Melissa R. Kaufman

Autologous muscle derived cells for treatment of stress urinary incontinence in women.

PURPOSE We assess the 12-month safety and potential efficacy of autologous muscle derived cells for urinary sphincter repair (Cook MyoSite Incorporated, Pittsburgh, Pennsylvania) in women with stress urinary incontinence. MATERIALS AND METHODS Pooled data from 2 phase I/II studies with identical patient selection criteria and outcome measures were analyzed. Enrolled patients had stress urinary incontinence refractory to prior treatment and no symptom improvement during the last 6 months. Patients received intrasphincter injection of 10 (16), 50 (16), 100 (24) or 200×10(6) (24) autologous muscle derived cells for urinary sphincter repair, derived from biopsies of each patients quadriceps femoris. The primary outcome measure was safety, determined by incidence and severity of adverse events. Potential efficacy was measured by changes in 3-day voiding diaries, 24-hour pad tests, and UDI-6 and IIQ-7 scores. RESULTS A total of 80 patients underwent injection of autologous muscle derived cells for urinary sphincter repair, and 72 completed diaries and pad tests at 12-month followup. No adverse events attributed to autologous muscle derived cells for urinary sphincter repair were reported. Higher dose groups tended to have greater percentages of patients with at least a 50% reduction in stress leaks and pad weight at 12-month followup. All dose groups had statistically significant improvement in UDI-6 and IIQ-7 scores at 12-month followup compared to baseline. CONCLUSIONS Autologous muscle derived cells for urinary sphincter repair at doses of 10, 50, 100 and 200×10(6) cells appears safe. Efficacy data suggest a potential dose response with a greater percentage of patients responsive to higher doses.

Voiding Function in Women with Orthotopic Neobladder Urinary Diversion

PURPOSE Most long-term morbidity after radical cystectomy is related to the urinary diversion or reconstruction. While there are benefits to an orthotopic neobladder, there can be a substantial risk of voiding dysfunction in women. We examine the prevalence of postoperative voiding complications in women who underwent orthotopic neobladder diversion. MATERIALS AND METHODS We identified all women who underwent radical cystectomy and orthotopic neobladder for bladder cancer at our institution from 1996 to 2011 (51) and included patients with regular clinic followup (49). The presence and severity of incontinence and hypercontinence were evaluated at routine clinic visits. Unadjusted analyses were performed to measure the association between patient variables and voiding symptoms, with p < 0.05 considered significant. RESULTS Daytime incontinence, nighttime incontinence and hypercontinence were reported by 43%, 55% and 31% of women, respectively. A neobladder-vaginal fistula developed in 3 women (6%). On unadjusted analysis having daytime incontinence was associated with a concurrent or previous hysterectomy (p = 0.031), but not with age, disease stage, preoperative incontinence, year of surgery or sparing the vaginal wall. The severity of daytime incontinence was associated with preoperative incontinence only (p = 0.02). The presence and severity of nighttime incontinence were associated with patient age only (p = 0.013, p = 0.005, respectively). Hypercontinence was not associated with any variable. CONCLUSIONS Among women with orthotopic neobladder after radical cystectomy we identified a significant prevalence of voiding dysfunction. We recommend preoperative discussion of these possible complications with any woman interested in orthotopic neobladder to establish realistic expectations. For properly selected women who understand these risks, orthotopic neobladder may be an appropriate diversion choice.

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.

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.

Immediate effects of the initial FDA notification on the use of surgical mesh for pelvic organ prolapse surgery in medicare beneficiaries

Prompted by increased reports of complications with the use of mesh for pelvic organ prolapse (POP) surgery, the FDA issued an initial public health notification (PHN) in 2008. We proposed to determine if the numbers of POP cases augmented with surgical mesh performed in U.S. Medicare beneficiaries changed relative to this PHN.

Urinary retention rates after intravesical onabotulinumtoxinA injection for idiopathic overactive bladder in clinical practice and predictors of this outcome

The purpose of this study was to find the rate of urinary retention in clinical practice after treatment with onabotulinumtoxinA (BTN/A) for refractory overactive bladder (OAB) symptoms and determine factors that predict this outcome.

Cystectomy With Urinary Diversion for Benign Disease: Indications and Outcomes

OBJECTIVE To analyze what factors contribute to a worse outcome after cystectomy and urinary diversion for benign disease as measured by the frequency of severe complications. METHODS A retrospective review was performed of consecutive patients who underwent a cystectomy for benign disease. The primary outcome was the type and severity of complications, according to Clavien-Dindo scale. RESULTS A total of 139 patients underwent cystectomy with diversion for benign diseases over the study period. The most common indications for surgery were spinal cord injury (32%) and radiation damage to the bladder (18%). The average preoperative age-adjusted Charlson comorbidity index was 4.6. Seventy-four patients (53%) underwent supratrigonal cystectomy. Mean surgery duration was 344±103 minutes, and the mean estimated blood loss was 476±379 mL. The most common complications were perioperative blood transfusion, prolonged ileus, and pyelonephritis. Seventy-nine patients (57%) had a complication grade≥II on the Clavien-Dindo scale. This did not differ based on indication for surgery, age, gender, body mass index, age-adjusted Charlson comorbidity index, estimated blood loss, or type of cystectomy. After adjustment, only duration of surgery in 10-minute increments (odds ratio, 1.07; 95% confidence interval, 1.02-1.12; P=.007) was associated with an increased incidence of serious complication. CONCLUSION Most of the patients experience some complication after cystectomy and urinary diversion for benign indications. Duration of surgery is an important variable that can affect outcome.

Obturator foramen dissection for excision of symptomatic transobturator mesh.

PURPOSE Groin pain after transobturator synthetic mesh placement can be recalcitrant to conservative therapy and ultimately requires surgical excision. We describe our experiences with and technique of obturator foramen dissection for mesh excision. MATERIALS AND METHODS The records of 8 patients treated from 2005 to 2010, were reviewed. Obturator dissection was performed via a lateral groin incision over the inferior pubic ramus at the level of the obturator foramen, typically in conjunction with orthopedic surgery. RESULTS Five patients had transobturator mid urethral sling surgery for stress urinary incontinence, 2 had mid urethral sling and trocar based anterior vaginal wall mesh kits with transobturator passage of mesh arms for stress urinary incontinence and pelvic organ prolapse, and 1 had an anterior vaginal wall mesh kit for pelvic organ prolapse. Patients had 0 to 2 prior transvaginal mesh excisions before obturator surgery. All patients presented with intractable pain in the area of the obturator foramen and/or medial groin for which conservative treatment measures had failed. Six patients underwent concurrent vaginal and obturator dissection and 2 underwent obturator dissection alone. In all cases residual mesh (3 to 11 cm) was identified and excised from the obturator foramen. Mesh was closely associated to or traversing the adductor longus muscle and tendon with significant fibrous reaction in all cases. Postoperatively 5 patients were cured of pain and/or infection, and 3 reported no or some improvement at a mean followup of 6 months (range 1 to 12). CONCLUSIONS Our experience suggests that surgical excision of residual mesh can alleviate many of the symptoms in many patients. In all cases mesh remnants were identified and removed, and typically involved neuromuscular structures adjacent to the obturator foramen.

Approach to Management of Iatrogenic Foreign Bodies of the Lower Urinary Tract Following Reconstructive Pelvic Surgery

PURPOSE Evolving techniques and materials for pelvic reconstruction have resulted in corresponding increases in the risk of iatrogenic foreign bodies in the lower urinary tract and vagina. We review the presentation, management and outcomes of iatrogenic foreign bodies in the female lower urinary tract and vagina. MATERIALS AND METHODS We performed a retrospective review of the records of all women undergoing removal of lower urinary tract foreign bodies during a 9-year period. All patients underwent a structured evaluation including history, physical examination, ancillary testing as indicated and subjective symptom appraisal. RESULTS A total of 85 women were identified, of whom 48 had vaginal, 40 had lower urinary tract, and 3 had concomitant vaginal and lower urinary tract excision of foreign material. Of the lower urinary tract cases the foreign body was located in the urethra in 12, bladder neck in 10, bladder wall in 18 and trigone in 3, while the remainder of the cases was vaginal in location. Aggressive surgical management aimed at removal or debulking of the exposed foreign body necessitated cystorrhaphy/partial cystectomy (20), urethroplasty (18) and fistula repair (3). Of the patients with vaginal excision 36 (75%) reported cure (of presenting symptoms), 10 (20.8%) reported improvement and 2 were unavailable for followup. Of the patients with lower urinary tract excision 21 (52.5%) reported cure, 14 (35%) indicated improvement and 5 were unavailable for followup. CONCLUSIONS In a complex group of women with vaginal or lower urinary tract foreign body extrusion, aggressive operative management resulted in high rates of subjective patient cure. Adequate assessment of newer reconstructive technologies is critical to assess the full impact of these complications.

Primary Endoscopic Realignment of Urethral Disruption Injuries--A Double-Edged Sword?

PURPOSE Controversy remains regarding initial management of traumatic urethral disruption injuries. We evaluated the outcomes of primary endoscopic realignment vs suprapubic tube placement in this patient population. MATERIALS AND METHODS We reviewed our urological trauma database for patients with blunt trauma related posterior urethral injuries from 2000 to 2014. Patients underwent primary endoscopic realignment or suprapubic tube placement alone. The primary outcome was the success of primary realignment, defined as no further need for urological intervention. Secondary outcomes were the need for endoscopic interventions and/or urethroplasty, time to urethroplasty, urethroplasty success and long-term functional outcomes. RESULTS A total of 27 patients underwent primary realignment and 14 underwent suprapubic tube placement. Mean followup was 40 months (median 24, range 1 to 152). Realignment was successful in 10 patients (37%) at a mean followup of 67.3 weeks (median 27.3, range 4 to 284). In the 17 cases (63%) that failed mean time to failure was 9.7 weeks (median 8.5, range 1 to 26). Seven patients (26%) treated with realignment and 11 (79%) with a suprapubic tube proceeded to urethroplasty. Mean ± SD time to urethroplasty was significantly shorter in the suprapubic tube group (14.6 ± 7.6 vs 5.8 ± 1.6 months, p = 0.003). There was no difference in operative time, complications, success or functional outcomes. CONCLUSIONS Management of traumatic urethral disruption injuries by primary endoscopic realignment serves as definitive therapy in more than a third of treated patients. It prevents the need for formal urethroplasty in more than half of failed cases.