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99 A COMPARISON OF URETHRAL STRICTURE FORMATION IN A PORCINE LARGE ANIMAL MODEL WITH HUMAN STRICTURE DEVELOPMENT
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THE JOURNAL OF UROLOGY姞
Vol. 185, No. 4, Supplement, Saturday, May 14, 2011
98 EXTENDED LONG-TERM RESULTS OF SURGERY FOR URETHRAL STRICTURES Sascha Ahyai*, Felix Chun, Oliver Engel, Luis Kluth, Angelika Jessel, Hendrik Isbarn, Hamburg, Germany; Thomas Kessler, Zu¨rich, Switzerland; Roland Dahlem, Friedhelm Schreiter, Margit Fisch, Hamburg, Germany INTRODUCTION AND OBJECTIVES: Our study group previously reported the long term results of 238 patients who underwent urethroplasty between 1993–2000. The cut-off date for the analysis was Nov. 2000 and the published overall success rate was 82% at 7.5 years (Kessler et al, J Urol 2003). To investigate extended long-term results of urethroplasty, we now reassessed 10 years later the overall success rate and specific success rates achieved by excision and primary reanastomosis (EPA), graft (buccal mucosa or prepuce), flap (penil or scrotal), and mesh graft urethroplasties of the same study cohort. METHODS: Patients were re-contacted and asked to fill out the previously used and self administered standardized non-validated questionnaire. Primary end point of this retrospective analysis was the stricture free survival rate. Secondly, a risk factor analysis for treatment failure was performed. For statistical calculation Kaplan-Meier (Log rank test) and Cox regression analyses were applied. RESULTS: Mean survival time of the study cohort was 14.3 years (limited to 17.8). At 14 years the overall success rate of all urethroplasties was 71.1% (Fig. 1) and 68.2%, 72.4%, 71.7%, 73.9% (Fig. 2) for EPA, graft, flap and mesh graft urethroplasties respectively. There was no statistically significant difference between these specific success rates (Log rankⱖ0.3). No risk factor for stricture recurrence such as aetiology, localisation, and length of stricture, surgical procedure or tissue used was identified. CONCLUSIONS: According to our data, despite different indications, the success rate of EPA, graft, flap, or mesh graft urethroplasties seems comparable. All types of urethroplasties tend to show some deterioration with time probably related with the nature of the disease process.
Source of Funding: none
99 A COMPARISON OF URETHRAL STRICTURE FORMATION IN A PORCINE LARGE ANIMAL MODEL WITH HUMAN STRICTURE DEVELOPMENT Jo¨rg Seibold*, Christin Selent-Stier, Julia Wiedemann, Tim-Oliver Greiner, Elisabeth Gustafsson, Brigitte Schuhmacher, Gerhard Feil, Arnulf Stenzl, Karl-Dietrich Sievert, Tu¨bingen, Germany INTRODUCTION AND OBJECTIVES: Urethral stricture has been described as a fibrotic process in scarred tissue that reduces the urethral lumen caliber. Urethral stricture development can be caused by indirect and direct trauma-like side effects of urethral slings for the urinary incontinence treatment and post transurethral prostate resection. The aim of the study was to establish a large animal model for the investigation of urethral stricture formation comparable to human stricture development. METHODS: In 12 male Go¨ttingen minipigs (mean body weight 20 kg) the stricture formation was evaluated with urethrography at 1, 8 and 12 weeks after stricture induction by ligation (L), urethrotomy (U), or thermocoagulation (T). The effect of urethral damage was investigated for the microvessel density (anti-von Willebrand factor antibody) and calculation of the collagen I/III ratio after western blot analysis. Normal human urethral tissue of 3 patients and stricture tissue of another 3 patients were compared to those of animal specimens. RESULTS: Postoperatively all 12 animals developed a stricture in the injured area. The animal urethral stricture formation was characterized by the loss of tissue integrity in early phases of stricture development compared to normal tissue. However, over time an increase of connective tissue, a narrowing of urethral lumen, a significant decrease of microvessel density (p⬍0.001), and a significantly increased collagen I/III ratio (p⬍0.001) was noted. The three methods for stricture induction resulted in different severities of stricture formation in the animal model (T⬎L⬎U). In normal human urethral tissue a 1.9 fold higher expression of collagen type I compared to collagen type III was observed. In human stricture tissue samples the collagen type I/III ratio showed a mean ratio of 4.8:1. Microvessel density was significantly reduced in human urethral stricture tissue compared to normal human urethral tissue (p⬍0.001). CONCLUSIONS: A large animal model to study urethral stricture formation after iatrogenic surgical interventions was successfully developed. The findings demonstrated a direct clinical context to human urethral strictures. The animal model enables investigations on new therapeutic approaches for urethral stricture therapy, e. g. based on tissue engineering. Source of Funding: none
THE JOURNAL OF UROLOGY姞
Vol. 185, No. 4, Supplement, Saturday, May 14, 2011
98 EXTENDED LONG-TERM RESULTS OF SURGERY FOR URETHRAL STRICTURES Sascha Ahyai*, Felix Chun, Oliver Engel, Luis Kluth, Angelika Jessel, Hendrik Isbarn, Hamburg, Germany; Thomas Kessler, Zu¨rich, Switzerland; Roland Dahlem, Friedhelm Schreiter, Margit Fisch, Hamburg, Germany INTRODUCTION AND OBJECTIVES: Our study group previously reported the long term results of 238 patients who underwent urethroplasty between 1993–2000. The cut-off date for the analysis was Nov. 2000 and the published overall success rate was 82% at 7.5 years (Kessler et al, J Urol 2003). To investigate extended long-term results of urethroplasty, we now reassessed 10 years later the overall success rate and specific success rates achieved by excision and primary reanastomosis (EPA), graft (buccal mucosa or prepuce), flap (penil or scrotal), and mesh graft urethroplasties of the same study cohort. METHODS: Patients were re-contacted and asked to fill out the previously used and self administered standardized non-validated questionnaire. Primary end point of this retrospective analysis was the stricture free survival rate. Secondly, a risk factor analysis for treatment failure was performed. For statistical calculation Kaplan-Meier (Log rank test) and Cox regression analyses were applied. RESULTS: Mean survival time of the study cohort was 14.3 years (limited to 17.8). At 14 years the overall success rate of all urethroplasties was 71.1% (Fig. 1) and 68.2%, 72.4%, 71.7%, 73.9% (Fig. 2) for EPA, graft, flap and mesh graft urethroplasties respectively. There was no statistically significant difference between these specific success rates (Log rankⱖ0.3). No risk factor for stricture recurrence such as aetiology, localisation, and length of stricture, surgical procedure or tissue used was identified. CONCLUSIONS: According to our data, despite different indications, the success rate of EPA, graft, flap, or mesh graft urethroplasties seems comparable. All types of urethroplasties tend to show some deterioration with time probably related with the nature of the disease process.
Source of Funding: none
99 A COMPARISON OF URETHRAL STRICTURE FORMATION IN A PORCINE LARGE ANIMAL MODEL WITH HUMAN STRICTURE DEVELOPMENT Jo¨rg Seibold*, Christin Selent-Stier, Julia Wiedemann, Tim-Oliver Greiner, Elisabeth Gustafsson, Brigitte Schuhmacher, Gerhard Feil, Arnulf Stenzl, Karl-Dietrich Sievert, Tu¨bingen, Germany INTRODUCTION AND OBJECTIVES: Urethral stricture has been described as a fibrotic process in scarred tissue that reduces the urethral lumen caliber. Urethral stricture development can be caused by indirect and direct trauma-like side effects of urethral slings for the urinary incontinence treatment and post transurethral prostate resection. The aim of the study was to establish a large animal model for the investigation of urethral stricture formation comparable to human stricture development. METHODS: In 12 male Go¨ttingen minipigs (mean body weight 20 kg) the stricture formation was evaluated with urethrography at 1, 8 and 12 weeks after stricture induction by ligation (L), urethrotomy (U), or thermocoagulation (T). The effect of urethral damage was investigated for the microvessel density (anti-von Willebrand factor antibody) and calculation of the collagen I/III ratio after western blot analysis. Normal human urethral tissue of 3 patients and stricture tissue of another 3 patients were compared to those of animal specimens. RESULTS: Postoperatively all 12 animals developed a stricture in the injured area. The animal urethral stricture formation was characterized by the loss of tissue integrity in early phases of stricture development compared to normal tissue. However, over time an increase of connective tissue, a narrowing of urethral lumen, a significant decrease of microvessel density (p⬍0.001), and a significantly increased collagen I/III ratio (p⬍0.001) was noted. The three methods for stricture induction resulted in different severities of stricture formation in the animal model (T⬎L⬎U). In normal human urethral tissue a 1.9 fold higher expression of collagen type I compared to collagen type III was observed. In human stricture tissue samples the collagen type I/III ratio showed a mean ratio of 4.8:1. Microvessel density was significantly reduced in human urethral stricture tissue compared to normal human urethral tissue (p⬍0.001). CONCLUSIONS: A large animal model to study urethral stricture formation after iatrogenic surgical interventions was successfully developed. The findings demonstrated a direct clinical context to human urethral strictures. The animal model enables investigations on new therapeutic approaches for urethral stricture therapy, e. g. based on tissue engineering. Source of Funding: none