Steven Siegel

Long-term results of a multicenter study on sacral nerve stimulation for treatment of urinary urge incontinence, urgency-frequency, and retention☆

Many patients have chronic, debilitating symptoms of voiding dysfunction that are refractory to conventional medical or surgical therapies. This multicenter, prospective study evaluated the long-term effectiveness of sacral nerve stimulation using the implantable Medtronic InterStim therapy for urinary control in patients with otherwise intractable complaints of urinary urge incontinence, urgency-frequency, or retention. Each patient first underwent temporary, percutaneous sacral nerve test stimulation. If at least a 50% reduction in target symptoms was documented for at least 3 days, patients received a permanent Medtronic InterStim sacral nerve stimulation system that includes a surgically implanted lead and neurostimulator. Regular follow-up was conducted with outcome data. We report here on patients who have been observed from 1.5 to 3 years postimplantation. The results demonstrate that after 3 years, 59% of 41 urinary urge incontinent patients showed greater than 50% reduction in leaking episodes per day with 46% of patients being completely dry. After 2 years, 56% of the urgency-frequency patients showed greater than 50% reduction in voids per day. After 1. 5 years, 70% of 42 retention patients showed greater than 50% reduction in catheter volume per catheterization. We conclude that the Medtronic InterStim therapy for urinary control system is an effective therapy with sustained clinical benefit for patients with intractable symptoms of urinary urge incontinence, urgency-frequency, or retention.

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.

Conservative surgery for renal cell carcinoma: a single-center experience with 100 patients.

From January 1956 to March 1987, 100 patients underwent a conservative (parenchyma-sparing) operation as curative treatment for renal cell carcinoma at our clinic. This series includes 56 patients with bilateral (28 synchronous and 28 asynchronous) and 44 with unilateral renal cell carcinoma; in the latter category the contralateral kidney was either absent or nonfunctioning (17 patients), functionally impaired (17), involved with a benign disease process (6) or normal (4). The pathological tumor stage was I in 75 patients, II in 9, III in 10 and IV in 6. A nephron-sparing operation was performed in situ in 86 patients and ex vivo in 14. Postoperatively, 93 patients experienced immediate function of the operated kidney, while 7 required dialysis (4 temporary and 3 permanent). The incidence of dialysis was greater after ex vivo than in situ surgery (p equals 0.0005). The mean postoperative serum creatinine level in 97 patients with renal function was 1.7 mg. per dl. (range 0.9 to 4.6 mg. per dl.). The over-all actuarial 5-year patient survival rate in this series is 67 per cent including death of any cause and 84 per cent including only deaths of renal cell carcinoma. Survival was improved in patients with stage I renal cell carcinoma (p less than 0.05). Survival also was improved in patients with unilateral renal cell carcinoma (p less than 0.05) and fewer patients in this category had recurrent disease postoperatively (p less than 0.0005). Nine patients (9 per cent) had local tumor recurrence postoperatively and 5 of these were rendered free of tumor by secondary surgical excision. Conservative surgery provides effective therapy for patients with localized renal cell carcinoma in whom preservation of renal function is a relevant clinical consideration.

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.

Long-term durability of percutaneous tibial nerve stimulation for the treatment of overactive bladder.

PURPOSE The Overactive Bladder Innovative Therapy Trial during phase 1 was a randomized trial demonstrating comparable effectiveness of percutaneous tibial nerve stimulation and extended-release tolterodine during 12 weeks of therapy for frequency, nocturia, urgency, voided volume and urge incontinence episodes. In this second phase of the Overactive Bladder Innovative Therapy Trial we assessed the sustained therapeutic efficacy of percutaneous tibial nerve stimulation in subjects with overactive bladder during 1 year. MATERIALS AND METHODS After 12 weeks subjects randomized to weekly percutaneous tibial nerve stimulation with Urgent((R)) PC were offered an additional 9 months of treatment with assessments at 6 and 12 months from baseline. Outcome measures included voiding diary data, overactive bladder questionnaires, global response assessments and safety assessments. RESULTS A total of 33 percutaneous tibial nerve stimulation responders continued therapy with 32 and 25 subjects completing 6 and 12 months of therapy, respectively. Subjects received a mean of 12.1 treatments during an average of 263 days, with a mean of 21 days (median 17) between treatments. Subject global response assessments showed sustained improvement from 12 weeks at 6 and 12 months, with 94% and 96% of responders, respectively. At 12 months mean improvements from baseline included a frequency of 2.8 voids daily (p <0.001), urge incontinence of 1.6 episodes daily (p <0.001), nocturia with 0.8 voids (p <0.05) and a voided volume of 39 cc (p <0.05). Overactive bladder questionnaire symptom severity was significantly improved from 12 weeks to 12 months (p <0.01) as well as from 6 to 12 months (p <0.01). No serious adverse events occurred. CONCLUSIONS Statistically significant overactive bladder symptom improvement achieved with 12 weekly percutaneous tibial nerve stimulation treatments demonstrates excellent durability through 12 months. The durability of response demonstrates the effectiveness of percutaneous tibial nerve stimulation as a viable, long-term therapy for overactive bladder.

Long–Term Effectiveness of Sacral Nerve Stimulation for Refractory Urge Incontinence

Objectives: To evaluate the long–term efficacy of sacral nerve stimulation for refractory urinary urge incontinence. Study Design and Methods: Urge incontinent patients qualified for surgical implantation of a neurostimulator system after trial screening with percutaneous test stimulation. Surgical implantation of the InterStim System (Medtronic Inc., Minneapolis, Minn., USA) was performed in cases where a >50% reduction in incontinence symptoms was documented during the 3– to 7–day test stimulation period. The InterStim System consists of an implantable pulse generator, a transforamenally placed quadripolar lead, and an extension that connects these two devices for unilateral stimulation of the S3 or S4 sacral nerve. Efficacy for 96 implanted patients was based on urinary symptom changes as quantified in voiding diaries collected at baseline and annually after surgical implantation. Results: As compared to baseline, the group of 96 implanted patients demonstrated significant reductions in urge incontinent symptoms at an average of 30.8±14.8 (range 12–60) months with respect to the number of urge incontinent episodes per day, severity of leaking, and the number of absorbent pads/diapers replaced per day due to incontinence (all p<0.0001, respectively). Gender, pretreatment variables, and age were not found to be relevant factors that affected these results. 11 of the 96 patients underwent device explant due to lack of efficacy, pain or bowel dysfunction. These data were conservatively included in the efficacy results. No permanent injuries associated with the devices or therapy were reported. Conclusion: Sacral nerve stimulation is an effective treatment for refractory urge incontinence with sustained long–term benefit through an average of 30.8 months.

Results of a Prospective, Randomized, Multicenter Study Evaluating Sacral Neuromodulation With InterStim Therapy Compared to Standard Medical Therapy at 6-Months in Subjects With Mild Symptoms of Overactive Bladder

This prospective, randomized, multicenter trial evaluated the 6‐month success rate of sacral neuromodulation (SNM) with InterStim® Therapy versus standard medical therapy (SMT) for overactive bladder (OAB).

Magnetic Resonance Imaging for Assessment of Vena Caval Tumor Thrombi: A Comparative Study with Venacavography and Computerized Tomography Scanning

We assessed the accuracy of magnetic resonance imaging in demonstrating the presence and extent of vena caval tumor thrombi. The study group included 20 patients with vena caval thrombi from renal cell carcinoma (18), renal pelvic transitional cell carcinoma (1) and adrenal pheochromocytoma (1). Preoperative diagnostic studies included magnetic resonance imaging in all patients, inferior venacavography in 16 and computerized tomography scanning in 15. All patients underwent an operation in which the presence and extent of the vena caval thrombus were confirmed. Magnetic resonance imaging accurately delineated the presence and extent of the thrombus in all 20 patients (100%). Venacavography was accurate in 15 patients (94%) but 8 (50%) required a retrograde and antegrade study. Computerized tomography scanning demonstrated the presence of a tumor thrombus in all 15 patients but accurately delineated the cephalad extent of the thrombus in only 5 (33%). In patients with vena caval tumor thrombi magnetic resonance imaging can provide accurate information regarding the extent of vena caval involvement while avoiding the need for an invasive contrast imaging study.

The role of neuromodulation in the management of urinary urge incontinence

Neuromodulation is increasingly becoming an important part of the treatment strategy for bladder dysfunction. In this issue a group of urologists have analysed outcome measures from all patients in pivotal clinical trials who have had this treatment, and have suggested that sacral nerve stimulation has an vital role in the management of refractory overactive bladder and retention problems.

Urodynamic evaluation of sacral neuromodulation for urge urinary incontinence

To evaluate the urodynamic data before and 6 months after implantation of sacral neuromodulation (SNM, an established treatment for voiding dysfunction, including refractory urge urinary incontinence, UI) and to assess the correlation between the urodynamic data and clinical efficacy in patients with UI.