Evaluation of the Impact of Ureteroscope, Access Sheath, and Irrigation System Selection on Intrarenal Pressures in a Porcine Kidney Model.

Introduction: Elevated intrarenal pressure (IRP) during flexible ureterorenoscopy (FURS) is a predictor of postoperative complications. The aim of this study is to evaluate IRP during FURS in a porcine kidney model to determine the safest combination of irrigation device, ureteral access sheath (UAS), and ureteroscope. Methods: Urinary tracts were harvested from Landrace pigs slaughtered for the food chain. Two flexible ureteroscopes, 8.7F and 9.5F, were evaluated. Irrigation systems evaluated included the following: TraxerFlow™ (Rocamed, France), SAPS™ single action pumping system (Boston Scientific), Pathfinder Plus™ (Utah Medical), and a manual "bag squeeze." This experiment was conducted with no UAS, followed by an 11/13F UAS and then a 12/14F UAS. IRPs were measured in the prepared porcine kidney during all possible combinations of scope, UAS, and irrigation system. Results: Pressures were significantly reduced when using 12/14F UAS compared with 11/13F UAS (16.45 ± 5.3 cmH2O vs 32.73 ± 35.66 cmH2O, p = 0.006), and when using 11/13F UAS compared with no UAS (32.73 ± 35.66 cmH2O vs 49.5 ± 29.36 cmH2O, p = 0.02). Pressures were significantly reduced with the 8.7F scope compared with the 9.5F scope (24.1 ± 21.24 cmH2O vs 41.68 ± 34.5 cmH2O, p = 0.001). SAPS generates significantly greater IRP than TraxerFlow, Pathfinder Plus, and a "bag squeeze" (p < 0.05). The most dangerous combination was using the SAPS, no UAS, and larger ureteroscope leading to an IRP of 100.6 ± 16.1 cmH2O. The safest combination was using Pathfinder Plus with a 12/14F UAS and smaller ureteroscope giving an IRP of 11.6 ± 3.65 cmH2O. Conclusion: IRPs are reduced by selecting larger UAS and a small ureteroscope. The SAPS generates significantly higher IRPs than other irrigation systems. To maintain safe IRPs during FURS, urologists should use large UAS, narrow ureteroscopes, and be cautious in the selection of an irrigation device.

Capsaicin receptor TRPV1 in urothelium of neurogenic human bladders and effect of intravesical resiniferatoxin.

OBJECTIVES: To study TRPV1 immunoreactivity in the urothelium of patients with neurogenic detrusor overactivity (NDO) before and after treatment with resiniferatoxin (RTX) and controls. Functional capsaicin TRPV1 receptors have been demonstrated in urothelial cells of rodent urinary bladder, and TRPV1-knockout mice exhibit diminished nitric oxide and stretch-evoked adenosine triphosphate release from urothelial cells. In patients with NDO, TRPV1 suburothelial nerve density is increased, which is reversed by successful treatment with intravesical RTX. However, the role of urothelial TRPV1 in human bladder disorders is unknown. METHODS: Flexible cystoscopic bladder biopsies were obtained from 14 patients with NDO before and after treatment with RTX and from 8 control patients. Using a specific antibody for immunostaining, TRPV1 immunoreactivity in the urothelium was quantified by image analysis. RESULTS: TRPV1 immunoreactivity was observed in basal and apical urothelial cells. Basal cell layer TRPV1 immunoreactivity was significantly increased in NDO compared with control bladders (P = 0.003). In 5 patients who responded clinically to RTX, basal cell layer and total urothelial TRPV1 immunoreactivity decreased significantly after treatment (P = 0.032 and P = 0.016, respectively). The decreases in the basal cell layer TRPV1 immunoreactivity after RTX were comparable to the decreases in suburothelial TRPV1 nerve fibers in the biopsies previously studied from the same patients. CONCLUSIONS: Increased urothelial TRPV1 in patients with NDO may play a role in the pathophysiology, in concert with increased TRPV1 nerve fibers. Although it is not known whether similar pathogenic mechanisms are involved in the increase of urothelial and neuronal TRPV1, both may be targeted by successful RTX therapy.

P2X3-immunoreactive nerve fibres in neurogenic detrusor overactivity and the effect of intravesical resiniferatoxin.

OBJECTIVES: The ATP-gated purinergic receptor P2X3 is expressed by small diameter sensory neurons and has been identified in normal and neurogenic human bladder suburothelial fibres. Animal models have shown that ATP is released by the urothelium during bladder distension, suggesting a mechanosensory role for P2X3 receptors in normal bladder function. Successful treatment of spinal neurogenic detrusor overactivity (NDO) with intravesical resiniferatoxin (RTX), which partly acts on suburothelial C fibres, provides evidence for the emergence of a C fibre-mediated spinal reflex. The aim of this study was to investigate the possible role of P2X3-positive innervation in this pathological voiding reflex by comparing suburothelial P2X3 immunoreactivity of controls and in patients with NDO before and after intravesical RTX. METHODS: Bladder biopsies were obtained from 8 controls and 20 patients with refractory NDO enrolled in a trial of intravesical RTX. P2X3 nerve fibre density and intensity were studied in the specimens by immunohistochemistry. RESULTS: P2X3-IR nerve fibres were significantly increased in patients with NDO compared to controls (p=0.014). Thirteen patients had pre- and post-RTX biopsies available for immunohistochemistry; 5 of them responded clinically and 8 were non-responders. In the 5 patients who responded to RTX, there was a significant decrease in P2X3-positive fibres (p=0.032), whereas in non-responders, P2X3-IR nerve fibre density did not change significantly. CONCLUSIONS: In patients with NDO, the numbers of P2X3-IR nerve fibres were increased in the suburothelium. There was a significant decrease in P2X3 immunoreactivity in responders to RTX, indicating a potential pathophysiological role for the P2X3 expressing fibres.

The ultrastructure of bladder lamina propria nerves in healthy subjects and patients with detrusor hyperreflexia.

PURPOSE: Detrusor hyperreflexia is a common finding in patients with neurological disease involving the spinal cord. In animal models it has been attributed to an emergent reflex mediated mostly by unmyelinated C-fibers. We describe and measure ultrastructural features of these nerves in the lamina propria in healthy subjects and patients with detrusor hyperreflexia. MATERIALS AND METHODS: Flexible cystoscopic bladder biopsies were obtained from 51 patients (8 controls, 8 with tropical spastic paraparesis, 23 with multiple sclerosis and 12 with spinal cord disease). Electron micrographs were obtained of every nerve profile seen in the midpoint of the biopsy specimen, and in each nerve profile a number of variables were measured and recorded. RESULTS: The mean nerve profile diameter was greater in patients with tropical spastic paraparesis (mean 2.19 microm.) compared to controls (1.59 microm.) and patients with multiple sclerosis (1.55 microm.) (p <0.001). We observed a sparse urothelial innervation by naked axonal varicosities but similar bare varicosities were more frequent in the superficial layer of the lamina propria. In deeper layers close membrane contacts between axonal varicosities and cells with cytological characteristics of myofibroblasts were seen. CONCLUSIONS: We described and measured ultrastructural characteristics of human bladder lamina propria nerves. The mean profile diameter is larger in patients with tropical spastic paraparesis compared to controls and patients with multiple sclerosis. This study provides a baseline to which other bladder disorders can be compared and may allow the effect of intravesical treatments on these nerves to be assessed. Some possible functional aspects of observed structural interrelationships are presented.

Maximum urethral closure pressure and sphincter volume in women with urinary retention.

PURPOSE: In 1988 a syndrome of isolated urinary retention in young women that is associated with electromyographic abnormality of the striated urethral sphincter was described. It was hypothesised that urinary retention resulted from a failure of sphincter relaxation. The electromyographic abnormality causes overactivity of the muscle and may induce changes of work hypertrophy. If the hypothesis that the electromyographic abnormality is the cause of urinary retention is correct, we would expect the urethral sphincter to be enlarged and the urethral pressure profile to be increased in these women. We evaluated the role of static urethral pressure profilometry and transvaginal ultrasound in women in urinary retention. MATERIALS AND METHODS: A total of 66 women in complete or partial urinary retention underwent electromyography of the striated urethral sphincter using a concentric needle electrode, followed by urethral pressure profile and/or urethral sphincter volume measurement by transvaginal ultrasound. RESULTS: Maximum urethral closure pressure plus or minus standard deviation was significantly increased in patients with versus without the electromyographic abnormality (103 +/- 26.4 versus 76.7 +/- 18.4 cm. water, p <0.001). Maximum urethral sphincter volume was also increased in women with versus without the abnormality (2.29 +/- 0.64 versus 1.62 +/- 0.32 cm.3, p <0.001). CONCLUSIONS: The results of this study are consistent with the hypothesis that a local sphincter abnormality is the cause of urinary retention in a subgroup of women. Urethral pressure profilometry and sphincter volume measurement are useful for assessing these cases, especially when sphincter electromyography is not readily available.