Vesicoureteral reflux (VUR) is common to observe in children with Neurogenic bladder (NB). While the treatment of VUR is well established, VUR management in NB is still unclear and challenging to treat. Different  options have been suggested: treatment of neurogenic bladder dysfunction only, VUR endoscopic mini-invasive treatment with subureteric injections of bulking agent, intravesical or extravesical reimplantation, augmentation. Aim of this study is to evaluate evaluate  the long-term results of a combined/total endoscopic management (TEM) with simultaneous injections of onabotulinum toxin A (BTX-A) and subureteric dextranomer/hyaluronic acid (Deflux) in order to better define its safety and efficacy.

A retrospective analysis was conducted in all patients who underwent TEM for VUR in NB in our center. Minimum follow-up of 18 months. Age 3-18 years. All patients underwent ultrasound, cystography and urodynamic exam before TEM and at follow-up. In all patients a cold cup endoscopy detrusor biopsy has been performed to evaluate bladder wall inflammation and fibrosis. All patients repeated BTX-A injections every 12 months. Operative time, hospital stay length, intra e post post operative complications have been recorded. Outcomes assessed: urinary tract infections (UTIs), resolution of VUR, need for surgery and incidence of iatrogenic ureteral obstruction.

23 patients, 12 female and 11 males. The median age at surgery was 6,9 years median follow-up 45 months . 7 patients had bilateral reflux, for a total of 30 ureters. VUR was Grade I-II in 2  ureters (all associated to severe controlateral reflux), Grade III in 9, Grade IV in 16 and Grade V in 3 . The median operative time has been 9 minutes. The median length of hospital stay was 1 day. No procedure related complications have been observed in short and long-term follow-up.  TEM was effective resolving VUR in 22 ureters (73%). In 8 ureters (27%) VUR persisted including  4 ureters downgraded, as confirmed by severe UTI occurrence. On the long-term only 4 (17,3%) patients (two of them with bilateral VUR) were operated: 3 augmentation (2 with bilateral reimplantation), 1 reimplantation. Higher failure rate has been observed in severely dilatated ureter (Grade IV-V) or when BTX-A injections showed less effectiveness for increasing bladder capacity and compliance. All no responders have been recorded in patients with severe fibrosis.

Our experience shows that TEM is a safe and effective procedure for the treatment of VUR in patients with NB. In particular, this treatment is more effective in patients with mild VUR (grade-II-III) and in those with urodynamic evidence of preserved bladder compliance. This may be explained by the better effect of botulinum toxin in reducing end filling pressure  and overactivity, where the  beneficial BTX-A effect is related  to the severity of pre-existing anatomical damage, fibrosis, as confirmed by our histological studies. Furthermore the subureteric Deflux injection could be less effective in hard fibrotic bladder wall. Comparing TEM to BTX-A alone, advantage of TEM could be to reduce the number of BTX-A injections required during time, that in pediatrics population is resulting in a reduced general anaesthesia procedures.

TEM is safe and effective in VUR management in children with NB without severe fibrosis and without severe ureteric dilation (grade V). Effectiveness seems higher respect to subureteric Deflux injections alone,  avoiding the risk of complications, as ureteric obstruction, that is the risk of this procedure. An early treatment could be useful in order to increase TEM success, for this reason we suggest to perform TEM in all patients with NB and VUR from the diagnosis, instead of BTX-A  alone. Multicentric studies could be useful  to confirm our results as well as a double blind study comparing effectiveness of TEM versus BTX- A alone.