Urethral Bulking Agents: Techniques and Outcomes Ahmed F. Kotb, MD, Lysanne Campeau, MD, and Jacques Corcos, MD
Corresponding author Jacques Corcos, MD Department of Urology, Jewish General Hospital, 3755 Côte Sainte-Catherine, Montreal, Quebec QC H3E 1T2, Canada. E-mail:
[email protected] Current Urology Reports 2009, 10:396–400 Current Medicine Group LLC ISSN 1527-2737 Copyright © 2009 by Current Medicine Group LLC
Stress urinary incontinence is a common health problem affecting women and interfering with their quality of life. The use of bulking agents for urethral augmentation seems to be a beneficial way of restoring continence in these patients while avoiding the risk of surgical intervention. Many agents are available for injection, but the ideal choice should be durable, nonmigratory, and hypoallergenic, while evoking healing with minimal scarring. We reviewed the literature to provide an update on the best techniques of bulking agent injection, to describe the different available injectable agents, and to give their outcome and possible complications.
Introduction Stress urinary incontinence (SUI) affects millions of women and is associated with a significant economic burden and quality-of-life (QOL) impact [1]. This condition often requires defi nitive treatment through procedures aimed at increasing urethral resistance and thereby decreasing the degree of urinary leakage. Bulking urethral agents are an attractive option and alternative to open surgery for many patients because of their minimally invasive nature and relatively safe side effect profi le.
Mechanism of Action It is suggested that the injection of bulking agents into the urethral submucosa is designed to create artificial urethral cushions, improving urethral coaptation and, hence, restoring continence. Klarskov and Lose [2] measured pressure and cross-sectional area in the urethra of women with SUI and mixed incontinence before and after urethral injection therapy, using a pressure profile reflectometer. This novel technique detected a more significant increase
in squeezing opening pressures in patients who had subjectively noticed an effect. They suggested that injection therapy functions as a central filler volume that increases the length of muscle fibers and thereby the power of the urethral sphincter. The external sphincter consists of muscle fibers, collagen, vessels, and nerves, with a central component compressing the lumen [3]. An increased central fi ller volume will augment the sarcomere length of muscle fibers, strengthening muscle power up to a sarcomere length of 2.2 μm [4]. The ideal bulking agent should be nonimmunogenic, hypoallergenic, deformable, biocompatible, and durable. Particle size should be larger than 110 μm to prevent migration. The injectable agent should demonstrate satisfactory wound-healing characteristics with minimal fibrotic ingrowth and extracapsular extension, if capsulated.
Technique Kuhn et al. [5] found that the injection of bulking agents at the bladder neck and midurethra almost equally improved patient satisfaction, with a small advantage for midurethral injection. The “integral theory” of Petros and Ulmsten [6] supports the argument that midurethral injection is more effective in patients with associated urethral hypermobility because it provides urethral stabilization. Elia and Bergman [7] reported that the relative position of material injected into the bladder neck determines continence outcome. In their study, a successful outcome was associated with a collagen distance of less than 7 mm from the bladder neck and a positive predictive value of 93.7%. In a recent study, Mitterberger et al. [8•] delivered bovine collagen into the lower urinary tract of 20 dead female pigs and compared the precision of transurethral endoscopic- versus ultrasound-guided injections given periurethrally or in the urethral wall. They concluded that the endoscopic application of injectables is an inaccurate technique, whereas endoluminal ultrasound-guided injections are precise and enable excellent control of the therapeutic procedure. However, this study did not demonstrate that higher accuracy of injection correlated with better clinical outcomes. In a prospective study by Schulz et al. [9], the authors concluded that both periurethral and transurethral methods
Urethral Bulking Agents: Techniques and Outcomes
of bulking agent injection for SUI are equally effective and cause minimal morbidity.
Outcomes Quality of life Although intervention for SUI is generally focused on minimizing urine leakage, the overall impact of treatment on patient QOL is arguably more important than the treatment outcome regarding leakage. A literature review by Chapple et al. [10] concluded that QOL improvement after urethral injections appears to be significant and comparable to that obtained with surgery, despite observing superior objective surgical efficacy.
Collagen injection Periurethral collagen injection (PCI) has been used in the treatment of SUI due to intrinsic sphincter deficiency (ISD) since 1993 when it was first approved for this application by the US Food and Drug Administration (FDA) [11]. However, collagen is antigenic and requires skin testing prior to injection. It has been reported that SUI associated with ISD can be treated with reasonable success by PCI [12]. Collagen, to correct bladder neck hypermobility, was evaluated in a prospective study, which concluded that this therapy was appropriate for patients who wished to avoid surgical risks [13]. Martins et al. [14•], who used PCI on 13 patients with bladder neck hypermobility and 27 women with ISD, concluded that PCI is equally effective in both groups. Cure or improvement was achieved on urodynamic studies in 46% of patients with bladder hypermobility and in 40.7% of patients with ISD. Therefore, the latter should no longer be considered as a contraindication to the urethral injection of bulking agents. Similar outcomes were reported by Corcos and Fournier [15] with urethral submucosal collagen injection for SUI. They demonstrated favorable results of improvement (40%) and cure (30%) at 50 months follow-up. Although PCI is considered an easy and safe procedure, it is not durable. Most patients need additional treatment sessions to achieve and maintain improvement or cure [14•,15]. Poon et al. [16] employed 3-dimensional ultrasound (3DUS) to demonstrate the natural history of collagen injected in tissues of the urethra. They detected a postoperative collagen volume of 2.8 mL located circumferentially or in a horse-shoe fashion around the proximal urethra in 80% of cases and concluded that a persistent, satisfactory clinical outcome is associated with maintenance of this configuration and volume over time. The technique is optimized with precise submucosal injection and avoidance of extravasation caused by excessive or forcible volume injection or by passage of the cystoscope through the freshly injected urethra. Previous findings were reinforced in another study by the results of Isom-Batz and Zimmern [17•], who demonstrated with 3DUS that most patients needing collagen reinjection showed an asymmetrical configuration or low
I
Kotb et al.
I
397
volume of collagen deposits. Koduri et al. [18] conducted a retrospective study, which established that prior anti-incontinence surgery was a factor showing a trend toward the long-term success of PCI. Sokol et al. [19] compared collagen injection alone and collagen combined with Durasphere injection for the treatment of ISD cases. They found that combined injection did not improve the outcome over collagen injection alone. Poon and Zimmern [20] investigated the effectiveness of PCI in patients presenting symptoms of mixed urinary incontinence and urodynamically demonstrated sphincter deficiency with detrusor overactivity (DO). They concluded that treating the sphincter deficiency with PCI before treating the bladder abnormality (DO) can produce satisfactory symptom improvement, not only in SUI, but also in urinary frequency and urge incontinence. Furthermore, patient QOL improved, and most did not require antimuscarinic medications. However, PCI was not demonstrated to be effective for the long-term treatment of urinary incontinence in children with myelomeningocele [21,22]. SUI treatment with PCI after radical cystectomy, for bladder cancer and orthotopic neobladder, has shown its effectiveness only in the presence of minimal symptoms. However, the long-term results in patients with severe disease were suboptimal [23].
Carbon bead injection Durasphere (carbon-coated zirconium oxide beads) was approved by the FDA in 1999 for the treatment of women with SUI due to ISD. Although Durasphere has a large particle size and chronic loss of bead material has not been documented, it does not provide more durability than collagen [24]. For unknown reasons, Chrouser et al. [24] found that previous hysterectomy was statistically associated with collagen injection success, but linked with Durasphere injection failure. Madjar et al. [25] modified the injection technique of bulking agents for easier implantation of Durasphere. The modified steps begin with hydrodissection, with the injection of 1.5 mL of 1% lidocaine through a single needle stick in the 4 o’clock position into the submucosa. The needle tip is then gradually withdrawn, advanced, or rotated until resistance is noted. The needle is held in this position for an additional 10 seconds after proper coaptation is achieved with injection of the agent to prevent the beads from leaking out of the needle puncture site. In another study, Madjar et al. [26] detected a 2.9% incidence of periurethral mass formation more than 12 months after periurethral Durasphere injection. They concluded that the new onset of irritative or obstructing voiding symptoms, or pelvic pain in patients with a history of Durasphere or other periurethral bulking agent injection may be warning signs of periurethral mass formation. McCrery and Appell [27] demonstrated that carbon beads can be safely injected under local anesthesia in patients on therapeutic warfarin anticoagulation without the need for its reversal.
398
I
Female Urology
Ethylene vinyl alcohol injection Ethylene vinyl was approved to treat SUI by the FDA in 2004. Its effectiveness was evaluated in a prospective study by Kuhn et al. [28]. The success rate in 33 women at 51 months was 45%. However, serious complications such as urethral erosions were demonstrated by Hurtado et al. [29] and Erekson et al. [30].
Polydimethylsiloxane injection The reported cure and success rates of polydimethylsiloxane (PDMS) for ISD are between 14% and 66.7%, and 46% and 80%, respectively [31]. No major complications are associated with PDMS. Urinary retention is reported in 5.9% to 17.5% of patients, frequency in 0% to 72.4%, dysuria in 0% to 100%, and urinary tract infection in 0% to 100%. Zullo et al. [32] showed an 18% cure rate of SUI, an improvement rate of 39%, and a failure rate of 43% at 60 months follow-up. They concluded that PDMS is a valid, minimally invasive surgical procedure to treat SUI due to ISD with decreased urethral mobility, delivering an acceptable long-term success rate and high subjective satisfaction. A recent multicenter study randomly assigned a total of 247 females with ISD in a 1:1 fashion to be treated with transurethral injection of either Macroplastique (Uroplasty, Inc., Minnetonka, MN) or Contigen (Bard, Inc., Covington, GA). The success rate at 1-year follow-up was statistically higher for Macroplastique vs Contigen (61% vs 48%). Ghoneim et al. [33••] concluded that Macroplastique is a safe, efficacious, minimally invasive, injectable silicone material that should be considered a primary or secondary treatment option for SUI. Plotti et al. [34] investigated the effectiveness of PDMS injected at least 12 months after radical hysterectomy for the treatment of SUI. They demonstrated a success rate of 84% at 12 months follow-up. They recommended the urethral injection of bulking agents as a valid therapeutic strategy to treat SUI after radical surgery without complications for cervical cancer that may improve the well-being of these patients. Plotti et al. [35] also studied PDMS urethral injection against SUI after radical vulvectomy. They believed that the insertion of a midurethral tension-free sling in patients who previously underwent radical surgery for vulvar cancer was unreasonable because the surgery caused severe paraurethral fibrosis and vulvar and vaginal retraction in short urethras. Moreover, the risk of complications during a retropubic or transobturator approach may be increased because most of these patients undergo a myocutaneous or fasciocutaneous V-Y flap at the time of vulvectomy. They reported two cases of PDMS urethral injection after radical vulvectomy with satisfactory results and improved patient well-being.
urethral bulking agent, appears to have a higher cure rate in urodynamic SUI than Macroplastique, and the results persist until a follow-up period of 6 months.
Calcium hydroxylapatite injection Mayer et al. [37] evaluated the safety and effectiveness of Coaptite (Boston Scientific Corporation, Natick, MA) compared with PCI in female patients with SUI due to ISD without associated urethral hypermobility. Their fi ndings confi rmed the hypothesis that Coaptite is as effective as PCI, at a lower injection volume than that used in collagen-treated subjects. Patients receiving Coaptite had better outcomes after a single injection compared with patients treated with collagen. Palma et al. [38] recorded the fi rst case of urethral granulomatous reaction leading to urethral prolapse, occurring 3 months after the transurethral injection of calcium hydroxylapatite. Several case reports of urethral prolapse in women with SUI treated with Coaptite have since been published [39,40].
Non-animal, stabilized hyaluronic acid/dextranomer injection A multicentric study by van Kerrebroeck et al. [41] concluded that a novel system, non-animal, stabilized hyaluronic acid/dextranomer (NASHA/Dx) copolymer, delivered by an Implacer device, was an effective and well-tolerated treatment for SUI in patients who had not undergone invasive therapy. Improvement was sustained up to 12 months. Similar results of successful treatment with Zuidex (Q-Med, Uppsala, Sweden) were confi rmed by Chapple et al. [42] and Kobelt and Fianu-Jonasson [43]. Papanikolaou and Ducket [44] reported a case of urethral damage and erosion caused by prolonged catheterization for Zuidex injection and placement of a suprapubic catheter. Fianu-Jonasson et al. [45] confi rmed with MRI the proper location of the bulking agent within the urethral wall in most cases of Zuidex injection without the need for endoscopic guidance. Complications after Zuidex injection, such as periurethral mass, urethral granulomas, urethral abscess, and pseudocysts, have since been reported [46–49].
Autologous myoblast injection Mitterberger et al. [50••] investigated donor myoblasts as potential autologous bulking agents. They concluded that autologous myoblasts can survive and differentiate into myofibers when implanted as small depots, while the vast majority of cells become necrotic when implanted as a large collection. Their fi nal recommendation stated that myoblasts should not be used to augment large volumes of tissue or as a bulking agent.
Porcine dermal implant injection Bano et al. [36] compared the efficacy of Permacol (Covidien, Dubin, Ireland) with Macroplastique for the treatment of SUI. Their results suggest that Permacol, as a
Conclusions SUI, the most common type of urinary incontinence in women, significantly interferes with the QOL of affected
Urethral Bulking Agents: Techniques and Outcomes
individuals. Radical hysterectomy, vulvectomy, and prostatectomy in men are often complicated by postoperative SUI, with limited surgical treatment options. Today, urethral bulking agents have gained wide popularity, with documented effectiveness and accepted morbidity. This technique has the added advantage of being injected under local anesthesia in an easy and effective way in patients who cannot withstand surgery because of comorbidity or age. Studies have shown virtually similar results with injection in the bladder neck or midurethra, with a slight preference for midurethral injection. Transurethral or periurethral injection does not affect the results of treatment. Endoluminal ultrasound may allow more precise implantation of bulking agents, but needs further trials to prove its efficacy and to justify its use instead of cystourethroscopy. Collagen is the fi rst and oldest agent studied with acceptable results, but is limited by its short duration of action in most cases. Many other injectable agents have become available, including carbon-coated zirconium, ethylene vinyl alcohol, Macroplastique, porcine dermal implant, Coaptite, and Zuidex. They have longer durability compared with collagen, but are associated with other limiting factors such as technical difficulty at injection (for Durasphere). Also, Coaptite and Zuidex reportedly cause urethral granuloma, abscess, and cysts. A literature review has shown that Macroplastique is a durable, injectable material with no major associated complications. The injection of bulking agents is an attractive treatment option for SUI in view of their safe side effect profi le. Their efficacy will improve with further technological advancements and the development of new, ideal agents.
Disclosure Dr. Jacques Corcos is a consultant for Bard Pharmaceuticals and Q-Med. No other potential confl icts of interest relevant to this article were reported.
References and Recommended Reading Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
2.
3. 4. 5.
Hampel C, Artibani W, Espuna Pons M, et al.: Understanding the burden of stress urinary incontinence in Europe: a qualitative review of the literature. Eur Urol 2004, 46:15–27. Klarskov N, Lose G: Urethral injection therapy: what is the mechanism of action? Neurourol Urodyn 2008, 27:789–792. Schafer W: Some biomechanical aspects of continence function. Scand J Urol Nephrol Suppl 2001, 207:44–60. Berne RM, Levy MN: Physiology, edn 3. St. Louis, MO: Mosby; 1993. Kuhn A, Stadlmayr W, Lengsfeld D, Mueller MD: Where should bulking agents for female urodynamics stress incontinence be injected? Int Urogynecol J Pelvic Floor Dysfunct 2008, 19:817–821.
6.
I
Kotb et al.
I
399
Petros PE, Ulmsten UI: An integral theory and its method for the diagnosis and management of female urinary incontinence. Scand J Urol Nephrol Suppl 1993, 153:1–93. 7. Elia G, Bergman A: Periurethral collagen implant: ultrasound assessment and prediction of outcome. Int Urogynecol J Pelvic Floor Dysfunct 1996, 7:335–338. 8.• Mitterberger M, Pinggera GM, Pelzer A, et al.: Comparison of the precision of transurethral endoscopic versus ultrasoundguided application of injectables. BJU Int 2008, 101:245–249. This study compares a new ultrasound-guided technique of injection of urethral bulking agents with the original endoscopic injection. 9. Schulz JA, Nager CW, Stanton SL, Baessler K: Bulking agents for stress urinary incontinence: short-term results and complications in a randomized comparison of periurethral and transurethral injections. J Urol 2005, 73:11–12. 10. Chapple CR, Brubaker L, Haab F, et al.: Patient perceived outcomes in the treatment of stress urinary incontinence: focus on urethral injection therapy. Int Urogynecol J Pelvic Floor Dysfunct 2007, 18:199–205. 11. Kershen RT, Dmochowski RR, Appell RA: Beyond collagen: injectable therapies for the treatment of female stress urinary incontinence in the new millennium. Urol Clin North Am 2002, 29:559–574. 12. McGuire EJ, Appell RA: Transurethral collagen injection for urinary incontinence. Urology 1994, 43:413–415. 13. Bent AE, Foote J, Siegel S, et al.: Collagen implant for treating stress urinary incontinence in women with urethral hypermobility. J Urol 2001, 66:1354–1357. 14.• Martins SB, Oliveira RA, Castro RA, et al.: Clinical and urodynamics evaluation in women with stress urinary incontinence treated by Periurethral collagen injection. Int Braz J Urol 2007, 33:695–703. This study evaluates the effectiveness of bulking agents for the treatment of SUI associated with urethral hypermobility. 15. Corcos J, Fournier C: Periurethral collagen injection for the treatment of female stress urinary incontinence: 4 year follow up results. Urology 1999, 54:815–818. 16. Poon CI, Zimmern PE, Wilson TS, et al.: Three dimensional ultrasonography to assess long term durability of Periurethral collagen in women with stress urinary incontinence due to intrinsic sphincter deficiency. Urology 2005, 65:60–64. 17.• Isom-Batz G, Zimmern PE: Collagen injection for female urinary incontinence after urethral or periurethral surgery. J Urol 2009, 181:701–704. This article is a retrospective review of patients who underwent collagen injection for persistent SUI following urethral surgery. It uses three-dimensional ultrasound to evaluate the configuration and volume of injected collagen and its association with treatment failure. 18. Koduri S, Goldberg RP, Kwon C, et al.: Factors influencing the long-term success of periurethral collagen therapy in the office. Int Urogynecol J Pelvic Floor Dysfunct 2006, 17:346–351. 19. Sokol ER, Aguilar VC, Sung VW, Myers DL: Combined trans- and periurethral injections of bulking agents for the treatment of intrinsic sphincter deficiency. Int Urogynecol J Pelvic Floor Dysfunct 2008, 19:643–647. 20. Poon CI, Zimmern PE: Is there a role for periurethral collagen injection in the management of urodynamically proven mixed urinary incontinence? Urology 2006, 67:725–729. 21. Kassouf W, Capolicchio G, Berardinucci G, Corcos J: Collagen injection for treatment of urinary incontinence in children. J Urol 2001, 165:1666–1668. 22. Block CA, Cooper CS, Hawtrey CE: Long term efficacy of periurethral collagen injection for the treatment of urinary incontinence secondary to myelomeningocele. J Urol 2003, 169:327–329. 23. Wilson S, Quek ML, Ginsberg DA: Transurethral injection of bulking agents for stress urinary incontinence following orthotopic neobladder reconstruction in women. J Urol 2004, 172:244–246. 24. Chrouser KL, Fick F, Goel A, et al.: Carbon coated zirconium beads in beta-glucan gel and bovine glutaraldehyde cross-linked collagen injections for intrinsic sphincter deficiency: continence and satisfaction after extended follow up. J Urol 2004, 171:1152–1155.
400 25.
I
Female Urology
Madjar S, Covington-Nichols C, Secrest CL: New periurethral bulking agent for stress urinary incontinence: modified technique and early results. J Urol 2003, 170:2327–2329. 26. Madjar S, Sharma AK, Waltzer WC, et al.: Periurethral mass formations following bulking agent injection for the treatment of urinary incontinence. J Urol 2006, 175:1408–1410. 27. McCrery RJ, Appell RA: Safety for carbon bead injection for incontinence in patients taking warfarin. Urology 2006, 67:97–99. 28. Kuhn A, Stadlmayr W, Sohail A, Monga A: Long-term results and patients’ satisfaction after transurethral ethylene vinyl alcohol (Tegress) injections: a two-centre study. Int Urogynecol J Pelvic Floor Dysfunct 2008, 19:503–507. 29. Hurtado E, McCrery R, Appell R: The safety and efficacy of ethylene vinyl alcohol copolymer as an intra-urethral bulking agent in women with intrinsic urethral deficiency. Int Urogynecol J pelvic Floor Dysfunct 2007, 18:869–873. 30. Erekson EA, Sung VW, Rardin CR, Myers DL: Ethylene vinyl alcohol copolymer erosions after use as a urethral bulking agent. Obstet Gynecol 2007, 109(2 Pt 2):490–492. 31. Ter Meulen PH, Berghmans LC, van Kerrebroeck PE: Systematic review: efficacy of silicone microimplants (Macroplastique) therapy for stress urinary incontinence in adult women. Eur Urol 2003, 44:573–582. 32. Zullo M, Plotti F, Bellati F, et al.: Transurethral polydimethylsiloxane implantation: a valid option for the treatment of stress urinary incontinence due to intrinsic sphincter deficiency without urethral hypermobility. J Urol 2005, 173:898–902. 33.•• Ghoneim G, Corcos J, Comiter C, et al.: Cross-linked polydimethylsiloxane injection for female stress urinary incontinence: results of a multicenter, randomized, controlled, single-blind study. J Urol 2009, 181:204–210. This multicentric, single-blind study demonstrates the long-term efficacy of Macroplastique over collagen. 34. Plotti F, Zullo MA, Sansone M, et al.: Post radical hysterectomy urinary incontinence: a prospective study of transurethral bulking agents injection. Gynecol Oncol 2009, 112:90–94. 35. Plotti F, Zullo MA, Palaia I, et al.: Urinary incontinence after radical vulvectomy treated with Macroplastique implantation. J Minim Invasive Gynecol 2008, 15:113–115. 36. Bano F, Barrington JW, Dyer R: Comparison between porcine dermal implant (Permacol) and silicone injection (Macroplastique) for urodynamic stress incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2005, 16:147–150. 37. Mayer RD, Dmochowski RR, Appell RA, et al.: Multicenter prospective randomized 52-week trial of calcium hydroxylapatite versus bovine dermal collagen for treatment of stress urinary incontinence. Urology 2007, 69:876–880. 38. Palma PC, Riccetto CL, Martins MH, et al.: Massive prolapse of the urethral mucosa following periurethral injection of calcium hydroxylapatite for stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2006, 17:670–671.
39.
Ko EY, Williams BF, Petrou SP: Bulking agent induced early urethral prolapse after distal urethrectomy. Int Urogynecol J Pelvic Floor Dysfunct 2007, 18:1511–1513. 40. Lai HH, Hurtado EA, Appell RA: Large urethral prolapse formation after calcium hydroxylapatite (Coaptite) injection. Int Urogynecol J Pelvic Floor Dysfunct 2008, 19:1315–1317. 41. Van Kerrebroeck P, ter Meulen F, Larsson G, et al.: Efficacy and safety of a novel system (NASHA/Dx copolymer using the Implacer device) for treatment of stress urinary incontinence. Urology 2004, 4:76–81. 42. Chapple CR, Haab F, Cervigni M, et al.: An open, multicentre study of NASHA/Dx Gel (Zuidex) for the treatment of stress urinary incontinence. Eur Urol 2005, 48:488–494. 43. Kobelt G, Fianu-Jonasson A: Treatment of stress urinary incontinence with non-animal stabilised hyaluronic acid/dextranomer (NASHA/Dx) gel: an analysis of utility and cost. Clin Drug Investig 2006, 26:583–591. 44. Papanikolaou NS, Ducket J: Treating urethral sphincter damage caused by long-term urethral catheterisation with a Zuidex periurethral injection and suprapubic catheter. J Obstet Gynaecol 2008, 28:361–362. 45. Fianu-Jonasson A, Edwall L, Wiberg MK: Magnetic resonance imaging to evaluate NASHA/Dx gel (Zuidex) for stress urinary incontinence. Int J Clin Pract 2006, 10:1181–1186. 46. Abdelwahab HA, Ghoniem GM: Obstructive suburethral mass after transurethral injection of dextranomer/hyaluronic acid copolymer. Int Urogynecol J Pelvic Floor Dysfunct 2007, 18:1379–1380. 47. Castillo-Vico MT, Checa-Vizcaino MA, Paya-Panades A, et al.: Periurethral granuloma following injection with dextranomer/hyaluronic acid copolymer for stress urinary incontinence. Int Urogynecol J Pelvic Floor Dysfunct 2007, 18:95–97. 48. Hagemeier T, Blau U, Gauruder-Burmester A, Tunn R: Paraurethral abscess developing after mid-urethral Zuidex-injection in women with stress urinary incontinence ? Management of complications and retrospective comparison with bladder neck located injection technique. Zentralbl Gynakol 2006, 128:68–70. 49. Loisel C, Secco M, Rocher-Barrat A, et al.: Periurethral pseudocysts following urethral injections of Zuidex: review of the literature. Prog Urol 2008, 18:1038–1043. 50.•• Mitterberger M, Marksteiner R, Schwaiger W, et al.: Can autologous myoblasts be used as a potential bulking agent? BJU Int 2008, 102:1731–1736. This is the fi rst trial to study the implantation of autologous myoblasts as a bulking agent for SUI treatment.
