Search PubMed⌕ Search

Biomedical subjects

M Marberger

Publications and source records attributed to M Marberger.

At least 73 records · Page 4Linked to original sources

Is one set of sextant biopsies enough to rule out prostate Cancer? Influence of transition and total prostate volumes on prostate cancer yield.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Aged↗

Optimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1,051 men.

PURPOSE: We compare the ability of total prostate specific antigen (PSA), percent free PSA, PSA density and transition zone PSA density to predict the outcome of repeat prostatic biopsy in men with serum total PSA 4 to 10 ng./ml. who were diagnosed with benign prostatic hyperplasia after initial biopsy. MATERIALS AND METHODS: In this prospective study 1,051 men with total PSA 4 to 10 ng./ml. underwent transrectal ultrasound guided sextant biopsy with 2 additional transition zone biopsies. In 254 subjects biopsy specimens were also obtained from suspicious areas identified during transrectal ultrasound and digital rectal examination. All subjects with biopsy specimens negative for prostate cancer underwent repeat biopsy 6 weeks after initial biopsy. The ability of total PSA, percent free PSA, PSA density and transition zone PSA density to improve the diagnostic power of PSA testing was assessed with univariate and multivariate analyses as well as receiver operating characteristics (ROC) curves. RESULTS: Initial biopsy was positive (prostate cancer) in 231 and negative (benign prostatic hyperplasia) in 820 of the 1,051 subjects. Prostate cancer was detected on repeat biopsy in 10% of subjects (83 of 820) with negative initial biopsy. Percent free PSA and transition zone PSA density were the most accurate predictors of prostate cancer in these subjects. At a cutoff of 30% percent free PSA would have detected 90% of cancers (sensitivity) and eliminated 50% of unnecessary repeat biopsies (specificity). Sensitivity and specificity of transition zone PSA density at a cutoff of 0.26 ng./ml./cc was 78% and 52%, respectively. ROC curve analysis also showed that percent free PSA was a significantly better predictor of repeat biopsy results than total PSA, PSA density and transition zone PSA density. The area under the ROC curve was 74.5% for percent free PSA, 69.1% for transition zone PSA density, 61.8% for PSA density and 60.3% for total PSA. CONCLUSIONS: At least 10% of patients with negative initial prostatic biopsy results will be diagnosed with prostate cancer on repeat biopsy. Percent free PSA and transition zone PSA density enhance the specificity of PSA testing compared to total PSA or PSA density when determining which patients should undergo repeat biopsy. Repeat biopsy should be performed in patients with percent free PSA less than 30% or transition zone PSA density 0.26 ng./ml./cc or greater. In our study percent free PSA was the most accurate predictor of prostate cancer in repeat biopsy specimens.

Aged↗

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.

Adult↗

Expression of the VEGF-receptor Flt-1 in benign, premalignant and malignant prostate tissues.

PURPOSE: Vascular endothelial growth factor (VEGF) is one of the most potent regulators of angiogenesis and has been shown to act upon two tyrosine kinase family receptors: c-fms-like tyrosine kinase (Flt-1) and fetal liver kinase. Preliminary reports have emphasized that expression of VEGF receptors is endothelial cell-specific. In this study we verified the localization and distribution of Flt-1 protein and mRNA expression in prostatic adenocarcinoma (CaP) as well as prostate intraepithelial neoplasia (PIN) and benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: 30 selected surgical specimens exhibiting areas with CaP, PIN and BPH histology were evaluated for Flt-1 protein expression by immunohistochemistry. Results were compared with tumor differentiation (Gleason-Score), serum-PSA and clinical followup. Flt-1 synthesis by prostatic carcinoma cell lines, freshly isolated BPH epithelial cells (BPH-EC) and stromal cells was investigated using RT-PCR and intron spanning primer. RESULTS: VEGF receptor Flt-1 specific anti-sera revealed significant staining of prostatic endothelial cells, but the reactivity was not restricted to endothelial cells. BPH-epithelial cells of all specimens reacted significantly with anti-Flt-1. In contrast, tumor cells failed to react with anti-Flt-1 in 56% of the specimens. BPH-EC revealed a uniform anti-Flt-1 reactivity, which was less pronounced and weaker in PIN. Loss of anti-Flt-1 reactivity of prostatic tumor cells did not correlate with preoperative PSA serum levels but increased with tumor dedifferentiation. Interestingly, tumor cells of all CaP specimens with a Gleason score of >8 exhibit no anti-Flt-1 immunoreactivity. Accordingly while PC3, DU145 and LNCaP cells were negative when tested using RT-PCR all BPH tissue derived BPH-EC revealed Flt-1 coding mRNA expression. CONCLUSIONS: Widespread distribution of VEGF receptor Flt-1 in BPH, PIN and prostate cancer specimens suggests that VEGF function in prostate is not restricted to endothelial cells and angiogenesis. However, since the receptor is lost in CaP cells and with tumor dedifferentiation, these yet unknown effects of VEGF on epithelial cells are obviously suppressed with malignant transformation.

Adenocarcinoma↗

Outcome predictors of high-energy transurethral microwave thermotherapy.

PURPOSE: Despite the good results of high-energy transurethral microwave thermotherapy (TUMT) for treatment of benign prostatic hyperplasia (BPH), it still is difficult to predict the response to treatment on an individual basis. In addition to clinical baseline parameters, histologic parameters seem to play a role in response variance after TUMT. High-energy TUMT has become widely accepted as a minimally invasive outpatient treatment in patients with lower urinary tract symptoms and BPH. Most patients benefit substantially from targeted microwave thermotherapy; however, little is known about optimal patient selection and the most relevant outcome parameters. MATERIALS AND METHODS: We evaluated Medline-based studies published between 1989 and 2000, including 900 patients suffering from lower urinary tract symptoms due to BPH who were undergoing TUMT. We evaluated outcome predictors for TUMT, such as histopathological parameters, prostate-specific antigen, and volume. RESULTS: Histologic and clinical outcome parameters were identified. Patient-to-patient differences in stromal-to-epithelial ratio of prostate tissue did affect outcomes. Poor responders to TUMT seemed to have a higher vessel density and a lower epithelial/stromal ratio. Relatively more abundant epithelial cells in the prostate tissue may lead to more favorable outcomes. Use of higher energy, patients with higher grade of obstruction, younger patient age, larger prostate volume (>25 mL), and higher prostate-specific antigen levels seemed to be associated with a better response to TUMT. CONCLUSIONS: New energy protocols could help tailor treatment to the individual needs of each patient. Nomograms based on volume, age, and pressure-flow parameters could assist in making clinical recommendations and identifying treatment responders; however, the total amount of energy appeared to have a high impact on the prediction of response.

Humans↗

Microwave thermotherapy in patients with chronic urinary retention.

PURPOSE: To evaluate the efficacy of high-energy transurethral microwave thermotherapy (TUMT) in the treatment of chronic urinary retention (CUR) due to benign prostatic hyperplasia (BPH). MATERIALS AND METHODS: In this prospective cohort study, 29 patients with CUR due to BPH underwent high-energy TUMT. Prior to treatment and during a 12-week follow-up, the following parameters were determined: quality of life (QOL) score, peak flow rate (Qmax) by uroflowmetry, and postvoid residual urine (PVR). In those with treatment failure (PVR > 150 mL or urinary retention), pressure-flow studies were performed and compared to pre-TUMT urodynamics. RESULTS: Of the 29 patients, 21 (72%) regained the ability to void spontaneously at 5 weeks. The actuarial median time for spontaneous voiding to be restored was 3.5 weeks (95% confidence interval [CI] 2.9-4.8 weeks). Mean QOL score at 12 weeks post-TUMT (2.2; 95% CI 1.5-2.7) was lower than that at 1 week (4.6; 95% CI 3.9-5.8) by 51% (p < 0.0005). Further, a 55% increase in mean Qmax (p < .0005) determined by uroflowmetry was observed by 12 weeks vs. 1 week after high-energy TUMT. TUMT failed in 8 patients due to a hypocontractile detrusor. CONCLUSIONS: We concluded that high-energy TUMT is a potentially useful option for patient with CUR who are not candidates for prostatectomy.

Aged↗

Minimally invasive procedures and medical management-their relative merits in treating lower urinary tract symptoms of benign prostatic hyperplasia.

Evidence is reviewed supporting the safety and efficacy of minimally invasive transurethral microwave thermotherapy and medical management in patients with benign prostatic hyperplasia. Recent data indicate more pronounced long-term beneficial effects of microwave treatment. alpha-Blockade, however, offers more rapid onset of action than does microwave treatment. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement in patients undergoing microwave treatment. Compared with medical management, microwave treatment also appears to possess greater versatility, allowing patients who fall within a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success.

Journal Article↗

Elastin gene expression in benign prostatic hyperplasia.

BACKGROUND: Benign prostatic hyperplasia (BPH) is mainly a stromal process, showing an increased ratio of stromal to epithelial elements, a collagen type III downregulation, and a collagen types I and IV upregulation. Little is known about elastin gene expression in BPH tissues due to difficulties related to extensive alternative splicing of the elastin gene. Therefore, we analyzed and quantified elastin gene expression in BPH. METHODS: A competitive reverse transcriptase-polymerase chain reaction (competitive RT-PCR) quantitative technique was used, and a quantitative elastin mRNA analysis with normal (n = 10) and BPH (n = 12) tissues was performed with two newly designed elastin primers. Small tissue samples (4-8 mg) were homogenized and sonicated, and cDNA was synthesized from mRNA using a RT reaction. Various target (wild-type) elastin cDNAs with unknown concentrations were competitively coamplified with known serial dilutions of the control mutant template, differing from the target cDNA by a short deletion. Gel fractions and computerized densitometry, were performed and cDNA concentration was calculated by linear regression. RESULTS: The primers identified in our study (BOB-1 and BOB-2) accurately amplified a consistent length of the elastin cDNA, avoiding areas of alternative splicing. The average elastin mRNA concentration in BPH tissues was 53 attomole/mg +/- 11.6 vs. 140.6 attomole/mg +/- 19.6 in normal prostatic tissue (P = 0.019). The variation within every sample was less than 10%. CONCLUSIONS: Our observations suggest a significant downregulation (70%) of the elastin mRNA gene in the transition zone of BPH patients.

Aged↗

Biologic behavior of and p53 overexpression in multifocal renal cell carcinoma of clear cell type: an immunohistochemical study correlating grading, staging, and proliferation markers.

BACKGROUND: In the treatment of small renal cell carcinoma (RCC), there is controversy between radical and nephron-sparing surgical treatment because of the risk of tumor multifocality. The biologic behavior of multifocal RCC compared with that of unifocal RCC is not well investigated, and the relevance of p53 and the proliferation markers MIB-1 and proliferating cell nuclear antigen (PCNA) to multifocal RCC is not yet established. METHODS: In this study, p53 protein overexpression was investigated immunohistochemically in 27 multifocal and 65 unifocal clear cell RCCs using a monoclonal antibody (DO-1). The nuclear expression of p53 was compared with the expression of PCNA and MIB-1 (Ki-67 antigen) and other prognostic factors, including grade and stage. RESULTS: Thirty-three RCCs (35.9%) had p53 positive nuclear staining. MIB-1 positivity was significantly higher in p53 positive tumors than in p53 negative tumors. PCNA positivity was not different in p53 positive tumors compared with p53 negative tumors. Proliferation marker expression was not associated with tumor focality. p53 overexpression was more often found in unifocal tumors than in multifocal tumors. Intracellular accumulation of the p53 protein was related to tumor grade but not to the T classification of tumor stage. In addition, lymph node involvement was significantly associated with p53 overexpression in tumors of the kidney. Focality did not influence progression free survival. CONCLUSIONS: This study demonstrated that there is no difference in the proliferative activity or biologic behavior of multifocal and unifocal tumors.

Adult↗

Interrelationships of bladder compliance with age, detrusor instability, and obstruction in elderly men with lower urinary tract symptoms.

Data on the interrelationships of bladder compliance (BC), detrusor instability (DI), and bladder outflow obstruction (BOO) in elderly men with lower urinary tract symptoms (LUTS) are scarce and were therefore assessed in this study. Principle inclusion criteria for this study were men aged > or = 50 years suffering from LUTS as defined by an International Prostate Symptoms Score (IPSS) of > or = 7 and a peak flow rate (Qmax) of < or = 15 ml/sec. Patients with previous surgery of the bladder, prostate, or urethra as well as a pathological neurourological status were excluded from this study. The following parameters were studied in all patients: IPSS, prostate volume calculated by transrectal ultrasonography, free uroflow study, post-void residual volume determined by transurethral catheterization, and a multichannel pressure flow study (pQS). A group of 170 men were included in the analysis. The mean BC in the overall group was 32 +/- 2 ml/cm H2O (mean +/- standard error of the mean [SEM]; range, 4-100 ml/cm H2O). In 36.5% of patients, BC was significantly reduced (< or = 20 ml/cm H2O), and in a further 37.1%, it ranged from 20 to 40 ml/cm H2O. BC decreased statistically significantly (p < 0.05) in patients with advanced age, lower Qmax, higher voiding pressures, and larger prostates. In men with DI (n = 61), mean BC was significantly lower (22 +/- 3 ml/cm H2O) compared to those without (37 +/- 3 ml/cm H2O; p = 0.001; n = 109). Patients with severe BOO as defined by a linear passive urethral resistance relationship of > or = 3 (n = 109), had a significantly lower BC (23 +/- 2 ml/cm H2O) compared to those without or minimal obstruction only (39 +/- 3 ml/cm H2O; p = 0.0002; n = 61). Stepwise logistic regression analysis revealed that DI, a low bladder capacity, and a high maximum detrusor pressure were independent predictors of markedly reduced BC (< 20 ml/cm H2O). BC is decreased in elderly men with high voiding pressures, BOO, and DI. The mechanism leading to the reduction of BC under these circumstances is largely unknown and could result from cytostructural alterations of the detrusor and changes in detrusor innervation.

Aged↗

The International Prostate Symptom score in both sexes: a urodynamics-based comparison.

The aim of our study was to determine the urodynamic basis for the observation that aging women report comparable benign prostatic hyperplasia (BPH) symptom scores as age-matched men. Sixty-seven women (mean age, 60.4 +/- 1.5 years; mean +/- standard error of the mean) and 70 age-matched men (mean age, 63.7 +/- 0.9 years; P > 0.05) entered this prospective study. Men were referred for the diagnostic workup of lower urinary tract symptoms (LUTS) due to BPH and women predominantly for urinary incontinence. All patients completed the International Prostate Symptom score (IPSS) with quality-of-life assessment and underwent a detailed clinical and urodynamic evaluation including a multichannel pressure-flow study. Results of the IPSS, quality-of-life assessment, and irritative and obstructive component of the IPSS were correlated with urodynamic findings and the respective data were compared in both sexes. The mean IPSS was 15.7 for men and 13.0 for women (P = 0.02), quality-of-life score was higher in women (4.2 vs. 3.4; P = 0.0008). The irritative score was significantly higher in women (8.7 vs. 6.8; P = 0.003). Incidence of detrusor instability (DI), however, was higher in men (women, 38.1%; men, 48.6%; P = 0.015) and bladder capacity was higher in women (425 vs. 333 ml; P = 0.0001). There was no correlation between incidence and degree of DI with the irritative score in both sexes. The obstructive score was significantly higher in men (8.8 vs. 4.4; P = 0.0001). Ninety-one percent (64/70) of men had urodynamically documented bladder outlet obstruction (BOO), whereas this was the case in only 9% (6/67) of women. In parallel to the irritative score, we could not identify a correlation between the degree of urodynamically proven BOO and the obstructive score in both sexes. This urodynamics-based comparison fails to give an explanation for the observation that aging women report similar BPH scores as men. These data suggest that other mechanisms, such as changes in diurnal urine production, structural alterations of the aging detrusor, endocrine disturbances affecting lower urinary tract function, and subtle urodynamic changes are responsible.

Adult↗

Immunocyt: a new tool for detecting transitional cell cancer of the urinary tract.

PURPOSE: The limitations of cytology and the invasiveness of cystoscopy for detecting bladder cancer generate increasing interest in noninvasive, urine bound diagnostic tools. We assessed the diagnostic value of the newly developed immunocytochemical test, Immunocyt, which detects cellular markers specific for transitional cell cancer in the voided urine of patients with bladder cancer. MATERIALS AND METHODS: Participating in our prospective study were 264 consecutive patients with a mean age of 65.9 years, including 114 in whom symptoms were suggestive of bladder cancer and 150 who were being followed after complete transurethral resection of superficial transitional cell carcinoma. Voided urine specimens were evaluated by standard cytology and the Immunocyt test, which traces the monoclonal antibodies M344, LDQ10 and 19A211 against transitional cell carcinoma in exfoliated urothelial cells. In all cases cystoscopy was subsequently performed and any suspicious lesion was evaluated by biopsy. RESULTS: Histologically proved transitional cell carcinoma was found in 79 patients. Immunocyt with cytology had 89.9% sensitivity overall (84, 88 and 96.5% in grades 1 to 3 disease, respectively). A total of 34 (43%), 3 (3.8%) and 34 (43%) cases were positive on Immunocyt only, cytology only and both evaluations, respectively. In 8 cases (10.1%) both tests were negative. Overall Immunocyt only was 86.1% sensitive (84, 84 and 89.6% in grades 1 to 3 disease, respectively) and 79.4% specific. Overall cytology only was 46.8% sensitive (4, 52 and 79.3% in grades 1 to 3 disease, respectively) and 98.2% specific. CONCLUSIONS: Immunocyt is a noninvasive, highly sensitive test for detecting transitional cell carcinoma of all grades and stages. When combined with conventional urinary cytology, it may replace cystoscopy in select patients, especially in followup protocols of low grade transitional cell carcinoma.

Adult↗

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.

Adult↗

Neoadjuvant and adjuvant alpha-blockade improves early results of high-energy transurethral microwave thermotherapy for lower urinary tract symptoms of benign prostatic hyperplasia: a randomized, prospective clinical trial.

OBJECTIVES: Improved long-term results with respect to symptoms, voiding function, and quality of life (QOL) in patients with lower urinary tract symptoms (LUTS) of benign prostatic hyperplasia (BPH) are achieved with targeted high-energy transurethral microwave thermotherapy (TUMT) compared with alpha-blocker treatment alone. However, maximal improvement after TUMT is not attained until 3 to 6 months after treatment. Measures to provide earlier symptom relief and improved voiding function and QOL would add to the clinical utility of TUMT. The objective of the present study was to determine whether neoadjuvant and adjuvant alpha-blockade is capable of accelerating a post-TUMT decrease in LUTS of patients with BPH. METHODS: In this randomized, prospective study of 81 patients with LUTS of BPH, 41 underwent TUMT with neoadjuvant and adjuvant tamsulosin (0.4 mg daily) treatment, and 40 had TUMT alone. International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and QOL score were determined before treatment and at periodic intervals thereafter up to 12 weeks after TUMT. RESULTS: Mean IPSS values in the TUMT plus tamsulosin group at 2 weeks (14.0, 95% confidence interval [CI] 13.1 to 14.9) and 6 weeks (8.6; 95% CI 7.7 to 9.5) were 15% and 24% lower, respectively, than those at 2 weeks (16.5, 95% CI 15.6 to 17.4) and 6 weeks (11.3, 95% CI 10.4 to 12.2) in the TUMT-alone group (P<0.0005). However, by the final evaluation at 12 weeks, no significant difference between the groups in mean IPSS was evident. A similar temporal pattern of difference between the two study groups was also observed in QOL score. No significant between-group difference in mean Qmax was evident after TUMT. Urinary retention 1 week or more in duration occurred in 5 (12%) of 40 TUMT-alone group patients compared with 1 (2%) of 41 TUMT plus tamsulosin group patients. CONCLUSIONS: Neoadjuvant and adjuvant alpha-blocker treatment results in significantly greater early symptom reduction and QOL score improvement after TUMT, adding to the clinical utility of this minimally invasive treatment modality. In addition, post-TUMT complications such as urinary retention may be reduced.

Adrenergic alpha-Antagonists↗

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.

Aged↗

Dehydroepiandrosterone in the treatment of erectile dysfunction: a prospective, double-blind, randomized, placebo-controlled study.

OBJECTIVES: In 1994, the Massachusetts Male Aging Study presented an inverse correlation of the serum levels of dehydroepiandrosterone (DHEA) and the incidence of erectile dysfunction (ED). We evaluated the efficacy of DHEA replacement in the treatment of ED in a prospective, double-blind, randomized, placebo-controlled study. METHODS: The inclusion criteria included ED, normal physical and neurologic examinations, serum levels of testosterone, dihydrotestosterone, prolactin, and prostate-specific antigen (PSA) within the normal range, and a serum DHEA sulfate level below 1.5 micromol/L. Also all patients had a full erection after a pharmacologic erection test with 10O microg prostaglandin E1; pharmacocavernosography showed no visualization in corporeal venous structures. Forty patients from our impotence clinic were recruited and randomly divided into two groups of 20 patients each. Group 1 was treated with an oral dose of 50 mg DHEA and group 2 with a placebo one time a day for 6 months. The International Index of Erectile Function (IIEF), a 15-item questionnaire, was used to rate the success of this therapy. RESULTS: Therapy response was defined as the ability to achieve or maintain an erection sufficient for satisfactory sexual performance according to the National Institutes of Health Consensus Development Panel on Impotence. DHEA treatment was associated with higher mean scores for all five domains of the IIEF. There was no impact of DHEA treatment on the mean serum levels of PSA, prolactin, testosterone, the mean prostate volume, and the mean postvoid residual urine volume. CONCLUSIONS: Our results suggest that oral DHEA treatment may be of benefit in the treatment of ED. Although our patient data base is too small to do relevant statistical analysis, we believe that our data show a biologically obvious trend that justifies further extended studies.

Adult↗

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.

Adult↗