Percutaneous Stone Manipulation.

Percutaneous stone manipulation by direct ultrasound disintegration, extraction or chemolysis was done on 34 patients. A total of 15 patients presented with an operatively established nephrostomy, while percutaneous nephrostomy and subsequent dilation of the nephrostomy channel were done in 19. The rate of complete stone clearance was 19 of 20 stones after percutaneous nephrostomy and 8 of 16 stones in the group with an operatively established nephrostomy. The primary goal, to remove obstructing pelvic stones, was achieved in all cases. There were no untoward side effects, such as back pressure damage owing to flushing of the collecting system during ultrasound disintegration, or persistent infection. Complications in 3 patients were managed conservatively.

A multicenter, double-blind, randomized, parallel group study comparing polyvinyl chloride and polyvinyl chloride-free catheter materials.

PURPOSE: In this study we compared a polyvinyl chloride catheter with a new polyvinyl chloride-free catheter with the same hydrophilic coating, and determined whether patient perception of ease and comfort of clean intermittent catheterization was independent of the catheter material. MATERIALS AND METHODS: This investigation was designed as a randomized, double-blind, parallel group, multicenter study. Eligible patients were experienced users of clean intermittent catheterization with a polyvinyl chloride catheter for a minimum of 1 month before randomization. They were randomized to continue to use the polyvinyl chloride catheter or switch to a polyvinyl chloride-free catheter for 4 weeks. Both catheters had a similar appearance. Patient perception of ease and comfort of clean intermittent catheterization was scored with questionnaires, and adverse events were documented. RESULTS: A total of 195 patients were recruited from 6 countries and 13 centers for the intent to treat analysis, and 179 were used for the per protocol analysis. Before randomization 94% to 98% of the patients rated the polyvinyl chloride catheter as easy or manageable to handle during different phases of clean intermittent catheterization and overall 92% of patients were satisfied. Of the eligible patients satisfaction was reported by 89% randomized to continue using the polyvinyl chloride catheter and by 78% randomized to switch to the polyvinyl chloride-free catheter (not significant). The rate of adverse events was low and comparable between the 2 groups. CONCLUSIONS: The study confirms that clean intermittent catheterization is easy and safe. Conversion from a polyvinyl chloride to a polyvinyl chloride-free core catheter material does not alter patient perception of catheterization.

Detecting prostate cancer by intracellular macrophage prostate-specific antigen (PSA): a more specific and sensitive marker than conventional serum total PSA.

BACKGROUND: Serum prostate-specific antigen (PSA) is a standard method and a widely used marker for prostate cancer, but it has a poor specificity for early detection. Herein we demonstrate that intracellular macrophage PSA (imPSA) enables screening and differentiation between benign and malignant prostate disease. MATERIALS AND METHODS: The efficacy of intracellular macrophage PSA in circulating and tissue macrophages was therefore investigated in a double-centre study of 38 prostate cancer patients and 36 healthy controls by fluorescent-activated cell sorting analysis and immunohistology. RESULTS: Both methods uncovered the existence of PSA-positive macrophages specific for patients with prostate cancer. In addition, we demonstrate the superiority of our new test over standard serum total PSA in a blinded double-centre trial. ImPSA had a marked higher sensitivity and specificity than serum total PSA (imPSA: sensitivity 92%, specificity 92%, positive predictive value 92%; serum total PSA: sensitivity 79.5%, specificity 87.5%, positive predictive value 26.8%). CONCLUSION: In this study, we demonstrate that imPSA is a new prostate cancer screening method that is highly sensitive and more specific than standard PSA testing.

Effect of high-intensity focused ultrasound on human prostate cancer in vivo.

Transrectal high-intensity focused ultrasound (HIFU) was recently established as a highly effective means of inducing contact and irradiation-free intraprostatic coagulative necrosis. This technique, therefore, appears potentially useful for treating localized prostate cancer (PC). To evaluate this issue, a total of 29 human prostates with localized cancer was subjected to HIFU treatment in vivo before radical retropubic prostatectomy. HIFU therapy was performed with the use of HIFU transducers with focal lengths of 3.0 cm (n = 3), 3.5 cm (n = 19), and 4.0 cm (n = 7), and the site intensity was varied from 1260 to 2000 W/cm2. The extent of intraprostatic necrosis was determined by planimetrical analysis of whole mount prostatic sections. Transrectal HIFU consistently induced sharply delineated intraprostatic coagulative necrosis within the target area, whereas alterations of perioprostatic structures were never observed. The cross-sectional area of necrosis increased from 1.1 +/- 0.7 cm2 (SD; n = 3; 3.0-cm focal length; 1428 W/cm2) to 1.2 +/- 0.7 cm2 (n = 2; 3.5-cm focal length; 1428 W/cm2), 1.8 +/- 0.17 cm2 (n = 8; 3.5-cm focal length; 1680 W/cm2), 2.8 +/- 0.32 cm2 (n = 9; 3.5-cm focal length; 2000 W/cm2) and 3.8 +/- 0.4 cm2 (n = 7; 4.0 cm focal length; 1260 W/cm2). HIFU beam transmission and the therapeutic effect were comparable in benign and malignant prostatic tissue. Interstitial thermometry (n = 6) revealed maximum intraprostatic temperatures in the focal zone up to 98.6 degrees C. Outside the focal zone and on the rectal wall, no significant temperature rises were noted. Subsequently, HIFU was applied to unilateral histologically proven T2a/T2b PC (n = 10) in an attempt to destroy all cancer before radical retropubic prostatectomy. PC was always correctly targeted. In 7 individuals, PC was partially (mean, 53%; range, 38-77%) destroyed; in the remaining 3 cases the entire tumor was ablated. Although these histological data permit no definitive conclusion on the clinical efficacy of this approach, transrectal HIFU seems to be an attractive novel minimally invasive treatment option for localized PC.

Twelve-year experience with two courses of adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

PURPOSE: During the past 30 years, radiation therapy with 28 to 30 Gy for para-aortic and ipsilateral iliac node areas was the standard adjuvant treatment for clinical stage I seminoma after orchiectomy. However, late effects of radiotherapy prompted a search for alternative adjuvant treatment approaches, including surveillance and application of carboplatin. In this retrospective analysis, we evaluated the efficacy and toxicity of two adjuvant single-agent carboplatin courses in 107 patients who were diagnosed with clinical stage I seminoma at our study centers between 1988 and 1999. PATIENTS AND METHODS: All 107 patients (median age, 39 years; range, 24 to 63 years) received two postoperative adjuvant cycles of carboplatin (400 mg/m(2)). The pathologic tumor stage was pT1 in 84 patients, pT2 in 18 patients, and pT3 in five patients. Whole blood count and serum chemistry were evaluated weekly during treatment to assess hematologic and nonhematologic toxicity. RESULTS: Six patients died from tumor-unrelated causes. The remaining 101 patients are currently alive and free of disease after a median follow-up of 74 months (range, 5 to 145 months). A detailed analysis of hematologic toxicity showed only World Health Organization (WHO) grade 1 leukocytopenia in 10.7% of all cycles and WHO grade 2 leukocytopenia in 2.1% of all cycles. CONCLUSION: Regarding the absence of tumor recurrences in our retrospective analysis and the favorable toxicity profile with no episodes of long-term toxicity, we suggest that two adjuvant courses of single-agent carboplatin for clinical stage I seminoma patients might be equivalent to radiotherapy.

mdm2 expression as a prognostic indicator in clear cell renal cell carcinoma: comparison with p53 overexpression and clinicopathological parameters.

The present study was designed to analyze the expression of p53 and mdm2 in clear cell renal cell carcinoma with special emphasis on their association with tumor grade and clinical outcome. In particular, the value of individual protein overexpression as well as combined p53/mdm2 positivity was evaluated because both proteins are functionally connected, and their expression is controlled by an autoregulatory feedback loop. A cohort of 97 clear cell renal cell carcinomas was analyzed. The overexpression of mdm2 and p53 proteins was investigated on paraffin-embedded material by using monoclonal antibodies. Eighteen tumors showed mdm2 positivity, whereas 35 of the tumors overexpressed p53. Whereas p53 and mdm2 positivity correlated significantly (P = 0.00004), no correlation could be found between mdm2 protein overexpression and tumor stage, lymph node involvement, and presence of distant metastases. mdm2 positivity was found significantly more frequently in tumors of higher grade. In univariate analysis, there was a statistically significant correlation between p53 and mdm2 overexpression in the same tumor and poor survival (P = 0.00179). Multivariate analysis revealed that coincident mdm2/p53 overexpression, the presence of distant metastases, and tumor grade were independent predictors for tumor progression. Our results indicate that mdm2/p53 co-overexpression, nuclear grade, and preoperative presence of distant metastasis are independent predictors for poor survival.

Local intratumoral tumor necrosis factor-alpha and systemic IFN-alpha 2b in patients with locally advanced prostate cancer.

To examine tolerability and activity of local, intratumoral tumor necrosis factor-alpha (TNF-alpha) and systemic interferon-alpha2b (IFN-alpha2b) in locally advanced, hormone-resistant prostate cancer (LA-HRPC), 10 patients with LA-HRPC (T4N x M0, n = 3, T4N x M1, n = 5; T4N1M1, n = 2) were treated with recombinant TNF-alpha injected locally into prostate tumor tissue at 4-week intervals (maximum of four cycles) combined with intermittent subcutaneous (s.c.) administration of 5 x 10(6) IU IFN-alpha2b. Twenty-nine TNF-alpha cycles were administered. Despite significant TNF-alpha leakage into the systemic circulation 2 h after intraprostatic application (from a mean of 9 to a mean of 416 pg/ml; p = 0.0034), TNF-alpha (and IFN-alpha2b) was well tolerated (WHO grade 1-2 toxicity), possibly because of its rapid neutralization by increasing soluble 55-kDa and 75-kDa TNF receptor levels in the serum (mean increase 268% and 91%, respectively) at the same time. TNF-alpha induced prostate tumor cell necrosis in all patients, leading to a significant reduction of prostate volume in 9 of 10 cases (mean 38%; p = 0.0025). The significant short-term increase of prostate-specific antigen (PSA) (mean 65%; p < 0.001), tissue polypeptide-specific antigen (TPS) (mean 85%; p = 0.001), and possibly interleukin-8 (IL-8) (mean 2687%; p < 0.009) serum levels within 4 h after TNF-alpha confirmed the cytotoxic effect in vivo. In the long term, serum PSA levels dropped by 18%-87%, reaching the nadir value 7 weeks after baseline. Objective responses of metastases were not seen. Intraprostatic administration of TNF-alpha is feasible at a tolerable toxicity in patients with LA-HRPC and, thus, may be a new treatment option for these patients.

Automated data acquisition by confocal laser scanning microscopy and image analysis of triple stained immunofluorescent leukocytes in tissue.

The aim of the study was to develop a novel system permitting automated analysis of multicolor immunofluorescence-staining of cells in solid tissues which would be comparable to the analytical capacity of flow cytometry. In the user friendly automated data acquisition and image processing system which was established, the software includes a set of pre-defined processing steps for improved object identification and can be either interactive or fully automatic. As with multi color flow cytometry, stained cells can be analyzed in a fully automated manner regardless of tissue type. The software organizes computerized sample movement, autofocus, laser readjustment, data capture and storage as well as calculation. Data are presented as histograms indicating the staining intensity and frequency of each antigen, and in dotplots with each channel plotted against the other. The calculated statistics give information about how many of the cells are single-, double- or triple-reactive and how intensely they react with the respective antibodies. Comparison of data generated by this automated fluorescence confocal laser scanning microscopy (AF-CLSM) with flow cytometry using triple stained peripheral blood lymphocytes revealed a highly significant correlation between the methods (P<0.001). A correlation was also observed when sections triple stained for anti-CD45, -CD3 and -CD8 were analyzed by AF-CLSM and the data were compared to visual/manual cell counting (P<0.01). The AF-CLSM system permits for the first time, fast (online) and reproducible analysis of immunofluorescence staining of an unlimited number of cells in tissue sections. The software, including a manual, is available for a small fee to cover the costs of printing and postage.

Proliferating cell nuclear antigen and MIB-1. An alternative to classic prognostic indicators in renal cell carcinomas?

Tumor progression and clinical outcome for patients with renal cell carcinomas (RCCs) cannot be predicted based solely on tumor staging and grading. In a retrospective study we have therefore attempted to analyze the capacity of proliferation markers to provide additional prognostic information. One hundred seven cases of RCC were investigated by immunohistochemical analysis using two different monoclonal antibodies: PC10, which recognizes a proliferating cell nuclear antigen (PCNA), and MIB-1, which identifies the Ki-67 antigen in formalin-fixed, paraffin-embedded material. PCNA frequency ranged from 0% to 71% (mean, 17%), and MIB-1 expression, from 0% to 43% (mean, 11%). PCNA scores correlated significantly with MIB-1 immunoreactivity. PCNA and MIB-1 immunoreactivity showed a significant correlation with tumor grade. A strong correlation was also observed for T-component of stage and MIB-1 scores, but no correlation was found between PCNA and T-component of stage. In univariate analysis, PCNA immunoreactivity and MIB-1 scores were significant predictors of survival. Multivariate analysis, using a Cox proportional hazard model, showed PCNA index, N-component of stage, and tumor grade to be independent predictors of tumor progression, which is not the case for MIB-1 index.

Long-term effects of finasteride in patients with benign prostatic hyperplasia: a double-blind, placebo-controlled, multicenter study. PROWESS Study Group.

OBJECTIVES: To compare the long-term effects of finasteride (5 mg/day) and placebo in patients with moderate symptoms of benign prostatic hyperplasia (BPH). METHODS: Patients aged 50 to 75 years, with at least two urinary symptoms indicating moderate BPH, and an enlarged prostate, were followed in a 2-year double-blind, randomized, placebo-controlled multicenter study. The effects of finasteride versus placebo were assessed by total symptom score (modified Boyarsky), obstructive symptom score, maximal urinary flow rate, prostate volume, and urologic end points (acute urinary retention, BPH-related surgical intervention). RESULTS: Of the 3270 men enrolled, 3168 contributed data to the safety analysis, and 2902 to the efficacy evaluation. Significantly greater improvement with finasteride compared to placebo was observed at 12 and 24 months for total symptom score (mean -2.9 versus -1.9 at 12 months, P < or =0.001; -3.2 versus -1.5 at 24 months, P < or =0.001), obstructive symptom score (mean -1.9 versus -1.3 at 12 months, P < or =0.001; -2.1 versus -1.1 at 24 months, P < or =0.001), maximal urinary flow rate (mean +1.2 versus +0.6 mL/s at 12 months, P = 0.010; +1.5 versus +0.7 mL/s at 24 months, P = 0.002), and prostate volume (mean -14.2 versus +5.4% at 12 months, P < or =0.01; -15.3 versus +8.9% at 24 months, P < or =0.001). Greater improvements in placebo-adjusted total symptom score occurred in men with large prostates than in men with small prostates (mean -2.4 versus -1.1 at 12 months; -3.2 versus -1.3 at 24 months, placebo-adjusted data, P = 0.053). Fifteen of 1450 men (1.0%) in the finasteride group experienced an acute urinary retention event, compared with 37 of 1452 (2.5%) in the placebo group, and the corresponding figures for surgery were 51 of 1450 (3.5%) and 86 of 1452 (5.9%), respectively. The hazard rate for occurrence, computed using the log-rank statistic, decreased by 57% for acute urinary retention and by 40% for surgery accompanied by finasteride therapy compared to placebo. CONCLUSIONS: Finasteride causes long-term symptomatic improvement and reduces the risk of acute urinary retention or surgery. Men with enlarged prostates benefit most from finasteride treatment.

Accessory phallic urethra in female pseudohermaphrodite.

The eighth case of a female pseudohermaphrodite with hypertrophy of the clitoris, a perineal and complete accessory phallic urethra, but without adrenal hyperplasia, is reported. The etiology of this syndrome and the rationale of its treatment are discussed and the literature reviewed.

Transurethral microwave thermotherapy: what role should it play versus medical management in the treatment of benign prostatic hyperplasia?

Both transurethral microwave thermotherapy (TUMT) and medical management by alpha-blockade or 5-alpha-reductase inhibition are increasingly being considered as alternatives to surgery for treatment of patients with benign prostatic hyperplasia (BPH). We review current evidence supporting the effectiveness and safety of TUMT and medical management. Factors for consideration in appropriately selecting patients for TUMT versus medical management are suggested. Available data indicate that TUMT confers greater long-term benefits than medical management as judged by symptom score and peak urinary flow rate improvements. TUMT-associated morbidity is comparatively low. Alpha-blockade affords more rapid relief than TUMT for patients with BPH; however, other strategies such as the use of temporary intraurethral endoprostheses during the acute post-TUMT recovery period may diminish or abolish the differences in time-course of symptom and flow rate improvement between TUMT and alpha-blockade. 5-Alpha-reductase inhibition with finasteride offers a favorable side-effect profile, although the magnitude of symptom and flow rate improvements is modest, and maximal effects of finasteride do not become manifest until after several months of treatment. As TUMT continues to evolve, increasing attention is being accorded the delivery of high thermal doses and precise targeting of the thermal energy delivered. The development of alpha-blockers with a more favorable side-effect profile continues to be a major focus of investigation. The potential clinical utility of combination therapy with TUMT and alpha-blockade is currently under investigation.

Spontaneous nontraumatic rupture of a contracted kidney with subcapsular and perirenal hematoma in a patient receiving chronic hemodialysis.

Spontaneous renal bleeding with diversion of blood into the subcapsular and/or perinephric spaces in a patient on chronic hemodialysis is a very rare clinical entity. We describe a patient on chronic hemodialysis in whom a spontaneous renal subcapsular hematoma and perirenal hemorrhage developed in a contracted kidney.

Serum dehydroepiandrosterone sulfate concentrations in men with erectile dysfunction.

OBJECTIVES: In 1994, the Massachusetts Male Aging Study presented the finding of an inverse correlation of the serum levels of dehydroepiandrosterone sulfate (DHEAS) and the incidence of erectile dysfunction (ED). Prompted by the positive results of a pilot study on the treatment of ED with dehydroepiandrosterone (DHEA), we performed a detailed investigation on the serum DHEAS levels in men with ED according to age category. METHODS: Inclusion criteria included a history of ED for more than 6 months, a body mass index less than 30, and a state of good general health. Serum DHEAS concentrations were determined in 309 patients with ED and 133 healthy volunteers. All participants were carefully screened to assess medical factors known or suspected to alter endocrine function. Questions 3 and 4 of the International Index of Erectile Function were used to evaluate erectile function. RESULTS: The mean serum levels of DHEAS in patients with ED were lower than in healthy volunteers until 60 years of age. The shape of the curve of the patients with ED indicated a quadratic decrease of DHEAS with age in contrast to a more linear decrease of DHEAS with age in the control group. CONCLUSIONS: Our results suggest that until the age of 60 years, the mean serum level of DHEAS is lower in patients with ED than in healthy volunteers.

Sperm analysis and serum follicle-stimulating hormone levels before and after adjuvant single-agent carboplatin therapy for clinical stage I seminoma.

OBJECTIVES: During the past 25 years, radiotherapy has been considered the standard adjuvant treatment for clinical Stage I seminoma after orchiectomy. However, the late effects of this treatment have prompted a re-examination of the alternatives, including surveillance and adjuvant administration of carboplatin. To our knowledge, the present clinical study is the first to report the effects of two adjuvant courses of single-agent carboplatin on the pituitary-testicular axis and on sperm analysis. METHODS: Twenty-two patients with clinical Stage I seminoma participated in a prospective investigation of gonadal function before and after carboplatin therapy. After orchiectomy but before chemotherapy, blood samples for determination of follicle-stimulating hormone (FSH) serum levels were obtained from all 22 patients. Seventeen patients provided a semen sample at the same time, but 5 were unable to do so. At the end of chemotherapy, all 22 patients provided repeated semen samples starting 1 year after the termination of treatment and continuing at intervals of 12 months. FSH serum levels were determined at the same time. The study period was 48 months. RESULTS: Before chemotherapy, 2 patients (12%) had azoospermia, 9 (53%) had oligospermia, and 6 (35%) had normospermia. During the study period, sperm counts continued to increase in all patients. After 4 years, 7 patients (32%) had oligospermia and 15 (68%) normospermia. The mean prechemotherapy FSH level (15.5 IU/L) was increased in accordance with subnormal spermatogenesis, but a constant trend toward normalization was observed thereafter. CONCLUSIONS: Our results show recovery of spermatogenesis after adjuvant single-agent carboplatin for clinical Stage I seminoma in a remarkably high percentage of patients.

The aging lower urinary tract: a comparative urodynamic study of men and women.

OBJECTIVES: The fact that aging women report similar voiding symptoms as age-matched men prompted us to compare age-related changes of urodynamic parameters in both sexes. METHODS: Four hundred thirty-six patients (253 men and 183 women) 40 years of age or older underwent the following investigations: free uroflowmetry, measurement of postvoid residual volume, and full urodynamic testing, including a pressure-flow study (pQs). Additional investigations were a urethral pressure profile in women and quantification of prostate volume by transrectal ultrasonography in men. All men were referred for lower urinary tract symptoms suspicious of bladder outflow obstruction and women predominantly for urinary incontinence. Patients with previous surgery of the lower urinary tract (prostate, bladder, urethra) and those taking medication with a major effect on voiding function (alpha-receptor blockers, 5 alpha-reductase inhibitors, anticholinergic agents) were excluded. RESULTS: The mean +/- standard deviation (SD) age in the female (f) population (n = 183) was 59 +/- 16 years (range 40 to 93), in the male population (m) (n = 253) 67 +/- 9 years (range 40 to 90). In both sexes, we observed a statistically significant increase of postvoid residual volume (f: P = 0.0001; m: P = 0.02) and a decrease of peak flow rate (f: P = 0.019; m: P = 0.014), average flow rate (f: P = 0.007; m: P = 0.04), voided volume (f: P = 0.007; m: P = 0.002), and bladder capacity determined by urodynamics (f: P = 0.003; m: P = 0.0004) with progressing age. In both sexes, there were no age-related changes (P >0.05), demonstrable for maximum detrusor pressure and detrusor pressure at peak flow rate. In women, there was a significant decrease of functional urethral length (P = 0.012) and maximum urethral closing pressure (P = 0.0001) with higher age; in men, the prostate volume increased significantly with age (P = 0.0001). With respect to detrusor instability, we observed an increase in men from 23.4% (40 to 60 years) to 46.7% (more than 80 years) (P = 0.004), whereas in women no significant age-related changes were present (P >0.05). CONCLUSIONS: These data show that age-associated urodynamic changes in both sexes are comparable for a number of parameters. They provide an explanation for the fact that aging women report comparable voiding symptoms as men and suggest a primary, non-sex-specific aging process of the urinary bladder.

Multifocality of transitional cell carcinoma results from genetic instability of entire transitional epithelium.

OBJECTIVES: Multifocality of transitional cell carcinoma (TCC) has been attributed to seeding of exfoliated tumor cells or to a general sensitivity of the entire urothelium to carcinogenic stimuli. By contrast, TCC has been shown to evolve as a consequence of genetic defects and chromosomal instability. We analyzed chromosomal patterns, total DNA content, and p53 and Ki67 expression in malignant and normal transitional cells to evaluate their relationship to the development of multifocal TCC. METHODS: Included in the study were 47 patients, 16 women and 31 men, with a mean age of 70.04 years (range 37 to 83). Of 47 patients, 45 had TCC of the urinary bladder and 7 of those had synchronous ureteral involvement. Two patients had ureteral TCC and a history of TCC of the bladder. Using fluorescence in situ hybridization, numerical aberrations of chromosomes 7, 9, and 17 were detected in imprint specimens of histologically verified tumor and "normal" urothelium and were compared with static ploidy and p53 and Ki67 expression. RESULTS: Chromosome 7 was altered in 93.6%, chromosome 9 in 63.8% (including monosomy), and chromosome 17 in 87.2% of the 47 analyzed tumor and normal imprints. Differences between tumor and normal epithelium were observed in aberrational frequencies (number of cells showing chromosomal aberrations calculated on 200 cells counted, given in percentages). DNA content was aneuploid in all tumor specimens, but diploid in 20 (42.5%) of 47 normal specimens, according to lower aberration frequencies in these patients. p53 detection was positive in 82.9% of the tumor specimens and 76.6% of the normal specimens. Ki67 was positive in 87.2% of the tumor imprints and in 72.3% of the normal specimens. CONCLUSIONS: These data suggest a general genetic instability as a reason for multifocality in the entire transitional epithelium.

Transperineal radiofrequency interstitial tumor ablation of the prostate: correlation of magnetic resonance imaging with histopathologic examination.

OBJECTIVES: Radiofrequency (RF) energy has recently been employed to destroy human tissue in vivo. The purpose of this study was to investigate the safety of this approach in localized carcinoma of the prostate (CaP) and specifically, the predictability of lesions obtained with radiofrequency interstitial tumor ablation (RITA). METHODS: Using RITA, a total of 21 lesions were induced in 10 patients with localized CaP (mean age 70.4 years). RF was delivered transperineally under transrectal ultrasound (TRUS) guidance. All patients underwent endorectal magnetic resonance imaging (MRI) before and after treatment. Radical prostatectomy was performed in all patients 1 to 7 days after RITA. Three of the patients were treated with local anesthesia only. The predictability of the thermal lesion was assessed by correlating the findings of intraoperative TRUS, pre- and post-RITA endorectal MRI, and the histologic examination of the specimen. RESULTS: Postoperatively, patients were catheterized for an average of 1.8 days (1 to 3 days). Lesions of 2 x 2 x 2 cm were targeted. Average lesion diameters obtained on MRI were 2.08 +/- 0.23 x 2.09 +/- 0.36 x 2.28 +/- 0.21 cm. Average lesion diameters defined by coagulative necrosis at histologic examination were 2.20 +/- 0.23 x 2.10 +/- 0.31 x 2.38 +/- 0.14 cm. There were no statistically significant differences (P = 0.377) between average lesion volume on MRI (5.37 +/- 1.83 cm3) and average lesion volume at histology (5.86 +/- 1.63 cm3). No complications or adverse events were noted. CONCLUSIONS: In this Phase I study, RITA was shown to be safe and feasible, and to result in lesions that were predictable in size and location. MRI accurately visualized and verified the area of coagulative necrosis as documented at histology. The procedure is technically simple and can even be performed under local anesthesia.

Numerical chromosomal aberrations in muscle invasive squamous cell and transitional cell cancer of the urinary bladder: an alternative to classic prognostic indicators?

OBJECTIVES: To evaluate the prognostic value of chromosomal aberrations in muscle invasive bladder cancer, because they are of diagnostic and prognostic significance in superficial bladder cancer. METHODS: One hundred ninety patients, who underwent radical cystectomy because of squamous cell carcinoma (SCC) of the urinary bladder in 94 cases and transitional cell carcinoma (TCC) in 96 cases, were studied retrospectively. Numerical aberrations of chromosomes 7, 9, and 17, p53 positivity, histologic stage and grade, histologic tumor type, lymph node status, and the presence of bilharzial eggs were investigated as possible prognostic factors. RESULTS: Univariate analysis demonstrated the prognostic significance of all parameters analyzed, excluding chromosome 9. Multivariate analysis revealed only T category (P = 0.01095266), lymph node involvement (P = 0.00054877), and p53 positivity (P = 0.0316974) to be independent prognostic factors in muscle invasive SCC and TCC. CONCLUSIONS: Although chromosomal aberrations are associated with progression-free survival, they are not independent prognostic factors and give the clinician no additional information on patients with muscle invasive bladder cancer.

Paclitaxel and carboplatin in patients with metastatic transitional cell cancer of the urinary tract.

OBJECTIVES: The combination of methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) is currently considered the most effective chemotherapy for metastatic transitional cell cancer (TCC) of the urinary tract, but because of its considerable toxicity, alternative regimens appear very interesting. We evaluated the efficacy and toxicity of a combination of paclitaxel and carboplatin as first-line therapy for metastatic TCC. METHODS: Thirty-two patients (8 women, 24 men; mean age 67.03 years, range 50 to 79) with metastatic TCC of the bladder or upper urinary tract were included in the study. Paclitaxel (175 mg/m2) was given as a 3-hour intravenous infusion, carboplatin was dosed to an area under the plasma concentration curve of 5 mg/m/min calculated according to the Calvert formula [(creatinine clearance + 25) x 5] as a 30-minute intravenous infusion immediately after paclitaxel. Response evaluation was performed after every 2 cycles and additional therapy depended on response. The maximum number of cycles was 6. RESULTS: With a mean follow-up of 13.1 months (range 2 to 28), 23 of 32 patients responded to treatment (response rate 71.9%), with 31.3% complete remission (CR) (10 of 32) and 40.6% partial remission (PR) (13 of 32). Four patients (12.5%) had stable disease, and 5 patients (15.6%) showed progression. These results compare well with the outcome after MVAC. Toxicity was mainly characterized by neurotoxicity grade 3 and 4 in 9.4%, grade 3 and 4 leukopenia in 37.5%, and grade 3 thrombocytopenia in 3.1% of the patients. No nephrotoxicity was observed, but all patients developed alopecia. Time to progression after CR was a mean of 7.0 months (range 4 to 13) and after PR a mean of 5.9 months (range 2 to 9). CONCLUSIONS: Paclitaxel/carboplatin is an effective therapy for metastatic TCC, with low toxicity.