Use of EPIC 26 to identify men likely to benefit from surgical interventions for urinary incontinence after radical prostatectomy.

PURPOSE: To examine outcomes of surgical procedures for urinary incontinence after radical prostatectomy (post-RP UI) and to identify patients who may benefit from a surgical intervention to treat post-RP UI. METHODS: A retrospective chart review identified men who underwent radical prostatectomy (RP) from July 2004 through July 2016 at our institution. Cases underwent surgical interventions for UI following RP. Controls had RP during the study period but did not have an intervention for UI following RP. We used the UI scale of the Expanded Prostate Index Composite (EPIC) 26 to: (1) quantify post-RP UI before and after UI intervention overall and for specific surgical procedures; (2) evaluate the significance of improvement in post-RP UI before and after UI intervention and (3) identify controls with levels of post-RP UI that were comparable to the cases. RESULTS: Two thousand nine hundred and sixty-eight RPs were performed; 48 patients underwent further surgical intervention (39 slings, 9 artificial urinary sphincter, AUS). For 20 cases with complete EPIC UI data (15 slings, 5 AUS), the median (IQR) pre-UI intervention score was 27.00 (IQR 22.75-42.75). Improvement was significant overall (p < 0.001) and for slings (p = 0.001). 71/2085 controls had post-prostatectomy UI scores ≤ 27.0, suggesting that they may have benefited from a post-RP surgical intervention for UI. CONCLUSION: Data support the effectiveness of surgery to treat post-RP UI. A sizeable population of unidentified men may benefit from a surgical intervention to treat urinary incontinence after RP.

Use of the Urethral Sling to Treat Symptoms of Climacturia in Men After Radical Prostatectomy.

BACKGROUND: Climacturia affects up to 45% of men after radical prostatectomy (RP). Although urethral slings decrease the severity and frequency of stress incontinence after RP, their efficacy as a treatment for climacturia after RP has not been well studied. AIM: The aim of this study was to assess patient-reported changes in climacturia symptoms after implantation of a urethral sling as a treatment for stress incontinence after RP. METHODS: After Institutional Review Board approval, a retrospective chart review identified males aged 18-80 years who received urethral slings for stress incontinence after RP at our institution from 2012 to 2017. These patients were mailed an 11-item questionnaire asking them about climacturia symptoms before and after implantation of a urethral sling. Written informed consent was obtained from patients participating in the mailed questionnaire. OUTCOMES: Respondents were asked to report on climacturia frequency and severity, bother, partner bother, and incontinence before and after implantation of urethral slings. RESULTS: A total of 42 questionnaires were mailed; 17 were available for analysis. The median age (and interquartile range, IQR) of the sample at RP was 64 (59.5, 68.0). Almost all (94.1%) of the men were sexually active at the time of the study and 64.7% reported experiencing urinary leakage during sexual arousal. Most (58.8%) underwent the urethral sling procedure to treat general incontinence; 35.3% underwent the procedure to treat both general incontinence and incontinence during sexual activity and 1 (5.9%) underwent it for other reasons. A median of 28.1 months elapsed between RP and sling procedure (IQR: 18.36, 53.88; minimum: 8.00; maximum: 108.36). Statistically significant shifts toward improvement from presling to postsling were noted for frequency of leakage during sexual arousal or orgasm (P = .041) and for the degree to which leakage of urine during sexual arousal or orgasm was a "bother" (P = .027). While almost all (94%) of the men were incontinent before sling, this percentage dropped to 53% after sling (P = .031). CLINICAL IMPLICATIONS: Urethral slings should be discussed as a treatment strategy for climacturia during clinical consultations with patients. STRENGTHS & LIMITATIONS: Strengths include consistent surgical technique. Limitations include retrospective design, lack of a nonsling comparison group, subjective nature of outcome measures, possible response bias, and variability in time interval between RP and sling procedure. CONCLUSION: Use of urethral slings after RP is associated with improvements in climacturia symptoms, bother, and incontinence. Nolan J, Kershen R, Staff I, et al. Use of the Urethral Sling to Treat Symptoms of Climacturia in Men After Radical Prostatectomy. J Sex Med 2020;17:1203-1206.

Caffeine ingestion causes detrusor overactivity and afferent nerve excitation in mice.

PURPOSE: We examined the effect of caffeine (Sigma®) on voiding patterns in mice and characterized potential changes in bladder function and sensory signaling. MATERIALS AND METHODS: A total of 12 mice were fed high dose (150 mg/kg) caffeine daily for 2 weeks. Micturition frequency and volume were recorded at baseline and at the end point. The effects of chronic low dose (10 mg/kg) caffeine on voiding patterns were examined in 7 mice, which were subsequently studied using awake cystometry. In a separate study to characterize the effects of acute caffeine consumption on bladder function and sensory signaling cystometry was performed in 6 mice. Bladder extracellular multifiber afferent signaling was recorded at baseline and 1 hour after feeding low dose caffeine. In a separate group of mice baseline cystometrograms were done using normal saline, followed by a caffeine filling solution. RESULTS: Compared to pretreatment conditions, daily oral high dose caffeine resulted in a significant increase in average micturition frequency and a decreased average volume per void. In animals fed low dose caffeine cystometry demonstrated a statistically significant increase in filling and threshold bladder pressure compared to caffeine naïve animals. Acute low dose caffeine ingestion resulted in a significant increase in filling pressure, an increased frequency of nonvoiding bladder contractions, a decrease in cystometric capacity and a 7.2-fold increase in the average firing rate of afferent nerves during filling. Caffeine administered intravesically had no effect on cystometric parameters. CONCLUSIONS: Oral caffeine administration results in detrusor overactivity and increased bladder sensory signaling in the mouse.

Autonomic dysfunction and plasticity in micturition reflexes in human α-synuclein mice.

Although often overshadowed by the motor dysfunction associated with Parkinson's disease (PD), autonomic dysfunction including urinary bladder and bowel dysfunctions are often associated with PD and may precede motoric changes; such autonomic dysfunction may permit early detection and intervention. Lower urinary tract symptoms are common in PD patients and result in significant morbidity. This studies focus on nonmotor symptoms in PD using a transgenic mouse model with overexpression of human α-synuclein (hSNCA), the peptide found in high concentrations in Lewy body neuronal inclusions, the histopathologic hallmark of PD. We examined changes in the physiological, molecular, chemical, and electrical properties of neuronal pathways controlling urinary bladder function in transgenic mice. The results of these studies reveal that autonomic dysfunction (i.e., urinary bladder) can precede motor dysfunction. In addition, mice with hSNCA overexpression in relevant neuronal populations is associated with alterations in expression of neurotransmitter/neuromodulatory molecules (PACAP, VIP, substance P, and neuronal NOS) within neuronal pathways regulating bladder function as well as with increased NGF expression in the urinary bladder. Changes in the electrical and synaptic properties of neurons in the major pelvic ganglia that provide postganglionic innervation to urogenital tissues were not changed as determined with intracellular recording. The urinary bladder dysfunction observed in transgenic mice likely reflects changes in peripheral (i.e., afferent) and/or central micturition pathways or changes in the urinary bladder. SYN-OE mice provide an opportunity to examine early events underlying the molecular and cellular plasticity of autonomic nervous system pathways underlying synucleinopathies.

Algorithms for the management of overactive bladder.

Overactive bladder (OAB) is a highly prevalent and bothersome condition that hampers quality of life in men and women. Increased awareness of available treatment has led growing numbers of patients to seek medical attention in search of relief. Clinical algorithms for the management of OAB would enable physicians who treat these patients to deliver up-to-date, effective care in an expeditious fashion. An algorithmic approach to OAB should allow most patients to receive therapy without the need for an extended evaluation. Patients who fail initial management or have more complicated clinical scenarios should have treatment directed by specialists who can precisely determine the nature of vesicourethral dysfunction underlying their symptoms. This article presents algorithms for the management of OAB in women, men, and patients with neurologic disease.

Preview of new drugs for overactive bladder and incontinence: darifenacin, solifenacin, trospium, and duloxetine.

This year, the US Food and Drug Administration will approve four new drugs indicated for the treatment of lower urinary tract dysfunction. Darifenacin, solifenacin, and trospium are antimuscarinic agents aimed at relieving the symptoms of overactive bladder and urge incontinence in men and women. Duloxetine will be the first drug approved for the treatment of female stress urinary incontinence. This article presents current data on the efficacy and tolerability of these new agents and invites the reader to decide whether they offer any potential advantages over existing therapies.

Microencapsulation of Leydig cells: a system for testosterone supplementation.

The use of testosterone supplementation for elderly men has increased markedly over the last decade due to a recognized gradual decline in serum testosterone, which may lead to decreased bone mass, muscle strength, and libido. Testosterone supplementation is also used widely to treat some forms of erectile dysfunction, androgen deficiency, and infertility. However, long-term exogenous testosterone therapy has been associated with several complications, such as fluid retention, nitrogen retention, and hypertension. Due to these problems, alternate treatment modalities, involving more physiological and longer-acting systems for androgen delivery, have been pursued. Alginate-poly-L-lysine-encapsulated Leydig cell microspheres were used as a novel method for the delivery of testosterone in vivo. Encapsulated Leydig cells, which were stimulated with human chorionic gonadotropin, secreted high levels of testosterone in culture. Unencapsulated cells injected i.p. or s.c. failed to produce any testosterone levels, even with human chorionic gonadotropin stimulation. Castrated rats that were administered encapsulated Leydig cells i.p. or s.c. maintained a serum testosterone level between 0.23 and 0.51 ng/ml. Similar levels of testosterone were obtained for 43 d when the encapsulated Leydig cells were injected s.c. (0.28-0.48 ng/ml). Approximately 10% of a normal adult rat Leydig cell population was injected into each castrated animal; however, this resulted in serum testosterone levels of up to 40% of normal. Clinically, testosterone is usually delivered for supplementation and not for full replacement therapy. Therefore, the findings of this study suggest that microencapsulated Leydig cells may be a viable option as a therapeutic modality involving testosterone supplementation.

Functional brain imaging and the bladder: new insights into cerebral control over micturition.

Mechanisms for cerebral control over the micturition process remain poorly elucidated. The knowledge is based largely on human pathophysiology and data derived from electrophysiologic testing in animals. Recent advances in dynamic functional brain imaging technologies including positron-emission tomography, single photon emission computed tomography, and functional magnetic resonance imaging have allowed new insights into how the human brain regulates this process. This article discusses animal studies, which provided the foundation for our understanding of cerebral control over micturition, and recent human studies, implementing functional brain imaging to enhance our knowledge of this complex phenomenon.

Beyond collagen: injectable therapies for the treatment of female stress urinary incontinence in the new millennium.

Previous experience with GAX-collagen has shown that the endoscopic correction of female SUI is both possible and effective. It is clear, however, that durability remains a primary concern when implementing this approach to treatment. The availability of recently developed and newly emerging materials, carefully designed using the tenets and techniques of biotechnology and materials science, may provide solutions to some of the difficulties beleaguering this treatment option. Results with currently available injectables are summarized in Table 1. Careful review and critical analysis of new bulking agents will soon reveal which materials approach the therapeutic ideal. It is likely that the ultimate choice of a particular substance, synthetic or biologic, may best be determined by the clinical circumstances involving the individual patient.

De novo urge syndrome and detrusor instability after anti-incontinence surgery: current concepts, evaluation, and treatment.

The onset of de novo irritative voiding symptoms after anti-incontinence surgery for stress urinary incontinence is troubling to both patient and physician alike. At present, mechanisms responsible for the development of these symptoms are incompletely elucidated. Although bladder outlet obstruction may certainly be a cause, correct diagnosis and treatment of this condition in its more insidious manifestation may be difficult. In addition, alternative etiologic factors related to surgical technique during outlet enhancing surgery may play a role, prompting a rethinking of these procedures. In this discussion, we review changes in voiding physiology and mechanisms for voiding dysfunction after anti-incontinence surgery, emphasizing de novo urge syndrome and detrusor instability. In addition, we present our approach to the evaluation, diagnosis, and treatment of these challenging patients.

Reconstitution of human corpus cavernosum smooth muscle in vitro and in vivo.

A large number of congenital and acquired abnormalities of the genitalia would benefit from the availability of transplantable, autologous corpus cavernosum tissue for use in reconstructive procedures. We describe the results of preliminary experiments designed to determine the feasibility of using cultured human corporal smooth muscle cells seeded onto biodegradable polymer scaffolds for the formation of corpus cavernosum smooth muscle in vitro and in vivo. Primary cultures of human corpus cavernosum smooth muscle cells were derived from operative biopsies obtained during penile prosthesis implantation. Cells were characterized in vitro and seeded as a contiguous multilayered sheet onto polymers of non-woven polyglycolic acid. The seeded polymer constructs were then implanted subcutaneously in athymic mice. Animals were killed 7, 14, and 24 days after surgery and implants were examined via histology, immunocytochemistry, and Western blot analyses. Cultured cell multilayers were identified as smooth muscle before implantation via phase-contrast microscopy, immunocytochemistry and Western blot analyses. Retrieved implants from all time points demonstrated corporal smooth muscle tissue grossly, and histologically, at the time of sacrifice. Intact smooth muscle cell multilayers were observed growing along the surface of the polymers. There was evidence of early vascular ingrowth at the periphery of the implants by 7 days. By 24 days, there was evidence of polymer degradation. Maintenance of the smooth muscle phenotype in vivo was confirmed immunocytochemically and by Western blot analyses with antibodies to alpha-smooth muscle actin. This study provides evidence that cultured human corporal smooth muscle cells may be used in conjunction with biodegradable polymer scaffolds to create corpus cavernosum smooth muscle tissue in vitro and in vivo.

Blood flow, pressure and compliance in the male human bladder.

PURPOSE: The regulation of human bladder blood flow during filling is poorly understood. We characterized changes in bladder blood flow with filling and examined the relationship of bladder compliance and blood flow. MATERIALS AND METHODS: A total of 17 awake male patients underwent saline cystometry followed by cystoscopy while under local anesthesia, during which a laser Doppler flow probe was placed into the posterior bladder wall detrusor. Systemic blood pressure, bladder blood flow and intravesical pressure were measured with the bladder empty and filled to 25%, 50%, 75% and 100% of awake maximum cystometric capacity as well as immediately after bladder drainage. RESULTS: Mean bladder blood flow was lowest in the empty bladder and increased with bladder filling. A mean peak flow plus or minus standard error of 7.6 +/- 1.1 ml. per minute per 100 gm. tissue was observed at volumes greater than 75% but less than 100% of maximum cystometric capacity. At 100% maximum cystometric capacity mean intravesical pressure increased by 73% from 25.2 to 43.5 cm. water and bladder blood flow decreased by 36%. Rapid bladder drainage was associated with a rebound in mean bladder blood flow to approximately 1.6 times baseline. Bladder compliance calculated for the whole filling curve positively correlated with bladder blood flow (p = 0.025), that is low compliance was associated with low blood flow. CONCLUSIONS: Human bladder blood flow tends to increase with increasing volume and pressure, and depends largely on local regulation. At capacity bladder blood flow is significantly decreased. Immediately after bladder drainage there is a rebound in blood flow, allowing reperfusion to occur. Decreased bladder blood flow and decreased bladder wall compliance correlated strongly, suggesting that ischemia may lead to structural changes in the bladder wall.