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ABSTRACT: Since the past 10 years, results have established laparoscopy's efficacy. It is actually a consistent surgical option for a lot of indications met in urology. The rational behind performing laparoscopic procedures includes shorter hospital stays, less postoperative pain and a more rapid return to usual activity. Drawbacks of laparoscopy include significant learning curve, longer operative times and higher overall costs. One particular focus is the oncologic applications of laparoscopy for nephrectomy and specially for radical prostatectomy. Laparoscopy become nowadays an usual part of the armamenturium of urological teams.
Revue medicale de Bruxelles 11/2003; 24(5):400-7.
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Urology 10/2001; 58(3):318-34. · 2.43 Impact Factor
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ABSTRACT: After an initial experience using transperitoneal laparoscopic radical prostatectomy as described by Vallancien and Guillonneau, we developed a pure extraperitoneal approach. This approach seems more comparable to the open technique and avoid potential risks of specific complications due to the transperitoneal approach. We evaluated the perioperative parameters (blood loss, operating time, transfusion rate) and postoperative results (oncological results, continence and potency) after our first 50 cases.
Between September 1999 and September 2000, we performed 50 laparoscopic radical prostatectomy. On average, patients were 63.3 years old (range 47-71), had preoperative mean PSA values of 9.14 ng/ml (1.1-23). Median Gleason score was 6 (4-10) with 2.5 (1-6) positive biopsies for a mean prostate volume of 40 cm(3) (17.5-95.0). Clinical stage was T1, T2a, T2b and T3 in 46.3, 41.5, 9.8 and 2.4% of the cases, respectively. We used a pure extraperitoneal approach and we performed a descending technique starting with the dissection at the bladder neck. The seminal vesicles dissection is comparable to the open approach.
42 extraperitoneal and 8 transperitoneal procedures were performed (2 in the initial experience, 3 because of previous abdominal surgery and 3 because of incidental peritoneal opening). Mean operative time was 317 min, mean blood loss 680 cm(3), transfusion rate of 13%. 1 patient/50 was converted to an open procedure. Pathological stage was pT1a, pT2a, pT2b, pT2c, pT3a and pT3b in 2.2, 8.5, 42.5, 2.2, 34 and 10.6% of cases, respectively. Positive surgical margins were observed in 22% of cases. The potency rate after neurovascular bilateral bundle preservation was 43% at 3 months (n = 7) and 67% at 6 months and (n = 6) without any further treatment. The continence rate (no pad) was 39% at 3 months and 85% at 6 months. Detectable postoperative PSA at 3 month was observed in 2 patients only. Two major complications occurred: one acute transient renal failure one uretrorectal fistula at day 20.
The extraperitoneal laparoscopic radical prostatectomy results seem comparable to transperitoneal laparoscopic radical prostatectomy or open surgery. This approach is reproducible and seems to avoid the potential risks of intraperitoneal injury. Long-term follow up and comparative series are however necessary to further evaluate these new techniques.
European Urology 08/2001; 40(1):65-9. · 8.49 Impact Factor
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ABSTRACT: The present paper gives a comprehensive overview of recent data, especially prospective randomized trials, which support an important role for nutrition in the development of prostate cancer. Prostate cancer seems to be an ideal candidate for chemoprevention, in order to interfere by modification of nutritional habits with its onset, its incidence and ultimately with its progression, especially in high risk groups.
Revue medicale de Bruxelles 05/2001; 22(2):87-92.
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The Lancet 03/2001; 357(9253):326-7. · 38.28 Impact Factor
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BJU International 01/2001; 86(9):1014-22. · 2.84 Impact Factor
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ABSTRACT: To evaluate the long-term effects of 3-month neoadjuvant hormonal treatment in patients treated by radical prostatectomy for locally confined prostate cancer.
We report the results of 402 patients (220 with a clinical T2 tumor and 182 with a clinical T3 tumor) of whom 192 randomly received neoadjuvant total androgen deprivation using a LHRH analogue (goserelin) plus flutamide for a period of 3 months and 210 underwent radical prostatectomy only.
'Clinical downstaging' was seen in 30% of cases in the neoadjuvantly treated group (NEO). 'Pathological downstaging' occurred in 7 and 15% of cases in the direct radical prostatectomy (DP) group and the NEO group, respectively (p<0.01). In patients with clinical T2 as well as in patients with clinical T3 tumors, a significant difference in the number of positive margins was shown in favor of the NEO group (cT2, p<0.01; cT3, p = 0.01). This advantage, although there was a trend in favor of the NEO group, specifically in cT2 tumors, did not translate in a significantly better PSA progression rate (p = 0.18). However, when evaluating the local control rate in cT2 tumors, we observed local recurrence in 3 of 102 (3%) patients in the NEO group versus 12 of 114 (11%) patients in the DP group. The difference is statistically significant (p = 0.03). In the cT3 group, this difference was not statistically significant (NEO group: 15 of 87 (17%), and DP group: 21 of 95 (22%) patients; p = 0.41).
In this study, the clinical revelance of pathological downstaging and the lower percentage of patients with positive margins in the neoadjuvantly treated group with a clinical T2 tumor is not confirmed by a lower PSA progression rate. However, this study indicates that there may be a trend that this advantage in favor of the NEO group directly translates into a better local control rate in clinical T2 tumors. Better local control in cT2 tumors is only going to be of relevance if subsequently you can show that there is a better survival for these patients. Unfortunately, this article reports a study which is not yet mature enough to show relevant information. Presently, neoadjuvant therapy should not be given outside clinical research settings.
European Urology 12/2000; 38(6):706-13. · 8.49 Impact Factor
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A R Zlotta,
J P Van Vooren,
O Denis,
A Drowart,
M Daffé,
P Lefèvre,
L Schandene,
M De Cock,
J De Bruyn,
P Vandenbussche,
F Jurion,
K Palfliet,
J Simon,
C C Schulman,
J Content,
K Huygen
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ABSTRACT: The subcomponents of bacille Calmette-Guérin (BCG) involved in the mechanism of action of intravesical BCG immunotherapy used for prophylaxis of superficial bladder cancer recurrences have been poorly investigated. We purified various BCG subcomponents and analyzed in vitro their ability to enhance a Th1 polarized immune response as well as to increase lymphocyte-mediated cytotoxicity against bladder tumors. Human peripheral blood mononuclear cells (PBMCs) from healthy purified protein derivative-positive subjects were incubated for 7 days with whole BCG and various fractions (BCG cell wall, plasma membrane, cytosol, purified polysaccharides as glucan or arabinomannan, purified native proteins from BCG culture filtrate, recombinant 22 kDa protein, phosphate transporter PstS-2 and -3 proteins). IFN-gamma, IL-12, IL-2, and IL-6 production by stimulated PBMCs was compared to unstimulated controls and the phenotype of expanded cells analyzed by flow cytometry (FACS analysis). A (51)Cr-release assay monitored the cytotoxicity of amplified effector cells against T24 bladder tumor cells. Live BCG and most of its subcomponents (with the exception of cytosol, PstS-2 and -3) significantly enhanced IFN-gamma and IL-12 secretion, expanded CD3(-)CD56(+) cells and the non-MHC-restricted cytotoxicity against bladder tumor cells compared to unstimulated controls (all P < 0.001, t-test). IL-2 receptor blockage resulted in a clear reduction in the cytotoxic activity of stimulated PBMCs. Numerous BCG subcomponents thus provide positive stimuli for Th1 cell differentiation and enhance in vitro, non-MHC-restricted cytotoxicity against bladder tumor cells. Our findings provide the basis for the therapeutic use of several of these subfractions in experimental animal models bearing bladder tumors.
International Journal of Cancer 09/2000; 87(6):844-52. · 5.44 Impact Factor
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ABSTRACT: Although the sextant biopsy technique has been widely used, concern has arisen that this method may not include an adequate sampling of the prostate, especially for large prostate volumes. We conducted a multicenter study in patients with PSA levels <10 ng/ml to determine the influence of the total and transition zone (TZ) volumes of the prostate for predicting whether one single set of biopsies was sufficient to rule out prostate cancer (PCa). These parameters were evaluated in patients in whom PCa was found after one set of systematic sextant biopsies and those in whom PCa was found after a repeat biopsy.
A total of 1,018 patients were included in this study. All underwent transrectal ultrasound-guided needle sextant and two TZ biopsies of the prostate. Total and TZ volumes of the prostate were measured (prolate ellipsoid method). From this cohort, all patients in whom a benign disease was found after the first set of biopsies underwent a second similar set of biopsies within 6 weeks. Only patients with PCa were included in this study, whether diagnosed on first or repeat biopsy. Uni- and multivariate statistical analysis using the SAS system (Cary, N.C., USA) and ROC curves were used to compare patients in whom the diagnosis was performed after the first set of biopsies and those who required a second set.
Of the 1,018 patients, 344 (33.8%) had PCa diagnosed, 285 (28%) after the first set of biopsies, and 59 (8.1%) on repeat biopsy. As compared to patients diagnosed with PCa after the first set of biopsies, patients diagnosed after the second set had larger total prostate and TZ volumes (43.1+/-13.0 vs. 32.5+/-10.6 cm(3), p<0.0001 and 20.5+/-8.3 vs. 12.8+/-6.0 cm(3), p<0.0001). ROC curves showed that total and TZ volumes of 45 and 22. 5 cm(3), respectively, provided the best combination of sensitivity and specificity for discriminating between patients diagnosed with PCa after the first from those diagnosed after a second set.
In patients with total prostate volume >45 cm(3) and TZ >22.5 cm(3), a single set of sextant biopsies may not be sufficient to rule out PCa. In these patients, a repeat biopsy should be considered in case of a negative first biopsy.
European Urology 08/2000; 38(2):218-24. · 8.49 Impact Factor
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World Journal of Urology 07/2000; 18(3):179-82. · 2.41 Impact Factor
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A R Zlotta,
J P van Vooren,
K Huygen,
A Drowart,
M Decock,
M Pirson,
F Jurion,
K Palfliet,
O Denis,
J Simon,
C C Schulman
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ABSTRACT: For more than 20 years, BCG intravesical therapy schedule has included 6 weekly instillations. Very few studies have, however, analyzed the rationale of this regimen. We previously demonstrated that intravesical BCG induced an increased peripheral immune response against mycobacterial antigens as compared to pretreatment values. In the present work, we have studied the weekly evolution of this immune response induced by intravesical BCG instillations.
The evolution of the lymphoproliferative response of peripheral blood mononuclear cells against BCG culture filtrate (CF), tuberculin (PPD) and BCG extract (EXT) was tested before, every week during the BCG instillations and at 3 and 6 months follow-up in 9 patients with superficial bladder cancer treated with 6 weekly BCG instillations. Lymphoproliferation was measured by means of a tritiated thymidine incorporation test.
A significant increase in the lymphoproliferative response against PPD, CF and EXT was observed in 9, 8 and 7 of the 9 patients, respectively, as compared to pre-BCG values. The maximal lymphoproliferation was achieved after 4 instillations in 4/5 patients initially reactive against mycobacterial antigens whereas 2 of 4 initially nonreactive patients required 6 instillations. At 6 months' follow-up, lymphoproliferation against BCG and the other mycobacterial antigens returned to pre-BCG values in all patients. In 3 patients who received additional instillations because of tumor recurrence within 1 year of follow-up, the maximum immune response was observed already after 2 instillations.
In most patients, the maximal peripheral immune response is already observed after 4 weekly instillations. However, patients not previously immunized against mycobacterial antigens may require 6 weekly instillations to achieve a maximum stimulation level. Our data support the need to further evaluate the role of this status before starting BCG instillations. It could be of interest to study whether 6 BCG instillations are really necessary in patients previously immune against mycobacterial antigens.
European Urology 05/2000; 37(4):470-7. · 8.49 Impact Factor
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ABSTRACT: This article reviews the literature on some of the available biomarkers such as p53 and its down-stream effector p21 on superficial bladder tumor biology and their prognostic significance. The role of p53 tumor suppressor gene is controversial in superficial bladder cancer, possibly because analyzing one single effector of a pathway might hide the role of downstream effectors. The aggressiveness of this condition is related to proliferative activity as measured by Ki-67. Further studies are still necessary to draw definitive conclusions about the role of these different biological markers in superficial bladder cancer.
Urologic Clinics of North America 03/2000; 27(1):179-89, xi-xii. · 1.82 Impact Factor
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Acta urologica Belgica 02/2000; 68(1):6-9.
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ABSTRACT: Prostate cancer lends itself ideally to chemoprevention due to a number of specific features of the disease. These include a high prevalence, long latency time, hormone dependency, the availability of an ideal marker (prostate serum antigen) and, last but not least, the availability of a defined precursor lesion (prostatic intraepithelial neoplasia) among the pathways leading to clinical disease. The large variability in the incidence of the tumor in different geographical regions suggests the possibility of nutritional influences regarding the stimulation and/or inhibition of clinical cancer, as there is a similar prevalence worldwide of the precursor lesion. A great number of publications have dealt with a number of nutritional factors, including fat, phytoestrogens, vitamins (especially vitamin E) and minerals such as selenium and calcium. These are among the most reported substances with a possible influence on disease development; however, unfortunately there are no conclusive results or study outcomes at present which satisfy accepted standards of evidence. Ongoing studies on nutrition and prostate cancer may bring the required evidence to support what is still only an hypothesis at present.
Scandinavian journal of urology and nephrology. Supplementum 02/2000;
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ABSTRACT: For more than 20 years, superficial bladder tumors have been demonstrated to be sensitive to several biological response modifiers and especially to immunomodulators. The best-known and studied immunomodulator is the bacillus Calmette-Guérin (BCG). However, despite its well-recognized efficacy, BCG is not a universal panacea and is associated with potentially significant side effects.
New perspectives in BCG therapy aiming to increase BCG efficacy or to decrease side effects include the use of genetically engineered BCG strains producing cytokines as well as the use of purified BCG subcomponents. Because a cascade of immunological reactions including the secretion of several cytokines has been demonstrated in the BCG mode of action, many other biological response modifiers and especially immunomodulators have been studied for superficial transitional cell carcinoma therapy. Some were investigated in human trials, others are still in laboratory studies; some are administered intravesically whereas others are given orally. Interferon-alpha (IFN-alpha) intravesical instillations have been evaluated in several controlled studies.
Although toxicity of intravesical IFN is minimal, its optimal dose, schedule and efficacy remain to be defined. Recent prospective studies comparing IFN to BCG intravesical therapy have been somewhat disappointing although this cytokine may be effective in some patients with T(a)-T(1) disease who have failed BCG therapy. Other immunomodulators administered intravesically investigated in clinical studies include interleukin 2 (recently used in a clinical study with a marker tumor response), levamisole, Rubratin, a Nocardia rubra cell wall skeleton, and keyhole limpet hemocyanin. Several biological response modifiers administered orally such as vitamin A (and its derivatives), Lactobacillus casei or bropirimine have been tested in clinical trials as well. In contrast, Allium sativum (garlic) or OK-432 (a streptococcal preparation) or BCG subfractions have been tested in laboratory studies only.
Published reports on several of these biological response modifiers suggest that these compounds may be an alternative in patients with superficial bladder cancer who have failed or have not tolerated BCG, but further evaluation to improve efficacy, durability and understand their mechanism of action is warranted.
European Urology 02/2000; 37 Suppl 3:10-5. · 8.49 Impact Factor
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Prostate cancer and prostatic diseases 12/1999; 2(S3):S36. · 2.10 Impact Factor
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ABSTRACT: To assess the accuracy and reliability of measurements of the volume of the transition zone (TZ, representing the hypertrophied benign component) and whole prostate by TRUS in patients with BPH or cancer, by comparing the radiological with pathological findings after surgery.
The study comprised 36 patients with prostate cancer undergoing radical prostatectomy and 34 patients with symptomatic BPH treated using retropubic adenectomy. The weights of the radical prostatectomy specimens and of the enucleated adenomas were correlated with the corresponding volumes of the TZ and of the whole prostate, respectively, measured by TRUS using the prolate ellipsoid method.
The mean (sd) TZ volume measured by TRUS was 36.9 (25.48) mL, whereas the weight of the enucleated specimen was 42.7 (33.58) g (correlation coefficient r=0.95, P<0.001). The TRUS estimate of the volume of the whole prostate was 29.2 (9.24) mL, while the radical prostatectomy specimens weighed 34.5 (10.76) g (r=0.78, P<0.001). The variability in the TZ volume estimate ranged from -17% to +18%, whereas the variability for whole prostate was -21% to +30% (P<0.05).
Measurements of the TZ of the prostate by TRUS are more accurate than those for the whole prostate. An assessment of the TZ volume may be sufficiently reliable to be used in the clinical management of BPH and to detect prostate cancer using the prostate-specific antigen density of the TZ as a marker.
BJU International 11/1999; 84(6):661-6. · 2.84 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the ability of prostate-specific antigen (PSA)-based parameters including PSA density (PSAD), PSAD of the transition zone (PSA-TZ), percent free PSA, PSA velocity, and their combination to enhance the specificity of PSA for prostate cancer detection in men with serum PSA levels between 4 and 10 ng/mL. We evaluated prospectively 559 consecutive men referred for early detection of prostate cancer who had serum PSA levels between 4 and 10 ng/mL. All men underwent prostatic ultrasonography and sextant biopsy with two additional TZ biopsies. In all cases, if first biopsies were negative an additional set of biopsies was obtained within 6 weeks. The ability of PSAD, PSA-TZ, PSA velocity, percent free PSA, and their combination to improve the detection of prostate cancer was evaluated by univariate and multivariate analysis as well as receiver operating characteristic (ROC) curves. In this prospective study of 559 patients, 217 had prostate cancer and 342 had histologically confirmed benign prostatic hyperplasia. Multivariate analysis and ROC curves showed that PSA-TZ and percent free PSA (f/t PSA) were the most powerful and highly significant predictors of prostate cancer. Areas under the ROC curve (AUC) for PSA-TZ and percent free PSA were 0.827 and 0.778, respectively (p = .01). Combination of f/t PSA with PSA-TZ (AUC = 88.1%) significantly increased AUC as compared to each of the other parameters alone as well as their combination (p = .02). The next best combinations were PSA-TZ + PSAD, PSA-TZ + PSA, and f/t PSA + PSA. PSA-TZ followed by f/t PSA and PSAD were the most powerful predictors of prostate cancer in referred patients with a serum PSA between 4 and 10 ng/mL. f/t PSA + PSA-TZ was the most effective combination. When volume-independent PSA parameters were taken into consideration, f/t PSA + PSA clearly outperformed the other options.
Techniques in urology 07/1999; 5(2):71-6.
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ABSTRACT: We determine if, before intravesical bacillus-Calmette Guerin (BCG) therapy, p53, p21WAF-1-CIP1 (a critical downstream effector of p53 pathway of cell growth control, inhibiting cyclin dependent kinases) and the cell proliferation marker Ki-67 (MIB-1) could be used as prognostic markers of response to BCG in patients with superficial bladder tumors.
The study included 47 patients with superficial bladder tumors at high risk for recurrence or progression treated with 6 weekly intravesical BCG instillations. We analyzed p53, p21 and Ki-67 on paraffin embedded samples by immunohistochemistry and the percentage of positive cells was determined in a blinded fashion. Quantitative immunostaining was analyzed in relation to time to recurrence and progression using univariate or multivariate analysis and the Kaplan-Meier method.
During a mean followup of 24.6 months 23 of the 47 patients (48.9%) presented with tumor recurrence and 10 (21.2%) had later progression to invasive disease. A p21 over expression (greater than 10%) was observed in 23 tumors (48.9%) and positively correlated with p53 (p = 0.0097) but not with Ki-67 (p = 0.327). Of the tumors 18 (38.2%) were p53 and p21 negative. Among p21 positive tumors 15 (65.2%) were p53 and p21 positive, suggesting that p21 may also be regulated by p53 independent pathways. However, p53 did not act as a predictor of recurrence or progression. In contrast, using Kaplan-Meier curves p21 over expression (greater than 10%) and Ki-67 at a 25% cutoff were associated with shorter recurrence-free survival (both p = 0.02 log rank test) but they did not predict additional information about risk of progression. However, multivariate analysis failed to demonstrate any independent prognostic value for p21 or Ki-67 in contrast to tumor stage.
Our results indicate that p21WAF-1-CIP1 seems to be regulated by p53 independent pathways in superficial bladder cancer. The present study did not indicate an independent prognostic significance in patients treated with BCG for p53, p21WAF-1-CIP1 or Ki-67 markers. Larger prospective studies are needed to evaluate further the independent value of these biological markers in superficial bladder cancer management.
The Journal of Urology 04/1999; 161(3):792-8. · 3.75 Impact Factor
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BJU International 03/1999; 83(3):341-2. · 2.84 Impact Factor
