Peter L. Rosenblatt

Randomized Trial of Percutaneous Tibial Nerve Stimulation Versus Extended-Release Tolterodine: Results From the Overactive Bladder Innovative Therapy Trial

PURPOSE The Overactive Bladder Innovative Therapy trial was a randomized, multicenter, controlled study that compared the effectiveness of percutaneous tibial nerve stimulation to extended-release tolterodine. The reduction in overactive bladder symptoms along with global response assessments was evaluated. MATERIALS AND METHODS A total of 100 adults with urinary frequency were randomized 1:1 to 12 weeks of treatment with weekly percutaneous tibial nerve stimulation or to 4 mg daily extended-release tolterodine. Voiding diaries and an overactive bladder questionnaire were completed at baseline and at the end of therapy to compare 24-hour voiding frequency, urinary urge incontinence episodes, voids causing waking, volume voided, urgency episodes and quality of life indices. Global response assessments were completed by subjects and investigators after 12 weeks of therapy. RESULTS The global response assessment demonstrated that subject assessment of overactive bladder symptoms compared to baseline was statistically significant in the percutaneous tibial nerve stimulation arm with 79.5% reporting cure or improvement compared to 54.8% of subjects on tolterodine (p = 0.01). Assessments by investigators were similar but did not reach statistical significance (p = 0.05). After 12 weeks of therapy objective measures improved similarly in both groups for reductions in urinary frequency, urge urinary incontinence episodes, urge severity and nighttime voids, as well as for improvement in voided volume. There were no serious adverse events or device malfunctions. CONCLUSIONS This multicenter, randomized trial demonstrates that percutaneous tibial nerve stimulation is safe with statistically significant improvements in patient assessment of overactive bladder symptoms, and with objective effectiveness comparable to that of pharmacotherapy. Percutaneous tibial nerve stimulation may be considered a clinically significant alternative therapy for overactive bladder.

PERCUTANEOUS AFFERENT NEUROMODULATION FOR THE REFRACTORY OVERACTIVE BLADDER: RESULTS OF A MULTICENTER STUDY

PURPOSE More than 20 million Americans have an overactive bladder, the predominant symptoms being frequency, urgency, urge incontinence and pelvic pain. While the etiology is not completely understood, most investigators believe the causes to be many and the pelvic floor to be intimately related. Whatever the etiology, traditional therapies, including dietary manipulation, bladder drill, medications and physical therapy, are often poorly tolerated and/or ineffective. We report a prospective, multicenter clinical trial that was undertaken to determine the safety and efficacy of percutaneous peripheral afferent nerve stimulation for treatment of refractive overactive bladder and/or pelvic floor dysfunction. MATERIALS AND METHODS A total of 53 patients with overactive bladders, in whom all traditional therapy failed, were enrolled in 1 of 5 sites within the United States. Patients received weekly percutaneous electrical stimulations via a 34 gauge needle placed near the tibial nerve 3 finger breadths above the ankle. Urodynamic studies, detailed voiding diaries, quality of life surveys, and incontinence impact questionnaires were completed before, during and after the study. RESULTS Of the patients with a mean age of 57.4 years 89% (47 of 53) completed the 12-week study. A total of 71% of patients were classified as treatment successes by the investigators and were started on long-term treatment. On average patients noticed a 25% reduction in mean daytime and 21% reduction in mean nighttime voiding frequencies (p <0.05). Urge incontinence was reduced by an average of 35% (p <0.05). Statistically significant improvements were noted in selective pain and quality of life indexes. No significant adverse events related to treatment were noted in any patients. CONCLUSIONS Percutaneous peripheral afferent nerve stimulation offers a safe, minimally invasive and effective treatment for managing refractive overactive bladder and/or pelvic floor dysfunction.

Quantitative PET studies of the serotonin transporter in MDMA users and controls using [11C]McN5652 and [11C]DASB

(±)3,4-Methylenedioxymethamphetamine (MDMA, ‘Ecstasy’) is a widely used illicit drug that produces toxic effects on brain serotonin axons and axon terminals in animals. The results of clinical studies addressing MDMAs serotonin neurotoxic potential in humans have been inconclusive. In the present study, 23 abstinent MDMA users and 19 non-MDMA controls underwent quantitative positron emission tomography (PET) studies using [11C]McN5652 and [11C]DASB, first- and second-generation serotonin transporter (SERT) ligands previously validated in baboons for detecting MDMA-induced brain serotonin neurotoxicity. Global and regional distribution volumes (DVs) and two additional SERT-binding parameters (DVspec and DVR) were compared in the two subject populations using parametric statistical analyses. Data from PET studies revealed excellent correlations between the various binding parameters of [11C] McN5652 and [11C]DASB, both in individual brain regions and individual subjects. Global SERT reductions were found in MDMA users with both PET ligands, using all three of the above-mentioned SERT-binding parameters. Preplanned comparisons in 15 regions of interest demonstrated reductions in selected cortical and subcortical structures. Exploratory correlational analyses suggested that SERT measures recover with time, and that loss of the SERT is directly associated with MDMA use intensity. These quantitative PET data, obtained using validated first- and second-generation SERT PET ligands, provide strong evidence of reduced SERT density in some recreational MDMA users.

Release of tension-free vaginal tape for the treatment of Refractory postoperative voiding dysfunction

OBJECTIVE To report our experience with surgical release of tension‐free vaginal tape (TVT) for the treatment of persistent post‐TVT voiding dysfunction. METHODS A total of 1175 women underwent TVT placement for treatment of genuine stress urinary incontinence and/or intrinsic sphincter deficiency over a 2‐year period. Additional procedures and vaginal repairs were performed as indicated. Among these patients, 23 women (1.9%) had persistent voiding dysfunction (urinary retention, incomplete bladder emptying, or severe urgency or urge incontinence) refractory to conservative management. This cohort underwent a simple vaginal TVT release procedure, performed on an outpatient basis. Preoperative characteristics, intraoperative, and postoperative details were assessed by review of operative notes, medical records, and office notes. Continence status was assessed using subjective and objective information. RESULTS Mean age was 67 years (range 46–86 years), and the mean interval between TVT placement and release was 17.3 weeks (range 2–69 weeks; median 8.6 weeks). For the release procedure, there were no intraoperative complications, and all patients were discharged on the day of surgery. All cases of impaired emptying were completely resolved, and all cases of irritative symptoms were resolved (30%) or improved (70%) by 6 weeks. Fourteen (61%) patients remained continent 6 weeks after the release procedure, six (26%) were improved over baseline, and three patients (13%) had recurrence of stress incontinence. CONCLUSION Refractory voiding dysfunction after TVT is a relatively uncommon situation and can be successfully managed with a simple midline release procedure. In most cases, the release procedure does not compromise overall improvement in symptoms of stress incontinence.

The Mersilene mesh suburethral sling: A clinical and urodynamic evaluation☆

Abstract OBJECTIVES: Our purpose was to determine the efficacy and safety of the Mersilene (Ethicon, Inc., Somerville, N.J.) mesh sling. STUDY DESIGN: A total of 110 women diagnosed at the University of Massachusetts Medical Center with recurrent genuine stress incontinence, low-pressure urethra, or chronically increased intraabdominal pressure underwent a Mersilene mesh sling procedure. The women were followed up with yearly clinical and 1-year urodynamic evaluations. Sixty-seven patients had both preoperative and postoperative complete urodynamic evaluations. Paired t test was used except where stated. RESULTS: Seventy-nine of 83 patients (95%) who were examined at a mean of 15 months reported complete stress continence. Objective cure rate ( n = 72) by 1-year postoperative stress test was 93%. The pressure transmission ratio increased from 75% to 112% ( p CONCLUSIONS: The suburethral sling with Mersilene mesh is a safe, effective treatment for specific types of genuine stress incontinence on the basis of yearly clinical and 1-year urodynamic follow-up, and it demonstrates a low rejection rate.

The Effect of Posterior Wall Support Defects on Urodynamic Indices in Stress Urinary Incontinence

Objective To determine if posterior vaginal wall defects affect urodynamic indices and mask stress urinary incontinence. Methods Ninety women with grade 0, 1, 2, or 3 posterior wall defects were evaluated prospectively by complete urodynamics to assess their urinary complaints. None had severe anterior or apical support defects. Urethral pressure profilometry and cough stress test were performed with the posterior wall in the unretracted position and then with the posterior wall retracted using a split speculum. Analysis of covariance was used to compare adjusted mean differences in maximum urethral closure pressure, functional urethral length, and units of leakage volume during the cough stress test in the unretracted and retracted positions among the posterior wall grade groups. Results In women with grade 3 posterior wall defects, there were significant changes from the unretracted to the retracted position in maximum urethral closure pressure of −7.0 cm H2O, (99% confidence interval [CI] −12.4, −1.6), functional urethral length of −0.3 cm (99% CI −0.5, −0.1), and leak volume units of +0.7 (99% CI 0.4, 1.0) during the cough stress test. There were four women with grade 3 posterior wall defects who demonstrated potential stress incontinence when their posterior wall was retracted. Conclusion A grade 3 posterior wall defect may artificially raise maximum urethral closure pressure, increase functional urethral length, and mask urinary stress incontinence during a cough stress test. Women with grade 3 posterior wall defects should be tested with the posterior wall retracted during urodynamic evaluation.

Laparoscopic Sacrocervicopexy for the Treatment of Uterine Prolapse : A Retrospective Case Series Report

STUDY OBJECTIVE To evaluate apical support in patients desiring uterine preservation with pelvic organ prolapse who underwent laparoscopic sacrocervicopexy. DESIGN Retrospective case series report (Canadian Task Force classification III). SETTING Academic community teaching hospital. PATIENTS Forty consecutive women who underwent laparoscopic sacrocervicopexy. INTERVENTIONS Synthetic mesh was used to attach the distal uterosacral ligaments and posterior endopelvic fascia to the anterior longitudinal ligament of the sacral promontory. MEASUREMENTS AND MAIN RESULTS Pelvic organ prolapse quantification system measurements were used and apical support was evaluated using point C. Mean C was -1.13 (+9 to -4) preoperatively, -5.28 (-3 to -13) at 6 weeks postoperatively, -5.26 (-3 to -8) at 6 months postoperatively, and -4.84 (-3 to -7) at 1 year postoperatively. CONCLUSION Laparoscopic sacrocervicopexy is an effective option for women with pelvic organ prolapse who desire uterine preservation.

TVT-Secur (Hammock) versus TVT-Obturator: a randomized trial of suburethral sling operative procedures.

Objectives This study aimed to compare TVT-Secur (TVT-S) and TVT-Obturator (TVT-O) suburethral slings for treatment of stress urinary incontinence (SUI). Methods This was a single-center, nonblinded, randomized trial of women with SUI who were randomized to TVT-S or TVT-O from May 2007 to April 2009. The primary outcome, SUI on cough stress test (CST), and quality-of-life and symptom questionnaires (Pelvic Floor Distress Inventory [PFDI-20] and Pelvic Floor Impact Questionnaire [PFIQ-7]) were assessed at 12 weeks and 1 year. Results Forty-three women were randomized to TVT-S and 44 to TVT-O. There were no differences in median baseline PFDI-20 and PFIQ-7. Twenty-two (52.4%) of 42 participants randomized to TVT-S had a positive CST result at evaluation after 12 weeks or 1 year, whereas 4 (9.1%) of the 44 in the TVT-O group had a positive CST result. The intent-to-treat analysis showed that the risk of a positive CST result was 6 times higher after TVT-S than TVT-O (risk ratio, 6.0; 95% confidence interval [CI], 2.3–16.0). Among women not lost to follow-up, the risk ratio for a positive CST result after TVT-S compared with TVT-O was 17.9 (95% CI, 2.5–128.0) at 12 weeks and 3.5 (95% CI, 1.1–11.0) at 1 year. Both TVT-S and TVT-O resulted in improved quality of life and symptoms at 12 weeks. There was no difference between the groups for PFDI-20 (P = 0.40) or PFIQ-7 (P = 0.43). A similar pattern was seen at 1 year (P = 0.85 and P = 0.36). Conclusions The TVT-S seems to have a higher risk of positive postoperative CST result; however, the procedures result in similar improvements in quality of life and symptoms.

Neuromodulation techniques for the treatment of the overactive bladder

Voiding dysfunction including urge incontinence, frequency/urgency syndromes, and chronic urinary retention is a common phenomenon in men and women that result from a variety of conditions ranging from local genitourinary factors to widespread neurologic disease. Although the ability to diagnose this condition has improved over the last decade with more precise definitions and better diagnostic equipment, treatment options and clinical outcomes have been less than satisfactory due to poor understanding of the pathophysiology of this challenging clinical problem. In some cases there is a clear etiologic factor underlying the patient’s symptoms like frequency associated with detrusor hyperreflexia due to stroke or multiple sclerosis or incomplete bladder emptying due to outlet obstruction in benign prostatic hypertrophy. Unfortunately, the majority of patients who present with voiding dysfunction symptoms have no obvious or treatable source of their symptoms and are confined to treatment primarily focused on symptomatic improvement. Current treatment options are associated with poor cure rates and significant associated adverse effects. This is particularly important considering the widespread scope of this problem, especially among the aging population of this country. Urge incontinence and frequency/urgency symptoms have recently been classified as subsets of Overactive Bladder (OAB) Syndrome by the International Continence Society. OAB is defined as “urgency, with or without urge incontinence, usually with frequency and nocturia in the absence of local or metabolic factors explaining these symptoms.” OAB most probably represents a spectrum of presenting symptoms that include enuresis and pelvic pain. Recently, it has been hypothesized that interstitial cystitis may be a pain variant of OAB. Further research regarding the etiologic pathways of interstitial cystitis is required. Using the criteria established by the ICS, a recent study estimated that 16.5% of the adult population Correspondence: Neeraj Kohli, MD, 300 Mount Auburn Street, Suite 302, Cambridge, MA 02138. E-mail: nkohli@caregroup.harvard.edu CLINICAL OBSTETRICS AND GYNECOLOGY Volume 45, Number 1, 218–232

Musculoskeletal pain in gynecologic surgeons.

OBJECTIVE To describe the prevalence of musculoskeletal pain and symptoms in gynecologic surgeons. DESIGN Prospective cross-sectional survey study (Canadian Task Force classification II-2). SETTING Virtual. All study participants were contacted and participated via electronic means. PARTICIPANTS Gynecologic surgeons. INTERVENTIONS An anonymous, web-based survey was distributed to gynecologic surgeons via electronic newsletters and direct E-mail. MEASUREMENTS AND MAIN RESULTS There were 495 respondents with complete data. When respondents were queried about their musculoskeletal symptoms in the past 12 months, they reported a high prevalence of lower back (75.6%) and neck (72.9%) pain and a slightly lower prevalence of shoulder (66.6%), upper back (61.6%), and wrist/hand (60.9%) pain. Many respondents believed that performing surgery caused or worsened the pain, ranging from 76.3% to 82.7% in these five anatomic regions. Women are at an approximately twofold risk of pain, with adjusted odds ratios (OR) of 1.88 (95% confidence interval [CI], 1.1-3.2; p = .02) in the lower back region, OR 2.6 (95% CI, 1.4-4.8; p = .002) in the upper back, and OR 2.9 (95% CI, 1.8-4.6; p = .001) in the wrist/hand region. CONCLUSION Musculoskeletal symptoms are highly prevalent among gynecologic surgeons. Female sex is associated with approximately twofold risk of reported pain in commonly assessed anatomic regions.