Marc Colaco

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.

Current recommendations for bladder instillation therapy in the treatment of interstitial cystitis/bladder pain syndrome.

Bladder instillation therapy refers to the direct introduction of medication into the bladder and is a common treatment modality for patients with interstitial cystitis/bladder pain syndrome (IC/BPS) who have failed conservative and oral therapies. The current American Urological Association (AUA) recommendations list three medications as options for IC/BPS instillation therapy: dimethyl sulfoxide, heparin, and lidocaine. The purpose of this review is to examine the evidence behind the recommendations for these medications. We also examine several historical or experimental therapies that do not hold recommendations but are still used on rare occasion. Finally, we discuss our bladder instillation strategies as well as potential future research and development in intravesicular therapy.

Evidence-based outcomes for mesh-based surgery for pelvic organ prolapse.

Purpose of review In light of all the recent controversy regarding the use of synthetic mesh for pelvic organ prolapse, we did a retrospective review of the evidence-based outcomes and complications for its use. Recent findings A total of 18 of the most recent studies in the last 5 years were selected. Studies selected were prospective randomized or quasi-randomized controlled trials that included surgical operations for pelvic organ prolapse for this review. Additionally, Cochrane review and meta-analysis of outcomes and complication were also analyzed. In terms of outcomes, the definition of successful surgery is currently being debated. Synthetic mesh provides superior anatomical and subjective cure rates compared with native tissue repair. Success rates varied greatly depending on the nature of prolapse and surgical approach. Furthermore, recurrence rates for mesh-based surgery are significantly lower than that for native tissue repair. The main unique complication of mesh is exposure and was reported in a mean of 11.4% of patients, with 6.8% of patients requiring surgical partial excision of mesh. Summary Mesh significantly improves anatomical outcomes with sacrocolpopexy and vaginal repair. Mesh does create the unique complication which can be reduced with training and proper patient selection. Further development of better materials is vital rather than reverting to tissue-based repair. Ultimately, the decision to use mesh should be based upon a patients personal goals and preferences after an informed conversation with her physician.

The scientific basis for the use of biomaterials in stress urinary incontinence (SUI) and pelvic organ prolapse (POP).

To review the scientific and clinical literature to assess the basis for the use of biomaterials in stress urinary incontinence (SUI) and pelvic organ prolapse (POP). Pelvic floor diseases (PFDS), such as SUI and POP, are common and vexing disorders. While synthetic mesh‐based repairs have long been considered an option for PFD treatment, and their efficacy established in randomised clinical trials, safety of its use has recently been called into question.

Current guidelines in the management of interstitial cystitis

Interstitial cystitis (IC) is a heterogeneous chronic disease of unknown etiology that impacts a very large number of women. Symptoms are highly variable: patients may suffer from pelvic pain that is exacerbated by bladder filling, and can be associated with a variety of lower urinary tract symptoms including frequency and urgency. Given the varying presentations and severities of corresponding treatment must be tailored to each specific patient. Current American Urological Association (AUA) guidelines separate the IC treatment recommendations into six tiers of increasing invasive therapies. These treatment guidelines begin with education and lifestyle modifications and progress through levels of physical, pharmacological, and ultimately surgical therapies for those that fail the less invasive therapies. The purpose of this review is to outline the recommendations for the treatment of IC and the evidence from which these recommendations arise. Furthermore, we examine the most up to date literature so that we may recognize future directions in the treatment of IC.

Waves of Change: National Trends in Surgical Management of Male Stress Incontinence

OBJECTIVE To determine the trend in surgical management of male stress urinary incontinence (SUI) in the context of the rate of radical prostatectomy (RP) as reported by a national database. Traditionally, the artificial urinary sphincter (AUS) has been the gold standard, but the male sling represents a newer and popular alternative. Refinements in prostate surgery may reduce the incidence and degree of subsequent SUI. MATERIALS AND METHODS A retrospective cross-sectional analysis was performed using the National Inpatient Survey database, which captures discharge data from inpatient and overnight admissions. Cases were identified by their International Classification of Diseases, Ninth Revision procedure codes. We queried the codes 58.93 (implantation of AUS), 59.4 (suprapubic sling operation), 59.5 (retropubic urethral suspension), and 59.6 (paraurethral suspension). We also queried 60.5 (RP) for comparison. Data were collected from January 2000 to December 2012 and weighted to a national average using National Inpatient Survey guidelines. RESULTS A total of 32,416 anti-incontinence operations (20,790 AUS and 11,625 sling procedures) were performed over the study period. There was a significant downward trend in the total number of incontinence procedures (F(1,11) = 6.15, P = .03). However, when stratifying the data by procedure type, only AUS placement demonstrated a significant decline (F(1,11) = 21.70, P <.01), whereas sling procedures significantly increased (F(1,11) = 12.95, P <.01). There was no significant change in the annual incidence of RP. CONCLUSION Inpatient surgery for male SUI is decreasing overall. Placement of the AUS declined significantly, whereas sling placement became more common. Future study will determine the etiology of these trends.

Anterior Urethroplasty Has Transitioned to an Outpatient Procedure Without Serious Rise in Complications: Data From the National Surgical Quality Improvement Program

OBJECTIVE To analyze the trend in inpatient vs outpatient performance of anterior urethroplasty and examine outcomes using data from the National Surgical Quality Improvement Program database. METHODS A retrospective cross sectional analysis was performed using the National Surgical Quality Improvement Program database. Cases of single-stage anterior urethroplasty from 2006 to 2013 were identified using the International Classification of Diseases, Ninth Revision, procedure code 53410. Univariate analysis was performed to compare 30-day complication rates for inpatient and outpatient cases. A linear regression model was created for all years with greater than 50 reported cases. RESULTS A total of 326 anterior urethroplasties were reported; 222 (68.1%) were inpatient procedures, and 104 (31.9%) were outpatient procedures. The most common complication, urinary tract infection, was consistent between inpatient (2.7%) and outpatient (2.9%) procedures. The rate of wound dehiscence was significantly higher among outpatient cases (1.92% vs 0%, P = .03). There were no significant differences in the rates of wound infection, bleeding, graft failure, deep vein thrombosis, pneumonia, or sepsis. The linear regression model shows a significant increase in outpatient procedures (R2 = 0.91) and equivalent decrease in inpatient procedures (R2 = 0.91) for the last 3 years of the study period. Resident involvement was associated with a decreased rate of reoperation (0% vs 8.3% P <.001). CONCLUSION There has been a shift in the performance of anterior urethroplasty toward outpatient management. Overall, complication rates appear low. Future research is necessary to determine how to decrease overall cost of single-stage urethroplasty without compromising quality of care.

The Relationship Between Temperament, Gender, and Childhood Dysfunctional Voiding

Objective. Dysfunctional voiding (DV) is an extremely common pediatric complaint. The goal of this study was to examine the relationship between DV and childhood temperament. Methods. Information about the voiding behaviors and temperaments of 50 children was examined using a case–control model. Caregivers were asked to fill out the Children’s Behavior Questionnaire in order to rate their child on the dimensions of surgency, negative affect, and effortful control. The relationship between DV and these dimensions was then evaluated. Results. Males with DV were found to have lower effortful control than males with normal voiding habits. Females with DV did not demonstrate a difference in effortful control, but did demonstrate a higher rate of surgency. Conclusions. The results suggest that temperament does have an association with DV. These findings are in line with temperamental associations with other externalizing trouble behaviors and may inform potential treatment strategies for DV.

Toilet Training Method Is Not Related to Dysfunctional Voiding

Background. Toilet training is an important marker of physical and psychosocial development, but the best strategy for implementing training is still unknown. The purpose of this study is to compare dysfunctional voiding outcomes for 2 common toilet training strategies: parent-oriented training and child-oriented training. Materials and methods. This study was completed using a case-control design, with participants between the ages of 4 and 12 years. All participants were asked to complete questionnaires related to demographics and toilet training method. Results were then analyzed between cases and controls. Results. In all, 215 patients with a mean age 7.76 years participated in this study. Cases and controls showed no significant difference for demographic measures and socioeconomic status. Furthermore, there was no significant difference in dysfunctional voiding between toilet training methods. Conclusion. Toilet training method does not seem to have any long-term effect on dysfunctional voiding. As such, clinicians should advise parents that both methods are acceptable.

Daily Enema Regimen Is Superior to Traditional Therapies for Nonneurogenic Pediatric Overactive Bladder

Our objective was to evaluate the efficacy of daily enemas for the treatment of overactive bladder (OAB) in children. This study was a prospective, controlled trial of 60 children with nonneurogenic OAB. The control patients (40) were treated with standard therapies, including timed voiding, constipation treatment with osmotic laxatives, anticholinergics, and biofeedback physical therapy, whereas the treatment patients (20) received only daily enemas and osmotic laxatives. On assessment of improvement of OAB symptoms, only 30% of the traditionally treated patients’ parents reported resolution of symptoms at 3 months, whereas 85% of enema patients did. At the onset of the study, the average pediatric voiding dysfunction score of all patients was 14, whereas on follow-up, the average scores for traditionally treated patients and enema-treated patients were 12 and 4, respectively. This study demonstrated that daily enema therapy is superior to traditional methods for the treatment of OAB.