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.
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.
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.
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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).
The β3-adrenoceptor agonist mirabegron is available for the treatment of storage symptoms of overactive bladder, including frequency, urgency, and incontinence. The off-target effects of mirabegron ...include binding to α1-adrenoceptors, which are central in the treatment of voiding symptoms. Here, we examined the structure–function relationships in the binding of mirabegron to a cryo-electron microscopy structure of α1A. The binding was simulated by docking mirabegron to a 3D structure of a human α1A-adrenoceptor (7YMH) using Autodock Vina. The simulations identified two binding states: slope orientation involving 10 positions and horizontal binding to the receptor surface involving 4 positions. No interactions occurred with positions constituting the α1A binding pocket, including Asp-106, Ser-188, or Phe-312, despite the positioning of the phenylethanolamine moiety in transmembrane regions close to the binding pocket by contact with Phe-288, -289, and Val-107. Contact with the unique positions of α1A included the transmembrane Met-292 during slope binding and exosite Phe-86 during horizontal binding. Exosite binding in slope orientation involved contact of the anilino part, rather than the aminothiazol end, to Ile-178, Ala-103, and Asn-179. In conclusion, contact with Met-292 and Phe-86, which are unique positions of α1A, accounts for mirabegron binding to α1A. Because of its lack of interactions with the binding pocket, mirabegron has lower affinity compared to α1A-blockers and no effects on voiding symptoms.
Abstract Context This review focuses on the prediction of recurrence and progression in non–muscle invasive bladder cancer (NMIBC) and the treatments advocated for this disease. Objective To review ...the current status of epidemiology, recurrence, and progression of NMIBC and the state-of-the art treatment for this disease. Evidence acquisition A literature search in English was performed using PubMed and the guidelines of the European Association of Urology and the American Urological Association. Relevant papers on epidemiology, recurrence, progression, and management of NMIBC were selected. Special attention was given to fluorescent cystoscopy, the new World Health Organisation 2004 classification system for grade, and the role of substaging of T1 NMIBC. Evidence synthesis In NMIBC, approximately 70% of patients present as pTa, 20% as pT1, and 10% with carcinoma in situ (CIS) lesions. Bladder cancer (BCa) is the fifth most frequent type of cancer in western society and the most expensive cancer per patient. Recurrence (in ≤80% of patients) is the main problem for pTa NMIBC patients, whereas progression (in ≤45% of patients) is the main threat in pT1 and CIS NMIBC. In a recent European Organisation for Research and Treatment of Cancer analysis, multiplicity, tumour size, and prior recurrence rate are the most important variables for recurrence. Tumour grade, stage, and CIS are the most important variables for progression. Treatment ranges from transurethral resection (TUR) followed by a single chemotherapy instillation in low-risk NMIBC to, sometimes, re-TUR and adjuvant intravesical therapy in intermediate- and high-risk patients to early cystectomy for treatment-refractory high-risk NMIBC. Conclusions NMIBC is a heterogeneous disease with varying therapies, follow-up strategies, and oncologic outcomes for an individual patient.
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