Sacral neuromodulation for neurogenic non-obstructive urinary retention in incomplete spinal cord patients: a ten-year follow-up single-centre experience.

OBJECTIVE: To determine the success rate of percutaneous first stage of sacral neuromodulation (SNM) and the efficacy and safety of permanent SNM for incomplete spinal cord lesion (SCL) patients suffering from chronic neurogenic non-obstructive urinary retention (N-NOR). METHOD: From January 2003 to December 2012, 85 individuals underwent the percutaneous first stage of SNM. Subsequently, only responders who reached a concomitant reduction by at least 50% of volume per catheterization and in the number of catheterizations per day comparing their 7-day voiding diaries at baseline underwent permanent SNM. Final follow-up was conducted by April 2013. RESULTS: Thirty-six individuals responded to percutaneous first stage of SNM. Post-surgery urodynamics documented all patients experiencing first sensation of bladder filling. A statistically significant increase in Qmax ml per sec and decrease in post-voiding residual urine per ml were documented. (P<0.01). First sensation of bladder filling at baseline represented a statistically significant parameter for the success of the first stage SNM (P<0.05). Eleven out of 34 patients at follow-ups were 'inconstant responders' because they returned to similar baseline voiding symptoms, but responded again with an implant on the controlateral S3 sacral root. Two failed twice and responded once again after an S4 sacral root implant. All but one failure occurred more than 3 years after the previous implant. Other drawbacks were resolved telemetrically. CONCLUSIONS: Research is needed to increase the success rate of the first stage SNM on incomplete SCL patients with N-NOR. Permanent SNM is highly efficacious in the medium follow-up.

Intravesical electrostimulation versus sacral neuromodulation for incomplete spinal cord patients suffering from neurogenic non-obstructive urinary retention.

OBJECTIVES: To compare the efficacy of intravesical electrostimulation (IVES) versus sacral neuromodulation (SNM) in patients with incomplete spinal cord lesions (SCL) and neurogenic non-obstructive urinary retention (N-NOR). METHODS: In this retrospective study, 77 N-NOR patients underwent IVES (minimum 28 sessions), then after returning to voiding baseline symptoms, percutaneous first stage of SNM (lasting for minimum 4 weeks). After the two neuromodulation treatments, responders were categorized as patients experiencing both a 50% reduction of volume per catheterization per ml and a 50% reduction in number of catheterizations per day when comparing the 7-day voiding diaries at the end of both procedures to baselines. New urodynamics were performed subsequently. Responders to first stage of SNM underwent permanent SNM. RESULTS: Forty-eight patients responded to neither of the treatments, whereas 29 responded to both IVES and first-stage SNM. No significant statistical differences (P>0.05) were detected in the voiding diaries. Following the two procedures, the first sensation of bladder filling was either maintained or recovered by all responders, whereas the same 11 patients reached a bladder contractility index of >100. The 29 IVES responders lost their clinical benefits in a mean follow-up of 9.6 months. Only 10 out of the 29 patients became nonresponsive to permanent SNM, in a mean follow-up of 54 months. CONCLUSION: A strict correlation in terms of clinical and urodynamic patterns was demonstrated in patients with incomplete SCL and N-NOR, following IVES and first stage of SNM. However, voiding improvement through IVES was short-term when compared with the effects of permanent SNM.

The gene encoding the mitogen-responsive phosphoprotein Dab2 is differentially regulated by GATA-6 and GATA-4 in the visceral endoderm.

Gene targeting studies have demonstrated that the zinc finger transcription factor GATA-6 lies upstream in a transcriptional cascade that controls differentiation of the visceral endoderm. To understand the function of GATA-6 in the visceral endoderm and to identify genes regulated by GATA-6 in this tissue, subtractive hybridization was performed using template cDNAs derived from differentiated wild-type embryonic stem (ES) cells and GATA-6(-/-) ES cells, respectively. These analyses revealed that the gene encoding Dab2, a mitogen-responsive phosphoprotein, is differentially expressed in wild-type and GATA-6-deficient ES cells. Consistent with these findings, Dab2 is expressed in the visceral endoderm of wild-type embryos but not in the visceral endoderm of GATA-6-deficient embryos. Cotransfection experiments demonstrate that the human Dab2 promoter can be transactivated by forced expression of GATA-6 in NIH-3T3 cells. In contrast, forced expression of GATA-4 does not transactivate the human Dab2 promoter and Dab2 is expressed in the visceral endoderm of GATA-4 null embryos. Surprisingly, the specificity of GATA-6-induced transactivation of the Dab2 promoter is not mediated through its zinc finger DNA-binding domain. Taken together, these data demonstrate that the mitogen-responsive phosphoprotein Dab2 is a downstream target of GATA-6 in the visceral endoderm. Moreover, these data demonstrate that molecular mechanisms have evolved that direct, and distinguish, the functional specificity of GATA family members when they are developmentally coexpressed.