Delayed Treatment With Low-intensity Extracorporeal Shock Wave Therapy in an Irreversible Rat Model of Stress Urinary Incontinence.

OBJECTIVE: To determine the outcomes and mechanisms of delayed low-intensity extracorporeal shock wave therapy (Li-ESWT) in a rat model of irreversible stress urinary incontinence (SUI). MATERIALS AND METHODS: Twenty-four female Sprague-Dawley rats were randomly assigned into 3 groups: sham control, vaginal balloon dilation + ß-aminopropionitrile (BAPN; SUI group), and vaginal balloon dilation + BAPN + treatment with Li-ESWT (SUI-Li-ESWT group). An irreversible SUI model was developed by inhibiting the urethral structural recovery with BAPN daily for 5 weeks. Thereafter, in the SUI-Li-ESWT group, Li-ESWT was administered twice per week for 2 weeks. After a 1-week washout, all 24 rats were evaluated with functional and histologic studies at 17 weeks of age. Endogenous progenitor cells were detected via the EdU-labeling method. RESULTS: Functional analysis with leak point pressure testing showed that the SUI-Li-ESWT group had significantly higher leak point pressures compared with untreated rats. Increased urethral and vaginal smooth and striated muscle content and increased thickness of the vaginal wall were noted in the SUI-Li-ESWT group. The SUI group had significantly decreased neuronal nitric oxide /tyrosine hydroxylase positive nerves ratio in the smooth muscle layers of the urethra, while the SUI-Li-ESWT group had neuronal nitric oxide/tyrosine hydroxylase+ nerves ratio similar to that of the control group. The continuality of urothelial cell lining was also improved in the SUI-Li-ESWT group. In addition, there were significantly increased EdU-positive cells in the SUI-Li-ESWT group. CONCLUSION: Li-ESWT appears to increase smooth muscle content in the urethra and the vagina, increase the thickness of urethral wall, improve striated muscle content and neuromuscular junctions, restore the integrity of the urothelium, and increase the number of EdU-retaining progenitor cells in the urethral wall.

Treatment of stress urinary incontinence with low-intensity extracorporeal shock wave therapy in a vaginal balloon dilation induced rat model.

BACKGROUND: To investigate the outcomes and mechanisms of low-intensity extracorporeal shock wave therapy (Li-ESWT) on stress urinary incontinence (SUI) in a vaginal balloon dilation (VBD) rat model. METHODS: Thirty Sprague-Dawley rats were randomly grouped into normal controls, VBD only, and VBD with Li-ESWT. Li-ESWT was administered twice per week for 3 weeks. Afterward, all 30 rats were assessed with functional and histological studies. To explore the acute effect of Li-ESWT, another 25 rats, given intraperitoneal 5-ethynyl-2-deoxyuridine (EdU) at birth, were treated with Li-ESWT followed by assessment of vascular endothelial growth factor (VEGF) expression and endogenous progenitor cells distribution at 24 hours or 1 week after the last Li-ESWT therapy. Additionally, rat myoblast L6 cells were used for myotube formation assay in vitro. RESULTS: Functional analysis with leak-point pressure (LPP) testing showed that rats treated with Li-ESWT following VBD had significantly higher LPP relative to those receiving VBD only (44.8±3.2 versus 27.0±2.9 cmH2O, P<0.01). Histological examinations showed increased urethral sphincter regeneration in Li-ESWT group. The rats treated with Li-ESWT also had increased vascularity, which was confirmed by immunohistochemistry of rat endothelial cell antigen, while reverse-transcriptase polymerase chain reaction (RT-PCR) showed VEGF expression was significantly enhanced. Additionally, there were significantly increased EdU+ cells in Li-ESWT treated rats at 24 hours. In vitro, Li-ESWT promoted myotube formation from L6 cells. CONCLUSIONS: Li-ESWT ameliorated SUI by promoting angiogenesis, progenitor cell recruitment, and urethral sphincter regeneration in a rat model induced by VBD. Li-ESWT represents a potential novel non-invasive therapy for SUI.

Identifying factors associated with need for flexible ureteroscope repair: a Western Endourology STone (WEST) research consortium prospective cohort study.

Maintenance of flexible ureteroscopes can involve high costs and administrative burden. Instrument fragility necessitates eventual repair, rendering scopes inaccessible during refurbishment. We conducted a multi-institutional prospective cohort study to identify perioperative factors influencing flexible ureteroscope durability. Patients undergoing flexible ureteroscopy (URS) at six United States endourology centers were enrolled between August 2014 and June 2015. Surgeon self-reported concern and satisfaction with scope performance as well as upward and downward angles of deflection for each scope tip were measured before and after each procedure. The need for scope repair was determined by the operating surgeon at the time of the procedure and recorded. 424 URS cases using 74 flexible ureteroscopes were identified. Scope repair was required in 28 cases (6.6%) involving 26 scopes (35.1%). Upon univariate analysis, shorter patient height, absence of guidewire use, presence of a ureteral access sheath (UAS), longer procedure time, larger stone size, lithotrite type, surgeon training level, and self-reported concern were associated with scope repair. Upon multivariate analysis, UAS use (OR = 2.53, p = 0.005) and degree loss of scope upward flexion during a case (OR = 1.02, p = 0.03) increased the odds of a scope needing repair while the use of safety guidewire decreased the odds of a scope repair (OR = 0.50, p = 0.045). Lithotrite use and surgeon concern were associated with degree loss of scope upward flexion. The use of a UAS, absence of a safety guidewire, and the loss of upward ureteroscope flexion should be considered when evaluating means of optimizing reusable ureteroscope durability.

Pubic Bone Resection Provides Objective Pain Control in the Prostate Cancer Survivor With Pubic Bone Osteomyelitis With an Associated Urinary Tract to Pubic Symphysis Fistula.

OBJECTIVE: To investigate pain intensity perception in prostate cancer survivors with pubic bone osteomyelitis with an associated urinary tract to pubic symphysis fistula before and after definitive surgical management. MATERIALS AND METHODS: We performed a review of an institutional review board-approved database of prostate cancer survivors with pubic bone osteomyelitis from 2010 to 2015. Demographic and clinical data were extracted. Pain scores were assessed in patients at varying points before and after definitive treatment using an 11-point numeric rating scale. Statistical analysis was performed using a Wilcoxon signed-rank test and NcNemar's test. RESULTS: We identified 16 patients with a median age of 72 who met inclusion criteria. Chronic narcotic use for pain management was noted in 6 of 16 (37.5%) patients preoperatively. No statistical difference was identified between the pain score at the time of diagnosis and after completion of conservative measures (5.5 vs 5.5, P = .76). A statistically significant decrease in median pain score at the first follow-up appointment was seen compared to the preoperative pain score (0 vs. 5.5, P = .0005). At a median follow-up of 9.4 months (interquartile range 3.7-16.5), a sustained decrease in the median pain intensity score was noted in our cohort compared to their preoperative baseline pain score (5.5 vs 0, P = .0005) and pain score at the time of diagnosis (5.5 vs 0, P = .004.) CONCLUSION: Pubic bone resection provides immediate and sustained improvement in pain intensity perception in the prostate cancer survivor with pubic bone osteomyelitis with an associated urinary tract to pubic symphysis fistula.

Genitourinary Prosthetics: A Primer for the Non-urologic Surgeon.

Genitourinary prosthetics are used for correction of functional deficits and to improve the quality of lives of affected patients. General surgeons must evaluate patients scheduled for nonurologic surgery with urologic devices that can impact their perioperative management. Lack of recognition of these prosthetics preoperatively can lead to unnecessary morbidity for the patient and have legal implications for the surgeon. Close consultation with a urologist may avoid common complications associated with these devices and allows for surgical assistance when operative misadventures do occur. This article reviews 3 common urologic prosthetics: testicular prosthesis, artificial urinary sphincter, and penile prosthesis.

Transurethral Unroofing of a Symptomatic Imperforate Cowper's Syringocele in an Adult Male.

Cystic dilatation of bulbourethral gland ducts (Cowper's gland syringocele) is a rare abnormality. The condition has been described among pediatric populations, but it is uncommon in adults. It can be asymptomatic or present with obstructive and irritative urinary symptoms. We report a case of a symptomatic imperforate Cowper's syringocele in a young patient that was successfully managed with transurethral unroofing of the cyst.

Management of the Recurrent Male Urethral Stricture.

Urethral stricture disease negatively impacts quality of life and leads to significant urologic pathology including lower urinary tract symptoms, recurrent urinary tract infections, and potentially more severe sequelae such as detrusor dysfunction, renal failure, urethral carcinoma, and Fournier's gangrene. Open urethral reconstruction is considered a durable and definitive treatment for urethral stricture with lifetime success rates ranging from 75-100%; however, strictures do recur up to 10 years after surgery. Recurrence rates vary by repair type. There also is no agreed-upon modality for recurrence surveillance, but there are many modalities with varying degrees of invasiveness. Recurrent strictures may be managed endoscopically or via open repair. We review stricture recurrence rates, surveillance modalities, risk factors, and management options.

Urethral musculature and innervation in the female rat.

AIMS: The urethral sphincter and urethral muscle innervation are critically involved in maintaining continence, especially in the female. However, the urethral muscle type and distribution, as well as the urethral nerves are far from being well documented. Our aim was to clearly identify the distribution of urethral striated muscle, smooth muscle, and urethral nerves. METHODS: In a cohort analysis of 3-month-old female Sprague-Dawley rats, cross and longitudinal sections of female rat urethra were extensively investigated using morphological techniques. Urethras were harvested to the sections, in order to provide both global and detailed visions of the urethra. H&E, Masson's Trichrome, phalloidin and immunoflourence stains were used. The cytoarchitecture, nitrergic, and cholinergic innervations were mainly investigated. Different layers of the segments of urethra were traced to draw curve graphs that represent the thickness of each muscle layer of urethral wall. RESULTS: The results showed that the primary peak of striated muscle is in the middle urethra. The inner layer close to mucosa was found to contain longitudinal smooth muscle. Near the bladder orifice, the circular smooth muscle dominates, which becomes thinner distally throughout the rest of urethra. In the middle urethra the vast majority of the urethral muscle are circularly oriented striated muscle cells. Typical nerve endings were present in high power images to show the different characteristic features of nerve innervation. CONCLUSIONS: This study has illustrated the detailed morphological structure and innervations of the normal female rat urethra and can serve as a basis for further study of stress urinary incontinence (SUI).

Penetrating Trauma to the Ureter, Bladder, and Urethra.

We describe the epidemiology, diagnosis, and management of adult civilian penetrating trauma to the ureter, bladder, and urethra. Trauma is a significant source of death and morbidity. Genitourinary injuries are present in 10% of penetrating trauma cases. Prompt recognition and appropriate management of genitourinary injuries, which are often masked or overlooked due to concomitant injuries, is essential to minimize morbidity. Penetrating trauma most commonly results from gunshot wounds or stab wounds. Compared to blunt trauma, these typically require surgical exploration. An understanding of anatomy and a high index of suspicion are necessary for prompt recognition of genitourinary injuries.

Lupus cystitis presenting with urinary symptoms.

We present a case of a young woman presenting with irritative lower urinary tract symptoms and microscopic hematuria who was diagnosed with systemic lupus erythematosus (SLE). Abdominal ultrasound revealed bilateral hydronephrosis and a thickened bladder wall. Cystoscopic evaluation revealed severe diffuse inflammation, erythema and hemorrhage at the trigone with punctate extensions to the bladder base. She was treated with prednisone and mycophenolate mofetil with improvements in her symptoms and ultrasound findings. Lupus cystitis is a rare manifestation of SLE.

The incidence, causes, mechanism, risk factors, classification, and diagnosis of pelvic fracture urethral injury.

BACKGROUND: Pelvic fracture urethral injury (PFUI) is an uncommon but potentially devastating result of pelvic fracture. It ranges in severity based on the cause and the mechanism of injury. METHODS: We reviewed previous reports to identify the incidence, causes, mechanisms of injury and risk factors of PFUI. In addition, we reviewed the current classification systems and diagnostic methods that have been described to assess the severity of PFUI, to identify optimal management strategies and evaluate outcomes. RESULTS: PFUI occurs more commonly in men, but is more likely to be severe in children. The most common cause is motor vehicle collisions, and the mechanism is typically a ligament rupture at the attachment to the urethra. There is no reliable classification system to differentiate partial and complete PFUI. Retrograde urethrography is the standard imaging method but it has its limitations. CONCLUSIONS: Despite many reports describing this injury, there is still a need to further clarify the incidence, aetiology and mechanism of injury to better determine optimal management strategies and evaluate outcomes. Consensus in the diagnosis of PFUI is lacking, and outcomes of primary realignment and the role of flexible cystoscopy as a diagnostic method are still to be determined.

Novel therapeutic approach for neurogenic erectile dysfunction: effect of neurotrophic tyrosine kinase receptor type 1 monoclonal antibody.

BACKGROUND: Erectile dysfunction (ED) is a major health issue in aged populations, and neurogenic ED is particularly difficult to treat. Novel therapeutic approaches are needed for treatment of neurogenic ED of peripheral origin. OBJECTIVE: To investigate the therapeutic effects of a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) on erectile function and sexual behavior in a rat model of cavernous nerve injury (CNI). DESIGN, SETTING, AND PARTICIPANTS: In one experiment, 84 male rats were randomly assigned to seven groups. The groups underwent either CNI or sham surgery, subsequent injection into the major pelvic ganglion (IMPG) of phosphate-buffered saline (PBS), an immunoglobulin G (IgG) control, or TrkA-mAb, and then intracavernosal (IC) injection of either PBS or varying TrkA-mAb concentrations immediately after surgery and then 1 wk later. Erectile function was assessed and histologic/molecular analyses were performed at 6 wk after surgery. In a second experiment, 36 male rats were randomly divided into three groups. The groups underwent CNI or sham surgery and then IC injection of PBS, IgG, or TrkA-mAb immediately after surgery and for 5 wk thereafter. At 6 wk after surgery, the performance of the rats in sexual behavior tests was videotaped. INTERVENTION: CNI or sham surgery; IMPG of PBS, IgG, or TrkA-mAb; IC injection of PBS or TrkA-mAb. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The intracavernous pressure response to cavernous nerve electrostimulation was measured and midpenile cross-sections were histologically examined. Western blotting (WB) of cavernous tissue protein was performed. Rats were assessed for chasing, mounting, intromission, and ejaculation behaviors during sexual behavior tests. The data were analyzed using one-way analysis of variance followed by the Tukey-Kramer t test. RESULTS AND LIMITATIONS: Recovery of erectile function of varying degrees was observed in the TrkA-mAb groups. TrkA-mAb treatment significantly suppressed tyrosine hydroxylase-positive nerve fibers in the corpus cavernosum and enhanced neuronal nitric oxide synthase-positive fibers in the dorsal nerve. The ratio of smooth muscle to collagen in the corpus cavernosum was significantly improved in TrkA-mAb treatment groups compared to PBS vehicle and IgG control groups. WB confirmed these biological changes. There was a nonsignificant increase in the average number of intromissions and ejaculations in the TrkA-mAb group. The study limitations include small sample size, variability in sexual behavior, lack of data on the neuromuscular mechanism involved, and lack of information of the role of neurotrophins or cytokines in regeneration. CONCLUSIONS: TrkA-mAb successfully inhibits sympathetic nerve regeneration, leads to parasympathetic nerve regeneration, and has therapeutic effects on ED and sexual behavior disorder in a rat model of CNI. PATIENT SUMMARY: This report provides strong evidence that a neurotrophic tyrosine kinase receptor type 1 monoclonal antibody (TrkA-mAb) inhibits sympathetic nerve regeneration, leads to parasympathetic nerve regeneration, and has therapeutic effects on erectile dysfunction and sexual behavior disorder in a rat model of cavernous nerve injury. The results raise the possibility that human patients with neurogenic erectile dysfunction may respond to TrkA-mAb in a manner that parallels the response seen in our rodent study.

The cost of surveillance after urethroplasty.

OBJECTIVE: To determine variability in urethral stricture surveillance. Urethral strictures impact quality of life and exact a large economic burden. Although urethroplasty is the gold standard for durable treatment, strictures recur in 8%-18%. There are no universally accepted guidelines for posturethroplasty surveillance. We performed a literature search to evaluate variability in surveillance protocols, analyzed costs, and reviewed performance of each commonly used modality. METHODS: MEDLINE search was performed using the keywords "urethroplasty," "urethral stricture," and "stricture recurrence" to ascertain commonly used surveillance strategies for stricture recurrence. We included English language articles from the past 10 years with at least 10 patients, and age >18 years. Cost data were calculated based on standard 2013 Centers for Medicare and Medicaid Services physician's fees. RESULTS: Surveillance methods included retrograde urethrogram or voiding cystourethrogram, cystourethroscopy, urethral ultrasound, American Urological Association Symptom Score, and postvoid residual and urine flowmetry (UF) measurement. Most protocols call for a retrograde urethrogram or voiding cystourethrogram at the time of catheter removal. After this, UF or PVR, cystoscopy, urine culture, or a combination of UF and American Urological Association Symptom Score was performed at variable intervals. The first-year follow-up cost of anterior urethral surgery ranged from $205 to $1784. For posterior urethral surgery, follow-up cost for the first year ranged from $404 to $961. CONCLUSION: Practice variability for surveillance of urethral stricture recurrence after urethroplasty leads to significant differences in cost.

Trends, utilization, and immediate perioperative complications of urethroplasty in the United States: data from the national inpatient sample 2000-2010.

OBJECTIVE: To determine national urethroplasty trends based on type of surgery and patient and hospital characteristics. We hypothesized that the number of complex urethroplasty procedures performed has increased over time and may be associated with increased periprocedure complications. METHODS: The National Inpatient Sample from years 2000 to 2010 was queried for patients with urethroplasty-associated International Classification of Diseases, Ninth Revision, Clinical Modification codes. We analyzed trends in urethroplasty procedures, patient demographics, comorbidities, and hospital characteristics. We evaluated the relationship between patient demographics and comorbid disease, length of hospital stay, hospital charges, and inpatient complications. RESULTS: During the study period, an estimated 13,700 men (95% confidence interval, 9507-17,894) underwent urethroplasty nationally. Excision with primary anastomosis, buccal graft, and other graft or flap urethroplasty comprised 80.3%, 14.3%, and 5.4%, respectively. Buccal mucosa graft procedures increased over time (P = .03). Only 1.6% of hospitals have ≥ 20 urethroplasties performed annually. Urethroplasty type and urethroplasty volume were not associated with immediate complication rates. Hypertension, diabetes, chronic pulmonary disease, and obesity were the most common comorbidities in urethroplasty patients. Complications during urethroplasty hospitalization occurred in 6.6% of men, with surgical or wound complications being the most common (5.2%). Postoperative mortality was exceedingly rare. Older patients, African Americans, and patients with increased comorbidities were more likely to have complications. CONCLUSION: An increasing number of buccal mucosa graft urethroplasties occurred over time. Urethroplasty patients have low immediate perioperative morbidity (6.6%) and mortality (0.07%). Patients who are older, African American, or have more comorbid conditions have greater risk for complications.

Case series of lipid accumulation in the human corpus cavernosum.

Erectile dysfunction is a prevalent problem affecting millions of men in the United States and around the world. There have been no reports of the presence of lipids within the human penile corporal bodies, whether in normal or diseased states. We present here a case series of 9 patients who underwent penile corporal tissue biopsy during penile prosthesis insertion with severe intracorporal fibrosis and difficulties during insertion.Oil Red O staining was done to identify lipids; LipidTOX and phalloidin double staining was used to identify lipid location within the corpora, and Masson's trichrome staining was done to assess fibrosis.We identified lipid accumulation in those 9 corporal tissue samples, and further analysis showed the distribution to be 10% intramyocellular lipids and 90% extramyocellular lipids. These 9 specimens contained increased amount of collagen when compared with controls. In addition, we analyzed corporal samples from 10 random erectile dysfunction patients presenting for penile prosthesis insertion and identified no lipid accumulation in those control patients.This is the first report of lipid accumulation in the human corpus cavernosum. Possible mechanisms of lipid accumulation include androgen deficiency and dedifferentiation of corpus smooth muscle cells into other phenotypes; however, the exact mechanism is unknown and further research is needed.

Stem cell treatment of erectile dysfunction.

Erectile Dysfunction (ED) is a common disease that typically affects older men. While oral type-5 phosphodieserase inhibitors (PDE5Is) represent a successful first-line therapy, many patients do not respond to this treatment leading researchers to look for alternative treatment modalities. Stem cell (SC) therapy is a promising new frontier for the treatment of those patients and many studies demonstrated its therapeutic effects. In this article, using a Medline database search of all relevant articles, we present a summary of the scientific principles behind SCs and their use for treatment of ED. We discuss specifically the different types of SCs used in ED, the methods of delivery tested, and the methods attempted to enhance SC therapy effect. In addition, we review the current preclinical literature on SC therapy for ED and present a summary of its findings in addition to the single clinical trial published.

Management of Peyronie's disease after collagenase (Xiaflex:®).

Although the prevalence of Peyronie's disease (PD) is reported to be 3-9% in men, the true prevalence is likely higher due to under-reporting. Many treatment modalities have been described for PD with varying degrees of success. In this article, we review and summarize the current literature pertaining to all pharmacotherapies (oral, intralesional, iontophoresis, and topical) and minimally invasive treatments available for PD (vacuum, traction device, shock wave therapy, and radiation treatment). Additionally, we discuss emerging therapies for PD that are still in pre-clinical development, including stem cell therapy.

Surgical management of Peyronie's disease.

Peyronie's disease (PD) has a significant impact on the quality of life of both patients and their partners due to the compromised sexual function and physical deformation resulting from the condition. PD is a connective tissue disorder marked by fibrotic healing of the tunica albuginea, leading to penile deformities including curvature, shortening, loss of girth, hourglass appearance, and hinging. Despite the multiple medical therapies available, surgery is the gold standard of treatment once the plaque has stabilized. We present a review of the disease process, preoperative evaluation, operative planning, surgical treatments with outcomes and complications, and nascent developments in surgical management and graft development. Options include tunical lengthening procedures, tunical shortening procedures, and penile prosthesis. Decision-making is governed by degree of curvature, erectile function, and associated penile deformities. In cases with curvature of less than 60-70 degrees, adequate penile length, and no hourglass deformity, patients are candidates for tunical shortening procedures. Patients with curvature greater than 60-70 degrees, penile hourglass or hinge-destabilizing deformities, and adequate erectile function should be counseled with regard to tunical lengthening procedures. Patients with poor preoperative erectile function should undergo inflatable penile prosthesis placement, with possible secondary straightening procedures. Technique selection should be based upon surgeon preference, expertise, and experience, as evidence does not necessarily support one procedure over another.

Presentation, management, and outcomes of complications following prostate cancer therapy.

OBJECTIVE: To characterize complications of prostate cancer therapy and operative management in patients referred to our institution for surgical intervention. MATERIALS AND METHODS: Data was abstracted from a retrospectively collected single surgeon database at a large tertiary care referral-based medical center. Variables included age, prostate cancer therapy, complication(s) and their management, and number of operations. Descriptive statistics were used. RESULTS: From 2006-2010, 890 patients underwent genitourinary surgery, of which 139 were to treat complications arising from prostate cancer therapy. Complications stemmed from radical prostatectomy (RP) monotherapy, RP and external beam radiation therapy (EBRT) or brachytherapy (BT), EBRT only, BT only, and combination EBRT and BT. Complications included urinary incontinence (UI), urethral strictures, bladder neck contractures, and fistulas. UI and bladder neck contractures were more common in patients treated with RP or RP with EBRT or BT. Strictures and fistulas were common in patients treated with EBRT or BT. Interventions included direct vision internal urethrotomy, artificial urinary sphincter, urethral reconstruction, UroLume urethral stent, urethral sling, repair of fistulas, and balloon dilation. Forty eight percent of patients required multiple operations. The median number of interventions was two. CONCLUSIONS: We operatively managed patients treated with non-surgical and surgical modalities for prostate cancer. Complications included UI, fistulas, strictures, and bladder neck contractures. These were managed with a variety of operative interventions. As more men undergo treatment for localized disease, more will inevitably have complications stemming from interventions.