Enabling national improvement in quality of care for renal colic.

OBJECTIVES: To report the results of a clinical audit conducted by the British Association of Urological Surgeons (BAUS) of ureteric stone care pathways, with results reported with reference to national quality standards. PATIENTS AND METHODS: The BAUS conducted a clinical audit of all patients presenting as an emergency to 107 hospitals in England during November 2020 with ureteric stones. All patients were followed up until 31 March 2021 and the inpatient and outpatient management received was recorded. RESULTS: Data for 2192 patients across 117 units were submitted. The median (interquartile range [IQR]) number of patients per unit was 16 (9-27); 70% of patients were male and the median (IQR) patient age was 46 (34-59) years. Initial management was conservative treatment for 70% of patients. Overall, primary shockwave lithotripsy was performed in 34% of patients and primary ureteroscopy in 23% of cases when surgical intervention was required to treat the stone. However, 40% of patients in whom active intervention was appropriate underwent placement of a temporizing ureteric stent rather than undergo definitive surgical intervention at the outset. Female patients were less likely to have a computed tomography (CT) scan of the kidneys, ureters and bladder performed within 24 h of presentation (13% vs 7.3% for men [chi-squared P = 0.01]) and to be given correct analgesia (66% vs 73% for men [chi-squared P = 0.03]). Patients aged 60 years or older were also significantly less likely to be offered nonsteroidal anti-inflammatory drug analgesia appropriately. In total, 87% of patients had their calcium measured within the last 2 years and 73% of patients had evidence of being offered stone prevention diet and fluid advice. CONCLUSIONS: The audit demonstrates that the National Institute of Health and Care Excellence Quality Standards are both measurable and achievable. However, there was considerable variation in the delivery of these standards, including with regard to sex and age, highlighting inequalities for patient care across the UK.

UK national bladder outlet obstruction surgery snapshot audit.

OBJECTIVES: To determine the preoperative assessment and perioperative outcomes of men undergoing bladder outlet obstruction (BOO) surgery in the UK. PATIENTS AND METHODS: A retrospective cohort study was conducted of all men undergoing BOO surgery in 105 UK hospitals over a 1-month period. The study included 1456 men, of whom 42% were catheter dependent prior to undergoing surgery. RESULTS: There was no evidence that a frequency-volume chart or urinary symptom questionnaire had been completed in 73% or 50% of men, respectively in the non-catheter-dependent group. Bipolar transurethral resection of the prostate (TURP) was the most common BOO surgical procedure performed (38%). Monopolar TURP was the next most prevalent modality (23%); however, minimally invasive BOO surgical procedures combined accounted for 17% of all procedures performed. Of the cohort 5% of men had complications within 30 days of surgery, only 1% had Clavien-Dindo Grade ≥III complications. Less than 1% of the cohort received a blood transfusion after BOO surgery and 2% were re-admitted to hospital after their BOO surgery. In total only 4% of the whole cohort were catheter dependent after BOO surgery. Pre- and postoperative paired International Prostate Symptom Score scores reviewed suggest that minimally invasive surgical procedures achieved comparable levels of improvement in both symptoms and bother at 3 months postoperatively in men who were not catheter dependent preoperatively. CONCLUSIONS: There has been a substantial shift in the available choice of procedure for BOO surgery around the UK in recent years. However, men can be reassured that overall BOO surgery treatments are safe and effective. Evidence of adherence to guidelines in the preoperative assessment of men with lower urinary tract symptoms undergoing surgery was poorly documented and must be improved.

Cost analysis of ureteroscopy (URS) vs extracorporeal shockwave lithotripsy (ESWL) in the management of ureteric stones <10 mm in adults: a UK perspective.

OBJECTIVES: To compare the total cost of a treatment strategy starting with ureteroscopy (URS) vs a strategy starting with extracorporeal shockwave lithotripsy (ESWL). METHODS: For ureteric stones of <10 mm, URS or ESWL are the main treatment options that are considered. Although the interventions differ, the goal of the interventions is to achieve a stone-free status. A systematic review and meta-analysis undertaken as part of the National Institute for Health and Care Excellence (NICE) guideline on 'Renal and ureteric stones: assessment and management' identified URS as more effective, in terms of getting people stone free, but has a higher probability of re-admission and adverse events (AEs) that contributes to downstream resource use. ESWL is initially less costly, but lower effectiveness means a greater need for repeat or ancillary procedures in order to get a patient stone free. Given these trade-offs between benefits and costs, a cost analysis of URS and ESWL was undertaken as part of the NICE guideline, using evidence from the literature of effectiveness, re-admission and AEs. The NICE guideline meta-analysis showed a lot of heterogeneity and differences in how outcomes were reported between studies. The costing analysis, therefore only used studies where: (i) patients were rendered stone free, and (ii) where effectiveness, was based on the first-line (initial) procedures. Exploratory quality adjusted life year (QALY) work was also undertaken to identify the QALY and quality of life (QoL) differences required for the most expensive intervention to be cost effective, based on the assumption that the difference in effectiveness between the initial procedures would be the main source of the QALY gain between the two strategies. RESULTS: The URS strategy was more costly overall than the ESWL strategy (incremental cost of £2387 [pounds sterling]). Sensitivity analysis varying the initial effectiveness of ESWL treatment (between the base case value of 82% and 40%) showed that URS would still be a more costly strategy even if the initial session of ESWL only had a success probability of 40%. A two-way sensitivity analysis as part of the exploratory QALY work showed that ESWL would have to have very low effectiveness and people would have to wait for further treatment for many weeks (following a failed ESWL treatment) for there to be feasible QoL gains to justify the additional cost of the URS strategy. CONCLUSIONS: ESWL is less effective at initial stone clearance and therefore requires more ancillary interventions than URS. However, the magnitude of the difference in costs means URS is unlikely to be cost effective intervention at a population level for first-line treatment, implying ESWL should be the first choice treatment.

Multi-length or 24 cm ureteric stent? A multicentre randomised comparison of stent-related symptoms using a validated questionnaire.

UNLABELLED: WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: One of the suggested factors for stent-related symptoms is that excess distal intravesical stent mass may cause bladder irritation. There is a lack of studies investigating this in a randomised controlled fashion using a validated questionnaire. This study compared two of the most commonly used length of stents (a 30 cm multi-length vs a 24 cm long stent) and showed no significance difference in stent-related symptoms in patients with either of these stents. OBJECTIVE: To investigate whether excessive redundant intravesical stent component contributes to the severity of stent-related symptoms in patients with a ureteric stent. We compared stent-related symptoms in patients who had either a standard 24 cm or multi-length ureteric stent. PATIENTS AND METHODS: In all, 162 patients with upper urinary tract calculi requiring ureteric stent insertion were randomised to receive either a 6 F × 24 cm Contour(TM) or multi-length 6 F × 22-30 cm Contour VL(TM) stent. Patients were requested to complete the validated Bristol Ureteric Stent Symptom Questionnaire (USSQ) at 1 and 4 weeks after stent insertion and 4 weeks after removal. The mean scores for each domain of the USSQ for both groups were compared using the Student's t-test. Any adverse events, e.g. stent migration, early removal of stent due to stent-related symptoms and failure of stent insertion, were also recorded. RESULTS: In all, 153 patients who had successful stent insertion were requested to complete the USSQ and 74% of patients returned at least the week 1 questionnaire. At 1 and 4 weeks with the stent in situ, comparison of the mean scores showed no significant difference in urinary symptoms, pain, general health, work performance, sexual dysfunction and number of days patients stayed in bed or reduced their routine activities. Three (2%) patients had their stent removed early due to stent-related symptoms and five (3%) had failed stent insertion. CONCLUSIONS: This study did not find any difference in symptoms between the 24 cm or multi-length Contour stents. However, the study was not powered to detect small differences particularly for the pain symptom domain. Stents should only be used sparingly and the stent dwell-time should be minimised.

Changing P2X receptor localization on maturing sperm in the epididymides of mice, hamsters, rats, and humans: a preliminary study.

OBJECTIVE: To study using immunohistochemistry the localization of P2X receptor subtypes on the head of immature sperm in the human, mouse, hamster, and rat caput epididymidis. DESIGN: Basic research. SETTING: University-based hospital. PATIENT(S): Three human epididymides were obtained from patients undergoing orchidectomy for metastatic prostate cancer. MAIN OUTCOME MEASURE(S): P2X(1), P2X(2), P2X(3), and P2X(4) receptor immunolocalization on sperm. RESULT(S): In the present study, P2X(1,2, and 3) receptor localization was immunohistochemically demonstrated on the head of immature sperm in the human, mouse, hamster, and rat caput epididymidis. P2X(4) receptor immunostaining was also observed on the head of sperm in the caput epididymidis of mice, hamsters, and humans, but not rats. There was a subsequent loss of receptor staining on sperm in the cauda epididymidis, except in humans where staining of P2X(4) receptors persisted. Comparision with peanut agglutinin (PNA) binding studies suggested the P2X receptors were located on the acrosome membrane. P2X(5-7) receptors were examined but found to be absent. CONCLUSION(S): The change in localization of receptor subtypes is coincidental with the functionally essential morphologic and maturational changes seen in sperm as they travel through the epididymis, and is suggestive of a role for purinergic signaling in sperm maturation and possibly fertility.

A functional study of purinergic signalling in the normal and pathological rabbit corpus cavernosum.

OBJECTIVE: To examine rabbit cavernosal smooth muscle (CSM) relaxation to ATP, ADP and UTP in normal rabbits and in models of conditions that predispose to erectile dysfunction (ED), diabetes mellitus (DM; induced for 6 months) and bladder outlet obstruction (BOO, 6 weeks after surgery). MATERIALS AND METHODS: Concentration-response curves (CRCs) were constructed to ATP, ADP and UTP on CSM from control rabbits in the absence and presence of antagonists. In addition, CRCs were constructed to ATP in CSM from rabbits with DM and BOO. RESULTS: ATP and UTP caused equipotent, dose-dependent relaxations of pre-contracted normal rabbit CSM; ADP was more potent. Relaxation was inhibited by Reactive Blue 2, but not by suramin, 8-p-sulfophenyltheophylline or L-N(G)-nitroarginine methyl ester. In rabbits with DM and those with partial BOO, ATP-mediated CSM relaxation was less than in control rabbits. Pharmacological profiling suggests that purine-induced CSM relaxation might be mediated by P2Y(1) and P2Y(4) receptors in the rabbit. CONCLUSIONS: In healthy rabbits, ATP released from nerves appears to produce relaxation of CSM via P2Y(4) receptors on smooth muscle, while ADP, acting on P2Y(1) receptors on endothelial cells, produces relaxation via nitric oxide. Alterations in CSM purinergic signalling might be implicated in the pathophysiology of ED associated with DM and BOO. Characterization of purinergic signalling in CSM might highlight new therapeutic targets for treating ED.

Randomized trial of laparoscopic v open nephrectomy.

BACKGROUND AND PURPOSE: Clayman and associates first described laparoscopic nephrectomy in 1990. This paper describes the first randomized controlled trial to compare laparoscopic with open surgery for simple and radical nephrectomy. PATIENTS AND METHODS: Between 2001 and 2004, 45 patients requiring simple or radical nephrectomy (tumors as large as 8 cm) were randomized to either open surgery through a loin incision or laparoscopic nephrectomy (transperitoneal). Outcome measures included operative time, complications, hospital stay, pain scores, time to return to normal activities, and quality of life scores (EuroQol). RESULTS: The mean operative time was 105 minutes in the laparoscopic group and 93 minutes in the open-surgery group (P = 0.4). Blood loss, complications, and the mortality rate were similar in the two groups, as was the hospital stay at a median of 4 days in the laparoscopic group and 5 days in the open group (P = 0.9). Postoperative visual analog pain scores averaged 3.6 in the laparoscopic group compared with 5.4 in the open group (P = 0.02). There was no difference in pain scores at 3 months. Return to normal activities was faster in the laparoscopic group at 42 days v 62 days in the open group (P = 0.04). CONCLUSIONS: Laparoscopic nephrectomy is associated with less postoperative pain and a faster return to normal activities than open nephrectomy.

The purinergic component of human vas deferens contraction.

OBJECTIVE: To examine purinergic signaling in human vas deferens. DESIGN: To study contractile responses of the scrotal vas deferens. SETTING: Research department of a university teaching hospital. PATIENT(S): Undergoing vasectomy or orchidectomy (aged 27-88 years, n = 14). INTERVENTION(S): Vasectomy or orchidectomy. MAIN OUTCOME MEASURE(S): Strips of vas deferens were suspended in an organ bath and subjected to electrical stimulation to establish frequency-response curves. These stimulations were repeated in the presence of pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2 receptor antagonist), prazosin (adrenergic alpha1 antagonist), and tetrodotoxin. Concentration-response curves were constructed to noradrenaline and the P2X agonists ATP and alpha,beta-methylene ATP (alpha,beta-meATP). The P2X receptor subtype distribution was assessed by immunohistochemistry using specific antibodies. RESULT(S): The response at 32 Hz in the presence of PPADS was reduced by 40% and in the presence of prazosin by 80%. Noradrenaline caused concentration-dependent contractions (EC50 = 11.8 microM). Contractions to ATP and alpha,beta-meATP (EC50 = 6.27 microM) suggested that the functional receptor was P2X1 and/or P2X3. However, immunohistochemistry demonstrated P2X1, but not P2X3, receptor immunoreactivity on the smooth muscle cells. CONCLUSION(S): This study demonstrated that ATP is a co-transmitter with noradrenaline in the contraction of the human vas deferens predominantly acting through the P2X1 receptor.

Alterations in purinergic and cholinergic components of contractile responses of isolated detrusor contraction in a rat model of partial bladder outlet obstruction.

OBJECTIVE: To study the effect of 3 weeks of partial bladder outlet obstruction (BOO), compared to a sham operation, on the cholinergic and purinergic components of detrusor contractile responses to agonists and to electrical field stimulation (EFS); the expression of P2X receptor subtypes was also examined. MATERIALS AND METHODS: Partial BOO was induced in female Sprague-Dawley rats by surgically applying a jeweller's silver 'jump' ring around the urethra, such that the urethra was constricted but not closed. Sham-operated female rats underwent an identical procedure without placement of a ring. RESULTS: After 3 weeks of partial BOO the rat bladders became significantly hypertrophied, doubling in weight. Spontaneous activity was markedly increased, but the contractile response to a single bolus of KCl (120 mM) was unaltered. The neurogenic-induced contractile responses of strips of detrusor from obstructed bladders were significantly greater than those from sham-operated bladders, and the responses of strips of detrusor from obstructed bladders to EFS showed a significantly greater atropine-sensitive component than sham-operated detrusor. However, the response of detrusor strips to EFS that was susceptible to desensitization by alpha,beta-methylene ATP was not significantly changed in obstructed bladders. The sensitivity of the strips from obstructed bladders to carbachol, ATP and beta,gamma-methylene ATP was less than in sham-operated detrusor. Immunohistochemical studies showed no difference in the P2X receptor subtypes expressed on detrusor smooth muscle from obstructed and sham-operated rats. CONCLUSION: In the rat, after moderate bladder hypertrophy, the atropine-sensitive component was significantly up-regulated, but the ATP-sensitive component was marginally reduced, although not significantly. These results suggest that up-regulation of the P2X component of bladder contraction seen in humans with bladder instability, and in other species models of BOO, is not mirrored in the rat, or occurs later in the pathological process of bladder hypertrophy.

Smooth muscle and purinergic contraction of the human, rabbit, rat, and mouse testicular capsule.

The smooth-muscle cells of the testicular capsule (tunica albuginea) of man, rat, and mouse were examined by electron microscopy. They were characteristically flattened, elongated, branching cells and diffusely incorporated into the collagenous matrix and did not form a compact muscle layer. Contractile and synthetic smooth-muscle cell phenotypes were identified. Nerve varicosities in close apposition to smooth muscle were seen in human tissue. Contractions induced by adenosine 5'-triphosphate (ATP), alpha, beta-methylene ATP, noradrenaline (NA), acetylcholine (ACh), and electrical field stimulation (EFS) of autonomic nerves were investigated. Nerve-mediated responses of the rabbit and human tunica albuginea were recorded. The EFS-induced human responses were completely abolished by prazosin. In the rabbit, EFS-induced contractile responses were reduced by pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid by 36% and by prazosin by 77%. Both antagonists together almost completely abolished all EFS-induced contractions. The human tunica albuginea was contracted by NA, ATP, and alpha, beta-methylene ATP, but not by ACh. The rabbit and rat tunica albuginea were contracted by NA, ATP, alpha, beta-methylene ATP, and ACh. The mouse tunica albuginea was contracted by ACh, ATP, and alpha, beta-methylene ATP, but relaxed to NA. Immunohistochemical studies showed that P2X1 (also known as P2RX1) and P2X2 (also known as P2RX2) receptors were expressed on the smooth muscle of the rodent testicular capsule, expression being less pronounced in man. The testicular capsule of the rat, mouse, rabbit, and man all contain contractile smooth muscle. ATP, released as a cotransmitter from sympathetic nerves, can stimulate the contraction of rabbit smooth muscle. Human, rat, and mouse testicular smooth muscle demonstrated purinergic responsiveness, probably mediated through the P2X1 and/or P2X2 receptors.

Urolithiasis and obesity: metabolic and technical considerations.

PURPOSE OF REVIEW: The increasing prevalence of obesity poses a challenge to urologists in the diagnosis and treatment of urolithiasis. This review summarizes the new evidence linking obesity and urolithiasis, and the technical considerations and modifications necessary in the diagnosis and treatment of stone disease in obese patients. RECENT FINDINGS: Recent studies have confirmed the epidemiological link between obesity and urolithiasis, and have provided some possible explanations for its underlying cause. New clinical series have demonstrated that flexible ureterorenoscopy and adapted percutaneous nephrolithotomy techniques can result in similar stone clearance rates and morbidity to the non-obese patient. New data, however, suggest that obesity may be an independent predictor of extracorporeal shock wave lithotripsy treatment failure for ureteric stones. Evidence of the efficacy of dietary modification and medical treatment of metabolic abnormalities has been reported in obese stone formers. SUMMARY: Urolithiasis can be safely and effectively managed in obese patients with minor modifications to the established surgical techniques. Increased understanding of the underlying metabolic abnormalities in obese patients with urolithiasis may improve prevention strategies in the future.

Immunocytochemical and pharmacological characterisation of P2-purinoceptor-mediated cell growth and death in PC-3 hormone refractory prostate cancer cells.

BACKGROUND: Extracellular nucleotides (e.g adenosine 5'-triphosphate, ATP) influence biological processes via purinergic receptors. We characterised the P2-purinoreceptors in human hormone refractory prostate cancer (HRPC) cells (PC-3 cells). RESULTS: 1. Immunofluorescent staining demonstrated P2X3 P2X, P2X5 P2X7 and P2Y2 receptors. 2. ATP inhibited cell growth by up to 91% over 72h. Pharmacological characterisation indicated a P2X-purinoreceptor-mediated response. 3. Comparable maximum growth inhibition was seen after either a single addition of 1mM or daily addition of 100mM ATP. ATP concentrations ([ATP]) returned to baseline levels within 24h if the initial [ATP] was < or =100 HM, while [ATP] remained high for 72h if a single concentration of 1 mM was used. 4. ATP 1 mM significantly (p<0.001) increased the proportion of cells undergoing apoptosis from 0.27% (+/- 0.04%) to 5.28% (+/- 0.77%). CONCLUSION: Threshold concentrations of ATP inhibited HRPC cell growth in vitro via the activation of P2X-purinoreceptors. The role of nucleotides in the treatment of HRPC requires further investigation.

Reduction of endothelin-1 binding and inhibition of endothelin-1-mediated detrusor contraction by naftidrofuryl.

Endothelin-1 (ET-1) causes urinary bladder smooth muscle contraction and the endothelin receptors A and B (ET(A) and ET(B)) are both known to be present in the rabbit urinary bladder. Alterations in ET-1 signalling have been implicated in the pathophysiology of urinary tract disorders secondary to bladder outlet obstruction and also in diabetic cystopathy. Naftidrofuryl (Naf) (marketed under the trade name Praxilene) improves walking distance in patients with peripheral vascular disease, an effect which may be partially attributed to ET-1 antagonism. The purpose of this study is to assess whether Naf will reduce ET-1 binding in the rabbit detrusor muscle and to assess whether there is inhibition of ET-1-mediated detrusor contraction. Detrusor smooth muscle strips were mounted in organ baths and cumulative response curves were measured for ET-1-mediated contractions in the presence and absence of 10(-6) M Naf (therapeutic concentration). In addition, ET-1 was added to the detrusor strips in the presence of the ET(A) antagonist, BQ123, and the ET(B) antagonist, BQ788, to identify the receptor subtype functionally involved. Overall inhibition of [(125)I]ET-1 binding by Naf was assessed using autoradiography. Identification of receptor-subtype binding reduction was assessed using the radioligands [(125)I]PD151242 and [(125)I]BQ3020. Naf inhibited ET-1-mediated detrusor contractions significantly (P<0.04), e.g. at 10(-10) M ET-1, contraction was completely abolished by Naf. Autoradiography indicated that Naf competitively inhibited [(125)I]ET-1 binding in a dose-dependent manner (IC(50)=3x10(-7) M). All radioligand binding was reduced indicating binding of Naf to both ET(A) and ET(B) receptors. Naf reduces binding of ET-1 to rabbit detrusor ET(A) and ET(B) receptors and inhibits ET-1-induced detrusor contractions mediated by ET(A) receptors. Naf may have therapeutic potential in the treatment of bladder disorders secondary to bladder outlet obstruction and diabetes mellitus.

Decreased urinary bladder apoptosis in a rabbit model of diabetes mellitus.

Urinary bladder dysfunction is a recognised complication of diabetes mellitus (DM). This is thought to be partly related to altered bladder morphology as DM is associated with increased bladder weight. In DM, increased cellular proliferation is well established. However, there is evidence that in other pathological states affecting the urinary tract, altered apoptosis may also play a role. We therefore used a rabbit model to investigate whether there are any changes in bladder apoptosis with DM. Diabetes was induced in adult New Zealand white rabbits. Age-matched controls were also used. After 6 months, the bladders were excised and weighed. The TUNEL technique was used to detect and quantify apoptosis in both DM and age-matched control bladders. Diabetes was confirmed as this group had significantly (P<0.001) elevated serum glucose-compared to controls. The bladder weights were also significantly (P<0.001) greater in the DM rabbits. Apoptosis was significantly (P<0.001) decreased in the urothelial cells of the DM bladders. Our results confirm previous findings that DM is associated with increased bladder weight. Although this is associated with increased cellular proliferation, we have demonstrated that decreased apoptosis may also play an important role. Therefore, decreased apoptosis may be important in the pathophysiology of DM cystopathy.