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B Djavan

Publications and source records attributed to B Djavan.

At least 37 records · Page 2Linked to original sources
PubMed2001

Prostate cancer gene therapy-what have we learned and where are we going?

With recent advances in genetic engineering, tumor biology, and immunology, gene therapy has been recognized as a promising new treatment option for various cancers, including prostate cancer. Several clinical trials of prostate cancer gene therapy, using therapeutic genes which include suicide genes, immunomodulatory genes, tumor suppressor genes, and anti-oncogenes, are under way and preliminary reports have emerged. Although gene therapy for prostate cancer is still at an early stage and requires additional technological breakthroughs, new insights obtained from recent clinical trials indicate a promising potential for prostate cancer gene therapy. In this report, general concepts, current progress, and future prospects in prostate cancer gene therapy are summarized.

Journal Article↗
PubMed2000

Editorial comment

Explore the source record for details and available documents.

Journal Article↗
PubMed2000

Pretreatment prostate-specific antigen as an outcome predictor of targeted transurethral microwave thermotherapy.

OBJECTIVES: To evaluate pretreatment serum prostate-specific antigen (PSA) as an outcome predictor of targeted microwave thermotherapy. METHODS: Seventy-one patients with lower urinary tract symptoms of benign prostatic hyperplasia underwent targeted transurethral microwave thermotherapy using the Targis system. Outcomes 12 months after treatment were evaluated by the International Prostate Symptom Score (IPSS), peak urinary flow rate (Qmax), and quality-of-life (QOL) score. The ability of PSA to predict outcomes was evaluated by linear and logistic regression and receiver operating characteristic curve analysis. RESULTS: Higher pretreatment PSA levels were significantly predictive of an absolute IPSS change of -7.5 or less for patients with moderate baseline symptoms or - 15 or less for those with severe baseline symptoms; an absolute Qmax change of 5 mL/s or greater; an absolute QOL score change of -3 or less; an IPSS at 12 months of 7 or less; a Qmax at 12 months of greater than 12 mL/s; and a QOL score at 12 months of 1 or less. Nevertheless, even without taking pretreatment PSA into account, most patients benefitted substantially from targeted microwave thermotherapy. Thus, 74%, 71%, and 79% of all eligible patients improved 50% or more in IPSS, Qmax, and QOL score, respectively, at 12 months compared with baseline. No significant association between PSA and either prostate or transition zone volume could be demonstrated. CONCLUSIONS: Most patients benefit substantially from targeted microwave thermotherapy. However, higher PSA levels are significantly predictive of more favorable outcomes. This association may reflect patient-to-patient differences in the relative abundance of PSA-producing epithelial cells in the transition zone of the prostate.

Aged↗
PubMed2000

Endocrine status in elderly men with lower urinary tract symptoms: correlation of age, hormonal status, and lower urinary tract function. The Prostate Study Group of the Austrian Society of Urology.

OBJECTIVES: To correlate endocrine parameters in elderly men with lower urinary tract symptoms (LUTS) to patient age and clinical parameters such as prostate volume, prostate-specific antigen (PSA) levels, and uroflowmetry and to compare the clinical and endocrinologic parameters in men with or without hypogonadism. METHODS: Men (40 years old or older) with untreated LUTS as defined by an International Prostate Symptom Score (IPSS) of 7 or greater due to benign prostatic hyperplasia were included in this study and underwent the following investigations: IPSS, free uroflow study, postvoid residual volume, transrectal ultrasound for assessment of prostate volume, serum PSA determination, and an endocrine study, including testosterone, human luteinizing hormone, human follicle-stimulating hormone, prolactin, dehydroepiandrostendione-sulphate (DHEA-S), and prolactin. RESULTS: Three hundred twelve men (mean age 62.8 +/- 10.6 years, range 40 to 91) were analyzed. The serum levels of estradiol (correlation coefficient [r] = 0.19), human luteinizing hormone (r = 0.32), human follicle-stimulating hormone (r = 0.19), and DHEA-S (r = -0.39) correlated (P <0.05) with age; no such correlation was seen for testosterone (r = 0.04; P0.05) or prolactin (r = 0.09; P0.05). Estradiol (but not testosterone) correlated (r = 0.17, P = 0.01) with prostate volume. The peak flow rate and PSA did not correlate with any endocrinologic parameter. Hypogonadism (serum testosterone less than 3.0 ng/mL) was detected in 22.1% of patients and had no impact on clinical (IPSS, peak flow rate, prostate volume, and PSA level) or endocrine (human luteinizing hormone, human follicle-stimulating hormone, estradiol, prolactin, and DHEA-S) parameters. CONCLUSIONS: A number of age-related endocrine changes are seen in elderly men with LUTS. Hypogonadism is seen in approximately one fifth of elderly men with LUTS, but in our study it had no impact on symptom status, PSA level, prostate volume, uroflowmetry, or endocrine parameters.

Adult↗
PubMed2000

Transurethral microwave thermotherapy: an alternative to medical management in patients with benign prostatic hyperplasia?

Transurethral microwave thermotherapy (TUMT) is being increasingly considered as an alternative to medical management with alpha-blockers or finasteride in patients with lower urinary tract symptoms (LUTS) of benign prostate hyperplasia (BPH). Enduring clinical benefits have been demonstrated after a single 1-hour microwave treatment session under topical anesthesia, and the associated morbidity is low. Optimal results are obtained with the delivery of high thermal doses and accurate targeting of microwave energy. Extensive evidence from randomized clinical trials supports the safety and efficacy of both microwave treatment and medical management, but randomized trial data have only recently become available directly comparing these two approaches to BPH treatment. These data indicate that greater long-term improvements in symptoms, peak urinary flow rates, and quality of life are attained with microwave treatment than with alpha-blockade. Furthermore, the actuarial rate of treatment failure is markedly lower in patients undergoing microwave v alpha-blocker treatment. However, the onset of action of alpha-blocker treatment is more rapid. The principal limitations of alpha-blockade are side effects and lack of efficacy leading to treatment failure in some patients. The maximal effects of finasteride are modest and require a period of months to be manifested, although the side effect profile and tolerability of this agent are favorable. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement after TUMT. In contrast to medical management, microwave treatment is highly versatile, allowing patients over a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success.

Adrenergic alpha-Antagonists↗
PubMed2000

Long-term outcome of transrectal high- intensity focused ultrasound therapy for benign prostatic hyperplasia.

OBJECTIVE: The aim of this study was to determine the long-term outcome after transrectal high-intensity focused ultrasound (HIFU) therapy for patients with lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH). METHODS: Between June 1992 and March 1995, 98 men (mean age: 66 years) with LUTS due to BPH underwent transrectal HIFU therapy at our institution, and the data of 80 patients were included in this long-term analysis. Principal inclusion criteria were a peak flow rate (Qmax) < or =15 ml/s, AUA/IPSS score > or =18 and a prostate volume < or =75 ml. Postoperatively, patients were seen at 6-month intervals with assessment of symptom score, uroflowmetry and post-void residual volume. In the present analysis, follow-up was terminated at 4 years. The mean follow-up of the study population (excluding the patients who underwent transurethral resection of the prostate, TURP, due to insufficient therapeutic response) was 41.3 months (range: 13-48 months). RESULTS: In treatment responders (HIFU only; n = 45), the symptom score decreased from preoperatively 19.6 to 8.5 (-53%) after 12 months and subsequently showed only marginal fluctuations within the 4-year study period. The Qmax increased from preoperatively 9.1 to 11.8 ml/s (+30%) after 12 months and gradually declined to 10.2 ml/s (+12%) after 4 years. 35 men (43.8%) underwent TURP due to insufficient therapeutic response during the 4-year study period. The mean time interval between HIFU therapy and TURP was 26.5+/-2.7 months (range: 1-48 months). The retreatment-free period was significantly longer for patients with a pretreatment average flow rate >5 ml/s (p = 0.05) and lower grades of urodynamically documented bladder outflow obstruction (p = 0.03). A similar trend, which did not reach statistical significance, was noted for individuals with higher Qmax and lower post-void residuals. CONCLUSIONS: These long-time data indicate that transrectal HIFU therapy for BPH, at least in its present form, did not stand the test of time, as 43.8% of patients had to undergo TURP within 4 years after initial therapy. These data underline the need for long-term studies with follow-ups over several years to reliably assess the role of less invasive treatment options for BPH.

Aged↗
PubMed2000

Two-year results of transurethral resection of the prostate versus four 'less invasive' treatment options.

OBJECTIVE: The aim of this study was to compare the efficacy or transurethral resection of the prostate (TURP) versus four less invasive treatment options during a 2-year follow-up. MATERIAL AND METHODS: 95 elderly men with lower urinary tract symptoms due to benign prostatic hyperplasia (BPH) were assigned prospectively to the following five treatment arms; transurethral resection of the prostate (TURP; n = 28), transurethral electrovaporization (TUVP; n = 17), visual laser ablation of the prostate (VLAP; n = 17), transrectal high intensity focused ultrasound (HIFU; n = 20) and transurethral needle ablation (TUNA); n = 15). Preoperative workup included the International Prostate Symptom Score (IPSS), uroflowmetry, post-void residual volume (PVR), prostate volume determined by transrectal ultrasonography and a multichannel pressure flow study. Postoperative follow-up at 6, 12, 18 and 24 months included assessment of IPSS, PVR and uroflowmetry. RESULTS: At study entry, patients assigned to one of the five treatment arms were comparable with respect to age, peak flow rate (Q(max)), IPSS, prostate size and the degree of bladder outflow obstruction. During study, 1 patient in the TURP group (4%) required a secondary TURP, as compared to 23.5% (n = 4) after TUVP, 26.7% (n = 4) after VLAP, 15% (n = 4) after HIFU and 20% (n = 3) following TUNA. In patients not subjected to a secondary procedure, the IPSS decreased a mean 13. 9 after TURP, as compared to 12.7 after TUVP, 12.9 after VLAP, 7.0 after HIFU, and 9.8 after TUNA. Q(max) increased 11.5 ml/s (mean) after TURP, as compared to 11.1 ml/s after TUVP, 5.6 ml/s after VLAP, 2.5 ml/s after HIFU and 2.3 ml/s after TUNA. CONCLUSION: In up to a quarter of the patients, a secondary TURP is performed within the first 2 years after 'less invasive' procedures. These data underline the need for long-term studies to reliably assess the role of less invasive procedures and to indicate that TURP is still competitive.

Aged↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

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↗
PubMed2000

Is transurethral microwave thermotherapy an alternative to medical therapy for patients with benign prostatic hyperplasia?

Scientific evidence supports the safety and efficacy of transurethral microwave thermotherapy (TUMT) as well as medical therapy for management of patients with benign prostatic hyperplasia (BPH). TUMT is being increasingly considered as an alternative to medical management with alpha-blockers or finasteride in patients with lower urinary tract symptoms of BPH. Enduring clinical benefits have been demonstrated after a single 1-hour microwave treatment session under topical anesthesia, and associated morbidity is low. Optimal results are obtained with the delivery of high thermal doses and accurate targeting of microwave energy. Extensive evidence from randomized clinical trials supports the safety and efficacy of both microwave treatment and medical management. Randomized clinical trial data have only recently become available directly comparing these two approaches to BPH treatment. These data indicate that greater long-term improvements in symptoms, peak urinary flow rates, and quality of life are attained with microwave treatment as compared with alpha-blockade. Furthermore, the actuarial rate of treatment failure is markedly lower in patients undergoing microwave vs. alpha-blocker treatment. However, the onset of action with alpha-blocker treatment is more rapid. Limitations of alpha-blockade are side effects and lack of efficacy leading to treatment failure in some patients. Maximal effects of finasteride are modest and require a period of months to be manifested, although the side effect profile and tolerability of this agent are favorable. Neoadjuvant and adjuvant alpha-blocker therapy can accelerate symptom and flow rate improvement after microwave treatment. In contrast to medical management, microwave treatment is highly versatile, allowing patients over a broad range of baseline symptom severities and prostate sizes to be treated with a high probability of success. 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.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed2000

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↗
PubMed1999

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↗
PubMed1999

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↗