Combined low-dose antimuscarinics for refractory detrusor overactivity in children.

INTRODUCTION AND AIMS: Behavioral therapy and bowel management are the initial and mainstay treatments for overactive bladder (OAB). Antimuscarinic agents are initiated if these measures fail or symptoms are severe. This study reported the results of treatment with a high dosage of a single drug in children with refractory detrusor overactivity (DO). After the children maintained their previous antimuscarinic medication, a second antimuscarinic drug (trospium chloride) was added as a combination therapy. MATERIALS AND METHOD: Seventy-two children with DO were enrolled in this prospective study (Figure). They had persistent urgency and urgency urinary incontinence (UUI), even with behavioral bowel therapy, and used an optimized dosage of oxybutynine. All patients demonstrated DO at urodynamic study and started on oxybutynin and trospium chloride at the lowest weight-adjusted dose (10-20 mg/day for trospium chloride). A bladder diary was recorded for 3 days, and urodynamic studies were repeated at 3 and 6 months. RESULTS: Sixteen children (22.2%) became dry. Thirty-three children (45.8%) attained a significant decrease in incontinence from an average of 5 to 1.3 episodes per day. A statistically significant increase of mean cystometeric bladder capacity (P = 0.006) was also observed at the 6-month follow-up. The overall success rate was 68%, since 23 children (32%) discontinued combined treatment due to persistent symptoms and/or intolerable side effects. A total of 41 children (57%) reported no side effects, 25 (34.7%) reported mild side effects, six (8.3%) reported moderate side effects, and two withdrew from the study due to their side effects. CONCLUSIONS: The addition of low-dose trospium chloride to oxybutynine seemed to be an effective and safe treatment approach for children with DO who were refractory to high-dosage monotherapy. Different combinations with different antimuscarinics drugs could be evaluated in the future.

Botulinum A toxin urethral sphincter injection in children with nonneurogenic neurogenic bladder.

PURPOSE: We evaluated botulinum-A toxin (Botox) injection into the urethral urinary sphincter in children with nonneurogenic neurogenic bladder to decrease urethral resistance and improve voiding. In these patients alpha-blocker medications had failed and injection was an alternative to unavailable biofeedback. MATERIALS AND METHODS: Prospective treatment was performed in 10 children 6 to 17 years old (mean age 8) with nonneurogenic neurogenic bladder using botulinum-A toxin (Botox). Preoperatively all children were evaluated by ultrasound, voiding cystourethrography, excretory urography, magnetic resonance imaging and urodynamic studies, including pressure flow, electromyography and uroflowmetry. One patient had unilateral G3 reflux and 4 had bilateral G1 to G3 hydronephrosis. Using a rigid pediatric endoscope and a 4Fr injection needle 50 to 100 IU botulinum-A toxin were injected into the external sphincter at the 3, 6 and 9 o'clock positions. Followup was 6 to 15 months. Repeat injections every month were given according to the response with a maximum of 3 injections. RESULTS: Immediately after botulinum-A toxin injection all except 1 patient were able to void without catheterization. No acute complications occurred. Four patients with bilateral hydronephrosis and the patient with the refluxing unit showed regression. Postoperatively post-void residual urine decreased by 89%, detrusor leak point pressure decreased significantly by a mean +/- SD of 66 +/- 18 vs 37 +/- 4 cm H(2)O and uroflowmetry showed a marked increase in maximum urine flow of 2 +/- 2 vs 17.8 +/- 8 ml per second. Three injections were needed in 1 patient to attain the desired response. CONCLUSIONS: Urethral sphincter botulinum-A toxin injection could be considered a reliable treatment modality in children with nonneurogenic neurogenic bladder after the failure of conservative therapy.

Urodynamic predictors of upper tract deterioration in children with myelodysplasia.

The clinical and urodynamic data of 62 children with myelodysplasia without previous urological treatment were tested statistically for the ability to predict upper tract deterioration. This was done by comparing these data among 26 children with dilated upper tracts and 36 children with normal upper tracts. Vesicoureteric reflux had a strong positive correlation with upper tract dilation but the maximum cystometric capacity, detrusor instability, compliance, maximum urethral closure pressure and peak flow rate all had no predictive value. Residual urine is sensitive and negatively predictive and leak pressure is specific and positively predictive; detrusor pressure at peak flow, opening pressure, pressure at least flow and the detrusor-adjusted mean passive urethral resistance relation factor (DAMPF) are sensitive and specific with high positive and negative predictive values.

Modified vascularized pedicled scrotal flap for complex hypospadias.

Surgical correction of complex hypospadias defects is a problem. A 1-stage technique using a scrotal septum pedicled skin flap was used in 7 patients with inadequate preputial skin and scarred ventral penile skin unsuitable for satisfactory repair. The results were satisfactory in 5 patients. Distal urethral stricture developed in the remaining 2 patients and 1 of them had a subcoronal urethrocutaneous fistula. Minor hair growth was noted in 1 patient. The pedicled scrotal septum flap is recommended in selected cases of complex hypospadias, particularly when other methods fail.

Perioperative antibiotic prophylaxis for transurethral resection of the prostate: is it justifiable?

The role of perioperative antimicrobial prophylaxis in transurethral resection of the prostate remains controversial. A total of 110 patients with preoperative sterile urine undergoing transurethral resection of the prostate was included in this open, prospective and randomized study to compare the prophylactic role of cefoperazone to no antibiotic prophylaxis. Patients were well matched between the 2 groups on all essential characteristics and risk factors at baseline. Owing to the strict selection criteria and aseptic measures used, the low incidence of postoperative urinary tract infections in the control group (1.8 per cent) compared to none in the cefoperazone group made conclusions and generalization limited due to sample size. In view of the extremely low infection rate it is doubtful that antibiotic prophylaxis had any beneficial role in this selected population.

The evolution of artificial sphincter cuff in growing animals.

An animal model was developed to simulate the effect of implantation of artificial sphincter cuff on the urethra in children. The study was conducted on 28 pigs, 15 castrated males, four uncastrated males and nine females, divided into four groups: control unoperated, and three operated groups. Group I contained young piglets (castrated males, uncastrated males and females), group II contained adult animals and group III contained sham operated animals. An AS 800 belt occlusion cuff was implanted in the deflated state distal to the bladder neck around the urethra in the young and adult groups, while no sphincter was implanted in the sham group. Neither primary nor secondary activation was done. The pigs were followed for a period of six to eight weeks and then sacrificed. The morphological and histological observations on the effects of the artificial sphincter cuff on the underlying urethral tissue showed significant transmural atrophy of the urethral and prostatic segment underlying the cuff in the young growing castrated and uncastrated male group with mild changes in the young female group. Bladder rupture occurred in three uncastrated males. There were no changes encountered in the adult or sham operated groups. Variable degrees of upper tract changes and renal deterioration were seen in the young group. These changes occurred mainly in the male piglets while a lesser degree occurred in the female piglets. No changes were demonstrated in the adult and sham groups. This study suggests the possibility of similar changes occurring in young male children who have undergone artificial sphincter implantation.

Dynamics of the ureterovesical junction: its resistance to upper urinary tract outflow in pigs.

In pigs, upper urinary tract outflow resistance at the ureterovesical junction (UVJ) has been investigated before and after changes of capacity and compliance of the bladder with ureterovesical perfusion pressure (UV-PP) measurements and cystometry (PB). Changes of UV-PP approximately paralleled changes of PB during volume changes and compression of the bladder, and during detrusor activity. Exceptions were: detrusor activity in all bladders, being nondistended, during which UV-PP always increased more than PB; and low and high compliant, and small capacity bladders in which UV-PP may change more than PB under all conditions once these bladders are so far filled that they are distended. From these findings and UVJ anatomy it is concluded that, besides intravesical pressure, anatomical factors and forces in the bladder wall also may determine upper urinary tract outflow resistance. The clinical implications are discussed.

Intravesical instillation of a calcium entry blocker and its effects on detrusor contractility: in vitro and vivo experiments.

The effects of intravesical instillation of a Ca2+ entry blocker (verapamil) on the contractility of the bladder detrusor muscle of the rabbit were investigated in vitro and in vivo. In in vitro experiments, using whole bladder preparations, spontaneous contractile activity and contraction induced by direct electric stimulation or acetylcholine were monitored. Both activities were inhibited in a time-dependent manner after the intravesical instillation of 7.5 mg. verapamil. The amplitude of spontaneous contraction 90 minutes after the instillation, was reduced to 10 per cent of control (before the instillation), and the response to electric stimulation and acetylcholine were inhibited to 16 per cent and 38 per cent of controls respectively. The detrusor contractility was still inhibited two hours after the removal of verapamil from the bladder. This inhibition of the detrusor contractility after removal of verapamil was completely reversed by adding four mM Ca2+ intravesically. During in vivo experiments, the changes of intravesical pressure elicited by pelvic nerve stimulation and the systemic arterial pressure were monitored. Sixty minutes after the intravesical instillation of 10 mg. verapamil, the rise of the intravesical pressure following the pelvic nerve stimulation was inhibited to 18 per cent of control, while the systemic arterial pressure was not affected. It is suggested that the intravesical instillation of verapamil can inhibit detrusor contractility without affecting cardiovascular status.

Dynamics of the ureterovesical junction: its fluid transport mechanism in the pig.

The peristaltic fluid transport mechanism of the ureterovesical junction was investigated with distal and juxtavesical ureteral perfusion pressure measurements. Elimination of the activity of the juxtavesical ureteral segment, juxtavesical or intravesical partial resection of the ureteral sheaths, and impediment of shortening of the muscular layers of the ureterovesical junction ureter segment, all reduced the effectiveness of ureterovesical junction peristalsis. From these findings and from the anatomy of the ureterovesical junction we concluded that peristaltic urine transport through the ureterovesical junction is effectuated by shortening and telescoping of the muscular layers of the ureterovesical junction ureter segment and its sheaths into each other and into the ureteric hiatus.