A porcine bladder model of pre-clinical urodynamics demonstrates increased afferent nerve activity during filling.

INTRODUCTION AND OBJECTIVES: Urodynamics are the accepted gold standard for the evaluation of multiple forms of voiding dysfunction. However, the tests are expensive, invasive, poorly reproducible, and often prone to artifacts. Therefore, there is a pressing need to develop next-generation urodynamics. The purpose of this study was to develop a novel ex vivo porcine bladder urodynamics model with afferent pelvic nerve signaling that can be used as a preclinical surrogate for bladder sensation. METHODS: Porcine bladders including the ureters and vascular supply were harvested from local abattoirs using an established protocol in both male and female animals. Ex vivo bladder perfusion was performed using physiologic MOPS (3-(N-morpholino) propanesulfonic acid) buffer solution. The pelvic nerve adjacent to the bladder was grasped with micro-hook electrodes and electroneurogram (ENG) signals recorded at 20 kHz. Bladders were filled with saline at a nonphysiologic rate (100 mL/min) to a volume of 1 L using standard urodynamics equipment to simultaneously record intravesical pressure. ENG amplitude was calculated as the area under the curve for each minute, and ENG firing rate was calculated as number of spikes (above baseline threshold) per minute. At the conclusion of the experiment, representative nerve samples were removed and processed for nerve histology by a pathologist (hematoxylin and eosin and S100 stains). RESULTS: A total of 10 pig bladders were used, and nerve histology confirmed the presence of nerve in all adequately processed samples. Vesical pressure, ENG firing rate, and ENG amplitude all increased as a function of filling. During filling tertiles (low fill: min 1-3, med fill: min 4-6, and high fill: min 7-10), normalized pressures were 0.22 ± 0.04, 0.38 ± 0.05, and 0.72 ± 0.07 (cmH2O). Similarly, normalized ENG firing rates were 0.08 ± 0.03, 0.31 ± 0.06, and 0.43 ± 0.04 spikes/minute, respectively, and normalized nerve amplitudes were 0.11 ± 0.06, 0.39 ± 0.06, and 0.56 ± 0.14) µV, respectively. Strong relationships between average normalized pressure values and averaged normalized ENG firing rate (r2 = 0.66) and average normalized ENG amplitude (r2 = 0.8) were identified. CONCLUSIONS: The ex vivo perfused porcine bladder can be used as a preclinical model for the development of next-generation urodynamics technologies. Importantly, the model includes a reproducible method to measure afferent nerve activity that directly correlates with intravesical pressure during filling and could potentially be used as a surrogate measure of bladder sensation.

Comparative-fill urodynamics in individuals with and without detrusor overactivity supports a conceptual model for dynamic elasticity regulation.

AIMS: Dynamic elasticity was previously identified in individuals with overactive bladder (OAB) using comparative-fill urodynamics (UD) and is a biomechanical mechanism for acutely regulating detrusor wall tension. On the basis of this data, a conceptual model of dynamic elasticity regulation mediated through a balance of passive mechanisms and active contractions was constructed. The present study tested this model by determining whether individuals with detrusor overactivity (DO) exhibit less dynamic elasticity than individuals without DO. METHODS: Individuals with and without urgency based on International Consultation on Incontinence Questionnaire-OAB surveys were prospectively enrolled in a comparative-fill UD study. An initial fill defined the presence or absence of DO and determined cystometric capacity. Three additional fills were employed with either passive emptying via a catheter or active voiding. To identify dynamic elasticity, average filling pressures (Pves ) were compared for fill 1 (before strain softening), fill 2 (after strain softening), and fill 3 (after active void). A dynamic elasticity index was defined. RESULTS: From 28 participants, those without DO showed decreased Pves during filling after strain softening and restored Pves during filling following active voiding, revealing dynamic elasticity. Participants with DO did not show dynamic elasticity. A dynamic elasticity index less than 1.0 cmH2 O/40% capacity was identified in 2 out of 13 participants without DO and 9 out of 15 with DO, revealing a significant association between DO and reduced/absent dynamic elasticity (P = .024). CONCLUSIONS: This study supports a conceptual model for dynamic elasticity, a mechanism to acutely regulate detrusor wall tension through a balance of competing active contractile and passive strain mechanisms. Improved understanding of this mechanistic model may help us to identify novel treatment strategies for OAB.

Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery.

BACKGROUND: Despite the known nephrotoxicity of gentamicin, in 2008 the American Urological Association recommended a weight-based gentamicin dose of 5 mg/kg for antimicrobial prophylaxis during urologic prosthetic surgery. AIM: To identify and characterize rates of acute kidney injury (AKI) in urologic prosthetic surgery, both before and after the implementation of weight-based gentamicin dosing. METHODS: We performed a single-institution retrospective study of patients receiving perioperative gentamicin during implant, revision, salvage, or explant of inflatable penile prostheses, malleable penile prostheses, or artificial urinary sphincters between the years 2000 and 2017. Patients were stratified into 2 groups, based on administration of either weight-based gentamicin (5 mg/kg or 2-3 mg/kg in cases of poor renal function) or standard-dose gentamicin (80 mg). Patient characteristics and perioperative outcomes were identified. Patients with available preoperative and postoperative (≤7 days) serum creatinine values were included. AKI was defined by Kidney Disease: Improving Global Outcomes criteria. Comparative analyses were performed between groups. MAIN OUTCOME MEASURE: Our primary outcome was incidence of AKI, with secondary outcomes including device infection rate and length of stay. RESULTS: Of the 415 urologic prosthetic surgeries performed during the study period, 124 met inclusion criteria with paired preoperative and postoperative serum creatinine values. 57 received weight-based gentamicin (median dose 5.06 mg/kg, interquartile range [IQR] 3.96-5.94) and 67 received standard-dose gentamicin (median dose 1.07 mg/kg, IQR 1.04-1.06), P < .001. There were no significant differences in preoperative renal function or comorbidities between groups; however, the weight-based group was older (median age 64.0 years, IQR 60.0-68.5) compared with the standard-dose group (median age 61.0 years, IQR 55.0-66.0), P = .01, and comprised fewer explant cases (1.8%, 1 of 57) than the standard-dose group (13.4%, 9 of 67), P = .02. The AKI rate was significantly higher in the weight-based group (15.8%, 9 of 57) compared with the standard-dose group (3.0%, 2 o67), P = .02. Device infection rate was similar between groups (5.3%, 3/56 vs 5.2%, 3 of 58), P = 1.00. CLINICAL IMPLICATIONS: Our data suggest weight-based perioperative gentamicin prophylaxis may be associated with an increased AKI risk, without noticeably improving infection rates. STRENGTH & LIMITATIONS: Strengths of our study include the Veterans Affairs population analyzed, as well as rigorous inclusion criteria that allowed for a sensitive assessment of postoperative renal function. Limitations include the retrospective design and small sample size. CONCLUSION: Weight-based gentamicin dosing may warrant closer perioperative monitoring of renal function, and merits larger investigations to further elucidate risks and benefits. Moore RH, Anele UA, Krzastek SC. Potential Association of Weight-Based Gentamicin with Increased Acute Kidney Injury in Urologic Prosthetic Surgery. J Sex Med 2019;16:137-144.

Racial disparities in bladder management in veterans with spinal cord injury and disorders.

AIMS: Neurogenic lower urinary tract dysfunction is common in individuals with spinal cord injury and disorders (SCI/D). The purpose of this study was to identify specific demographic, neurologic, and urologic factors associated with different bladder management methods (BMMs) in individuals with SCI/D. METHODS: A retrospective review of BMMs at a large Veterans Affairs SCI/D center was performed to identify associated risk factors including demographics, neurologic factors, and urologic factors. Bivariate analysis was performed to identify factors associated with specific BMMs. Then, a propensity-matched racial group analysis was performed to identify independent factors associated with differences in BMM. RESULTS: Data from 833 patients with SCI/D were reviewed and included 52.1% Caucasians and 39.6% African Americans. On bivariate analysis, current age, years since the injury, the severity of functional impairment, nonmedical mechanism of injury, and Caucasian race were associated with increased rates of indwelling catheter use. In an analysis of propensity-matched racial groups, African-American race was found to be an independent risk factor for not using indwelling catheters on multivariate analysis (odds ratio = 0.55). This finding was not related to access to care, as the rate of urodynamic testing was similar between races ( P = 0.174). CONCLUSIONS: Caucasians were more likely to use indwelling catheters and less likely to use conservative BMMs despite proper urodynamic evaluation. The racial discrepancy suggests a need for future research aimed at identifying unknown psychosocial factors associated with the use of indwelling catheters in individuals with SCI/D.

An external compress-release protocol induces dynamic elasticity in the porcine bladder: A novel technique for the treatment of overactive bladder?

INTRODUCTION: Dynamic elasticity is an acutely regulated bladder material property through which filling and passive emptying produce strain softening, and active voiding restores baseline pressure. The aim of this study was to test the hypothesis that strain softening produced by filling-passive emptying is equivalent to that produced by compression-release in a porcine bladder model. METHODS/MATERIALS: Latex balloons and ex vivo perfused pig bladders were used for a series of alternating fill-passive emptying ("Fill") and external compress-release ("Press") protocols. For the Fill protocol balloons/bladders were (1) filled to defined volumes (prestrain softening), (2) filled to capacity to strain soften (reference), and (3) passively emptied to the original volume (poststrain softening). For the Press protocol, balloons/bladders were (1) filled to defined volumes (prestrain softening), (2) externally compressed to reference pressure and then released for five cycles (poststrain softening). After each protocol, bladders were voided with high-KCl buffer to induce "active" voiding. RESULTS: In both balloons and porcine bladder, both the Fill and Press protocols produced significant strain softening (P < 0.05) and poststrain softening pressures were not different for Fill and Press protocols (P > 0.05), indicating a similar degree of strain softening with both methods. CONCLUSIONS: Repeated external compression can induce bladder strain softening similar to filling and passive emptying. This technique may represent a means to acutely regulate bladder compliance and potentially be used as a mechanical treatment for urinary urgency.

An innovative, non-invasive sensation meter allows for a more comprehensive understanding of bladder sensation events: A prospective study in participants with normal bladder function.

AIMS: There is currently no standardized method of characterizing changes in bladder sensation during bladder filling outside of the urodynamics laboratory. The purpose of this investigation was to characterize real-time bladder sensation events using a sensation meter during oral hydration in individuals with normal bladder function. METHODS: Participants enrolled in an accelerated hydration study drank 2 L Gatorade-G2® and utilized a sensation meter to record real-time bladder sensation (0-100%), verbal sensory thresholds, and sensation descriptors of "tense," "pressure," "tingling," "painful," and "other" for two consecutive fill-void cycles. RESULTS: Data from 21 participants (12 females/9 males) were obtained and demonstrated an average of 8-9 sensation events (significant changes in sensation) per fill with no differences in the total number of sensation events and volume between sensation events (fill 1 vs fill 2). An increased number of sensation events occurred at higher capacity quartiles. Event descriptors of "pressure" and "tingling" were the most commonly chosen descriptors in both fills. CONCLUSIONS: The innovative sensation meter includes the sensation event descriptors of "tense," "tingling," "pressure," and "painful," to enable a more comprehensive understanding of bladder sensation as well as real-time identification, quantification, and characterization of sensation events. The study demonstrates 8-9 events per fill, acceleration of sensation during filling, and unique sensation event descriptor patterns. This technology may be helpful in the identification of novel sensation patterns associated with overactive bladder (OAB) and aging.

Bladder volume correction factors measured with 3D ultrasound and BladderScan.

INTRODUCTION: The aim of this study was to investigate conventional 3D ultrasound and portable BladderScan volume measurements and implement correction factors to ensure accurate volume metrics. MATERIALS AND METHODS: Healthy participants without urinary urgency were recruited for a prospective hydration study in which three consecutive voids were analyzed for two separate visits. Just before and after voiding, 3D ultrasound and BladderScan volumes were measured. Estimated voided volumes were calculated as the volume immediately prior to void minus any post void residual and were compared to actual voided volumes measured using a graduated container. Percent errors were calculated, and an algebraic method was implemented to create correction factors for 3D ultrasound and BladderScan. RESULTS: Sixteen individuals completed the study, and six voids were recorded for each participant. A total of 96 volume measurements ranging from 0 mL to 1050 mL with an average of 394 +/- 26 mL were analyzed. Both 3D ultrasound and BladderScan significantly underestimated voided volumes with averages of 296 +/- 22 and 362 +/- 27, respectively. Average percent error for the 3D ultrasound group was 30.1% (pre-correction) and 20.7% (post-correction) (p < 0.01) and 22.4% (pre-correction) and 21.8% (post-correction) for the BladderScan group (p = 0.20). The voided volume correction factors for 3D ultrasound and BladderScan were 1.30 and 1.06, respectively. CONCLUSION: BladderScan and 3D ultrasound typically underestimate voided volumes. Correction factors enabled more accurate measurements of voided volumes for both 3D ultrasound and BladderScan. Accurate volume measurements will be valuable for the development of non-invasive urodynamics techniques.

Effects of vesical and perfusion pressure on perfusate flow, and flow on vesical pressure, in the isolated perfused working pig bladder reveal a potential mechanism for the regulation of detrusor compliance.

AIMS: Although there is evidence that deficits in bladder blood flow negatively impact bladder function, the effects of vesical, and perfusion pressures on bladder perfusion (perfusate flow), and of perfusate flow on vesical pressure, remain poorly understood. The present study used the isolated perfused working pig bladder model to examine the relationships between blood flow, and vesical and perfusion pressures. METHODS: Vesical arteries of pig bladders obtained from a local slaughterhouse were cannulated and perfused with Krebs-Henseleit solution at different pressures, and with carbachol to cause bladder contraction. The urethra of each bladder was cannulated to permit filling (10 mL/min), isovolumetric contraction and emptying. A ureter was cannulated with a pressure sensor to monitor vesical pressure. RESULTS: When at rest (50 mL vesical volume), bladder vesical pressure was 8.06 ± 1.5 mmHg and perfusate flow driven by a pressure gradient of 105 mmHg was 22.5 ± 2 mL/min (58.9 ± 7.8 mL/min-100 g). During filling, vesical pressure increased and flow decreased, but not necessarily in-parallel. Perfusate flow decreased transiently during isovolumetric contraction, and flow increased during emptying. A reduction in perfusion pressure from ∼105 to ∼40 mmHg reduced flow from ∼70 to ∼20 mL/min-100g, and reduced flow correlated with reduced vesical pressure. CONCLUSION: Perfusate flow is dependent on bladder perfusion pressure, and not necessarily reciprocally dependent on vesical pressure. Vesical pressure is highly sensitive to the level of perfusate flow, which supports the hypothesis that vesical pressure is dependent on the level of detrusor smooth muscle contractile activity (tone), and that compliance is dependent on bladder perfusion.

Potential vascular mechanisms in an ex vivo functional pig bladder model.

AIMS: Chronic ischemia is a recognized factor in the pathophysiology of underactive bladder (UAB). Although relative ischemia (ie, low blood flow) is known to occur during filling, little is known regarding the pathophysiology that leads to UAB. Therefore, we developed an ex vivo functional porcine model to investigate the role of transient ischemia and whether autoregulation, a mechanism that maintains tissue oxygenation in certain vital organs, also exists in the bladder. METHODS: Using bladders from slaughtered pigs, we prepared an isolated perfused model where we studied the effects of bladder perfusion flow rate on perfusion pressure and tissue oxygenation during the filling phase. Bladders were perfused at an initial flow rate of 20 mL/min and then clamped in a sequentially decreasing stepwise manner down to no flow and back to the initial flow rate. RESULTS: We found a linear relationship between flow rate and perfusion pressure until the flow rate decreased below 5 mL/min at which point the vascular resistance decreased; however, tissue pO2 remained stable after an initial decline. CONCLUSIONS: These findings suggest that there may be an intrinsic autoregulatory mechanism in the bladder that allows it to undergo cyclic episodes of relative ischemia during its normal function. Factors that overcome this mechanism such as complete or chronic ischemia may be critical in the progression to detrusor underactivity and thereby highlight the importance of intervention during the early phases of this disease process.

Slowly cycling Rho kinase-dependent actomyosin cross-bridge "slippage" explains intrinsic high compliance of detrusor smooth muscle.

Biological soft tissues are viscoelastic because they display time-independent pseudoelasticity and time-dependent viscosity. However, there is evidence that the bladder may also display plasticity, defined as an increase in strain that is unrecoverable unless work is done by the muscle. In the present study, an electronic lever was used to induce controlled changes in stress and strain to determine whether rabbit detrusor smooth muscle (rDSM) is best described as viscoelastic or viscoelastic plastic. Using sequential ramp loading and unloading cycles, stress-strain and stiffness-stress analyses revealed that rDSM displayed reversible viscoelasticity, and that the viscous component was responsible for establishing a high stiffness at low stresses that increased only modestly with increasing stress compared with the large increase produced when the viscosity was absent and only pseudoelasticity governed tissue behavior. The study also revealed that rDSM underwent softening correlating with plastic deformation and creep that was reversed slowly when tissues were incubated in a Ca2+-containing solution. Together, the data support a model of DSM as a viscoelastic-plastic material, with the plasticity resulting from motor protein activation. This model explains the mechanism of intrinsic bladder compliance as "slipping" cross bridges, predicts that wall tension is dependent not only on vesicle pressure and radius but also on actomyosin cross-bridge activity, and identifies a novel molecular target for compliance regulation, both physiologically and therapeutically.

Low amplitude rhythmic contraction frequency in human detrusor strips correlates with phasic intravesical pressure waves.

PURPOSE: Low amplitude rhythmic contractions (LARC) occur in detrusor smooth muscle and may play a role in storage disorders such as overactive bladder and detrusor overactivity. The purpose of this study was to determine whether LARC frequencies identified in vitro from strips of human urinary bladder tissue correlate with in vivo LARC frequencies, visualized as phasic intravesical pressure (p ves) waves during urodynamics (UD). METHODS: After IRB approval, fresh strips of human urinary bladder were obtained from patients. LARC was recorded with tissue strips at low tension (<2 g) and analyzed by fast Fourier transform (FFT) to identify LARC signal frequencies. Blinded UD tracings were retrospectively reviewed for signs of LARC on the p ves tracing during filling and were analyzed via FFT. RESULTS: Distinct LARC frequencies were identified in 100% of tissue strips (n = 9) obtained with a mean frequency of 1.97 ± 0.47 cycles/min (33 ± 8 mHz). Out of 100 consecutive UD studies reviewed, 35 visually displayed phasic p ves waves. In 12/35 (34%), real p ves signals were present that were independent of abdominal activity. Average UD LARC frequency was 2.34 ± 0.36 cycles/min (39 ± 6 mHz) which was similar to tissue LARC frequencies (p = 0.50). A majority (83%) of the UD cohort with LARC signals also demonstrated detrusor overactivity. CONCLUSIONS: During UD, a subset of patients displayed phasic p ves waves with a distinct rhythmic frequency similar to the in vitro LARC frequency quantified in human urinary bladder tissue strips. Further refinements of this technique may help identify subsets of individuals with LARC-mediated storage disorders.

Improvement in lower urinary tract symptoms across multiple domains following ventriculoperitoneal shunting for idiopathic normal pressure hydrocephalus.

AIMS: The purpose of this study was to evaluate the change in lower urinary tract symptoms following ventriculoperitoneal shunting in patients with idiopathic normal pressure hydrocephalus (iNPH). METHODS: Lower urinary tract symptoms in patients with new-onset iNPH were prospectively evaluated using validated questionnaires from the International Consultation on Incontinence to assess overactive bladder (ICIq-OAB), incontinence (ICIq-UI), and quality of life (ICIq-LUTqol), as well as the American Urological Association Symptom Score bother scale, prior to and following ventriculoperitoneal shunting for iNPH. Sub-analysis was performed based on gender, age, and medical comorbidities. RESULTS: Twenty-three consecutive patients with new-onset iNPH were evaluated prior to, and following, surgical intervention for iNPH via ventriculoperitoneal shunting. Shunting resulted in a significant improvement in urinary urgency, urge incontinence, ability to perform physical activities, and overall quality of life. Women had improvement across more domains than men following shunting, particularly in terms of urinary urgency and overall quality of life. Younger patients experienced significant improvement in scores following shunting as compared to older patients. Patients with two or more medical comorbidities, as well as those with fewer than two comorbidities, reported a significant improvement in overall quality of life. CONCLUSIONS: Surgical intervention for iNPH results in significant improvement in urinary symptoms, specifically in terms of urinary urgency and urge incontinence as well as overall quality of life, particularly in women and younger patients.

Characterization of lower urinary tract symptoms in patients with idiopathic normal pressure hydrocephalus.

AIMS: The purpose of this study was to evaluate lower urinary tract symptoms (LUTS) in idiopathic normal pressure hydrocephalus (iNPH). METHODS: Patients with new-onset iNPH were prospectively evaluated for LUTS via detailed history and physical, and administration of questionnaires from the International Consultation on Incontinence to assess incontinence (ICIq-UI), overactive bladder (ICIq-OAB), and quality of life (ICIq-LUTqol), as well as the American Urological Association Symptom Score bother scale. All patients with moderate-to-severe LUTS were offered urodynamic testing. Sub-analysis was performed based on gender, medical comorbidities, and age. RESULTS: Fifty-five consecutive patients with iNPH completed the initial evaluation and surveys. Total urinary incontinence score was mild to moderate (8.71 ± 0.64: 0-21 scale) with 90.9% experiencing leakage and 74.5% reporting urge incontinence. The most common OAB symptom was nocturia (2.2 ± 0.14: 0-4 scale) with urge incontinence the most bothersome (3.71 ± 0.44: 0-10 scale). Quality-of-life impact was moderate (4.47 ± 0.4: 0-10 scale) and American Urological Association Symptom Score bother scale was 2.89 ± 0.22 (0-6 scale). Urodynamics testing revealed 100% detrusor overactivity and mean bladder capacity of 200 mL. Several differences were identified based on gender, medical comorbidities, and age. CONCLUSIONS: Patients with iNPH present with mild-moderate incontinence of which nocturia is the most common symptom, urge incontinence the most bothersome, with 100% of patients having detrusor overactivity. Younger patients experienced greater bother related to LUTS. To our knowledge, this is the only prospective evaluation of urinary symptoms in patients with new-onset iNPH.

Non-invasive characterization of real-time bladder sensation using accelerated hydration and a novel sensation meter: An initial experience.

AIMS: The purpose of this investigation was to develop a non-invasive, objective, and unprompted method to characterize real-time bladder sensation. METHODS: Volunteers with and without overactive bladder (OAB) were prospectively enrolled in a preliminary accelerated hydration study. Participants drank 2L Gatorade-G2® and recorded real-time sensation (0-100% scale) and standardized verbal sensory thresholds using a novel, touch-screen "sensation meter." 3D bladder ultrasound images were recorded throughout fillings for a subset of participants. Sensation data were recorded for two consecutive complete fill-void cycles. RESULTS: Data from 14 normal and 12 OAB participants were obtained (ICIq-OAB-5a = 0 vs. ≥3). Filling duration decreased in fill2 compared to fill1, but volume did not significantly change. In normals, adjacent verbal sensory thresholds (within fill) showed no overlap, and identical thresholds (between fill) were similar, demonstrating effective differentiation between degrees of %bladder capacity. In OAB, within-fill overlaps and between-fill differences were identified. Real-time %capacity-sensation curves left shifted from fill1 to fill2 in normals, consistent with expected viscoelastic behavior, but unexpectedly right shifted in OAB. 3D ultrasound volume data showed that fill rates started slowly and ramped up with variable end points. CONCLUSIONS: This study establishes a non-invasive means to evaluate real-time bladder sensation using a two-fill accelerated hydration protocol and a sensation meter. Verbal thresholds were inconsistent in OAB, and the right shift in OAB %capacity-sensation curve suggests potential biomechanical and/or sensitization changes. This methodology could be used to gain valuable information on different forms of OAB in a completely non-invasive way.

A pilot study to measure dynamic elasticity of the bladder during urodynamics.

AIMS: Previous studies using isolated strips of human detrusor muscle identified adjustable preload tension, a novel mechanism that acutely regulates detrusor wall tension. The purpose of this investigation was to develop a method to identify a correlate measure of adjustable preload tension during urodynamics. METHODS: Patients reporting urgency most or all of the time based on ICIq-OAB survey scores were prospectively enrolled in an extended repeat fill-and-empty urodynamics study designed to identify a correlate of adjustable preload tension which we now call "dynamic elasticity." Cystometric capacity was determined during initial fill. Repeat fills to defined percentages of capacity with passive emptying (via syringe aspiration) were performed to strain soften the bladder. A complete fill with active voiding was included to determine whether human bladder exhibits reversible strain softening. RESULTS: Five patients completed the extended urodynamics study. Intravesical pressure (pves ) decreased with subsequent fills and was significantly lower during Fill 3 compared to Fill 1 (P = 0.008), demonstrating strain softening. Active voiding after Fill 3 caused strain softening reversal, with pves in Fill 4 returning to the baseline measured during Fill 1 (P = 0.29). Dynamic elasticity, the urodynamic correlate of adjustable preload tension, was calculated as the amount of strain softening (or its reversal) per %capacity (Δaverage pves between fills/Δ%capacity). Dynamic elasticity was lost via repeat passive filling and emptying (strain softening) and regained after active voiding regulated the process (strain softening reversal). CONCLUSIONS: Improved understanding of dynamic elasticity in the human bladder could lead to both improved sub-typing and novel treatments of overactive bladder. Neurourol. Urodynam. 36:1086-1090, 2017. © 2016 Wiley Periodicals, Inc.

Follow the Stream: Imaging of Urinary Diversions.

Urinary diversion is a surgical technique to redirect the stream of urine, most often after cystectomy. Cystectomy may be performed both for benign and for malignant conditions. Bladder cancer is the most common indication for cystectomy, and most patients who undergo radical cystectomy and urinary diversion have muscle-invasive or high-risk non-muscle-invasive bladder cancer. There are two major surgical approaches for urinary diversions performed after radical cystectomy: continent and incontinent diversions. For incontinent urinary diversions, a cutaneous ostomy is used for continuous urine drainage (eg, ileal conduit). With a continent diversion procedure, the patient may void through the native urethra or self-catheterize through a surgically created stoma. The goals of imaging after urinary diversion are to assess postoperative anatomy, detect postoperative complications, evaluate for residual or recurrent tumor and metastatic disease, and monitor for upper tract distention and/or deterioration. Multiple imaging modalities and techniques may be used to evaluate urinary diversions, including computed tomographic and magnetic resonance urography, intravenous pyelography, ultrasonography, pouchography, loopography, and nephrostomy studies. Knowledge of the expected postoperative appearance after urinary diversions and potential postoperative complications is crucial because many complications may be clinically silent. Radiologists must be able to recognize the expected postoperative appearance as well as complications to facilitate appropriate diagnosis and treatment of patients after cystectomy and urinary diversion. (©)RSNA, 2016.

Acute length adaptation and adjustable preload in the human detrusor.

AIMS: The biomechanical properties of length adaptation and adjustable preload have been previously identified in detrusor smooth muscle in animal models. This in vitro study aims to show that human detrusor smooth muscle exhibits length adaptation and adjustable preload tension which could play an important role in both overactive bladder and detrusor underactivity. METHODS: In order to demonstrate length adaptation, human detrusor smooth muscle strips are stretched and contracted beyond an optimum length and then contracted three times at the previous optimum length to determine if maximum active tension could be re-established. To demonstrate adjustable preload (Tap ), human detrusor smooth muscle strips are subjected to a pre-defined loading-unloading (strain softening) sequence to reduce preload. Then, tissues are contracted and the sequence is repeated to determine if this active process restored preload. RESULTS: Nine patients (average age, 62) provide tissue: 89% are men with urothelial carcinoma and a minority (22%) also have neurogenic bladder dysfunction. In the length adaptation protocol, contractions show progressive increases in active tension (P < 0.05). In the Tap protocol, a significant amount of preload is lost to strain softening (P < 0.05) and is restored after active contraction (P = 0.50). Exposure to the rho-kinase inhibitor, H-1152, prevents the restoration of preload (P < 0.05). CONCLUSIONS: This study demonstrates that human detrusor smooth muscle displays both length adaptation and Tap . Furthermore, Tap may be regulatable through a rho-kinase pathway. These biomechanical processes may be important in the pathophysiology of both overactive bladder and detrusor underactivity. Neurourol. Urodynam. 35:792-797, 2016. © 2015 Wiley Periodicals, Inc.

A review of post-stroke urinary incontinence.

INTRODUCTION: Cerebrovascular accidents, or strokes, are a common cause of morbidity and mortality in the United States. Urinary incontinence is a prevalent morbidity experienced by post-stroke patients that is associated with long term disability and institutionalization effects on these patients. MATERIALS AND METHODS: An extensive literature review was conducted using multiple academic search engines using the keywords: 'stroke,' 'CVA,' 'urinary incontinence,' 'urodynamics,' 'pharmacologic treatments,' and 'conservative treatments.' Articles were reviewed and summarized to explain incidence, assessment, and treatments of urinary incontinence in post-stroke individuals. RESULTS: Twenty-eight percent to seventy-nine percent of stroke survivors experience urinary incontinence with detrusor overactivity being the most common type of incontinence assessed by urodynamic studies. There continues to be insufficient data studying the effects and benefits of non-pharmacologic and pharmacologic treatments in post-stroke patients. Similarly, urinary incontinence remains an indicator of increased morbidity, disability, and institutionalization rates in the post-stroke patient. CONCLUSIONS: Stroke is a debilitating disease which causes urinary incontinence in many patients. As a result, patients have increased rates of hospitalization and disability compared to post-stroke patients without urinary incontinence. The history and physical exam are key in diagnosing the type of urinary incontinence with urodynamic studies being an adjunctive study. Non-pharmacologic treatment, such as behavioral therapy, and pharmacologic agents including antimuscarinics and beta adrenergic medications, are not well studied in the post-stroke patient. Urinary incontinence in stroke patients needs to be further studied to help decrease morbidity and mortality rates within this population.

A new and automated method for objective analysis of detrusor rhythm during the filling phase.

INTRODUCTION: There is growing acceptance that the detrusor muscle is not silent during the filling phase of the micturition cycle but displays low-amplitude phasic contractions that have been associated with urinary urgency. Unfortunately, there is currently no standardized methodology to quantify detrusor rhythm during the filling phase. Therefore, the purpose of this study was to develop an automated computer algorithm to analyze rat detrusor rhythm in a quick, accurate, and reproducible manner. MATERIALS AND METHODS: Strips of detrusor smooth muscle from rats (n = 17) were placed on force transducers and subjected to escalating doses of PGE2 to generate contractile rhythm tracings. An automated computer algorithm was developed to analyze contractile frequency, amplitude, and tone on the generated rhythm tracings. Results of the automated computerized analysis were compared to human (n = 3) interpretations. Human interpreters manually counted contractions and then recounted the same data two weeks later. Intra-observer, inter-observer, and human-to-computer comparisons were performed. RESULTS: The computer algorithm quantified concentration-dependent changes in contractile frequency, amplitude, and tone after administration of PGE2 (10(-9)-10(-6)M). Concentration-response curves were similar for all contractile components with increases in frequency identified mainly at physiologic concentrations of PGE2 and increases in amplitude at supra-physiologic concentrations. The computer algorithm consistently over-counted the human interpreters, but with less variability. Differences in inter-observer consistency were statistically significant. CONCLUSIONS: Our computerized algorithm accurately and consistently identified changes in detrusor muscle contractile frequency, amplitude, and tone with varying doses of PGE2. Frequency counts were consistently higher than those obtained by human interpreters but without variability or bias. Refinements of this method may allow for more standardized approach in the study of pharmacologic agents on filling phase rhythmic activity.

The role of cystectomy for non-malignant bladder conditions: a review.

INTRODUCTION: Few studies have adequately addressed the indications, efficacy, and quality-of-life for cystectomy performed for non-malignant bladder conditions. Patients with debilitating non-malignant bladder conditions who have failed all previous conservative therapies may undergo various forms of cystectomy, including partial, simple or radical cystectomy. We provide a review of the current literature and recommendations for cystectomy for various non-malignant bladder conditions. MATERIALS AND METHODS: A systematic review of MEDLINE was conducted to find prospective and retrospective studies using the keywords "cystectomy", "benign", and `non-malignant`. Articles were reviewed and triaged, background articles were added as supplements, leaving a final review of 67 papers. RESULTS: Data from the final review suggests that common benign indications for cystectomy are interstitial cystitis/painful bladder syndrome (IC/PBS), neurogenic bladder, hemorrhagic/radiation cystitis, infectious diseases of the bladder and miscellaneous conditions of the bladder such as endometriosis and total refractory incontinence. The most common perioperative complications include urinary tract and wound infections. Efficacy of cystectomy in patients with IC/PBS is greater than 80%, while efficacy in patients with neurogenic bladder is greater than 90%. Finally, improved urinary quality-of-life has been demonstrated in patients with neurogenic bladder post-cystectomy. CONCLUSION: Cystectomy for non-malignant conditions can be considered for patients who have failed previous conservative therapy. The limited data in existence suggests fertility can be adequately preserved after cystectomy in younger males. The data regarding the forms of urinary diversion suggests no significant advantage between any of the major forms of urinary diversion. Finally, while newer pharmacologics and technological advances are widely used in the treatment of various benign urological conditions, their role in preventing or treating refractory benign bladder conditions have not been fully characterized.