Physiological and pathological regulation of the autonomic control of urinary bladder contractility

The urinary bladder stores urine for most of the day, a process facilitated by beta-adrenergic receptor-mediated detrusor relaxation and alpha(1)-adrenergic receptor-mediated contraction of the bladder neck. Physiological voiding is caused by detrusor contraction induced by muscarinic receptor stimulation. This manuscript reviews data on alterations of alpha(1)- and beta-adrenergic and of muscarinic responsiveness of the detrusor related to gender, developmental maturation, ageing and pathophysiological conditions such as diabetes, arterial hypertension and bladder outlet obstruction, all of which can be associated with alterations of bladder function such as bladder overactivity. The existing data show that none of the conditions associated with bladder overactivity exhibit increased muscarinic receptor responsiveness which could explain the clinical observations; while not being fully consistent, they if anything show a reduced responsiveness. On the other hand, more limited data demonstrate that alpha(1)-adrenergic responsiveness may be enhanced and beta-adrenergic responsiveness reduced in states associated with bladder overactivity. However, the existing data are too sparse and/or too inconsistent to allow definitive conclusions. Thus, alterations distinct from those of autonomic receptors may be better candidates to explain bladder dysfunctio

Is the use of parasympathomimetics for treating an underactive urinary bladder evidence-based?

An underactive urinary bladder (UUB), often occurring after surgery, can lead to urinary retention even in otherwise healthy people. We systematically reviewed published reports to determine whether the use of parasympathomimetic agents is warranted in patients with a UUB. Agents allegedly useful in treating UUB were identified from urology and pharmacology textbooks. A systematic search for randomized clinical trials in patients with UUB using these agents revealed 10 such studies. Controls typically received placebo or no treatment. While three studies reported statistically significant improvements relative to the control group, six did not and one even reported a significant worsening of symptoms. There was no evidence for differences between individual drugs, specific uses of such drugs, or in outcome measures. We conclude that the available studies do not support the use of parasympathomimetics for treating UUB, specifically when frequent and/or serious possible side-effects are taken into accoun

Do alpha1-adrenoceptor antagonists improve lower urinary tract symptoms by reducing bladder outlet resistance?

AIMS: To test the hypothesis that improvements of lower urinary tract symptoms (IPSS) upon treatment with an alpha-blocker are due to reduction of bladder outlet obstruction (assessed as the bladder outlet obstruction index, BOOI); relationships of either with free flow Q(max) were also explored. METHODS: The database of a large placebo-controlled, randomized, double-blind study with the alpha-blocker tamsulosin was analyzed retrospectively. Patients were stratified into lower and upper halves according to baseline IPSS, Q(max) or BOOI and treatment-associated alterations thereof. In these strata differences between values for the other two parameters were analyzed, for example, improvement of IPSS and Q(max) were compared in patients with below and above median improvement of BOOI. RESULTS: Patients with below and above median baseline for one parameter, for example, IPSS had rather similar values for the other two parameters, for example, Q(max) and BOOI. Likewise, patients based upon baseline strata for one parameter had rather similar improvements of the other two parameters. Most importantly, patients with below and above median treatment-associated improvements of one parameter, for example, BOOI exhibited only small if any difference for alterations of the other two parameters, for example, IPPS and Q(max). CONCLUSIONS: We conclude that IPSS, free flow Q(max) and BOOI are only loosely related at baseline. More importantly, treatment-induced improvements of these parameters are also only loosely related. These data do question the hypothesis that alpha-blockers largely improve lower urinary tract symptoms by reducing bladder outlet obstruction and suggest that they may also act independent of prostatic smooth muscle ton

Renal Cell Carcinoma : Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review

Background: The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA) microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Materials and Methods: Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. Results: The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Conclusion: Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future

Renal Cell Carcinoma : Alternative Nephron-Sparing Treatment Options for Small Renal Masses, a Systematic Review

Background: The standard treatment of T1 renal cell carcinoma (RCC) is (partial) nephrectomy. For patients where surgery is not the treatment of choice, for example in the elderly, in case of severe comorbidity, inoperability, or refusal of surgery alternative treatment options are available. These treatment options include active surveillance (AS), radiofrequency ablation (RFA), cryoablation (CA) microwave ablation (MWA), or stereotactic body radiotherapy (SBRT). In the present overview, the efficacy, safety, and outcome of these different options are summarized, particularly focusing on recent developments. Materials and Methods: Databases of MEDLINE (through PubMed), EMBASE, and the Cochrane Library were systematically searched according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The search was performed in December 2016, and included a search period from 2010 to 2016. The terms and synonyms used were renal cell carcinoma, active surveillance radiofrequency ablation, microwave ablation, cryoablation and stereotactic body radiotherapy. Results: The database search identified 2806 records, in total 73 articles were included to assess the rationale and clinical evidence of alternative treatment modalities for small renal masses. The methodological quality of the included articles varied between level 2b and level 4. Conclusion: Alternative treatment modalities, such as AS, RFA, CA, MWA, and SBRT, are treatment options especially for those patients who are unfit to undergo an invasive treatment. There are no randomized controlled trials available comparing surgery and less invasive modalities, leading to a low quality on the reported articles. A case-controlled registry might be an alternative to compare outcomes of noninvasive treatment modalities in the future

Role of transforming growth factor beta in rat bladder smooth muscle cell proliferation

Conditions associated with hypertrophy of the urinary bladder have repeatedly been associated with an increased urinary excretion of transforming growth factor (TGF) beta in both rats and patients. Because TGFbeta can have both growth-promoting and -inhibiting effects, we have studied its effects on cell growth and death in primary cultures of rat bladder smooth muscle cells. TGFbeta1, TGFbeta2, or TGFbeta3 did not cause apoptosis, but all three isoforms inhibited DNA synthesis with similar potency (EC(50) of approximately 0.1 ng/ml) and efficacy. Such inhibition was antagonized by a specific TGFbeta receptor antagonist and independent of the presence of serum. Mitogen-activated protein kinases (MAPKs) are involved in the control of cell growth, and all three TGFbeta isoforms inhibited activation of the extracellular signal-regulated kinase, c-Jun NH(2)-terminal kinase, and p38 MAPK subfamilies. Nevertheless, the inhibitory effects of the TGFbeta isoforms on DNA synthesis were not affected by presence of inhibitors of the three MAPK pathways. TGFbeta did not alter cell size as measured by flow cytometry or mitochondrial activity, an integrated measure of cell size and number. We conclude that our data do not support the hypothesis that TGFbeta is a mediator of rat bladder hypertroph