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.

Tumor-associated myeloid cells can be activated in vitro and in vivo to mediate antitumor effects.

Tumor growth is often accompanied by the accumulation of myeloid cells in the tumors and lymphoid organs. These cells can suppress T cell immunity, thereby posing an obstacle to T cell-targeted cancer immunotherapy. In this study, we tested the possibility of activating tumor-associated myeloid cells to mediate antitumor effects. Using the peritoneal model of B16 melanoma, we show that peritoneal cells (PEC) in tumor-bearing mice (TBM) had reduced ability to secrete nitric oxide (NO) following in vitro stimulation with interferon gamma and lipopolysaccharide, as compared to PEC from control mice. This reduced function of PEC was accompanied by the influx of CD11b(+) Gr-1(+) myeloid cells to the peritoneal cavity. Nonadherent PEC were responsible for most of the NO production in TBM, whereas in naïve mice NO was mainly secreted by adherent CD11b(+) F4/80(+) macrophages. Sorted CD11b(+) Gr-1(-) monocytic and CD11b(+) Gr-1(+) granulocytic PEC from TBM had a reduced ability to secrete NO following in vitro stimulation (compared to naïve PEC), but effectively suppressed proliferation of tumor cells in vitro. In vivo, treatment of mice bearing established peritoneal B16 tumors with anti-CD40 and CpG resulted in activation of tumor-associated PEC, reduction in local tumor burden and prolongation of mouse survival. Inhibition of NO did not abrogate the antitumor effects of stimulated myeloid cells. Taken together, the results indicate that in tumor-bearing hosts, tumor-associated myeloid cells can be activated to mediate antitumor effects.

Long-term Follow Up of Ileal Ureteral Replacement for Complex Ureteral Strictures: Single Institution Study.

OBJECTIVE: To report our 16-year experience with ileal ureter interposition for complex ureteral stricture. Ureteral reconstruction continues to evolve to include less invasive techniques to successfully manage ureteral stricture. However, long, complex, obliterative and especially radiated ureteral strictures are not amenable to less invasive techniques and may require Ileal ureter interposition. MATERIALS AND METHODS: Retrospective review of a single institution's ureteral reconstruction database was performed. Demographics, operative details, success rate, complication rate, and length of follow-up were noted. Unilateral replacements utilized ileal ureteral interposition. Success rate was defined as no need for further open intervention. RESULTS: Between 2003 and 2019, 188 ureteral reconstructions were performed, of which 46 required ileal ureter interposition. Of these 46 patients, 10 required bilateral reconstruction. Average age was 53 years, 26 (57%) were female. The average stricture length was 9.1 cm (2-20 cm). Stricture etiology included iatrogenic causes (n = 24, 52%), radiation causes (n = 12; 26%), vascular disease (n = 3; 7%), and idiopathic retroperitoneal fibrosis (n = 3; 7%). Forty-three surgeries were performed by open abdominal approach; 3 were performed robotically. The average length of operation was 412 minutes, blood loss 417 mL and LOS was 10 days. At mean follow up of 4.4 years (1-16 years), overall success rate was 83%, with 17% (n = 8) patients requiring subsequent major surgery (5 successful ureteral revision, 3 nephrectomy) and 11 (24%) patients experiencing a major complication. CONCLUSION: In our long-term follow up of over 4 years, ileal ureteral interposition remains a successful option for complex ureteral strictures in properly selected patients.

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.

Physiological and pharmacological aspects of the vas deferens-an update.

The vas deferens, a muscular conduit conveying spermatozoa from the epididymis to the urethra, has been used as a model tissue for smooth muscle pharmacological and physiological advancements. Many drugs, notably α-adrenergic antagonists, have effects on contractility and thus normal ejaculation, incurring significant side effects for patients that may interfere with compliance. A more thorough understanding of the innervation and neurotransmitter pharmacology of the vas has indicated that this is a highly complex structure and a model for co-transmission at the synapse. Recent models have shown clinical scenarios that alter the vas contraction. This review covers structure, receptors, neurotransmitters, smooth muscle physiology, and clinical implications of the vas deferens.

Changing stone composition profile of children with nephrolithiasis.

OBJECTIVE: To determine if this trend toward calcium phosphate stone formation exists in children. METHODS: This is a retrospective study of medical records of 179 children managed at our medical center from 1992-2010 for whom stone analysis and other pertinent laboratory data were available. A comparison of patients managed from 1992-2000 (P1) and 2001-2010 (P2) was undertaken. Statistical analysis included nonparametric tests. RESULTS: There were no significant differences in the mean age of the 2 cohorts. During both periods, boys comprised a significantly higher proportion during the first decade of life, whereas girls comprised a significantly higher proportion during the second decade. A higher percentage of patients had calcium oxalate (CaOx) stones in P1 compared to P2 (60% vs 47%, P = .0019). There was a significant increase in the percentage of patients having calcium phosphate stones in P2 compared to P1 (27% vs 18.5%, P = .008). Twenty-seven patients had recurrent stones. A comparison of the compositions of the first and last stones of patients within this group demonstrated an increasing proportion of brushite stones (3.7% vs 11.1%, P = .04). Twenty-four hour urine testing results were similar for those with CaOx and calcium phosphate stones. CONCLUSION: An increasing proportion of children have calcium phosphate calculi. Brushite stones are more prevalent in children with recurrent stone events. The impetus of these shifts is not readily apparent.