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EARLY PELVIC-FLOOR BIOFEEDBACK TRAINING PROMOTES LONG-TERM IMPROVEMENT OF URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY
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THE JOURNAL OF UROLOGY®
1882 EARLY PELVIC-FLOOR BIOFEEDBACK TRAINING PROMOTES LONG-TERM IMPROVEMENT OF URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY Lucia S Ribeiro, Cristina Prota, Cristiano M Gomes*, Milena P Boldarine, Elcio Nakano, Marcos Dall’Oglio, Homero Bruschini, Miguel Srougi, Sao Paulo, Brazil INTRODUCTION AND OBJECTIVES: Urinary incontinence is a common complication after radical prostatectomy (RP). Although recovery of continence is achieved by most patients, it can take up to one year. Pelvic floor biofeedback training (PFBT) may decrease the duration and severity of urinary incontinence in the short term following RP, but it is believed to have no impact in the long-term continence rates. METHODS: A total of 74 patients with a mean age of 66.3 ± 7.2 years (range 51 to 76) who elected RP for treatment of clinically localized prostate cancer and who could comply with the ambulatory treatment schedule were prospectively randomized for a treatment group (n=37) receiving PFBT once a week for 3 months and home exercises or a control group (n=37), in which patients received the usual instructions to contract the pelvic floor. Patients were evaluated before surgery and 1, 3, 6 and 12 months postoperatively. Incontinence severity was measured by the 24h pad test and the number of pads/day. Patients were considered continent when the weight gain of the pad was a 2g and/or when the use of pads was a 1/day. Incontinence symptoms were assessed with the incontinence questions of the International Continence Society male short form questionnaire. The Oxford score was used to assess the pelvic floor muscles (PFM) strength. RESULTS: A total of 11 (29.7%) patients in the treatment group and 9 (24.3%) in the control group were excluded due to failure to return for the evaluations (12 patients), development of urethral stenosis (4 pts) or need for adjuvant radiotherapy (4 pts). Preoperative assessment did not show differences in age, body mass index, voiding symptoms and PFM strength between the groups. Continence rates one month postoperatively were 54.2% and 32.1% in the treatment and control groups, respectively (p=0.109); 76.0% and 38.5% (p=0.007) at 3 months, 90.9% and 48.6% (p=0.001) at 6 months and 100% and 78.6% (p=0.031)at 12 months. Patients in the treatment group had significantly less incontinence symptoms after 1 month (p=0.011), 3 (p=0.002) and 12 months (p=0.040), and marginally after 6 months (p=0.063). Improvements in the PFM strength were superior for the treatment group after 1 month (p=0.004), 3 (p<0.001), 6 (p=0.021) and 12 months (p=0.035). CONCLUSIONS: Early pelvic-floor biofeedback training not only hasten the recovery of urinary continence after radical prostatectomy but allows for significant improvements in the continence rates, voiding symptoms and PFM strength 12 months postoperatively. Source of Funding: Grant FAPESP 2003/07656-7
1883 EARLY RECOVERY OF URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY USING EARLY PELVIC FLOOR ELECTRIC STIMULATION AND BIOFEEDBACK ASSOCIATED TREATMENT Alessandro Sciarra*, Stefano Salciccia, Alessandro Gentilucci, Andrea Alfarone, Giovanni Battista Di Pierro, Gianna Mariotti, Susanna Cattarino, Francesca Antonini, Franco Di Silverio, Vincenzo Gentile, Rome, Italy INTRODUCTION AND OBJECTIVES: To analyse the benefit of the early combined use of functional pelvic floor electrical stimulation (FES) and biofeedback (BF) as learning tools for pelvic floor muscle exercises (PME) , in terms of time to recovery and rate of continence after radical prostatectomy (RRP). METHODS: 60 consecutive patients submitted to RRP in our institution were included in the study and prospectively randomized to a treatment (Group A) versus a control (Group B) group. In group A a FES+BF program began 7 days after catheter removal ( twice a week for 6 weeks). The control group (Group B) received only usual verbal and written instruction to conduct PME. The evaluation of continence was performed at time 0 and at 2,4 weeks and 2,3,4,5,6 months during
Vol. 181, No. 4, Supplement, Wednesday, April 29, 2009
follow-up. Evaluations were performed using the 24-hours pad test and the incontinence section of the International Continence Society (ICS)questionnaire. Urinary continence was defined as no pads use from the patient. Moreover patients were asked to perform a voiding diary. Because urodynamic studies are invasive, they were avoided and used only in patients with UI after the 6 -month follow-up. RESULTS: No complication related to the treatment was found in all cases; no patient in Group A complained of discomfort or irritation and discontinued treatment. The mean leakage weight became significantly lower (p<0.05) in Group A than in Group B starting from 4 weeks till 6 months during follow-up. Mean time to regain continence was 8.0 ± 6.49 weeks (median 4 weeks;range 2 - 20 weeks) in Group A and 13.88.± 8.32weeks (median 16 weeks;range 2- 24 weeks) in Group B (p= 0.003).A significant difference (p<0.05) between Group A and Group B in terms of percentage of continent patients was achieved from 4 weeks (63.3 % Group A and 30.0 % Group B) till 6 months (96.7 % Group A and 66.7 % Group B). In both groups, patient age and nerve sparing procedure were the only two variables significantly ( p< 0.05) associated with rate and time of continence achievement. CONCLUSIONS: As shown by several studies urinary incontinence after RRP is mainly determined by a sphincteric deficiency. Therefore, we believe that the early non invasive physical treatment with BF and FES has a significant positive impact on the early recovery of urinary continence after RRP. It can represent a non invasive and non harmful treatment for all patients submitted to RRP, so to reduce the duration and the degree of PPI. Source of Funding: None
1884 RHO/ROCK SIGNAL REGULATES MYOGENIC DIFFERENTIATION VIA MRTF-A-DEPENDENT TRANSCRIPTION OF THE ID3 GENE. Kazuhiro Iwasaki*, Morioka, Japan; Ken’ichiro Hayashi, Osaka, Japan; Tomoaki Fujioka, Morioka, Japan; Kenji Sobue, Osaka, Japan INTRODUCTION AND OBJECTIVES: Myoblasts implantation has recently been tried for stress urinary incontinence. In order to operate safety and secure procedure, it is needed to elucidate a mechanism of myogenic differentiation. RhoA is one of the most important factors in myogenic differentiation, but whether its acts as a positive or negative regulator are controversial. To resolve this issue, we investigated the differentiation-stage-specific roles of RhoA and its effector, Rhoassociated kinase (ROCK). METHODS: C3 toxin and Y-27632, which are RhoA and ROCK specific inhibitor respectively, were added into C2C12 myoblasts, and we analyzed the influence of these reagents for myogenic differentiation via evaluating the expression of myogenic makers such as MyoD and myosin heavy chain (MHC). The gene expression was analyzed using polymerase chain reaction (PCR) and immunoblotting. The promoter function was evaluated by measurement of luciferase activity. RESULTS: Proliferating myoblasts show high levels of RhoA and SRF activities and strong expression of RhoA’s downstream target, myocardin-related transcription factor-A (MRTF-A or MAL); these activities and expression are markedly lower in differentiating myocytes. We further demonstrated that, in proliferating myoblasts, an increase in MRTF-A, which forms a complex with Smad 1/4, strikingly activates the expression level of the Id3 gene; the Id3 gene product is a potent inhibitor of myogenic differentiation. Finally, we found that during differentiation, one of the forkhead transcription factors (FKHR) translocates into the nucleus and suppresses Id3 expression by preventing the association of the MRTF-A/Smad complex with the Id3 promoter, which leads to the enhancement of myogenic differentiation. CONCLUSIONS: We conclude that RhoA/ROCK signaling plays positive and negative roles in myogenic differentiation, mediated by MRTF-A/Smad-dependent transcription of the Id3 gene in a differentiation-stage-specific manner. Source of Funding: Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (15GS0312 to K.S.)
THE JOURNAL OF UROLOGY®
1882 EARLY PELVIC-FLOOR BIOFEEDBACK TRAINING PROMOTES LONG-TERM IMPROVEMENT OF URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY Lucia S Ribeiro, Cristina Prota, Cristiano M Gomes*, Milena P Boldarine, Elcio Nakano, Marcos Dall’Oglio, Homero Bruschini, Miguel Srougi, Sao Paulo, Brazil INTRODUCTION AND OBJECTIVES: Urinary incontinence is a common complication after radical prostatectomy (RP). Although recovery of continence is achieved by most patients, it can take up to one year. Pelvic floor biofeedback training (PFBT) may decrease the duration and severity of urinary incontinence in the short term following RP, but it is believed to have no impact in the long-term continence rates. METHODS: A total of 74 patients with a mean age of 66.3 ± 7.2 years (range 51 to 76) who elected RP for treatment of clinically localized prostate cancer and who could comply with the ambulatory treatment schedule were prospectively randomized for a treatment group (n=37) receiving PFBT once a week for 3 months and home exercises or a control group (n=37), in which patients received the usual instructions to contract the pelvic floor. Patients were evaluated before surgery and 1, 3, 6 and 12 months postoperatively. Incontinence severity was measured by the 24h pad test and the number of pads/day. Patients were considered continent when the weight gain of the pad was a 2g and/or when the use of pads was a 1/day. Incontinence symptoms were assessed with the incontinence questions of the International Continence Society male short form questionnaire. The Oxford score was used to assess the pelvic floor muscles (PFM) strength. RESULTS: A total of 11 (29.7%) patients in the treatment group and 9 (24.3%) in the control group were excluded due to failure to return for the evaluations (12 patients), development of urethral stenosis (4 pts) or need for adjuvant radiotherapy (4 pts). Preoperative assessment did not show differences in age, body mass index, voiding symptoms and PFM strength between the groups. Continence rates one month postoperatively were 54.2% and 32.1% in the treatment and control groups, respectively (p=0.109); 76.0% and 38.5% (p=0.007) at 3 months, 90.9% and 48.6% (p=0.001) at 6 months and 100% and 78.6% (p=0.031)at 12 months. Patients in the treatment group had significantly less incontinence symptoms after 1 month (p=0.011), 3 (p=0.002) and 12 months (p=0.040), and marginally after 6 months (p=0.063). Improvements in the PFM strength were superior for the treatment group after 1 month (p=0.004), 3 (p<0.001), 6 (p=0.021) and 12 months (p=0.035). CONCLUSIONS: Early pelvic-floor biofeedback training not only hasten the recovery of urinary continence after radical prostatectomy but allows for significant improvements in the continence rates, voiding symptoms and PFM strength 12 months postoperatively. Source of Funding: Grant FAPESP 2003/07656-7
1883 EARLY RECOVERY OF URINARY CONTINENCE AFTER RADICAL PROSTATECTOMY USING EARLY PELVIC FLOOR ELECTRIC STIMULATION AND BIOFEEDBACK ASSOCIATED TREATMENT Alessandro Sciarra*, Stefano Salciccia, Alessandro Gentilucci, Andrea Alfarone, Giovanni Battista Di Pierro, Gianna Mariotti, Susanna Cattarino, Francesca Antonini, Franco Di Silverio, Vincenzo Gentile, Rome, Italy INTRODUCTION AND OBJECTIVES: To analyse the benefit of the early combined use of functional pelvic floor electrical stimulation (FES) and biofeedback (BF) as learning tools for pelvic floor muscle exercises (PME) , in terms of time to recovery and rate of continence after radical prostatectomy (RRP). METHODS: 60 consecutive patients submitted to RRP in our institution were included in the study and prospectively randomized to a treatment (Group A) versus a control (Group B) group. In group A a FES+BF program began 7 days after catheter removal ( twice a week for 6 weeks). The control group (Group B) received only usual verbal and written instruction to conduct PME. The evaluation of continence was performed at time 0 and at 2,4 weeks and 2,3,4,5,6 months during
Vol. 181, No. 4, Supplement, Wednesday, April 29, 2009
follow-up. Evaluations were performed using the 24-hours pad test and the incontinence section of the International Continence Society (ICS)questionnaire. Urinary continence was defined as no pads use from the patient. Moreover patients were asked to perform a voiding diary. Because urodynamic studies are invasive, they were avoided and used only in patients with UI after the 6 -month follow-up. RESULTS: No complication related to the treatment was found in all cases; no patient in Group A complained of discomfort or irritation and discontinued treatment. The mean leakage weight became significantly lower (p<0.05) in Group A than in Group B starting from 4 weeks till 6 months during follow-up. Mean time to regain continence was 8.0 ± 6.49 weeks (median 4 weeks;range 2 - 20 weeks) in Group A and 13.88.± 8.32weeks (median 16 weeks;range 2- 24 weeks) in Group B (p= 0.003).A significant difference (p<0.05) between Group A and Group B in terms of percentage of continent patients was achieved from 4 weeks (63.3 % Group A and 30.0 % Group B) till 6 months (96.7 % Group A and 66.7 % Group B). In both groups, patient age and nerve sparing procedure were the only two variables significantly ( p< 0.05) associated with rate and time of continence achievement. CONCLUSIONS: As shown by several studies urinary incontinence after RRP is mainly determined by a sphincteric deficiency. Therefore, we believe that the early non invasive physical treatment with BF and FES has a significant positive impact on the early recovery of urinary continence after RRP. It can represent a non invasive and non harmful treatment for all patients submitted to RRP, so to reduce the duration and the degree of PPI. Source of Funding: None
1884 RHO/ROCK SIGNAL REGULATES MYOGENIC DIFFERENTIATION VIA MRTF-A-DEPENDENT TRANSCRIPTION OF THE ID3 GENE. Kazuhiro Iwasaki*, Morioka, Japan; Ken’ichiro Hayashi, Osaka, Japan; Tomoaki Fujioka, Morioka, Japan; Kenji Sobue, Osaka, Japan INTRODUCTION AND OBJECTIVES: Myoblasts implantation has recently been tried for stress urinary incontinence. In order to operate safety and secure procedure, it is needed to elucidate a mechanism of myogenic differentiation. RhoA is one of the most important factors in myogenic differentiation, but whether its acts as a positive or negative regulator are controversial. To resolve this issue, we investigated the differentiation-stage-specific roles of RhoA and its effector, Rhoassociated kinase (ROCK). METHODS: C3 toxin and Y-27632, which are RhoA and ROCK specific inhibitor respectively, were added into C2C12 myoblasts, and we analyzed the influence of these reagents for myogenic differentiation via evaluating the expression of myogenic makers such as MyoD and myosin heavy chain (MHC). The gene expression was analyzed using polymerase chain reaction (PCR) and immunoblotting. The promoter function was evaluated by measurement of luciferase activity. RESULTS: Proliferating myoblasts show high levels of RhoA and SRF activities and strong expression of RhoA’s downstream target, myocardin-related transcription factor-A (MRTF-A or MAL); these activities and expression are markedly lower in differentiating myocytes. We further demonstrated that, in proliferating myoblasts, an increase in MRTF-A, which forms a complex with Smad 1/4, strikingly activates the expression level of the Id3 gene; the Id3 gene product is a potent inhibitor of myogenic differentiation. Finally, we found that during differentiation, one of the forkhead transcription factors (FKHR) translocates into the nucleus and suppresses Id3 expression by preventing the association of the MRTF-A/Smad complex with the Id3 promoter, which leads to the enhancement of myogenic differentiation. CONCLUSIONS: We conclude that RhoA/ROCK signaling plays positive and negative roles in myogenic differentiation, mediated by MRTF-A/Smad-dependent transcription of the Id3 gene in a differentiation-stage-specific manner. Source of Funding: Grants-in-Aid for Scientific Research from the Ministry of Education, Science, Sports, and Culture of Japan (15GS0312 to K.S.)