This study reveals that combination therapy consisting of alpha1-adrenoceptor antagonists with antimuscarinics represents an effective and relatively safe treatment modality in select patients with OAB coexisting with benign prostatic obstruction.
Pelvic diaphragm thickness and the ratio of levator ani thickness to prostate volume are independent factors predictive of post-prostatectomy incontinence. Patients with better developed pelvic floor muscles, especially in relation to the size of the prostate, can be expected to achieve earlier recovery of continence after radical prostatectomy.
An accurate measurement of the peak urinary flow rate could predict women at risk for postoperative urinary retention that compromises global satisfaction after the highly curative TVT procedure.
Interstitial cystitis/bladder pain syndrome (IC/BPS) is an intractable disease characterized by severe pelvic pain and urinary frequency. Mesenchymal stem cell (MSC) therapy is a promising approach to treat incurable IC/BPS. Here, we show greater therapeutic efficacy of human embryonic stem cell (hESC)-derived multipotent stem cells (M-MSCs) than adult bone-marrow (BM)-derived counterparts for treating IC/BPS and also monitor long-term safety and in vivo properties of transplanted M-MSCs in living animals. Controlled hESC differentiation and isolation procedures resulted in pure M-MSCs displaying typical MSC behavior. In a hydrochloric-acid instillation-induced IC/BPS animal model, a single local injection of M-MSCs ameliorated bladder symptoms of IC/BPS with superior efficacy compared to BM-derived MSCs in ameliorating bladder voiding function and histological injuries including urothelium denudation, mast-cell infiltration, tissue fibrosis, apoptosis, and visceral hypersensitivity. Little adverse outcomes such as abnormal growth, tumorigenesis, or immune-mediated transplant rejection were observed over 12-months post-injection. Intravital confocal fluorescence imaging tracked the persistence of the transplanted cells over 6-months in living animals. The infused M-MSCs differentiated into multiple cell types and gradually integrated into vascular-like structures. The present study provides the first evidence for improved therapeutic efficacy, long-term safety, and in vivo distribution and cellular properties of hESC derivatives in preclinical models of IC/BPS.
Interstitial cystitis (IC) is a syndrome characterized by urinary urgency, frequency, pelvic pain, and nocturia in the absence of bacterial infection or identifiable pathology. IC is a devastating disease that certainly decreases quality of life. However, the causes of IC remain unknown and no effective treatments or cures have been developed. This study evaluated the therapeutic potency of using human umbilical cord-blood-derived mesenchymal stem cells (UCB-MSCs) to treat IC in a rat model and to investigate its responsible molecular mechanism. IC was induced in 10-week-old female Sprague-Dawley rats via the instillation of 0.1 M HCl or phosphate-buffered saline (PBS; sham). After 1 week, human UCB-MSC (IC + MSC) or PBS (IC) was directly injected into the submucosal layer of the bladder. A single injection of human UCB-MSCs significantly attenuated the irregular and decreased voiding interval in the IC group. Accordingly, denudation of the epithelium and increased inflammatory responses, mast cell infiltration, neurofilament production, and angiogenesis observed in the IC bladders were prevented in the IC + MSC group. The injected UCB-MSCs successfully engrafted to the stromal and epithelial tissues and activated Wnt signaling cascade. Interference with Wnt and epidermal growth factor receptor activity by small molecules abrogated the benefits of MSC therapy. This is the first report that provides an experimental evidence of the therapeutic effects and molecular mechanisms of MSC therapy to IC using an orthodox rat animal model. Our findings not only provide the basis for clinical trials of MSC therapy to IC but also advance our understanding of IC pathophysiology.
contraction and storage function after RP were compared for changes in subjective symptoms.
RESULTSOn serial UDS, there were reductions in maximum cystometric capacity, maximum detrusor pressure and maximum urethral closure pressure (MUCP) at 3 months, after which all remained relatively unchanged. On the questionnaire, the voiding symptom domain score improved (8.04 to 4.82, P < 0.001) while the storage domain score significantly and progressively worsened, beginning from 3 months (2.25 to 3.78, P = 0.04), resulting in an unchanged overall urinary symptom-related quality of life at 3 years. The incidence of detrusor overactivity increased from 37.5% before RP, to 45.8% at 3 months and 51.4% at 3 years. At 3 years, a recurring postvoid residual urine volume was the cause of the deterioration in the voiding symptom domain score, while a prominent reduction in MUCP resulted in a deterioration in the storage symptom score.
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