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Defective chorionic villous vascularization has been suggested to be associated with embryonic death. There are no reports, however, describing chorionic vascular profiles in spontaneous miscarriage tissue. Therefore, we investigated chorionic villous vascularization by both histopathology and an image analysis system combined with CD34 immunohistochemistry in spontaneous miscarriage tissue of 19 women with recurrent early pregnancy loss (REPL). Subsequently, we studied the vascular profile parameters (median vascular area, perimeter, number of vascular elements per measured chorionic area, and the median area, perimeter and diameter per vascular element) in relation to the maternal plasma total homocysteine concentrations (an independent risk factor for REPL). The histopathological scores and the measured number of vascular elements per mm(2) chorionic tissue were not significantly different between women with elevated and those with normal total homocysteine concentrations. However, women with elevated total homocysteine concentrations (fasting >18.3 micromol/l and/or 6 h after methionine load >61.5 micromol/l) showed (per measured chorionic area) significant smaller median vascular areas and perimeters. The single chorionic vascular elements in these women had significant smaller median areas, perimeters and diameters. Furthermore, the fasting total homocysteine was negatively correlated with the perimeter of the vascular element (r = -0.54: P <0.05). In conclusion, in REPL, elevated maternal total homocysteine concentrations are associated with defective chorionic villous vascularization. [ABSTRACT FROM AUTHOR]

Objective: To determine the number interventions and outcomes in patients referred with two consecutive Pap 2 cervical smear results who were managed either by a wait-and-see policy or aggressively, and to determine whether triage with high-risk human papillomavirus (hr-HPV) detection, resulting in the referral of only hr-HPV positive patients, would lead to the detection of all patients with cervical intraepithelial neoplasia (CIN)., Design: Retrospective comparison and retrospective cohort study., Method: 282 patients referred in 1997/'99 with 2 consecutive Pap 2 cervical smears in the screening program were included. Patients referred to the UMC St Radboud Hospital (n = 140; mean age: 45 years) underwent a colposcopy during which only lesions suggestive for CIN 3 were treated. All other colposcopic lesions (CIN 2 or less) were not treated but followed prospectively. Patients referred to the Canisius Wilhelmina Hospital (CWZ) (n = 142; mean age: 44 years) underwent colposcopy during which all colposcopic lesions (including CIN 2 or less) were treated directly. The two groups were compared in terms of the final cytological follow-up, the number of loop excisions, and the number of patients with CIN. The mean follow up was 40 months. In the first group, the effect of triage using hr-HPV detection was also investigated retrospectively., Results: With the wait-and-see approach, statistically significantly fewer diathermic loop excisions were done: 13 versus 124. After the follow-up period there was no statistically significant difference between the two groups in terms of the number of patients with persisting Pap 2: 16 (11%) versus 12 (8%). Triage with hr-HPV detection would identify all patients with CIN 3, 50% of the patients with CIN 2, and none of the patients with CIN 1; of the 48 hr-HPV-positive women, 1 had a CIN 3 lesion and 3 had a CIN 2 lesion; of the remaining 92 women, 2 had a CIN 1 lesion and 3 had a CIN 2 lesion., Conclusion: The wait-and-see approach led to fewer interventions, while the number of women with persisting Pap 2 smears was not higher than with the aggressive approach. Triage with hr-HPV may reduce the number of referrals and colposcopies, but follow-up remains necessary in all women regardless of hr-HPV status.

Recent Dutch and non-Dutch studies have shown that the absence of endocervical cells (ecc-) in an adequate cervical smear does not present an increased risk for the presence or occurrence of cervical cancer or premalignant abnormalities in a later phase. Based on these findings, the Coordination Committee Cervical Cancer Screening of the Dutch Health Insurance Council had advised dropping the repeat advice for non-abnormal ecc- smears by January 1st 2002. The National Health Insurance Council has agreed to this advice. The following measures have been taken: (a) no repeat advice for ecc- smears; in the case of negative findings the woman waits until the next five-yearly invitation from the screening programme; (b) whether the portio cervicis was seen has to be stated on the national request form; (c) the reporting of an ecc- in the cytology report and periodical feedback to general practitioners remains unchanged; (d) in the case of a non-abnormal ecc- smear with an uninspected portio or doubts as to whether the transformation zone was adequately scraped, either the smear will have to be repeated or the patient will have to be referred to the gynaecologist.

Objective: To determine whether the alpha-catenin expression pattern and DNA content have additional value over primary tumour histology, including information on vascular invasion and tunica albuginea invasion, in detecting occult metastasis in patients with clinical stage I nonseminomatous germ cell tumours of the testis (NSGCT)., Patients and Methods: Fifty consecutive patients with clinical stage I NSGCT underwent retroperitoneal lymphadenectomy (RPLND) between 1986 and 1992. The orchidectomy specimens were histopathologically reviewed and immunohistochemically stained with mouse monoclonal anti-alpha-catenin antibody. The presence of an aberrant or negative staining in >10% of the malignant cells was defined as abnormal; in all other cases tumours were classified as normal. Furthermore, intact nuclei were isolated from 50 microm thick paraffin sections of the primary tumour, Feulgen stained, and analysed with an image-analysis system., Results: Of the 50 patients, 14 had positive retroperitoneal nodes (stage IIa, 28%), one pathologically staged I patient developed a lung metastasis (stage IV) within 3 months of RPLND. Univariate analysis showed that the presence of embryonal cell carcinoma, vascular invasion and tunica albuginea invasion were predictive for occult metastases. In multivariate logistic regression analysis only vascular and tunica albuginea invasion were significant. All 11 patients with no embryonal cell carcinoma in the primary tumour were classified as having pathological stage I disease. Also, the tumours which were DNA-diploid (three) or DNA-polyploid (two) were pathologically stage I. In screening for occult metastases the DNA content and the alpha-catenin expression pattern had no additional value., Conclusion: Vascular and tunica albuginea invasion have prognostic value in identifying patients with clinical stage I NSGCT at high risk for occult retroperitoneal disease. In contrast, the absence of embryonal cell carcinoma could predict all patients at low risk for metastasis. The DNA-ploidy also identified patients at low risk. Other DNA-analyses and the alpha-catenin expression pattern provided no additional information. Further studies are recommended to identify patients who are at low or high risk for metastasis.

Introduction: The localization and distribution of single or multiple HPV genotypes in the uterine cervix has not been studied thus far. The present study was undertaken to determine whether single or multiple HPV genotypes detected in cervical smears originate from a single (dysplastic) area, or from different areas (dysplastic or normal) of the uterine cervix., Methods: Of eight patients with moderate or severe dysplasia, 31 colposcopically guided biopsies of different dysplastic lesions of the uterine cervix, as well as of normal epithelium were investigated. A highly sensitive, broad spectrum, short fragment polymerase chain reaction (SPF-10 PCR) HPV detection method in combination with a line probe assay (LiPA) for simultaneous genotyping was used., Results: In the uterine cervix of four of the eight patients, multiple HPV genotypes were detected. These multiple HPV genotypes were detected in different biopsies as well as within a single biopsy. In three patients, all with carcinoma in situ or microinvasive carcinoma, only a single HPV genotype, HPV 16, was found all over the cervix including in the normal epithelium., Conclusion: Different HPV genotypes can be detected in different dysplastic lesions as well as within single lesions, especially in patients with severe dysplasia. The severity of the lesion may possibly have a relation with the distribution of the HPV genotypes. The low number of patients and biopsies does not allow definite conclusions. However, the impact of these findings on the outcome of screening and vaccination programs remains to be elucidated.