Biomedical subjects

T Janssen

Publications and source records attributed to T Janssen.

At least 37 records · Page 2Linked to original sources

PubMed1998

Prognostic value of stem cell line identification for renal cell carcinomas.

OBJECTIVE: To investigate the prognostic value of nuclear DNA content (DNA ploidy level) in a series of 95 renal cell carcinomas (RCCs). STUDY DESIGN: Eight variables were used to characterize DNA ploidy levels. They included DNA index and seven others characterizing the presence of specific stem cell lines in each of the 95 RCCs under study. All these variables were determined by means of computer-assisted microscopy applied to Feulgen-stained nuclei. The actual information contributed by each of the eight variables was determined by means of univariate statistical analyses. RESULTS: The results showed that in the DNA ploidy-related eight variables, the presence of at least 4% aneuploid nuclei with > 5C DNA content was associated with the most significant prognostic value in RCCs with intermediate (T2, T3) invasion levels. CONCLUSION: The present study clearly showed that stem cell line characterization, and particularly the presence of highly aneuploid cells (with > 5C DNA content), is associated in RCCs with significant prognostic value. This kind of marker may help the identification of patients who will develop metastases after surgery and for whom adjuvant therapy might thus be indicated.

Adult↗

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↗

PubMed1997

[Transrectal prostatic biopsy: the role of preventive measures].

Biopsies are indispensable for the diagnosis of the adenocarcinoma of the prostate. Multiple transrectal ultrasound-guided prostatic biopsies are accurate and sure. However, haemorrhagic and infectious complications are not rare. The anamnesis and the intermission of anticoagulant drugs are the best prophylaxis to prevent haemorrhagic complications. The advantage of prophylactic antibiotic therapy has not been absolutely demonstrated. Nevertheless, before biopsies, bacteriuria must be treated. Indeed, pre-biopsy bacteriuria seems to be correlated to septic complications after the procedure.

Adenocarcinoma↗

PubMed1996

In vitro characterization of prolactin-induced effects on proliferation in the neoplastic LNCaP, DU145, and PC3 models of the human prostate.

BACKGROUND: Proliferation of normal and tumoral prostate tissue is regulated by androgens and various growth factors. We characterized the in vitro proliferative influence of prolactin (PRL) in androgen-sensitive and androgen-insensitive human prostate cancers. METHODS: The biologic models employed included the androgen-sensitive LNCaP and the androgen-insensitive DU145 and PC3 cell lines. PRL-induced influences (0.1-10 mIU/ml of medium) on proliferation were assessed using the colorimetric methylthiotetrazole assay. Androgen sensitivity in the three cell lines was determined by assessing the proliferative influence of dihydrotestosterone (DHT) (0.1-10 nM). PRL-induced modifications in PC3 cell kinetics were assessed using Feulgen-stained nuclear image cytometry. RESULTS: Although DHT markedly stimulated LNCaP proliferation, it had no proliferative effect on the DU145 and PC3 cell lines. By contrast, PRL significantly modulated the proliferation of the DU145 and PC3 lines, but exerted weak, if any, effect on the proliferation of the LNCaP cell line. PRL increased the percentage of PC3 proliferating cells (i.e., cells in the S/G2 phases of the cell cycle) at low doses (0.1 mIU/mL) and decreased this percentage at high doses (10 mIU/ml). CONCLUSIONS: Proliferation of androgen-insensitive human prostate cell lines can be significantly modulated by prolactin.

Androgens↗

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

Prostatic intraepithelial neoplasia: influence of clinical and pathological data on the detection of prostate cancer.

PURPOSE: We attempted to characterize patients diagnosed with prostatic intraepithelial neoplasia without concurrent cancer on biopsy who had prostate cancer on subsequent biopsy. MATERIALS AND METHODS: The records of 93 patients with low and high grade prostatic intraepithelial neoplasia without concurrent cancer on initial biopsy were analyzed. The relationships among prostatic intraepithelial neoplasia grades, patient age, digital rectal examination, serum prostate specific antigen (PSA), transrectal ultrasound appearance and final pathological results were investigated. RESULTS: Subsequent carcinoma was found on repeat biopsy in 13.3% of patients with low grade and 47.9% with high grade prostatic intraepithelial neoplasia (p < 0.001). In the former group digital rectal examination, patient age, serum PSA and transrectal ultrasound were not predictive of cancer. Transrectal ultrasound appearance, digital rectal examination and serum PSA were statistically different between high grade prostatic intraepithelial neoplasia with and without subsequent cancer (p < 0.001, p = 0.008 and p = 0.016, respectively, univariate analysis). On multivariate analysis of patients with high grade prostatic intraepithelial neoplasia only digital rectal examination and PSA were predictive of subsequent carcinoma. CONCLUSIONS: High grade prostatic intraepithelial neoplasia is a strong predictor of subsequent cancer, especially in men with abnormal digital rectal examination and elevated serum PSA. Patients with high grade prostatic intraepithelial neoplasia should undergo repeat biopsy to exclude cancer. Further investigations are needed to optimize the treatment of patients with low grade prostatic intraepithelial neoplasia.

Aged↗

PubMed1996

Differential histochemical peanut agglutinin stain in benign and malignant human prostate tumors: relationship with prostatic specific antigen immunostain and nuclear DNA content.

The histochemical binding pattern of the peanut (Arachis hypogaea) lectin (PNA) was quantitatively described by means of computer-assisted microscope analysis in 28 benign prostatic hyperplasias (BPH), 15 prostatic intraepithelial neoplasias (PIN), and 119 prostatic adenocarcinomas. PNA exhibits nonimmune but selective binding to glycoproteins with beta-D-galactosyl(1,3)-N-acetyl-D-galactosamine residues. We also investigated whether a relationship existed between the number of histochemical-related PNA acceptors and the histochemical prostate-specific antigen (PSA) stain intensity, and between the number of PNA receptors and DNA ploidy level. The results show that neoplastic prostate tissues and high-grade intraepithelial prostatic neoplasias (PIN2_3) exhibit a significantly higher number of PNA acceptors than benign prostatic hyperplasias and low (PIN1) grade prostatic intraepithelial neoplasias. A statistically significant correlation was observed between the number of histochemically related PNA acceptors and PSA immunostain intensity. Lastly, diploid prostatic tumors, whether benign or malignant, exhibited a significantly higher number of PNA acceptors than aneuploid ones. These results suggest that PNA acceptors play an important role in the biology of prostate tumors.

Adenocarcinoma↗

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

[High-grade intraepithelial prostatic neoplasms: diagnosis and association with prostate cancer].

Prostatic intraepithelial neoplasia (PIN) fulfils the majority of requirements for a premalignant change in the human prostate. Forty-eight patients were diagnosed to have high grade PIN on prostatic needle biopsy. During a follow-up period, 23 (47.9%) were found to have adenocarcinoma on subsequent biopsies. We compared the patients age, the digital examination, the transrectal ultrasound appearance (TRUS) and the serum PSA level between those in whom cancer was detected subsequently and those with PIN alone. There was a statistically significant difference in the transrectal ultrasound appearance (TRUS) and the serum PSA level between the two groups (p < 0.001, p < 0.016 respectively). In conclusion, patients with high grade PIN, elevated serum PSA with hypoechoic zone on TRUS should be rebiopsied 3 months after the initial diagnosis. If the results are negative, close follow-up is mandatory.

Adenocarcinoma↗

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

Influence of dihydrotestosterone, epidermal growth factor, and basic fibroblast growth factor on the cell kinetics of the PC3, DU145, and LNCaP prostatic cancer cell lines: relationship with DNA ploidy level.

The cell kinetics (percentage of cells in the S+G2 phases of the cell cycle) and the DNA ploidy levels (nuclear DNA content) were determined in 108 samples each of the PC3, DU145, and LNCaP prostate cancer models. This was carried out by means of the digital cell image analysis of Feulgen-stained nuclei. Two to three hundred cell nuclei were analyzed for each of the 324 samples under study. The three cell lines were submitted to experimental conditions including the addition of dihydrotestosterone (DHT), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), either alone or in combination, to the culture media. The results show that under the present culture conditions, the PC3 cell line was DHT-, EGF- and bFGF-insensitive. In contrast to what is generally reported in the literature, the DU145 cell line was DHT- and EGF-sensitive under the present culture conditions, but bFGF-insensitive. The LNCaP cell line was DHT-sensitive, but EGF- and bFGF-insensitive. While mainly tetraploid, the three cell lines nevertheless exhibited a significant level of heterogeneity in their nuclear DNA content distributions. Indeed, the proportions of non-tetraploid (diploid, hyperdiploid, triploid, hypertriploid, hypertetraploid, polymorphic) DNA histograms were 14% in the PC3, 16% in the DU145, and 29% in the LNCaP cell lines. These results suggest that the DNA ploidy level would not influence the hormone sensitivity level in the cell lines since they had significantly distinct hormone sensitivity profiles while remaining mainly tetraploid.

Cell Division↗

PubMed1995

Suppression tuning characteristics of the 2 f1-f2 distortion-product otoacoustic emission in humans.

The suppression tuning properties of the 2 f1-f2 distortion-product otoacoustic emission (DPOAE) were measured in 16 ears of normally hearing human subjects. DPOAE were elicited by fixed, low-level primary tones in four frequency regions with the second primary tone frequency f2 at 1, 2, 4, and 6 kHz. For various suppressor frequencies, suppression of the DPOAE was measured as a function of the suppressor tone level, enabling the assessment of the threshold and the growth of suppression. Depending on the distance of the suppressor tone to f2, there were marked differences in the suppression behavior of different suppressor frequencies. The threshold of suppression was minimal slightly above f2 and hardly increased with increasing frequency, but increased continuously with decreasing suppressor frequency. The growth of suppression, however, did not systematically change below f2, but decreased rapidly above f2. Both changes resulted in asymmetrical, V-shaped suppression tuning curves. They were sharply tuned to a frequency slightly above f2, with Q10 dB values up to 7.87. This is consistent with the assumption that the main source of the DPOAE is at the f2 site. In some cases, the DPOAE was particularly sensitive to suppressor tones near the DPOAE frequency. In one individual case, facilitation was found for corresponding frequency-level ranges of the suppressor tone. This may suggest a secondary emission source at the distortion product place.

Acoustic Stimulation↗

PubMed1995

Tumour-associated trypsin inhibitor and renal cell carcinoma.

In the absence of a specific marker for renal cell carcinoma (RCC), we evaluated the tumour-associated trypsin inhibitor (TATI) in patients with RCC. Between November 1990 and November 1993, 63 patients with RCC and 23 patients with benign renal disease underwent a competitive radioimmunoassay of TATI. The cutoff value was defined on a series of serum samples of 96 healthy subjects (normal n < 20 micrograms/l, then 25 micrograms/l after April 1993). We related the value of TATI to the tumour stage and compared the sensitivities of TATI and other markers (CEA, CA 15-3, CA 125, CA 19-9, ferritin). In 24 patients the TATI assay was repeated 3-12 months after radical nephrectomy. 15 patients with benign disease had a normal value of TATI (specificity: 65%). 44 of the 63 patients had a value of TATI above the cutoff point (sensitivity: 69%). Sensitivities of CEA, CA 15-3, CA 125, CA 19-9 and ferritin were 5, 10, 13, 5, 35%, respectively. The TATI value was correlated with the stage of the disease. Among the 15 patients without metastasis, the mean preoperative value was 112 micrograms/l (14-760) versus 46 micrograms/l (24-180) postoperatively. In the 9 patients with metastasis, the preoperative mean value was 100 micrograms/l (20-434) versus 240 micrograms/l (22-544) postoperatively. TATI showed a better sensitivity than other markers for RCC but its specificity is limited. Nevertheless it can be useful for a postoperative follow-up. TATI remains one of the best serum markers for RCC.

Biomarkers, Tumor↗

PubMed1995

[Organ culture of human tissue as study model of hormonal and pharmacological regulation of benign prostatic hyperplasia and of prostatic cancer].

We have established organ cultures of human prostate in vitro analysis of the hormone responsiveness of prostatic carcinoma. The influence of dihydrotestosterone (DHT), the epidermal growth factor (EGF) and prolactin (PRL) was assessed on the proliferation rate of 30 benign human prostatic hyperplasias (BPH) maintained for 48 hours as short-term primary cultures. The influence exerted by the EGF, the DHT and the PRL on the BPH cell proliferation was characterized by adding these compounds alone or in combination to the culture media. The proliferation rate was assessed by means of histo-autoradiographical nuclear labeling with titriated thymidine. The results show that of the DHT, EGF and PRL, the first two induced a statistically significant increase in the cell proliferation rate in a proportion of BPH significantly higher than the proportion of BPHs whose cell proliferation was increased significantly by the PRL. Furthermore, the PRL was able to antagonize the EGF-induced stimulatory effect on the BPH glandular cell proliferation rate. Lastly, the EGF- and PRL-mediated effects on the BPH glandular cell proliferation correlated with each other, while the DHT-mediated did not correlate with either the PRL- or the EGF-mediated effects. This model of organ, culture provide a basis for developing a method for in vitro testing of the individual hormone and drug responsiveness of a prostatic carcinoma.

Aged↗

PubMed1995

[Predictive value of the serum PSA level in patients having undergone neo-adjuvant hormone treatment before radical prostatectomy].

Great interest has been generated recently in preoperative androgen deprivation for clinical stage B ou C (T2 ou T3) prostate cancer. The influence of neoadjuvant hormonal therapy on down-staging and down-grading is still controversial. To assess the influence of preoperative androgen deprivation on serum PSA levels, we compared pre- and post-treatment serum PSA levels in 54 patients who received complete pre-operative androgen blockade (LHRH agonist + flutamide) 3 months prior to surgery. All patients with a pretreatment PSA > 20 ng/ml had extra-prostatic disease excepted two patients who presented lesions of acute prostatitis with adenocarcinoma. After hormonal deprivation, 51/54 patients experienced a return of PSA to normal values (< 4 ng/ml). Among this patient, 33 had undetectable PSA levels (< 0.25 ng/ml). 90% of the patients with undetectable had tumor confined to the gland (pT2/B). On the other hand, patients who still have PSA > 4 ng/ml after hormonal deprivation, had extra-prostatic cancer (pT3-pT4). Thus, PSA levels after 3 months neo-adjuvant hormonal treatment might have a useful predictive value in patients selection for radical surgery.

Adenocarcinoma↗

PubMed1994

Ureteral and bladder lesions after ballistic, ultrasonic, electrohydraulic, or laser lithotripsy.

Four techniques of intracorporeal lithotripsy are now available: ballistic, ultrasonic, electrohydraulic, and laser. Their therapeutic efficacies have generally been evaluated and compared, but very few data have been available on their relative risks of iatrogenic trauma to the urothelial wall. We conducted a comparative analysis of this risk by testing the pig ureteral and bladder wall with the EMS Lithoclast, Olympus ultrasonic lithotripter, Walz Lithotron EL 23, and Versa Pulse Ho:YAG Coherent Laser. We measured the number of shockwaves or the energy required to perforate the ureter and bladder by delivering shocks perpendicular to the walls. Ureteral perforation was impossible with the 1.0-mm Lithoclast transducer and the 1.5-mm ultrasound transducer. Perforation was induced after 250 shocks with the 0.8-mm Lithoclast transducer, after 110 shocks with the 3F electrohydraulic electrode, and after 0.02 kJ with the laser. Bladder perforation was impossible with the 2.0-mm Lithoclast device and the 3.4-mm ultrasound transducer but was induced after 0.04 kJ had been delivered with the laser. We evaluated the iatrogenic risk under normal conditions of use by delivering the shocks tangentially to the ureteral wall and perpendicular to the bladder wall. We sacrificed animals on days 0, 1, and 6. The immediate histologic lesions induced by the Lithoclast and the ultrasound lithotripter were similar, consisting of a moderate reduction of the epithelial layers or intraepithelial detachments. Electrohydraulic shocks induced almost complete abrasion of the urothelium, and the laser induced extensive lesions of partial or complete necrosis of the urothelial wall.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Microsurgical arterio-arterial and arterio-venous penile revascularization in patients with pure arteriogenic impotence.

OBJECTIVE: To restore physiological erection by performing microsurgical penile revascularization. PATIENTS AND METHODS: The records of 21 patients with pure arteriogenic impotence were reviewed. Thirteen patients with localized obstruction of the internal pudendal or common penile artery underwent a Michal II arterio-arterial penile revascularization. Eight patients with a more distal arterial obstruction underwent a penile deep dorsal vein arterialization (DDVA). The mean follow-up period was 22 months. Surgery was considered successful when the patients had a permeable anastomosis and were able to achieve satisfactory erections resulting in normal intercourse. RESULTS: Potency was restored in eight of the 13 patients who had a Michal II procedure and in five of the eight patients who had a DDVA. Under antithrombotic therapy graft occlusion occurred in four patients. CONCLUSION: Microsurgical penile revascularization restored erectile function in two-thirds of patients in this study. However, further research must be performed to reach a greater understanding of the revascularization process.

Adult↗