Association of polymorphisms in CYP19A1 and CYP3A4 genes with lower urinary tract symptoms, prostate volume, uroflow and PSA in a population-based sample.

PURPOSE: The known importance of testosterone for the development of benign prostatic hyperplasia (BPH) prompted us to test the hypothesis whether polymorphisms of two genes (CYP19A1 and CYP3A4) involved in testosterone metabolism are associated with clinical BPH-parameters. METHODS: A random sample of the population-based Herne lower urinary tract symptoms cohort was analysed. All these men underwent a detailed urological work-up. Two polymorphisms in the CYP19A1 gene [rs700518 in exon 4 (A57G); rs10046 at the 3'UTR(C268T)] and one in the 3'UTR of CYP3A4 [rs2740574 (A392G)] were determined by TaqMan assay from genomic DNA of peripheral blood. These polymorphisms were correlated to clinical and laboratory BPH-parameters. RESULTS: A total of 392 men (65.4 ± 7.0 years; 52-79 years) were analysed. Mean International Prostate Symptom Score (IPSS; 7.5), Q (max) (15.4 ml/s), prostate volume (31 ml) and prostate specific antigen (PSA) (1.8 ng/ml) indicated a typical elderly population. Both polymorphisms in the CYP19A1 gene were not correlated to age, IPSS, Q (max), prostate volume and post-void residual volume. Serum PSA was higher in men carrying the heterozygous rs10046 genotype (2.0 ± 0.1 ng/ml) than in those with the CC-genotype (1.7 ± 0.2 ng/ml, P = 0.012). Men carrying one a mutated allele of the CYP3A4 gene had smaller prostates (27.0 ± 2.0 vs. 32 ± 0.8 ml, P = 0.02) and lower PSA levels (1.6 ± 0.3 vs. 1.9 ± 0.1 ng/ml). CONCLUSIONS: The inconsistent associations observed herein and for other gene polymorphisms warrant further studies. In general, the data regarding the association of gene polymorphism to BPH-parameters suggest that this disease is caused by multiple rather than a single genetic variant. A rigorous patient selection based on anatomo-pathological and hormonal profile may possible reduce the number of confounders for future studies thus enabling a more detailed assessment of the association between genetic factors and BPH-parameters.

Initial experiences with real-time elastography guided biopsies of the prostate.

PURPOSE: Based on our first experiences with real-time elastography in the field of prostate diagnostics we evaluate its usefulness for biopsy guidance for prostate cancer detection. MATERIALS AND METHODS: After imaging with conventional B-mode ultrasound in conjunction with real-time elastography 404 men underwent systematic sextant biopsy. RESULTS: Overall prostate cancer was found in 151 of 404 cases (37.4%). In 127 of 151 cases (84.1%), prostate cancer was detected using real-time elastography as an additional diagnostic feature. CONCLUSIONS: The results show that it is possible to detect prostate cancer with a high degree of sensitivity using real-time elastography in conjunction with conventional diagnostic methods for guided prostate biopsies.

Analysis of the inflammatory network in benign prostate hyperplasia and prostate cancer.

INTRODUCTION: The complexity of acute and chronic inflammatory processes may either lead to benign prostate hyperplasia (BPH) and/or prostate cancer. Obviously, various tissue cells are activated by chemokines via different chemotaxin receptors which then trigger subsequent processes in angiogenesis, cellular growth, and extravasation as well as neoplasia. METHODS: Using the surgically obtained tissue of patients (n = 36) with BPH or prostate carcinoma (PCA), we studied among others the expression of chemokines (Rantes, IL-8), chemotaxin receptors (CXCR-3 and -4, CCR-3, CCR-5), of matrixmetalloproteinases (MMP-2 and 9), of Toll-like (TL) receptors 1, 2, 3, 4, 5, 7, and 9 and of the inducible cyclooxygenase-2 (cox-2) by RT-PCR. Further support for the different properties of tissue from PCA was obtained using two different PCA cell lines (PC3 = androgen resistant cell) or LNCAP cells (androgen sensitive) with emphasis on IL-8, Il-6, and PGE(2) release. Cell lines were stimulated with either the tumor necrosis factor-alpha (TNF-alpha) and lipopolysacharide (LPS) over time. In addition to cytokine release, the quantification of mRNA by lightcycler for cox-2, IL-6, and IL-8 was performed on these cell lines. RESULTS: Remarkable differences in expression were obtained by RT-PCR when BPH tissue versus PCA was analyzed. Expression of CXCR-1 after incubation with LPS and TNF-alpha showed time-dependent differences for androgen-sensitive LNCAP as compared to androgen-resistant PC-3 cells. TNF-alpha incubation leads to a time-dependent induction of cox-2 expression unlike to activation with LPS. Differences with regard to cox-2, IL-6, and IL-8 expression were seen by quantitative lightcycler analysis. Significant differences were also observed when TL receptors 4, 5, 7, and 9 were analyzed which were significantly expressed in BPH- as compared to PCA-tissue. CONCLUSIONS: Our data clearly demonstrate that various inflammatory and cell biological cascades are involved which either lead to BPH or can be linked to the development of PCA. The exact cell biological mechanisms may provide novel therapeutic options in the treatment of both diseases.

Results of extracorporeal shock wave lithotripsy with a new electrohydraulic shock wave generator.

OBJECTIVE: Since 1999, the lithotriptor LDM (Philips, Germany) is used routinely for treatment of urinary stones in our department. We evaluated the complication rate and treatment success of extracorporeal stone treatment with the new lithotriptor. MATERIAL AND METHODS: We performed a prospective, two-step clinical study: (1) Complication rate: From January to May 1999, 312 consecutive treatments in 225 patients (136 male, 89 female) were evaluated. (2) Success rate: From February to April 2000, 88 consecutive patients (61 male, 27 female) with 113 concrements were evaluated. RESULTS: (1) Complication rate: Overall complication rate was 10%. Most of them were minor complications. Most significant complications were subcapsular renal hematomas, which were detected by routinely performed renal ultrasound in 1%. (2) Success rate: After single treatment, overall success rate was 87%. 15 of 16 in situ treated ureteral stones (94%) were sufficiently disintegrated by a single treatment. Disintegration rates after single treatment were 93.6% for renal stones smaller than 1 cm and 86% for renal stones 1-2 cm, respectively. CONCLUSIONS: Stone therapy by SWL with the new lithotriptor LDM is a highly effective therapy of renal and ureteral stones and has a low complication rate.

Prostate size and PSA serum levels in male patients with spinal cord injury.

OBJECTIVES: To evaluate prostate size and serum prostate-specific antigen (PSA) levels in male patients with spinal cord injury (SCI). As a result of improved medical care, the life expectancy in patients with SCI today equals the life expectancy of the general population. Therefore, male patients with SCI are likely to develop benign prostatic hyperplasia or prostate cancer. Although animal experiments indicate that neurogenic factors play an important role in prostate growth, the influence of these factors is not well examined in humans. METHODS: The data of 100 male patients with SCI and 575 noninjured men were evaluated. The inclusion criteria were age older than 35 years and SCI for longer than 2 years. The exclusion criteria were previous prostate surgery, acute urinary tract infection, and bladder or prostate cancer. PSA was measured by an immunoenzymatic assay, and the prostatic volume was assessed by transrectal ultrasonography. For analysis, patients were grouped according to age. RESULTS: With increasing age, the mean prostate volume increased in the patients with SCI and in the control group. The mean PSA level increased with age in the control group and to a far lesser extent in the patients with SCI. Neither for the entire cohort nor for the subgroups delineated by age were the differences in mean PSA level and mean prostate volume between patients with SCI and the control group statistically significant. CONCLUSION: Prostate growth is detectable in patients with SCI. Although there is a tendency toward a lower prostate volume and lower serum PSA level in patients with SCI, the differences were not statistically significant. According to our results, the reference ranges for PSA levels are not vastly different from the general reference ranges.

New way to deliver fluids: endoscopic jet injection into the beagle prostate.

PURPOSE: Local therapy of the prostate could have a role in the treatment of benign prostatic hyperplasia as well as prostate cancer. Endoscopic jet injection could simplify these treatments. We evaluated the tissue effects of endoscopic jet injection in an animal model. MATERIALS AND METHODS: An endoscopic jet injector was developed. In 12 beagle dogs the prostate was injected with single shot and continuous mode jet injection. Macroscopic and histological analysis was performed 0, 2 and 14 days after jet injection. RESULTS: Jet injection allowed complete penetration of the beagle prostate. The single shot technique resulted in only minimal tissue effects. However, the continuous mode led to major tissue damage, even complete aseptic necrosis, in the injected area. CONCLUSIONS: A new method for endoscopic application of fluids is described. Depending on the jet injection technique it could be used to apply pharmaceutical agents or plasmids, and/or induce aseptic necrosis.

Ultrasonic multifeature tissue characterization for prostate diagnostics.

A new system for prostate diagnostics based on multifeature tissue characterization is proposed. Radiofrequency (RF) ultrasonic echo data are acquired during the standard transrectal ultrasound (US) imaging examination. Nine spectral, texture, first order and morphologic parameters are calculated and fed into two adaptive neuro-fuzzy inference systems (FIS) working in parallel. The outputs of the FISs are fed into a postprocessing procedure evaluating contextual information before being combined to form a malignancy map in which areas of high cancer probability are marked in red. The malignancy map is presented to the physician during the examination to improve the early detection of prostate cancer. The system has been evaluated on 100 patients undergoing radical prostatectomy. The ROC curve area using leave-one-out cross-validation over patients is A(Z) = 0.86 when distinguishing between hyperechoic and hypoechoic tumors and normal tissue and A(Z) = 0.84 when distinguishing between isoechoic tumors and healthy tissue, respectively. Tumors that are not visible in the conventional B-mode image can be located. Diagnosis of the prostate carcinoma using multifeature tissue characterization in combination with US imaging allows the detection of tumors at an early stage. Also, biopsy guidance and therapy planning can be improved.