Iltamiocel Autologous Cell Therapy for the Treatment of Female Stress Urinary Incontinence: A Double-Blind, Randomized, Stratified, Placebo-Controlled Trial.

AIMS: This study aimed to determine the efficacy and safety of iltamiocel investigational autologous muscle cell therapy in females with stress urinary incontinence (SUI). METHODS: Adult females were randomized 2:1 to iltamiocel (150 × 106 cells) or placebo and stratified by severity and prior SUI surgery. The primary objective was efficacy based on the frequency of stress incontinence episodes (SIE) recorded in a 3-day diary at 12 months posttreatment. After 12 months, placebo participants could elect to receive open-label iltamiocel. Efficacy and safety analyses were performed using all patients as treated populations. RESULTS: The study enrolled 311 patients, 297 were randomized to either iltamiocel (n = 199) or placebo (n = 98). Of the 295 participants that completed 12 months blinded follow-up, the proportion achieving the primary endpoint of ≥ 50% SIE reduction was not statistically different between treatment groups (52% vs. 53.6%; p = 0.798). A significantly greater proportion of iltamiocel participants in the prior SUI surgery stratum group achieved ≥ 75% SIE reduction compared with placebo, (40% vs. 16%; p = 0.037). Treatment response was maintained at 24 months in 78.4% and 64.9% of iltamiocel participants who achieved ≥ 50% and ≥ 75% SIE reduction, respectively, at Month 12. Adverse events related to the treatment were reported in 19 (9.5%) iltamiocel participants and 6 (6.1%) placebo participants. CONCLUSION: The study did not meet its primary endpoint however, iltamiocel cell therapy is safe and may be ideally suited to female patients who have undergone prior surgery for SUI. Additional study in this group of patients with high unmet medical needs is warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01893138; EudraCT number: 2014-002919-41.

Analysis of Benign Prostatic Hyperplasia Patients' Perspective Through a Third Party-administered Survey.

OBJECTIVE: To assess patient-reported functional and quality-of-life (QoL) outcomes associated with various surgical treatments for benign prostate hyperplasia (BPH). MATERIALS AND METHODS: An independent third-party survey was sent to all patients who underwent any surgical treatment for BPH at our institution from January 2007 through January 2013. Overall satisfaction and urinary and sexual outcomes were evaluated using Sexual Health Inventory for Men (SHIM), International Prostate Symptoms Score (IPSS) for urinary function, and International Continence Society-Short Form (ICSmaleSF) questionnaires. RESULTS: Four hundred and seventy-nine respondents (response rate, 55.6%) had undergone holmium laser enucleation of the prostate (HoLEP; n = 214), transurethral resection of the prostate (n = 210), holmium laser ablation of the prostate (n = 21), photoselective vaporization (n = 18), transurethral incision of the prostate (n = 9), and open simple prostatectomy (n = 7). Postoperatively, Sexual Health Inventory for Men scores were not different. However, total IPSS varied significantly among surgical techniques (P < .001). Mean (standard deviation) IPSS was lowest for open simple prostatectomy (4.0 [2.6]), followed by HoLEP (5.8 [5.4]). For individual domains, significant differences were in intermittency (P < .001), weak stream (P = .003), straining (P < .001), and QoL (P = .001). In all these domains, HoLEP had the lowest scores. Regarding International Continence Society-Short Form, we observed a significant difference favoring transurethral resection of the prostate in incontinence (P < .001) and favoring HoLEP in voiding (P = .02) and QoL domains (P = .03). Most patients were satisfied with their surgical intervention, independent of the procedure type. Regret was least in patients who underwent HoLEP (P = .02). CONCLUSION: Patients generally expressed satisfaction with various interventions for BPH. However, those who underwent HoLEP had the best outcomes.

A comparison of 30-day surgical outcomes for minimally invasive and open sacrocolpopexy.

AIMS: Minimally invasive sacrocolpopexy (MISC) has gained widespread acceptance without randomized or population-based data to support its use. This study compares 30-day outcomes after MISC and open sacrocolpopexy (OSC) using population-based data. METHODS: The National Surgical Quality Improvement Program (NSQIP) database was used to acquire 1,786 sacrocolpopexy operations (659 OSC and 1,127 MISC) performed from 2005 to 2011. A propensity-weighted comparative analysis of perioperative morbidity was performed. RESULTS: Among women undergoing sacrocolpopexy, the proportion of MISC procedures increased from 7.1% in 2006 to 68.8% in 2011. Women undergoing OSC were older (P < 0.001) and had somewhat higher American Society of Anesthesiologists classifications (P = 0.11). Unadjusted comparisons between groups revealed higher rates of superficial (P < 0.001) and deep surgical (P = 0.009) site infections in the OSC group. There was also a higher rate of blood transfusions (P = 0.02), a longer length of hospitalization (P < 0.001), and a shorter operative time (P < 0.001) among patients undergoing OSC. In the propensity-weighted analysis, MISC was associated with lower rates of wound infections (1.1% vs. 3.0%; P = 0.01), lower blood transfusion rates (0.7% vs. 2.3%; P = 0.01), a shorter mean hospitalization (1.4 vs. 3.0 days; P < 0.001), and a longer mean operative time (224.8 vs. 188.6 min; P < 0.001). No differences were noted among renal, infectious, or neurologic complications, although pulmonary complications were higher in the OSC group (0.3% vs. 1.0%; P = 0.08). No differences in 30-day mortality were noted (0.1% vs. 0.2%; P = 0.61). CONCLUSIONS: MISC was associated with lower perioperative morbidity in this propensity-weighted analysis.

Comparison of midurethral sling outcomes with and without prolapse repair.

INTRODUCTION: To compare the outcome of single incision and retropubic midurethral slings when performed with and without concomitant repair of pelvic organ prolapse (POP). MATERIALS AND METHODS: A retrospective chart review was conducted of all midurethral slings performed with and without concomitant POP repair by a single provider from September 2008 to April 2010. Prolapse was repaired transvaginally with light-weight polypropylene mesh or robotically via sacrocolpopexy based on the nature of the prolapse and surgeon preference. Success of the sling procedure was defined as complete resolution of leakage or great improvement of leakage based on the Patient Global Impression of Improvement score. RESULTS: Eighty-nine patients underwent a midurethral sling procedure. Forty-five patients received a single incision sling, 18 of which had concomitant POP repair. Forty-four received a retropubic sling, 16 of which had concomitant POP repair. Successful treatment of SUI in the single incision sling group was 89% (24/27) which was not significantly different from the retropubic only sling group 93% (26/28), p = 0.61. However, a significant difference was seen in the successful treatment of SUI in the single incision sling plus prolapse repair group 67% (12/18) versus the retropubic sling plus prolapse repair group 94% (15/16), p = 0.05. CONCLUSION: We found a higher incidence of single incision mid-urethral sling failure when done at the same time as repair of pelvic organ prolapse in comparison to sling placement alone. There is no difference in the success of retropubic slings when done with or without concomitant prolapse repair.

Bladder capacity on preoperative urodynamics may impact outcomes on transobturator male slings.

AIMS: Stress incontinence is frequently seen after prostate surgery. We sought to evaluate preoperative urodynamic (UDS) parameters on functional outcomes after transobturator male sling placement. METHODS: 49 male patients with stress urinary incontinence (SUI) after radical prostatectomy or transurethral resection of the prostate underwent transobturator sling (TOS) placement from December 2008 through June 2011 (AdVance® and Virtue®). A retrospective review was performed of those patients who underwent preoperative UDS and had a minimum of 6 weeks of follow up. In total 38 patients were identified. There were 28 patients considered a success and 10 patients considered a failure. We then evaluated the preoperative UDS parameters between these two groups to identify potential adverse parameters. RESULTS: Overall success rate was 74% (28/38) with an average follow up of 3 months. Comparing the success and failure groups there was no difference between the pre-operative parameters. On pre-operative UDS, only bladder capacity was found to be significantly lower in those who failed TOS. Univariate comparisons of sling outcomes stratified by bladder capacity tertiles was performed. These values were chosen as they represented the 25th, 50th, and 75th percentiles, respectively. All patients (10/10) with bladder capacities in the top tertile experienced success with the sling, compared to only 62% and 50% of patients in the 50th and 25th tertiles, respectively; these differences were significant (Fisher's exact P-value = 0.044). CONCLUSION: TOS is an effective therapy for men with SUI. Bladder capacity based on pre-operative UDS may impact the success of the procedure.

Early outcomes of the transobturator male sling based on body mass index.

INTRODUCTION: Little is known regarding factors that contribute to the long term success or failure of the transobturator male sling for stress urinary incontinence. The objective of this study was to compare the outcomes of the transobturator male sling for stress urinary incontinence based on body mass index (BMI). MATERIALS AND METHODS: A retrospective review was performed of 31 transobturator male slings placed at a single institution from 2008 to 2010. Success of the procedure was defined as resolution of leakage or great improvement of leakage by the Patient Global Impression of Improvement scale and lack of urinary leakage on postoperative physical exam. Patients were divided into one of three groups: ideal weight (BMI 18.5-24.9 kg/m(2)), overweight (25-29.9 kg/m(2)), and obese (> 30 kg/m(2)). Outcomes and complications were compared between groups. RESULTS: Etiology of urinary incontinence was radical prostatectomy in 28 patients and a transurethral procedure for infection or benign prostatic hypertrophy (BPH) in 3 patients. Successful treatment of incontinence was significantly higher in the ideal weight (7/8 or 88%) and overweight group (13/14 or 93%) in comparison to the obese group (4/9 or 44%), (p = 0.019). Postoperative complications were similar between groups. CONCLUSIONS: Obese patients had lower success rates after transobturator sling in comparison to ideal and overweight patients. We feel this may be due to increased intra-abdominal pressure transmission to the bladder, urethra, and sling itself. These patients may be better candidates for an artificial urinary sphincter or should be counseled to undergo pre-preoperative weight loss to improve sling outcomes.

Temporary prostatic urethral stenting as a provocative tool to determine surgical eligibility in complex bladder outlet obstructed patients: our initial experience.

BACKGROUND/AIMS: To evaluate the usefulness of a temporary prostatic urethral stent to determine which complex surgical patients would benefit from definitive surgical management of their benign prostatic hyperplasia. METHODS: We retrospectively analyzed our benign prostatic hyperplasia database and identified all patients that received at least one temporary prostatic urethral stent between April 2008 and December 2010. RESULTS: Forty Spanner(TM) stents were placed in 20 patients. Mean age was 78.1 years and prostate size was 62.1 cm(3). Urinary retention was present in 60% (12/20) of patients. No statistically significant changes in mean maximal flow rate, average flow rate, and post void residual was noted. Seven patients (35%) did well with the stent and progressed to definitive surgical management whereas 10% of the cohort (2/20) leaked urine with the stent in place and subsequently went back to catheter management. Another 30% (6/20) were unable to tolerate the stent while 1 patient passed away unrelated to the stent. CONCLUSIONS: The use of the temporary prostatic urethral stent provided a good provocative test that enabled patients to experience what their voiding status would be if they were to undergo definitive surgical management.

Urologic surgical simulation: an endoscopic bladder model.

INTRODUCTION: With the explosion of endoscopic techniques in urology as well as the increasing work restrictions with resident duty hours, training programs are faced with the challenges of how to adequately train residents while still being proficient and safe in the operating room. Surgical simulation with models is an excellent tool to help bridge the gap between practice and experience and allow residents to learn basic skills in a low stress environment that can be later transferred to the operating room. METHODS: We present a high-fidelity endoscopic boar bladder model for first-year urology resident training in preparation for real-time experience in the operating room. RESULTS: The boar bladder model held up for the residents to complete six separate tasks. In each of the six assigned tasks, both residents had a percent improvement ranging from 13% to 97% when comparing an average of the first attempts with the final attempt. CONCLUSIONS: The novel simulation model we describe demonstrates is a high-fidelity tissue surrogate that can be used for simulation training for improvement in core urologic skills by novice residents. This model may be a useful tool in documenting proficiency-based competence of cystoscopic skills.

Incontinence after radical prostatectomy: a patient centered analysis and implications for preoperative counseling.

PURPOSE: Incontinence after radical prostatectomy is common yet poorly defined in the current literature. We aimed to accurately characterize incontinence after robot-assisted radical prostatectomy to achieve improved preoperative patient counseling. MATERIALS AND METHODS: After receiving institutional review board approval we performed a cross-sectional survey of the first 600 patients with prostate cancer who underwent robot-assisted radical prostatectomy at our institution. The International Consultation on Incontinence Modular Questionnaire-Lower Urinary Tract Symptoms Quality of Life and Urinary Incontinence Short Form were used to evaluate incontinence and quality of life after robot-assisted radical prostatectomy. Surveys were mailed by a third party. Data were analyzed on the prevalence of incontinence after robot-assisted radical prostatectomy. More specifically we characterized in detail the nature of incontinence and its effect on quality of life. RESULTS: The response rate was 68% (408 of 600 participants). Response time since surgery was 2.5 months to 4 years. Overall incontinence bother scores and ratings of life interference were quite low. Patients reported that most incontinence occurred during physical activity but 35% reported interference with sleep. Of the patients 31% experienced some anxiety due to urinary difficulties and 51% had to occasionally change clothes due to leakage. Patients did not report much interference with traveling, visiting friends or family and family life. The most bothersome aspects of incontinence were its effects on partner relationship, sexual life and energy levels. CONCLUSIONS: Despite patient concerns of incontinence after prostatectomy they report little interference with quality of life.

Mixed incontinence and cystocele: postoperative urge symptoms are not predicted by preoperative urodynamics.

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) frequently presents with urinary incontinence, either urge (UUI), stress (SUI), or mixed (MUI). We sought to determine the effect of high-grade prolapse repair on MUI. METHODS: A retrospective review was performed for 111 patients with anterior POP repair and sling over 4 years. RESULTS: Sixty patients (54%) presented symptomatically with MUI, 25% with SUI, and 9% with UUI, 12% asymptomatic. Occult SUI was found in 21% (UUI plus asymptomatic). Success was seen for SUI in 92% and for POP in 89%. Urge symptoms were present in 63% pre-op and 30% post-op. MUI patients were significantly more likely to experience post-op urgency (p = 0.033). Detrusor overactivity (DO) was seen in 22 MUI patients, but was not predictive of post-op urgency (p = 0.91). CONCLUSIONS: Cystocele patients with MUI are at significant risk for postoperative urge symptoms regardless of DO, and counseling regarding persistent urgency is imperative.

Older age does not impact perioperative complications after robot-assisted radical prostatectomy.

To determine whether men aged 70 years and older had more perioperative complications after robot-assisted radical prostatectomy (RARP) compared with younger patients, a retrospective review was performed on patients who underwent RARP between March 2004 and September 2009. Subjects were stratified according to age into four groups (age 30-49, 50-59, 60-69, and ≥70 years). American Society of Anesthesiologists (ASA) scores were obtained. Complication rates in the perioperative period, transfusion rates, and length of stay were compared. Complications were classified using the previously validated Clavien system. There were a total of 293 patients aged 70 years and older amongst the 1,223 total subjects. ASA comorbidity scores did vary significantly amongst the different age groups, and there was modest correlation noted between ASA and age. There was no statistically significant difference amongst complication rates in men aged 70 years and older (15%) compared with the other cohorts (P = 0.832). There was also no significant difference in transfusion rates (P = 0.170) or length of stay (P = 0.131). Patients with higher ASA scores (ASA 3-4) had more Clavien I-II complications compared with patients with ASA scores of 1-2 (15.5% versus 10.3%, P = 0.03). There was no difference in transfusion rates or length of stay between the ASA scores. There are no more complications in men aged 70 years and older compared with men <70 years of age undergoing robot-assisted radical prostatectomy. RARP is a safe treatment option to offer to the selected elderly patient.

Genitourinary fistula experience in Sierra Leone: review of 505 cases.

PURPOSE: We reviewed cases of genitourinary fistula resulting from birth trauma in Sierra Leone to determine factors predictive of successful operative repair. MATERIALS AND METHODS: A total of 505 operative repairs of genitourinary fistula were completed at 2 centers in Sierra Leone from 2004 to 2006. Statistical analysis of patient demographics, fistula characteristics, outcomes and surgical complications was performed. RESULTS: Primary repairs, defined as the first repair, accounted for 68% of repairs in the population with 92% classified as vesicovaginal fistula alone. Only 56% of women were deemed to have an intact urethra at presentation and 68% were diagnosed with moderate or severe fibrosis surrounding the fistula. On univariate analysis parameters that demonstrated significant differences with primary operative success were patient age at fistula occurrence (p = 0.0192), index pregnancy (p = 0.0061), location (p <0.0001), surface area (p <0.0001), urethral status (p <0.0001) and fibrosis (p <0.0001). On multivariate analysis the fistula parameter that correlated with successful repair was the extent of fibrosis (severe fibrosis OR 3.7). CONCLUSIONS: Genitourinary fistula as a result of prolonged obstructed labor is a cause of considerable morbidity in sub-Saharan Africa, including Sierra Leone. The most profound factor correlating with a positive operative outcome was the extent of fibrosis surrounding the fistula. These data are important to help predict the likelihood of successful repair and assist in selecting women for the appropriate surgical procedure.

Removal of transobturator midurethral sling for refractory thigh pain.

Polypropylene midurethral slings have become the most common surgical procedure for the treatment of stress urinary incontinence. The efficacy has been well established through prospective and systematic evaluation. Transobturator midurethral slings have demonstrated comparable efficacy relative to the retropubic approach with the potential to minimize the morbidity associated with retropubic needle passage. We present a case of recalcitrant medial thigh pain after transobturator midurethral sling placement that ultimately required medial thigh/transobturator exploration and sling excision.

The evolution of obstruction induced overactive bladder symptoms following urethrolysis for female bladder outlet obstruction.

PURPOSE: Bladder outlet obstruction following stress incontinence surgery may present as a spectrum of lower urinary tract symptoms. We evaluated the prevalence and impact of persistent overactive bladder symptoms following urethrolysis for iatrogenic bladder outlet obstruction. MATERIALS AND METHODS: In a retrospective review we identified 40 patients who underwent urethrolysis. All patients underwent a standardized urological evaluation. Patients identified with genitourinary erosion, neurogenic bladder dysfunction and preexisting overactive bladder were excluded. Urethrolysis outcomes were determined by subjective bladder symptoms and objective parameters. Validated questionnaires were completed to assess symptom bother, patient satisfaction and quality of life. Statistical analyses were performed using Stata, version 9.0. RESULTS: A total of 40 patients were included in the study with a mean +/- SD followup of 13 +/- 11 months (range 3 to 38). Of the patients 34 patients presented with obstructive symptoms, while 36 had overactive bladder symptoms. Obstructive symptoms resolved in 28 of the 34 patients (82%), while overactive bladder symptoms resolved completely in only 12 (35%) and they were significantly improved in 4 (12%). Overall 20 patients (56%) were on antimuscarinics for refractory overactive bladder and 8 ultimately required sacral neuromodulation. Pre-urethrolysis detrusor overactivity was more likely in patients with persistent overactive bladder symptoms than in those in whom overactive bladder symptoms resolved (70% vs 38%). Patients with persistent overactive bladder had significantly greater symptom severity/bother, and decreased perception of improvement and quality of life following urethrolysis. CONCLUSIONS: Following urethrolysis overactive bladder symptoms may remain refractory in 50% or greater of patients, which has a negative impact on quality of life and the impression of improvement after surgery. Detrusor overactivity demonstrated preoperatively may be useful for predicting who may have persistent overactive bladder symptoms despite an effective urethrolysis procedure.

Refractory overactive bladder after urethrolysis for bladder outlet obstruction: management with sacral neuromodulation.

Refractory overactive bladder (OAB) after urethrolysis for iatrogenic bladder outlet obstruction (BOO) is a clinical dilemma without established guidelines for management. We sought to evaluate the efficacy of sacral neuromodulation (SNM) in the management of this complex patient population. Retrospective review identified eight patients who underwent SNM secondary to refractory OAB after urethrolysis or sling take-down. SNM was performed with the Interstim device (Medtronic, Minneapolis) using a two-stage implant technique. SNM outcomes were determined subjectively during follow-up. Validated questionnaires were completed to assess symptom bother, patient satisfaction, and quality of life. Statistical analyses were conducted using Stata version 9.0. Six patients had a favorable response to SNM during test stimulation and underwent implantation of the implantable pulse generator (IPG). With follow-up of 15.7 +/- 11.1 months (6-34), all patients significantly improved, with three patients being dry and three patients having one to two urgency incontinence episodes per week. Patient-reported outcomes indicated that patients perceived themselves as very much improved (3) or much improved (3) after SNM, while those failing test stimulation perceived no change. Quality of life and symptom bother were significantly better in SNM responders vs nonresponders. SNM appears to be an effective and viable treatment option in this complex patient population. Further work is needed to determine clinical factors predictive of outcome and durability of response.

Management of refractory urinary urge incontinence following urogynecological surgery with sacral neuromodulation.

AIMS: We sought to explore our patient outcomes utilizing sacral neuromodulation in the management of refractory urinary urge incontinence following urogynecological surgical procedures. METHODS: A total of 25 women with urinary urge incontinence following urogynecological surgery were selected for SNS therapy and retrospectively analyzed. All patients completed a comprehensive urological evaluation. Clinical data was recorded to determine outcomes and identify parameters that would be predictive of response to neuromodulation. Outcomes were determined via subjective patient questionnaire and graded as follows: significant response (> or =80% improvement), moderate response (> or =50% and <80% improvement), and poor response (<50% response). RESULTS: Nineteen patients had a previous pubovaginal sling (10 with concomitant pelvic prolapse repair), 3 a previous retropubic suspension, and 3 a transperitoneal vesicovaginal fistula repair. Urethrolysis was performed in 4 patients to alleviate bladder outlet obstruction prior to sacral neuromodulation. Mean patient age was 59.8 years and length of follow-up was 7.2 months. Twenty-two women (88%) had the IPG placed during a Stage 2 procedure. Twenty patients maintained at least a 50% improvement in clinical symptoms at last follow-up and 6 patients were continent. Overall, the number of pads/day improved from 4.2 to 1.1 (P < 0.001). There were no significant differences in response to neuromodulation based upon age, duration of symptoms, type of surgery, or urodynamic parameters. CONCLUSION: Sacral neuromodulation appears to be an effective therapy in patients with refractory urge incontinence following urogynecological surgery. Larger prospective studies with longer follow-up are needed to assess the durability of this therapeutic modality.

The hydrophilic-coated inflatable penile prosthesis: 1-year experience.

INTRODUCTION: Penile prosthesis infections are a devastating complication for both patient and surgeon. Efforts to reduce the risk of infection from these elective procedures are a major focus of research and development by the major prosthesis companies. The Titan inflatable penile prosthesis (Mentor Corporation, Santa Barbara, CA) is coated with polyvinylpyrrolidone (PVP), a hydrophilic substance that reduces bacterial adherence and absorbs and elutes the antibiotics the device is immersed in intraoperatively. The Titan device was introduced to the American market in September 2002. This study reports the 1-year experience in the U.S. with the Titan and compares infection rates with the noncoated Alpha-1 IPP made by Mentor. MATERIALS AND METHODS: Two thousand three hundred and fifty-seven Titan prostheses were implanted in the U.S. from September 2002 to August 2003, compared with the 482 noncoated Alpha-1 IPPs implanted over the same time period. Infection rates were compared, along with bacterial culture data. All data were collected from Mentor's internal database, as generated from the FDA's mandatory reporting of explanted medical devices, and available on the internet. RESULTS: The infection rate for the coated Titan IPP was 1.06% (25/2,357). During the same time period, the infection rate for the Alpha-1 noncoated prosthesis was 2.07% (10/482). Staphylococcus species predominated in both groups (9/25 Titan, 6/10 Alpha-1). CONCLUSIONS: At 1 year of follow-up, the data demonstrate that the hydrophilic coating on the Titan IPP confers a significant advantage in reducing the rate of infection over the noncoated device. Long-term follow-up on this first year database is needed before this innovation is accepted as the standard of care for prosthetic surgery. Nevertheless, the theoretical reduction in bacterial adhesion conferred by the hydrophilic PVP surface and the ability to choose which antibiotic the device is immersed in intraoperatively gives the implanting surgeon distinct advantages with this new product.