Brian L. Cohen

The impact of lower urinary tract symptoms and urinary incontinence on female sexual dysfunction using a validated instrument.

INTRODUCTION Lower urinary tract symptoms (LUTS) is a common problem in women and frequently coexists with female sexual dysfunction (FSD). However, the relationship of LUTS and FSD is poorly characterized. AIM To evaluate the relationship of LUTS and urinary incontinence (UI) to FSD using a validated instrument, the female sexual function index (FSFI). METHODS We performed an institutional review board-approved retrospective evaluation of 236 female patients over a 3-year time-period who completed an FSFI-validated questionnaire and underwent urodynamics (UDS) evaluation for LUTS or UI. Patients were categorized based upon history and physical exam into different LUTS groups. Additionally, the presence or absence of UI, detrusor overactivity (DO), stress urinary incontinence, and maximal cystometric capacity (MCC) > or <200 mL on UDS were used to further evaluate these patients. FSFI domain and total scores were compared between the different LUTS groups. MAIN OUTCOME MEASURE FSFI scores were evaluated for women with similar clinical LUTS diagnosis and UDS findings. The Kruskal-Wallis nonparametric test and the Dwass-Steel test determined statistical significance and performed multiple pairwise comparisons between the different voiding dysfunction groups and those with normal UDS (Leak-/DO-/urodynamic stress incontinence-). RESULTS The mean age of the cohort was 49.5 (range 18-69), and there was no statistically significant difference in mean age within each LUTS subgroup. MCC < 200 mL did not significantly impair female sexual function. Patients with clinical diagnosis of overactive bladder (OAB)-Dry had the highest sexual function while those with mixed urinary incontinence had the worst. Additionally, women with UI and DO had the greatest degree of FSD, which was significantly worse than those with normal UDS. Additionally, for women with or without UI, the presence of DO on UDS resulted in a trend toward worse sexual function. CONCLUSIONS The sexual function of women is negatively impacted by the presence of LUTS, with UI and DO causing the greatest degree of FSD. The sexual domains most affected are desire, lubrication, orgasm, and sexual satisfaction.

Predictors of Success for First Stage Neuromodulation: Motor Versus Sensory Response

PURPOSE We investigated whether intraoperative motor or sensory response is more predictive of successful sacral neuromodulation using the InterStim system. MATERIALS AND METHODS A total of 35 patients with medically refractory frequency, urgency and urge incontinence were enrolled in the study. All patients underwent lead placement for quadripolar test stimulation under local anesthesia with intravenous sedation. Confirmation of correct lead placement was by observation of known motor and sensory responses that result from third sacral nerve stimulation. Motor and sensory responses were documented intraoperatively. Patients had a 1-week trial of stimulation, and those who had greater than 50% improvement in symptoms had placement of the implantable pulse generator. Those without at least 50% improvement in their symptoms had the quadripolar lead removed. RESULTS Of the 35 patients enrolled 21 had successful quadripolar test stimulation and went on to permanent implantable pulse generator placement. Of the patients who had successful quadripolar test stimulation 95% demonstrated positive intraoperative motor response whereas only 21.4% of patients with unsuccessful quadripolar test stimulation demonstrated positive motor response. If only a positive sensory response was elicited, patients had only a 4.7% chance of having a positive quadripolar test stimulation. CONCLUSIONS A positive quadripolar test stimulation (greater than 50% improvement in symptoms) with InterStim sacral neuromodulation is more likely when intraoperative lead placement results in positive motor response vs only sensory response.

Cyclooxygenase-2 (cox-2) expression is an independent predictor of prostate cancer recurrence

Lack of reliable prognostic markers hinders accurate prediction of disease progression in prostate cancer. The inducible proinflammatory enzyme cyclooxygenase‐2 (COX‐2) is implicated in prostate carcinogenesis, but its role in cancer progression is less clear. We examined whether COX‐2 expression evaluated by immunohistochemistry (IHC) in radical prostatectomy (RP) specimens can predict biochemical recurrence. Archival prostate cancer specimens (n = 60) were obtained from patients who underwent RP, but had not received neoadjuvant hormonal therapy. Twenty‐three patients had biochemical or clinical recurrence (mean time of recurrence: 38.2 months), and 37 patients were recurrence free (mean follow‐up: 95 months). COX‐2 expression was determined by IHC, using an anti‐COX‐2 antibody. Three individuals scored the staining independently, as high‐ or low‐expression. COX‐2 was expressed in prostate cancer cells, in adjacent normal glands and in specimens from patients who later progressed. At 62‐months follow‐up, COX‐2 staining predicted progression with 82.4% sensitivity and 81.3% specificity. Sensitivity (86.4%) and specificity (86.7%) improved at ≥ 100‐months follow‐up. In univariate analysis, Gleason score, preoperative PSA, extraprostatic extension, margin, seminal vesicle invasion, and high COX‐2 expression were significant predictors of biochemical recurrence (p < 0.05). In multivariate analysis, preoperative PSA (hazard ratio/unit PSA change 1.080; p = 0.0036) and COX‐2 expression (hazard ratio 16.442; p < 0.0001) were independent prognostic indicators. Patients with PSA > 7 ng/ml and high COX‐2 expression had the highest probability of recurrence (Kaplan‐Meier analysis). COX‐2 expression is an independent predictor of prostate cancer progression following RP and underscores the significance of inflammatory factors in this process.

Preliminary results of a dose‐finding study for botulinum toxin‐A in patients with idiopathic overactive bladder: 100 versus 150 units

To evaluate the clinical outcomes of two different doses of BTX‐A in patients with I‐OAB.

HAS1 expression in bladder cancer and its relation to urinary HA test

Hyaluronic acid (HA) levels are elevated in bladder cancer tissues and regulate tumor growth and progression. Urinary HA levels measured by the HA test are an accurate marker for bladder cancer. In cells, HA is synthesized by one of the 3 HA‐synthase(s) i.e., HAS1, HAS2 and HAS3. In this study, we examined HAS1 expression in bladder cancer cells and tissues. Real‐time RT‐PCR and northern blot analyses showed that HAS1 transcript levels are elevated 5‐ to 10‐fold in bladder cancer tissues, when compared with normal tissues (p < 0.001). Among the 3 HAS1 splice variants, only HAS1‐va was expressed in bladder tissues, but the expression was significantly lower than the wild type HAS1 transcript. Increased HAS1 expression in bladder tumor tissues correlated with increased tissue HA levels (p < 0.001). Size of the large HA species (2.0 × 106 D) present in bladder tissues was consistent with the size of the HA polymer synthesized by HAS1. The amount of HA produced by bladder cancer cell lines correlated with the expression of HAS1 protein. Immunohistochemical analyses of bladder tumor tissues showed that HAS1 and HA expression had 79–88% sensitivity and 83.3–100% specificity. Both HAS1 and HA expression in bladder cancer tissues correlated with a positive HA urine test (p < 0.001). HAS1 expression correlated with tumor recurrence, prior treatment (p < 0.05) and possibly disease progression (p = 0.058). Therefore, elevated HAS1 expression in bladder tumor tissues contributes to a positive HA urine test and may have some prognostic potential.

Predictors of Response to Intradetrusor Botulinum Toxin-A Injections in Patients with Idiopathic Overactive Bladder

Objectives. To evaluate whether there are any demographic or urodynamic differences in patients with idiopathic overactive bladder (I-OAB) that respond and do not respond to intradetrusor injections of botulinum toxin-A (BTX-A). Methods. This represents a secondary analysis of data collected from an investigator initiated randomized trial designed to evaluate clinical differences in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Preinjection demographic and urodynamic data were collected. Patients were evaluated 12 weeks after injection and were determined to be responders or nonresponders as defined by our criteria. Statistical comparisons were made between groups. Results. In patients with overactive bladder without incontinence (OAB-Dry), there were no variables that could be used to predict response to BTX-A. On univariate analysis, younger patients with overactive bladder with incontinence (OAB-Wet) were more likely to respond to BTX-A than older patients. However, this relationship was no longer statistically significant on multivariate analysis. Conclusions. We were unable to identify any preinjection demographic or urodynamic parameters that could aid in predicting which patients will achieve clinical response to BTX-A. Future studies are necessary to further evaluate this question.

THE NEED FOR INTERMITTENT CATHETERIZATION DURING REPEATED BOTOX® INJECTIONS FOR IDIOPATHIC OAB

Hypothesis / aims of study In this prospective, IRB approved, randomized, ongoing study we evaluated the efficacy of intra-detrusor injection of BOTOX ® botulinum A toxin (BTX) in patients (pts) with idiopathic overactive bladder (IOAB) resistant to antimuscarinic therapy. The aim of this study was to evaluate the post-void residual volume (PVR) throughout the study and to assess how many patients will need self intermittent catheterization (CIC).