Antimuscarinic drugs are generally thought to exert their therapeutic action on detrusor overactivity by reducing the ability of the detrusor muscle to contract. We review currently available published data to establish whether there is any evidence to support this contention. Using a PubMed data search, only 14 original articles (including two abstracts) were found that contained cystometric data for both filling and voiding phases and where the actions of antimuscarinic drugs have been reported in detail. These articles were separated into three groups dealing with neuropathic patients (three papers), patients with idiopathic overactive bladder (four papers) and a group whose aetiology was unclear (seven papers). Variables relating to bladder function during the filling phase (time of first desire to void, time to first unstable contraction, and bladder capacity) were identified. Similarly, variables relating to voiding were identified and compared (e.g. maximum detrusor pressure and detrusor pressure at maximum flow rate). The antimuscarinic drugs have a clearly significant effect on sensations of urge, time to first sensation to void, maximum bladder capacity, decrease in voiding frequency and reduction in incontinence episodes. However, only one article (studying neuropaths) reported a significant reduction of the variables associated with detrusor contraction. The remaining four studies (idiopaths/not stated), reported no change in bladder contractility with antimuscarinic drugs. Thus the available data do not support the conclusion that antimuscarinic drugs at doses used in current clinical practice exert their therapeutic action by inhibiting detrusor contractility, but they suggest effects on variables associated with sensation.
What ' s known on the subject? and What does the study add? Apart from bladder tumour multiplicity, size, stage, grade and presence of cis, early recurrence following white light TURBT for new bladder tumours is also determined by surgeon experience, completeness of resection and presence or absence of detrusor muscle in the specimen.This study aims to validate surgeon experience and detrusor muscle as independent predictors of early recurrence following apparently complete white light TURBT in new bladder tumours. OBJECTIVE• To validate in patients undergoing fi rst transurethral resection of bladder tumour (TURBT) for non-muscle-invasive bladder cancer (NMIBC), the presence/absence of detrusor muscle (DM) in the specimen and surgeon experience as independent predictors of the quality of TURBT. PATIENTS AND METHODS• Patients with new NMIBC, who had undergone complete fi rst resections were recruited from a prospectively maintained cohort from the 1980s at the Western General Hospital, Edinburgh, UK and a contemporary cohort from the Aberdeen Royal Infi rmary, UK.• Tumour size, multiplicity, surgeon category, presence or absence of DM in the specimen, grade, stage, fi ndings at fi rst check cystoscopy and early re-TURBT were evaluated.• Surgeons were stratifi ed into a senior group (consultant and trainees in year fi ve or six) and a junior group (trainees below year fi ve).• Early recurrence, or recurrence rate at the fi rst follow up cystoscopy (RRFFC), was used to measure quality and was defi ned as fi nding pathologically confi rmed tumour at early re-TURBT or the fi rst check cystoscopy. RESULTS• From a total of 566 patients evaluated from both cohorts, 473 NMIBC specimens were suitable for analysis.• Logistic regression multivariate analysis revealed that the absence of DM was associated with a higher RRFFC (odds ratio [ OR ] = 3.6, 95% CI = 1.7 -7.5, P < 0.001).• Senior surgeons were more likely to resect DM (OR = 4.9, 95% CI = 2.3 -10.7, P < 0.001)• Senior surgeons were independently associated with a lower RRFFC (OR = 5.3, 95% CI = 2.1 -12.9, P < 0.001). CONCLUSIONS• Detrusor muscle status at the fi rst, apparently complete, TURBT and surgeon ' s experience independently predict the quality of TURBT.• Documented complete resection by experienced surgeons with DM presence (good quality white-light TURBT) should be considered a benchmark for white-light TURBT in NMIBC. KEYWORDSbladder cancer , transurethral resection of bladder tumour , quality control , recurrence , detrusor muscle Study Type -Therapy (cohort) Level of Evidence 2b
Study Type – Aetiology (case series) Level of Evidence 4 What's known on the subject? and What does the study add? The factors taken into consideration when determining when and where to void are poorly understood. Studies on bladder sensations, obtained during cystometry of from voiding diaries, are proving difficult to transfer to everyday experiences. There is therefore a need to explore what does influence when and where to void. This study, using focus groups, highlights the fact that many voids are driven by behavioural factors not by sensations of desire or need to void. It is further noted that a key factor in the final decision to void is an awareness of bladder volume. The concepts of ‘cognitive voiding’ informed by ‘bladder awareness’ are introduced and, if correct, will influence the way studies are devised and interpreted to explore lower urinary tract dysfunction and pharmacotherapy. OBJECTIVE To investigate the inter‐relationship between conscious decision‐making processes and bladder sensation in determining the need, time and place to void SUBJECTS AND METHODS The approach used interview focus groups and qualitative thematic analysis. In this preliminary study, 25 women were included (aged 21–90 years) meeting in groups of one to five on four occasions. RESULTS The thematic analysis yielded six themes: temporal and cognitive maps, risk issues, habituation and opportunistic behaviour and awareness of the bladder. For most voids, the decision to void was not based on sensation but determined by multiple factors: personal knowledge of time of last void, anticipated time to next void, proximity of toilets, a risk assessment or habituated behaviour. As the bladder filled the subjects described an increasing awareness of their bladder. Such sensations were not immediately associated with desire to void. Rather, these sensations were described as influencing the cognitive processes of considering when and where to void. A sub‐group of subjects reported little awareness as their bladder filled, experiencing only sudden strong sensations that needed immediate action for fear of leakage. CONCLUSIONS The decision to void is primarily a cognitive process influenced by multiple elements of which bladder awareness is only one. Mechanisms generating awareness may be intensified or lost reflecting possible different pathological states. The importance of these observations in relation to current views of normal and abnormal voiding is discussed.
OBJECTIVES To analyse pressure changes induced by muscarinic agonists on the isolated bladder in order to examine whether there are different responses representing different components of a motor/sensory system within the bladder wall. MATERIALS AND METHODS Whole isolated bladders from 19 female guinea‐pigs (280–400 g) were used. A cannula was inserted into the urethra to monitor intravesical pressure and the bladder was suspended in a heated chamber containing carboxygenated physiological solution at 33–36 °C. Initially, the responses to the cholinergic agonists, arecaidine but‐2‐ynyl ester tosylate and carbachol were assessed. Then, in an attempt to identify the muscarinic receptor subtypes involved, the effects of selective muscarinic antagonists on the arecaidine‐induced bladder responses were assessed. The antagonists used were the relatively M3‐selective 4‐diphenylacetoxy‐N‐methylpiperidine methobromide (4‐DAMP) and darifenicin, and relatively M2‐selective AFDX‐116. All drugs were added to the solution bathing the ablumenal surface of the bladder. RESULTS The whole bladders exposed to cholinergic agonists respond with complex changes in intravesical pressure. Immediately after application of the agonist there was a burst of high frequency transient contractions. During continued application of agonist the frequency of the transients decreased and their amplitude increased. Thus, there appear to be two components to the response: an initial fast phase and a later slow component. The maximum frequency of the initial burst increased with increasing concentrations of agonist. By contrast, the frequency of the transients in the steady state showed little dependence on agonist concentration. There were quantitative differences between the responses to arecaidine and carbachol. Arecaidine was less effective in generating the initial burst of high‐frequency activity and the transients were significantly larger. At low dose, arecaidine was more effective in producing the large transients in the steady state. Pre‐exposure of the bladder to 4‐DAMP (0.1–10 nm) or darifenicin (0.1–10 nm) significantly reduced the frequency of the initial burst of activity; 0.3 nm 4‐DAMP reduced the frequency by half. In this concentration range, 4‐DAMP reduced the amplitude of the initial transients but did not affect the frequency of the transients in the steady state. There were similar results with darifenicin. However, darifenicin was less effective in reducing the amplitude of the initial transients. By contrast, ADFX‐116 had little effect on the frequency of the initial transients but did reduce amplitude; 300 nm AFDX‐116 was needed to reduce the frequency of the initial burst by half. CONCLUSIONS This analysis suggests that there are different but interrelated mechanisms in the isolated bladder contributing to complex contractile activity. Three components can be identified: a mechanism operating during voiding to produce a global contraction of the whole bladder and two mechanisms, pacemaker and conductive, involved in generati...
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