Christine Tran

The potential role of stem cells in the treatment of urinary incontinence.

Voiding dysfunction encompasses a wide range of urologic disorders including stress urinary incontinence and overactive bladder that have a detrimental impact on the quality of life of millions of men and women worldwide. In recent years, we have greatly expanded our understanding of the pathophysiology of these clinical conditions. However, current gold standard therapies often provide symptomatic relief without targeting the underlying etiology of disease development. Recently, the use of stem cells to halt disease progression and reverse underlying pathology has emerged as a promising method to restore normal voiding function. Stem cells are classically thought to aid in tissue repair via their ability for multilineage differentiation and self-renewal. They may also exert a therapeutic effect via the secretion of bioactive factors that direct other stem and progenitor cells to the area of injury, and that also possess antiapoptotic, antiscarring, neovascularization, and immunomodulatory properties. Local injections of mesenchymal, muscle-derived, and adipose-derived stem cells have all yielded successful outcomes in animal models of mechanical, nerve, or external urethral sphincter injury in stress urinary incontinence. Similarly, direct injection of mesenchymal and adipose-derived stem cells into the bladder in animal models of bladder overactivity have demonstrated efficacy. Early clinical trials using stem cells for the treatment of stress urinary incontinence in both male and female patients have also achieved promising functional results with minimal adverse effects. Although many challenges remain to be addressed prior to the clinical implementation of this technology, novel stem-cell-based therapies are an exciting potential therapy for voiding dysfunction.

Sexual dysfunction in chronic prostatitis/chronic pelvic pain syndrome

Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), or NIH category III prostatitis, is a common clinical syndrome characterized by genital/pelvic pain and lower urinary tract symptoms in the absence of urinary tract infection. There is also growing recognition of the association of sexual dysfunction with CP/CPPS including erectile dysfunction, ejaculatory pain, and premature ejaculation. In this review, we discuss the association between CP/CPPS and sexual dysfunction, potential mechanisms for sexual dysfunction, and treatment strategies for erectile dysfunction in CP/CPPS.

Erosion of Inflatable Penile Prosthesis Reservoir into Neobladder

INTRODUCTION Erosion of the reservoir into surrounding tissues is a rare complication after inflatable penile prosthesis (IPP) implantation. AIM To present a new case and a review of the literature including discussion of pathogenesis, risk factors, and management options. METHODS We present the case of a 75-year-old male who underwent placement of an IPP for postoperative erectile dysfunction with a history of bladder cancer requiring radical cystoprostatectomy and Studer neobladder. Six years after IPP placement, he presented with recurrent febrile urinary tract infection that seemed to be precipitated by cycling of his penile prosthesis. Cystoscopy and cross-sectional computed tomography imaging demonstrated erosion of the inflatable penile prosthesis reservoir into the neobladder. RESULTS Patient underwent open removal of the IPP reservoir and cystorrhaphy with a plan for future prefascial reimplantation of an IPP reservoir. CONCLUSIONS In patients with a history of abdomino-pelvic surgery or radiation therapy, the retroperitoneal space may be extremely fibrotic and the transversalis fascia may have thickened. Potential intraoperative complications as well as reservoir erosion may be avoided by using a two-piece device or ectopic reservoir placement. Management options for reservoir erosion include explantation of the entire device as well as reservoir removal with salvage of remaining components.

Anterior Urethral Valve Associated With Posterior Urethral Valves: Report of 2 Cases and Review of the Literature

Anterior urethral valve (AUV) associated with posterior urethral valves (PUVs) is an extremely rare congenital urologic anomaly resulting in lower urinary tract obstruction. We present our experience with 2 children with concomitant AUV and PUV as well as a literature review. The clinical presentation of concomitant AUV and PUV is variable. Successful endoscopic management can result in improvement in renal function, reversal of obstructive changes, and improvement or resolution of voiding dysfunction.

Propranolol for Treatment of Genital Infantile Hemangioma

PURPOSE Genital infantile hemangiomas are vascular anomalies that often require complex management and interdisciplinary care. Propranolol was first used to treat patients with infantile hemangiomas in 2008 and has since gained acceptance as first-line therapy. MATERIALS AND METHODS We review the presentation, course, management and outcomes of all cases of genital infantile hemangiomas managed by propranolol administration at a single institution from April 2010 to July 2014. RESULTS During the study period 9 patients with genital infantile hemangiomas were referred to our hemangioma treatment clinic. Propranolol was initially administered under careful outpatient monitoring at a dose of 1 mg/kg daily in 8 patients. One patient, a 700 gm premature infant, was started on therapy in the inpatient setting at 0.5 mg/kg daily, given the history of prematurity. All patients underwent successful increase of dose to at least 2 mg/kg for the observation phase after tolerating the starting doses. One patient discontinued propranolol prematurely per parental request due to concern regarding peripheral vasoconstriction. Otherwise, no patient demonstrated significant hypotension, symptomatic bradycardia, hypoglycemia or other major side effect requiring treatment discontinuation. All patients who continued the treatment protocol had excellent response to therapy. CONCLUSIONS Propranolol therapy for genital infantile hemangiomas was successfully initiated and the dosage increased in 9 young children without significant side effects and with marked improvement in all patients who continued on treatment. Propranolol is the only Food and Drug Administration approved therapy for treatment of patients with this vascular anomaly and should be considered first-line therapy for genital infantile hemangiomas.

AB306. SPR-33 Systemic treatment of stress urinary incontinence with human urine-derived stem cells

Objective Stem cell based therapy has emerged as a promising treatment alternative for stress urinary incontinence (SUI). Human urine-derived stem cells (USCs) have no risk from biopsy and therefore may be a better option than other adult stem cells. Possible therapeutic mechanisms of action of stem cells are homing of cells to areas in need of repair and secretion of bioactive paracrine factors acting systemically as well as locally. We hypothesized that USCs or their secretome alone would promote functional recovery in a rodent model of female SUI even when given systemically. Methods Thirty two-female Sprague-Dawley rats were randomized into three groups and underwent vaginal distension (VD) followed by intraperitoneal (ip) delivery of USCs (VD + USCs) VD and ip delivery of saline as a vehicle control, or sham VD with ip saline. Three additional groups (32 rats) were utilized to investigate if factors secreted by USCs alone facilitate recovery from VD: concentrated conditioned media (CCM) from USCs given ip after VD, concentrated control media (CM) given ip after VD, and CM given ip after sham VD. All treatments were given 1 hour after VD or sham VD. CCM was generated by incubating confluent USCs in serum-free media for 24 hours. Cultured supernatant was then extracted, washed, and concentrated to form CCM. One week after injury, treatment efficacy was assessed by measurement of leak point pressure (LPP), and qualitative anatomical assessment of the urethra. Quantitative data were analyzed by one-way analysis of variance (ANOVA) and Holm-Sidak post hoc tests with P<0.05 indicating a significant difference. Results LPP significantly increased after VD in rats treated with USCs or CCM, compared to animals that received saline, but not significantly different from sham VD. Collagen infiltration of striated muscle in the external urethral sphincter, along with substantial muscle fiber attenuation and disruption of the striated muscle layers were noted, as has been observed previously in this model. External urethral sphincter structure was greatly improved with USC implantation, and was more similar to that of sham-injured animals than injured rats treated with saline. Elastin fibers in VD + USCs and VD + CCM animals were long, thickened, and mostly oriented compared to the short, thin, and disoriented fibers in VD + saline and VD + CM animals. No human USCs were found in the region of urethra. Conclusions Ip injection of USCs and their secretions facilitate recovery from SUI in a rat model, likely via systemic and paracrine mechanisms. Elastogenesis may play a role in recovery of urethral function. USCs represent an attractive, alternate stem cell source with no biopsy risk to target the underlying pathophysiology in SUI. Funding Source(s) NIH NIDDK R56 DK100669-01A1, the Research Projects Committee of the Cleveland Clinic, and the Rehabilitation R&D Service of the Department of Veterans Affairs

Renal Transplantation in Patients with Lower Urinary Tract Dysfunction

Lower urinary tract (LUT) dysfunction is a leading cause of pediatric end-stage renal disease (ESRD). It is estimated that 15–25 % of children with ESRD have associated anatomic urological abnormalities that result in LUT dysfunction [1]. These problems may persist into adulthood and also comprise an important cause of ESRD in approximately 6 % of the older population [2]. It was previously thought that renal transplantation in the setting of an abnormal LUT was unfeasible and these patients were generally considered poor candidates for transplantation [1, 3–5].

Testicular Myeloid Sarcoma: A Rare Manifestation of Acute Myeloid Leukemia in an Infant

Myeloid sarcoma manifesting in the testis is rare and may occur concomitantly with bone marrow disease or as a separate entity. We describe our experience with a 6-month-old boy who presented with painless scrotal swelling and was found to have bilateral testicular masses on ultrasonography. The patient underwent unilateral radical inguinal orchiectomy. Surgical pathology revealed myeloid sarcoma of the testicle. He developed peripheral blood involvement 1 week postoperatively. Bone marrow biopsy showed acute myeloid leukemia. He is in remission after 2 cycles of induction chemotherapy, local radiation therapy, and allogeneic bone marrow transplantation.