What is the predictive value of urodynamics to reproduce clinical findings of urinary frequency, urge urinary incontinence, and/or stress urinary incontinence?

INTRODUCTION AND HYPOTHESIS: The aim of this study was to determine the predictive value of urodynamics to reproduce clinical findings of urinary frequency (UF), urge urinary incontinence (UUI), and/or stress urinary incontinence (SUI). METHODS: We retrospectively reviewed the data of patients diagnosed with UF, UUI, and/or SUI and subsequently underwent urodynamics. Urodynamic findings were correlated with clinical findings to determine the predictive value of urodynamics. RESULTS: A total of 537 patients (366 females and 171 males) met study criteria. Two hundred seventy-eight patients had symptoms of UUI; 59% demonstrated detrusor overactivity on urodynamics. Three hundred eight patients had SUI on history and physical examination; 45% had urodynamic stress incontinence. A low maximum cystometric capacity (<200 ml) was not significantly associated with urinary frequency (p = 0.4). CONCLUSIONS: Urodynamics has a low predictive value to reproduce clinical findings of UF, UUI, and/or SUI. Many patients with evidence of UF, UUI, and/or SUI on history and/or physical examination do not demonstrate supporting urodynamic evidence.

Small cell carcinoma of the bladder in transplant recipients: a report of 2 cases.

Small cell carcinoma (SCC) of the urinary bladder is a rare disease accounting for 0.5% to 0.7% of all primary bladder cancers. Transplant recipients are a special subset of patients with increased risk for various urologic malignancies, including transitional cell carcinoma of the bladder. However, to the best of our knowledge, a SCC of the urinary bladder has not been reported in transplant recipients. We report what we believe are the first 2 reported cases of transplant recipients with SCC of the bladder. Small cell carcinoma was diagnosed 5 years after transplantation in both patients and they died due to metastatic SCC. Our report emphasizes the highly aggressive nature of SCC and also the rapid progression seen in transplant recipients.

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.

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

AIMS: To evaluate the clinical outcomes of two different doses of BTX-A in patients with I-OAB. METHODS: This investigator initiated, randomized trial was designed to evaluate clinical differences in outcomes for 100 versus 150 U BTX-A in patients with I-OAB. Patients with OAB-Wet and OAB-Dry were randomized to receive 100 or 150 U BTX-A intra-detrusor injection. For patients with OAB-Wet, the primary outcome of interest was change in daily UUI episodes, and for those with OAB-Dry the primary outcome measure was change in number of daily voids as determined by 3-VD. Statistical comparisons were made both pre- and post-injection and also between different treatment groups to assess the superiority of one dose versus the other. RESULTS: Forty-four patients enrolled in the study; 10 OAB-Dry and 12 OAB-Wet patients received 100 U and another 10 OAB-Dry and 12 OAB-Wet patients received 150 U. No significant differences in outcome measure were noted between those receiving 100 versus 150 U. Patients with OAB-Wet tended to be completely dry more frequently if they received the 150 U dose, but this was not statistically significant. No differences in urodynamics outcomes were noted between the groups. QOL was significantly improved in both groups with no difference between the different doses. CONCLUSIONS: In patients with I-OAB, preliminary results indicate that 100 U BTX-A and 150 U BTX-A are equivalent in terms of symptom reduction and QOL improvement.

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.

Current techniques for vesicovaginal fistula repair: surgical pearls to optimize cure rate.

Vesicovaginal fistulas (VVFs) are a devastating consequence of prolonged labor in developing countries and pelvic surgery in developed countries. Clinical history, physical examination, and pertinent radiographic studies are necessary for proper diagnosis. Endoscopic management can lead to successful closure of small fistulas; the advent of tissue bioglues has made this modality more promising. However, the majority of patients will require transvaginal or transabdominal repair of the fistula. This article reviews the basic principles of fistula closure and discusses adjuvant techniques with tissue interposition grafts; techniques for successful closure of fistulas; and newer modalities for repair using tissue bioglues, laparoscopy, and robotic surgery.

Safety and tolerability of sedation-free flexible cystoscopy for intradetrusor botulinum toxin-A injection.

PURPOSE: Intradetrusor botulinum toxin-A injection is a promising emerging therapy for neurogenic and idiopathic overactive bladder that is refractory to current antimuscarinic agents. We evaluated a sedation-free procedure using flexible endoscopy to perform intradetrusor botulinum toxin-A injection using a validated pain score to assess the tolerability of this technique. MATERIALS AND METHODS: Five men and 22 women with idiopathic overactive bladder refractory to antimuscarinics were prospectively evaluated and randomized to 100 U (14) or 150 U botulinum toxin-A (13). Subjects underwent BTA injection with intravesical lidocaine using a 14Fr Olympus flexible cystoscope, which accommodates a 27 gauge flexible Olympus injection needle. Patients were evaluated with the visual analog scale to evaluate discomfort during and 15 minutes after the procedure. Procedure time was recorded. RESULTS: In 22 female patients the mean pain score was 3.1 (range 0 to 10) during the procedure and 0.7 (range 0 to 7) 15 minutes after the procedure. In 5 male patients the mean pain score was 1.6 (range 0 to 3.5) during the procedure and 0.0 with all reporting no pain 15 minutes after the procedure. Mean procedure time was 4.5 minutes (range 4 to 6). Only 1 of the 27 patients requested sedation before any subsequent injections. CONCLUSIONS: Sedation-free intradetrusor botulinum toxin-A injection using intravesical lidocaine and flexible endoscopy is a well tolerated and safe procedure to perform in an office setting.

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 x 10(6) 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 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 > or = 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.

Racial differences in prostate androgen levels in men with clinically localized prostate cancer.

PURPOSE: We sought to determine whether there are racial differences in androgenic stimulation within the prostate tissue microenvironment. MATERIALS AND METHODS: Steroid hormones were extracted from snap frozen tissue obtained intraoperatively from radical prostatectomy specimens of 36 black and 59 white Americans. Testosterone, dihydrotestosterone (DHT), androstenedione (ASD), dehydroepiandrosterone, dehydroepiandrosterone sulfate, sex hormone-binding globulin (SHBG) and prostate specific antigen (PSA) were measured using radioimmunoassay. The Wilcoxon 2 group test was performed to compare clinical characteristics and tissue steroid levels between white and black Americans. Nonparametric rank ANOVA was used to consider race and other clinical factors in a multivariable way. RESULTS: Black and white American men were similar with respect to serum PSA, and pathological grade and stage. However, black men were younger (p = 0.01) and had a significantly higher body mass index (p = 0.02). Black and white men had similar testosterone and DHT. However, black men had higher ASD (p = 0.006) and SHBG (p = 0.009). Racial differences in ASD (p = 0.015) and SHBG (p = 0.008) persisted after controlling for age, body mass index, PSA, and pathological Gleason sum and stage. CONCLUSIONS: Tissue levels of testosterone and DHT did not differ by race. However, black men had higher tissue ASD and SHBG than white men. Higher tissue ASD did not result in a greater conversion of ASD to testosterone in the prostate of black men. Higher tissue SHBG may activate the androgen receptor through cyclic adenosine monophosphate dependent pathways.