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PERIURETHRAL FAT INJECTION IN THE TREATMENT OF RECURRENT GENUINE STRESS INCONTINENCE
0022-5347/98/1592-0411$03.00/0 THE JOURNAL OF UROLOGY Copyright 0 1998 by AMERICANUROLOGICAL ASSOCIATION,INC.
Vol. 159.411-414,February 1998 Printed in U S A .
PERIURETHRAL FAT INJECTION IN THE TREATMENT OF RECURRENT GENUINE STRESS INCONTINENCE TSUNG-HSIEN SU, KUO-GON WANG, CHIN-YUAN HSU, HSLAO-JUI WEI, HONG-JEN YEN AND FON-CHOU SHIEN From the Urodynamic Unit, Department of Obstetrics and Gynecology,Mackay Memorial Hospital and Taipei Medical College, Taipei Medical College Hospital, Taipei, Fu-Tai Hospital, Taoyuan and National Taiwan University Hospital, Taipei, Taiwan
ABSTRACT
Purpose: We evaluated the efficacy, safety and mechanism of periurethral fat injection in the treatment of recurrent genuine stress incontinence. Materials and Methods: Periurethral fat injections were performed in 26 patients for the treatment of recurrent genuine stress incontinence. A complete urogynecological study, including a 1-hour pad test, urodynamic studies and chain urethrocystography were done in each case and were repeated at least 3 months aRer operation. Each patient was followed for at least 12 months. Results: Of 26 patients 13 (50%)were dry aRer operation and 4 (15.4%) showed improvement and were satisfied with the results of the operation, giving a total success rate of 65.4%. There were 6 cases of immediate postoperative minor complications (23%).Average volume of injected fat was 14.8 2 4.8 cc, which did not affect the success rate. Preoperative and postoperative chain urethrocystographic values for bladder neck descent in reference to the pubosacral tip line showed no statistical difference between successfully and unsuccessfully treated groups. Urodynamic studies in all cases showed no differences relating to operation. However, minimal urethral resistance increased from 0.122 5 0.061 to 0.205 ? 0.134 (p = 0.023) in the treatment success group. This change was not demonstrated in the treatment failure group. Conclusions: Periurethral fat injection for the treatment of recurrent genuine stress incontinence is a simple technique that works by the increment of urethral resistance. It has an acceptable success rate without financial outlay for the injected material. KEYWORDS: bladder, urinary incontinence, urodynamics, urethra
During the last few decades, more than 100 different operative procedures have been proposed for treating genuine stress incontinence, with reported success rates varying from 30 to loo%.’.* The large number of reports reflect the inadequacy of 1 procedure to deal satisfactorily with all cases.3.4 The most common surgical procedure for cure of urinary incontinence is restoration of the bladder neck from a dependent position in the pelvis to high behind the symphysis pubis. Thus the proximal urethra can be appropriately repositioned in an intra-abdominal location where it can properly receive transmitted intra-abdominal pressure.5.6 To achieve good results patient selection criteria should include a compliant vaginal wall and descent of the bladder neck. However, successful treatment of genuine stress incontinence cannot be expected for every surgical attempt. For those patients in whom surgical treatment fails, a second attempt at surgical therapy becomes a challenge. Fat tissue transplants were first used for filling scars? and survival of the transplant can be documented by neovascularization within 4 days of t r a n ~ p l a n t a t i o n .Subsequently ~.~ there were further reports of fat grafts used in plastic surgery. lo. Periurethral injection of autologous fat has also recently been documented by limited studies.12-15 However, the role of this method in treatment of recurrent genuine stress incontinence is still to be determined. The purpose of this study was to evaluate the efficacy, safety and mechanism of periurethral fat injection for the treatment of recurrent genuine stress incontinence. Accepted for publication August 22, 1997.
MATERIALS AND METHODS
From March 1993 through December 1994,26 periurethral fat injections were performed for recurrent genuine stress incontinence. Before this operation, each patient had undergone unsuccessful anti-incontinence surgery. Failure of the operation was proven by a urodynamic study and the 1-hour extended pad test. To assess the efficacy of periurethral fat injection in the treatment of urethral sphincter insufficiency, inclusion criteria were a fixed or scarred vaginal wall and nonmobile urethra. Patients who had bladder neck descent at rest and/or with straining, hypermobile urethra or good vaginal capacity were excluded from this study. Candidates for treatment were required to sign a consent form and agree to attend followup visits as specified in the protocol and to undergo required evaluations a t specified intervals. Preoperative urogynecological evaluation included pelvic floor relaxation assessmentl6 (standard pelvic examinations by Sims speculum) to evaluate the degree of urethral mobidity and the integrity of the support of the urethra, bladder and other pelvic organs, the 1-hour extended pad test,17-18 x-ray chain urethrocystography, uroflowmetry, fillinglvoiding cystometry, and statiddynamic urethral pressure profilometry, all of which were repeated at least 3 months &er operation. Followup ranged from 12 to 30 months (mean 17.4 5 2.91, with patients being seen every 3 to 6 months. Our definition of a cure was the patient being dry by the end of the followup period, as documented by a 1-hour extended pad test and urodynamic study. Significant improvement was defined as patients experiencing only rare, minimal leakage and who were personally satisfied with the results of the operation by third party questioning. Student’s
411
412
PERIURETHRAL FAT INJECTION FOR INCONTINENCE
t test was used for statistical analysis and p c0.05 was considered statistically significant. OPERATIVE TECHNIQUES
Patients were given general anesthesia and placed in the lithotomy position. Fat was aspirated manually from the abdominal wall by liposuction. A small incision was made in the lower abdomen and a 5 to 7 mm. cannula was inserted into the adipose layer of the abdomen. The cannula was connected to a 2-way receptacle by a silicone tube and subsequently to a suction pump. Using a back-and-forth maneuver, liposuction of at least 20 cc of fatty tissue was performed. An abdominal elastic bandage was applied immediately aRer liposuction to prevent hemorrhage in the adipose tissue. The fat tissue was placed on a gauze pad and rinsed with Ringer's solution to remove any cell debris and as much blood as possible. Then the fat was transferred to a 5 cc syringe for injection. With a regular 18 gauge spinal needle, periurethral injection of the fat was performed at the bladder neck under cystoscopic vision to ensure proper location of the needle and good apposition of the mucosa. At least 3 injections were done, mainly at the 3, 6 and 9 o'clock areas. Suprapubic cystostomy was performed after completion of the fat injection. Patients were instructed regarding adequate hydration to ensure good urine output. On the morning of postoperative day 2 the suprapubic catheter was clamped and the patient was encouraged to void every 2 hours. Residual urine was measured with the catheter unclamped for 15 minutes. If on 2 successive voidings the voided amount was greater than 200 ml. and the residual amount was less than 100 ml., the catheter was clamped overnight. If the voided amount was more than 200 ml. and the residual amount of urine was still less than 100 ml. the next morning, the suprapubic cystostomy catheter was removed. RESULTS
Mean age of the patients was 53.2 2 10.8 years and mean parity was 4.3 f 1.8. Of the patients 13 (50%)were menopausal but none was on hormone replacement therapy. Of the 26 patients, 16 (61.5%)had previously undergone anterior repair. The type and frequency of any previous operations are shown in table 1. Preoperative and postoperative chain urethrocystographic values for bladder neck descent in reference to the pubosacral tip line showed no statistical differences between successfully and unsuccessfully treated groups. Urodynamic studies in all cases showed no difference relating to the operation. However, minimal urethral resistance increased from 0.122 f 0.061 to 0.205 2 0.134 (p = 0.023) in the successfully treated group (table 2).19 This change was not demonstrated in the treatment failure group. Time of operation was 83.4 2 30.4 minutes and estimated blood loss was minimal. The number of days before removal of the cystostomy catheter was 7.3 2 3.6 for all patients. The average volume of injected fat was 14.8 f 4.8 ml. (range 8 to 25) with no effect on the success rate (succesdfailure group 15.5 ? 4.3/14.3 2 4.3 ml., p = 0.31) (table 3). Of26 patients 13 (50%) were dry by the end of the followup period and 4 (15.4%) showed improvement and remained satisfied with the results of the operation, giving a total success rate of 65.4%.None of the symptoms worsened after TABLE1. Types and frequency of previous operations for incontinence Operation No. h. (%I Antemposterior repair Stamey operation Laparoscopic colposuspenaion Burch colposuspension
16 (61.6) l(26.9) 1 (3.8) 2 (7.7)
;he operation. There were 6 cases of immediate complications .23%)including 1 case of dysuria, 2 with voiding difficulties, 1 with gross hematuria, 1 with lower abdominal pain at the 1liposuction site occurring immediately after operation and 1 with urinary tract infection. All of these complications resolved by 3 months postoperatively. However, there was 1 case with detrusor instability that persisted postoperatively, for a total late complication rate of 3.8%. DISCUSSION
The causes of failed conventional surgery have been summarized as related to failure of elevation of the bladder neck or approximate alignment of the urethra to the posterior superior aspect of the symphysis pubis, lack of support to the posterior aspect of the proximal urethra and bladder, and creation of a rigid and functionless urethra as a result of postoperative fibrosis.16 It may be that in several of our patients the original bladder neck suspension procedures failed because of undetected intrinsic sphincteric deficiency. To our knowledge ours is the first study of periurethral fat injection for the treatment of recurrent genuine stress incontinence. Of 26 patients 23 (88.4%)who underwent anterior repair or Stamey operation, had a fixed or scarred vaginal wall and the bladder neck had already been elevated before study entry. The remaining 3 patients underwent colposuspension and each had an elevated bladder neck, although the vaginal capacity was still acceptable. As with the suburethral sling procedure, bulk enhancing agents are best used for patients with urinary incontinence secondary to intrinsic sphincter deficiency.20-23 All patients entering this study met the sampling criteria. Thus, the results could be verified objectively and the operative method justified. Two other materials have become popular for periurethral bulking. Polytetrafluoroethylene, a paste consisting of a sterile colloidal suspension of polytetrafluoroethylene micropolymer particles, can be injected into the urinary sphincter in male and female patients to improve incontinence.22Teflonpolytetrafluoroethylene itself, however, has several disadvantages that curtail its acceptance for urethral augmentation.23 It is difficult to administer, requiring injection at high pressure through a large bore needle. Submucosal extrusion of the paste has been observed and the polytetrafluoroethylene particles have been found t o migrate from the injection site, and distant polytef granulomas and emboli have been found in the lungs, liver, spleen and brain.24 The other material is contigen, which is a sterile nonpyogenic material composed of a highly purified bovine dermal collagen that is cross-linked with glutaraldehyde and dispersed in phosphate buffered physiological saline.23 The resultant implant material is a sterile homogenous gel that condenses after injection into a soft cohesive fibrous network colonized by host connective tissue cells and vasculature. However, alloplastic material may cause allergic reactions, may require as long as 1 month of skin testing and is expensive. The technique for periurethral fat injection is simple, avoids the use of foreign materials and only briefly extends the length of cystoscopic examination. Reported success rates for the injection of bulk enhancing agents have differed widely and varied from 50 to loo%,with a single injection or multiple injections.21-23.25326 Periurethral fat injection has a reported success rate ranging from 23 to 57%.12-15The success rate in our series was 65.4%for a single injection of fat with a 50% cure rate and a 15.4%rate of improvement, which is better than that of other series involving periurethral fat injection with a single or multiple injections. The success rate in our study may be due to over correction of the urethral sphincter defect. Regarding the volume of fat injected, to our knowledge there has been no documented study of how much fat is adequate for peri-
413
PERIURETHRAL FAT INJECTION FOR INCONTINENCE TABLE2. Comparison of urodynamics preoperatiuely and postoperatively between treatment success and failure groups Preop.
Urodynamic Data Transmission ratio: First proximal quarter of urethra Second proximal quarter of urethra Third proximal quarter of urethra Distal quarter of urethra Minimal urethral resistance * p = 0.023 (paired t test).
Failure Group
Success Group
Failure Group
0.956? 0.167 0.985 ? 0.118 0.9442 0.104 0.209 ? 0.162 0.122t 0.061:
0.992t 0.118 1.0782 0.160 0.979 t 0.287 0.134 2 0.051 0.156t 0.155
1.004? 0.191 1.022 2 0.164 0.868? 0.021 0.244 2 0.188 0.205 2 0.134:
1.018 C 0.105 0.980 2 0.020 0.8782 0.232 0.149 ? 0.097 0.136 2 0.068
TABLE3. Results relating to surgical technique No.pts. Time of operation b i n . ) Estimated blood loss (ml.) Vol. fat injected (m1.1: Range
Av.: Success group Failure moup
Postop.
Success Group
26 83.4 Minimal 8 to 25 14.82 4.8 15.5 t 4.3 14.3 ? 4.3
urethral injection. Santarosa and Blavias used 5 to 15 ml. autologous fat.15 The main disadvantage of using fat as a bulking substance is the variability of reabsorption and the degree of eventual connective tissue replacement. Long-term resorption rates of fat grafts of between 30 and 60%have been reported.g.11327.28 Horl et a1 used magnetic resonance imaging to demonstrate a 55%volume loss by 6 months and had no further volume loss at 9 and 12 months of followup.27 To achieve over correction and resolve this disadvantage we used a greater amount of fat (mean volume 14.8 ml., range 8 to 25 ml.) than was needed in previous studies. The total success rate of 65.4% was achieved. However, we found that the average volume of injection did not differ significantly between successful and unsuccessful procedures. The reason may be that the amount of fat injected in both groups provided the critical volume after absorption for effective bulking of the urethra. The mechanism responsible for success can also be documented by functional assessments. In the treatment success group, minimal urethral resistance was increased significantly, while bladder neck position on chain urethrocystography and pressure transmission ratio showed little change, suggesting that success is not dependent on anatomical change. The group in whom treatment failed likewise showed no change in bladder neck position but in addition they had no increase in resistance, which may be related to treatment failure. In other words, cure of the disease may depend mainly on compression rather than on suspension of the urethra. Graft longevity is related to the recipient site. As Horl et a1 documented, no further loss could be detected 6 months after operation.27 Chajchir and Benzaquen reported a 4-year followup of pathology specimens from patients who underwent fat injection for soft tissue augmentations.29 Specimens obtained 3 months postoperatively showed zones of cystosteatonecrosis, lipophagic granulomas, lymphocytes, adipocytes, giant cells and new vessel formations. Biopsies 1year later revealed large amounts of connective tissue and a fibrotic reaction as the final result. The tissue that followed the cysto-steatonecrotic process demonstrated a cicatrical reaction that maintained the desired volume of the area for a considerable period. Therefore, a 1-year followup period may be enough for a preliminary conclusion, although the rule for surgical treatment of genuine stress incontinence is that the failure rate increases with time. In our series the duration of bladder drainage was 7.3 2 3.6 days, which is longer than in other repork using bulk enhancing procedures. The reason for this longer duration of bladder drainage may be over correction of the urethral
sphincter defect. The advantages of this procedure are that age and obesity are not contraindications. Reported complications for the injection of bulk enhancing agents are few and have been limited mainly to infection, low grade fever and prolonged urinary catheterization immediately after operation.22.23.25.26 Similar complications, all minor, were observed in our patients. The immediate complication rate was 23%, but the delayed complication rate was low (1case with detrusor instability, 3.8%)in our series. The reason for a low delayed complication rate may be that autografts cause little tissue reaction. CONCLUSIONS
Recurrent genuine stress incontinence is unlikely to be treated successfully by procedures that correct mainly the bladder neck position, particularly in patients who have elevated bladder neck and narrow vaginal capacity. The success rate for periurethral fat injection is acceptable. Also, the procedure has a low complication rate, technical simplicity and no financial outlay for the injected material. Although this procedure may be used for primary genuine stress incontinence, especially for those patients who have low urethral resistance, we suggest that it be reserved for those in whom surgery has failed and who are unsuitable for major operations. Since the followup of this study was relatively brief and the number of patients small, further studies with a longer followup and more patients are necessary. REFERENCES
1. Stanton, S. L.: Surgery of urinary incontinence. Clin. Obst. Gynec., 5: 83, 1978. 2. Hilton, P.: Which operation and for which patients? In: Micturition. Edited by I. Drife, P. Hilton and S. L. Stanton. London: Springer-Verlag, p. 225, 1990. 3. Hilton, P.: Bladder drainage: a survey of practices among gynecologists in the British Isles. Brit. J. Obst. Gynec., 95: 1178, 1988. 4. Jarvis, G. J.: Surgery for genuine stress incontinence. Brit. J. Obst. Gynec., 101: 371, 1994. 5. Sand, P. K.and Ostergard, D. R.: The effect of retropubic urethropexy on the dynamic urethral closure profile. In: Urodynamics and the Evaluation of Female Incontinence-A Practical Guide. Edited by P. K. Sand and D. R. Ostergard. London: Springer-Verlag, p. 161, 1995. 6. Stanton, S.L.: Classification of incontinence. In: Clinical Gynecologic Urology. Edited by S. L. Stanton. St. Louis: C. V. Mosby, p. 165, 1984. 7. Neuber, F. Cited by Horl, H. W., Feller, A. M. and Biemer, E.: Technique for liposuction fat reimplantation and long-term volume evaluation by magnetic resonance imaging. AM. Plast. Surg., 2 6 248, 1991. 8. Peer, L. A,: The neglected free "fat graR", its behavior and clinical use. h e r . J. Surg., 92: 40, 1956. 9. Peer, L. A.: Loss ofweight and volume in human fat grafts. Plast. Reconstr. Surg., 5 217, 1950. 10. Billing, E., Jr. and May, J. W., Jr.: Historical review and present status of free graft autotransplantation in plastic and reconstructive surEery. Plast. Reconstr. Surn., 83: 368, 1989. 11. Pinski, K. S. &d koenigk, H. H., Jr.: Au~logousfat transplantation: long-term follow-up.J. Dermatol. Surg. Oncol., 18: 179, 1992.
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PERIURETHRAC FAT INJECTION FOR INCONTINENCE
12. Santiago Gonzalez de Garibay, A. M., Castm Morrondo, J. and Castillo Jimeno, J. M.: Endoscopic injection of autologous adipose tissue in the treatment of female incontinence. Arch. Esp. Urol., 42:143, 1989. 13. Gonzalez, G. S.,Jimeno, C. and York, M.: Endoscopic autotransplantation of fat tissue in the treatment of urinary incontinence in the female. J. d'urol., 8tk 363, 1989. 14. Gonzalez de Garibay, A. S., Castillo Jimeno, J. M. and Villanueva Perez, I.: Treatment of urinary stress incontinence using paraurethral injection of autologous fat. Arch. Esp. Urol., 44:595,1991. 15. Santarosa, R. P. and Blaivas, J. G.: Periurethral injection of autologous fat for the treatment of sphincteric incontinence. J. Urol., 151: 607,1994. 16. Stanton, S. L.: Stress incontinence: why and how operations work. Urol. Clin. N. h e r . , 12: 279, 1985. 17. Sutherst, J. and Brown, M.: Assessing the severity of urinary incontinence in women by weighing perineal pads. Lancet, I: 1128,1981. 18. International Continence Society. Quantification of urine loss. Fifth report on the standardization of terminology. Acaden, West Germany: International Continence Society, 1983. 19. Abram, P., Feneley, R. and Torrens, M.: Urodynamic investigations. In: Urodynamics.Edited by P. Abram, R. Feneley and M. Torrens. Berlin: Springer-Verlag,p. 28,1983. 20. Berg,S.:Polytef augmentation urethroplasty: correction of surgically incurable urinary incontinence by injection technique. Arch. Surg.,101: 379, 1973.
21. Politano, V. A., Small, M. P., Harper, J. M. and Lynne, C. M.: Periurethral Teflon injection for urinary incontinence. J. Urol., 111: 180,1974. 22. Politano, V. A.: Periurethral polytetrafluoroethylene injection for urinary incontinence. J. Urol., 127: 439, 1982. 23. Shortme, L.M. D., Freiha, F. S., Kessler, R., Stamen, T. A. and Constantinou, C. E.: Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen. J. Urol., 141: 538,1989. 24. Malizia, A. A., Jr., Reiman, H. M. and Myers, R. P.: Migration and granulomatous reaction after periurethral injection of polytef (Teflon).J.A.M.A., 261: 3277, 1984. 25. Lim, K. B.,Ball, A. J. and Feneley, R. C.: Periurethral Teflon injection: a simple treatment for urinary incontinence. Brit. J. Urol., 55: 208, 1983. 26. Lockhart, J. L., Walker, R. D., Vorstman, B. and Politano, V. A: Periurethral polytetrafluoroethylene injection following urethral reconstruction in female patients with urinary incontinence. J. Urol., 140:51, 1988. 27. Horl, H. W., Feller, A. M. and Biemer, E.: Technique for liposuction fat reimplantation and long-term volume evaluation by magnetic resonance imaging. Ann. Plast. Surg., 2 6 248,1991. 28. Ersek, R. A.: Transplantation of purified autologous fat: a 3-year follow-up is disappointing. Plast. Reconstr. Surg., 87: 219, 1991. 29. Chajchir, A. and Benzaquen, I.: Fat-grafting injection for so& tissue augmentation. Plast. Reconstr. Surg., 84: 921, 1989.
Vol. 159.411-414,February 1998 Printed in U S A .
PERIURETHRAL FAT INJECTION IN THE TREATMENT OF RECURRENT GENUINE STRESS INCONTINENCE TSUNG-HSIEN SU, KUO-GON WANG, CHIN-YUAN HSU, HSLAO-JUI WEI, HONG-JEN YEN AND FON-CHOU SHIEN From the Urodynamic Unit, Department of Obstetrics and Gynecology,Mackay Memorial Hospital and Taipei Medical College, Taipei Medical College Hospital, Taipei, Fu-Tai Hospital, Taoyuan and National Taiwan University Hospital, Taipei, Taiwan
ABSTRACT
Purpose: We evaluated the efficacy, safety and mechanism of periurethral fat injection in the treatment of recurrent genuine stress incontinence. Materials and Methods: Periurethral fat injections were performed in 26 patients for the treatment of recurrent genuine stress incontinence. A complete urogynecological study, including a 1-hour pad test, urodynamic studies and chain urethrocystography were done in each case and were repeated at least 3 months aRer operation. Each patient was followed for at least 12 months. Results: Of 26 patients 13 (50%)were dry aRer operation and 4 (15.4%) showed improvement and were satisfied with the results of the operation, giving a total success rate of 65.4%. There were 6 cases of immediate postoperative minor complications (23%).Average volume of injected fat was 14.8 2 4.8 cc, which did not affect the success rate. Preoperative and postoperative chain urethrocystographic values for bladder neck descent in reference to the pubosacral tip line showed no statistical difference between successfully and unsuccessfully treated groups. Urodynamic studies in all cases showed no differences relating to operation. However, minimal urethral resistance increased from 0.122 5 0.061 to 0.205 ? 0.134 (p = 0.023) in the treatment success group. This change was not demonstrated in the treatment failure group. Conclusions: Periurethral fat injection for the treatment of recurrent genuine stress incontinence is a simple technique that works by the increment of urethral resistance. It has an acceptable success rate without financial outlay for the injected material. KEYWORDS: bladder, urinary incontinence, urodynamics, urethra
During the last few decades, more than 100 different operative procedures have been proposed for treating genuine stress incontinence, with reported success rates varying from 30 to loo%.’.* The large number of reports reflect the inadequacy of 1 procedure to deal satisfactorily with all cases.3.4 The most common surgical procedure for cure of urinary incontinence is restoration of the bladder neck from a dependent position in the pelvis to high behind the symphysis pubis. Thus the proximal urethra can be appropriately repositioned in an intra-abdominal location where it can properly receive transmitted intra-abdominal pressure.5.6 To achieve good results patient selection criteria should include a compliant vaginal wall and descent of the bladder neck. However, successful treatment of genuine stress incontinence cannot be expected for every surgical attempt. For those patients in whom surgical treatment fails, a second attempt at surgical therapy becomes a challenge. Fat tissue transplants were first used for filling scars? and survival of the transplant can be documented by neovascularization within 4 days of t r a n ~ p l a n t a t i o n .Subsequently ~.~ there were further reports of fat grafts used in plastic surgery. lo. Periurethral injection of autologous fat has also recently been documented by limited studies.12-15 However, the role of this method in treatment of recurrent genuine stress incontinence is still to be determined. The purpose of this study was to evaluate the efficacy, safety and mechanism of periurethral fat injection for the treatment of recurrent genuine stress incontinence. Accepted for publication August 22, 1997.
MATERIALS AND METHODS
From March 1993 through December 1994,26 periurethral fat injections were performed for recurrent genuine stress incontinence. Before this operation, each patient had undergone unsuccessful anti-incontinence surgery. Failure of the operation was proven by a urodynamic study and the 1-hour extended pad test. To assess the efficacy of periurethral fat injection in the treatment of urethral sphincter insufficiency, inclusion criteria were a fixed or scarred vaginal wall and nonmobile urethra. Patients who had bladder neck descent at rest and/or with straining, hypermobile urethra or good vaginal capacity were excluded from this study. Candidates for treatment were required to sign a consent form and agree to attend followup visits as specified in the protocol and to undergo required evaluations a t specified intervals. Preoperative urogynecological evaluation included pelvic floor relaxation assessmentl6 (standard pelvic examinations by Sims speculum) to evaluate the degree of urethral mobidity and the integrity of the support of the urethra, bladder and other pelvic organs, the 1-hour extended pad test,17-18 x-ray chain urethrocystography, uroflowmetry, fillinglvoiding cystometry, and statiddynamic urethral pressure profilometry, all of which were repeated at least 3 months &er operation. Followup ranged from 12 to 30 months (mean 17.4 5 2.91, with patients being seen every 3 to 6 months. Our definition of a cure was the patient being dry by the end of the followup period, as documented by a 1-hour extended pad test and urodynamic study. Significant improvement was defined as patients experiencing only rare, minimal leakage and who were personally satisfied with the results of the operation by third party questioning. Student’s
411
412
PERIURETHRAL FAT INJECTION FOR INCONTINENCE
t test was used for statistical analysis and p c0.05 was considered statistically significant. OPERATIVE TECHNIQUES
Patients were given general anesthesia and placed in the lithotomy position. Fat was aspirated manually from the abdominal wall by liposuction. A small incision was made in the lower abdomen and a 5 to 7 mm. cannula was inserted into the adipose layer of the abdomen. The cannula was connected to a 2-way receptacle by a silicone tube and subsequently to a suction pump. Using a back-and-forth maneuver, liposuction of at least 20 cc of fatty tissue was performed. An abdominal elastic bandage was applied immediately aRer liposuction to prevent hemorrhage in the adipose tissue. The fat tissue was placed on a gauze pad and rinsed with Ringer's solution to remove any cell debris and as much blood as possible. Then the fat was transferred to a 5 cc syringe for injection. With a regular 18 gauge spinal needle, periurethral injection of the fat was performed at the bladder neck under cystoscopic vision to ensure proper location of the needle and good apposition of the mucosa. At least 3 injections were done, mainly at the 3, 6 and 9 o'clock areas. Suprapubic cystostomy was performed after completion of the fat injection. Patients were instructed regarding adequate hydration to ensure good urine output. On the morning of postoperative day 2 the suprapubic catheter was clamped and the patient was encouraged to void every 2 hours. Residual urine was measured with the catheter unclamped for 15 minutes. If on 2 successive voidings the voided amount was greater than 200 ml. and the residual amount was less than 100 ml., the catheter was clamped overnight. If the voided amount was more than 200 ml. and the residual amount of urine was still less than 100 ml. the next morning, the suprapubic cystostomy catheter was removed. RESULTS
Mean age of the patients was 53.2 2 10.8 years and mean parity was 4.3 f 1.8. Of the patients 13 (50%)were menopausal but none was on hormone replacement therapy. Of the 26 patients, 16 (61.5%)had previously undergone anterior repair. The type and frequency of any previous operations are shown in table 1. Preoperative and postoperative chain urethrocystographic values for bladder neck descent in reference to the pubosacral tip line showed no statistical differences between successfully and unsuccessfully treated groups. Urodynamic studies in all cases showed no difference relating to the operation. However, minimal urethral resistance increased from 0.122 f 0.061 to 0.205 2 0.134 (p = 0.023) in the successfully treated group (table 2).19 This change was not demonstrated in the treatment failure group. Time of operation was 83.4 2 30.4 minutes and estimated blood loss was minimal. The number of days before removal of the cystostomy catheter was 7.3 2 3.6 for all patients. The average volume of injected fat was 14.8 f 4.8 ml. (range 8 to 25) with no effect on the success rate (succesdfailure group 15.5 ? 4.3/14.3 2 4.3 ml., p = 0.31) (table 3). Of26 patients 13 (50%) were dry by the end of the followup period and 4 (15.4%) showed improvement and remained satisfied with the results of the operation, giving a total success rate of 65.4%.None of the symptoms worsened after TABLE1. Types and frequency of previous operations for incontinence Operation No. h. (%I Antemposterior repair Stamey operation Laparoscopic colposuspenaion Burch colposuspension
16 (61.6) l(26.9) 1 (3.8) 2 (7.7)
;he operation. There were 6 cases of immediate complications .23%)including 1 case of dysuria, 2 with voiding difficulties, 1 with gross hematuria, 1 with lower abdominal pain at the 1liposuction site occurring immediately after operation and 1 with urinary tract infection. All of these complications resolved by 3 months postoperatively. However, there was 1 case with detrusor instability that persisted postoperatively, for a total late complication rate of 3.8%. DISCUSSION
The causes of failed conventional surgery have been summarized as related to failure of elevation of the bladder neck or approximate alignment of the urethra to the posterior superior aspect of the symphysis pubis, lack of support to the posterior aspect of the proximal urethra and bladder, and creation of a rigid and functionless urethra as a result of postoperative fibrosis.16 It may be that in several of our patients the original bladder neck suspension procedures failed because of undetected intrinsic sphincteric deficiency. To our knowledge ours is the first study of periurethral fat injection for the treatment of recurrent genuine stress incontinence. Of 26 patients 23 (88.4%)who underwent anterior repair or Stamey operation, had a fixed or scarred vaginal wall and the bladder neck had already been elevated before study entry. The remaining 3 patients underwent colposuspension and each had an elevated bladder neck, although the vaginal capacity was still acceptable. As with the suburethral sling procedure, bulk enhancing agents are best used for patients with urinary incontinence secondary to intrinsic sphincter deficiency.20-23 All patients entering this study met the sampling criteria. Thus, the results could be verified objectively and the operative method justified. Two other materials have become popular for periurethral bulking. Polytetrafluoroethylene, a paste consisting of a sterile colloidal suspension of polytetrafluoroethylene micropolymer particles, can be injected into the urinary sphincter in male and female patients to improve incontinence.22Teflonpolytetrafluoroethylene itself, however, has several disadvantages that curtail its acceptance for urethral augmentation.23 It is difficult to administer, requiring injection at high pressure through a large bore needle. Submucosal extrusion of the paste has been observed and the polytetrafluoroethylene particles have been found t o migrate from the injection site, and distant polytef granulomas and emboli have been found in the lungs, liver, spleen and brain.24 The other material is contigen, which is a sterile nonpyogenic material composed of a highly purified bovine dermal collagen that is cross-linked with glutaraldehyde and dispersed in phosphate buffered physiological saline.23 The resultant implant material is a sterile homogenous gel that condenses after injection into a soft cohesive fibrous network colonized by host connective tissue cells and vasculature. However, alloplastic material may cause allergic reactions, may require as long as 1 month of skin testing and is expensive. The technique for periurethral fat injection is simple, avoids the use of foreign materials and only briefly extends the length of cystoscopic examination. Reported success rates for the injection of bulk enhancing agents have differed widely and varied from 50 to loo%,with a single injection or multiple injections.21-23.25326 Periurethral fat injection has a reported success rate ranging from 23 to 57%.12-15The success rate in our series was 65.4%for a single injection of fat with a 50% cure rate and a 15.4%rate of improvement, which is better than that of other series involving periurethral fat injection with a single or multiple injections. The success rate in our study may be due to over correction of the urethral sphincter defect. Regarding the volume of fat injected, to our knowledge there has been no documented study of how much fat is adequate for peri-
413
PERIURETHRAL FAT INJECTION FOR INCONTINENCE TABLE2. Comparison of urodynamics preoperatiuely and postoperatively between treatment success and failure groups Preop.
Urodynamic Data Transmission ratio: First proximal quarter of urethra Second proximal quarter of urethra Third proximal quarter of urethra Distal quarter of urethra Minimal urethral resistance * p = 0.023 (paired t test).
Failure Group
Success Group
Failure Group
0.956? 0.167 0.985 ? 0.118 0.9442 0.104 0.209 ? 0.162 0.122t 0.061:
0.992t 0.118 1.0782 0.160 0.979 t 0.287 0.134 2 0.051 0.156t 0.155
1.004? 0.191 1.022 2 0.164 0.868? 0.021 0.244 2 0.188 0.205 2 0.134:
1.018 C 0.105 0.980 2 0.020 0.8782 0.232 0.149 ? 0.097 0.136 2 0.068
TABLE3. Results relating to surgical technique No.pts. Time of operation b i n . ) Estimated blood loss (ml.) Vol. fat injected (m1.1: Range
Av.: Success group Failure moup
Postop.
Success Group
26 83.4 Minimal 8 to 25 14.82 4.8 15.5 t 4.3 14.3 ? 4.3
urethral injection. Santarosa and Blavias used 5 to 15 ml. autologous fat.15 The main disadvantage of using fat as a bulking substance is the variability of reabsorption and the degree of eventual connective tissue replacement. Long-term resorption rates of fat grafts of between 30 and 60%have been reported.g.11327.28 Horl et a1 used magnetic resonance imaging to demonstrate a 55%volume loss by 6 months and had no further volume loss at 9 and 12 months of followup.27 To achieve over correction and resolve this disadvantage we used a greater amount of fat (mean volume 14.8 ml., range 8 to 25 ml.) than was needed in previous studies. The total success rate of 65.4% was achieved. However, we found that the average volume of injection did not differ significantly between successful and unsuccessful procedures. The reason may be that the amount of fat injected in both groups provided the critical volume after absorption for effective bulking of the urethra. The mechanism responsible for success can also be documented by functional assessments. In the treatment success group, minimal urethral resistance was increased significantly, while bladder neck position on chain urethrocystography and pressure transmission ratio showed little change, suggesting that success is not dependent on anatomical change. The group in whom treatment failed likewise showed no change in bladder neck position but in addition they had no increase in resistance, which may be related to treatment failure. In other words, cure of the disease may depend mainly on compression rather than on suspension of the urethra. Graft longevity is related to the recipient site. As Horl et a1 documented, no further loss could be detected 6 months after operation.27 Chajchir and Benzaquen reported a 4-year followup of pathology specimens from patients who underwent fat injection for soft tissue augmentations.29 Specimens obtained 3 months postoperatively showed zones of cystosteatonecrosis, lipophagic granulomas, lymphocytes, adipocytes, giant cells and new vessel formations. Biopsies 1year later revealed large amounts of connective tissue and a fibrotic reaction as the final result. The tissue that followed the cysto-steatonecrotic process demonstrated a cicatrical reaction that maintained the desired volume of the area for a considerable period. Therefore, a 1-year followup period may be enough for a preliminary conclusion, although the rule for surgical treatment of genuine stress incontinence is that the failure rate increases with time. In our series the duration of bladder drainage was 7.3 2 3.6 days, which is longer than in other repork using bulk enhancing procedures. The reason for this longer duration of bladder drainage may be over correction of the urethral
sphincter defect. The advantages of this procedure are that age and obesity are not contraindications. Reported complications for the injection of bulk enhancing agents are few and have been limited mainly to infection, low grade fever and prolonged urinary catheterization immediately after operation.22.23.25.26 Similar complications, all minor, were observed in our patients. The immediate complication rate was 23%, but the delayed complication rate was low (1case with detrusor instability, 3.8%)in our series. The reason for a low delayed complication rate may be that autografts cause little tissue reaction. CONCLUSIONS
Recurrent genuine stress incontinence is unlikely to be treated successfully by procedures that correct mainly the bladder neck position, particularly in patients who have elevated bladder neck and narrow vaginal capacity. The success rate for periurethral fat injection is acceptable. Also, the procedure has a low complication rate, technical simplicity and no financial outlay for the injected material. Although this procedure may be used for primary genuine stress incontinence, especially for those patients who have low urethral resistance, we suggest that it be reserved for those in whom surgery has failed and who are unsuitable for major operations. Since the followup of this study was relatively brief and the number of patients small, further studies with a longer followup and more patients are necessary. REFERENCES
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21. Politano, V. A., Small, M. P., Harper, J. M. and Lynne, C. M.: Periurethral Teflon injection for urinary incontinence. J. Urol., 111: 180,1974. 22. Politano, V. A.: Periurethral polytetrafluoroethylene injection for urinary incontinence. J. Urol., 127: 439, 1982. 23. Shortme, L.M. D., Freiha, F. S., Kessler, R., Stamen, T. A. and Constantinou, C. E.: Treatment of urinary incontinence by the periurethral implantation of glutaraldehyde cross-linked collagen. J. Urol., 141: 538,1989. 24. Malizia, A. A., Jr., Reiman, H. M. and Myers, R. P.: Migration and granulomatous reaction after periurethral injection of polytef (Teflon).J.A.M.A., 261: 3277, 1984. 25. Lim, K. B.,Ball, A. J. and Feneley, R. C.: Periurethral Teflon injection: a simple treatment for urinary incontinence. Brit. J. Urol., 55: 208, 1983. 26. Lockhart, J. L., Walker, R. D., Vorstman, B. and Politano, V. A: Periurethral polytetrafluoroethylene injection following urethral reconstruction in female patients with urinary incontinence. J. Urol., 140:51, 1988. 27. Horl, H. W., Feller, A. M. and Biemer, E.: Technique for liposuction fat reimplantation and long-term volume evaluation by magnetic resonance imaging. Ann. Plast. Surg., 2 6 248,1991. 28. Ersek, R. A.: Transplantation of purified autologous fat: a 3-year follow-up is disappointing. Plast. Reconstr. Surg., 87: 219, 1991. 29. Chajchir, A. and Benzaquen, I.: Fat-grafting injection for so& tissue augmentation. Plast. Reconstr. Surg., 84: 921, 1989.