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Stephan Madersbacher

Publications and source records attributed to Stephan Madersbacher.

45 records · Page 3Linked to original sources

Association of polymorphisms within androgen receptor, 5alpha-reductase, and PSA genes with prostate volume, clinical parameters, and endocrine status in elderly men.

BACKGROUND: The aim of this study was to assess the impact of polymorphisms of three genes within the androgen pathway on prostate volume, clinical parameters, and endocrine status. METHODS: Elderly men with lower urinary tract symptoms underwent clinical and endocrine work-up. In parallel, polymorphisms within the 5alpha-reductase gene (SRD5A2 V89L and A49T), the androgen receptor gene (AR; number of CAG repeats), and the prostate specific antigen (PSA) gene (A --> G substitution at position-158) were determined by polymerase chain reaction and restriction-length polymorphism analysis by using DNA from peripheral blood. RESULTS: A total of 190 men (66.5 +/- 9.2 yr) were analyzed. The number of CAG repeats within the AR and the PSA polymorphism revealed no associations to clinical and endocrine parameters. Individuals carrying the mutated SRD5A2 A49T allele (5.3% of the total population) had larger prostates (54.1 vs. 39.3 ml), higher PSA levels (12.2 vs. 4.3 ng/ml), and a 35% reduction in prostatic stroma/epithelial cell ratio. Men with the mutated SRD5A2 V89L gene had lower testosterone levels. CONCLUSIONS: In contrast to prostate cancer, polymorphisms within AR and PSA genes do not seem to be of importance for benign prostatic hyperplasia. Polymorphisms within the 5alpha-reductase gene are interesting biomarkers for the development of benign prostatic hyperplasia and benign prostatic enlargement.

Aged↗

Vitamin D receptor gene polymorphism and prostate cancer risk.

BACKGROUND: 1,25-dihydroxyvitamin D, the active form of vitamin D, exerts antiproliferative effect on prostatic cells, mediated through the vitamin D receptor. In a case-control study, we examined whether the vitamin D receptor (VDR) gene polymorphism in exon 9 could affect prostate cancer susceptibility. METHODS: One hundred ninety newly diagnosed prostate cancer patients and 190 age-matched men with benign prostatic hyperplasia (BPH), in whom the presence of prostate cancer was excluded clinically or histologically, were recruited for this study. The VDR TaqI polymorphism was investigated by polymerase chain reaction (PCR) following restriction fragment length polymorphism using DNA from lymphocytes. Depending on the presence or absence of the TaqI restriction site at the third position of codon 352, patients were classified as TT, Tt, or tt. RESULTS: The frequency of the tt genotype was not significantly different between prostate cancer patients (18%) and controls (12%; P = 0.07). The odds ratio (OR), calculated relative to individuals with the TT genotype was 1.76 (95% confidence limit (CL) = 0.90-3.45). After stratification for Gleason score and prostate specific antigen levels in a case-case comparison (n = 190), no significant associations with the VDR genotypes were detectable either. CONCLUSIONS: In this case-control study of Austrian Caucasians, no statistically significant association of the VDR TaqI polymorphism and prostate cancer risk was found.

Aged↗

Contemporary cystectomy and urinary diversion.

Radical cystectomy has emerged as the standard therapy for patients with invasive bladder cancer. Controversy is related to the indication, i.e. a low or high threshold. Meticulous pelvic lymphadenectomy can cure 20%-30% of patients with lymph node metastases, particularly those with limited node involvement. Unilateral nerve-sparing surgery is feasible in most patients without compromising oncological outcome and, besides erectile function, has an impact on the continence status after orthotopic bladder substitution. The excellent local control rates following radical cystectomy indicate that the weight of the problem in the future lies in reducing distant metastases. Orthotopic bladder substitution with a low-pressure ileal reservoir is currently the preferred method to reconstruct the lower urinary tract for both sexes following cystectomy. Long-term experience with follow-ups exceeding 10 years demonstrates a sustained favourable voiding outcome with slightly increasing incontinence rates as patients age.

Cystectomy↗

Is ileal orthotopic bladder substitution with an afferent tubular segment detrimental to the upper urinary tract in the long term?

PURPOSE: We determine long-term morphological changes of the upper urinary tract following ileal orthotopic bladder substitution with an afferent tubular segment without a flap-valve type antireflux procedure. MATERIALS AND METHODS: A consecutive series of long-term survivors (5 years or greater) following ileal orthotopic bladder substitution underwent regular radiological followup with excretory urography. Preoperative and postoperative renal size, parenchymal thickness, pelvicaliceal dilatation and upper urinary tract obstruction were assessed by 2 radiologists. RESULTS: A total of 76 patients with a median followup of 84 months (range 60 to 155) were evaluable. Four patients (2.6%) underwent unilateral nephroureterectomy during followup. Of the remaining 148 renoureteral units 141 (95%) revealed no significant changes in size or parenchymal thickness during followup. Renal size decreased in 6 (4%) and parenchymal thickness in 7 (5%) renoureteral units, 5 of which already had renal pathologies (dilatation, obstruction or hypoplastic kidney) preoperatively. De novo shrinkage of the parenchyma of a preoperatively normal kidney was observed in 2 (1%) renoureteral units associated with stenosis of the ureteroileal anastomosis. Of the 148 renoureteral units 14 (9%) presented with nonobstructive dilatation and 4 (3%) with complete obstruction. Preoperatively average serum creatinine level +/- SD was 98 +/- 19 micromol./l. and 10 years thereafter it was 83 +/- 27 micromol./l. CONCLUSIONS: These data suggest that unidirectional peristalsis of ureters and the afferent tubular ileal segment sufficiently protect the upper urinary tract following ileal bladder substitution up to a decade provided there are no preoperative renal pathology and no anastomotic stricture postoperatively. Additional antireflux flap-valve type implantation techniques are not required.

Aged↗

Impact of radical prostatectomy and TURP on the hypothalamic-pituitary-gonadal hormone axis.

OBJECTIVES: To assess the impact of prostate cancer (PCa) and benign prostatic hyperplasia (BPH) on the hypothalamic-pituitary hormone axis, we determined the endocrine changes after radical prostatectomy (RP) and transurethral resection of the prostate (TURP) for BPH and in a group of men with BPH followed up conservatively. METHODS: Patients with PCa before RP (n = 49), those who underwent TURP for BPH (n = 51), and men with lower urinary tract symptoms for whom a wait-and-see strategy was chosen (n = 46) were included. Serum levels of total testosterone, luteinizing hormone, and follicle-stimulating hormone were determined at baseline and 6 and 12 months later in all patients. RESULTS: No significant endocrine changes were observed in the wait-and-see and TURP groups 6 and 12 months after baseline. In contrast, luteinizing hormone increased from 5.2 to 8.9 mIU/mL (P = 0.0004) and follicle-stimulating hormone from 5.7 to 9.3 mIU/mL (P = 0.0003) 12 months after RP. The rise of total testosterone from 3.9 to 4.4 ng/mL failed to reach statistical significance (P = 0.18). Patients with Gleason score 2 to 6 PCa had higher testosterone values (4.2 ng/mL) at baseline than did those with Gleason score 7 to 10 PCa (2.2 ng/mL, P < 0.05). Although 12 months after RP no changes in testosterone were observed in the low Gleason score group, the testosterone levels more than doubled in those with high-grade tumors. The increases in luteinizing hormone and follicle-stimulating hormone at 12 months, however, were comparable in both groups. CONCLUSIONS: Our findings suggest a significant impact of PCa on the hypothalamic-pituitary axis that is more profound in high-grade cancer. Such an effect was not demonstrable for the transition zone in BPH.

Aged↗

Polymorphic CAG repeats in the androgen receptor gene, prostate-specific antigen polymorphism and prostate cancer risk.

As the development of prostate cancer is androgen-dependent, it has been hypothesized that variation in transcriptional activity by the androgen receptor (AR) related to polymorphic CAG repeats in exon 1, influences prostate cancer risk. The AR regulates gene transcription by binding to androgen-response elements (AREs) in target genes, such as the prostate-specific antigen (PSA). In the ARE-I sequence of the PSA gene an adenine to guanine polymorphism is described. It has been hypothesized that the AR binds the two PSA alleles (A and G) with differing affinities and may, thereby, differentially influence prostate cancer risk. To examine the role of the polymorphisms in the AR and PSA genes in prostate cancer susceptibility, we conducted a case-control study of Austrian Caucasians with 190 newly diagnosed prostate cancer patients and 190 age-matched control men with benign prostatic hyperplasia (BPH). The polymorphisms were determined by polymerase chain reaction (PCR)-based methods using DNA from peripheral white blood cells. Logistic regressions were performed to calculate odds ratios (OR) and confidence limits (CL) and to control for possible confounders. Our data provide no evidence for an association between prostate cancer and CAG repeat length. However, we found a significant influence of the ARE-I PSA polymorphism on prostate cancer risk, when calculating the combination of the A/G and G/G genotypes relative to subjects with the A/A genotype (OR = 0.63; 95% CL 0.39-0.99; P = 0.048), suggesting that the G allele has a protective effect. In a case analysis according to Gleason score, the PSA G/G genotype was significantly more frequent in patients with Gleason score >7 (35.1%) than in patients with Gleason score <7 (21.5%), providing evidence that the PSA G/G genotype is associated with more advanced disease at time of diagnosis. However, the ambivalent role of the PSA during prostate carcinogenesis needs further investigation.

Aged↗

Long-term voiding pattern of patients with ileal orthotopic bladder substitutes.

PURPOSE: Good long-term functional outcome of orthotopic bladder substitution will ultimately decide whether it is here to stay. Therefore, we analyzed exclusively voiding patterns of long-term survivors with an orthotopic ileal bladder substitute. MATERIALS AND METHODS: In all patients with an ileal orthotopic bladder substitute day and nighttime continence status, voiding frequency, bladder capacity and pad usage were prospectively assessed by frequency volume charts and a standardized questionnaire. All men surviving 5 or more years with a median followup of 95 months (range 60-132) were evaluated. RESULTS: Spontaneous voiding was possible in 82 of 86 (95.3%) evaluable patients after catheter removal. Daytime continence increased from 61% after 3 months to 92% at 12 months and remained stable throughout the following 4 years yet decreased slightly thereafter. Nocturnal continence rates were 10% to 15% lower throughout the study period. Functional reservoir capacity averaged 473 ml. after 12 months and did not change in subsequent years. After a decrease during the first 12 months, daytime frequency (4.1 to 4.8 times daily) and nocturia (1.8 to 2.3 a night) did not change in the next decade. Patient age at surgery was an important determinant for long-term reservoir capacity, nocturia and continence status. CONCLUSIONS: These data provide evidence for good long-term functional outcome following orthotopic ileal bladder substitution up to 11 years. We attribute the sustained ability to void to the relatively small reservoir size, which is made of 40 to 44 cm. of ileum, the avoidance of any funnel shaped outlet but rather a side-to-end intestine-urethral anastomosis as well as lifelong meticulous followup.

Adult↗