The extracellular matrix molecules versican and hyaluronan in urethral and vaginal tissues in stress urinary incontinence.

PURPOSE: Abnormal extracellular matrix (ECM) changes are correlated with stress urinary incontinence (SUI). The ECM components versican (Vcan) and hyaluronan (HA) play key roles in regulating tissue inflammation and maintaining connective tissue homeostasis. We analyzed the localization and expression of these ECM components in urethral and vaginal tissues from a rat model of urinary incontinence and from human clinical specimens. METHODS: Nulliparous rats underwent vaginal distension (VD), a rodent model of SUI, or a sham procedure. Tissues were harvested from six rats per group at days 1, 4, and 21 for immunohistochemistry and RNA expression analysis of ECM components. Periurethral vaginal samples from female patients with SUI were also examined. RESULTS: High-intensity staining for Vcan was observed 1 day after procedure in both control and VD animals. This level of abundance persisted at day 4 in VD compared to control, with concurrent reduced messenger RNA (mRNA) expression of the Vcan-degrading enzymes ADAMTS5 and ADAMTS9 and reduced staining for the Vcan cleavage epitope DPEAAE. Abundance of HA was not different between VD and control, however mRNA expression of the HA synthase Has2 was significantly reduced in VD tissues at day 4. Abundant Vcan staining was observed in 60% of SUI patient samples, which was strongest in regions of disrupted elastin. CONCLUSION: Reduction of Vcan-degrading enzymes and HA synthases at day 4 postsurgery indicates a potential delay in ECM turnover associated with SUI. Abundant Vcan is associated with inflammation and elastin fiber network disruption, warranting further investigation to determine its role in SUI pathogenesis.

Management of nocturia in the female.

Nocturia is a common but overlooked lower urinary tract symptom that substantially reduces patient health and quality of life. Though traditionally viewed as occurring predominantly in males, nocturia has been found to be equally as prevalent in females. The recent emphasis on the importance of nocturia has resulted in a surge of research studies, providing a foundation for current and future management decisions. In this review, we describe the current recommendations for the female patient in light of the most recently published studies, including a unique interest in predicting treatment response.

Mixed incontinence: what takes precedence in its management?

Mixed urinary incontinence is a commonly encountered condition for urologists, urogynecologists, and primary care providers. In this review, we discuss the approach to the evaluation and management of patients with simultaneous stress and urgency urinary incontinence. The available evidence for treatment modalities in the setting of mixed urinary incontinence is presented, and we discuss our treatment algorithm for this common but challenging clinical scenario. An accurate assessment of stress and urge symptoms and their relative impact on quality of life help guide the management plan, appropriate counseling, and appropriate appraisal of patient expectations for treatment.

Grading variability of urothelial carcinoma: experience from a single academic medical center.

INTRODUCTION: Tumor grade plays a critical role in the management of papillary non-invasive urothelial carcinoma (UC). Since grading of UC relies on morphologic criteria, variability in interpretation exists among pathologists. The objective of this study was to examine inter-observer variability in the grading of papillary non-invasive UC at a single academic medical center. MATERIALS AND METHODS: One general pathologist and two genitourinary pathologists were blinded to patient identity and graded 98 consecutive UC specimens using the 1973 and 2004 classification systems. Kappa statistics (κ) were used to measure inter-observer reproducibility to account for agreement expected purely by chance. By convention, Ï° values from 0.21-0.4 represent "fair", from 0.41-0.6 represent "moderate", and > 0.6 represent "substantial" agreement. RESULTS: Raw percentage agreement among all three pathologists was only 26% using the 1973 system and 47% using the 2004 system. When measured by kappa, overall agreement was only "fair" for both systems and while higher for the 2004 system than the 1973, this was not significant (: 0.38 versus 0.26, respectively). There were no significant differences in agreement when comparing the specialists agreement between themselves with agreement between each specialist and the generalist (Ï°: 0.31-0.37 versus Ï°: 0.18-0.46). CONCLUSIONS: The current grading system continues to demonstrate challenges in reproducibility among general and specialized pathologists. The degree of variability has significant implications on management decisions for non-invasive UC. Our findings underscore the need to identify molecular markers that can provide a more objective and reliable risk stratification system to guide patient management.

Comparison of health-related quality-of-life outcomes for African-American and Caucasian-American men after radical prostatectomy.

UNLABELLED: What's known on the subject? and What does the study add? In addition to a higher prevalence and biological aggressiveness of prostate cancer, African-Americans tend towards narrower pelvises than Caucasians resulting in a potentially more difficult surgical dissection doing radical prostatectomy and increased positive surgical margins. In this study, there was no difference in urinary or sexual HRQL or overall satisfaction between African-Americans and Caucasians 2 years after radical prostatectomy, suggesting that the potential technical challenges of a narrower pelvis do not translate into poorer outcomes for African-Americans. OBJECTIVE: To determine if any differences exist in postoperative health-related quality-of-life (HRQL) outcomes, e.g. erectile function and continence, after radical prostatectomy (RP) in African-American (AA) vs Caucasian-American (CA) men. PATIENTS AND METHODS: Between October 2000 and July 2008, 1338 CA and 56 AA men underwent open RP by a single surgeon and signed informed consent to participate in a prospective longitudinal outcomes study. The American Urological Association Symptom Score (AUA-SS) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) and a global assessment of satisfaction were self-administered at baseline and after RP 24 months. Urinary, sexual, and satisfaction outcomes were compared at 24 months. RESULTS: AA men had significantly higher rates of hypertension and diabetes. There were no other significant baseline differences in age, co-morbidities, body mass index, phosphodiesterase type 5 inhibitor use, preoperative prostate-specific antigen level, AUA-SS, and UCLA-PCI scores. There were no differences in the percentage of men undergoing nerve-sparing procedures, estimated blood loss, transfusion rates, or complication rates between the groups. At 24 months after RP the mean UCLA-PCI urinary and sexual function and bother scores and global satisfaction scores were similar between the groups. CONCLUSION: AA and CA men experience no significant differences in urinary and sexual HRQL or overall satisfaction after open RP when performed by a single experienced surgeon.

National Practice Patterns of Infection Prophylaxis for Sacral Neuromodulation Device: A Survey of High Volume Providers.

INTRODUCTION: Sacral neuromodulation using the InterStim® device is a safe, effective treatment for urgency, frequency, urgency incontinence, nonobstructive urinary retention and fecal incontinence. However, there is no standard recommendation regarding infection prophylaxis. Therefore, we surveyed the infection prophylaxis patterns of high volume device providers to describe current practice patterns of perioperative infection prophylaxis. METHODS: A web based survey was sent to 35 high volume providers, including urologists, gynecologists and colorectal surgeons. RESULTS: Our response rate was 89% (31 of 35 participants). Of the providers 51% were urologists, 39% were gynecologists and 10% were colorectal surgeons. Of the respondents 74% had performed more than 200 procedures and 22% had done more than 500. The testing period was generally 1 to 2 weeks. Only 13% of the surveyed providers routinely screened for methicillin resistant Staphylococcus aureus. All providers administered antibiotics preoperatively, most commonly cefazolin or vancomycin, and 81% administered antibiotics postoperatively, most commonly cephalexin and trimethoprim-sulfamethoxazole. Most providers prescribed 5 to 7 days of treatment but 6 (19%) prescribed no postoperative antibiotics. In addition, 71% of respondents used adjunctive measures, frequently intraoperative wound irrigation and/or a preoperative chlorhexidine shower. After stages 1 and 2, 19% of providers prohibited showering for more than 3 days postoperatively while 61% permitted showering after 1 or 2 days and 19% recommended no bathing restriction. CONCLUSIONS: We present the infection prevention practices of high volume InterStim sacral neuromodulation device implanters in the United States. Further study is warranted to guide evidence-based practice in InterStim infection prophylaxis.

Outcomes of Sacral Neuromodulation for Overactive Bladder in Octogenarian Females.

PURPOSE: Elderly women have a high incidence of refractory overactive bladder. Clinicians and elderly patients may be hesitant to consider sacral neuromodulation. We investigated outcomes of sacral neuromodulation in women 80 years old or older. MATERIALS AND METHODS: From 2000 to 2013, 24 octogenarians with overactive bladder underwent stage 1 implantation of the InterStim® sacral neuromodulation device. We defined stage 1 success as 50% or greater improvement in incontinence episodes and/or pads. Those patients underwent placement of an implantable pulse generator. The primary study outcome was the rate of stage 1 success. Secondary outcomes were the complication rate and patient reported improvement/satisfaction. RESULTS: We identified 24 octogenarians with a median age of 85 years (range 80 to 89), of whom 18 (75%) experienced stage 1 success. At a mean 17-month followup (range 1 to 59) success was sustained in 13 patients (72%) and 15 (83%) were medication free. Two patients (12%) experienced complications, including urinary tract infection in 1 and pain at the implantable pulse generator site in 1, which resolved within 1 month. Three patients (17%) underwent lead revision and 2 subsequently regained success. Five of the 10 patients (50%) who returned the PGI-I questionnaire reported that their condition was very much or much improved, 3 felt a little improved and 2 reported no change. The self-reported satisfaction rate was 60%. CONCLUSIONS: Octogenarian women treated with sacral neuromodulation had a high rate of stage 1 success with no major complications. Most of them reported improvement and satisfaction at a mean followup of 17 months. Advanced age alone should not preclude consideration of sacral neuromodulation as a treatment option for overactive bladder in the properly selected elderly patient.

Minimally invasive ablative therapies for definitive treatment of localized prostate cancer in the primary setting.

Traditionally, the patient with a new diagnosis of localized prostate cancer faces either radical therapy, in the form of surgery or radiation, or active surveillance. A growing subset of these men may not be willing to accept the psychological burden of active surveillance nor the side effects of extirpative or radiation therapy. Local ablative therapies including cryotherapy, high-intensity focused ultrasound, and vascular-targeted photodynamic therapy have emerged as a means for minimally invasive definitive treatment. These treatments are well tolerated with decreased morbidity in association with improvements in technology; however, long-term oncologic efficacy remains to be determined.

Intravesical bacille Calmette-Guérin therapy for non-muscle-invasive bladder cancer: effects of concurrent statin therapy.

BACKGROUND: Recent studies provide conflicting evidence about the association of statin use and decreased efficacy of intravesical bacille Calmette-Guérin (BCG) therapy for bladder cancer. Because statin drugs have immunomodulatory properties that could reduce the effectiveness of BCG, we investigated whether concurrent use of statin drugs was associated with worsened clinical outcomes in patients undergoing BCG treatment for non-muscle-invasive bladder cancer. STUDY DESIGN: We retrospectively analyzed records of 120 patients undergoing BCG treatment during 1997 through 2007 at a single Department of Veterans Affairs Medical Center. Tumor-progression events, total recurrences, disease-specific and overall mortality were the outcomes relative to statin use. Fisher's exact, Student's t-tests, and logistic regression were used to compare the groups. RESULTS: Among the 90 evaluable patients, there were no significant differences between groups with regard to tumor grade and stage distribution or smoking status. Statins were used during BCG therapy by 47.8% of patients. Comparing patients with no use versus use of statins, 8.5% versus 11.6% had local tumor progression (p = 0.44); 10.6% versus 9.3% underwent cystectomy, chemotherapy, or radiation therapy (p = 0.56); and metastatic disease developed in 6.7% versus 11.6% (p = 0.33). Of the 27 patients who died of any cause, 12.5% (2 of 16) versus 27.3% (3 of 11) in the nonstatin versus statin groups, respectively, died of disease (p = 0.32). CONCLUSIONS: Concurrent statin use was not associated with adverse outcomes for patients undergoing BCG treatment for bladder cancer. While statins have a plausible biologic mechanism to reduce BCG efficacy, no differences were seen in this small pilot study.

Small intestinal submucosa for patch grafting after plaque incision in the treatment of Peyronie's disease.

OBJECTIVE: Report the results using porcine small intestinal submucosa (SIS) as a graft material in the surgical management of Peyronie's disease (PD). MATERIALS AND METHODS: We performed a retrospective chart review of men with PD who underwent surgical correction of the curvature by plaque "H" incision and patch grafting with 4-ply SIS (Cook, Bloomington, IN) by a single surgeon at our institution. Degree and direction of curvature, sexual function, and co-morbidities were assessed pre- and postoperatively. RESULTS: Thirteen patients were identified. Mean age was 57 +/- 8, range 42-70 years. Median follow-up was 14 months, range 3-89 months. At presentation, all reported penile curvature. Also reported were difficulty with vaginal penetration (determined by question number 2 of the sexual encounter profile questionnaire - SEP2), palpable plaque, hourglass deformity, difficulty with firmness, and difficulty with sustaining erection (determined by SEP3) in 77%, 69%, 77%, 62%, and 46% of patients, respectively. Mean and median degrees of curvature of the primary deformity were 71 and 67.5 degrees, respectively. Three patients had secondary curves of less than 30 degrees in a different direction. Mean and median plaque size were 3.5 and 2.7 cm2, respectively. Seven patients had one graft and six patients had two grafts placed with a mean size of 15 +/- 0 cm2. CONCLUSIONS: For the patient with PD, SIS grafting can achieve a functionally straight erection with durable results yet with relatively high rates of erectile dysfunction. SIS is a viable graft material for use in the surgical treatment of PD.

Management of the bladder during surgical treatment of enterovesical fistulas from benign bowel disease.

BACKGROUND: Management of the bladder in enterovesical fistulas from benign bowel disease is not well described in the literature and there is no clear consensus. STUDY DESIGN: A retrospective chart review was done of all patients with benign bowel disease and an enterovesical fistula who underwent definitive surgical management between January 1993 and December 2005. Patients were excluded if they had any history of abdominal cancer or pelvic radiation. Surgical management protocol for enterovesical fistulas included a period of perioperative bowel rest, surgical exploration, separation of the fistulized bowel from the bladder, resection of the diseased bowel segment, and Foley catheter placement for 1 week. RESULTS: Seventy-four patients were eligible for the study. The average patient age was 54.3 years (range 19 to 88 years old). Twenty-six women and 48 men underwent celiotomy and segmental resection of the offending bowel and bowel side of the fistula. The bladder side of the fistula was managed by Foley catheter alone in 68% and by surgical repair in 32%. Fifty-two patients had diverticulitis (70.3%) and 22 had Crohn's disease (29.7%). Mean followup was 26.4 months, and median followup was 6.45 months. One patient developed a colocutaneous and vesicocutaneous fistula after celiotomy. The remaining bladder defects healed within 1 week. CONCLUSIONS: Successful surgical management of most enterovesical fistulas from diverticulitis or Crohn's disease requires only resection of the diseased bowel, with minimal need for repair or resection of the bladder side of the fistula. Indwelling Foley catheter placement alone is typically sufficient for bladder healing. Only when there are overt defects into the bladder should formal repair be undertaken.