Garrick Simmons

OnabotulinumtoxinA for the Treatment of Patients with Overactive Bladder and Urinary Incontinence: Results of a Phase 3, Randomized, Placebo Controlled Trial

Purpose: Overactive bladder affects 12% to 17% of the general population and almost a third experience urinary incontinence, which may severely impact health related quality of life. Oral anticholinergics are the mainstay of pharmacological treatment but they are limited by inadequate efficacy or side effects, leading to a high discontinuation rate. We report the results of the first large (557 patients), phase 3, placebo controlled trial of onabotulinumtoxinA in patients with overactive bladder and urinary incontinence inadequately managed with anticholinergics. Materials and Methods: Eligible patients with overactive bladder, 3 or more urgency urinary incontinence episodes in 3 days and 8 or more micturitions per day were randomized 1:1 to receive intradetrusor injection of onabotulinumtoxinA 100 U or placebo. Co‐primary end points were the change from baseline in the number of urinary incontinence episodes per day and the proportion of patients with a positive response on the treatment benefit scale at posttreatment week 12. Secondary end points included other overactive bladder symptoms and health related quality of life. Adverse events were assessed. Results: OnabotulinumtoxinA significantly decreased the daily frequency of urinary incontinence episodes vs placebo (−2.65 vs −0.87, p <0.001) and 22.9% vs 6.5% of patients became completely continent. A larger proportion of onabotulinumtoxinA than placebo treated patients reported a positive response on the treatment benefit scale (60.8% vs 29.2%, p <0.001). All other overactive bladder symptoms improved vs placebo (p ≤0.05). OnabotulinumtoxinA improved patient health related quality of life across multiple measures (p <0.001). Uncomplicated urinary tract infection was the most common adverse event. A 5.4% rate of urinary retention was observed. Conclusions: OnabotulinumtoxinA 100 U showed significant, clinically relevant improvement in all overactive bladder symptoms and health related quality of life in patients inadequately treated with anticholinergics and was well tolerated.

Bilateral testicular tumors: Management and outcome in 21 patients

The authors examined the clinical course of patients with bilateral testicular tumors to determine whether the outcome after treatment was different from patients with unilateral tumors.

The Indiana Experience With Artificial Urinary Sphincters in Children and Young Adults

PURPOSE We reviewed a 22-year single institutional experience with the artificial urinary sphincter in children and adolescents. To our knowledge this report represents the largest series in the world in children. MATERIALS AND METHODS Between 1980 and 2002, 142 patients underwent implantation of an artificial urinary sphincter, of whom 93 males and 41 females with a median age of 10 years (range 3 to 39) were available for analysis. A total of 59 patients initially received an AMS 742/792 (American Medical Systems, Inc., Minnetonka, Minnesota) artificial urinary sphincter, of whom 33 were subsequently changed to an AMS 800, while 75 initially received an AMS 800 model. Sphincter followup was terminated at device removal or at the last documented contact. The etiology of incontinence was neuropathic bladder in 107 cases (80%), the exstrophy/epispadias complex in 21 (16%) and other in 6 (4%). Outcome measures included continence, mechanical complications (leakage, tube kink and pump malfunction), functioning sphincter revisions (change in cuff size, pump repositioning and bulbar cuff placement), surgical complications (erosion, infection and misplacement) and associated surgical procedures. Mean followup of the pre-800 and 800 models was 6.9 (range 0.2 to 21.5) and 7.5 years (range 0.1 to 17.1), respectively. Fishers exact test, Kaplan-Meier life analysis and the chi-square test were used for statistical analysis. RESULTS After artificial urinary sphincter placement in the 134 patients continence was achieved in 86%, improved in 4% and not achieved in 10%. Of those with a sphincter in place 92% were continent. In terms of bladder emptying after artificial urinary sphincter insertion 22% of patients voided, 11% voided combined with clean intermittent catheterization, 48% performed clean intermittent catheterization only via the urethra, 16% performed it via a catherizable channel and 3% used urinary diversion. A mechanical complication developed in 38 of the 59 patients (64%) with pre-800 model compared with 33 of the 109 (30%) with the 800 model (p <0.0001). A mechanical complication occurred every 7.6 versus 16 patient-years for the pre-800 versus 800 models (p = 0.0001). Revision was required in 15 of the 59 patients (25%) with a pre-800 model versus 17 of the 109 (16%) with the 800 model (p = 0.103). Revision was performed every 22.7 versus 44.3 patient-years for the pre-800 versus the 800 model (p = 0.023). The artificial urinary sphincter eroded in 11 of the 59 patients (19%) with the pre-800 versus 17 of the 109 (16%) with the 800 model (p = 0.52). Ten patients experienced a total of 12 perforations of the augmented bladder after artificial urinary sphincter implantation. A total of 164 secondary surgical procedures were performed, including 38 of 134 bladder augmentations (28%). A total of 30 sphincters were permanently removed. CONCLUSIONS The artificial urinary sphincter is the only bladder neck procedure that allows spontaneous voiding in the neuropathic population, obviates the need for clean intermittent catheterization and yet is compatible with it when necessary. It is also equally versatile in the 2 genders. Mechanical complications occur but they were dramatically decreased by the modifications of the AMS 800 model. In addition, secondary bladder augmentation was required in 28% of our patients. Lifelong followup is mandatory in all patients with an artificial urinary sphincter.

Holmium laser enucleation of the prostate: morbidity in a series of 206 patients

OBJECTIVES To review the complications associated with 206 holmium laser enucleation of the prostate (HoLEP) procedures. HoLEP is a minimally invasive surgical treatment for benign prostatic hyperplasia. METHODS A retrospective review was conducted of HoLEPs performed from April 1, 1999 to October 1, 2001. Patients with previous diagnoses of prostate carcinoma or who had undergone HoLEP after admission for unrelated problems were excluded. Demographic, intraoperative, and immediate postoperative data were recorded to determine the incidence of complications. Patients were also contacted by telephone or mailed surveys for documentation of longer term complications. RESULTS The mean age and procedure time was 70.5 years (range 45 to 91) and 133.6 minutes (range 25 to 473), respectively. The mean specimen weight was 68.2 g (range 3 to 376), with 20 (9.7%) of 206 patients diagnosed with adenocarcinoma. The mean hospital stay was 1.1 days, with 86.9% of patients discharged after an overnight stay without a catheter. Two patients required postoperative transfusions (1.0%). No deaths, major complications (myocardial infarction or pulmonary embolism), or transurethral resection syndrome episodes occurred. Intraoperative complications consisted of three capsular perforations (1.5%), one bladder neck false passage (0.5%), four incomplete morcellations (1.9%), and four minor bladder mucosal morcellation injuries (1.9%). Of 206 patients, 173 (84.0%) provided follow-up data (mean 19.0 +/- 8.4 months), allowing documentation of longer term complications, including five clot retention episodes (2.4%), five urethral strictures (2.4%), eight bladder neck contractures (3.9%), and 16 patients requiring re-catheterization (7.8%). CONCLUSIONS HoLEP can be performed with minimal complication risks and blood loss. Patients can expect an overnight hospital stay and discharge without an indwelling catheter.

Repair of hypospadias complications using the previously utilized urethral plate

OBJECTIVES To review our results of patients who underwent repeat hypospadias surgery using local skin flaps with preservation of the urethral plate. METHODS We retrospectively reviewed the medical records of all patients who underwent a reoperative hypospadias repair using the urethral plate between 1988 and 1996. A total of 53 patients were identified who developed either a large fistula (47 patients) or severe stricture (6 patients) after the initial repair. Seventeen patients underwent a repeat Mathieu flip-flap and 36 an onlay flap. The mean age at the time of surgery was 5.2 years (range 1 to 27). The mean duration of follow-up was 17 months (range 6 to 108). RESULTS The initial failed hypospadias repair was corrected with a single procedure in 44 (83%) of the 53 patients. The 9 patients who had further complications required 17 additional procedures. A meatal-based flap had been used in 4 of these patients and an onlay flap in 5. Three of the 9 patients who had further complications presented with urethral strictures after the previous repair. CONCLUSIONS Fistula and stricture are common complications of hypospadias surgery. The use of the urethral plate in primary repairs has helped decrease the complication rate. We report the effectiveness of using local skin flaps and preserving the urethral plate in complex reoperative hypospadias surgery. These techniques were successful in 83% of these challenging patients. Patients with stricture after hypospadias surgery are at increased risk of further complications.

Salvage Procedure For Infected Noneroded Artificial Urinary Sphincters

PURPOSE We report our experience with removal, antiseptic irrigation and immediate reimplantation of infected noneroded artificial urinary sphincters. MATERIALS AND METHODS From April 1996 to October 2000, 8 patients with an infected artificial urinary sphincter underwent a total of 9 salvage operations. All patients underwent cystoscopy before salvage to ensure nonerosion of the sphincter cuff. All previously implanted material was removed, the wounds were copiously irrigated according to a 7 solution protocol and an identical new system was implanted. All patients were discharged home the following morning on oral antibiotics. RESULTS Followup was 5 to 66 months (mean 33). The predominant organisms cultured at salvage were gram-positive cocci. Time from implantation to salvage was from 2 weeks to 64 months (mean 13.7 months). Prostatectomy was the etiology of incontinence in all except 1 case. In 5 of the 8 men a double cuff system was placed and 3 underwent concurrent 3-piece inflatable penile prosthesis salvage. The salvage procedure was done twice in 1 patient 5 months apart. The system was removed 16 months later secondary to urethral erosion. At the most recent followup the other 7 patients were free of infection with a functioning artificial urinary sphincter. CONCLUSIONS Salvage and immediate reimplantation of an infected, noneroded single or double cuff artificial urinary sphincter appears to be a valid option. Our overall success rate was 87%. The usual offending organisms are gram-positive skin flora. An associated inflatable penile prosthesis does not prohibit simultaneous salvage of the 2 devices.

ARTIFICIAL URINARY SPHINCTER IN THE TREATMENT OF URINARY INCONTINENCE: PREOPERATIVE URODYNAMICS DO NOT PREDICT THE NEED FOR FUTURE BLADDER AUGMENTATION

PURPOSE The artificial urinary sphincter has been used to treat urinary incontinence in pediatric patients with neurogenic bladders secondary to myelodysplasia. Frequently bladder augmentation is performed in conjunction with the artificial urinary sphincter implantation. Identifying patients with adequate urinary reservoirs who are candidates for implantation without bladder augmentation is a clinical challenge. We reviewed our experience with the artificial urinary sphincter in children with myelodysplasia to determine whether preoperative urodynamic findings predict the need for future augmentation cystoplasty. MATERIALS AND METHODS We identified 38 patients younger than 18 years at artificial urinary sphincter implantation who did not undergo augmentation enterocystoplasty before or at implantation. We evaluated preoperative bladder capacity and compliance to determine whether these standard preoperative urodynamic measurements predict the eventual need for bladder augmentation in these patients. RESULTS In the 15 patients who required eventual bladder augmentation after artificial urinary sphincter implantation mean bladder capacity plus or minus standard deviation was 62.9+/-29.9% of age expected capacity and mean bladder compliance was 8.0+/-4.8 ml./cm. water. In the 23 patients who did not require eventual bladder augmentation mean bladder capacity was 59.2+/-25.4% of age expected capacity and compliance was 7.0+/-3.3 ml./cm. water. There was no statistically significant difference between the 2 groups. CONCLUSIONS Standard preoperative urodynamics do not predict the patients who undergo isolated artificial urinary sphincter implantation and eventually require bladder augmentation.

Laparoscopic Transverse Hemicystectomy with Ileocystoplasty in a Porcine Model

BACKGROUND AND PURPOSE The ideal replacement for bladder tissue is yet to be described, although multiple alternatives have been studied. Currently, enterocystoplasty, despite its limitations, is considered the gold standard for bladder augmentation. This study evaluated the feasibility, safety, and morbidity of laparoscopic ileocystoplasty in a large-animal model. MATERIALS AND METHODS In eight minipigs, laparoscopy was performed using four ports. A segment of ileum was delivered through a 3-cm umbilical incision and detubularized and refashioned using standard open surgical technique. Laparoscopic hemicystectomy was then performed, followed by laparoscopic suturing of the ileal patch to the bladder. The bladder was drained with a Foley catheter, but no pelvic drain was placed. All animals were followed for for a minimum of 3 months. Preoperative and postoperative evaluation included measurement of bladder capacity, ultrasound imaging of the kidneys, blood counts, and serum electrolyte and creatinine measurements. Two of the animals were sacrificed at 3 months and one at 6 months, and the bladders were harvested. RESULTS Eight animals underwent ileocystoplasty without intraoperative or postoperative complications. The average operating and anastomosis time was 250 minutes and 96 minutes, respectively. All animals had normal preoperative blood values that remained normal during follow-up. Bladder capacity decreased initially to 71% of the baseline volume and then increased to 83% and 117% at 3 and 6 months. One of three animals sacrificed was noted to have a right midureteral stricture. CONCLUSIONS We developed a reliable laparoscopic technique for ileocystoplasty that may extend the advantages of laparoscopy, including better cosmesis and reduced risk of postoperative adhesions, to bladder augmentation.