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.

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.

Sacral neuromodulation in the treatment of urgency-frequency symptoms: a multicenter study on efficacy and safety.

PURPOSE: Neuromodulation of sacral nerves has shown promising results in correcting voiding dysfunction. We report the results of a multicenter trial designed to assess the efficacy of sacral nerve neuromodulation in patients presenting with refractory urinary urgency-frequency. MATERIALS AND METHODS: A total of 51 patients from 12 centers underwent baseline assessment, including a detailed voiding diary, urodynamic evaluation and percutaneous test stimulation of the sacral nerves at S3 and/or S4. All patients enrolled in the study had undergone prior conventional treatment, such as pharmacotherapy, hydrodistention and surgical intervention, which failed. All patients demonstrated a satisfactory response to trial stimulation and were randomly divided into a stimulation group (25 patients) and a control group (26). A sacral nerve stimulation device was implanted after 6 months in the control group. Patients were followed at 1, 3 and 6 months, and at 6-month intervals for up to 2 years after implantation of a neuroprosthetic InterStim* system. dagger The study variables included the number of voids daily, volume voided per void and degree of urgency before void. RESULTS: Compared to the control group, 6-month voiding diary results demonstrated statistically significant improvements (p <0.0001) in the stimulation group with respect to the number voids daily (16.9 +/- 9.7 to 9.3 +/- 5.1), volume per void (118 +/- 74 to 226 +/- 124 ml.) and degree of urgency (rank 2.2 +/- 0.6 to 1.6 +/- 0.9). Patients in the control group showed no significant changes in voiding parameters at 6 months. Significant improvements in favor of the stimulation group were noted in various parameters with respect to water cystometry and quality of life (SF-36). At 6 months after implant, neurostimulators were turned off in the stimulation group and urinary symptoms returned to baseline values. After reactivation of stimulation sustained efficacy was documented at 12 and 24 months. CONCLUSIONS: Neuromodulation of the sacral nerves is an effective, safe therapy that successfully treats significant symptoms of refractory urgency-frequency.

Sacral root neuromodulation in the treatment of refractory urinary urge incontinence: a prospective randomized clinical trial.

OBJECTIVES: To compare the effectiveness of sacral root neuromodulation with that of conservative management in ameliorating symptoms of refractory urinary urge incontinence and enhancing quality of life, to assess the objective response to neuromodulation as revealed by urodynamic testing, and to delineate the long-term outcomes of neuromodulation. METHODS: Forty-four patients with refractory urge incontinence were randomized to undergo neuromodulation with an implantable impulse generator (n = 21) or to continue their prior conservative management (n = 23). At 6 months the control group was eligible for crossover to implant. Patient evaluation included voiding diaries, quality of life questionnaires, urodynamic testing, and documentation of adverse events. Long-term follow-up evaluations were conducted at 6-month intervals up to 36 months. RESULTS: At 6 months mean leakage episodes, leakage severity and pad usage in the implant group were significantly lower by 88% (p < 0.0005), 24% (p = 0.047) and 90% (p < 0.0005), respectively, than the corresponding control group mean values. Improvements in leakage episodes and pad usage of >/=90% were attained by 75 and 85% of the implant group, respectively, but none of the control group. One third of implant patients, but none of the control patients, achieved >/=50% improvement in leakage severity. Over half of the implant patients (56%) were completely dry compared with 1 control patient (4%). Implant patients, but not control patients, exhibited significant improvement with respect to two quality of life measures. Neuromodulation resulted in increases of 220% (p < 0.0005) and 39% (p = 0.013), respectively, in urodynamically assessed bladder volume at first contraction and maximum fill. At 36 months the actuarial rate of treatment failure was 32.4% (95% CI, 17.0-56.0%). Adverse events most frequently involved pain at the implant site, and the incidence of serious complications was low. CONCLUSIONS: Neuromodulation is markedly more effective than conservative management in alleviating symptoms of refractory urge incontinence. Quality of life and urodynamic function are also improved by neuromodulation. The effects of neuromodulation are long-lasting, and associated morbidity is low.

Treatment of anastomotic strictures and urinary incontinence after radical prostatectomy with urolume wallstent and AMS 800 artificial sphincter.

Anastomotic strictures and urinary incontinence are severe complications after a radical prostatectomy. We report on two patients suffering from both complications. We treated the anastomotic stricture with a Urolume Wallstent and inserted an AMS 800 artificial sphincter prosthesis 4 to 6 months later for treating urinary incontinence. Finally, the patients were fully continent with no evidence of recurrent strictures.

Validity of a non-invasive determination of the isovolumetric bladder pressure during voiding in men with LUTS.

Invasive pressure flow analysis is the gold standard for discriminating between hypocontractile bladder muscle function and infravesical obstruction in male patients with lower urinary tract symptoms. Here a non-invasive method to determine the isovolumetric bladder pressure to judge contractility is presented. This is based on interruption of urine flow by sudden occlusion of a specially fixed condom catheter. The pressure inside the condom is recorded and used to estimate the isovolumetric bladder pressure. Combined with, for example, home uroflowmetry, this non-invasive method may overcome some of the disadvantages (e.g., invasiveness, cost) of the conventional pressure flow test. To determine the isovolumetric bladder pressure reliably with this non-invasive method, two constraints have to be met. First, the bladder neck and urethra have to remain open after occlusion of the condom catheter. This was tested combining the non-invasive test with radiography in five patients. Second, a steady state has to be reached, i.e., the flow in the urethra, due to the elastic properties of the biological and the condom systems, should come to a stop when the bladder pressure and the condom pressure equilibrate. This was investigated by comparing the non-invasively recorded condom pressure with the simultaneously invasively recorded intravesical pressure in 52 patients. In these patients, three different methods of condom fixation were evaluated. The results show that the bladder neck and urethra remain open during the test. However, a steady state is often not reached. In more than 80% of the cases with the best condom fixation, the bladder pressure has not stabilized, although the condom pressure reached a plateau. Therefore, this method of sudden occlusion is not yet clinically applicable for determining the isovolumetric bladder pressure. Neurourol. Urodynam. 18:477-486, 1999.

Sacral nerve stimulation for treatment of refractory urinary urge incontinence. Sacral Nerve Stimulation Study Group.

PURPOSE: A prospective, randomized study was performed to evaluate sacral nerve stimulation for the treatment of refractory urinary urge incontinence. MATERIALS AND METHODS: Primary outcome variables were obtained from voiding diaries. After baseline evaluation candidates who satisfied inclusion criteria were enrolled into the study. Test stimulation results determined eligibility for randomization into a stimulation (treatment) or delay (control) group. The stimulation group included 34 patients who underwent implantation and were followed for 6 months. The delay group comprised 42 patients who received standard medical therapy for 6 months and then were offered implantation. The stimulation group completed a therapy evaluation test (on versus off) after 6 months. RESULTS: At 6 months the number of daily incontinence episodes, severity of episodes and absorbent pads or diapers replaced daily due to incontinence were significantly reduced in the stimulation compared to the delay group (all p<0.0001). Of the 34 stimulation group patients 16 (47%) were completely dry and an additional 10 (29%) demonstrated a greater than 50% reduction in incontinence episodes 6 months after implantation. Efficacy appeared to be sustained for 18 months. During the therapy evaluation test the group returned to baseline levels of incontinence when stimulation was inactivated. Urodynamic testing confirmed that sacral nerve stimulation did not adversely affect voiding function. Complications included implantable pulse generator site pain in 15.9% of the patients, implant site pain in 19.1% and lead migration in 7.0%. Surgical revision was required in 32.5% of patients with implants to resolve a complication. There were no reports of permanent injury or nerve damage. CONCLUSIONS: Sacral nerve stimulation is safe and effective in treating refractory urinary urge incontinence.

The neuronal control of the lower urinary tract: A model of architecture and control mechanisms.

The human micturition cycle is controlled by central and peripheral nervous structures and connections. In literature, no complete or generally accepted model describes the principles of micturition control. In this paper, the integration of (neuro-)anatomy, (neuro-)physiology and control theory is used to describe and model the neuronal control of the lower urinary tract. Neuroanatomy supplies the most basic information necessary for the modellation of the peripheral pathways and central connections involved in the control of the uropoetic system. It is found that not all the nervous structures and connections have been identified as such yet. The linking up between several nervous structures (e.g., the presence of central and peripheral relay stations) is not completely clear. A s a consequence, each model to describe the micturition cycle from the perspective of control theory is yet of limited physiological value as it cannot exceed a rather general level of modellation. Adding functional considerations (neurophysiology and control theory) to the neuroanatomical skeleton completes the model. Some control mechanisms active during the micturition cycle can still not be revealed in detail. Crucial questions on the neuronal innervation of the human uropoetic system and the control mechanisms active during the micturition cycle remain, like how the supraspinal trigger mechanisms for micturition are organised, or how the voluntary cessation of voiding is realised. A simplified version of the model discussed in this paper can already be used for mathematical modelling, e.g., neural network simulations.

Clinical results of sacral neuromodulation for chronic voiding dysfunction using unilateral sacral foramen electrodes.

The aim of this study was to determine the long-term clinical efficacy and complications of neuromodulation with a unilateral sacral foramen electrode in 36 patients with chronic voiding dysfunction. Following a positive effect of a percutaneous nerve evaluation test, patients underwent open surgery. A permanent electrode was implanted in 24 patients with urge incontinence, in 6 with urgency-frequency syndrome, and in 6 with nonobstructive urinary retention. After an average follow-up period of 37.8 months, 19 patients (52.8%) continue to benefit from the neuromodulation with a significant improvement of symptoms and urodynamic parameters. The median duration of the therapeutic effect for the total study population was longer than 60 months. No significant difference in the median duration of therapeutic effect with regard to sex, the type of voiding disorder, or the implant pulse generator was found. However, in patients with previous psychological disorders the median duration of therapeutic effect was only 12 months (P = 0.008). Complications were mild. In the group of patients in whom the therapeutic effect remains, 37 reoperations have had to be performed. We conclude that although reoperations were needed to overcome technical problems, patients can achieve lasting symptomatic improvement. Since technical changes in the equipment have reduced the number of complications, even better results can be expected in terms of the reoperation rate.

A non-invasive method for bladder electromyography in humans.

No convincing correlation of bladder EMG in humans to simultaneously measured intravesical pressure has been reported in the literature. In most studies on bladder EMG the electrodes contact the bladder wall itself. This causes problems in the discrimination between very small extracellular signals, reflecting actual membrane potential changes of bladder muscle cells, and large electro-mechanical artefact caused by electrode movement as the tissue contracts. Aim of this study is to investigate whether bladder EMG can be performed non-invasively with Ag-AgCl surface electrodes that are placed on the abdominal skin of healthy volunteers. Bipolar electrode signals are obtained in a diagonal, vertical and horizontal direction of the abdominal electrodes. A conventional urodynamic investigation is performed according to International Continence Society standards simultaneously with bladder EMG. This new method shows that voiding is accompanied by a slow voltage change in bipolar electrode signals. The contribution of abdominal and other striated muscle activity to the bipolar electrode signals can clearly be distinguished from the slow voltage changes related to voiding. Free flowmetry shows that the electrical activity picked up by the abdominal electrodes is related to bladder emptying. In pressure/flow studies a relation between the electrical activity and the detrusor pressure is found. The present results suggest that the slow voltage changes found during bladder contraction are caused by summed membrane potential changes of bladder muscle cells, but this concept needs further testing. Also, validation for clinical use remains to be established.

Future trends in neurourology.

Attention is drawn to the fact that neurourology should be a regular subspecialty within urology. The urologist should consider himself an organ specialist for the lower urinary tract, meaning that he has the knowledge and the skills to perform diagnostic procedures, as well as all treatment options - either by medication, exercise, operations or electrical stimulation techniques. Beyond general urological knowledge and skills, the requirements for a neurourologist are briefly outlined.

The effects of the calcium-restricted diet of urolithiasis patients with absorptive hypercalciuria type II on risk factors for kidney stones and osteopenia.

The calcium (Ca)-restricted diet of urolithiasis patients with absorptive hypercalciuria type II may decrease Ca excretion but increase biochemical markers of risk for osteopenia. We randomly allocated 25 patients from six hospitals into an experimental group (Ca restriction to 500 mg/day, oxalate-rich products discouraged and normalization of animal protein and sodium) and a control group (no restrictions) for one month. The urinary Ca excretion did not decrease significantly, but the oxalate excretion decreased, although not significantly. The hydroxyproline:creatinine ratio in fasting urine seemed to increase and the calcium:creatinine ratio to decrease. The deoxypyridinoline:creatinine ratio in fasting urine did not change. We conclude that our Ca-restricted diet, which is lower in Ca, animal protein and table salt due to the omission of dairy products, may be of benefit for absorptive hypercalciuria type II patients without enhancing the risk for osteopenia. However, a long-term clinical trial is required.

Determinants of doctor consultation for micturition problems in an elderly male population.

OBJECTIVE: To study which factors influence doctor consultation when a subject has micturition problems. METHODS: Postal questionnaire in an open population of older men (n = 1,695), followed by investigations in 10 general practices, including uroflowmetry. RESULTS: 25% of the men had micturition problems, of which 10-30% presented their symptoms to a doctor. Almost 60% experienced an influence of their micturition habits on activities of daily living. More than 85% of the men were not able to compare their micturition pattern with others. In multiple logistic regression, presentation to a doctor was independently associated with obstructive symptoms, dysuria, men defining their situation as a complaint, depressive mood, more frequent sexual desire and smoking. Many other factors which might play a role in diagnosis and timing of treatment were not found to influence consultation. CONCLUSION: Most men deal with micturition problems without consulting, although symptoms have a substantial impact on daily life. Consultation was associated with symptoms, psychological factors and smoking.

Utility of ultrasound of the upper urinary tract in elderly men with indicators of obstructive symptoms or abnormal flow: how often can silent hydronephrosis be detected in general practice?

BACKGROUND AND OBJECTIVE: While the prevalence of hydronephrosis is very low in obduction studies, a prevalence of 3-13% is reported for patients with an obstruction who are listed for prostatectomy. In order to evaluate the usefulness of transabdominal ultrasound in primary care, we determined the occurrence of hydronephrosis in males with symptoms of urinary obstruction in a general practice setting. METHOD: A micturition questionnaire (a modified Boyarsky) was sent to all men of 55 years or more who were registered in 10 general practices in Maastricht, and was followed by an examination at their general practice. Men with obstructive symptoms and/or with a free-flow abnormality were examined in the hospital with transabdominal ultrasound in order to detect dilatation of the upper urinary tract. This ultrasound was repeated approximately 15 months later. RESULTS: At the first measurement, none of the examined men (n = 178) had hydronephrosis, and this was still the case for 94 men 15 months later. CONCLUSION: Renal ultrasound is not necessary in general practice for men with uncomplicated obstructive complaints.

Long-term efficacy and safety of nilutamide plus castration in advanced prostate cancer, and the significance of early prostate specific antigen normalization. International Anandron Study Group.

PURPOSE: We studied the long-term efficacy and tolerability of nilutamide, a nonsteroidal antiandrogen, combined with orchiectomy in patients with advanced prostate cancer. MATERIALS AND METHODS: A large double-blind trial was done on 457 patients randomized to receive nilutamide or placebo after orchiectomy. RESULTS: At 8.5 years of followup significant benefits were found for progression and survival in favor of patients receiving nilutamide and orchiectomy. In addition, normalized prostate specific antigen levels at 3 months from the start of therapy were predictive of good long-term outcome. Moreover, combined androgen blockade with nilutamide increased the chance of patients having normal prostate specific antigen levels at 3 months. Nilutamide was well tolerated in the long term with no increase in the incidence of drug specific adverse events. CONCLUSIONS: With long-term followup of patients with advanced prostate cancer, the combination of nilutamide and orchiectomy has significant benefits in interval to progression and improved survival compared to orchiectomy and placebo.

Serum markers as a predictor of response duration and patient survival after hormonal therapy for metastatic carcinoma of the prostate.

PURPOSE: Prostate specific antigen (PSA), prostatic acid phosphatase and alkaline phosphatase were analyzed in 2 large prospective multicenter and multinational trials to assess their correlation with time to progression and overall survival after hormonal therapy for metastatic carcinoma of the prostate. MATERIALS AND METHODS: A total of 868 patients who underwent medical or surgical castration was randomized to receive an oral antiandrogen (nilutamide) or placebo. The serum markers under study were measured at baseline and at 1, 3, 6 and every 6 months thereafter. RESULTS: At baseline the strongest predictive factor was serum alkaline phosphatase. Patients with an alkaline phosphatase of 2 or less times normal lived almost twice as long as those with a level of more than 2 times normal (p < 0.0001). The longer survival was observed in patients whose PSA became normal 3 months after initiation of hormonal therapy compared to those whose PSA never reached normal (p < 0.0001). CONCLUSIONS: Serum markers at baseline and during the few months after initiation of hormonal therapy can provide prognostic information for the clinical treatment of patients with metastatic carcinoma of the prostate. In addition, the PSA level at month 3 can serve as a surrogate end point in clinical trials.