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1.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Article in English | MEDLINE | ID: mdl-33771918

ABSTRACT

Knockout of ERß in the mouse leads to nuclear expression of epidermal growth factor receptor (EGFR) in the prostate. To examine whether ERß plays a similar role in the human prostate, we used four cohorts of men: 1) a Swedish cohort of normal prostates and PCa (prostate cancer) of different Gleason grades; 2) men with benign prostatic hyperplasia (BPH) treated with the 5α-reductase inhibitor, finasteride, and finasteride together with the ERß agonists, soy isoflavones; 3) men with PCa above Gleason grade 4 (GG4), treated with ADT (androgen deprivation therapy) and abiraterone (AA), the blocker of androgen synthesis for different durations; and 4) men with GG4 PCa on ADT or ADT with the AR (androgen receptor) blocker, enzalutamide, for 4 mo to 6 mo. In men with BPH, finasteride treatment induced EGFR nuclear expression, but, when finasteride was combined with isoflavones, EGFR remained on the cell membrane. In GG4 patients, blocking of AR for 4 mo to 6 mo resulted in loss of ERß and PTEN expression and increase in patients with nuclear EGFR from 10 to 40%. In the men with GG4 PCa, blocking of adrenal synthesis of testosterone for 2 mo to 7 mo had the beneficial effect of increasing ERß expression, but, on treatment longer than 8 mo, ERß was lost and EGFR moved to the nucleus. Since nuclear EGFR is a predictor of poor outcome in PCa, addition of ERß agonists together with abiraterone should be considered as a treatment that might sustain expression of ERß and offer some benefit to patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Estrogen Receptor beta/agonists , Prostatic Hyperplasia/drug therapy , Prostatic Neoplasms/drug therapy , Active Transport, Cell Nucleus/drug effects , Androgen Antagonists/pharmacology , Androgen Antagonists/therapeutic use , Androstenes/pharmacology , Androstenes/therapeutic use , Animals , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Benzamides/pharmacology , Benzamides/therapeutic use , Biopsy , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Cohort Studies , ErbB Receptors/metabolism , Estrogen Receptor beta/metabolism , Finasteride/pharmacology , Finasteride/therapeutic use , Humans , Male , Mice , Mice, Knockout , Neoplasm Grading , Nitriles/pharmacology , Nitriles/therapeutic use , PTEN Phosphohydrolase/metabolism , Phenylthiohydantoin/pharmacology , Phenylthiohydantoin/therapeutic use , Phytoestrogens/pharmacology , Phytoestrogens/therapeutic use , Prostate/cytology , Prostate/drug effects , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology , Receptors, Androgen/metabolism , Receptors, Estrogen/genetics , Receptors, Estrogen/metabolism
2.
Front Surg ; 6: 72, 2019.
Article in English | MEDLINE | ID: mdl-31921886

ABSTRACT

Background: The urinary incontinence system ATOMS (A.M.I., Austria) generates suburethral compression through its sphincter cushion. To what extent the ATOMS may lead to overactive bladder (OAB) symptoms or which risk factors for these symptoms exist remain unknown to date. We report on our multicentre evaluation on the prevalence, status, and therapy of OAB after ATOMS. Methods: Between 10/09 and 01/17, a total of 361 patients received an ATOMS device in Vienna and Halle. A prerequisite for surgery was persistent male stress urinary incontinence lasting at least 6 months after the primary intervention, as well as the failure of conservative treatment. Patients with a preoperative untreated anastomotic stricture or detrusor overactivity were excluded. In addition to continence and voiding parameters, patient's age, BMI, comorbidities, and pre-treatment strategies of the underlying disease and urinary incontinence were examined. If de novo OAB was present, urodynamics were used for further clarification. Statistical analysis was performed with GraphPad Prism 7® (GraphPad Software, Inc., La Jolla, USA), p < 0.05 considered significant. Results: OAB presented 18 patients (4.9%). Regarding the degree of urinary incontinence as well as uroflowmetry, residual volume and comorbidities, patients with an OAB showed no differences compared to patients without an OAB (p < 0.05). Only previous radiotherapy or urinary incontinence surgery and urethral stricture interventions resulted in statistically significant differences based on the bivariate analysis (p = 0.030, p = 0.006, p = 0.007). The consecutive postoperative urodynamics revealed a sensory OAB in 17 patients and a low-compliance bladder in a patient with newly diagnosed insulin-dependent type II diabetes mellitus. OAB was treated with a standard dose of antimuscarinic drugs and for the low-compliance bladder with botulinum toxin type A. Conclusion: OAB symptoms can occur after ATOMS implantation, but are rare and have no clear correlation to the incontinence device but rather are due to urinary incontinence-related underlying diseases and previous treatments.

3.
Urology ; 114: 139-146, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29330001

ABSTRACT

OBJECTIVE: To evaluate the diagnostic performance and complication rate of the in-bore magnetic resonance imaging-guided transrectal targeted prostate biopsy (MRGB) in a repeat biopsy population on the basis of a nearly 4-year learning curve (2014-2017). MATERIALS AND METHODS: A total of 142 consecutive males with previous biopsies and persistent suspicion of prostate cancer (PCa) due to high prostate-specific antigen level initially underwent MRGB in the case of prostate imaging reporting and data system (PI-RADS) 3-5 lesions. Cancer detection rate (CDR), number and length of cores, biopsy time, operator experience, complications, and prediction of clinically significant (cs) PCa (Gleason score ≥7) were investigated. RESULTS: PCa was found in 57% of patients. CDR in PI-RADS 3, 4, and 5 lesions were 46%, 52%, and 74%, respectively. csPCa was found in 9%, 25%, and 48% of patients. In univariate analysis the PI-RADS score (P = .0067) was a significant predictor of csPCa. In the multivariate logistic regression, age (P = .0007), number of previous biopsies (P = .0236), and prostate-specific antigen density (P = .0250) were significant predictors of csPCa. Location and size of the index lesion, number and length of cores obtained, and operator experience did not affect CDR. Concerning learning curve, biopsy time and number of cores obtained improved significantly after 10 procedures. Complications requiring medical intervention were seen in 6% (infections 2%). CONCLUSION: In a re-biopsy setting the MRGB showed sufficient diagnostic performance in detecting csPCa in PI-RADS 3-5 lesions, with low complication rate. The skill of performing biopsy is quickly acquired, and location of index lesion did not have an impact on CDR.


Subject(s)
Image-Guided Biopsy , Magnetic Resonance Imaging , Prostate/pathology , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/pathology , Age Factors , Aged , Humans , Image-Guided Biopsy/adverse effects , Image-Guided Biopsy/standards , Learning Curve , Male , Middle Aged , Neoplasm Grading , Operative Time , Prostate-Specific Antigen/blood , Reoperation
4.
Urology ; 110: 148-153, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28844600

ABSTRACT

OBJECTIVE: To assess prostate cancer (PCa) detection and prediction by combining the in-bore magnetic resonance imaging-guided transrectal targeted prostate biopsy (MRGB) with prostate-specific antigen (PSA) parameters and the Prostate Health Index (PHI) in case of negative 12-core standard biopsy. MATERIALS AND METHODS: A total of 112 men (2014-2016) underwent 3-T multiparametric magnetic resonance imaging and subsequent MRGB of Prostate Imaging-Reporting and Data System (PI-RADS) lesions 3-5. Ancillary PSA parameters (PSA ratio [%fPSA] and PSA density [PSAD]) and the PHI and PHI density (PHID) were recorded. With these parameters in combination with MRGB, PCa prediction was calculated. RESULTS: The most common lesions biopsied were PI-RADS 4 (66%), located in the peripheral zone (64%), in the middle (58%) and anterior (65%) sections of the prostate, and 13 mm (IQR 10-15) in size. PCa was found in 62 (55%) patients (28% Gleason score ≥7). PSAD (0.15 vs 0.21; P = .0051), %fPSA (16 vs 13; P = .0191), PHI (45 vs 69; P < .0001), PHID (0.7 vs 1.5; P < .0001), and prostate volume (56 mL vs 45 mL; P = .0073) were significantly different in patients with PCa and those without PCa. PHI and PHID were the strongest predictors of PCa with areas under the curve of 0.79 and 0.77, respectively. Using optimal thresholds of 59 and 0.79, PHI and PHID were 69% and 84% sensitive and 82% and62% specific for PCa, respectively. CONCLUSION: Following negative standard biopsy of the prostate, the MRGB achieved an overall PCa detection rate of 55% in patients with PI-RADS 3-5 lesions. By considering PHI and PHID, 82% and 62% of unnecessary biopsies could have been avoided, failing to detect 31% and 16% of cancers.


Subject(s)
Magnetic Resonance Imaging, Interventional , Prostate-Specific Antigen/blood , Prostate/pathology , Prostatic Neoplasms/blood , Prostatic Neoplasms/pathology , Aged , Biopsy, Large-Core Needle/methods , False Negative Reactions , Health Status Indicators , Humans , Image-Guided Biopsy , Male , Middle Aged , Predictive Value of Tests , Rectum , Retrospective Studies
5.
Urology ; 109: 184-189, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28712889

ABSTRACT

OBJECTIVE: To investigate the efficacy and safety of the Adjustable Transobturator Male System (ATOMS) in men with stress urinary incontinence after transurethral resection of the prostate (TURP). MATERIALS AND METHODS: From a large international prospectively administrated ATOMS register, we identified 49 patients with an ATOMS device as a result of persistent stress urinary incontinence after TURP. For evaluation, the men were divided into standard transurethral resection of the prostate (sTURP) and palliative transurethral resection of the prostate (pTURP) in radiated patients. Baseline and follow-up measurements included continence parameters, urodynamics, quality-of-life surveys (Patient Global Impression-Improvement and International Consultation on Incontinence Questionnaire-Short Form), and pain ratings. The dry rate (0-1 security pad/<10 mL urine loss), the success rate (overall improvement), removals, complications, and treatment failures were recorded. A P value of <.05 was considered statistically significant. RESULTS: After a median of 34 and 22 months' follow-up and 2-3 adjustments, the sTURP and pTURP cohorts had 58% and 50% dry rates and 90% and 87% success rates. Hence, no improvement was seen in 10% and 13%. The removal rate was higher in pTURP (50% vs 10%, P = .0171) and infection was the most common side effect (50%) observed. Neither intraoperative nor Clavien-Dindo 4 and 5 adverse events were recorded. In sTURP and pTURP, the median daily pad count and the pad test improved significantly (all P <.001), and quality-of-life parameters shifted to a high satisfaction level (P <.001 and P = .001). Urodynamics remained unchanged and postoperative pain was not an issue. CONCLUSION: The ATOMS device shows promising treatment outcomes in patients after TURP and a similar efficacy as in postprostatectomy incontinence. There is no difference in continence outcome between sTURP and pTURP; however, a higher removal rate was found after pTURP, which may be important for patient counseling.


Subject(s)
Postoperative Complications/surgery , Suburethral Slings , Transurethral Resection of Prostate , Urinary Incontinence, Stress/surgery , Aged , Aged, 80 and over , Cross-Sectional Studies , Humans , Male , Retrospective Studies , Suburethral Slings/adverse effects , Treatment Outcome
6.
Urol Int ; 99(4): 429-435, 2017.
Article in English | MEDLINE | ID: mdl-28641294

ABSTRACT

INTRODUCTION AND OBJECTIVES: Bladder cancer is characterized by gender-dependent disparities. To further address this issue, we analysed a prospective, multicentre cystectomy registry. METHODS: An online database was developed that included patient demographics, intra/perioperative data, surgical data and in-house complications. RESULTS: Four hundred fifty-eight patients (112 [24.5%] women and 346 [75.5%] men) were analysed. Men and women were comparable regarding age (mean 68 years), body mass index (mean 26.5) and the mean Charlson score (4.8). Women had more advanced tumour-stages (pT3/pT4; women: 57.1%; men: 48.1%). The rate of incontinent urinary diversion was higher in women (83.1%) than in men (60.2%) and in a multivariate analysis, the strongest predictors were M+ status (OR 11.2), female gender (OR 6.9) and age (OR 6.5). Women had a higher intraoperative blood transfusion rate. The overall rate of in-house complications was similar in both genders (men: 32.0%, women: 32.6%). Severe (Clavien-Dindo grade >2) medical (women: 6.3%; men: 5.2%) and surgical (women: 21.5%; men: 14.4%) in-house complications, however, were more frequent in women. CONCLUSIONS: This multicentre registry demonstrates several gender-related differences in patients undergoing radical cystectomy. The higher transfusion rate, the rare use of orthotopic bladder substitutes and the higher in-house complication rate underline the higher complexity of this procedure in women.


Subject(s)
Clinical Decision-Making , Cystectomy/adverse effects , Healthcare Disparities , Postoperative Complications/etiology , Urinary Bladder Neoplasms/surgery , Urinary Diversion/adverse effects , Aged , Austria , Chi-Square Distribution , Databases, Factual , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasm Staging , Odds Ratio , Patient Selection , Prospective Studies , Registries , Risk Factors , Sex Factors , Time Factors , Treatment Outcome , Urinary Bladder Neoplasms/pathology , Urinary Diversion/methods
7.
BJU Int ; 119(5): 785-792, 2017 05.
Article in English | MEDLINE | ID: mdl-27868328

ABSTRACT

OBJECTIVE: To evaluate the long-term effectiveness and safety of the adjustable transobturator male system (ATOMS® , Agency for Medical Innovations A.M.I., Feldkirch, Austria) in a European-wide multicentre setting. PATIENTS AND METHODS: In all, 287 men with stress urinary incontinence (SUI) were treated with the ATOMS device between June 2009 and March 2016. Continence parameters (daily pad test/pad use), urodynamics (maximum urinary flow rate, voiding volume, residual urine), and pain/quality of life (QoL) ratings (visual analogue scale/Leeds Assessment of Neuropathic Symptoms and Signs, International Consultation on Incontinence Questionnaire-Short Form [ICIQ-SF]/Patient Global Impression of Improvement [PGI-I]) were compared preoperatively and after intermediate (12 months) as well as after individual maximum follow-up. Overall success rate, dry rate (<10 mL/day and 0-1 pad/day), device durability, treatment failure, and device complications were recorded. Nonparametric tests were used for statistical analyses. RESULTS: After a median (interquartile range [IQR]) follow-up of 31 (10-54) months and a median (IQR) of 3 (2-4) adjustments, the overall success rate was 90% (258 men) and the dry rate was 64% (184). Daily pad test and pad use decreased from a median of 400 mL/day and 4 pads/day to a median of 18 mL/day and 1 pad/day (both P < 0.001), concomitantly QoL ratings significantly improved and changed to a high level of satisfaction (PGI-I 4 to 2, ICIQ-SF 17 to 5; both P < 0.001). The UI results at 12 months were comparable to those at final follow-up. Chronic pain and intraoperative complications did not occur. Most of the postoperative complications were Clavien-Dindo grade I-III (no grade IV or V). At present, 231 (80%) of all the ATOMS devices are still functioning; 56 (20%) were removed, the most common reason being local titanium intolerance (41%) and leak/dysfunction (30%). The operating time and continence outcome varied between port generations. In this regard the latest port generation (silicone-covered scrotal port) was superior to its predecessors. Primary implantation (P = 0.002), good physical health (P = 0.001), and no history of radiotherapy (P < 0.001) were prognostic factors for beneficial treatment outcome. CONCLUSION: The ATOMS device is safe and shows high treatment efficacy and patient satisfaction in the largest cohort study to date. The latest generation, with its pre-attached silicone-covered scrotal port, is superior to its predecessors. Significantly better results were achieved with primary implantation and in those without a history of radiotherapy.


Subject(s)
Suburethral Slings , Urinary Incontinence, Stress/surgery , Aged , Humans , Male , Prosthesis Design , Retrospective Studies , Suburethral Slings/adverse effects , Time Factors , Treatment Outcome
8.
Arch Ital Urol Androl ; 87(4): 306-11, 2016 Jan 14.
Article in English | MEDLINE | ID: mdl-26766803

ABSTRACT

OBJECTIVES: To investigate erectile function and sexuality before/after implantation of the ATOMS device including continence outcome, pain perception and co-morbidities. MATERIALS AND METHODS: We collected data from 34 patients (2010-2014) who were provided with an ATOMS implant due to mild or moderate stress urinary incontinence (SUI) after radical prostatectomy (RPE), transurethral resection (TURP) or radiotherapy. Previous failed implants were no contraindication. Sexuality was evaluated with the International Index of Erectile Function (IIEF-5). The Visual Analog Scale (VAS) and Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) were used to analyse pain perception. Results regarding continence, influence of co-morbidities and drug intake were interpreted. RESULTS: IIEF-5 score increased 6 months after ATOMS implantation with a mean difference of 2.18 (Cl: 1.22, 3.14), p < 0,001). Non-sexually active patients had the greatest benefit. However, 50% of patients achieved a mean IIEF-5 of 10.1 and 38% of patients reported a new onset of sexual activity at follow up (mean IIEF-5 score of 12.9). This is in accordance with reduced SUI and absence of persistent pain syndrome. Overall success rate regarding 24h pad-use was 88% (no pad rate 38%). Previous failed implants did not influence results but diabetes, obesity and drug intake (beta-blockers, antidepressants) led to poorer outcomes. CONCLUSION: Sexuality and erectile function improves significantly 6 months after ATOMS implantation. We postulate that reduced SUI (also during sexual activity) and absence of chronic pain are the improving factors. ATOMS should be offered to men with mild to moderate SUI who are interested in regaining their erectile function and sexual activity.


Subject(s)
Patient Satisfaction , Penile Erection , Penile Prosthesis , Sexuality , Urinary Incontinence, Stress/surgery , Aged , Aged, 80 and over , Austria/epidemiology , Follow-Up Studies , Humans , Male , Middle Aged , Prospective Studies , Prosthesis Design , Risk Factors , Sexuality/statistics & numerical data , Surveys and Questionnaires , Treatment Outcome , Urinary Incontinence, Stress/diagnosis , Urinary Incontinence, Stress/epidemiology , Urinary Incontinence, Stress/etiology
9.
Urology ; 90: 189-94, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26773347

ABSTRACT

OBJECTIVE: To identify risk factors for treatment failure of men with the adjustable transobturator male system (ATOMS) for treating stress urinary incontinence (SUI). PATIENTS AND METHODS: Sixty-two patients with SUI after prostate surgery were provided with an ATOMS. The self-defined criteria for treatment failure (implant removal [A], no improvement or ≥3 pads/24 hours [B], and no improvement or ≥150 mL urine loss/24 hours [C]) were compared to anamnestic, clinical, and time-specific parameters: age, Charlson comorbidity index (CCI), urine culture (UC), previous ineffective implants, body mass index, radiotherapy, renal function (serum creatinine), smoker status, urethral strictures, SUI severity, surgery time, time to and season at implantation, and port system application. RESULTS: After a median follow-up of 17.7 months, 9 ATOMS (15%) were removed due to infection (8) or dysfunction (1); 23% and 16% had treatment failure of criteria B and C. Dry rate/overall success rate was 61%/87%. Age alone was no risk factor but the CCI and a positive UC were univariate significant predictors of the criteria A, B, and C. Besides, previous devices and renal failure were significantly associated with implant removal (A) and SUI severity with criterion C. In multivariate analysis, previous devices (P = .0163), positive UC (P = .0190), and SUI severity (P = .0123) were the strongest predictors of A, B, and C, respectively. CONCLUSION: A poor CCI, preoperative positive UC, severe SUI, and previous implants lead to more treatment failure and removal. Age, body mass index, radiotherapy, urethral strictures, current smoking, time-specific parameters, seasonality, and port system application did not influence the outcome.


Subject(s)
Suburethral Slings , Urinary Incontinence, Stress/surgery , Aged , Aged, 80 and over , Humans , Male , Prosthesis Design , Retrospective Studies , Risk Factors , Treatment Failure , Urologic Surgical Procedures, Male/methods
10.
BJU Int ; 111(2): 296-303, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23186285

ABSTRACT

OBJECTIVE: To report our experience with a new self-anchoring adjustable transobturator male system (ATOMS®; AMI, Vienna, Austria) for the treatment of stress urinary incontinence (SUI) in men. PATIENTS AND METHODS: A total of 99 men, in a number of centres, were treated for SUI with the new ATOMS® device. The device was implanted in all patients using an outside-in technique by passing the obturator foramen and anchoring the device to the inferior pubic ramus. The titanium port was placed s.c. on the left symphysis region. Adjustments were performed via port access. Postoperative evaluation consisted of physical examination, 24-h pad test, and 24 h-pad count. Preoperatively and at 6-month follow-up, patients completed a validated quality-of-life questionnaire. Two-way ANOVA was used to analyse changes over time. Within-group effects for time were tested using post hoc Dunnett's contrasts of baseline values vs subsequent measurements. RESULTS: The most common indication was SUI after radical prostatectomy (92.9%). Failure of previous surgeries was present in 34.3% patients and 31.3% patients had undergone secondary radiation. The mean (SD; range) surgery time was 47 (13.8; 29-112) min. Temporary urinary retention occurred in two patients (2%) and transient perineal/scrotal dysaesthesia or pain was reported by 68 patients (68.7%) and resolved after 3-4 weeks of non-opioid analgesics. There were four (4%) cases of wound infection at the site of the titanium port leading to explantation. No urethral or bladder injuries related to the device or erosions occurred. The mean (SD; range) number of adjustments to reach the desired result (dryness, improvement and/or patient satisfaction) was 3.8 (1.3; 1-6). After a mean (SD; range) follow-up time of 17.8 (1.6; 12-33) months, the overall success rate was 92% and the mean pad use decreased from 7.1 to 1.3 pads/24 h (P < 0.001). Overall, 63% were considered dry and 29% were improved. CONCLUSION: Treatment of male SUI with this self-anchored adjustable system is safe and effective.


Subject(s)
Suburethral Slings , Urinary Incontinence, Stress/surgery , Aged , Aged, 80 and over , Analysis of Variance , Humans , Male , Middle Aged , Operative Time , Postoperative Care , Postoperative Complications/etiology , Prospective Studies , Prostatectomy/adverse effects , Prosthesis Design , Quality of Life , Urinary Incontinence, Stress/etiology , Urinary Sphincter, Artificial
11.
Anticancer Res ; 32(3): 1033-6, 2012 Mar.
Article in English | MEDLINE | ID: mdl-22399628

ABSTRACT

BACKGROUND: To evaluate the reliability of sentinel lymphadenectomy compared to extended lymphadenectomy in men undergoing radical prostatectomy (RP). PATIENTS AND METHODS: A consecutive cohort of men with intermediate- to high-risk prostate cancer underwent RP with sentinel LA with intraoperative frozen section. In addition, extended LA was carried out in all cases. The endpoint was lymph node-positivity. RESULTS: In total, 54 men with a mean age of 65.3 (50.9-75.6) years were analyzed. The mean preoperative prostate-specific antigen was 10.6 (2.8-66.5) ng/ml, mean number of disease-positive cores was 5.8 (1-13), digital rectal examination was positive in 29 men (53.7%). In 12 men (22.2%), a positive lymph node was found (pN1). sLA was positive in 11 cases. One patient had a positive lymph node in eLA not found with sLA. The positive predictive value of frozen section was 50%; the respective figure for sLA compared to eLA was 91.6%. CONCLUSION: In this cohort, revealing a high prevalence of disease-positive lymph nodes, sLA was a reliable technique with a low rate of false negativity.


Subject(s)
Lymph Node Excision , Prostatectomy , Prostatic Neoplasms/surgery , Aged , Cohort Studies , Humans , Male , Middle Aged , Sentinel Lymph Node Biopsy
12.
Urol Int ; 85(3): 287-90, 2010.
Article in English | MEDLINE | ID: mdl-20664240

ABSTRACT

AIM: To analyze demographics, perioperative mortality and overall survival of radical cystectomy (RC) in patients aged 70+ years in Austria in a nation-wide registry cohort. PATIENTS AND METHODS: All patients >69 years who underwent RC in public hospitals (covering >95% of all surgical procedures) in Austria between 1992 and 2004 were analyzed. Data were provided by the Austrian Health Institute (ÖBIG). RESULTS: A total of 845 patients aged 70-89 years (mean 74) entered the analysis. The annual number of cystectomies in this age group increased from 27 in 1992 to 79 (+292%) in 2004. The mean length of hospital stay declined from 37.1 days (in 1992) to 27.1 days (in 2004). The 60-day mortality of the entire cohort was 1.5% and increased to 5.2% in patients aged 80+ years. Almost 50% of patients had to be rehospitalized within 30 days. The 5-year overall survival declined from 62% in those aged 70-74 years to 61% in those aged 75-79 years to 46% in the oldest age group (80+ years). CONCLUSIONS: The annual number of cystectomies in patients aged 70+ years increased substantially during the study period. These nation-wide registry data provide insights into the current status of RC in the elderly in Austria and demonstrate that cystectomy in this age cohort can be done with an acceptable perioperative mortality and overall survival.


Subject(s)
Cystectomy/methods , Urinary Bladder Neoplasms/surgery , Age Factors , Aged , Aged, 80 and over , Austria , Cohort Studies , Humans , Medical Oncology/methods , Registries , Time Factors , Urinary Bladder/surgery , Urinary Bladder Neoplasms/epidemiology , Urinary Bladder Neoplasms/mortality
13.
Proc Natl Acad Sci U S A ; 106(8): 2859-63, 2009 Feb 24.
Article in English | MEDLINE | ID: mdl-19196965

ABSTRACT

Benign prostatic hyperplasia (BPH) is usually described as a pathological proliferation of prostatic fibroblasts/myofibroblasts and epithelial cells. In the present study of BPH samples, we have made a morphological and immunohistochemical study of BPH prostatic sections using markers of proliferation, apoptosis, hormone receptors, and TGF-beta signaling. We found no evidence of proliferation in the stroma but in the epithelium of some ducts; 0.7% of the basal and 0.4% of luminal cells were positive for Ki67 and PCNA. Androgen receptor and estrogen receptor beta (ERbeta)1 and ERbetacx were abundant in both stromal and epithelial compartments but cells expressing ERalpha were very rare. What was very common in all BPH samples was the following: (i) regions of the ductal epithelium where the epithelial cells did not express E-cadherin, had lost their polarization, and become spindle shaped (the nuclei of these cells were strongly positive for pSmad 3 and Snail); and (ii) regions where the walls of the blood vessels were extremely thick and there was loss of endothelial layer. Loss of E-cadherin, increased pSmad 3, and high expression of Snail are all characteristic of epithelial-mesenchymal transition (EMT). We conclude that BPH is not a disease of prostatic stromal proliferation but rather of accumulation of mesenchymal-like cells derived from the prostatic epithelium and the endothelium. TGF-beta is thought to play a key role in EMT. Our data suggests that TGF-beta/Smad should be considered as targets for treatment of BPH.


Subject(s)
Prostatic Hyperplasia/etiology , Apoptosis , Cell Adhesion , Cell Proliferation , Epithelial Cells/cytology , Estrogen Receptor alpha/metabolism , Estrogen Receptor beta/metabolism , Humans , Immunohistochemistry , Male , Mesoderm/cytology , Prostatic Hyperplasia/metabolism , Prostatic Hyperplasia/pathology , Receptors, Androgen/metabolism , Signal Transduction , Transforming Growth Factor beta/metabolism
14.
Eur Urol ; 51(3): 684-8; discussion 689, 2007 Mar.
Article in English | MEDLINE | ID: mdl-16835007

ABSTRACT

OBJECTIVES: To analyse demographics and outcome of radical prostatectomy (RPE) in Austria in a nationwide series. METHODS: All patients (n=16,524) who underwent RPE in public hospitals (covering 95% of all surgical procedures) in Austria between 1992 and 2003 were analysed. Patient demographics, interventions for anastomotic strictures/urinary incontinence/inguinal hernias, perioperative mortality, and overall survival (OS) were determined. Data were provided by the Austrian Health Institute (OBIG). For decades Austria has had a public and equal access health system with compulsory insurance coverage. RESULTS: The annual number of RPEs increased from 396 in 1992 to 2640 (+666%) in 2003; the mean age at surgery declined from 64+/-6.3 yr (1992) to 62.0+/-6.7 yr (2003). An endourologic intervention for anastomotic strictures was performed in 8.5% (45-49 yr: 5.8%; 70-74 yr: 10.8%). An artificial urinary sphincter was implanted in 1.6% with a 5-fold increase from the youngest (0.5%; 45-49 yr) to 2.5% in those aged 70-74 yr. Overall, 6.4% of men underwent an inguinal herniotomy after RPE. The 30-d mortality rate was 0.12%. The 5-yr OS declined from 95% in those aged 50-59 yr to 89.8% in those aged 60-69 yr to 82% in the oldest age group (70-79 yr). CONCLUSIONS: This nationwide analysis describes the current standard of RPE in Austria. The perioperative mortality was low, the risk of total incontinence acceptable, and the OS indistinguishable to the life expectancy of the age-matched male population in Austria.


Subject(s)
Prostatectomy , Prostatic Neoplasms/surgery , Aged , Austria , Humans , Male , Middle Aged , Prostatectomy/adverse effects , Prostatic Neoplasms/mortality , Survival Rate
15.
Urol Int ; 76(4): 327-31, 2006.
Article in English | MEDLINE | ID: mdl-16679834

ABSTRACT

INTRODUCTION: A number of studies suggest that the low incidence of prostate cancer as well as benign prostatic enlargement in Asia depends on the extended consumption of phyto-oestrogens in these parts of the world. In most Asian men, phyto-oestrogen levels are multiple higher compared to Austrian (European) men. The aim of our study was to evaluate, according to the East-West decline, whether there were significant differences within the Austrian population. We compared prostate phyto-oestrogen tissue levels of men living in three different geographical regions of Austria. We further compared men living in rural and urban environments. MATERIAL AND METHODS: Prostatic tissue samples of 103 men undergoing surgery for benign prostatic hyperplasia or prostate cancer were collected and frozen at -40 degrees C. In tissue samples, enterolactone (representative for lignans) and genistein levels (representative for isoflavones) were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared tissue levels of men living in rural and urban environments and different geographical regions of Austria. RESULTS: Prostatic enterolactone tissue levels were similar in men living in an urban (median 19.1 ng/g dry weight, range 1.5-76.4) or rural environment (median 15.7 range 0.6-140.6) p = 0.99. The respective values for genistein were 20.5 ng/g dry weight (range 4.6-47.4) and 9.3 (range 0.1-156.7) p = 0.77. Furthermore, enterolactone (p = 0.1) and genistein (p = 0.65) levels were similar in three different geographic regions in Austria. CONCLUSION: No significant differences regarding genistein and enterolactone were found between our study populations. However, we found a wide variation between individual patients.


Subject(s)
Isoflavones/analysis , Phytoestrogens/analysis , Prostate/chemistry , Austria , Humans , Male , Rural Population , Urban Population
16.
World J Urol ; 24(3): 325-30, 2006 Aug.
Article in English | MEDLINE | ID: mdl-16688458

ABSTRACT

The objective of this study was to assess lower urinary tract symptoms (LUTS), urinary incontinence (UI), erectile dysfunction (ED) and quality of life after radical prostatectomy (RPE) and external beam radiation therapy (EBRT) in a "real-life" setting. A consecutive series of patients undergoing routine follow-up after RPE and EBRT at 28 Austrian institutions were analyzed. Men who received adjuvant therapy were excluded. All patients completed a questionnaire on (a) LUTS and UI, (b) sexual function and (c) quality of life. A total of 364 patients following RPE and 82 after EBRT entered this study and were compared in a matched pair analysis (1:1) based on age, PSA at diagnosis and follow-up (RPE: n=82; EBRT: n=82). Mean time-interval between treatment and current investigation was 4.6 years for RPE and 4.4 years for EBRT (n.s.). UI was reported by 41.3% after RPE and 18.8% after EBRT (P=0.001). Urgency was more frequent after EBRT, this difference, however, did not reach statistical significance. Moderate to severe ED (IIEF-5, <17) was present in 80.0% after RPE and in 80.8% after EBRT (n.s.). On a ten-point scale, RPE-patients rated their quality of life higher (7.3) than after EBRT (6.7) (P=0.01). In this "real-life" setting, RPE and EBRT had significant, yet divergent effects on LUTS, UI and sexual function. The respective numbers were substantially higher than those usually reported by physician-directed studies and centers of excellence.


Subject(s)
Kidney Diseases/diagnosis , Prostatic Neoplasms/radiotherapy , Prostatic Neoplasms/surgery , Sexual Dysfunction, Physiological/diagnosis , Urinary Incontinence/diagnosis , Austria , Humans , Kidney Diseases/therapy , Male , Prostatectomy , Quality of Life , Sexual Dysfunction, Physiological/therapy , Treatment Outcome , Urinary Incontinence/therapy
17.
World J Urol ; 23(6): 419-21, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16328554

ABSTRACT

The aim of this study is to evaluate the proportion of repeat biopsies after 7 years in men with an initial benign six- or ten-core biopsy as well as the incidence of prostate cancer (PC) in the repeat biopsies. In this retrospective longitudinal study, 116 men with an elevated prostate-specific antigen (PSA) and/or a suspicious digital rectal examination (DRE) who have had a benign prostate biopsy between January 1997 and September 1997 were included. Fifty-eight men had an initial benign six-core biopsy (median PSA 7.5 ng/ml, range 0.3-67) (group A), and 58 men had an initial benign ten-core biopsy (median PSA 7.5 ng/ml, range 0.8-91.4) (group B). We analysed men with a pathological PSA velocity, a persistently elevated PSA, an abnormal DRE, a high-grade prostatic intraepithelial neoplasia or atypical adenomatous hyperplasia, or atypical small acinar proliferation as indication for rebiopsy. Furthermore, we analysed a subgroup with exclusively an increased PSA velocity (>0.75 ng/ml per year) as indication for rebiopsy. In group A, 14 men had a follow-up biopsy. In this group, follow-up biopsies yielded PC in eight men (13.8%), six (10.3%) had a negative follow-up biopsy. In contrast, in group B only four men (3.4%) had a follow-up biopsy (P=0.005). Two of them (3.4%) had PC (P=0.02), two cases (3.4%) showed a benign histology (P=0.06). The use of an extended biopsy protocol at the initial evaluation reduces the number of repeat biopsies required and decreases the number of PC detection in the follow-up biopsy cohort.


Subject(s)
Biopsy/methods , Biopsy/statistics & numerical data , Prostate/pathology , Adult , Aged , Follow-Up Studies , Humans , Longitudinal Studies , Male , Middle Aged , Retrospective Studies , Time Factors
18.
Eur Urol ; 47(4): 499-504, 2005 Apr.
Article in English | MEDLINE | ID: mdl-15774249

ABSTRACT

OBJECTIVE: To analyse long-term rates of reoperation, myocardial infarction and mortality after transurethral (TURP) and open prostatectomy (open PE) in a nation-wide analysis. MATERIAL AND METHODS: Patients who underwent TURP (n=20,671) or open PE (n=2452) in Austria between 1992 and 1996 entered this study and were followed for up to 8 years. Actuarial cumulative incidences of reoperation (TURP, urethrotomy, bladder neck incision), myocardial infarction and death after 1, 5 and 8 years were calculated. Data were provided by the Austrian Health Institute (OBIG). RESULTS: Actuarial cumulative incidences of a secondary TURP after primary TURP at 1, 5 and 8 years were 2.9%, 5.8% and 7.4%; the respective numbers after open PE 1.0%, 2.7% and 3.4%. The overall incidence of a secondary endourological procedure (TURP, urethrotomy, bladder neck incision) within 8 years was 14.7% after TURP and 9.5% after open PE. The 8 years incidence of myocardial infarction was identical after TURP (4.8%) and open PE (4.9%). In parallel, mortality rates at 90 days (TURP: 0.7%; open PE: 0.9%), one year (2.8% vs. 2.7%), 5 years (12.7% vs. 11.8%) and 8 years (20% vs. 20.9%) was identical after TURP and open PE. CONCLUSIONS: This large-scale, contemporary, nation-wide analysis confirms the higher reoperation rate after TURP compared to open PE. We observed no excess risk of myocardial infarction or death after TURP compared to open PE.


Subject(s)
Myocardial Infarction/epidemiology , Myocardial Infarction/etiology , Prostatectomy/adverse effects , Actuarial Analysis , Adult , Aged , Aged, 80 and over , Austria , Follow-Up Studies , Humans , Male , Middle Aged , Reoperation , Risk Factors , Time Factors
19.
Urology ; 64(4): 707-11, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15491706

ABSTRACT

OBJECTIVES: To compare phytoestrogen tissue levels in men with small-volume benign prostatic hyperplasia (BPH), large-volume BPH, and prostate cancer (PCa). METHODS: Prostatic tissue samples of men consuming a Western diet who underwent surgery for BPH (n = 63) or PCa (n = 31) were collected and frozen at -40 degrees C. In the tissue samples, the enterolactone and genistein levels were determined in duplicate by monoclonal antibody-based immunoassays. We subsequently compared the tissue levels in patients with BPH and PCa and studied the impact of enterolactone and genistein on prostate volume. RESULTS: The enterolactone tissue levels were comparable in patients with BPH and PCa and revealed no correlation to prostate volume. The genistein tissue levels tended to be lower in patients with PCa (median 8.4 ng/g dry weight) compared with the entire BPH group (11.0 ng/g dry weight; P = 0.072). In addition, the genistein tissue levels were significantly greater in men with small-volume BPH (median 20.9 ng/g dry weight) compared with those with large-volume BPH (8.8 ng/g dry weight; P = 0.023). CONCLUSIONS: Our data suggest an involvement of genistein in the pathogenesis of BPH and, possibly, of PCa. The impact of enterolactone is currently unknown.


Subject(s)
4-Butyrolactone/analogs & derivatives , 4-Butyrolactone/analysis , Adenocarcinoma/chemistry , Genistein/analysis , Lignans/analysis , Phytoestrogens/analysis , Prostate/chemistry , Prostatic Hyperplasia/metabolism , Prostatic Neoplasms/chemistry , Adenocarcinoma/pathology , Aged , Aged, 80 and over , Diet , Humans , Male , Middle Aged , Organ Size , Prostate/pathology , Prostatic Hyperplasia/pathology , Prostatic Neoplasms/pathology
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