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Objective: To determine the additional value of the presence of microscopic haematuria in patients with benign prostatic hyperplasia (BPH)., Methods: In 750 consecutive patients with BPH urinalysis was performed and the grade of microhaematuria was correlated with other clinical findings., Results: Microscopic haematuria was found in one third of the patients. Only 3 had a bladder tumour and 49 patients had urinary calculi for which only one patient required treatment. There was no correlations between any clinical parameter and the finding of microscopic haematuria., Conclusion: Microscopic haematuria is a frequent finding in assessment of BPH patients and additional tests should only be performed if indicated.

Analysis of the pressure/flow relation renders objective and detailed information on bladder outlet obstruction. The benefit of pressure/flow analysis for clinical and fundamental research questions, however, cannot be acknowledged without comparison of the different methods that exist. We compared one parameter analysis (URA) with two parameter (PURR) analysis in 99 consecutive patients with benign prostatic enlargement. The normal (instantaneous intrapatient) variability of both the PURR parameter Pvoidmin (minimal pressure during voiding) and the URA is approximately 10-15 cm H2O. Within these limits agreement between the two methods of analysis in the quantification of (minimal) outlet obstruction was observed in about 50% of the cases. However, when Qmax is less than 6 ml/s (in 49.5% of the patients) the URA number exceeds the value Pvoidmin in 96% of the cases. Predominantly this is caused by the fact that in the majority of these cases the type of bladder outlet obstruction is more constrictive than the URA curve, based on Pdet at Qmax indicated. In patients with a low flow rate and/or a constrictive type of obstruction, the Pvoidmin resulting from PURR analysis indicates a lower minimal pressure during voiding compared to URA.

The hypothesis that exposure of a solid tumor to high-energy shock waves (HESW) could lead to an increase of metastases was investigated in an animal model. The highly metastatic AT-6 Dunning R3327 rat prostate cancer subline was implanted in the hind limb of a Fisher-Copenhagen rat and was exposed to 6000 shock waves delivered by an experimental lithotripter, or sham-treated, as soon as the tumor had reached a volume of 175-225 mm3. The tumor-bearing leg was amputated 24 h later and the number of metastases was examined 12 weeks thereafter at autopsy. Metastases were seen in 82% of the animals exposed to HESW and in 25% of the sham-treated animals. There was no significant difference in weight of the lungs that contained metastases, between sham and treated animals. These results were confirmed in a second experiment. We conclude that the metastatic spread of tumors with a high metastatic potential may be enhanced by shock-wave exposure.

Objectives: Despite disadvantages such as time-consuming and tedious to the user, planimetric volumetry is considered to be the most accurate method for prostate volume determination. This study investigates the possibilities of formula-derived volume determination and reveals the best alternative to planimetric volumetry., Methods: The prostate volume is calculated using prostatic dimensions (length, height and width) in four mathematical descriptions for prostate volume calculations. As reference, the planimetric results obtained with 4 mm step size were used., Results: Compared to the results of planimetric volumetry obtained with 4-mm intersection distance, the best results for volume determination with mathematical calculation were obtained with a formula describing a spheroid volume using half the mean of width, height and length as radius., Conclusion: Although planimetric volumetry remains the most accurate method for prostate volume determination, the spheroid formula is the best alternative method for quick volume assessment with reasonable accuracy.

Objective: The incidence of ureterointestinal strictures following urinary diversion ranges from 4 to 8%. Traditionally, the treatment consists of open ureteral reimplantation. During the last decade, however, percutaneous techniques have gained increased interest for treatment of these strictures. We evaluated the outcome of anterograde percutaneous treatment of ureterointestinal strictures after urinary diversion., Methods: Since 1985, we attempted treatment of 15 ureterointestinal strictures, either by percutaneous anterograde dilatation (n = 10) or cold-knife incision (n = 2). In 3 patients the stricture could not be passed with a guide wire, precluding percutaneous treatment. Anterograde dilatation was performed with semirigid fascial dilators in 6 patients and additionally with a Grüntzig balloon catheter in 4. Routinely, following a successful procedure, a 12-Fr multihole stent was left in place for 6 weeks., Results: Restenosis was seen in 4 patients 2, 2, 19, and 36 months, respectively following the procedure. In 8 patients no stenosis developed so far (follow-up 8-96 months). Morbidity after the procedure consisted of fever after nephrostomy puncture in 1 patient and stent occlusion in another. Both were managed conservatively., Conclusion: Anterograde percutaneous treatment of ureterointestinal strictures after urinary diversion is a safe primary procedure with a permanent success rate in half of the patients (53%).

Purpose: Because we have found that random mucosal biopsies have no additional prognostic value to conventional histopathology, we studied biopsies of histologically normal bladder mucosa with several molecular markers believed to be associated with the development of transitional cell carcinoma., Materials and Methods: Six groups of patients with an increasing stage of bladder tumor were selected: (1) benign disease (for example, benign prostatic hyperplasia, n = 8); (2-4) low (n = 10), intermediate (n = 9) and high risk (n = 7) superficial tumors; (5) progressive superficial tumors resistant to optimal conservative therapy (n = 6); (6) invasive or disseminated tumors at presentation (n = 5). We studied the expression of cytokeratin (used as an epithelial marker), fibronectin, E-cadherin (HECD-1), I-CAM, human leukocyte antigen (HLA)-I, HLA-II and epidermal growth factor receptor (EGF-R) in cold-cup biopsies of normal mucosa., Results: Fibronectin, HECD-1, I-CAM and HLA-II expression showed no significant changes in the different groups. There was a significant increase in the expression of HLA-I (p = .003) and EGF-R (p = .0001) with a higher stage of the tumor., Conclusion: An increasing EGF-R expression in normal looking mucosa of patients with increasing stages of bladder tumors could be a prognostic factor or might indicate that this increase in expression is not tumor specific but is seen in the whole bladder.

Background: Alterations of the tumor suppressor gene p53 are known to occur in bladder cancer. Although p53 overexpression is associated with mutation of the p53 gene, a substantial discrepancy between molecular genetic alteration in p53 and overexpression of the protein has been found., Experimental Design: Tumor specimens of 39 bladder cancer patients were immunohistochemically analyzed for p53 overexpression, and the results were compared with the presence of a mutation as assessed by single strand conformation polymorphism (SSCP) and direct sequencing. Both clinical and biologic aspects were studied., Results: A significant correlation between p53 overexpression and poor survival in the whole group studied was found (p < 0.01). No association between p53 overexpression and decreased survival was found for invasive tumors in contrast with other studies. Differences in treatment of the patients and different Ab and scoring systems used might explain these differences. In our study, the Kaplar-Meier curves showed the same result for p53 overexpression and p53 mutation when the whole group and the invasive tumors were studied. However, in the group of superficial tumors, which was unfortunately too small for statistical analysis, we found p53 overexpression in three tumors, and no p53 mutations were found. A good concordance between p53 mutation and p53 overexpression was found (p < 0.02). However, two out of eight tumors with an SSCP-proven p53 mutation showed no p53 immunoreactivity, probably as a result of loss of the nuclear localization signal. Twenty three percent (7/31) of the tumors showed p53 overexpression without any sign of a mutation., Conclusions: Our results indicate that, despite good concordance between p53 mutation and p53 overexpression, there is no direct casual relationship between mutation and protein accumulation. Apparently, other events than mutation can trigger p53 stability.

Purpose: We evaluate the relationship among post-voiding residual urine volume, bladder outlet obstruction and maximum detrusor contractility power., Materials and Methods: We investigated urodynamically and retrospectively 242 elderly men with various grades of bladder outlet obstruction and symptoms., Results: Residual urine predominantly correlated with bladder outlet obstruction and not with maximum detrusor contractility power. Maximum detrusor contractility power showed significant positive correlation with bladder outlet obstruction. Urodynamically, the detrusor compensates for bladder outlet obstruction with elevated maximum detrusor contractility power. Decay of contraction during micturition however, hampers effective emptying., Conclusions: Maximum detrusor contractility power limits for normal detrusor contractility must be related to bladder outlet obstruction grade. Based on the results of our analysis, new limits showing improved correlation with complete emptying were derived.

The aim of this study is to investigate theoretically the possibility for activation of small myelinated nerve fibres without activating larger ones when stimulating a nerve fibre bundle using a monopolar point electrode. Therefore, the sensitivity of excitation and blocking threshold currents of nerve fibres to fibre diameter, electrode-fibre distance and pulse duration has been simulated by a computer model. A simple infinite, homogeneous volume conductor and a cathodal point source were used in combination with a model representing the electrical properties of a myelinated nerve fibre. The results show that selective activation of small myelinated fibres may be possible in a region at some distance from the electrode.

Objective: To determine if bladder outlet obstruction can be adequately relieved after laser prostatectomy., Patients and Methods: Since November 1992, a total of 105 patients underwent laser treatment of the prostate because of complaints related to benign prostatic enlargement (BPE). To date, urodynamic data from a study of pressure flow analysis are available for 79 patients both at baseline and at 6 months after treatment. Patients were evaluated using changes in symptoms (IPSS symptom score), peak flow rate (Qmax), post-voiding residual volume (PVR), detrusor pressure at maximum flow (Pdet at Qmax), and the linear passive urethral resistance relation (LPURR). Moreover, patients with minimal bladder outlet obstruction were compared to patients with severe bladder outlet obstruction., Results: There was a significant improvement in mean IPSS score from 21.3 at baseline to 5.3 at the 6-month follow-up. The Qmax improved from 7.9 mL/s to 17.8 mL/s, and the PVR decreased from 91.6 mL to 15.6 mL. At baseline, > 80% of the patients were considered obstructed according to the analysis of pressure flow, whereas 6 months after laser treatment, only 5% of the patients were still considered obstructed. A comparison of the outcome between minimally obstructed patients and severely obstructed patients showed comparable improvements., Conclusion: Laser therapy of the prostate was, according to urodynamic parameters, capable of relieving outlet obstruction and minimally obstructed patients also showed a significant relief of outlet obstruction.

Purpose: The reliability and objectivity of computer assisted transrectal ultrasound are examined., Materials and Methods: Pathological examination of radical prostatectomy specimens was compared prospectively to automated cancer detection in corresponding transrectal ultrasound images., Results: For automated cancer detection, a sensitivity of 0.75 and a specificity of 0.78 were obtained. Moreover, 74% of human interpretation of the percentage of malignancy in the analyzed images was equal to the actual calculated percentage (Pearson's product moment correlation coefficient 0.85)., Conclusions: Comparing these results to those obtained with normal transrectal ultrasound, automated analysis provides additional information in the interpretation of transrectal ultrasound images by color coding them in an objective manner according to the probability of malignancy.

Prognostic factors in superficial bladder tumours are highly correlated with each other. In this study, their relative importance is examined and grouping of patients in three different prognostic groups suggested. 576 patients (from EORTC protocols 30790 and 30782) were analysed. They have been followed from 3 months to 8.6 years with a median of 4 years. 76 patients developed an invasive tumour (> or = T2); the shortest time to invasion was 12 weeks, the longest was 6.6 years. Time from invasion to death ranged from 3 weeks to 4.4 years with a median of 2 years. Prognostic factors contributing to recurrence, invasion and survival were investigated: age, sex, size of largest tumour, number of tumours, T-category, G-grade, time from diagnosis (years), prior recurrence rate/year, site of involvement. The relative importance of these factors was measured by performing a multivariate analysis based on Cox's proportional hazards regression model. Based on the most important prognostic factors and their association with invasion and death, an index was computed reflecting the risk of both invasion and death due to malignant disease, respectively. The index was used to assign patients to one of three prognostic groups. Three main factors determined patient's prognosis: tumour size, G-grade and prior recurrence rate/year. The model coefficients for invasion were 0.51 (recurrence rate < 1/year, 1-3/year, > 3/year), 84 (grade 1, 2, 3), 0.48 (size < 1.5, 1.5-3, > 3 cm) and for death due to malignant disease 0.89 (recurrence rate), 0.73 (grade) and 0.44 (size), respectively. Risk groups are suggested based on the index. Additional treatment in patients with superficial transitional cell carcinoma of the bladder may be decided depending on the risk group to which the patient belongs.

Planimetric volumetry is used in clinical practice when accurate volume determination of the prostate is needed. The prostate volume is determined by discretization of the 3D prostate shape. The are of the prostate is calculated in consecutive ultrasonographic cross-sections. This area is multiplied by the distance between the cross-sections and the total volume is determined by summation of all contributions. Besides the quality of the automated outlining, the accuracy of this method depends on this intersection distance and on the angle of the scan plane with the probe. Also, the location of the first cross-section is of influence. This paper describes the influences of these parameters on the accuracy of the volume determination using a simple prostate model. This theoretical influence is compared to clinical volume determinations using automated planimetric volumetry with different step sizes. From our data, it is concluded that a step size of 4 mm for planimetric prostate volume determination is a good compromise between investigation time and accuracy in a clinical setting.

Multiple sclerosis affects the lower urinary tract in many patients. The relationship between lower urinary tract abnormalities and disease-related parameters of multiple sclerosis is not well described. We screened urologically and neurologically 212 patients according to a standard protocol. Micturition complaints were noted in 52% of the patients and urodynamic abnormalities were found in 64%. A statistical correlation was found between detrusor hyperactivity and detrusor hypoactivity with disease-related parameters, that is disease duration, disability status, myelin basic protein concentration in the cerebrospinal fluid and neurophysiological investigations. No relationship was found between detrusor hypersensibility or detrusor hyposensibility and the aforementioned disease-related parameters. In 1 patient upper urinary tract abnormalities were noted in combination with urodynamic abnormalities. We conclude that lower urinary tract abnormalities can be found in every patient with multiple sclerosis unrelated to the state of the disease. Severe upper urinary tract abnormalities are rare.

Purpose: A urodynamic study was done to judge the capability of laser treatment to relieve bladder outlet obstruction., Materials and Methods: Advanced urodynamic studies with pressure-flow analysis were performed before and 6 months after laser treatment using 3 different laser devices., Results: Forty patients showed significant improvement in all obstruction parameters (detrusor pressure at maximum flow rate, urethral resistance relation, theoretical cross-sectional urethral area, minimal detrusor pressure and linear passive urethral resistance relation) together with significant subjective improvement in international prostate symptom score. After treatment 82 to 92% of the patients could no longer be considered to have obstruction. No difference in outcome among the devices used was found., Conclusions: Laser prostatectomy is indeed capable of relieving bladder outlet obstruction.

An information system was developed to manage the data for a large number of research projects simultaneously. The system, called URIS, has facilitated the management of research data in an academic urological department. It enables end-users, who are not necessarily skilled computer scientists, to design their own databases semi-automatically, by supporting data entry screen design and the specification of research items. The system creates the database tables automatically after these activities. The specification of research items is the most important but also most difficult part in this process.

In the literature the determination of the vibration sensitivity threshold of the penile glans by means of biothesiometry has been introduced as a cost-effective office test for the evaluation of penile neuropathy in impotent men. At our facility we have gained extensive experience with neuro-urophysiological tests for the evaluation of penile innervation. These neuro-urophysiological tests have the disadvantage of complexity, invasiveness and time consumption. In our study both methods were compared in 31 impotent patients. The results showed that penile glans biothesiometry yields consistent results when measurements are repeated during 1 session. However, no relationship was found between the outcome of penile glans biothesiometry and neuro-urophysiological tests of the dorsal penile nerve, which is probably due to the fact that vibration is not an adequate stimulus to the skin of the penile glans that contains free nerve endings (that is pain receptors) only, and hardly any vibration receptors. We conclude that biothesiometric investigation of penile glans innervation is unsuited for the evaluation of penile innervation and cannot replace neuro-urophysiological tests.

A method for automated determination of the prostate volume based on planimetric volumetry was developed to overcome subjectivity in prostate volume measurements using ultrasonography. An edge detection method is applied to locate the prostate boundary in sequential ultrasonographic images. During regular examinations, the volume was assessed automatically in 55 patients. The Pearson correlation coefficient of the automated volume compared to the reference prostate volume was 0.93. The estimated ratio of the automated volume to the reference volume was 0.92. This method overcomes the individual subjectivity when interpreting ultrasonographic images, and provides accurate and objective results for followup of benign prostatic hyperplasia treatments and for comparison of multicenter trials. Also, this method is a useful tool for objective determination of prostate specific antigen in proportion to the volume (prostate specific antigen density).

Erectile dysfunction (ED) may be caused by abnormalities of intracavernous penile structures. In order to investigate whether specific proteins could be identified that might be related to ED, the composition of structural proteins in cavernous tissues of patients with ED was compared to that of normal cavernous tissues by gel electrophoresis. Increased expression of a 68-kDa nonionic detergent extraction-resistant protein was demonstrated in tissues of more than half of the patients with vasculogenic ED, whereas only one out of nine normal cavernous tissues showed the same phenomenon. Increased expression was not related to a specific type of vascular insufficiency, aging, or diabetic constituency. Histochemical and immunochemical studies revealed that the increased amount of the 68-kDa protein is not merely the result of a surplus of nervous, smooth muscle, or elastic tissues. Furthermore, antibodies specific for 68-kDa neurofilament and 62- to 67.5-kDa tropoelastin did not recognize the 68-kDa protein on Western blots. The possibility that the 68-kDa protein may help us understand the etiology of certain cases of erectile dysfunction is discussed.

Urodynamic investigation becomes increasingly important in the diagnosis of bladder outflow obstruction in patients with benign prostatic hyperplasia. To date, different methods for evaluation of the pressure-flow relationship and quantification of the grade of obstruction are available. Models for pressure-flow analysis are briefly explained. The variability of the parameters is investigated by evaluation of 75 patients in whom 2 sequential voidings during urodynamic investigation were analyzed. The results showed that in 87% of these patients individual maximum flow differences of first and second voidings were less than 2 ml. per second. Individual detrusor pressure at maximum flow differences were less than 15 cm. water in 80% of these patients, while in 80% the intra-individual variation of the pressure-flow results was less than 15 cm. water for the minimal voiding pressure parameters (minimal urethral opening detrusor pressure and urethral resistance factor). For the pressure-flow parameter that defines the theoretical urethral lumen during voiding, the variation was less than 1.5 mm.2 in 84% of the patients. Patients with larger intra-individual differences are discussed. We concluded that the observed, aforementioned differences can be regarded as an indication of normal intra-individual variability of voiding during urodynamic investigation. This intra-individual variability, however, seldom leads to a change in the clinical grade of bladder outflow obstruction. We conclude that investigators involved in therapeutic trials of benign prostatic hyperplasia must be aware of this intra-individual variability of micturition, since this variability is greater than the refined scale of the pressure-flow analysis models.

There is accumulating evidence that some biochemical pathways observable by magnetic resonance spectroscopy, e.g., citrate acid and phospholipid metabolism, are altered in human prostate cancer. Four well-established human prostate cancer cell lines were therefore studied with magnetic resonance spectroscopy to compare differences in metabolic content with tumor biological behavior. Herein we demonstrate that, although each cell line has its own metabolic profile, relative creatine and citrate levels can be used to discriminate the androgen-dependent LNCaP cell line from the androgen-independent DU-145, TSU, and PC-3 cell lines.

Objectives: In this article we describe the long-term follow-up of patients with carcinoma in situ (CIS) of the urinary bladder and examine whether the extent of CIS, the presence of associated papillary tumors, or the response to treatment influence the course of the disease., Methods: Fifty-two patients with CIS of the bladder, treated in a randomized prospective study, are described. In 23 patients with concomitant papillary tumors all macroscopically visible lesions were completely resected transurethrally (TUR). CIS was histologically confirmed in all patients by biopsy, 29 of whom had primary CIS. The patients were treated with intravesical mitomycin, bacille Calmette-Guérin (BCG)-RIVM or BCG-Tice and followed regularly by urine cytology, cystoscopy, and biopsy., Results: Complete response was achieved in 65% of the patients. Of these responders, 24% later had a recurrence of CIS or a superficial tumor and 18% had progressive disease (PD). In the nonresponding patients, progression occurred in 67%. In the whole group, PD was seen in 35% of the patients, and radical cystectomy was performed in 21%. The disease-related death rate was 13%. The risk for recurrence or PD was not higher in patients with more extensive CIS, defined as three or more positive biopsy results or when CIS was associated with papillary tumors compared to patients with one or two biopsy specimens positive for CIS or CIS alone. Nonresponding patients showed a significantly higher progression rate and cystectomy rate than responding patients (P = 0.0012 and 0.008, respectively)., Conclusions: CIS of the bladder is a malignancy with a poor prognosis, especially in patients not responding after intravesical treatment. Early detection and adjuvant intravesical treatment after TUR of concomitant papillary tumors are required. In patients not responding after intravesical treatment, radical surgery is necessary before progression occurs. The number of biopsies positive for CIS, not the presence of concomitant superficial tumors, was an indicator for progression or recurrence.

Objective: To report on the use of automated image analysis in the interpretation of transrectal ultrasonographic images of the prostate., Patients and Methods: During transrectal ultrasonography, images were recorded from biopsies performed in 127 patients. Subsequently in the image, the puncture place was marked and analysed. Analysis of the images was performed with the Automated Urologic Diagnostic Expert (AUDEX) system, consisting of a personal computer connected to the ultrasound machine. From the images collected, parameters can be calculated for image classification. The parameters obtained with this procedure were correlated with the histological result., Results: Evaluation showed a sensitivity of 84.8% and specificity of 87.5%. The positive and negative predictive values, to predict prostate carcinoma, were 84.8% and 87.5%, respectively., Conclusion: Automated image analysis can help in the diagnosis of prostate carcinoma. In patients with non-palpable lesions or with poorly visualized tumours, image analysis is superior to the standard current diagnostic techniques.

Results of a randomized prospective study are reported in which mitomycin C, Tice bacillus Calmette-Guerin (BCG) and RIVM-BCG were compared in 437 patients with primary or recurrent pTa and pT1 bladder tumors, including carcinoma in situ. The followup (or time in study) varied from 2 to 81 months (mean 36 months). After complete transurethral resection of all visible tumors the patients were treated with 30 mg. mitomycin C once a week for 4 consecutive weeks and thereafter every month for a total of 6 months, and 5 x 10(8) colony-forming units Tice BCG or RIVM-BCG once a week for 6 consecutive weeks. For papillary tumors mitomycin C and RIVM-BCG treatments were equally effective (p = 0.53), and mitomycin C was more effective than Tice BCG therapy (p = 0.01).

We have shown that six different internal image antiidiotype antibodies (Ab2) raised against the combining site of the murine monoclonal antibody G250 (MAbG250; Abl), which specifically reacts with a human renal cell carcinoma (RCC)-associated antigen, induce antigen specific humoral and cellular responses in mice. These six Ab2 can be divided into four mutually exclusive groups: (1) NUH31 and NUH51, (2) NUH44 and NUH82, (3) NUH71, and (4) NUH91. Immunization with NUH82 or NUH91 resulted in Ab3 sera that gave complete protection against tumor challenge. In this study, we tested the antitumor efficacy of NUH82- and NUH91-induced mouse sera (Ab3 sera; Ab3-82 and Ab3-91) in mice with established subcutaneous human RCC xenografts. Mice were treated 3 times per week by intraperitoneal injection of Ab3 sera (0.2 ml) or MAbG250 (250 μg) for 6 weeks. Treatment of NU12 human RCC xenografts of approximately 20 mm(3) expressed as tumor size index (TSI) with NUH-Ab3 sera or MAbG250 resulted in significant tumor growth inhibition compared with tumors treated with Ab3 sera from mice immunized with control immunoglobulin (Ab3-MOPC). In all Ab3-NUH treated mice, tumors stabilized or disappeared completely. In contrast, Ab3-MOPC treatment did not result in any antitumor effects. Tumor remnants in Ab3-NUH treated animals contained viable tumor cells surrounded by infiltrating mouse cells, whereas no infiltration was observed in control tumors. These findings demonstrate that Ab3 sera obtained from NUH82- or NUH91-immunized mice are very effective in eradicating established RCC [i.e., Ab2 vaccination may be able to eradicate (minimal) residual disease in RCC patients].

This study was designed to evaluate the practical use of the combination of a low-dose intracavernous injection test (ICI) and visual erotic stimulation (VES) in the assessment of patients with erectile dysfunction. Additionally, a postinvestigation questionnaire (PIQ) was used to rate the erection following the investigation when the patient had left the office. It was hypothesized that the combination (ICIVES) and the PIQ would yield a higher erectile response rate than ICI or VES alone and would minimize the occurrence of prolonged erection. Of the 90 patients studied, 17 (19%) showed adequate erections to VES, 10 (11%) to ICI, and 60 (67%) to ICIVES. Of the 30 non-responders, 7 (23%) reported adequate erections on the PIQ. Overall, in 75% of the patients adequate erections were achieved. No prolonged erections were encountered. It is concluded that the combination of a low-dose ICI and VES, and the application of a postinvestigation questionnaire, is a powerful and safe test to select patients for autoinjection therapy.

Hormonal therapy represents first-line treatment for patients with advanced prostate cancer. Generally, surgical castration is viewed as the 'gold standard' but carries with it a psychological effect. Medical alternatives include LHRH analogues, antiandrogens, and oestrogens, though the last of these is associated with cardiovascular problems. For complete androgen ablation, it is generally believed that androgens of both testicular and adrenal origin need to be blocked. Combined androgen blockade (CAB) by the addition of antiandrogen to castration (medical or surgical) may, therefore, be an appropriate treatment for advanced prostate cancer. Recent trials have shown that CAB may have treatment advantages compared with castration alone, and these benefits are greatest in patients with minimal metastatic disease. For these patients CAB may now be considered as standard therapy. In the treatment of non-metastatic disease, recent trends based on the experience gained in advanced prostate cancer include the possible use of hormonal therapy in neoadjuvant and adjuvant settings along with prostatectomy or radiotherapy. There is also growing interest in the use of intermittent rather than continuous hormonal therapy. New treatments offer an increasing range of management options to help improve the quality of life of prostate cancer patients.

A new longer-acting depot formulation containing 10.8 mg Zoladex administered every 12 weeks was compared to the 3.6-mg Zoladex depot administered every 28 days, in a randomised trial in patients with advanced prostatic carcinoma in which pharmacodynamic efficacy and safety were assessed. Effective induction of mean serum testosterone suppression into the surgically castrate range by 21 days and maintenance of suppression for the duration of therapy was achieved with both the 3.6-mg and the 10.8-mg depot formulations. The Zoladex 10.8-mg depot was well tolerated both locally and systemically. This new formulation which is equivalent to three successive 3.6-mg depots will provide a more convenient dosing regime for both patient and doctor in this indication.

Laser treatment of benign prostatic hyperplasia has enjoyed growing popularity among urologists over the last few years. Various applicators and techniques have been reported. Because this may result in a different overall performance, we performed a prospective randomized study comparing the results of treatment using the Ultraline fiber (n = 44) with that using the Urolase fiber (n = 49). Although different types of fibers and techniques were used, the results of this study were surprisingly similar for both fibers used. The uroflow for the Ultraline group increased from an average of 7.9 ml/s at baseline to 19.3 ml/s at 3 months and 16.9 ml/s at 6 months. In the patients treated with the Urolase fiber the uroflow improved from an average of 7.8 ml/s at baseline to 19.5 and 16.3 ml/s at 3 months and 6 months, respectively. The improvement in symptoms, reflected by changes in the I-PSS symptom scores, for the Ultraline group went from 21.0 at baseline to 7.9 at 3 months and 6.0 at 6 months. The Urolase patients improved from 21.0 at baseline to 8.2 and 5.6 at 3 and 6 month, respectively. The morbidity mainly consisted of a prolonged need for posttreatment catheterization and irritative symptoms lasting for about 2-4 weeks. From this study we conclude that the results achieved by laser treatment of the prostate using the Ultraline and Urolase fibers are both equivocal and excellent; however, the morbidity of these treatments remains considerable.

The effects of repeated high-energy shock wave (HESW) tumor administration on tumor blood flow (TBF) were studied in NU-1 human kidney cancer xenografts. Deuteriated water was used as a magnetic resonance spectroscopic detectable tracer for measuring tumor blood flow. Tumors were exposed twice to 800 electromagnetically generated HESW, with a 24-h interval or sham exposed. No changes in TBF occurred after sham exposure to HESW. TBF levels 2 h after the first and second HESW application were, respectively, 46% and 37% lower than the mean preexposure TBF value and returned to normal levels within 16 h. There was statistically no difference found between the effects on tumor blood flow after the first and second HESW exposure. These observations are in agreement with earlier studies and provide a rationale to shorten the time interval between HESW monotreatments to 2 to 3 h.

Analysis of 185 consecutive patients with BPH revealed concomitant detrusor instability in 20% of the patients. Of all patients 30.9% were not obstructed, 51.8% were moderately obstructed and 17.3% were severely obstructed. Patients with detrusor instability during filling cystometry revealed no differences in average age, prostate volume or symptoms. Mean filling cystometry parameters revealed earlier sense of urge correlating with higher pressures at lower volumes in patients with detrusor instability. Pressure-flow analysis showed no differences between the patients with and without detrusor instability in bladder outflow obstruction parameters. Further analysis, however, revealed that the prevalence of patients with detrusor instability reaches a "steady state" at a moderate level of obstruction. On clinical epidemiological grounds, the conclusion is made that detrusor instability is developing in the early phase of obstruction. Probably detrusor instability and bladder outflow obstruction are concomitant, due to the aging process in many of these patients.

In this overview, Bacillus Calmette-Guérin (BCG) immunotherapy in superficial bladder cancer items are discussed on which consensus has been reached and on which controversies exist. The evaluation of the optimal route of administration has shown that intravesical instillation of BCG alone is accepted as the best route of administration. In searching for the appropriate BCG strain, the analysis of the results of 6 substrains has made clear that no particular strain has shown superiority over others. In finding the optimal treatment schedule there is strong evidence that maintenance therapy is superior to induction therapy alone. No consensus has been reached about the optimal dose for BCG therapy nor about how the toxicity of BCG treatment can be reduced. Although some reports have stated that BCG immunotherapy is superior to chemotherapy for the treatment of patients with superficial bladder cancer, more data are needed to prove this statement. In conclusion, although BCG has been proven to be very effective in the treatment of patients with superficial bladder cancer, it is certainly not a panacea for all patients with superficial bladder cancer.

In 90 patients treated with laser prostatectomy using the Urolase (n = 50) or Ultraline (n = 40) laser fiber, the fiber-tip durability was investigated. In general the Urolase fiber tips were less damaged than the Ultraline fiber tips. At visual inspection, 62% of the Urolase fiber tips were graded as minimally damaged in comparison with 28% of the Ultraline group. The Urolase fiber tips are more susceptible than the Ultraline fiber tips to damage caused by tissue contact, whereas the latter seem more fragile. Transmission measurements were performed in a laboratory setting to estimate the loss of energy output at the fiber tip due to damage. These measurements showed a major loss in almost all fibers. None of the Ultraline fibers had less than 10% transmission loss, and 18% of the Urolaser fibers had a transmission value of more than 90%. Finally, there seemed to be a poor correlation between the visual aspects of the fibers used and the changes in transmission.

Patients with advanced prostate cancer have a beneficial effect from maximal androgen blockade in terms of the subjective and objective delay of progression and median duration of survival, although side effects do occur more often in the combination treatment than in testicular suppression alone. Significant improvement or delayed deterioration in subjective parameters such as metastatic pain, performance status and urinary disorders strongly suggest (in the absence of validated questionnaires of quality of life at the time of this study) that orchiectomy plus nilutamide improves the quality of life as assessed by the subjective delay of progression, according to NPCP criteria, to an extent which outweighs the majority of adverse events.

Transrectal ultrasound (TRUS) offers a valuable complement to digital rectal examination (DRE) in diagnosing prostate diseases. However, in case of prostatitis syndromes, contradictions are found with regard to characteristic ultrasound features in these patients. Therefore we sought for better imaging techniques. This paper describes a study on the automated analysis of ultrasonographic prostate images (AUDEX). With image processing, in the present study, tissue characterization is performed to predict the probability of the presence of inflammated prostate tissue. This technique already proved its validity in patients with prostate cancer. During prostate examinations, images were recorded with clear indication of the puncture position. Only patients with an unambiguously inflamed or noninflamed benign histologic result were included. Evaluation showed that a sensitivity of 90.6% and a specificity of 64.2% was reached. Finally, the prospective positive and negative predictive value for prostatitis was 50.0% and 94.6%, respectively. This means that AUDEX predicts the diagnosis 'prostatitis' in a large number of patients with no infection. In case of prostatitis, however, this prediction is almost always right.

The current status of iodine 131-radiolabeled monoclonal antibody G250 (mAb G250) in renal-cell carcinoma (RCC) is described. This mAb recognizes a tumor-associated antigen that is expressed on the cell surface of almost all RCC but is not expressed on normal tissues, with the exception of gastric mucosa and larger bile ducts. On the basis of these favorable characteristics, this mAb seemed a prime candidate for clinical investigations. Preclinical animal studies and ex vivo perfusion experiments in tumor-bearing kidneys showed excellent targeting of mAb G250 to RCC tumors. Supported by these investigations, a phase I study was initiated to define the imaging and biodistribution characteristics of 131I-labeled mAb G250 in RCC patients. Specific localized of [131I]-mAb G250 to G250-antigen-positive primary and metastatic RCC was observed. In several patients, [131I]-mAb G250 imaging revealed thus far unrecognized, i.e., occult, disease. Values obtained for [131I]-mAb G250 uptake, relative as well as absolute, were among the highest reported for tumor biopsies obtained 8 days after intravenous mAb administration. The specific localization and high accumulation encouraged us to begin a phase I/II radiotherapy trial with [131I]-mAb G250. The maximal tolerable dose was reached at 90 mCi/m2 [131I]-mAb G250. In the subsequent phase I/II radiotherapy study, we observed stable disease in a great number of patients as well as minor responses in a small number of patients. Multiple treatments seemed necessary to achieve better response rates. However, anti-mouse responses prevented multiple dosing with the murine mAb G250.(ABSTRACT TRUNCATED AT 250 WORDS)

We have previously isolated and characterized 6 anti-idiotype antibodies (Ab2s) directed against monoclonal antibody G250 (MAbG250) which reacts with a tumor-associated antigen (TAA) expressed in a large proportion of human renal-cell carcinomas (RCC). These 6 Ab2s (NUH31, 51, 71, 82, 91: IgG1, NUH44: IgG2a) showed MAbG250 binding site specificity and induction of anti-TAA antibody resembling MAbG250 (so-called AbI') in rabbits, indicating that they are internal image antibodies. To investigate whether these Ab2s could induce G250-TAA-specific cell-mediated immunity, delayed-type hypersensitivity (DTH) tests were carried out with G250 antigen-positive and/or -negative cells in the ears of BALB/c mice. Mice primed with Ab2 showed antigen-specific DTH responses, whereas no significant DTH response was observed with G250-negative cells. This antigen-specific DTH could be transferred to naive mice by lymphocytes harvested from Ab2-sensitized mice. In addition to the classical DTH responses observed 24 and 48 hr after tumor challenge, an early-phase antigen-specific hypersensitivity response was seen 2 hr after challenge. This early component of the specific hypersensitivity reaction but not the classical DTH could be transferred to naive mice by serum from Ab2-sensitized mice, indicating that the early reaction was due to serum factors. These findings demonstrate that all Ab2s induced tumor-specific cellular immune responses directed against human RCC, and suggest that they may be useful as RCC-TAA surrogates, i.e., as tumor vaccines for RCC patients.

Chronic lower urinary tract dysfunction can be treated by sacral neuro-stimulation. Clinical parameters for selection of patients for this expensive and invasive treatment modality are not well defined to date. Therefore, before implantation of a permanent stimulator, the effect is tested by temporary implantation of a wire electrode connected to an external stimulator. According to the literature, many patients do not respond during temporary implantation and a mean of 25% of the patients with a permanent stimulator implanted fail to respond as well. To improve patient selection, we attempted to define clinical parameters to predict the outcome of sacral neuro-stimulation in 100 consecutive patients who were tested with temporary sacral stimulation. A total of 34 patients achieved a complete cure on trial stimulation. It appeared that detrusor overactivity and urethral instability responded best but they were not predictors of success. We conclude that neither gender, patient age, history nor diagnosis are predictors of success in sacral neuro-stimulation of lower urinary tract dysfunction.

The influence of high energy shock waves (HESW) on the local concentration of systemically given TNF-alpha was studied in a syngeneic rat bladder tumor model. 125I-TNF-alpha was injected intravenously and within 1 minute was followed by HESW tumor exposure. High energy shock waves were generated using an experimental shock wave emitter based on the Siemens Lithostar Plus. Administration of HESW to RBT323 tumors resulted in a 3-fold increase in uptake of 125I-TNF-alpha in the tumor compared with nontreated tumors, whereas the tissue distribution and pharmacokinetics of nontumor tissue were similar irrespective of HESW exposure. These results demonstrate that HESW administration leads to an increase in the local concentration of a systemically given drug. The capacity of HESW to increase local drug concentrations will be of importance in designing more effective combined treatment strategies.

Benign prostatic hyperplasia is one of the most common pathological processes to afflict men. Strikingly, there is a large variety of methods of evaluation and therapeutic strategies for BPH in various countries. Before adequate treatment is possible, the process of benign adenomatous hyperplasia has to be distinguished from malignant or inflammatory prostatic disease. Furthermore, secondary alterations of the bladder and upper urinary tract have to be evaluated. A wide range of imaging techniques of the lower and upper urinary tract have evolved over the years. The specific benefits and restrictions of each of them are discussed. Finally, the recent developments and possibilities of computer-aided tissue characterisation and volume determination are outlined. The development of imaging techniques for BPH has just begun...

The effects of high energy shock waves (HESW) on tumor cell metabolism and tumor blood flow were studied in the NU-1 kidney cancer xenograft by multinuclear 1H/2H/31P magnetic resonance spectroscopy. Tumor xenografts were exposed to 800 HESW using an experimental electromagnetic shock wave emitter based on the Siemens Lithostar Plus, which is used for clinical lithotripsy. Exposure of tumors to 800 HESW resulted in a temporary decrease of tumor blood flow (TBF) determined by the 2H NMR monitoring of the 2HO1H wash-out after intratumoral injection. By concomitant recording of 31P and 1H NMR spectra, tumor pH, high-energy phosphates and lactate levels were followed. Tumor treatment with HESW transiently resulted in acidification, ATP decrease, P(i) increase and lactate increase. In contrast, HESW administration adjacent to the tumor did not significantly influence TBF, tumor pH, high-energy phosphates or lactate levels, showing that the observed alterations are caused by an interaction of HESW and tumor tissue. The most likely explanation for these observations is that HESW administration causes local vascular malfunctioning followed by a reduction in oxygen and nutrient supply to the tumor which leads to a decreased aerobic energy metabolism. The results of this study may be used to aid the design of HESW-based therapies.

Evidence is accumulating that the tumour-suppressor gene p53 is involved in the development of bladder cancer. Therefore we studied p53 mutations in 47 bladder cancers obtained from 45 patients using polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) analysis. Eight out of 24 invasive tumours appeared to have a p53 mutation, while no p53 mutations were found in the superficial tumours. All the p53 mutations were found in grade 3 tumours. The tumours with altered p53 showed a higher frequency of allelic loss (FAL) than the tumours without a mutation (55.8% vs 21.1%, P < 0.05, chi 2 test). This increase in FAL suggests a correlation between p53 mutations and genetic instability. A significant correlation between mutated p53 and poor survival in the whole group studied was found (P < 0.001, log-rank test). However, within the group of muscle-invasive tumours the occurrence of p53 mutations had no additional prognostic value. Therefore, even though p53 mutations were found in aggressive tumours, the clinical usefulness of its detection seems limited. Nevertheless, these results imply that p53 is involved in the clinical behaviour of bladder cancer; its role in the progression of superficial cancer to invasive disease merits further attention.

Objective: Determining the therapeutic efficacy of transurethral microwave thermotherapy (TUMT) in benign prostatic hyperplasia (BPH)., Design: Prospective., Setting: Department of Urology, University Hospital Nijmegen, the Netherlands., Method: In the outpatient clinic, 130 BPH patients (mean age: 65.9 years (SD: 6.9); mean prostatic volume 50.2 cm3 (SD: 18.4)) received TUMT in a single session lasting 60 min. The prostate was heated to above 45 degrees C by a microwave antenna in a urethral catheter, resulting in tissue necrosis. In the first year after treatment the Madsen symptom score, maximal flow, residual volume, prostatic volume and concentration of prostate-specific antigen in blood were collected., Results: After 1 year 98 patients could be evaluated; of the other 32, 16 withdrew from follow-up, 10 underwent transurethral prostate resection and 6, other treatment. The maximal flow increased by 1.2 ml/s (SD: 4.0). The residual volume decreased by 15.8 ml (SD: 55.6). Symptom scores improved by 5.9 points (SD: 5.0). A 50% increase in symptom score was seen in 49.5% of all patients; 24.3% showed no improvement of complaints. There was no change in prostatic volume, whereas PSA concentration showed a transient increase in the first week after TUMT. Preliminary results after 6 months' follow-up of a randomised placebo-controlled study in 50 patients showed subjective and objective improvement of miction., Conclusion: TUMT results in distinct subjective improvement. Urodynamic findings show a less pronounced improvement.

We have previously isolated and characterized 6 different internal image mouse monoclonal anti-idiotype antibodies (Ab2) directed against the paratope of mouse monoclonal antibody G250 (MAbG250, Ab1), which specifically reacts with human renal cell carcinoma (RCC). These Ab2s (NUH31, 44, 51, 71, 82 and 91) demonstrated specificity for the combining site of Ab1, and appeared to recognize 2 partly overlapping idiotopes on Ab1. In this study, we further characterize the fine specificity of the Ab2, investigate whether the immunogenicity of Ab2 could be enhanced by conjugation to a carrier and investigate the anti-tumor efficacy of Ab3 sera in mice challenged with RCC. Immunization of animals with Ab2 conjugated to keyhole limpet hemocyanin as carrier protein resulted in a 2-fold increase in antigen-specific anti-anti-idiotype antibodies (Ab3) as compared with immunization using Ab2 alone. Specific reactivity was observed with antigen-positive cell lysates, and all Ab3 sera contained immunoglobulin resembling Ab1 (Ab1'), as shown by competitive Ab1-antigen binding assays. Fine-specificity studies of Ab3 sera revealed that the Ab2s can be divided into 4 mutually exclusive groups, showing that the 6 Ab2s recognize 4 slightly different idiotopes in the Ab1 binding pocket. Treatment of RCC-challenged mice with Ab3 sera resulted in significant tumor growth inhibition and lower tumor take rates as compared with control groups. Ab3 sera obtained from NUH-91-immunized animals showed superior characteristics as compared to the other Ab3 sera: no tumors remained after 5 weeks of Ab3-NUH91 treatment. Our findings indicate that the Ab2 elicit powerful anti-tumor effects in immune-competent animals.