Morbidity associated with operative management of bladder stones in spinal cord-injured patients.

STUDY DESIGN: Retrospective cohort study of spinal cord-injured (SCI) patients undergoing bladder stone removal operations between 1999 and 2013. OBJECTIVES: To determine the morbidity associated with different operative management of bladder stones in SCI patients. SETTING: National Spinal Injuries Unit, Stoke Mandeville Hospital, UK. METHODS: Data on age, sex, level and Frankel classification of spinal cord injury, method of bladder drainage, method of bladder stone removal, complications and length of stay were collected from patient records. Complication was defined as bladder perforation, sepsis or persistent haematuria. Predictors of complications and length of stay were determined using univariate and multivariate regression analyses. RESULTS: Overall, 112 consecutive bladder stone removal operations were performed, one open cystolithotomy and 111 transurethral procedures utilising simple washout, stone punch or electrohydraulic lithotripsy (EHL). Of these procedures, 17% (19/112) had complications; 0/11 (0%) following washout, 5/44 (11%) after stone punch, 3/12 (25%) following EHL and 10/26 (38%) after combined procedures using stone punch and EHL. In a multivariate model, patients with a cervical-level injury and those undergoing a combined procedure were significantly more likely to have a complication (P=0.032 and P=0.046). Length of stay was longer following a complication, the mean was 4.18 days compared with 1.37 days without a complication (P<0.001). Controlling complications and age, use of a combined procedure was associated with significantly longer stay than use of stone punch alone. CONCLUSION: This study provides important outcome data that should guide operative procedure choice and inform patients about possible risks during consent. It sets a benchmark that other centres can evaluate their outcomes against.

Obtaining patient feedback in an outpatient lithotripsy service is facilitated by use of a touch-screen tablet (iPad™) survey.

There is now a requirement for every doctor in the UK to obtain patient feedback for revalidation. This can be an onerous and time-consuming task. The objective of this study was to evaluate a novel electronic patient feedback method in an outpatient lithotripsy service setting. Between September 2013 and January 2014, 100 patients attending an outpatient lithotripsy service in Oxford were asked to complete a selection of pre-approved NHS questions about the service they had received. Questions were presented on a tablet device (iPad™) and answered using the touch screen. Departmental staff were unaware of the questions in the survey. Patients were asked to complete the survey by an independent research nurse. Questions were created online in a free-to-use web-based survey application and presented on the tablet device in a user-friendly format via an application. Data were uploaded via wifi™ to the online system. Data were viewed, automatically analysed and displayed graphically. The age range of the patients surveyed was 20-80 years of age. All 100 patients completed the survey without difficulty. All patients answered every question. Data could be automatically viewed, analysed and presented graphically. This method of collecting patient feedback proved to be rapid and efficient. The feedback highlighted a high patient satisfaction with the lithotripsy service. A touch screen tablet device is an efficient and effective method of collecting truly objective patient feedback. This method of patient feedback could be employed in other clinical environments to collect data for revalidation purposes.

Label-free quantitative proteomics reveals differentially regulated proteins influencing urolithiasis.

Urinary proteins have been implicated as inhibitors of kidney stone formation (urolithiasis). As a proximal fluid, prefiltered by the kidneys, urine is an attractive biofluid for proteomic analysis in urologic conditions. However, it is necessary to correct for variations in urinary concentration. In our study, individual urine samples were normalized for this variation by using a total protein to creatinine ratio. Pooled urine samples were compared in two independent experiments. Differences between the urinary proteome of stone formers and nonstone-forming controls were characterized and quantified using label-free nano-ultraperformance liquid chromatography high/low collision energy switching analysis. There were 1063 proteins identified, of which 367 were unique to the stone former groups, 408 proteins were unique to the control pools, and 288 proteins were identified for comparative quantification. Proteins found to be unique in stone-formers were involved in carbohydrate metabolism pathways and associated with disease states. Thirty-four proteins demonstrated a consistent >twofold change between stone formers and controls. For ceruloplasmin, one of the proteins was shown to be more than twofold up-regulated in the stone-former pools, this observation was validated in individuals by enzyme-linked immunosorbent assay. Moreover, in vitro crystallization assays demonstrated ceruloplasmin had a dose-dependent increase on calcium oxalate crystal formation. Taken together, these results may suggest a functional role for ceruloplasmin in urolithiasis.

Understanding waiting lists as the matching of surgical capacity to demand: are we wasting enough surgical time?

If surgical 'capacity' always matched or exceeded 'demand' then there should be no waiting lists for surgery. However, understanding what is meant by 'demand', 'capacity' and 'matched' requires some mathematical concepts that we outline in this paper. 'Time' is the relevant measure: 'demand' for a surgical team is best understood as the total min required for the surgery booked from outpatient clinics every week; and 'capacity' is the weekly operating time available. We explain how the variation in demand (not just the mean demand) influences the analysis of optimum capacity. However, any capacity chosen in this way is associated with only a likelihood (that is, a probability rather than certainty) of absorbing the prevailing demand. A capacity that suitably absorbs the demand most of the time (for example, > 80% of weeks) will inevitably also involve considerable waste (that is, many weeks in which there is spare, unused capacity). Conversely, a level of capacity chosen to minimise wasted time will inevitably cause an increase in size of the waiting list. Thus the question of how to balance demand and capacity is intimately related to the question of how to balance utilisation and waste. These mathematical considerations enable us to consider objectively how to manage the waiting list. They also enable us critically to analyse the extent to which philosophies adopted by the National Health Service (such as 'Lean' or 'Six Sigma') will be successful in matching surgical capacity to demand.

Sphincterotomy and the treatment of detrusor-sphincter dyssynergia: current status, future prospects.

STUDY DESIGN: Literature review of current treatment options for detrusor-sphincter dyssynergia (DSD) in spinal cord injury. OBJECTIVES: To review the outcomes and complications associated with external sphincterotomy and to summarise the results and complications of alternative treatment options for detrusor-sphincter dyssynergia in spinal cord injury. In addition, we propose a potential alternative future drug treatment for external sphincter dyssynergia based upon recent research on the neuropharmacology of the external urethral sphincter. SETTING: The National Spinal Injuries Centre, Stoke Mandeville Hospital, Aylesbury, UK. METHODS: Medline search from 1966 to 2002 using the words 'external sphincterotomy', 'detrusor-sphincter dyssynergia' and 'neurogenic bladder combined with surgery'. RESULTS: While external sphincterotomy is an effective treatment for DSD, a significant number of men following this procedure continue to have high intrarenal pressures, recurrent urinary infection or troublesome autonomic dysreflexia and a worryingly high proportion demonstrate persistently raised leak point pressures, putting them at subsequent risk of renal damage. Alternative treatments for external sphincter dyssynergia include urethral stents and balloon dilatation, both of which are effective. However, over the long term stents can undergo encrustation and there remains a definite risk of stent migration necessitating stent removal or replacement. Balloon dilatation of the external sphincter is associated with a risk of subsequent stricture formation. Intraurethral Botulinum A toxin seems to be effective though there have been no large randomised studies comparing it against placebo. However, it is not a durable treatment option and it has not found a common place in the treatment of DSD. There is now a considerable amount of experimental data from both animal and human studies to suggest that nitric oxide (NO) is an important physiological inhibitory neurotransmitter in the urethral sphincter, mediating relaxation of the external urethral sphincter. The potential role of sphincter NO augmentation for treatment of DSD is discussed. CONCLUSION: External sphincterotomy remains the mainstay of treatment for urodynamically significant detrusor-sphincter dyssynergia, but in recent years a number of effective, alternative treatment options have become available. While at present there is no effective systemic drug treatment, recent research into external sphincter neuropharmacology suggests that systemic or topical augmentation of external sphincter NO may provide an effective method for lowering sphincter pressure.

Radiation-induced haemorrhagic cystitis.

OBJECTIVES: In this article we review the literature concerning the frequency and management of severe haemorrhagic radiation-induced cystitis. METHODS: A Medline search was performed from 1966 to 1999 for articles in English. A total of 309 references were found. Abstracts and complete articles were reviewed. RESULTS: Severe haemorrhagic cystitis following radiotherapy remains a relatively rare event. However, the fact that it is relentlessly progressive and that treatment options are suboptimal makes it clinically important. The incidence of severe haematuria following pelvic irradiation is difficult to determine from the literature although most studies state an incidence of less than 5% which increases with time since irradiation. Methods of treatment include simple bladder irrigation, cystodiathermy, oral, parenteral and intravesical agent, hyperbaric oxygen therapy, hydrodistension, internal iliac embolisation, urinary diversion and cystectomy. No management strategy is 100% successful and a stepwise progression in treatment intensity is often required. CONCLUSION: The articles available on radiation-induced haemorrhagic cystitis are principally retrospective and involve small numbers of patients who have had several different treatment modalities. In the absence of randomised studies comparing treatments, it is impossible to set definitive rules about management but patients with this condition probably warrant early and aggressive treatment.

Augmentation of nitric oxide to treat detrusor-external sphincter dyssynergia in spinal cord injury.

Detrusor-external sphincter dyssynergia (DSD) is a common cause of bladder outlet obstruction in men with spinal cord injuries, which if left untreated leads ultimately to renal failure. External sphincterotomy is currently the main treatment for DSD. However, obstruction persists in a substantial proportion of cases after this procedure. There is no effective drug treatment for DSD. Nitric oxide is an inhibitory neurotransmitter synthesised by nitric oxide synthase. Both animal and human studies suggest that nitric oxide mediates urethral sphincter relaxation. Nitric-oxide-synthase staining neurons have been identified in very high density in the urethral sphincters of a variety of animals and in human beings. Relaxation of the urethral sphincter is abolished by inhibitors of nitric oxide synthase and enhanced by nitric oxide donors. Mice with targeted deletion of the gene, for neuronal nitric oxide have urethral sphincters that do not relax in response to electrical stimulation. We hypothesise that augmentation of external sphincter nitric oxide could be an effective pharmacological treatment for DSD. Currently available nitric oxide donors such as glyceryl trinitrate or isosorbide mononitrate could be used to deliver nitric oxide to the urethral sphincter. The variable pharmacokinetics of these drugs combined with different modes of delivery (sublingual, buccal, or oral) could be used to achieve both short-term and long-term increases in concentrations of sphincter nitric oxide, thereby resulting in either acute or chronic lowering of urethral pressure. The safety and efficacy of this potential treatment for DSD needs to be established in clinical trials of men with spinal cord injures with DSD.

Relation of nocturnal polyuria of the elderly to essential hypertension.

Nocturnal polyuria is common in the elderly. In this condition the normal circadian rhythm of urine production is reversed so that urine flow is higher at night than during the day. Elderly men with nocturnal polyuria are commonly referred for prostate surgery, which, not surprisingly, fails to relieve their symptoms. Compared with controls, patients with nocturnal polyuria have higher nocturnal sodium excretion but not higher nocturnal free-water clearance. Similar results have been obtained in children with nocturnal enuresis. Use of vasopressin analogues to induce water retention in elderly patients with nocturnal polyuria is illogical and potentially hazardous; nocturia can be more safely alleviated by diuretic therapy. Nocturnal polyuria in the elderly is associated with hypertension: this is consistent with studies in younger age groups that show that essential hypertension is associated with nocturia and with increased night/day ratios for sodium excretion. We propose that nocturnal polyuria and essential hypertension share some of the same pathophysiological determinants. Specifically, we suggest that a defect in the nitric-oxide pathway may lead to resetting of the pressure-natriuresis relation in the kidney, sodium retention, and compensatory nocturnal natriuresis. This suggestion is consistent with evidence that ageing and essential hypertension are both associated with defects in the nitric-oxide pathway. Our hypothesis has obvious therapeutic implications. More generally, studying the pathogenesis of nocturnal polyuria in the elderly may advance our understanding of the pathogenesis of essential hypertension.

Failure to void after transurethral resection of the prostate and mode of presentation.

OBJECTIVES: Contemporary audits and reviews of outcome after transurethral resection of the prostate (TURP) make little reference to failure to void following catheter removal after this operation. There have been few reports of the likelihood of a successful trial without a catheter after TURP related to mode of presentation. We report the results of a retrospective review of outcome of TURP related to mode of presentation, age, and prostate histologic findings in a consecutive series of patients in a London Teaching Hospital. METHODS: A consecutive series of 379 patients (381 TURPs) was reviewed to document the incidence of and risk factors for failure to void following initial trial without a catheter after TURP. RESULTS: Twelve percent of men failed to void after TURP on the initial trial without a catheter. In those patients presenting with lower urinary tract symptoms, there were no instances of failure to void. Ten percent of patients with acute retention (painful inability to void, urine volume less than 800 mL), 38% with chronic retention (maintenance of spontaneous voiding, bladder volume greater than 500 mL), and 44% with acute on chronic retention (painful retention, urine volume greater than 800 mL) failed to void after TURP. Only 1% of patients required management by long-term catheterization. Failure to void on catheter removal was not related to age or prostate histologic findings. CONCLUSIONS: Bladder volume at initial presentation in patients with urinary retention provides important information about the likelihood of re-establishing spontaneous voiding catheter removal following TURP. Patients should be warned that there is a significant chance of failure to void after TURP, the exact risk depending on their mode of presentation, but that most will ultimately not require a permanent indwelling catheter.

The ICS-'BPH' Study: uroflowmetry, lower urinary tract symptoms and bladder outlet obstruction.

OBJECTIVE: To explore the relationship between uroflow variables and lower urinary tract symptoms (LUTS): to define performance statistics (sensitivity, specificity, positive and negative predictive values) for maximum urinary flow rate (Qmax) with respect to bladder outlet obstruction (BOO) at various threshold values; and to investigate the diagnostic value of low-volume voids. PATIENTS AND METHODS: The study comprised 1271 men aged between 45 and 88 years recruited from 12 centres in Europe, Australia, Canada, Taiwan and Japan over a 2-year period. Symptom questionnaires, voiding diaries, uroflowmetry and pressure-flow data were recorded. The relationship between uroflow variables and symptoms, Qmax and BOO, and the diagnostic performance of low volume voids were analysed. RESULTS: The relationship between symptoms and uroflow variables was poor. The mean difference between home-recorded and clinic-recorded voided volumes was -48 mL. Qmax was significantly lower in those with BOO (9.7 mL/s for void 1) than in those with no obstruction (12.6mL/s; P<0.001) and Qmax was negatively correlated with obstruction grade (Spearman's correlation coefficient -0.3, P<0.001), even when controlling for the negative correlation between age and Qmax (Spearman's partial correlation coefficient -0.29, P<0.001). A threshold value of Qmax of 10 mL/s had a specificity of 70%, a positive predictive value (PPV) of 70% and a sensitivity of 47% for BOO. The specificity using a threshold Qmax of 15 mL/s was 38%, the PPV 67% and the sensitivity 82%. Those voiding <150 mL (n=225) had a 72% chance of BOO (overall prevalence of BOO 60%). In those voiding >150 mL the likelihood of BOO was 56%. The addition of a specific threshold of 10 mL/s to these higher volume voiders improved the PPV for BOO to 69%. CONCLUSION: While uroflowmetry cannot replace pressure-flow studies in the diagnosis of BOO. it can provide a valuable improvement over symptoms alone in the diagnosis of the cause of lower urinary tract dysfunction in men presenting with LUTS. This study provides performance statistics for Qmax with respect to BOO: such statistics may be used to define more accurately the presence or absence of BOO in men presenting with LUTS, so avoiding the need for formal pressure-flow studies in everyday clinical practice, while improving the likelihood of a successful outcome from prostatectomy. This study also shows that low-volume uroflowmetry can provide useful diagnostic information and that, as such, the data from such voids should not be discarded.

A novel therapy for nocturnal polyuria: a double-blind randomized trial of frusemide against placebo.

OBJECTIVE: To report a randomized, double-blind, placebo-controlled trial of an afternoon dose of the diuretic frusemide, used to establish an early evening diuresis and so diminish nocturnal voiding frequency and voided volume in elderly men presenting with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: After a 2-week placebo run-in period, 49 men aged > 50 years were randomized to receive 40 mg of frusemide or placebo, taken 6 h before their usual bedtime. Day and night-time frequency and voided volume during the run-in and treatment periods were compared between the placebo and frusemide groups. RESULTS: In the 43 men completing the study, there was a significant reduction in night-time frequency (-0.5 and 0) and percentage night-time voided volume (-18% and 0%) in those taking frusemide compared with placebo. Of patients on active treatment, seven of 19 had a reduction in night-time frequency of > or = 1, compared with only one of 20 on placebo, and 14 of 21 felt that frusemide had helped their nocturia, compared with only five of 22 on placebo. CONCLUSION: Men with LUTS whose most prominent symptom is nocturia should complete a frequency-volume chart. In those with nocturnal polyuria, 40 mg of frusemide resulted in a significant reduction in night-time frequency and percentage voided volume.

A new approach using tissue alkaline phosphatase activity to identify early testicular cancer.

OBJECTIVE: To establish the specificity and sensitivity of alkaline phosphatase activity in testicular tumours for the early detection of testicular germ cell tumours (GCTs). MATERIALS AND METHODS: Samples from patients with GCTs of the testis were sectioned and stained using the nitroblue tetrazolium salt (NBT)/5 bromo-4-chloro-3-indolylphosphate (BCIP) Sigma Fast substrate technique (referred to as MEDC) and peroxidase antiperoxidase (PAP) assay. Additionally, several cell lines from GCTs and other tumours were cultured using standard techniques and stained using both methods, and lysates from all samples were stained after gel electrophoresis. RESULTS: MEDC showed strong and specific staining of testicular tumours only. The activity on gel electrophoresis appeared as two bands, one at 75 and one at 95 kDa, which was a unique combination for testicular tumours and testis cell lines. CONCLUSION: The MEDC method has extreme sensitivity and intensity for testicular tumour tissue and has potential use as a powerful tool for the early detection of testicular GCTs by analysing semen samples, particularly in patients with equivocal findings on testicular ultrasonography.

The value of multiple free-flow studies in men with lower urinary tract symptoms.

OBJECTIVE: To assess the variability of free-flow studies in men presenting with lower urinary tract symptoms (LUTS) suggestive of benign prostatic obstruction (BPO) and to determine the sensitivity, specificity and predictive values of consecutive measurements of maximum flow rate for the presence of bladder outlet obstruction (BOO) at several threshold values. PATIENTS AND METHODS: The value of multiple free-flow studies was assessed in 165 men presenting with LUTS suggestive of BPO. Each patient was requested to void four times into a uroflowmeter and the voided volume and post-void residual urine volume (PVR) were also measured. The variability of the maximum flow rate (Qmax), voided volume and PVR between consecutive voids was assessed. In addition, the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of various thresholds of Qmax for the presence of BOO were calculated for each consecutive void. RESULTS: The mean Qmax on void 1 was 10.2 mL/s and the mean maximum value for Qmax between voids 1 and 2 was 12.5 mL/s. For voids 1, 2 and 3, the mean maximum Qmax was 13.9 mL/s and for voids 1 to 4 it was 15.2 mL/s. There were no significant changes in PVR among any of these voids. There was a statistically significant, although small, decrease in voided volume between voids 1 to 3 and voids 1 to 4. The specificity and PPV of Qmax for BOO increased with each subsequent void, such that using a threshold value for Qmax of 10 mL/s on the fourth void, the specificity and PPV for BOO were 96% and 93%, respectively. CONCLUSIONS: There was a significant increase in Qmax with each successive void when men with LUTS suggestive of BPO performed multiple free-flow measurements and consequently, single free-flow measurements substantially underestimated the maximum Qmax that these patients achieved. The specificity and PPV of Qmax for BOO can be improved considerably by performing multiple free-flow studies and by carefully selecting an appropriate threshold value (although whether pressure-flow studies are unnecessary will depend on what level of specificity and PPV is deemed acceptable in clinical practice). These findings should be considered if free-flow studies are to be used as the basis for deciding the clinical management of men with LUTS and may be particularly useful for urologists with limited facilities for pressure-flow studies.

The significance of terminal dribbling in men with lower urinary tract symptoms.

OBJECTIVE: To determine the relationship between the symptom of terminal dribbling, objective evidence of terminal dribbling on recordings of uroflow, benign prostatic enlargement (BPE) and bladder outlet obstruction (BOO) in men with lower urinary tract symptoms (LUTS). PATIENTS AND METHODS: The prevalence of the symptom of terminal dribbling was determined from a symptom questionnaire completed by 165 men presenting with LUTS. Objective evidence of terminal dribbling during voiding was assessed from uroflow recordings and prostate volume was measured by transrectal ultrasonography. Combined pressure-flow studies were performed to determine the presence or absence of BOO. RESULTS: There was relatively poor agreement between the symptom of terminal dribbling and objective evidence of its presence; 48% of the patients who reported terminal dribbling most or all of the time showed no objective evidence of terminal dribbling on uroflowmetry. The symptom of terminal dribbling was not significantly related to the presence of BOO (P = 0.74) and the group-specific urethral resistance factor (URA) did not differ significantly (P = 0.79) between those men who complained of terminal dribbling and those who did not (median URA 33 and 31 cmH2O, respectively). However, objective evidence of terminal dribbling on uroflow traces was significantly related to BOO (P < 0.001) and those patients with objective evidence of terminal dribbling had higher values of URA (median 39 compared with 28 cmH2O). Objective terminal dribbling had a specificity of 92% and positive predictive value of 88% for the presence of BOO. Neither the symptom of terminal dribbling nor objective evidence of its presence were significantly related to prostatic enlargement. CONCLUSION: While the symptom of terminal dribbling is probably not related to BOO or prostatic enlargement, objective evidence of terminal dribbling on flow curve recording is specific for BOO and as such, its presence could potentially be of value in the assessment of men with LUTS.

Determination of prostatic volume with transrectal ultrasound: A study of intra-observer and interobserver variation.

PURPOSE: We assessed the intra-observer and interobserver variation in measurements of prostatic volume using transrectal ultrasound. MATERIALS AND METHODS: Two volume estimations were performed by 1 observer in 40 patients and by 2 observers in 75. RESULTS: Mean prostatic volumes measured ranged from 18.9 to 87.0 ml. (median 39.8) for 1 observer and from 15.5 to 95.4 ml. (median 42.4) for 2 observers. The mean difference plus or minus standard deviation and limits of agreement between the paired volume estimations were 0.1 +/- 3.3 ml. and -6.5 +/- 6.7 ml., respectively, for 1 observer, and -0.3 +/- 5.3 ml and -10.9 to 10.3 ml., respectively, for 2 observers. The mean difference was 9.8% for 2 observers. The mean difference was 9.8% for 2 observers compared to 4.6% for 1. CONCLUSIONS: The results show that there is considerable variation in repeated measurements of prostatic volume and the variation is greatest for 2 observers compared to 1 observer.

The obstructive effect of a urethral catheter.

PURPOSE: The effect of a urethral catheter on pressure-flow relationships of the urethra has important implications for the practice to this question in the past in men with benign prostatic hyperplasia. We assessed the obstructive effect of an 8 Ch. urethral catheter in men who presented with lower urinary tract symptoms due to benign prostatic hyperplasia. MATERIALS AND METHODS: During combined pressure-flow studies 59 men completed 2 voids of similar volume with and without a urethral catheter in situ. Maximum flow rate, detrusor pressure at maximum flow and the group of specific urethral resistance factor were measured and compared between these 2 voids. RESULTS: There was no significant difference in maximum flow rate between voids (with catheter 9.1 ml. per second versus without catheter 8.6 ml. per second). Although detrusor pressure was significantly greater with the urethral catheter in situ (80 versus 67 cm. water), voids (with catheter 42.1 cm, water versus without catheter 36.6 cm water). CONCLUSIONS: A 8 Ch. catheter does not appear to have a significant obstructive effect in the urethra. This finding has important implications for the practice and interpretation of pressure-flow studies.