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R van Velthoven

Publications and source records attributed to R van Velthoven.

16 recordsLinked to original sources
PubMed1997

Coregulatory effects of epidermal growth factor, dihydrotestosterone, and prolactin on benign human prostatic hyperplasia tissue culture proliferation.

BACKGROUND: A variety of hormones have demonstrated effects on prostatic tissue growth dynamics. Our goal was to define the effect of dihydrotestosterone (DHT), epidermal growth factor (EGF), and prolactin (PRL) on prostate cellular proliferation. METHODS: Thirty benign human prostatic hyperplasias (BPH) were maintained 48 hr as in vitro cultures. Culture media were supplemented with EGF, DHT, and PRL alone and in combinations. Proliferation was assessed by labeling with tritiated thymidine. RESULTS: The proliferative response of individual BPH cultures was heterogeneous. DHT and EGF tended to have a greater proliferative effect than PRL, both in terms of the percent cultures responding and the magnitude of the response. PRL antagonized EGF-induced proliferative effects. EGF- and PRL-mediated effects correlated with each other, while DHT-mediated effects did not correlate with either those of PRL or EGF. CONCLUSIONS: The proliferative response of individual BPH to DHT, EGF, and PRL, alone or in combination, is too variable to define a predictable response to their influence. Our methodology represents a technique with the capacity to define therapeutic potential for individual cases.

Aged↗
PubMed1996

The use of the decision tree technique and image cytometry to characterize aggressiveness in World Health Organization (WHO) grade II superficial transitional cell carcinomas of the bladder.

The aggressiveness of human bladder tumours can be assessed by means of various classification systems, including the one proposed by the World Health Organization (WHO). According to the WHO classification, three levels of malignancy are identified as grades I (low), II (intermediate), and III (high). This classification system operates satisfactorily for two of the three grades in forecasting clinical progression, most grade I tumours being associated with good prognoses and most grade III with bad. In contrast, the grade II group is very heterogeneous in terms of their clinical behaviour. The present study used two computer-assisted methods to investigate whether it is possible to sub-classify grade II tumours: computer-assisted microscope analysis (image cytometry) of Feulgen-stained nuclei and the Decision Tree Technique. This latter technique belongs to the Supervised Learning Algorithm and enables an objective assessment to be made of the diagnostic value associated with a given parameter. The combined use of these two methods in a series of 292 superficial transitional cell carcinomas shows that it is possible to identify one subgroup of grade II tumours which behave clinically like grade I tumours and a second subgroup which behaves clinically like grade III tumours. Of the nine ploidy-related parameters computed by means of image cytometry [the DNA index (DI), DNA histogram type (DHT), and the percentages of diploid, hyperdiploid, triploid, hypertriploid, tetraploid, hypertetraploid, and polyploid cell nuclei], it was the percentage of hyperdiploid and hypertetraploid cell nuclei which enabled identification, rather than conventional parameters such as the DI or the DHT.

Adult↗
PubMed1996

The additional predictive value contributed by quantitative chromatin pattern description as compared to DNA ploidy level measurement in 257 superficial bladder transitional cell carcinomas.

The results of quantitative chromatin pattern description were compared with the determination of the DNA ploidy level, and the histological grading and clinical staging of superficial transitional cell carcinomas (sTCCs) of the bladder. We investigated whether this quantitative description adds useful information to the one obtained by the other methods used for predicting the biological behavior of sTCCs. The quantitative chromatin pattern description was carried out by means of the digital cell image analysis of Feulgen-stained nuclei in a series of 257 sTCCs. The results show that according to the clinical sequence "remission (134 patients) --> stable recurrence (101 patients) --> progression (13 patients) --> death (9 patients)', quantitative chromatin pattern description shows that certain areas of the nucleus undergo a continual process of condensation and that the distribution and spread of the chromatin becomes more and more heterogeneous. This is accompanied by a more frequent appearance of pale areas in the nucleus and an increase in nuclear size. Of the 257 sTCC patients, 148 had pTa/PpT1 grade I or III tumors. Of these 148, histological grading and clinical staging made it possible to correctly predict the biological behavior of the tumors of 120/148 (81%). DNA ploidy level determination increased this correct prediction from 81 to 84%. When the information contributed by quantitative chromatin pattern description was added to that contributed by the combination of histological grading, clinical staging and DNA ploidy level determination, the prediction level was 93%.

Adult↗
PubMed1996

The computer-assisted microscope analysis of Feulgen-stained nuclei linked to a supervised learning algorithm as an aid to prognosis assessment in invasive transitional bladder cell carcinomas.

The aim of the present work is to ascertain whether additional information to grading and staging can be obtained for the prognosis of invasive bladder tumours (T2, T3, T4) by means of two computer-assisted methodologies. The first methodology relates to the digital image analysis of Feulgen-stained nuclei and the second to a supervised learning algorithm named Decision Tree. The digital image analysis of Feulgen-stained nuclei generated 11 variables for nuclear DNA content and 15 for quantitatively describing chromatin pattern. These 26 variables were submitted to a Decision Tree technique which produces multi-attribute logical classification rules by selecting informative variables and determining discriminatory values for each of them. A series of 41 patients for which the majority of the T2 bladder tumours (68%) were associated with a 'good' prognosis (remission) while the majority of the T3-T4 ones (77%) were associated with a 'bad' one (clinical progression or death) were submitted to the proposed approach. The results show that the decision tree was able to characterise the tumours associated with a 'bad' prognosis in the T2 sub-group (32%) and the tumours associated with a 'good' prognosis in the T3-T4 one (23%), by using only few image-generated variables (added to the clinical stage).

Adult↗
PubMed1996

Does any correlation exist between the Gleason classification system and the computer-assisted microscope analysis of Feulgen-stained nuclei features in human prostate adenocarcinoma?

Grading prostatic adenocarcinomas remains an important problem. Various systems exist (including those proposed by Gleason) but none of these systems seems able to reliably predict either the lethal potential of a tumor in an individual patient or the responsiveness of an individual tumor to various forms of therapy. The most frequently used grading system, as proposed by Gleason, is essentially based on the description of tumor growth pattern. The aim of the present work is therefore to investigate whether the quantitative description of morphonuclear features (including cell anaplasia) and the DNA ploidy level can contribute significant information to the Gleason grading, thus partly at least reducing its subjective nature. This quantitative description was carried out by means of the Feulgen-stained nuclei image cytometry computation of 24 variables in 101 prostatic adenocarcinomas. The results show that both DNA ploidy- and morphonuclear-related variables were weak discriminators for the various grades of the Gleason classification system, and particularly between the high (Gleason 4 and 5) and the other Gleason-grades, i.e. the low (Gleason 1 and 2) and intermediate (Gleason 3) ones. The morphonuclear evidence of anaplasia is thus not redundant data on tumor growth pattern and may be expected to provide additional diagnostic information.

Adenocarcinoma↗
PubMed1995

The use of digital image analysis of chromatin texture in Feulgen-stained nuclei to predict recurrence of low grade superficial transitional cell carcinoma of the bladder.

BACKGROUND: Identifying a marker enabling prediction of recurrence in the group of superficial transitional cell carcinomas (sTCCs) of the bladder remains an important challenge today. This report quantitatively describes chromatin patterns with respect to such sTCC recurrence. MATERIALS AND METHODS: Twenty-nine patients with sTCCs who did not exhibit tumor recurrence within a minimum of 24 months were compared with 21 patients with sTCCs who exhibited tumor recurrence two or three times in a 24-month period, for a total of 74 sTCCs. Quantitative chromatin pattern description was performed by the digital cell image analyses of Feulgen-stained nuclei. Six morphonuclear parameters were thus described and subsequently used to determine a score, allowing biological behavior of sTCCs to be described, i.e., recurrence versus non-recurrence in one calculation step. DNA ploidy level was also determined in each sTCC by assessing its DNA histogram type. RESULTS: Of 32 patients with Grade 1 pathologically classified pTa/pT1 tumors, DNA ploidy level determination permitted correct prediction of tumor nonrecurrence or recurrence of 13 (41%), whereas determination of the score values enabled prediction of nonrecurrence or recurrence of 25 (78%). Combining DNA ploidy level data and the score values enabled recurrence or nonrecurrence to be predicted for 29/32 of the patients (91%). CONCLUSIONS: The quantitative description of chromatin patterns by digital cell image analysis of Feulgen-stained nuclei can provide helpful information, in addition to DNA ploidy level determination, in predicting tumor recurrence of low grade superficial transitional cell carcinomas of the bladder.

Carcinoma, Transitional Cell↗
PubMed1995

Image cytometry determination of ploidy level, proliferative activity, and nuclear size in a series of 314 transitional bladder cell carcinomas.

Image cytometry was carried out on 281 superficial (Ta and T1) and 33 invasive (T2 to T4) bladder cancers. The parameters used to characterize these bladder tumors were: (1) histopathological grading, (2) clinical staging, (3) tumor size, (4) deoxyribonucleic acid (DNA) index (DI), (5) DNA histogram type (DHT), (6) percentage of euploid (diploid plus tetraploid) cells, (7) percentage of polyploid cells (> 5C DNA content), (8) proliferative activity (S phase fraction value), and (9) nuclear area (NA). The proliferative activity of the tumors was not related to either histopathological grade or to clinical stage, but it was related to the DHT parameter, which made it possible to identify diploid, hyperdiploid, triploid, hypertriploid, tetraploid, and polymorphic tumors. The hypertriploid tumors exhibited a significantly lower proliferative activity than the nonhypertriploid ones. Although both the DI and the NA values correlated significantly with histopathological grading, only the NA values correlated significantly with clinical staging. We further observed that some grade III bladder tumors were definitely diploid, whereas some grade I tumors were highly aneuploid. We thus hypothesize that the ploidy level of a given tumor reflects its age directly and its aggressiveness only very indirectly. In our opinion aneuploidy is only an indirect marker of aggressiveness because it reflects the fact that a malignant tumor is old, ie, has been present in a patient over a long period of time and has had ample time to express its malignancy at the clinical level. A significant relationship was accordingly obtained between tumor size and ploidy level with the highest proportion of aneuploid tumors and the highest percentage of polyploid cell nuclei being observed among the largest bladder tumors.

Adult↗
PubMed1994

Computer-assisted chromatin texture characterization of Feulgen-stained nuclei in a series of 331 transitional bladder cell carcinomas.

The chromatin patterns of Feulgen-stained nuclei in a series of six specimens of normal mucosa and 331 transitional bladder carcinomas, including 293 superficial (Ta and T1) and 38 invasive (T2-T4) cases, were quantitatively described by means of eight parameters relating to densitometric, run-length distribution, and co-occurrence matrix features. The results show that the chromatin texture of the superficial lesions was markedly different from that of the invasive tumours, which exhibited a distinctly more dense and heterogeneous chromatin pattern. The data also show that the increasing level of malignancy, as revealed by the increasing clinical stage, was accompanied by an increase in the overall chromatin condensation level. Only some areas of the nucleus actually increased in density; other pale areas appeared concomitantly with these increasingly denser chromatin areas. This chromatin density increase corresponded to a marked increase in the frequency of small dense chromatin clumps; these joined together into very large dense chromatin clumps, which were distributed more and more heterogeneously in the nucleus as the clinical stage of the tumour increased.

Adult↗
PubMed1994

Influence of culture media on the morphological differentiation of the PC-3 and DU145 prostatic neoplastic cell lines.

The concept of differentiation of prostate cancer in terms of morphonuclear characteristics and population dynamics was investigated on the PC-3 and DU145 cell lines. A software based on the concept of Voronoi paving was set up in order to characterize the structure of these cell lines growing in vitro on histological slides. The morphonuclear characteristics were assessed by means of the digital cell image analyses of Feulgen-stained nuclei. The in vitro "morphonuclear" and "pseudo-tissular" differentiations of the PC-3 and DU145 cells were described in terms of the use of various culture media, i.e., media supplemented with either 10% (F10 medium) or 1% (F1 medium) fetal calf serum and with (or without) platelet-derived growth factor and dihydrotestosterone (PA10 and PA1 media). The present data reveal that the PC-3 cell line would be more hormone-sensitive than the DU145 one. Indeed, decreasing the FCS concentration in the culture medium while adding DHT and PDGF led to marked modifications to the morphonuclear characteristics of the PC-3 cells, but not to the DU145 cells. These modifications corresponded to an increase in nuclear size occurring concomitantly with chromatin decondensation. In the same way, spectacular modifications in terms of medium-induced pseudo-tissular differentiation were observed in the PC-3 cell line, but not in the DU145 one. Such modifications corresponded to an increase in clone size related to an increase in the mean distances between neighboring cell nuclei in a given clone. Thus, according to the criteria defined in this study, the PC-3 cell line would seem to maintain a higher degree of differentiation than the DU145 cell line.

Animals↗
PubMed1994

Operative strategy in laparoscopic nephrectomy.

Nephrectomy is a debilitating procedure because of the trauma to the abdominal wall. Laparoscopy could be a solution in this matter. Four patients underwent laparoscopic nephrectomy. In 3 patients with renal cancer, the transperitoneal route was used in order to obtain quicker access to the hilus. In the fourth patient with benign disease, a retroperitoneal route was chosen. There was no morbidity or mortality. Mean hospital stay was 5 days. Laparoscopic nephrectomy is safe and effective. Larger series are needed for evaluation of the long-term results in the treatment or renal cancer.

Abdomen↗
PubMed1991

Morphonuclear relationship between prostatic intraepithelial neoplasia and cancers as assessed by digital cell image analysis.

Using digital cell image analysis performed on Feulgen-stained nuclei, the nuclear characteristics of prostatic neoplasia, ranging from benign (benign prostatic hyperplasia [BPH]), through dysplastic (prostatic intraepithelial neoplasia [PIN] 1-3), to carcinoma were studied. Four histopathologic groups were studied: group IA (18 samples) contained BPH, PIN 1, and PIN 2 lesions that were from 9 prostate samples free of cancer. Group IB (23 samples) was identical to group IA, contained also BPH, PIN 1, and PIN 2 lesions, but lesions that were from 7 prostate samples where malignant foci were detected elsewhere. Group II (11 samples) were PIN 3 specimens. Group III (24 samples) were carcinomas. Features of neoplastic nuclei were quantified objectively through morphometric (nuclear size), densitometric (nuclear DNA content), and textural (chromatin organization and heterogeneity) parameters. Cell kinetic parameter, i.e., cell proliferation index, was assessed from the densitometric measurement. The proliferation index was significantly higher in PIN 3 and cancers as compared to BPH, PIN 1, and PIN 2 tissues. Morphonuclear characteristics were also dramatically distinct among the four groups. Indeed, the nuclear size and the hyperchromatism of severe prostatic dysplasia were similar to those of carcinomas, these two lesion types showing mean parameter values that were higher as compared to BPH, PIN 1, and PIN 2 lesions. Finally, benign tissues related to mild or moderate dysplasia taken in histologic material in which cancer was present already share the morphonuclear characteristics of severe dysplasia, although they are nonproliferating.

Cell Nucleus↗
PubMed1991

Use of computerized cell image analysis to characterize cell nucleus populations from normal and neoplastic renal tissues.

We studied 55 renal tissue samples from 16 patients corresponding to normal (19 samples, group 1), low-grade (18 samples, group 2), and high-grade (18 samples, group 3) tumoral tissues. For this purpose, we used digital cell image analysis (the SAMBA 200 processor) to describe the morphonuclear patterns of Feulgen-stained nuclei from the 3 above-mentioned groups. Our results show that nuclear DNA ploidy is positively correlated with histopathological differentiation, which is also positively correlated with an increase in nuclear DNA heterogeneity. Morphometric and textural parameters computed on such Feulgen-stained nuclei make it possible to describe the typical morphonuclear patterns of normal, low-grade, and high-grade neoplastic renal tissues. Using multiparametric, i.e. principal-component and canonical analyses, we set up preliminary morphonuclear data banks that we used to assess the diagnosis of 6 ungraded samples. We expect that this kind of morphonuclear data banks might be helpful, on one hand, to select specific morphonuclear parameters related to patient survival, and on the other hand to establish the cytological diagnosis of deep fine-needle aspiration material, sonographically assisted, on suspicious kidneys. Such hypotheses are now under further study.

Aged↗
PubMed1990

Characterization of the morphonuclear features and DNA ploidy of prostatic disease.

The relationship between several morphonuclear parameters related to nuclear densitometry (DNA content and ploidy), and the chromatin pattern of Feulgen-stained nuclei is confronted to the histopathological grading of 39 prostatic samples obtained from surgical adenomatous or transurethral resection. We use a SAMBA 200 cell image processor with software allowing for the setting up of preliminary data banks that enable carrying out an objective and reproducible grading of unknown cases obtained from core biopsies of fine-needle aspirations. The present approach must be validated prospectively on a large series of cases in order to create an expert system for diagnosing such fine-needle aspirations from prostate.

Analysis of Variance↗