David Koslov

Protective Effect of a β3-Adrenoceptor Agonist on Bladder Function in a Rat Model of Chronic Bladder Ischemia

BACKGROUND The β3-adrenoceptor (AR) agonist mirabegron has been introduced as a treatment for the overactive bladder. Its effects on the function of the ischemic bladder are not known. OBJECTIVE To investigate the effect of mirabegron in a rat model of chronic ischemia-related bladder dysfunction. DESIGN, SETTING, AND PARTICIPANTS Male Sprague-Dawley rats were divided into three groups: control (n=10), arterial endothelial injury (AI; n=16), and AI with mirabegron treatment (AI-mirabegron; n=10). AI and AI-mirabegron groups underwent endothelial injury of the iliac arteries and received a 2% cholesterol diet following AI. AI-mirabegron rats received mirabegron (10mg/kg/d) orally for 8 wk. The control group received a regular diet. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS After 8 wk, urodynamic investigation was performed in awake animals. Pharmacologic in vitro studies and histologic examination of the iliac arteries and bladders were performed. RESULTS AND LIMITATIONS Iliac arteries from both AI and AI-mirabegron rats displayed neointimal formation and luminal occlusion. Micturition interval (MI), bladder capacity (Bcap), and voided volume (VV) in the AI group were significantly less than in the control group (p<0.01). In the AI-mirabegron group, MI, Bcap, and VV were significantly larger than in the AI group (p<0.05) but significantly less than in the control group (p<0.05). Contractile responses of bladder strips to potassium chloride, electrical field stimulation, and carbachol were significantly lower after AI than in controls; responses in preparations from AI-mirabegron-treated animals were similar to those of controls. The AI group showed a significantly higher percentage of collagen (28.6 ± 1.57%) compared with the controls (8.65 ± 0.67%) and AI-mirabegron-treated animals (17.2 ± 2.32%). The mirabegron dose used in this study may potentially limit the translational value of the results. CONCLUSIONS In the chronically ischemic rat bladder, treatment with mirabegron seems to protect bladder function and morphology, resulting in reduced bladder hyperactivity. If the results are valid for humans, they support β3-AR agonism as a potential treatment of chronic ischemia-related bladder dysfunction.

Correlation of Gene Expression with Bladder Capacity in Interstitial Cystitis/Bladder Pain Syndrome

PURPOSE Interstitial cystitis and bladder pain syndrome are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, our understanding of disease etiology is poor. We molecularly characterized interstitial cystitis/bladder pain syndrome and determined whether there are clinical factors that correlate with gene expression. MATERIALS AND METHODS Bladder biopsies from female subjects with interstitial cystitis/bladder pain syndrome and female controls without signs of the disease were collected and divided into those with normal and low anesthetized bladder capacity, respectively. Samples then underwent RNA extraction and microarray assay. Data generated by these assays were analyzed using Omics Explorer (Qlucore, Lund, Sweden), GeneSifter® Analysis Edition 4.0 and Ingenuity® Pathway Analysis to determine similarity among samples within and between groups, and measure differentially expressed transcripts unique to each phenotype. RESULTS A total of 16 subjects were included in study. Principal component analysis and unsupervised hierarchical clustering showed clear separation between gene expression in tissues from subjects with low compared to normal bladder capacity. Gene expression in tissue from patients with interstitial cystitis/bladder pain syndrome who had normal bladder capacity did not significantly differ from that in controls without interstitial cystitis/bladder pain syndrome. Pairwise analysis revealed that pathways related to inflammatory and immune response were most involved. CONCLUSIONS Microarray analysis provides insight into the potential pathological condition underlying interstitial cystitis/bladder pain syndrome. This pilot study shows that patients with this disorder who have low compared to normal bladder capacity have significantly different molecular characteristics, which may reflect a difference in disease pathophysiology.

The Role of Urinary Diversion for Bladder Pain

Interstitial cystitis/bladder pain syndrome is a complex urologic disorder often managed in a non-operative fashion, but patients with severe symptoms occasionally require surgical intervention. Several approaches to reconstruction have been reported, including trigone-sparing cystectomy with enterocystoplasty, simple cystectomy with diversion, and diversion without cystectomy. While a trigone-sparing approach offers the potential for spontaneous voiding, it leaves bladder and urethral tissue that can cause pain postoperatively. Final choice of surgery is based upon surgeon and patient preference. In recent years, enhanced recovery after surgery (ERAS) protocols modeled after colorectal surgery have been utilized for radical cystectomy postoperative management with success. These approaches can be used for cystectomy for non-malignant cases as well.

Bladder and Ureteral Dysfunction Leading to Hydronephrosis and Hydroureteronephrosis in Adults

Chronic non-stone-related hydronephrosis from supravesical or bladder dysfunction in adults is often detected incidentally. This study aims to review the literature regarding supravesical obstruction or bladder dysfunction leading to bilateral hydronephrosis in adults and to develop an algorithm to identify patients at risk of renal failure. Cross-sectional studies, retrospective and prospective cohorts, clinical trials, and systematic reviews from 1980 to 2017 were included. From 8115 articles screened, 39 met the inclusion criteria. Despite the lack of studies addressing this issue, this review brings up a rational evidence-based algorithm to diagnose and manage adults with bilateral hydronephrosis due to supravesical or bladder disease or dysfunction.

Impact of Cystectomy with Urinary Diversion upon Tracked Receipt of Opioid Prescriptions among Patients with Interstitial Cystitis/Bladder Pain Syndrome

OBJECTIVE To compare opioid requirements before and after cystectomy for end-stage Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) using a statewide tracking system. METHODS Narcotic prescriptions were captured using the North Carolina Controlled Substance Reporting System for patients at a single institute undergoing cystectomy with urinary diversion (CWUD) for refractory, end-stage IC/BPS between 2010 and 2017. Values were documented for the year before and the year after surgery (excluding 30 days postoperatively to account for surgical pain) and converted to morphine equivalents (ME). Values were compared using Student t test. RESULTS Following CWUD, there was a mean decrease in opioid receipt per patient of 6535 ME/year (P = .321). 8/26 (31%) had not filled any opiate prescriptions for the preceding 3 months at time of manuscript writing. CONCLUSION In certain patients with end-stage, refractory IC/BPS, CWUD can help reduce opioid requirements.

Transcriptome analysis of bladder biopsy from interstitial cystitis/bladder pain syndrome patients.

Interstitial cystitis and bladder pain syndrome (IC/BPS) are terms used to describe a heterogeneous chronic pelvic and bladder pain disorder. Despite its significant prevalence, the disease etiology is not well understood and providing diagnosis and treatment can be challenging. In our study, published recently in the Journal of Urology (Colaco et al., 2014), we describe the use of microarrays as a tool to characterize IC/BPS and to determine if there are clinical factors that correlate with gene expression. This data-in-brief article describes the methodology for that study, including data analysis, in further detail. Deposited data can be found in the Gene Expression Omnibus (GEO) database: GSE57560.