Results of a BoNT/A antibody study in children and adolescents after onabotulinumtoxin A (Botox®) detrusor injection.

BACKGROUND: Onabotulinumtoxin A (OnaBoNT/A, Botox®) is effective in the treatment of neurogenic detrusor overactivity, however this therapy can fail. In a prospective study, we analyzed patient serum for BoNT/A antibodies (BoNT/A-AB) as a possible cause of therapy failure. METHODS: 17 patients (average age 14.5 years) who had neurogenic detrusor overactivity were admitted for repeated OnaBoNT/A injection into the detrusor muscle. We analyzed their serum for BoNT/A-AB. The clinical findings were correlated with the incidence of BoNT/A-AB. RESULTS: Positive BoNT/A-AB were clearly or marginally determined in 6 patients. Therapy had failed in all 6. In 4 of the 6, therapy might have failed because of a low-compliance bladder (3 patients) or tethered-cord syndrome (1), but BoNT/A-AB were found as the only possible cause in 2 patients. Thus, the incidence of BoNT/A-AB in the 17 patients was 35%, and the antibodies were clinically significant in 12%. All patients with BoNT/A-AB had a history of recurrent urinary tract infections. CONCLUSIONS: Patients who show a failure of therapy after OnaBoNT/A injections for which no other causes can be determined should have their serum checked for BoNT/A-AB. Recurrent urinary tract infection might be a predisposing factor for BoNT/A-AB.

[A look beyond urology: vaginal cancer]. / Ein Blick diesseits des Tellerrandes: Das Vaginalkarzinom.

Primary carcinomas of the vagina are very rare. Nevertheless, they need to be included in differential diagnoses when carrying out a urological examination of the pelvic floor and the vagina in patients with micturition problems, also in younger patients: we report a case of a 35-year-old woman with a primary carcinoma of the vagina and present a review of the literature.

Pubovaginal bone anchor fixation with polyethylene versus fascia lata slings in the treatment of female stress incontinence: sling material and processing are predominant factors in success.

OBJECTIVE: The opponents of the In-Taca bone anchor system note the risk of a high rate of wound infection and osteitis pubis. We evaluated whether there is a difference in the outcome of the use of two different sling materials--polyethylene and fascia lata--with regard to wound infection, and analyzed the incidence of osteitis pubis further in a larger series. MATERIAL AND METHODS: A total of 61 women (mean age = 65.4 years) were treated for stress urinary incontinence (SUI) type II and III using the In-Taca bone anchor system. In 15 of 61 patients, we used a synthetic sling of polyethylene, and in 46, a fascia lata sling. The subjective success rate was determined with validated questionnaires (Urinary Distress Inventory-6, Symptom Severity Index and Symptom Impact Index). The objective assessment included a pad test according to the ICS- standard and a urogynecologic evaluation. Mean follow-up was 10.2 months. RESULTS: Wound inflammation of only very mild degree occurred in 15% in the fascia lata group, whereas 33% in the polyethylene group developed serious sling infection; in three patients explantation of the sling was necessary. Accordingly, satisfaction with the procedure was low in the polyethylene group. In both groups, there were no hints of osteitis pubis. The sling material used did not affect continence rate. CONCLUSION: Using the bone anchor system, the infection rate depends primarily on the sling material used and its processing: polyethylene is well tolerated in other reconstructive procedures (such as TVT, where a netlike mesh is used), so the processing of synthetic sling material plays an extremely important role in infection rate: platelike, dense synthetic material tends to cause wound infection.

A new option for the management of urethral trauma: primary reconstruction of posterior urethral disruption with a buccal mucosa transplant.

Up to now, the management of traumatic posterior urethral disruption ranges from primary realignment to delayed urethroplasty. However, we reconstructed the membranous part of the urethra with an onlay graft of buccal mucosa after traumatic complete disruption as a first line therapy. After 7 months followup, the clinical outcome is very good. Because primary reconstruction of the urethra with a buccal mucosa graft after traumatic disruption has not yet been reported, the question arises whether this technique should be routinely included as an option for primary urethral reconstruction after trauma of the posterior urethra.

[Subjective patient satisfaction after injection of botulinum-a toxin in detrusor overactivity]. / Subjektive Patientenzufriedenheit nach Botulinumtoxin-A-Injektionen bei Detrusorhyperaktivität.

PURPOSE: The established treatment for overactive detrusor function consists of anticholinergic drugs. But this treatment can fail or produce intolerable side effects. We therefore investigated the effect of botulinum-A toxin in treating overactive detrusor function in patients with neurogenic and nonneurogenic bladder dysfunction. We were particularly interested in patient satisfaction with this therapy. MATERIAL AND METHODS: The subjects were 38 patients who had overactive detrusor function of different origins and in whom therapy with anticholinergic drugs had failed. To measure results, we used urodynamic studies and a questionnaire that consisted of 27 validated questions ("Urogenital Distress Inventory UDI-6", "Symptom Severity Index" and "Symptom Impact Index") as well as a satisfaction questionnaire. We injected 200 - 300 U of botulinum-A toxin (Botox) cystoscopically. RESULTS: At least 4 weeks after injection, 90 % of the patients reported clear improvement of their voiding situation and 93 % stated that they would undergo this procedure again. The frequency of micturition decreased by 29 % in average, and the increased postvoid residual volume was clinically irrelevant. Patients reported side effects or complications in 6.7 % of cases. The satisfaction scale (0 - 10) averaged 6.9. Urodynamically, reflex volume increased by 85 %, maximal bladder capacity increased by 47 %, and bladder pressure decreased by 33 %. CONCLUSIONS: Botulinum-A toxin injection into the overactive detrusor muscle seems to be very effective. The effect is not only reflected in urodynamic studies but also in the subjective patient satisfaction.

Acetylsalicylic acid inhibition of n-butyl-(4-hydroxybutyl)nitrosamine-induced bladder carcinogenesis in rats.

We examined the effect of acetylsalicylic acid (ASA) on n-butyl-(4-hydroxybutyl)nitrosamine (BHBN)-induced bladder carcinogenesis in male Wistar rats. Of 29 rats that received 0.05% BHBN in their drinking water for 9 weeks, 8 developed bladder cancer. Only 1 out of 29 rats that received 0.1% ASA in their diet for 20 weeks, including the period of BHBN consumption, developed a tumor. That difference is statistically significant. Bladder weight was significantly higher in rats given BHBN than in controls and in rats given both BHBN and ASA. We conclude that ASA inhibits BHBN-induced bladder carcinogenesis.

Effect of nitric oxide-donor, linsidomine chlorhydrate, in treatment of human erectile dysfunction caused by venous leakage.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. We studied the effect of a direct NO-donor, linsidomine chlorhydrate (SIN-1), in 30 patients with venous leakage confirmed by dynamic pharmacocavernosography and pharmacocavernosometry that was refractory to prostaglandin E1 (PGE1) under the assumption that the more physiologic approach might give better results. In all 30 patients, response to SIN-1 was no better, and in 22 cases it was less than the response to PGE1. No systemic or local side effects of SIN-1 were observed. SIN-1 is not superior to PGE1 in the treatment of erectile dysfunction caused by venous leakage, and failure of NO-mediated smooth muscle relaxation does not play a part in the entity, "venous leakage."

Nitric oxide mediates neurogenic relaxation induced in rabbit cavernous smooth muscle by electric field stimulation.

We investigated the relaxant effect of electric field stimulation (EFS) on rabbit cavernous smooth muscle strips in vitro precontracted by phenylephrine. Effects of EFS were monitored alone, and following muscarinic receptor blockade, and inhibition of nitric oxide (NO) formation by L-N-monomethylarginine (L-NMMA) or by L-N-nitroarginine (L-NOARG). Atropine only slightly reduced the relaxant effect of EFS to 89.0 +/- 6.1 percent. Additional application of L-NMMA further reduced the relaxant effect to 37.3 +/- 15.3 percent. Substitution of L-NOARG for L-NMMA led to a more pronounced inhibition of relaxant effects to 16.2 +/- 8.7 percent. The results indicate that neurogenically induced relaxation of rabbit cavernous smooth muscle is mediated mainly by NO formation and argue against a substantial role of relaxing peptidergic neurotransmitters, such as vasoactive intestinal polypeptide and calcitonin-gene-related peptide, in penile erection.

Urodynamic effects of oral oxybutynin chloride in children with myelomeningocele and detrusor hyperreflexia.

OBJECTIVES: To investigate the effects of oral oxybutynin chloride (OC) on standard urodynamic measures in children with myelomeningocele (MMC) and detrusor hyperreflexia. METHODS: Forty-one MMC children with detrusor hyperreflexia (19 boys and 22 girls, aged 2 months to 15 years; mean 4.9 years) were evaluated urodynamically before and within 3 months after initiation of oral OC therapy (0.2 to 0.3 mg/kg/day). Therapy with oral OC was always combined with clean intermittent catheterization (CIC). RESULTS: Oral OC treatment caused an increase in bladder capacity from 141 +/- 96 to 197 +/- 99 mL (+ 40%; P < 0.01), a decrease in detrusor pressure at maximal capacity from 45 +/- 32 to 28 +/- 23 cm H2O (-38%; P < 0.01), and an increase in detrusor compliance from 6.5 +/- 5.6 to 16.8 +/- 13.7 mL/cm H2O (+ 158%; P < 0.01). Improvement in urodynamic measures and continence were correlated. After a follow-up of at least 2 years, effective protection of renal function was achieved in 38 of the 41 children (93%) with conservative therapy alone. Adverse effects resulted in discontinuation of oral OC treatment in only 2 cases. CONCLUSIONS: Treatment with oral OC and CIC is effective and safe in children with MMC and detrusor hyperreflexia and should be initiated early when indicated by urodynamic findings.

Efficacy of linsidomine chlorhydrate, a direct nitric oxide donor, in the treatment of human erectile dysfunction: results of a double-blind cross over trial.

Recent experimental work has demonstrated that nitric oxide (NO) is the neurotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor SIN-1 (linsidomine chlorhydrate) in patients with erectile dysfunction have come to conflicting results. We have performed a double-blind cross over trial in 40 patients with erectile dysfunction of mixed etiology comparing SIN-1, SIN-1 plus the alpha-blocker Urapidil, and prostaglandin E1 (PGE1) in order to determine the effectiveness of SIN-1. PGE1 achieved the best response, the combination of SIN-1 and Urapidil performed slightly, statistically insignificantly poorer with significantly increased side effects. SIN-1 alone performed statistically significantly (p < 0.0068) worse. SIN-1 is not a useful alternative to PGE1. The combination of SIN-1 and Urapidil performs equally as good as PGE1 but cannot be recommended due to intolerable side effects.

Laparoscopic management of hydronephrosis in a woman with rare genitourinary anomalies: unicornous uterus, contralateral agenesis of the kidney, and contralateral ectopic ovary in the groin.

A 40-year-old woman had infected right-sided hydronephrosis and rare genitourinary anomalies-a dextroposed unicornous uterus-as the cause of the hydronephrosis, which had to be mobilized laparoscopically by dissecting the scar tissue. Furthermore, the patient had left-sided agenesis of the kidney and a left-sided ectopic ovary with a rudimentary tube in the inner inguinal canal.

Pneumatic lithotripsy applied through deflected working channel of miniureteroscope: results in 143 patients.

Although extracorporeal shockwave lithotripsy (SWL) is a successful treatment for ureteral calculi, introduction of miniureteroscopes has advanced endoscopic management. We combined the use of a semirigid ureteroscope with a pneumatic lithotripter (Swiss Lithoclast) for the treatment of ureteral calculi. From January 1992 to August 1994, 143 patients (87 male, 56 female; mean age 48.7 years; age range 22-74 years) with urolithiasis underwent endoscopic lithotripsy with the Swiss Lithoclast under general anesthesia. The 0.8 = mm probe was inserted through the deflected working channel (3.4F) of the Micro-6L ureteroscope (tip diameter 6.9F). The calculi were in the distal (N = 96; 67.1%), mid (N = 34; 23.8%), and proximal part (N = 13; 9.1%) of the ureter. The mean stone size was 6.8 mm (range 5-26 mm). Of the 137 patients whose stones we could access adequately, 70 (51.1%) were stone free immediately after the procedure, and another 31 (22.6%) had residual fragments <3 mm that passed spontaneously. The remaining 36 patients underwent another 50 procedures; 30 SWL sessions in 26 patients (19%), 17 further endoscopic lithotripsies in 14 (10.2%), and open surgery in 3. Application of the Swiss Lithoclast through semirigid miniureteroscopes is highly effective for endoscopic lithotripsy, regardless of stone composition. Deflection of the probe up to 30 degrees did not impair the disintegration rate. Because of the high migration rate of mid and proximal ureteral stones, the Swiss Lithoclast is not recommended in these cases as a primary procedure. Low capital cost and simple and safe handling are the device's major advantages over laser lithotripsy.

Nitric oxide donor, linsidomine chlorhydrate (SIN-1), in the diagnosis and treatment of erectile dysfunction: critical appraisal and review of the literature.

Recent experimental work has demonstrated that nitric oxide (NO) is the neutrotransmitter responsible for cavernous smooth muscle relaxation. Different studies on the performance of the direct NO-donor linsidomine chlorhydrate (SIN-1) in patients with erectile dysfunction have come to conflicting results ranging from highest praise to complete dismissal. We reviewed all published studies on the use of SIN-1 for intracorporeal injection in erectile failure including our own. To this date, 3 groups published their data. Only the uncontrolled data from Hannover claim good results. The controlled data from Hamburg and Berlin on patients with erectile failure due to venous leakage, to a mixed aetiology in a double-blind fashion and to mixed aetiology with drug increase (1 mg versus 2 mg of SIN-1) showed a significantly worse performance of SIN-1 compared to the standard drug for penile injection, prostaglandin E1. We conclude that there is no place for linsidomine chlorhydrate in either the diagnosis or the treatment of erectile dysfunction.

[Botulinum toxin in urology. An inventory]. / Botulinumtoxin in der Urologie. Eine Bestandsaufnahme.

Botulinum toxin (BTX) is highly potent in neurogenic and non-neurogenic voiding disorders. Experience with it in neurourology began 15 years ago in the treatment of neurogenic detrusor-sphincter dyssynergia. Indications were expanded not only to neurogenic detrusor hyperactivity but also to non-neurogenic detrusor hyperactivity, other forms of dysfunctional voiding, and some types of pelvic pain syndrome. Sphincter injections can be recommended for patients with symptomatic post-voiding residual urine due to insufficient detrusor contractility, and detrusor injections can be recommended for patients with neurogenic detrusor hyperactivity in which anticholinergic drugs are not sufficient. Because of the lack of evidence-based studies, botulinum toxin is not approved for urologic use, although there is a desperate need for it.

[Endoscopic lithotripsy with pneumatic shockwave (Swiss Lithoclast) using a mini-ureteroscope]. / Endoskopische Lithotripsie mit der pneumatischen Stosswelle (Swiss Lithoclast) durch Miniureteroskope.

We performed endoscopic lithotripsy for 23 urinary stones (21 ureteral and 2 bladder stones) with a pneumatic shockwave unit (Swiss Lithoclast; EMS, Angiomed), for the first time applying the probe through the tangential working channel of a semirigid 6.9-Fr ureteroscope (Circon, ACMI). Disintegration was successful in all stones (5-24 mm). Immediately after treatment, the 2 patients with bladder calculi and 10 of the patients with ureteral stones (47.6%) were stone free, while another 5 had residual fragments < 3 mm. Migration of fragments in 4 patients (19%) led to subsequent extracorporeal shock wave lithotripsy. There were no ureteral perforations in this series. Routine application of double-J stents avoided any serious postoperative complications. Endoscopic lithotripsy with the pneumatic shockwave unit was shown to be highly effective regardless of stone composition. The ltihotripsy probe is easily applied through mini-ureteroscopes.

Rupture of the Left Renal Fornix after Vaginal Repair of Postpartum Vesicovaginal Fistula.

Surgical repair of vesicovaginal fistulas carries a risk of postoperative obstruction of the upper urinary tract. In the case described here, a postoperative intramural edema led to urinary retention and subsequent rupture of the renal pelvis. This is a rare but typical urological emergency. If patients complain postoperatively of flank pain, ultrasound should be carried out promptly. If the findings are unclear (no urinary retention despite clinical symptoms), additional computed tomography should be performed to determine whether rupture of the fornix has occurred.

Efficacy of botulinum-A toxin bladder injections for the treatment of neurogenic detrusor overactivity in multiple sclerosis patients: an objective and subjective analysis.

AIMS: We studied the use of botulinum-a toxin (BTX-A) injections into the bladder as an alternative approach in patients with neurogenic detrusor overactivity due to multiple sclerosis (MS) with drug-refractory overactive bladder (OAB) symptoms. METHODS: Sixteen MS patients--11 women, 5 men; mean age 48.6 years--with refractory OAB symptoms were included in a one-center prospective study. For outcome analysis, we used a bladder diary, a complete urodynamic study, and validated questionnaires for subjective assessment. We injected 300 U of BTX-A (Botox) into the bladder and into the external sphincter muscle to reduce the probability of posttreatment urine retention. RESULTS: There was an increase in residual volume from 81.3 +/- 23.8 to 126.3 +/- 32.9 ml after 4 weeks. In one woman, transient self-catheterization was unavoidable. Four weeks and 3 and 6 months after BTX-A injection, the significant results were as follows: daytime frequency was reduced by 29%, 44%, and 30%, respectively. Nocturia diminished by 33%, 72%, and 40%. Use of pads was be reduced by 38% after 4 weeks and by 64% after 3 months. Urodynamically, reflex volume and maximal cystometric bladder capacity increased by 73%, 77%, and 58% (at 6 months, the increase was not significant) and by 36%, 27%, and 36% (not significant). Maximal detrusor pressure decreased by 35%, 22%, and 57%. Subjective outcome indicated significant improvement of symptoms at 4 weeks and 3 months, but not at 6 months. Patient satisfaction with the therapy was very high. CONCLUSIONS: BTX-A detrusor injections are very effective in the treatment of drug-resistant OAB symptoms in MS patients as reflected in urodynamic measurements and in patient satisfaction. Build up of residual urine remains a problem of which patients must be informed.

Penile venous surgery in impotence: results in highly selected cases.

Currently, indications for penile venous surgery are dynamic pharmacocavernosographic findings in impotent patients who fail to respond to intracorporeal application of vasoactive substances and who demonstrate unimpaired arterial perfusion. We used pharmacocavernosometry to measure penile intracorporeal maintenance flow rate in 48 impotent men: 20 had maintenance flow rates higher than 30 ml/min, 12 of the 20 had leakage mainly via Santorini's plexus. In 7 of this 12, venous ligation procedures were initially successful, and in 6 of them erectile function returned. After a mean follow-up, seven of the 12 eventually had to be treated with penile implants. Another 4 used self-injection of prostaglandin E1; only 1 patient reported spontaneous erections sufficient for intercourse. Poor long-term results of surgery and recent data on active mechanisms in venous outflow restriction raise doubts as to whether penile venous surgery can ever cure so-called venous incompetence.

Evaluation of vasculogenic impotence by monitoring of cavernous oxygen tension.

Color coded duplex sonography, regarded as the gold standard in penile vascular evaluation, does not yield data on cavernous oxygenation itself. In addition to using color coded duplex sonography to measure peak flow velocity in cavernous arteries after injection of 20 micrograms. prostaglandin E1 in 34 unselected patients with impotence, we monitored cavernous oxygen tension with oxygen-sensitive Eppendorf needle electrode. During flaccidity the mean cavernous oxygen tension of 38 mm. Hg increased to 61 mm. Hg after injection of prostaglandin E1. Peak flow shown with color coded duplex sonography and maximal oxygen tension correlated well in 24 men (71%). However, in 10 men (29%) normal peak flow did not result in a cavernous oxygen tension of greater than 65 mm. Hg, so this might have been isolated cavernous perfusion defects. In contrast, there was no case of impaired arterial inflow and high oxygen tension. Monitoring of cavernous oxygen tension allows for characterization of patients with cavernous perfusion deficiency. This new and simple diagnostic method might help to improve diagnosis and followup after penile vascular surgery. However, more data on patients and controls will be required to define normal ranges.