On the performance and cost-effectiveness of semiautomated Papanicolaou smear screening.
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Costa Rica↗
Biomedical subjects
G P Vooijs
Publications and source records attributed to G P Vooijs.
The problem of replacement and differentiation of the intestinal epithelium: its relation to squamous metaplasia in the uterine cervix.
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Animals↗
The effect of the family physician on improving follow-up after an abnormal PAP smear.
OBJECTIVE: The aim of this study was to assess the effect of the family physician on improving compliance with follow-up of abnormal smears in cervical cancer screening. DESIGN: Observational study. SETTING: Two Regional Health Authority districts in the east of The Netherlands. STUDY PARTICIPANTS: Family practices with a national call system for cervical cancer screening and family practices with a family-practice-based call system. In a number of practices the family physicians had introduced a fail-safe system for follow-up. MAIN OUTCOME MEASURES: Follow-up of women who participated in the first screening round and in whom a cytological abnormality had been diagnosed in the first smear. Criteria for adequate follow-up were defined with regard to the severity of the cytological abnormality. RESULTS: The overall compliance with follow-up in the study-group was 88%. The study showed a strong relationship between involvement of the family physician and compliance with follow-up. The compliance in practices that had a fail-safe system for follow-up was 93% compared to 82% in the practices without a fail-safe system. The highest follow-up was found in practices involved in the family-practice-based system.
Adult↗
Sum variance--a most valuable parameter in computer-assisted image analysis of voided urines.
The chromatin pattern of retrospectively Feulgen-Schiff-stained exfoliative urothelial cells was determined by computer-assisted analysis for 12 detailed texture image parameters. These were compared with density parameters and geometric parameters for their ability to discriminate between benign and malignant samples. The discriminatory power of the mean variable of the texture parameter sum variance was found to equal that of densitometric parameters which reflect the nuclear DNA content of the cell. The results suggest that determination of the texture parameter sum variance is valuable in distinguishing nuclei of specimens negative from those positive for malignancy.
Cell Nucleus↗
Endocervical columnar cell intraepithelial neoplasia (ECCIN). 3. Interobserver variability in feature use.
In our previous studies on endocervical columnar cell abnormalities, the ability of 5 cytotechnicians was tested to distinguish between cases of: no abnormalities, different grades of intraepithelial endocervical columnar cell atypias and invasive adenocarcinoma. On the basis of stepwise multiple regression analysis, nuclear chromatin distribution, variation in cellular and nuclear size, cytoplasmic eosinophilia and architectural features such as cell-crowding, cluster formation, formation of gland-like structures and pseudostratification appeared to be of primary diagnostic importance to discriminate between no abnormalities, different grades of cervical columnar cell atypias, adenocarcinoma in situ and adenocarcinoma. The present paper reports the results of a study which was designed to assess the individual performance in feature use and classification of endocervical lesions. The results of this study indicate that observers use different characteristics and different grading for the level of expression of these characteristics. However, all observers illustrated a strong relationship between the presence and the expression grade of a certain feature and the degree of endocervical columnar cell atypia. With acceptance of one grade of difference in grades of severity, an overall correct diagnosis was made in 87.6% of cases (range 80-98.2%).
Adenocarcinoma↗
Individual use of cytomorphologic characteristics in the diagnosis of endocervical columnar cell abnormalities: selection of preferred features with help of the 'Navigator' microscope.
In our previous interobserver studies on endocervical columnar cell abnormalities, we studied architectural, cellular and nuclear features in cervical smears of women known to have columnar cell atypias of variable severity, to determine cytomorphologic criteria, discriminating between mild, moderate and severe intraepithelial columnar cell lesions and adenocarcinoma. The results of these studies revealed a number of architectural, cellular and nuclear characteristics in different grades of expression, which were of importance for the primary diagnosis of: no abnormalities, different grades of intraepithelial endocervical columnar cell lesions and adenocarcinoma. Furthermore we concluded that observers used different characteristics and different grades of expression of these characteristics for comparable diagnoses. The present study was undertaken to determine those features, which were considered discriminating by each individual for the diagnosis of mild, moderate and severe atypia, adenocarcinoma in situ and adenocarcinoma. Features selected by five observers with knowledge of the final diagnosis, were stored and reviewed with help of a motor driven stage ('Navigator')-microscope and a high definition television-monitor. The results confirmed individual observer variability in the number and type of features used in the diagnosis of endocervical columnar cell abnormalities. Features such as 'variation in nuclear size and shape', 'irregular chromatin distribution' and 'coarsely granular chromatin' were selected preferentially by all observers in the diagnosis of endocervical columnar cell lesions, conversely striking differences were observed in the application of 'architectural'-and, especially in cases of 'adenocarcinoma', 'nucleolar' characteristics.
Adenocarcinoma↗
A model for evaluation of in situ hybridization spot-count distributions in tissue sections.
The interpretation of in situ hybridization (ISH) spot-count distributions, obtained from evaluation of ISH signals in tissue sections, is complicated by the unknown impact of nuclear truncation and of the localization of ISH spots within the nuclei. In this study, a mathematical model was developed to investigate the effects of nuclear truncation and of the distribution of ISH spots within the nucleus on the ISH spot-count distribution in tissue sections. In this model, it was assumed that nuclei are spherical and of constant diameter and that ISH spots have negligible size and are distributed randomly within the nucleus ("volume model") or along the nuclear membrane ("surface model"). A minimal nuclear profile diameter was introduced in order to study the effect of rejecting small nuclear fragments for spot-count evaluation. Given the section thickness, the nuclear size, the minimal nuclear profile diameter, and the true number of ISH spots per nucleus and their spatial distribution within the nucleus, the model predicts the proportion of nuclei observable in the section with a specific number of ISH spots. A program that performs the model calculations was developed for PC and is available upon request. For section thickness greater than 50% of the nuclear diameter, the main effect of increasing section thickness on spot-count distributions was the increase of the proportion of nuclei with the true chromosome copy number of spots. For lower section thickness, the total distribution shifted towards lower spot frequencies. The influence of the minimal profile diameter was most notable for values close to the nuclear diameter. The effect of the localization of ISH spots within the nucleus was shown to be prominent, especially for sections with thickness smaller than the nuclear diameter. Good correspondence between model-predicted distributions and measured distributions was obtained using the volume model and taking into account only large nuclear profiles.
Animals↗
Review of the endometrial safety during intravaginal treatment with estriol.
To gain more insight into whether intravaginal treatment of local urogenital complaints with the mild-acting oestrogen estriol is capable of inducing proliferation of the endometrium, the results of the clinical studies that have been published over the years have been pooled. Of a total of 19 studies that initially had been selected, four were excluded from the analysis because no baseline biopsies were available, two because endometriae had been evaluated using methods other than with histology, and one study because a sustained-release preparation was used. Pooling of 12 studies (214 subjects) revealed a reasonable amount of long-term data on intravaginal estriol treatment with 61 evaluable biopsies after 6 months and 58 after 12 months. In addition, 13 biopsies were available after 2 years. It appeared that intravaginal estriol treatment using the recommended dosages did not result in endometrial proliferation. All 337 post-baseline biopsies that have been reported in the literature were classified as atrophic. It can be concluded that single daily treatment with intravaginal estriol in the recommended doses in postmenopausal women is safe and without an increased risk of endometrial proliferation or hyperplasia. Consequently, there is no need to add sequential progestogens with these preparations and no withdrawal bleedings will be induced.
Administration, Intravaginal↗
Cellular composition of cervical smears taken by general practitioners.
The quality of the cervical smears taken by general practitioners, and also by some practice assistants, of the Dutch Screening Programme in the region of Nijmegen was evaluated. Of 18,398 preventive cervical smears taken by GPs in this region, 437 (2%) were diagnosed as "class" 0 and 2907 (16%) smears did not contain endocervical cells (EC-). The quality of the smears per general practitioner varied enormously. The percentage of smears without endocervical cells taken by six practice assistants was 18. During the screening period the percentage of smears without endocervical cells taken by GPs decreased from 19 (1989) to 14 (1992). In February 1990 the six practice assistants followed a theoretical and practical course on cervical smear-taking. Remarkable was the decrease in the percentage of smears without an endocervical component from 25% in 1990 to 13% in 1991. The quality of smears taken by GPs would improve if the general practitioner had more experience in smear-taking. We recommend to offer GPs the opportunity to take practical training courses in smear-taking, just as the practice assistants in this project.
Adult↗
Complete hydatidiform mole in twin pregnancy: differentiation from partial mole with interphase cytogenetic and DNA cytometric analyses on paraffin embedded tissues.
Six cases of hydatidiform mole associated with normal chorionic villi and a normal embryo/fetus (in five cases) were investigated with interphase cytogenetic and DNA cytometric analyses for diagnostic purposes. DNA probes specific for the pericentromeric regions of chromosomes 1 and X and for the long arm of chromosome Y were used. In four cases a dizygotic twin pregnancy could be proven. In these cases, the histologically normal chorionic villi showed an XY DNA-diploid pattern, consistent with a normal male conceptus, and the molar chorionic villi a XX pattern. In the other two cases an identical sex chromosomal pattern was found in the normal and in the molar villi (XX/XX and XY/XY respectively). In all six cases the molar placental tissues showed prominent trophoblastic hyperplasia with DNA-polyploidy, consistent with a complete hydatidiform mole. In two cases persistent gestational trophoblastic disease developed. It is emphasized that twin pregnancies composed of a normal conceptus and a complete mole have a relatively high risk for the development of persistent trophoblastic disease and therefore, should be carefully differentiated from triploid partial moles with a relatively low risk of persistent gestational trophoblastic disease. These case reports indicate that additional interphase cytogenetic and DNA cytometric analyses are useful in this differential diagnosis.
Adult↗
Practical aspects of fixatives in high resolution nuclear image analysis.
Three different methods of fixation (ethanol/Carbowax, formaldehyde, and Carnoy) and four different protocols (without Böhm post-fixation on an uncoated slide, and with Böhm post-fixation on Poly-L-Lysine coated slide, an uncoated slide and a previously Papanicolaou stained slide) were evaluated for their application in high resolution image analysis of Feulgen stained nuclei. The aim of the study was to find a combination with the best reproducibility and the least variance under normal laboratory conditions. Care was taken not to exclude any "normal" laboratory variability. The combinations were evaluated for densitometric, geometric, as well as texture features. Selected features were determined on a CAS-100 using the Cell Measurement Program (Cell Analysis Systems, Inc. Lombard, IL). Diploid and tetraploid rat liver nuclei were used. Ethanol/Carbowax fixation-with Böhm post-fixation proved most stable. This fixation method also gave feature values for previously Papanicolaou stained slides that were comparable to direct Feulgen stained nuclei. Acceptable results were achieved with all three fixatives and the various combinations if one adhered strictly to protocol. In routine practice this usually does not happen. Therefore Ethanol/Carbowax fixation with Böhm post-fixation was considered most suited for routine determination of feature values on the CAS-100.
Acetates↗
Detection of keratin subtypes in routinely processed cervical tissue: implications for tumour classification and the study of cervix cancer aetiology.
We investigated the expression of keratin subtypes 7, 8, 10, 13, 14, 17, 18 and 19 in the normal cervix, in cervical intraepithelial neoplasia (CIN) lesions and in cervical carcinomas, using a selected panel of monoclonal keratin antibodies, reactive with routinely processed, formalin fixed paraffin embedded tissue fragments. The reaction patterns derived for each keratin antibody were compared with known expression patterns of the various epithelia, previously examined in frozen tissues. Although the reactivity of the antibodies was generally acceptable, considerable modifications to the manufacturers' staining instructions were often necessary. For some antibodies, which were previously thought to be reactive with fresh frozen tissue only, we developed staining protocols rendering them reactive with routinely processed material. As with previous findings in frozen sections we observed increasing expression of keratins 7, 8, 17, 18 and 19 with increasing grade of CIN. In cervical carcinomas the differences in keratin detectability between the main categories were more pronounced than in frozen sections, probably due to fixation and processing. For routine pathology, keratin phenotyping of cervical lesions may be of value in classification. The fact that keratin 7 was detected for the first time in reserve cells, and that this keratin was also found to be expressed in a considerable number of CIN lesions and cervical carcinomas supports the suggestion that reserve cells are a common progenitor cell for these lesions.
Adenocarcinoma↗
GROPAP--a new staining method.
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Bronchi↗
Identification of aneuploid cells in cytological specimens by combined in situ hybridization and immunocytochemistry.
The purpose of our study was the application of non-isotopic in situ hybridization with chromosome-specific repetitive DNA probes for the determination of cytogenetically aberrant cells in routine cytological materials, such as cervical smears and breast tumour aspirates. Hyperdiploid cells in fine needle aspirates (FNA) of breast tumours could be visualized by in situ hybridization with a chromosome 1-specific repetitive DNA probe. However, for the evaluation of a specific cell type in heterogeneous cell populations, i.e. cervical smears, a procedure combining immunocytochemistry and in situ hybridization can be required. Therefore, we developed a combination protocol using beta-galactosidase/ferri-ferrocyanide (blue-green) for immunocytochemistry and peroxidase/DAB (brown-black) for detection of the DNA probe. The described protocol enabled us to distinguish squamous epithelial cells within heterogeneous cell populations. By combining the chromosome 1 DNA probe with a specific cytokeratin marker it was possible to identify the chromosomal abnormal cells within cervical smears.
Aneuploidy↗
DNA cytometric and interphase cytogenetic analyses of paraffin-embedded hydatidiform moles and hydropic abortions.
The combined application of DNA cytometric and interphase cytogenetic analyses was used to find objective criteria for the differential diagnosis of complete hydatidiform mole, partial hydatidiform mole and hydropic abortion. DNA ploidy and G0/G1 exceeding rates were determined using image and flow cytometric analyses on paraffin-embedded tissues of 166 cases: 71 cases of complete mole, 20 cases of partial mole, and 75 cases of abortions. To determine the existence and histological distribution of cell subpopulations with numerical chromosome aberrations, interphase cytogenetic analysis using probes specific for chromosomes 1, X, and Y was applied to paraffin tissue sections of 23 cases: 12 cases of complete mole, 3 cases of partial mole, and 8 cases of abortions. In contrast to previously reported findings that complete moles are diploid, the results of this study showed that complete moles are DNA-polyploid (96 per cent), with high G0/G1 exceeding rates and a high frequency of numerical chromosomal aberrations in the trophoblast hyperplasia. The majority of the partial moles were DNA-triploid (55 per cent). This study, however, also showed the presence of DNA-polyploid partial moles (30 per cent). Abortions were DNA-diploid (60 per cent) or DNA-triploid (39 per cent). DNA cytometric analysis, especially image DNA cytometric analysis with determination of the G0/G1 exceeding rate, and interphase cytogenetic analysis provide objective measurements which are contributory in the differential diagnosis between complete mole, partial mole, and hydropic abortion.
DNA↗
Identification of numerical chromosome aberrations in archival tumours by in situ hybridization to routine paraffin sections: evaluation of 23 phaeochromocytomas.
We have applied non-isotopic in situ hybridization (ISH) to interphase cell nuclei of 23 phaeochromocytomas (18 primary and 5 metastatic tumours) within routine paraffin-embedded tissue sections. Each tumour was screened for numerical aberrations with a defined alphoid repetitive DNA probe set containing DNA probes specific for chromosomes 1, 7, 15, and Y. Normal adrenal medullas and other normal human cell types served as cytogenetic controls. Preservation of tissue morphology enabled targeted analysis of tumour cells. The presence of numerical chromosome changes in the tumour cells could easily be evaluated by comparing the ISH results of the DNA probes. Numerical abnormalities not previously reported in this neoplasm included overrepresentation of chromosomes 1 and 7, loss of chromosome 15, and both gain and loss of chromosome Y (P values < 0.01). The percentage of aneuploid cell nuclei in a tumour correlated well with the percentage of cells in the 4C peak of flow cytometric DNA histograms from these neoplasms. We conclude that interphase ISH can be used for the identification of new and reported cytogenetic changes in tumour cell nuclei within archival tissue sections. This novel procedure also allows for retrospective analysis of previously not karyotyped material.
Adrenal Gland Neoplasms↗
Epithelial markers to detect occult microinvasion in serous ovarian tumors.
Ovarian serous lesions with severe cytological and architectural atypia without obvious destructive stromal invasion may be diagnosed as serous borderline malignant tumor or as serous cystadenocarcinoma, depending on the criteria that individual pathologists use. The recent introduction of the diagnosis "serous borderline tumors with stromal microinvasion" seems an important improvement for the accuracy of the diagnosis of serous ovarian tumors. The aim of this study was to determine if immunohistochemical epithelial markers could help to detect stromal microinvasion in serous ovarian tumors and to compare these findings with the occurrence of "eosinophilic metaplastic" cells. Therefore, we studied the presence of eosinophilic metaplastic cells. Three immunohistochemical epithelial markers were applied in a group of 42 borderline and invasive serous tumors. The histopathologic diagnosis of the tumors was established by a reference center for gynecologic pathology in the Netherlands. We found that "eosinophilic metaplastic" cells were a constant feature in the serous borderline tumor lesions both with and without microinvasion. The presence of these cells should therefore not be considered as pathognomonic for microinvasion. The three investigated antibodies against epithelial epitopes helped to detect microinvasion, with the monoclonal antikeratin (CAM5.2) the best of these antibodies. Serous tumors diagnosed as carcinoma with dubious invasion showed no evidence of microinvasion in 83% of cases. In 13% of serous borderline malignant tumors, microinvasion was detected by the antibodies.(ABSTRACT TRUNCATED AT 250 WORDS)
Aged↗
Monotypic plasma cells in labial salivary glands of patients with Sjögren's syndrome: prognosticator for systemic lymphoproliferative disease.
AIMS: To determine the prevalence of plasma cell monotypia in labial salivary gland tissue of patients with and without Sjögren's syndrome, and to evaluate its relation to the development of systemic monoclonal lymphoproliferative disorders. METHODS: A quantitative immunohistological study was performed on labial salivary gland tissue of 45 patients with Sjögren's syndrome, 18 with rheumatoid arthritis without Sjögren's syndrome, and 80 healthy controls. In none of the patients with Sjögren's syndrome was there evidence of systemic monoclonal lymphoproliferative disease at the time of biopsy. RESULTS: Monotypic plasma cell populations, defined by a kappa:lambda ratio of > or = 3, were only observed in older patients (above 43 years) with Sjögren's syndrome. In almost all these patients monotypic plasma cell populations were present in multiple labial salivary gland tissues and the IgM/kappa monotypia was observed most frequently. The prevalence of monotypic plasma cell populations in the group with Sjögren's syndrome was 22% (10/45) and there was no significant predilection for primary Sjögren's syndrome. Of special clinical interest was the observation that progression to systemic monoclonal lymphoproliferative disease had occurred exclusively in this subgroup of patients with Sjögren's syndrome, with a prevalence of 30% (3/10). CONCLUSION: Quantitative immunohistological examination of labial salivary gland tissues provides pathologists with a simple method to select those patients with Sjögren's syndrome who have an increased relative risk at the time of biopsy to develop benign or malignant lymphoproliferative disorders.
Adolescent↗