Is long-term bladder deterioration inevitable following successful isolated bladder outlet procedures in children with neuropathic bladder dysfunction?

PURPOSE: Bladder decompensation is well described following artificial urinary sphincter implantation in neurogenic bladders. We evaluated the long-term results of various bladder outlet procedures in a subset of patients with neurogenic bladder and isolated outlet deficiency. MATERIALS AND METHODS: We retrospectively reviewed the charts of 15 consecutive patients who underwent bladder outlet procedures during a 10-year period for urinary incontinence associated with neuropathic bladder dysfunction. Postoperative success was defined as a dry interval of at least 4 hours. RESULTS: Preoperative evaluation showed a smooth bladder in 11 patients with vesicoureteral reflux and hydronephrosis in 2. Using the minimal acceptable capacity for age, mean percent expected bladder capacity for age was 89% +/- 25%, capacity below 20 cm H(2)O was 81% and capacity below 30 cm H(2)O was 89%. Mean preoperative expected capacity for age was 60% +/- 18%. Mean postoperative followup was 11.2 years. Postoperatively, 11 patients achieved initial dryness but 9 subsequently presented with recurrent incontinence and 2 presented with upper tract deterioration. Four cases failed the initial bladder outlet procedure. Salvage procedures included augmentation cystoplasty in all 15 patients, combined with repeat bladder outlet procedure in 4 and bladder neck closure in 2. Mean time to augmentation cystoplasty was 39.6 +/- 28 months. CONCLUSIONS: Isolated bladder outlet procedures for neurogenic incontinence portend a poor long-term outcome, requiring augmentation cystoplasty despite the use of anticholinergic medications and strict followup. Preoperative urodynamic evaluation does not predict the need or timing from the initial bladder outlet procedure for future augmentation cystoplasty.

Severe bladder trabeculation obviates the need for bladder outlet procedures during augmentation cystoplasty in incontinent patients with neurogenic bladder.

OBJECTIVE: To evaluate whether the degree of preoperative bladder trabeculation in neurogenic bladder (NB) patients is a marker of significant outlet resistance. If so, severe trabeculation may obviate the need for concomitant bladder outlet procedure (BOP) during augmentation cystoplasty (AC). PATIENTS AND METHODS: We retrospectively reviewed 48 incontinent patients with NB who had surgery. The patients were divided into two groups: group 1 (23 patients) had AC alone; group 2 (10) had AC with BOP. Children who had a BOP alone (15) were excluded from the study. Success was defined as a dry period of > or = 4 h. Preoperative bladder trabeculation was classified as mild or severe. Data collected included continence status, imaging and urodynamic findings. RESULTS: In group 1 patients before surgery, there was severe bladder trabeculation in 14 (61%), hydronephrosis in 13 (57%) and associated vesico-ureteric reflux (VUR) in 16 (70%). The mean detrusor leak-point pressure (DLPP) was 49.7 cmH2O and the bladder neck was open in nine (39%). Dryness with AC alone was achieved in 91% of group 1 patients. In group 2 patients (10 patients), there was severe bladder trabeculation in five, hydronephrosis in three, and VUR in two. The mean DLPP was 42.8 cmH2O and the bladder neck was open in eight. After surgery, eight of 10 patients achieved a dry period of 4 h. There was no significant difference between group 1 and 2 patients for age at surgery, gender, ambulatory status, hydronephrosis, degree of trabeculation, detrusor overactivity, DLPP and eventual outcome. The incidence of VUR was higher in group 1 patients (P = 0.009) and more patients in group 2 had an open bladder neck (P = 0.031). CONCLUSION: Severe bladder trabeculation in incontinent patients with NB might predict an element of intrinsic outlet resistance. In this subset of patients, dryness was achieved by AC alone without further BOP. The degree of bladder trabeculation should be considered in the surgical decision-making process for incontinent children with NB.

Regulation of insulin-like growth factor-mammalian target of rapamycin signaling by microRNA in childhood adrenocortical tumors.

MicroRNAs (miRNAs) act at the posttranscriptional level to control gene expression in virtually every biological process, including oncogenesis. Here, we report the identification of a set of miRNAs that are differentially regulated in childhood adrenocortical tumors (ACT), including miR-99a and miR-100. Functional analysis of these miRNAs in ACT cell lines showed that they coordinately regulate expression of the insulin-like growth factor-mammalian target of rapamycin (mTOR)-raptor signaling pathway through binding sites in their 3'-untranslated regions. In these cells, the active Ser(2448)-phosphorylated form of mTOR is present only in mitotic cells in association with the mitotic spindle and midbody in the G(2)-M phases of the cell cycle. Pharmacologic inhibition of mTOR signaling by everolimus greatly reduces tumor cell growth in vitro and in vivo. Our results reveal a novel mechanism of regulation of mTOR signaling by miRNAs, and they lay the groundwork for clinical evaluation of drugs inhibiting the mTOR pathway for treatment of adrenocortical cancer.