present in 8 (31%) of them. Seven of these eight patients had VIN 2 or 3. During follow-up, three patients progressed to (early) invasive carcinoma. In two of these patients, differentiated VIN was observed overlying early invasive SCC. CONCLUSIONS: VIN related to LS without coexisting SCC is likely to be undifferentiated, in contrast to what was previously thought. HPV DNA was demonstrated in 31% of the lesions, and was strongly related to high-grade VIN.

Adult↗
PubMed2005

CA125 and transvaginal ultrasound monitoring in high-risk women cannot prevent the diagnosis of advanced ovarian cancer.

OBJECTIVES: The main objective of screening is to identify cases of ovarian cancer in early stages. However, screening of women in the general population is ineffective due to a failure of detecting early-stage disease and high false positive rates of CA125 and transvaginal ultrasound (TVU) monitoring. The purpose of this study is to evaluate ovarian cancer screening by means of pelvic examination, serum CA125 and TVU in a consecutive series of high-risk women. METHODS: Clinical data were collected from 132 BRCA1, 20 BRCA2 germ line mutation carriers, 72 members of hereditary breast and ovarian cancer (HBOC) families and 88 breast cancer patients from a hereditary breast cancer (HBC) family, seen between January 1996 and December 2002. RESULTS: Among 10 women with an elevated CA125 level and a positive TVU, three screening carcinomas (one FIGO stage IC, one stage IIIB and one stage IV) and one interval carcinoma (stage IV) were detected. Five occult ovarian/fallopian tube carcinomas (two stage IA, one stage IC, one stage IIIB and one stage IV) after bilateral prophylactic (salpingo-) oophorectomy (BP(S)O) have been found in 152 women. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) of the combination of CA125 and TVU were the highest (40%, 99%, 40% and 99%) followed by CA125 alone (50%, 96%, 13% and 99%), pelvic exam (40%, 98%, 21% and 99%) and TVU, separately (40%, 90%, 6% and 99%). CONCLUSION: By combining CA125 with TVU results, a PPV of 40% was achieved. However, the diagnostic tools appear to be only sensitive in detecting ovarian cancer at an advanced stage, while three of four tumors with early-stage disease in this series had normal screening tests prior to the diagnosis.

Adult↗
PubMed2004

Clinical outcome of prophylactic oophorectomy in BRCA1/BRCA2 mutation carriers and events during follow-up.

A retrospective study was performed to assess the histopathologic findings in high-risk women undergoing bilateral prophylactic (salpingo)-oophorectomy. The medical files of BRCA1 or BRCA2 mutation carriers and members of a hereditary breast/ovarian cancer (HBOC) family, who had undergone prophylactic surgery, were reviewed. In all, 38 women underwent a bilateral oophorectomy (26 BRCA1, three BRCA2 and nine HBOC, respectively). A total of 90 women underwent bilateral salpingo-oophorectomy (58 BRCA1, six BRCA2, one BRCA1 and 2, 25 HBOC, respectively). At the time of salpingo-oophorectomy, five of 58 BRCA1 carriers (8.6%) were diagnosed with an occult carcinoma: two fallopian tube carcinomas, two ovarian carcinomas and one case was defined as a fallopian tube/ovarian carcinoma. No occult carcinomas were found in the other groups. Of the 38 patients, who underwent a bilateral oophorectomy (mean follow-up 45 months), three of 26 BRCA1 mutation carriers (3.4 in 100 women-years) developed peritoneal papillary serous carcinoma (PPSC) during follow-up. So far, no PPSC have occurred in the 90 women, who underwent a salpingo-oophorectomy (mean follow-up 12 months), including 58 BRCA1 carriers (0 in 60 in women-years). These results contribute to the thesis that BRCA1 germline mutation carriers are not only at risk for ovarian cancer, but also for fallopian tube carcinoma and peritoneal papillary serous carcinoma. Our data suggest that PPSC risk among BRCA2 carriers is lower than among BRCA1 carriers.

Adult↗
PubMed1999

The contribution of MIB 1 in the accurate grading of vulvar intraepithelial neoplasia.

AIM: To determine the interobserver variation in scoring presence and grade of vulvar intraepithelial neoplasia (VIN) in haematoxylin/eosin (H/E) slides, MIB 1 slides, and the combined use of H/E and MIB 1 slides. METHODS: 10 slides were stained with H/E and MIB 1 with each of the following diagnoses: normal vulvar skin, VIN 1, VIN 2, and VIN 3. Six observers first scored the H/E slides separately from the MIB 1 slides and second the combined H/E and MIB 1 slides. RESULTS: Unweighted group kappa for MIB 1 was 0.62 and the weighted group kappa was 0.91. This was significantly better than the unweighted group kappa for H/E slides (0.47, p = 0.023) as well as the weighted group kappa for H/E slides (0.82, p = 0.014). There was no improvement by the combined use of H/E and MIB 1 slides. VIN 2 is far less confused with VIN 3 in the combined use of H/E and MIB 1 slides (9%) than in H/E slides (38%) (p = 0.007). There is a tendency to grade VIN in a two tailed grading system rather than a three tailed grading system, which became more apparent with the combined use of H/E and MIB 1 slides. CONCLUSIONS: The interobserver variation with sole use of MIB 1 is better than with the use of H/E stain in VIN. The use of MIB 1 in grading VIN diminishes confusion between VIN 2 and VIN 3 fourfold. A two tailed grading system for VIN seems already to work in daily practice.

Antibodies, Monoclonal↗
PubMed1998

Human papillomavirus DNA in multicentric vulvar intraepithelial neoplasia.

Human papillomavirus (HPV) DNA in vulvar intraepithelial neoplasia (VIN) is associated with multifocality of VIN III and with multicentricity of other neoplastic squamous lesions in the cervix and vagina. The aim of this study was to establish the prevalence and type of HPV DNA in the lesions of vaginal intraepithelial neoplasia (VaIN) and cervical intraepithelial neoplasia (CIN) in patients with VIN III using the polymerase chain reaction (PCR). HPV DNA detection and histologic analysis were performed on alternating sections of paraffin-embedded biopsies of concomitant CIN and VaIN in 27 patients with VIN III. PCR was performed with consensus primers and HPV typing was performed by direct sequencing of the PCR amplimers. HPV DNA was detected in all VIN III lesions (93% contained HPV-16 DNA); in 96% of the CIN lesions (73% contained HPV-16 DNA); and in all VaIN lesions (75% contained HPV-16 DNA). The HPV type was not the same in 22% of the different lesions of VIN, CIN, and VaIN, even if the biopsies were taken at the same time.

Adult↗
PubMed1997

Normal findings in vulvar examination and vulvoscopy.

OBJECTIVE: To determine the normal vulvar findings by naked eye examination and by vulvoscopy in healthy women without vulvar complaints. DESIGN: Observational study. POPULATION: Forty healthy volunteers without vulvar complaints recruited via a newspaper advertisement. METHODS: Vulvar examination, human papillomavirus (HPV) polymerase chain reaction of vulvar and cervical swabs, saline and KOH smears and vulvoscopy before and after the application of 5% acetic acid. MAIN OUTCOME MEASURES: Prevalence of vestibular erythema, vestibular papillomatosis, HPV infection on the vulva and in the cervix and vulvoscopic findings. RESULTS: The mean age of the women was 37.8 years (median 38.0, range 21-56). Nine women were current smokers and 21 had previously smoked. Naked eye vulvar examination showed vestibular papillomatosis in 13 women (33%) and vestibular erythema in 17 women (43%). The touch test was positive in 9 of the 17 women (53%) with vestibular erythema. Vulvoscopy after the application of acetic acid 5% showed an acetowhite vestibule in all women. Twelve women (30%) had acetowhite lesions outside the vestibule. Six women (15%) were positive for HPV DNA. The presence of HPV DNA did not correlate with vestibular erythema or vestibular papillomatosis. There was a weak association between HPV DNA and acetowhite lesions outside the vestibule (P = 0.055, Fisher's exact test). In this group the younger women significantly more often had vestibular papillomatosis (t-statistic = 3.07; P = 0.003) and women who smoke more often had a genital HPV infection (P = 0.016, Fisher's exact test). CONCLUSIONS: Vestibular erythema, vestibular papillomatosis, and acetowhite lesions are common in this group of healthy women without vulvar complaints.

Adult↗
PubMed1996

Reproducibility of the interpretation of hysterosalpingography in the diagnosis of tubal pathology.

The aim of the study was to estimate the inter- and intra-observer reproducibility of the interpretation of hysterosalpingography (HSG) in the diagnosis of tubal pathology, and associate reproducibility with diagnostic accuracy. Four observers evaluated 143 HSGs twice, on proximal tubal obstruction, distal tubal obstruction, hydrosalpinx and peritubal adhesions. Diagnostic laparoscopy with chromopertubation was considered to be the reference strategy. Reproducibility (inter- and intra-observer agreement) was expressed in terms of kappa-values. Accuracy was expressed in terms of sensitivity, specificity and likelihood ratios. kappa-values for reproducibility between observers were almost perfect for proximal obstruction, substantial for distal obstruction and hydrosalpinx, and moderate for adhesions. kappa-values for reproducibility within observers were almost perfect for proximal obstruction and substantial for distal obstruction, hydrosalpinx and adhesions. HSG had a high specificity for proximal obstruction, but a low sensitivity. Distal obstruction, absence of hydrosalpinx and adhesions had a poor accuracy. The likelihood ratio for the presence of hydrosalpinx was high. In conclusion, proximal tubal obstruction detected on HSG changes the pre-test probability of proximal tubal obstruction from 16 to 50%. Proximal tubal patency detected on HSG changes the pre-test probability of proximal tubal patency from 16 to 9%. It is unlikely that a lack of reproducibility of the interpretation of proximal tubal patency is responsible for the low sensitivity; alternative explanations are artefacts occurring while performing HSG or an imperfect reference strategy diagnostic laparoscopy. HSG is of limited use in diagnosing distal tubal obstruction and hydrosalpinx, and has no value in the detection of peritubal adhesions.

Fallopian Tube Diseases↗
PubMed1995

Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus.

BACKGROUND: The incidence of vulvar intraepithelial neoplasia Grade III (VIN III) is increasing and is diagnosed at a younger age than previously. VIN III is often multifocal and frequently coexists with multicentric dysplastic lesions in the cervix and vagina. Warty-type VIN III more often has been found to contain human papillomavirus (HPV) DNA than basaloid-type VIN III: The authors performed HPV DNA polymerase chain reaction (PCR) analysis in 48 VIN III biopsies and reverse transcriptase (RT)-PCR in 8 HPV-16 DNA-positive multifocal VIN III biopsies to detect E6/E7 transcripts. METHODS: Human papillomavirus DNA detection and histologic analysis were performed on alternating slides of paraffin embedded biopsies. Polymerase chain reaction was performed with consensus primers, and HPV typing was performed by direct sequencing. Total RNA was isolated from frozen biopsies by centrifuging a guanidinium thiocyanate (GTC) lysate through a cesium chloride (CsCl) cushion. The RT reaction was performed using a 3' primer, located just downstream of the E7 stop codon, and the PCR reaction was performed using the same 3' primer and a 5' primer located just downstream of the E6 start codon. RESULTS: The mean age of the 48 patients was 37.7 years. Eighty-one percent had multifocal VIN III: Sixty-six percent had multicentric neoplasia. Forty-six percent of the biopsies were warty-type, 17% basaloid-type, 35% mixed-type and 2% differentiated-type. Ninety-two percent were HPV-positive and 83% contained HPV-16 DNA. Human papillomavirus DNA was more often present in multifocal VIN III lesions than in unifocal VIN III lesions and also more often in VIN III lesions coexisting with other dysplastic multicentric lesions than in unicentric VIN III lesions. Warty-type VIN III more often contained koilocytes than basaloid-type VIN III: A correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found. Both types of VIN III often coexist in one lesion. In all the RT-PCRs, a 593-base-pair fragment was detected, corresponding to the expected length of the major E6*-E7 mRNA. CONCLUSIONS: The observed high prevalence of transcriptionally active HPV DNA associated with multifocal and multicentric dysplasia suggests a role of HPV in the pathogenesis of these lesions. A positive correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found.

Adult↗
PubMed1995

The accuracy of hysterosalpingography in the diagnosis of tubal pathology: a meta-analysis.

OBJECTIVE: To assess the value of hysterosalpingography (HSG) in diagnosing tubal patency and peritubal adhesions using laparoscopy with chromopertubation as the gold standard. DESIGN: Meta-analysis of 20 studies comparing HSG and laparoscopy for tubal patency and peritubal adhesions. PATIENTS: Four thousand one hundred seventy-nine patients with infertility in 20 studies. INTERVENTION: Hysterosalpingography and diagnostic laparoscopy as part of infertility workup. MAIN OUTCOME MEASURE: Tubal patency and peritubal adhesions. RESULTS: For tubal patency the reported sensitivity and specificity differed between studies. In a subset of studies that evaluated HSG and laparoscopy independently, a point estimate of 0.65 for sensitivity and 0.83 for specificity was calculated. For peritubal adhesions a summary receiver operating characteristic curve could be estimated. CONCLUSIONS: Although HSG is of limited use for detecting tubal patency because of its low sensitivity, its high specificity makes it a useful test for ruling in tubal obstruction. For the evaluation of peritubal adhesions HSG is not reliable.

Fallopian Tube Diseases↗
PubMed1990

Feasibility of transposition of the ovaries in the surgical and radiotherapeutical treatment of cervical cancer.

Ovaries are seldom subject to metastases and therefore their preservation is possible in radical cervical cancer surgery. However, with postoperative radiotherapy they cannot be preserved unless they are placed outside the radiation field. The practicality of this transposition was analysed in a series of 126 patients with cervical cancer. The ovaries were transposed intraperitoneally in a lateral and cranial direction in 44 of the 64 women under the age of 50 years. In 16 of these 44 women, only one ovary could be preserved and transposed. A critical analysis was performed of the ovaries' new location by plotting their position, marked by 2 clips each, in a single pelvis. In 68% of the women at least one ovary was placed outside the radiation field. However, because of scattered radiation, i.e. 5% of the total radiation dose at a distance of 4 cm outside the radiation field, a substantial loss of ovarian function may occur. In 32% of the women at least one ovary received less than this 5%. Optimal transposition may be achieved after extension of the abdominal incision. However, this will be unnecessary in most cases, since postoperative radiotherapy will be indicated in only approximately 15% of the women.

Adult↗
PubMed1987

Estrogenic effects of phenolphthalein on human breast cancer cells in vitro.

There is a structural similarity between phenolphthalein and the triphenylethylenes which are known to interact with the estrogen receptor of human breast tissue. Phenolphthalein (10 microM) competed with estrogen for binding to MCF-7 human breast cancer cells in tissue culture and induced the synthesis of the progesterone receptor. The antiestrogen 4-hydroxytamoxifen blocked progesterone receptor induction both by estradiol and by phenolphthalein. Both estradiol (0.1 nM) and phenolphthalein (10 microM) stimulated cell growth as measured by DNA and protein assays. This growth stimulation was blocked by 4-hydroxytamoxifen. Phenolphthalein glucuronide, the major phenolphthalein metabolite, did not inhibit estrogen binding, induce progesterone receptor synthesis, or stimulate MCF-7 cell growth in culture. Yellow phenolphthalein, an impure phenolphthalein preparation used in nonprescription laxative preparations, had similar properties to pure phenolphthalein. Physicians should be aware of the weak estrogenic action of phenolphthalein, especially when recommending laxatives for breast cancer patients with confirmed liver and mesenteric metastases.

Binding, Competitive↗