Katherine Moore

Double Anticholinergic Therapy for Refractory Overactive Bladder

PURPOSE Using 2 anticholinergic medications simultaneously (10 to 30 mg oxybutynin, 4 mg tolterodine and/or 5 to 10 mg solifenacin) we optimized the medical therapy for children in whom single agent anticholinergic therapy failed. We evaluated efficacy, tolerability and safety. MATERIALS AND METHODS Children with refractory overactive bladder and incontinence were included in a prospective, open label protocol. Study inclusion criteria were persistent symptoms on medical and behavioral therapy, absence of correctable neurological anomalies, and partial clinical and urodynamic responses on an optimal dose of 1 well tolerated, long acting anticholinergic. Patients were followed prospectively every 3 months. The primary end point was efficacy for continence and the secondary end points were tolerability and safety. RESULTS We enrolled 14 girls and 19 boys in the study, and followed 19 patients with neurogenic bladder and 14 with overactive bladder a minimum of 3 months. Mean age at enrollment was 12 years and double medication was given for a mean of 16 months (range 3 to 42). Mean +/- SD urodynamic capacity improved from 192 +/- 92 to 380 +/- 144 ml, no deterioration in compliance was noted and maximal contraction pressure decreased from 77 +/- 27 to 18 +/- 15 cm H(2)O. Continence improved in all patients, of whom 17 were dry, and 14 and 2 were significantly and moderately improved, respectively. No, mild and moderate side effects were reported by 12, 16 and 5 patients, respectively. In 3 of the 17 patients who voided greater than 20% post-void residual urine developed. Blood tests and electrocardiogram remained normal. CONCLUSIONS In children with refractory overactive bladder double anticholinergic therapy is an efficient and serious alternative to surgery. Patients and families were satisfied with this nonoperative, innovative approach.

Prospective Open Label Study of Solifenacin for Overactive Bladder in Children

PURPOSE We evaluated the effect of solifenacin for urinary incontinence in children with overactive/neurogenic bladder refractory to oxybutynin or tolterodine. MATERIALS AND METHODS Pediatric patients presenting with refractory overactive bladder with incontinence were offered the opportunity to enter a prospective, open label protocol using adjusted dose regimens of 1.25 to 10 mg solifenacin. Study inclusion criteria were absent correctable neurological anomalies on magnetic resonance imaging, failure of symptoms to improve on intensive behavioral and medical (oxybutynin or tolterodine) therapy, and/or significant side effects of those agents. Followup consisted of a voiding diary, post-void residual urine measurement, urine culture, ultrasound and urodynamics. Families were questioned about continence, side effects, compliance, behavior change and quality of life. The primary end point was efficacy for continence and secondary end points were tolerability and safety. RESULTS Enrolled in the study were 42 girls and 30 boys. Of the patients 27 with neurogenic bladder, of whom 11 were on clean intermittent catheterization, and 45 with overactive bladder completed a minimum 3-month followup. Patients were on solifenacin a mean of 15.6 months. Mean age at study initiation was 9.0 years. Mean ± SD urodynamic capacity improved from 146 ± 64 to 311 ± 123 ml and uninhibited contractions decreased from 70 ± 29 to 20 ± 19 cm H(2)O (p <0.01). Continence improved in all patients, including 24 who were dry, and 42 and 6 who were significantly and moderately improved, respectively. Of the patients 50 reported no side effects while 15 had mild and 3 had moderate side effects. Four patients withdrew from the protocol due to intolerable side effects. Four patients had significant post-void residual urine (greater than 20 ml). CONCLUSIONS In children with overactive bladder refractory to oxybutynin or tolterodine solifenacin is an effective alternative to improve symptoms. Tolerability was acceptable and the adjusted dose regimen appeared safe.

Prospective Pilot Study of Mirabegron in Pediatric Patients with Overactive Bladder

BACKGROUND Antimuscarinics are the pharmacologic mainstay of overactive bladder (OAB) management, but side effects limit their use. Mirabegron, a new molecule with a distinct mechanism of action (β3-adrenoreceptor agonist), was recently approved as monotherapy for idiopathic OAB in adults but has not been studied in the pediatric population. OBJECTIVE To evaluate the efficacy and safety of mirabegron to treat urinary incontinence in children with idiopathic OAB who were refractory to and/or intolerant of antimuscarinics. DESIGN, SETTING, AND PARTICIPANTS A prospective off-label study using mirabegron was conducted. Pediatric patients without symptom improvement under behavioral and medical therapies and/or with significant side effects with at least two different antimuscarinic agents were recruited. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Our primary outcome was better reported efficacy than with the use of prior anticholinergic medication. Secondary end points were tolerability, safety, and satisfaction. Efficacy and tolerability were assessed with voiding diaries, postvoid residuals, urine cultures, electrocardiogram, and vital signs. Families were questioned for continence, side effects, compliance, and Patient Perception of Bladder Condition (PPBC) questionnaire. The Wilcoxon rank sum test and Wilcoxon signed rank test were used for statistical analysis. RESULTS AND LIMITATIONS A total of 58 patients were recruited at a median age of 10.1 yr and were on mirabegron for a median of 11.5 mo. Median bladder capacity improved from 150ml to 200ml (p<0.001). Continence improved in 52 of 58, with 13 being completely dry. Median PPBC improved from 4.0 to 2.0 (p<0.001). Eight patients reported mild or moderate side effects. Absence of a placebo group is a limitation of the study. CONCLUSIONS Mirabegron, a novel first-in-class therapy, appeared as a safe and effective alternative for children with idiopathic OAB refractory to antimuscarinics. PATIENT SUMMARY We evaluated the efficacy and safety of mirabegron to treat incontinence in pediatric patients. Continence, median voided volumes, and quality of life were improved after the introduction of mirabegron, and few side effects were reported.

Modified Scrotal (Bianchi) Mid Raphe Single Incision Orchiopexy for Low Palpable Undescended Testis: Early Outcomes

PURPOSE We compared the results of low transscrotal mid raphe orchiopexy, high scrotal incision (Bianchi) and conventional inguinal approach in patients with palpable undescended testes. MATERIALS AND METHODS Orchiopexies performed between January 2003 and September 2009 with a minimum 3-month followup were included. Low scrotal incision (group 1) and high scrotal incision (group 2) were compared to the traditional inguinal 2-incision technique (group 3). We retrospectively reviewed operative time, success as defined by mid or lower scrotal position of the testis, and complications at 12 weeks and 1 year postoperatively. RESULTS A total of 286 orchiopexies were performed in 214 patients with palpable undescended testes. Group 1 included 81 patients with 125 undescended testes. Group 2 consisted of 44 patients with 60 undescended testes. Group 3 included 89 patients with 101 undescended testes. Postoperatively the testes were located in a good position within the scrotum in 99% of patients in group 1, 98% in group 2 and 100% in group 3. Mean±SD operative time for unilateral undescended testes was significantly shorter for low transscrotal compared to inguinal orchiopexy (28±10 vs 37±12 minutes, p<0.0001) but equivalent to a high scrotal incision (27±10 minutes, p=0.59). For all 160 children followed for 1 year no long-term atrophy or secondary reascent was observed. CONCLUSIONS Low transscrotal mid raphe orchiopexy appears to be an excellent alternative to high scrotal incision or standard inguinal orchiopexy for low palpable undescended testes, especially bilateral cases.

Dual Therapy for Refractory Overactive Bladder in Children: A Prospective Open-Label Study

Purpose: Mirabegron (&bgr;3 adrenoreceptor agonist) is a new molecule with a mechanism of action distinct from antimuscarinics. Combination therapy with solifenacin was recently studied in an adult population. We evaluated the efficacy and safety of mirabegron as add‐on therapy to treat urinary incontinence in children with idiopathic overactive bladder refractory/intolerant to antimuscarinics. Materials and Methods: A prospective off‐label study using add‐on regimens of mirabegron was conducted in pediatric patients presenting with no symptom improvement while undergoing intensive behavioral and medical therapies and/or significant side effects while undergoing antimuscarinic dose escalation. Our primary outcome was better reported efficacy than with the use of prior antimuscarinic monotherapy. Secondary end points were tolerability, safety and satisfaction. Efficacy and tolerability were assessed based on voiding diaries, post‐void residuals, urine cultures, electrocardiograms and vital signs. Families were questioned regarding continence, side effects and compliance. Wilcoxon signed‐rank test was used for statistical analysis. Results: A total of 35 patients were recruited at a median age of 10.3 years and were administered add‐on mirabegron for a median of 16.4 months. Median bladder capacity improved from 50% to 74% expected bladder capacity (p <0.001). Continence improved in all patients, with 12 being completely dry. Post‐void residual was increased in 2 patients and 1 urinary tract infection was reported. Seven patients reported mild or moderate side effects, with 2 withdrawals because of side effects (1 patient) and post‐void residual (1). Conclusions: Add‐on mirabegron appears to be a safe alternative for children with refractory overactive bladder. Dual therapy is well tolerated and adjusted dose regimen appears safe in this first pediatric study.

Treatment of vesicoureteral reflux in adults by endoscopic injection.

OBJECTIVES To prospectively evaluate the efficacy of endoscopic injection in the adult population with vesicoureteral reflux (VUR). The search for VUR is a part of the standard workup of children with febrile urinary tract infections. However, VUR can present later in life and should be investigated in the case of recurrent pyelonephritis. METHODS From 2005 to 2009, 27 postpubertal patients (3 males and 24 females) were treated endoscopically with injection of polydimethylsiloxane (Macroplastique) in 13 or dextranomer/hyaluronic acid copolymer (Deflux) in 14 patients; 41 renal units were injected. The median age was 23 years (range 12-65). The VUR was evaluated as grade I in 5 ureters, grade II in 28, grade III in 7, and grade IV in 1. The indications for surgery were recurrent pyelonephritis in all patients, except for 1. Of the 27 patients, 5 (12%) had undergone previous ureteral surgery. The patients were followed up with renal ultrasonography and voiding cystourethrography. RESULTS VUR was corrected in 38 (93%) of 41 ureteral units. Of the 3 failures, 1 patient had a large Hutch diverticulum and another had previously undergone ureterocele incision. All the patients with treatment failure had been injected with dextranomer/hyaluronic acid copolymer. Thus, the success rate was 100% with polydimethylsiloxane and 87% with dextranomer/hyaluronic acid copolymer. De novo hydronephrosis appeared in 1 renal unit. The obstruction was confirmed by a mercaptoacetyltriglycine-Lasix technetium-99m scan and treated with temporary diversion using a double-J stent. CONCLUSIONS Endoscopic injection is an effective treatment of VUR after puberty. In cases of recurrent pyelonephritis, imaging should be mandatory to detect scars and VUR because the endoscopic treatment is simple and noninvasive and has a good success rate, comparable to that reported for children.

Massive hemorrhage from spontaneous rupture of a retroperitoneal lymph node in patient with metastatic mixed germ cell tumor.

Spontaneous hemoperitoneum secondary to metastatic foci of testicular germ cell tumor is a rare finding and is usually precipitated by the beginning of chemotherapy treatments. This acute presentation is usually due to the rupture of hepatic or gastrointestinal metastasis. We present the case of a 16-year-old boy who was admitted to the emergency room with acute abdominal pain and unstable vital signs, 10 days after a left orchiectomy for a testicular mixed nonseminomatous tumor. An urgent laparotomy demonstrated a significant peritoneal effusion (3 L) secondary to a ruptured retroperitoneal lymph node. More than 90% of the mass was resected with 3 cm of adherent jejunum. Pathologic findings revealed the mass to be composed of more than 95% of choriocarcinoma. The patient recovered well from the surgery and received standard chemotherapy with good response and no residual disease. Two and a half years after diagnosis, the patient is still in remission.

Intrascrotal extratesticular schwannoma: A first pediatric case

Scrotal nerve sheath tumours unassociated with neurofibromatosis or schwannomatosis are extremely rare. Very few cases of benign intrascrotal and extratesticular schwannomas have been reported, but none of them occurred in childhood. This current report describes for the first time a case of benign intrascrotal extratesticular solitary schwannoma in a 16-year-old male.

Dimercaptosuccinic acid scintigraphy vs. ultrasound for renal parenchymal defects in children

INTRODUCTION Dimercaptosuccinic acid (DMSA) scintigraphy is the gold standard in the evaluation of renal parenchymal defects and is widely used in the pediatric population. As more recent ultrasound equipment was purchased at our tertiary pediatric centre, our objective was to evaluate if renal ultrasound (US) results are equivalent or sufficient when compared to DMSA scintigraphy in the assessment of renal anomalies. METHODS The charts of all 463 patients who underwent DMSA scintigraphy between January 2009 and May 2014 at our pediatric tertiary centre were reviewed. The objective was to look for correlation between US and DMSA scan results for renal scars/dysplasia. A hundred and sixty pediatric patients followed with US and DMSA scan for a total of 285 renal units remained for evaluation after exclusions. Timing of the exams, urinary tract infection (UTI), and indication for imaging were reviewed. Results with older (105 patients) and newer (55 patients) US equipment were compared. RESULTS Among the 285 renal units evaluated, 39 (14%) had renal parenchymal defects shown by US and 87 (31%) by DMSA scintigraphy (sensitivity 36%, specificity 96%). The DMSA scan was normal for eight abnormal kidneys (3%) on US. The results were not statistically significant when compared to exams performed with newer or older US machines. CONCLUSIONS At our institution, US data are not sensitive enough to give reliable information about renal parenchymal defects, even with newer equipment. DMSA scintigraphy still remains mandatory for the evaluation of renal anomalies, but could be optional if the US exam indicates parenchymal defects.

Efficacy of dextranomer hyaluronic acid and polyacrylamide hydrogel in endoscopic treatment of vesicoureteral reflux: A comparative study

INTRODUCTION Various bulking agents are available for vesicoureteral reflux (VUR) endoscopic treatment, but their inconsistent success rates and costs are concerns for urologists. Recently, polyacrylamide hydrogel (PAHG) has been shown to have a good overall success rate, which seems comparable to dextranomer hyaluronic acid (Dx/HA), currently the most popular bulking agent. Our objective was to compare the short-term success rate of PAHG and Dx/HA for VUR endoscopic treatment in children. METHODS We performed a prospective non-randomized study using PAHG and Dx/HA to treat VUR grades I to IV in pediatric patients. All patients underwent endoscopic sub-ureteric injection of PAHG or Dx/HA, using the double-HIT technique, followed by a 3-month postoperative renal ultrasound and voiding cystourethrogram. Treatment success was defined as the absence of de novo or worsening hydronephrosis and absence of VUR. RESULTS A total of 90 pediatric patients underwent an endoscopic injection: 45 patients (78 ureters) with PAHG and 45 patients (71 ureters) with Dx/HA. The mean injected volume of PAHG and Dx/HA was 1.1 mL and 1.0 mL, respectively. The overall success rate 3 months after a single treatment was 73.1% for PAHG and 77.5% for Dx/HA. Postoperatively, 1 patient in each group presented with acute pyelonephritis and 2 patients in the Dx/HA group developed symptomatic ureteral obstruction. CONCLUSION Success rates of PAGH and Dx/HA in endoscopic injections for VUR treatment were comparable. The rate of resolution obtained with Dx/HA was equivalent to those previously published. The lower cost of PAHG makes it an interesting option.