Dieter Hauri

BOTULINUM-A TOXIN FOR TREATING DETRUSOR HYPERREFLEXIA IN SPINAL CORD INJURED PATIENTS: A NEW ALTERNATIVE TO ANTICHOLINERGIC DRUGS? PRELIMINARY RESULTS

PURPOSE We evaluated the efficacy of botulinum-A toxin injections into the detrusor muscle in patients with spinal cord injury, detrusor hyperreflexia and urge incontinence resistant to anticholinergic drugs. The purpose of treatment was to suppress incontinence episodes and increase functional bladder capacity. MATERIALS AND METHODS Included in our prospective nonrandomized study done at 2 clinics were 31 patients with traumatic spinal cord injury who emptied the bladder by intermittent self-catheterization. These patients had severe detrusor hyperreflexia and incontinence despite a high dose of anticholinergic medication. Pretreatment evaluation included a clinical examination and complete urodynamic investigation. Under cystoscopic control a total of 200 to 300 units of botulinum-A toxin were injected into the detrusor muscle at 20 to 30 sites (10 units per ml. per site), sparing the trigone. Clinical and urodynamic followup was planned for 6, 16 and 36 weeks after treatment. Patients were asked to decrease their intake of anticholinergic drugs during week 1 after treatment. RESULTS Of the 21 patients 19 underwent a complete examination 6 weeks after the botulinum-A toxin injections, and 11 at 16 and 36 weeks. At the 6-week followup complete continence was restored in 17 of 19 cases in which anticholinergic medication was markedly decreased or withdrawn. Less satisfactory results in 2 cases were associated with an insufficient dose of 200 units botulinum-A toxin. After the injections overall mean reflex volume and mean maximum cystometric bladder capacity plus or minus standard deviation significantly increased from 215.8 +/- 90.4 ml. to 415.7 +/- 211.1 (p <0.016) and 296.3 +/- 145.2 to 480.5 +/- 134.1 (p <0.016), respectively. There was also a significant decrease after treatment in mean maximum detrusor voiding pressure from 65.6 +/- 29.2 cm. water to 35 +/- 32. 1 (p <0.016). Mean post-void residual urine volume catheterized at the end of the urodynamic examination increased significantly from a mean of 261.8 +/- 241.3 ml. to 490.5 +/- 204.8 (p <0.016). Moreover, autonomic dysreflexia associated with bladder emptying that manifested as a hypertensive crisis during voiding disappeared after treatment in the 3 patients with tetraplegia. Satisfaction was high in all successfully treated patients and no side effects were observed. Ongoing improvement in urodynamic parameters and incontinence was already present in all patients reevaluated at 16 and 36 weeks. CONCLUSIONS Botulinum-A toxin injections into the detrusor seem to be a safe and valuable therapeutic option in spinal cord injured patients with incontinence resistant to anticholinergic medication who perform clean intermittent self-catheterization. Successfully treated patients become continent again and may withdraw from or markedly decrease anticholinergic drug intake. A dose of 300 units botulinum-A toxin seems to be needed to counteract an overactive detrusor. The duration of bladder paresis induced by the toxin is at least 9 months, when repeat injections are required.

Comparison of phytotherapy (Permixon®) with finasteride in the treatment of benign prostate hyperplasia: A randomized international study of 1,098 patients

Controversy regarding the relative efficacy of treatments for the relief of the symptoms of benign prostatic hyperplasia (BPH).

Experience With 100 Cases Treated With Botulinum-A Toxin Injections in the Detrusor Muscle for Idiopathic Overactive Bladder Syndrome Refractory to Anticholinergics

PURPOSE In this prospective, nonrandomized, ongoing study we evaluated the efficacy and safety of botulinum-A toxin injections in the detrusor muscle to treat patients with idiopathic overactive bladder resistant to conventional treatment, such as anticholinergic drugs. MATERIALS AND METHODS A total of 23 men and 77 women with a mean age of 63 years (range 24 to 89) with nonneurogenic overactive bladder, including urgency-frequency syndrome, and incontinence despite the administration of maximal doses of anticholinergics were consecutively treated with injections of 100 U botulinum-A toxin in the detrusor muscle at 30 sites under cystoscopic guidance. Micturition diary, full urodynamics, neurological status and urine probes were performed in all participants before treatment. Bladder biopsies were done only in cases of suspected bladder fibrosis or unclear findings. Special attention was given to reflex volume, maximal bladder capacity, detrusor compliance, post-void residual urine, urgency and frequency/nocturia. Clinical, urodynamic and quality of life assessments were performed at baseline, and 4, 12 and 36 weeks after botulinum-A toxin treatment. RESULTS Overall after 4 and 12 weeks 88% of our patients showed significant improvement in bladder function in regard to subjective symptoms, quality of life and urodynamic parameters (p <0.001). Urgency disappeared in 82% of the patients and incontinence resolved in 86% within 1 to 2 weeks after botulinum-A toxin injections. Mean frequency decreased from 14 to 7 micturitions daily (-50%) and nocturia decreased from 4 to 1.5 micturitions. Mean maximal bladder capacity increased 56% from 246 to 381 ml, mean detrusor compliance increased from 24 to 41 ml/cm H(2)O and pretreatment detrusor instability (mean reflex volume 169 ml) resolved in 74% of patients. Mean volume at first desire to void increased from 126 to 212 ml and mean urge volume increased from 214 to 309 ml. There were no severe side effects except temporary urine retention in 4 cases. Only in 8 patients was the clinical benefit poor and analysis revealed preoperative low detrusor compliance. Mean efficacy duration +/- SD was at least approximately 6 +/- 2 months and then symptoms began to increase. CONCLUSIONS Our results show that intradetrusor botulinum-A toxin injections may be an efficient and safe treatment option in patients with severe overactive bladder resistant to all conventional treatments.

Pheochromocytomas: can malignant potential be predicted?

OBJECTIVES The presence of metastatic lesions is the only acceptable fact to confirm malignant pheochromocytoma. Patients with malignant pheochromocytomas, however, have a very poor survival rate. The aim of our study was to postulate predictive values for malignant pheochromocytomas. METHODS We evaluated symptoms, diagnostic modalities, treatment, and long-term follow-up of 86 patients with 85 benign and 10 malignant pheochromocytomas. Parameters from the benign were compared with those of the malignant pheochromocytomas. RESULTS Preoperative 24-hour urinary dopamine was in the normal range for benign pheochromocytomas but increased in malignant pheochromocytomas (P<0.0001). Vanillylmandelic acid was elevated in both benign and malignant pheochromocytomas but higher in malignant than in benign tumors (P = 0.01). No differences could be shown in urinary epinephrine and norepinephrine samplings. Tumor location was divided into 77 adrenal (81%) and 18 extra-adrenal (19%) sites. Malignant pheochromocytomas were located more often at extra-adrenal sites (P = 0.03). There was no increased incidence of malignancy in patients with familial bilateral pheochromocytomas or multiple endocrine neoplasia. Tumors greater than 80 g in weight corresponded to malignancy (P<0.0001). Dopamine tumor concentration was higher in malignant than in benign pheochromocytomas (P = 0.01). Persistent arterial hypertension occurred in 9 (13%) of 72 benign and 6 (60%) of 10 malignant pheochromocytomas (P = 0.001). The 10-year survival rate was 94% for benign pheochromocytomas. All patients with malignant pheochromocytomas died within this period (P = 0.0001). CONCLUSIONS High preoperative 24-hour urinary dopamine levels, extra-adrenal tumor location, high tumor weight, elevated tumor dopamine concentration, and postoperative persistent arterial hypertension are all factors that increase the likelihood of malignant pheochromocytoma. Patients with these characteristics should have more frequent follow-up evaluations to identify malignancy at earlier states.

The Ultrastructure of the Erectile Tissue in Priapism

The ultrastructure of erectile tissue from the corpora cavernosa penis of patients suffering from stasis priapism and high-flow priapism has been studied. Trabecular interstitial edema was confirmed as the first reaction of the tissue to the hemodynamic impairment. At the cellular level trabecular smooth muscle cells were found to be the first affected by the altered environmental conditions. Their reaction consisted of structural and functional transformation to fibroblast-like cells. Severe cellular damage and widespread necrosis were not seen in high flow priapism; such damage existed in stasis priapism, but only when the priapic episode lasted more than 24 hours. Blood clot formation within the cavernae and destruction of the endothelial lining occurred in stasis priapism lasting over 48 hours. At this time trabecular inflammation became conspicuous and most of the smooth muscle cells were either transformed to fibroblast-like cells or had undergone necrosis. This stage was not reached in high flow priapism, a fact supporting the view that high flow priapism is a more benign and prognostically more favorable form of priapism. Massive smooth muscle cell transformation and the loss of contractile trabecular elements may play an important role in the evolution of irreversible erectile failure following stasis priapism persisting longer than 24 hours.

Erection and Priapism: A New Physiopathological Concept

For normal erection two mechanisms are essential: the first provides increased arterial inflow, most probably this is obtained due to the activity of the intimal cushions within the arteriae helicinae and within the shunt vessels. The second mechanism uses increased arterial blood flow; this could be obtained due to the activity of the trabecular muscle fibers of the corpora cavernosa. In consequence, we would deal with two different types of priapism: one type--high-flow priapism--occurs at the level of the arteriae helicinae and the intimal cushions and provokes a high-flow situation, and the second type, with blood stasis in the corpora cavernosa, occurs at the level of the trabeculae due to persistent contraction of the smooth muscle fibers. The prognosis of the second type is much less favorable and should be cured by surgery within the first 48 h.

Seminal vesicle-sparing radical prostatectomy: a novel concept to restore early urinary continence

OBJECTIVES Urinary incontinence after radical prostatectomy continues to be a distressing problem, even with preservation of the neurovascular bundles and meticulous apical dissection. Recent studies suggest that motor and sensory components of the pelvic nerve may be affected by surgery, since both components are anatomically located in intimate contact with the seminal vesicles. We propose seminal vesicle-sparing radical prostatectomy to preserve pelvic innervation and improve the rate of urinary continence. METHODS Fifty-four patients were enrolled in this prospective study. A standard retropubic radical prostatectomy was performed in 34 patients. A seminal vesicle-sparing radical prostatectomy was performed in a pilot series of 20 consecutive patients. The seminal vesicle tip and surrounding tissue were preserved and carefully handled. In all patients, a modified pad test and posterior urethral sensory threshold test were performed preoperatively and 6 weeks and 6 months postoperatively and correlated with urinary continence. RESULTS The intraoperative preservation of the seminal vesicle tip was possible in all patients in this pilot series (n = 20). In the seminal vesicle-sparing radical prostatectomy group, the continence rate was 60% after 6 weeks and 95% after 6 months. These rates were significantly higher than the continence rates in the standard prostatectomy group (18% and 82% at 6 weeks and 6 months, respectively). The sensory threshold levels in the seminal vesicle-sparing group were similar to the preoperative values and were significantly lower than the postoperative threshold levels in the standard prostatectomy group. CONCLUSIONS Seminal vesicle tip-sparing radical prostatectomy may be a surgical option to preserve pelvic innervation and maintain urinary continence after radical prostatectomy. Further randomized studies are necessary to elucidate the impact of seminal vesicle-sparing radical prostatectomy on restoration of urinary continence.

NERVE AND SEMINAL SPARING RADICAL CYSTECTOMY WITH ORTHOTOPIC URINARY DIVERSION FOR SELECT PATIENTS WITH SUPERFICIAL BLADDER CANCER: AN INNOVATIVE SURGICAL APPROACH

Purpose: Radical cystectomy is advocated for high risk patients with superficial bladder cancer. To preserve complete urinary continence, normal sexual function and fertility in young patients, we developed an innovative technique based on nerve and seminal sparing radical cystectomy.Materials and Methods: Radical cystectomy was recommended for 8 patients with superficial bladder cancer that was not conservatively manageable. Average patient age was 44 years (range 36 to 48), and all patients were extremely anxious to maintain potency and fertility. The surgical procedure consisted of transurethral resection of the prostate, pelvic iliac lymph node dissection and extraperitoneal radical cystectomy performed while preserving the vas deferens seminal vesicles and neurovascular bundles. Urinary diversion was accomplished with a W-shaped ileal reservoir anastomosed to the prostatic capsule.Results: Patients were generally discharged from the hospital 15 days after surgery, and postoperative morbidity was limi...

Sildenafil in the Treatment of Sexual Dysfunction in Spinal Cord–Injured Male Patients

Objectives: The aim of this study was to evaluate the efficacy and safety of sildenafil in the treatment of erectile dysfunction (ED) in spinal cord–injury (SCI) patients. Moreover, we looked for neurological conditions permitting therapeutic success and for the ideal dose needed to achieve sufficient erections.Methods: 41 SCI patients were prospectively examined. Sexual dysfunction was assessed by means of anamnesis, the International Index of Erectile Function (IIEF) questionnaire, and neurological examination. Psychogenic erection capacity was tested by audiovisual stimulation and reflexive erection using a vibrator device. Neurophysiological recordings and cystomanometry were performed in parallel to clinical examinations. Neurophysiological recordings included sympathetic skin responses (SSR), pudendus somatosensory evoked potentials (pSSEP), and bulbocavernous reflex (BCR). Urodynamics aimed at classifying the neurogenic bladder dysfunction (upper motoneuron lesion versus lower motoneuron lesion). Intracavernous injection tests with PGE1 were performed in all patients to exclude major organic disease. 50 mg sildenafil was first given 3 times. Thereafter, the doses were adapted according to patients’ reports.Results: Clinically, 28 subjects preserved either reflexive erections (24) or psychogenic erections (4), 11 had both types and only 2 presented with a complete loss of erection. 38 patients (93%) had a positive response to sildenafil and reached a penile rigidity sufficient to permit sexual intercourse. 3 patients dropped out because of non–response despite having increased the dosis up to 100 mg. 22 patients (58%) showed functional erections 1 h after 50 mg sildenafil, whereas 14 (37%) required higher doses of 75–100 mg. By comparing the IIEF questionnaire scores before and after therapy, there was a significant improvement in erectile function and intercourse satisfaction from 9.2±4.4 SD) and 4.5 (±2.5 SD) to 25.5 (±4.2 SD) and 10.5 (±2.1 SD) points, respectively (p<0.05). Nearly 10% (4/41) suffered from side effects such as headache or dizziness. Two of them stopped therapy because of the side effects. At least 36 patients (88%) continue treatment with sildenafil. Absence of both psychogenic (nonsomesthetic supraspinally elicited) and reflexive (somesthetic spinally elicited) erections, confirmed by urodynamical and electrophysiological findings (SSR perineum, BCR and pSSEP), seems to exclude a successful treatment. In contrast, SCI male patients with preserved function of at least one component of the erection phenomenon (psychogenic/reflexive) responded well to sildenafil and the dose required to achieve erections sufficient for sexual intercourse did not differ between the two groups.Conclusions: Sildenafil proves to be a valuable and safe therapeutic management in ED of SCI patients. Therefore, patient acceptance and satisfaction are high. The most common dose required to achieve a satisfying erection is 50 mg. The efficacy of sildenafil depends on sparing of either sacral (S2–S4) or thoracolumbar (T10–L2) spinal segments which, in this study, have been shown to be of relevance in mediating psychogenic erections in male SCI patients. Complete disturbance of any neurogenic impulses excludes successful treatment.

Noninflammatory Chronic Pelvic Pain Syndrome: Immunological Study in Blood, Ejaculate and Prostate Tissue1

Objectives: The aim of this prospective study was to observe immunophenotypic patterns in patients with noninflammatory chronic pelvic pain syndrome (Cat IIIB CPPS) for further description and as possible surrogate markers for diagnosis and treatment. Methods: Eighty–eight patients with a referral diagnosis of chronic prostatitis underwent fractionated urinary cultures including expressed prostate secretion (EPS) and ejaculate analysis twice on two occasions. Monthly serum analyses included C3c, C4, IL–1α, sIL–2R, and IL–6. One hundred samples from healthy individuals were used as the control group for serum analysis. Monthly ejaculate testing was done for IgG, IgA, IgM, IL–1α, sIL–2R, and IL–6. The control group for ejaculate analysis was composed of 96 normal ejaculates (according to the WHO criteria). Immunohistochemical detection of CD3 cells (T lymphocytes) and CD20 cells (B lymphocytes) was performed in 71 biopsy cylinders of Cat IIIB CPPS patients and in 25 prostate biopsy cylinders of men without symptoms or obstruction. Results: Complete sampling of urinary, serum and ejaculate specimens was achieved in 50/88 (57%) patients. Cat IIIB CPPS was observed in 44/50 (88%) patients. Intra–acinar T–lymphocytic infiltrates were dominated by T cytotoxic cells (p = 0.05). Immunohistochemical studies showed inflammatory expression in serum complement, serum interleukin, and ejaculate interleukin concentrations in relation to the presence of large numbers of T cells (all p values ≤0.01). No difference was found in the proportion of B lymphocytes in patients with Cat IIIB CPPS compared to the control group. Serum and ejaculate IL–6 and ejaculate IgA increased significantly and dropped again, correlating with a release of clinical symptoms. Conclusions: Interleukin, complement and immunoglobulin determinations in serum and ejaculate reveal an inflammatory process even in Cat IIIB CPPS. The findings of intra–acinar T–cell–rich infiltrates and the associated inflammatory reaction may be a significant advance in defining Cat IIIB CPPS caused by a possible autoimmune component. Serum and ejaculate IL–6 and ejaculate IgA are possible surrogate markers for the diagnosis and treatment of Cat IIIB CPPS.