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A FOLLOWUP ON TRANSURETHRAL COLLAGEN INJECTION THERAPY FOR URINARY INCONTINENCE
oM2-5347/9&r1591-010.~
Vol. 159,106-108,January 1998 Printed in U.SA.
"HE JOURNAL OF UROLOCY copyright 8 1998 by ANEUICAN UROII)OICAL Assocuno~,INC.
A FOLLOWUP ON TRANSURETHRAL COLLAGEN INJECTION THERAPY FOR URINARY INCONTINENCE CINDY A. CROSS, SHARON F. ENGLISH, R. DUANE CESPEDES
AND
EDWARD J. McGUIRE
From the Department of Obstetrics, Gynecobgy and Reproductive Medicine and the Division of Urology,University of Texas Medical School at Houston, Houston, and the apartment of UmlogylPSSU, Wilford Hall Medical Center, Lackland Air Force Base, Texas
ABSTRACT
Purpose: Transurethral collagen injection therapy has been used successfully in treating stress urinary incontinence due to intrinsic sphincter deficiency since United States Food and Dmg Administration approval in October 1993. Materials and Methods: Telephone interview and chart review were performed on 139 women with intrinsic sphincter deficiency documented using video urodynamics, of whom 73% had grade 3 incontinence (leakage without effort). Median followup was 18 months (range 6 to 36).Median patient age was 72 years. Results: A total of 103 patients (74%) was substantially improved after collagen therapy, 29 (20%) were improved and 7 had no improvement. Of the substantially improved group 72% obtained continence after 2 or fewer injections. Of the patients 11% required a "booster" injection more than 6 months after initial treatment. Complications, such as hematuria, urinary tract infections or transient urinary retention, were rare. Conclusions: Our results confirm the safety and efficacy of transurethral collagen. Once continence is achieved further collagen therapy is rarely necessary. KEY WORDS: urinary incontinence, stress;collagen; urinary tract; urination disorders METHODS Intrinsic sphincter deficiency is characterized by a poorly functioning proximal urethra that leaks urine at relatively Patients with urinary incontinence complaints were aslow intra-abdominal pressures. In women this condition is signed grades according to the Stamey scoring system for known as type I11 stress urinary incontinence and it can be incontinence,6 and a pelvic examination was performed and identified by measuring abdominal pressure required to graded according to the Baden and Walker Halfway system.7 cause leakage. If leakage is produced at abdominal pressures Abdominal leak point pressure of less than 60 cm. water below 60 cm. water, proximal urethral sphincter function is verified intrinsic sphincter deficiency. Abdominal leak point poor or absent. The most common treatments used today are pressure was determined during video urodynamics and by a sling procedures, artificial sphincters and injectable agents. technique described by McGuire et al.* With the patient erect These treatments compress or narrow the urethral lumen and in the oblique position neglible urethral hypermobility and increase the efficiency with which the urethra opposes was documented if the urethral radiopaque marker rotated less than 30 degrees during a Valsalva maneuver. Patients changes in intra-abdominal pressure. Injectable agenta provide an attractive nonsurgical option underwent collagen skin testing 1 month before the procefor the treatment of intrinsic sphincter deficiency. Initially dure. Exclusion criteria included grade I11 to IV prolapse at polybtrafluoroethylene (Teflon), autologous fat and silicone any vaginal site, abdominal leak point pressure greater than were used. Problems with polytetrafluoroethylene and sili- 60 cm. water, urethral hypermobility on video urodynamics cone included particle migration and granuloma forma- or allergic reaction to the collagen skin test. A total of 139 tion.1-2 and autologous fat often resulted in poor graft sur- patients qualified for transurethral collagen injections. Collagen iqjections were performed with local anesthesia vival.3 More promising as an injectable agent was glutaraldehyde cross-linked bovine collagen, which does not by a single surgeon at an outpatient clinic. The patient was cause granuloma formation, and encourages fibroblast a-given an oral preoperative antibiotic, the perineum and vatration and neovascularization while being minimally an- gina were prepared with antiseptic, and 2% lidocaine jelly tigenic and nonmigratory.4.6 Since its approval in October was placed intraurethrally. A 21F aspiratiodinjection rigid 1993, glutaraldehyde cross-linked bovine collagen has panendoscope was inserted and the bladder was emptied. Collagen was injected at the 4 and 8 o'clock positions in an been used at our institution for treating intrinsic sphincter area 1 to 1.5 cm. distal to the bladder neck. Initially 1% deficiency in women. We report our results with transure- lidocaine was injected in the submucosal plane, which anesthral collagen therapy from February 1994 to February thetized the urethra and dissected the appropriate plane. 1997. After discomfort from the lidocaine subsided approximately 2.5 cc collagen, or 1syringe, were injected into the submucosa Accepted for publication July 18, 1997. on either side. Average injection time was 5 minutes. PaThe opiniom contained herem are those of the authora and are not tients voided before leaving the clinic and if there was any to be c0nst"Bd aa reflecting the views of the Air Force or the difficulty with voiding, the patient was taught to perform Department of Defense. intermittent catheterization. The interval between injections &dilor~ Note: Thir article b the fourth ofI published in thie h e for which ca ry 1 CME eredib can be earned. In- was 4 to 8 weeks. Post-procedural evaluation of all patients included medical .trpctionr ibr credits are given with the questions Om pages 886 and 837. chart review and telephone urinary symptom questionnaire
*&
106
COLLAGEN TREATMENT FOR INTRINSIC SPHINCTER DEFICIENCY IN WOMEN
conducted by a third party physician. Patients were substantially improved if they had a 70% or greater reduction in daily pad usage compared to pre-collagen pad usage documented on the chart or grade 0 incontinence. Cases were classified as improved if they had 50 to 70% reduction in daily pad usage or at least 1grade improvement in incontinence, and failed if pad usage was reduced by less than 50% or the incontinence was grade 3. All patients whose urinary incontinence was not improved after the third collagen injection underwent video urodynamic evaluation with abdominal leak point pressure measurement. If stress incontinence was confirmed the patient was offered a rectus fascia pubovaginal sling. Patients who were initially substantially improved or improved and then had an increase in pad usage required video urodynamic confirmation of stress incontinence before receiving a booster collagen injection. All data were compared using paired t tests and p <0.05 was considered significant. RESULTS
Median patient age was 72 years and median pretreatment abdominal leak point pressure was 54 cm. water (range 18 to 60). Quantitatively, 93% used 4 pads or more a day with an average of 4.6 pads a day. Of the patients 73% had grade 3 incontinence, and 55 patients (40%) complained of urge and stress incontinence. Average duration of incontinence was 3.5 years. A total of 88 patients (63%) had undergone a previous incontinence procedure, such as bladder neck suspension, retropubic urethropexy or vaginal walllpubovaginal fascia1 sling, and 28 patients (20%) had undergone pelvic surgery that did not include a urethral procedure. Four patients had received radiotherapy for cervical carcinoma and 19 (14%)had had no previous pelvic surgery or trauma. The average duration since last collagen was 18 months (range 6 to 36). Of the 139 patients 103 (74%)were substantially improved after collagen therapy, 100 (72%) were substantially improved after 2 or fewer sessions and 29 (20%)were improved. In 7 patients treatment failed, of whom 4 underwent successful pubovaginal sling, and 3 previously had radiotherapy for cervical cancer. The 3 patients had improvement in stres! incontinence but poor bladder compliance and required detrusor myedomies. When comparing patients grouped as substantially improved, improved or failed, there was no statistical difference with respect to prior incontinence procedure, duration of incontinence and average number of pads before surgery (table 1).However, there was a correlation between complaints of urge incontinence and patient perception of success. Of patients with pre-procedural urge incontinence 53% continued to complain of the symptoms after the collagen injections, and 39 (28%) complained of de novo urge incontinence without intrinsic sphincter deficiency documented by video urodynamics. With respect to collagen durability and improvement in stress incontinence, 11.6% of the substantially improved or improved patients required an additional injection 6 months after the last injection of the initial treatment because of slightly decreased efficacy (table 2). A fourth of the patients reported a physical activity increase that they attributed to incontinence improvement. As an office procedure collagen therapy was well tolerated by the majority of patients. Three patients (2.0%) experienced ery-
TABLE1. Preoperative evduatwn NO.pts.
NO. previous Incontinence pmeedUres(96)
Substantiallyimproved Improved Failed
103 29
I
72 (70) 12 (41) 4 (57)
Duration Incontinence No. Pads (p.) 4.5 5
6 6
I
8
107
TABLE2. Post-procedural evaluation
Substantially improved Improved Failed
103 29 7
23 (22) 12(41) 467)
17 (16) 9 (31) 3 (43)
10 6
4 slings, 3 myedomies
thematous reaction at the skin test site after transurethral injection. However, no complications developed h m transurethral collagen injection. One patient reported transient hematuria and 2 requiredtreatment for urinary tract infection. Transient post-procedural urinary retention occum?d in 5 patients requiring intermittent self-catheterization for less than 1day. Finally, collagen injections did not preclude surgical success in the unresponsive cases. DISCUSSION
Patients with stress incontinence due to intrinsic sphincter deficiency are the best candidates for transurethral collagen therapy. Previous studies have suggested that patients with urethral hypermobility, in addition to intrinsic sphincter deficiency, have decreased efficacy with collagen and are best served with a sling procedure.g.10 In our study only patients with minimal urethral mobility were included. Experience with collagen injection therapy has varied with different techniques and followup intervals. Success rates range between 68 and 94%.11-13 Since proximal urethral function is best evaluated by determining abdominal leak point pressure and because improvement in stress incontinence correlates with increases in abdominal leak point pressure, all patients reporting no improvement in urinary incontinence were reevaluated with video urodynamics to rule out stress incontinence.9-14 Similar to other studies, we found that patients with urge incontinence reported lower continence success rates with increased pad usage.g.15 Our study revealed that 11.6% of the patients needed further injection at a later date to maintain the same efficacy, compared to an earlier multicenter series that reported a 20% subsequent booster injection rate.13 The incontinence questionnaire was a reliable tool for posttreatment evaluation. The survey was conducted by a third party physician who had chart documentation of patient pretreatment grade of incontinence and pad usage. The patient had only to describe the current situation with the knowledge that she could be evaluated if the incontinence persisted. Collagen delivery may be transurethral or periurethral. However, some investigators using the periurethral technique have reported an increased amount of collagen necessary for a successful outcome.11-16 Technique is also extremely important. For example if the injection is too superficial or if too much collagen is injected at one time, mucosal disruption will occur with subsequent collagen loss. On the other hand too deep of an injection will waste material and will not be effective. Since glutaraldehyde cross-linked bovine collagen loses some of its volume as a result of water resorption and some permanent "molding" occurs, urinary retention does not result. Collagen causes minimally obstructive changes based on urinary flow rates and residual volume data.17 Nevertheless, the glutaraldehyde cross-linked collagen is resistant to fibroblast secreted collagenases. Therefore, collagen integrates into the host tissue with neovascularity resulting in host collagen deposition in the implant site. In conclusion, our study c othat in patient8 with stress incontinence due to intrinsic sphincter deficiency, col-
108
COLLAGEN TREATMENT FOR INTRINSIC SPHINCTER DEFICIENCY IN WOMEN
lagen therapy is an option with rare complications and durability that requires minimal intervention.
8. McGuire, E. J., Fitzpatrick, C. C., Wan, J., Bloom, D., Sapvordenker, J., Ritchy, M. and Gormley, E. A.: Clinical assessment of urethral sphincter function. J. Urol., 1M): 1452,
REFERENCES
1993. 9. Herschorn, S., Rodomski, S. B. and Steele, D. J.: Early experi-
1. Malizia, A. A., Reiman, H. M. and Meyers, R. P.: Migration and
granulomatous reaction after periurethral injection of polytef. JAMA., 251: 3277, 1984. 2. Henly, D.R., Barrett, D. M., Weiland, T. L., OConnor, M. K, Malizia, A. A. and Wein, A. J.: Particulate silicon for use in periurethral injections: a study of local tissue effects and a search for migration. J. Urol., part 2,147: 3 7 6 4 abstract 654, 1992. 3. Santrosa, R. P. and Blavias, J. G.: Periurethral injection of
autologous fat for the treatment of sphincter incontinence. J. Urol., 151: 607, 1994. 4. Leonard, M. P., Canning, D.A. and Epstein, J. I.: Local tissue reaction to the suburethral mection of glutaraldehyde crosslinked bovine collagen in humans. J. Urol., 43: 1209,1990. 5. McPherson,J. M., Ledger, P. W. and Sawamura, S.: The preparation and physiochemical characterization of an injectable form of reconstituted, glutaraldehyde cross-linked, bovine corium collagen. J. Biomed. Matur. Res., u):79, 1986. 6. ShortWe, L. M. D. and Stamey, T. A: Urinary incontinence in the female. Stress urinary incontinence. In: Campbell's Urolo w ,5th ed. Edited bv C. Walsh. R. F. Gittes. A. D. Perlmutter &d T. C. Stamey. Philadelphia: W. B. SaLders, vol. 3, pp. 2680-2711,1986. 7. Baden, W. F. and Walker, T.: Fundamentals, symptoms and
classification.In: SurgicalRepair of Vaginal Defects. Edited by W. F. Baden and T. Walker. Philadelphia: J. B. Lippincott, pp. 9-23,1992.
ence with intraurethral collagen injection for urinary incontinence. J. Urol., 148: 1797,1992. 10. McGuire, E. J. and Appell, R. A.: Transurethral collagen injections for urinary incontinence. Urology, 43:413, 1994. 11. Shortliffe, L. M. D., Freiha, E. S., Kessler, R., Stamey, T. A. and Constantinou, C. E.: Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen. J. Urol., 141: 538, 1989. 12. Kieswettler, M., Fischer, M., Wober, L. and Flamm, J.: Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence. Brit. J. Urol., 69:22, 1992. 13. Contigen, R and Bad, R: Collagen implant product monograph. Bard Urologic Division. C.R Bard, Inc., Corington, Georgia,1993. 14. Richardson, T. D., Kennelly, M. J. and Faerber, G. J.: Endoscopic injection of glutaraldehyde cross-linked collagen for the treatment of intrinsic sphincter deficiency in women. Urology, 4 6 378, 1995. 15. Appell, R. A: Injectables for urethral incompetence. World J. Urol., 8: 208, 1990. 16. O'Connell, M. E., McGuire, E. J., Aboseif, S. and Usui, A.: Transurethral collagen therapy in women. Urol. Neurol. Urodynam., 154: 1463, 1995. 17. Moore, K. N., Chetner, M. P., Metcalfe, J. B. and Grifiths, D. J.:
Penurethral implantation of glutaraldehyde cross-linked collagen (contigen)in women with type I1 or I11 SUI: quantitative outcome measures. Brit. J. Urol., 75: 359, 1995.
Vol. 159,106-108,January 1998 Printed in U.SA.
"HE JOURNAL OF UROLOCY copyright 8 1998 by ANEUICAN UROII)OICAL Assocuno~,INC.
A FOLLOWUP ON TRANSURETHRAL COLLAGEN INJECTION THERAPY FOR URINARY INCONTINENCE CINDY A. CROSS, SHARON F. ENGLISH, R. DUANE CESPEDES
AND
EDWARD J. McGUIRE
From the Department of Obstetrics, Gynecobgy and Reproductive Medicine and the Division of Urology,University of Texas Medical School at Houston, Houston, and the apartment of UmlogylPSSU, Wilford Hall Medical Center, Lackland Air Force Base, Texas
ABSTRACT
Purpose: Transurethral collagen injection therapy has been used successfully in treating stress urinary incontinence due to intrinsic sphincter deficiency since United States Food and Dmg Administration approval in October 1993. Materials and Methods: Telephone interview and chart review were performed on 139 women with intrinsic sphincter deficiency documented using video urodynamics, of whom 73% had grade 3 incontinence (leakage without effort). Median followup was 18 months (range 6 to 36).Median patient age was 72 years. Results: A total of 103 patients (74%) was substantially improved after collagen therapy, 29 (20%) were improved and 7 had no improvement. Of the substantially improved group 72% obtained continence after 2 or fewer injections. Of the patients 11% required a "booster" injection more than 6 months after initial treatment. Complications, such as hematuria, urinary tract infections or transient urinary retention, were rare. Conclusions: Our results confirm the safety and efficacy of transurethral collagen. Once continence is achieved further collagen therapy is rarely necessary. KEY WORDS: urinary incontinence, stress;collagen; urinary tract; urination disorders METHODS Intrinsic sphincter deficiency is characterized by a poorly functioning proximal urethra that leaks urine at relatively Patients with urinary incontinence complaints were aslow intra-abdominal pressures. In women this condition is signed grades according to the Stamey scoring system for known as type I11 stress urinary incontinence and it can be incontinence,6 and a pelvic examination was performed and identified by measuring abdominal pressure required to graded according to the Baden and Walker Halfway system.7 cause leakage. If leakage is produced at abdominal pressures Abdominal leak point pressure of less than 60 cm. water below 60 cm. water, proximal urethral sphincter function is verified intrinsic sphincter deficiency. Abdominal leak point poor or absent. The most common treatments used today are pressure was determined during video urodynamics and by a sling procedures, artificial sphincters and injectable agents. technique described by McGuire et al.* With the patient erect These treatments compress or narrow the urethral lumen and in the oblique position neglible urethral hypermobility and increase the efficiency with which the urethra opposes was documented if the urethral radiopaque marker rotated less than 30 degrees during a Valsalva maneuver. Patients changes in intra-abdominal pressure. Injectable agenta provide an attractive nonsurgical option underwent collagen skin testing 1 month before the procefor the treatment of intrinsic sphincter deficiency. Initially dure. Exclusion criteria included grade I11 to IV prolapse at polybtrafluoroethylene (Teflon), autologous fat and silicone any vaginal site, abdominal leak point pressure greater than were used. Problems with polytetrafluoroethylene and sili- 60 cm. water, urethral hypermobility on video urodynamics cone included particle migration and granuloma forma- or allergic reaction to the collagen skin test. A total of 139 tion.1-2 and autologous fat often resulted in poor graft sur- patients qualified for transurethral collagen injections. Collagen iqjections were performed with local anesthesia vival.3 More promising as an injectable agent was glutaraldehyde cross-linked bovine collagen, which does not by a single surgeon at an outpatient clinic. The patient was cause granuloma formation, and encourages fibroblast a-given an oral preoperative antibiotic, the perineum and vatration and neovascularization while being minimally an- gina were prepared with antiseptic, and 2% lidocaine jelly tigenic and nonmigratory.4.6 Since its approval in October was placed intraurethrally. A 21F aspiratiodinjection rigid 1993, glutaraldehyde cross-linked bovine collagen has panendoscope was inserted and the bladder was emptied. Collagen was injected at the 4 and 8 o'clock positions in an been used at our institution for treating intrinsic sphincter area 1 to 1.5 cm. distal to the bladder neck. Initially 1% deficiency in women. We report our results with transure- lidocaine was injected in the submucosal plane, which anesthral collagen therapy from February 1994 to February thetized the urethra and dissected the appropriate plane. 1997. After discomfort from the lidocaine subsided approximately 2.5 cc collagen, or 1syringe, were injected into the submucosa Accepted for publication July 18, 1997. on either side. Average injection time was 5 minutes. PaThe opiniom contained herem are those of the authora and are not tients voided before leaving the clinic and if there was any to be c0nst"Bd aa reflecting the views of the Air Force or the difficulty with voiding, the patient was taught to perform Department of Defense. intermittent catheterization. The interval between injections &dilor~ Note: Thir article b the fourth ofI published in thie h e for which ca ry 1 CME eredib can be earned. In- was 4 to 8 weeks. Post-procedural evaluation of all patients included medical .trpctionr ibr credits are given with the questions Om pages 886 and 837. chart review and telephone urinary symptom questionnaire
*&
106
COLLAGEN TREATMENT FOR INTRINSIC SPHINCTER DEFICIENCY IN WOMEN
conducted by a third party physician. Patients were substantially improved if they had a 70% or greater reduction in daily pad usage compared to pre-collagen pad usage documented on the chart or grade 0 incontinence. Cases were classified as improved if they had 50 to 70% reduction in daily pad usage or at least 1grade improvement in incontinence, and failed if pad usage was reduced by less than 50% or the incontinence was grade 3. All patients whose urinary incontinence was not improved after the third collagen injection underwent video urodynamic evaluation with abdominal leak point pressure measurement. If stress incontinence was confirmed the patient was offered a rectus fascia pubovaginal sling. Patients who were initially substantially improved or improved and then had an increase in pad usage required video urodynamic confirmation of stress incontinence before receiving a booster collagen injection. All data were compared using paired t tests and p <0.05 was considered significant. RESULTS
Median patient age was 72 years and median pretreatment abdominal leak point pressure was 54 cm. water (range 18 to 60). Quantitatively, 93% used 4 pads or more a day with an average of 4.6 pads a day. Of the patients 73% had grade 3 incontinence, and 55 patients (40%) complained of urge and stress incontinence. Average duration of incontinence was 3.5 years. A total of 88 patients (63%) had undergone a previous incontinence procedure, such as bladder neck suspension, retropubic urethropexy or vaginal walllpubovaginal fascia1 sling, and 28 patients (20%) had undergone pelvic surgery that did not include a urethral procedure. Four patients had received radiotherapy for cervical carcinoma and 19 (14%)had had no previous pelvic surgery or trauma. The average duration since last collagen was 18 months (range 6 to 36). Of the 139 patients 103 (74%)were substantially improved after collagen therapy, 100 (72%) were substantially improved after 2 or fewer sessions and 29 (20%)were improved. In 7 patients treatment failed, of whom 4 underwent successful pubovaginal sling, and 3 previously had radiotherapy for cervical cancer. The 3 patients had improvement in stres! incontinence but poor bladder compliance and required detrusor myedomies. When comparing patients grouped as substantially improved, improved or failed, there was no statistical difference with respect to prior incontinence procedure, duration of incontinence and average number of pads before surgery (table 1).However, there was a correlation between complaints of urge incontinence and patient perception of success. Of patients with pre-procedural urge incontinence 53% continued to complain of the symptoms after the collagen injections, and 39 (28%) complained of de novo urge incontinence without intrinsic sphincter deficiency documented by video urodynamics. With respect to collagen durability and improvement in stress incontinence, 11.6% of the substantially improved or improved patients required an additional injection 6 months after the last injection of the initial treatment because of slightly decreased efficacy (table 2). A fourth of the patients reported a physical activity increase that they attributed to incontinence improvement. As an office procedure collagen therapy was well tolerated by the majority of patients. Three patients (2.0%) experienced ery-
TABLE1. Preoperative evduatwn NO.pts.
NO. previous Incontinence pmeedUres(96)
Substantiallyimproved Improved Failed
103 29
I
72 (70) 12 (41) 4 (57)
Duration Incontinence No. Pads (p.) 4.5 5
6 6
I
8
107
TABLE2. Post-procedural evaluation
Substantially improved Improved Failed
103 29 7
23 (22) 12(41) 467)
17 (16) 9 (31) 3 (43)
10 6
4 slings, 3 myedomies
thematous reaction at the skin test site after transurethral injection. However, no complications developed h m transurethral collagen injection. One patient reported transient hematuria and 2 requiredtreatment for urinary tract infection. Transient post-procedural urinary retention occum?d in 5 patients requiring intermittent self-catheterization for less than 1day. Finally, collagen injections did not preclude surgical success in the unresponsive cases. DISCUSSION
Patients with stress incontinence due to intrinsic sphincter deficiency are the best candidates for transurethral collagen therapy. Previous studies have suggested that patients with urethral hypermobility, in addition to intrinsic sphincter deficiency, have decreased efficacy with collagen and are best served with a sling procedure.g.10 In our study only patients with minimal urethral mobility were included. Experience with collagen injection therapy has varied with different techniques and followup intervals. Success rates range between 68 and 94%.11-13 Since proximal urethral function is best evaluated by determining abdominal leak point pressure and because improvement in stress incontinence correlates with increases in abdominal leak point pressure, all patients reporting no improvement in urinary incontinence were reevaluated with video urodynamics to rule out stress incontinence.9-14 Similar to other studies, we found that patients with urge incontinence reported lower continence success rates with increased pad usage.g.15 Our study revealed that 11.6% of the patients needed further injection at a later date to maintain the same efficacy, compared to an earlier multicenter series that reported a 20% subsequent booster injection rate.13 The incontinence questionnaire was a reliable tool for posttreatment evaluation. The survey was conducted by a third party physician who had chart documentation of patient pretreatment grade of incontinence and pad usage. The patient had only to describe the current situation with the knowledge that she could be evaluated if the incontinence persisted. Collagen delivery may be transurethral or periurethral. However, some investigators using the periurethral technique have reported an increased amount of collagen necessary for a successful outcome.11-16 Technique is also extremely important. For example if the injection is too superficial or if too much collagen is injected at one time, mucosal disruption will occur with subsequent collagen loss. On the other hand too deep of an injection will waste material and will not be effective. Since glutaraldehyde cross-linked bovine collagen loses some of its volume as a result of water resorption and some permanent "molding" occurs, urinary retention does not result. Collagen causes minimally obstructive changes based on urinary flow rates and residual volume data.17 Nevertheless, the glutaraldehyde cross-linked collagen is resistant to fibroblast secreted collagenases. Therefore, collagen integrates into the host tissue with neovascularity resulting in host collagen deposition in the implant site. In conclusion, our study c othat in patient8 with stress incontinence due to intrinsic sphincter deficiency, col-
108
COLLAGEN TREATMENT FOR INTRINSIC SPHINCTER DEFICIENCY IN WOMEN
lagen therapy is an option with rare complications and durability that requires minimal intervention.
8. McGuire, E. J., Fitzpatrick, C. C., Wan, J., Bloom, D., Sapvordenker, J., Ritchy, M. and Gormley, E. A.: Clinical assessment of urethral sphincter function. J. Urol., 1M): 1452,
REFERENCES
1993. 9. Herschorn, S., Rodomski, S. B. and Steele, D. J.: Early experi-
1. Malizia, A. A., Reiman, H. M. and Meyers, R. P.: Migration and
granulomatous reaction after periurethral injection of polytef. JAMA., 251: 3277, 1984. 2. Henly, D.R., Barrett, D. M., Weiland, T. L., OConnor, M. K, Malizia, A. A. and Wein, A. J.: Particulate silicon for use in periurethral injections: a study of local tissue effects and a search for migration. J. Urol., part 2,147: 3 7 6 4 abstract 654, 1992. 3. Santrosa, R. P. and Blavias, J. G.: Periurethral injection of
autologous fat for the treatment of sphincter incontinence. J. Urol., 151: 607, 1994. 4. Leonard, M. P., Canning, D.A. and Epstein, J. I.: Local tissue reaction to the suburethral mection of glutaraldehyde crosslinked bovine collagen in humans. J. Urol., 43: 1209,1990. 5. McPherson,J. M., Ledger, P. W. and Sawamura, S.: The preparation and physiochemical characterization of an injectable form of reconstituted, glutaraldehyde cross-linked, bovine corium collagen. J. Biomed. Matur. Res., u):79, 1986. 6. ShortWe, L. M. D. and Stamey, T. A: Urinary incontinence in the female. Stress urinary incontinence. In: Campbell's Urolo w ,5th ed. Edited bv C. Walsh. R. F. Gittes. A. D. Perlmutter &d T. C. Stamey. Philadelphia: W. B. SaLders, vol. 3, pp. 2680-2711,1986. 7. Baden, W. F. and Walker, T.: Fundamentals, symptoms and
classification.In: SurgicalRepair of Vaginal Defects. Edited by W. F. Baden and T. Walker. Philadelphia: J. B. Lippincott, pp. 9-23,1992.
ence with intraurethral collagen injection for urinary incontinence. J. Urol., 148: 1797,1992. 10. McGuire, E. J. and Appell, R. A.: Transurethral collagen injections for urinary incontinence. Urology, 43:413, 1994. 11. Shortliffe, L. M. D., Freiha, E. S., Kessler, R., Stamey, T. A. and Constantinou, C. E.: Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen. J. Urol., 141: 538, 1989. 12. Kieswettler, M., Fischer, M., Wober, L. and Flamm, J.: Endoscopic implantation of collagen (GAX) for the treatment of urinary incontinence. Brit. J. Urol., 69:22, 1992. 13. Contigen, R and Bad, R: Collagen implant product monograph. Bard Urologic Division. C.R Bard, Inc., Corington, Georgia,1993. 14. Richardson, T. D., Kennelly, M. J. and Faerber, G. J.: Endoscopic injection of glutaraldehyde cross-linked collagen for the treatment of intrinsic sphincter deficiency in women. Urology, 4 6 378, 1995. 15. Appell, R. A: Injectables for urethral incompetence. World J. Urol., 8: 208, 1990. 16. O'Connell, M. E., McGuire, E. J., Aboseif, S. and Usui, A.: Transurethral collagen therapy in women. Urol. Neurol. Urodynam., 154: 1463, 1995. 17. Moore, K. N., Chetner, M. P., Metcalfe, J. B. and Grifiths, D. J.:
Penurethral implantation of glutaraldehyde cross-linked collagen (contigen)in women with type I1 or I11 SUI: quantitative outcome measures. Brit. J. Urol., 75: 359, 1995.