Purpose Transurethral resection of the prostate has for decades been the standard surgical therapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia, the most common benign ...neoplasm in men. To generate a contemporary reference for evolving medical and minimally invasive therapies we analyzed complications and immediate outcomes of transurethral prostate resection in a statewide multicenter study. Materials and Methods We prospectively evaluated 10,654 patients undergoing transurethral prostate resection in the state of Bavaria, Germany from January 1, 2002 until December 31, 2003. Case records containing 54 items concerning preoperative status, operation details, complications and immediate outcome, were recorded for each patient. Results The mortality rate for transurethral prostate resection was 0.10%. The cumulative short-term morbidity rate was 11.1%. The most relevant complications were failure to void (5.8%), surgical revision (5.6%), significant urinary tract infection (3.6%), bleeding requiring transfusions (2.9%) and transurethral resection syndrome (1.4%). The resected tissue averaged 28.4 gm. Incidental carcinoma of the prostate was diagnosed by histological examination in 9.8% of patients. Urinary peak flow rate increased significantly to 21.6 ± 9.4 ml per second (baseline 10.4 ± 6.8 ml per second, 1 tail p <0.0001), while post-void residual decreased to 31.1 ± 73.0 ml (baseline 180.3 ± 296.9 ml, 1-tail p <0.0001). Conclusions In a large scale evaluation comprising 44 mostly nonacademic urological departments in Bavaria, unique real-world data for transurethral prostate resection were prospectively generated. This most contemporary information should be of use to potential patients and facilitate subsumption of emerging surgical and nonsurgical benign prostatic hyperplasia treatment options.
The key of success of extraintestinal pathogenic Escherichia coli (ExPEC) to colonize niches outside the intestinal tract and to establish infection is the coordinated action of numerous virulence ...and fitness factors. The so-called high-pathogenicity island (HPI), responsible for synthesis, secretion and uptake of the siderophore yersiniabactin, proved to be an important virulence determinant. In this study we investigated the interaction of the flagellum-mediated motility and the HPI. The impairment of yersiniabactin production by deletion of irp2 or ybtA affected significantly motility. The gain of yersiniabactin production improved motility in both pathogenic and non-pathogenic E. coli strains. The loss of flagella expression had no adverse effect on the HPI. Strikingly, external iron abundance was not able to suppress activation of the HPI during motility. The HPI activity of swarming bacteria was comparable to iron deplete conditions, and could even be maximized by supplementing excessive iron. This fact is the first description of a regulatory mechanism, which does not follow the known hierarchical regulation of siderophore systems. Transcriptional reporter fusions of the ybtA promoter demonstrated that the entire promoter region with all YbtA binding sites is necessary for complete induction in both HPI-positive and HPI-negative strains. Altogether, these results suggest that the HPI is part of a complex regulatory network, which orchestrates various virulence mechanisms to optimize the overall fitness of ExPEC.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
TURP has a high rate of success, but has a perioperative morbidity rate of around 20% and long-term complications that should be acknowledged, including ejaculatory dysfunction (65%), erectile ...dysfunction (10%), urethral strictures (7%), urinary tract infection (4%), urinary incontinence (2%), and bleeding requiring transfusion (2%).2,3 To overcome these adverse effects, many alternative surgical approaches, including laser-based techniques, have been introduced. ...prospective randomised clinical trials are needed to evaluate new surgical approaches to treat benign prostatic obstruction compared with TURP using clinically meaningful outcome variables. ...tissue retrieval by laser technique was inferior to TURP (7 g vs 20 g).
Summary Background Vascular-targeted photodynamic therapy, a novel tissue-preserving treatment for low-risk prostate cancer, has shown favourable safety and efficacy results in single-arm phase 1 and ...2 studies. We compared this treatment with the standard of care, active surveillance, in men with low-risk prostate cancer in a phase 3 trial. Methods This randomised controlled trial was done in 47 European university centres and community hospitals. Men with low-risk, localised prostate cancer (Gleason pattern 3) who had received no previous treatment were randomly assigned (1:1) to vascular-targeted photodynamic therapy (4 mg/kg padeliporfin intravenously over 10 min and optical fibres inserted into the prostate to cover the desired treatment zone and subsequent activation by laser light 753 nm with a fixed power of 150 mW/cm for 22 min 15 s) or active surveillance. Randomisation was done by a web-based allocation system stratified by centre with balanced blocks of two or four patients. Best practice for active surveillance at the time of study design was followed (ie, biopsy at 12-month intervals and prostate-specific antigen measurement and digital rectal examination at 3-month intervals). The co-primary endpoints were treatment failure (histological progression of cancer from low to moderate or high risk or death during 24 months' follow-up) and absence of definite cancer (absence of any histology result definitely positive for cancer at month 24). Analysis was by intention to treat. Treatment was open-label, but investigators assessing primary efficacy outcomes were masked to treatment allocation. This trial is registered with ClinicalTrials.gov , number NCT01310894. Findings Between March 8, 2011, and April 30, 2013, we randomly assigned 206 patients to vascular-targeted photodynamic therapy and 207 patients to active surveillance. Median follow-up was 24 months (IQR 24–25). The proportion of participants who had disease progression at month 24 was 58 (28%) of 206 in the vascular-targeted photodynamic therapy group compared with 120 (58%) of 207 in the active surveillance group (adjusted hazard ratio 0·34, 95% CI 0·24–0·46; p<0·0001). 101 (49%) men in the vascular-targeted photodynamic therapy group had a negative prostate biopsy result at 24 months post treatment compared with 28 (14%) men in the active surveillance group (adjusted risk ratio 3·67, 95% CI 2·53–5·33; p<0·0001). Vascular-targeted photodynamic therapy was well tolerated. The most common grade 3–4 adverse events were prostatitis (three 2% in the vascular-targeted photodynamic therapy group vs one <1% in the active surveillance group), acute urinary retention (three 2% vs one <1%) and erectile dysfunction (two 1% vs three 1%). The most common serious adverse event in the vascular-targeted photodynamic therapy group was retention of urine (15 patients; severe in three); this event resolved within 2 months in all patients. The most common serious adverse event in the active surveillance group was myocardial infarction (three patients). Interpretation Padeliporfin vascular-targeted photodynamic therapy is a safe, effective treatment for low-risk, localised prostate cancer. This treatment might allow more men to consider a tissue-preserving approach and defer or avoid radical therapy. Funding Steba Biotech.
Abstract Context There is a continuous decline in the number of transurethral resections of the prostate (TURP) and an increase use of minimally invasive surgical therapy (MIST) for lower urinary ...tract symptoms resulting from benign prostatic enlargement. Current results from randomised controlled trials (RCT) and methodologically sound prospective studies suggest that some of the proposed procedures have the potential to replace TURP. Objective To determine the contemporary status of TURP and of the currently most commonly applied transurethral MISTs: (1) bipolar TURP, (2) bipolar transurethral vaporisation of the prostate (bipolar TUVP), (3) holmium laser enucleation of the prostate (HoLEP), and (4) potassium-titanyl-phosphate (KTP) laser vaporisation of the prostate. Evidence acquisition This meta-analysis was based on a systematic Medline search assessing the period 1997–2009. All RCTs comparing TURP and the most commonly discussed ablative treatments were included. The end points of our analyses were functional outcomes and treatment-related adverse events. Evidence synthesis Twenty-seven publications involving 23 different RCTs with a total of 2245 patients provided the highest level of evidence available (level 1b) and were fully assessed. Meta-analysis was conducted with SAS v.9.1.3 (SAS Institute, Cary, NC, USA). Forest plots were produced using the R software. Pooled odds ratios and 95% confidence intervals were calculated between various operative techniques versus TURP. Functional results between the specific transurethral procedures versus TURP were summarised as differences in means. Conclusions This meta-analysis demonstrates statistically comparable efficacy and overall morbidity for MISTs versus contemporary TURP. Type, category (minor vs major), and the number of complications (safety profile) vary specifically for each of the different transurethral techniques. We feel that the individual patient’s clinical profile should be carefully assessed to identify the most appropriate transurethral technique.
Mirabegron is used for treatment of storage symptoms in overactive bladder (OAB) caused by spontaneous bladder smooth muscle contractions. However, owing to limitations in available studies using ...human tissues, central questions are still unresolved, including mechanisms underlying improvements by mirabegron and its anticontractile effects in the detrusor. Here, we assessed concentration-dependent mirabegron effects on contractions of human detrusor tissues in frequency-response curves and concentration-response curves for different cholinergic and noncholinergic agonists. Detrusor tissues were sampled from patients undergoing radical cystectomy. Contractions were induced by electric field stimulation (EFS) and by cumulative concentrations of cholinergic agonists, endothelin-1, and the thromboxane A
analog U46619. EFS-induced contractions were inhibited using 10
M mirabegron, but not using 1
M. Inhibition by 10
M mirabegron was resistant to the
-adrenergic antagonist L-748,337. Concentration-dependent contractions by carbachol were not inhibited by 1
M or 10
M mirabegron. Concentration-response curves for methacholine were slightly right-shifted by 10
M, but not 1
M mirabegron. Concentration-dependent contractions by endothelin-1 or U46619 were not changed by mirabegron. In contrast, the muscarinic antagonist tolterodine right-shifted concentration-response curves for carbachol and methacholine and inhibited EFS-induced contractions. In conclusion, inhibition of neurogenic contractions in isolated detrusor tissues by mirabegron requires concentrations highly exceeding known plasma levels during standard dosing and the known binding constant (K
values) for
-adrenoceptors. Full contractions by cholinergic agonists, endothelin-1, and U46619 are not affected by therapeutic concentrations of mirabegron. Improvements of storage symptoms are most likely not imparted by inhibition of
-adrenoceptors in the bladder wall itself. SIGNIFICANCE STATEMENT: Mirabegron is used for overactive bladder (OAB) treatment, but the underlying mechanisms are unclear, and preclinical and clinical findings are controversial due to limitations in available studies. Our findings suggest that inhibition of detrusor contractions by mirabegron is limited to neurogenic contractions, which requires unphysiologic concentrations and does not involve
-adrenoceptors. Mechanisms accounting for improvements of OAB by mirabegron are located outside the urinary bladder.
To provide an overview on the current status of the long-term outcomes of instrumental treatment options for patients with lower urinary tract symptoms that are suggestive of bladder outlet ...obstruction.
Based on MEDLINE database searches, we performed a systematic review of the literature with a focus on peer-reviewed articles about surgical benign prostatic hyperplasia (BPH) therapy published between 2000 and 2005. Special emphasis was given to randomized controlled trials on long-term outcome with a minimum follow-up of five years.
Data on clinical outcome with a follow-up of more than 10 years are available for open prostatectomy (OP), transurethral resection of the prostate (TURP), and transurethral microwave therapy. Studies with a follow-up of at least five years are obtainable for transurethral incision of the prostate, transurethral vaporisation of the prostate, transurethral needle ablation of the prostate, Holmium:YAG laser enucleation of the prostate, potassium-titanyl-phosphate laser vaporization of the prostate, and interstitial laser coagulation of the prostate. Among these long-term reports, OP and TURP provide the most durable results.
The most substantial long-term data on surgical procedures for BPH are available for conventional therapy, namely TURP. Concerning the techniques that have emerged within the last decade, there is clear evidence that the outcomes are more sustainable for truly ablative and thus deobstructing procedures.
PDF
